The document discusses prion diseases in humans, specifically Creutzfeldt-Jakob disease (CJD). It notes that CJD consists of three main types: sporadic, familial, and iatrogenic CJD. Sporadic CJD accounts for 85% of cases and occurs equally in both sexes, with onset typically between ages 60-69. It results from the spontaneous misfolding of prion proteins in the brain. The document provides details on the clinical presentation and pathological findings of sporadic CJD.
Mad Cow Disease, also known as Bovine Spongiform Encephalopathy (BSE), is a fatal neurodegenerative disease affecting cattle. It belongs to a group of diseases called Transmissible Spongiform Encephalopathies (TSEs) that can affect both animals and humans. A related human disease is variant Creutzfeldt-Jakob disease (vCJD), which is believed to be caused by eating beef infected with BSE. Both diseases are caused by an abnormal prion protein that changes the shape of normal prion proteins in the brain, causing neurodegeneration. There is currently no treatment for either disease, so prevention focuses on restricting animal feed and meat imports.
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and
offering a wide range of dental certified courses in different formats.
A SURVEY ON PARKINSON’S DISEASE DETECTION TECHNIQUESIRJET Journal
This document discusses techniques for detecting Parkinson's disease through analysis of voice recordings. It provides an overview of several machine learning and deep learning algorithms that have been applied to classify Parkinson's disease based on voice data, including artificial neural networks, random forest classifiers, convolutional neural networks and adaptive backpropagation neural networks. Accuracy rates between 85-88% were reported. The document also discusses the use of techniques like fuzzy C-means clustering and efficient randomized feature selection algorithms to improve Parkinson's disease detection from voice recordings.
TSE/BSE is a type of disease affected to the animals which may transmit to the humans if any products obtained by the disease caused animal may affect to humans also
The many biologic products are expracted from the animal source so before the extraction the animal should be tested for TSE/BSE organism in their source/Body
Prions are infectious proteins that can cause neurodegenerative diseases such as mad cow disease and CJD in humans. Prions lack nucleic acids and are composed solely of abnormal versions of host-encoded proteins. They propagate by converting normal protein molecules into the abnormal prion form. This causes disease by disrupting normal protein folding in the brain. While prion diseases are generally untreatable and fatal, research on yeast prions has provided insights into prion transmission and conversion mechanisms at the molecular level.
Prions are infectious protein particles that cause fatal neurodegenerative diseases in humans and animals. Prions are composed solely of protein and lack DNA or RNA. They are the cause of transmissible spongiform encephalopathies (TSEs), diseases which destroy brain tissue and cause large vacuoles, giving the brain a spongy appearance. Prions convert normal cellular prion proteins (PrPc) into an abnormal disease-causing form (PrPsc) which aggregates to form plaques that damage brain tissue. Common symptoms of TSEs include dementia, loss of motor coordination, insomnia, and eventually death.
This dissertation examines biomarkers of atherosclerosis and their association with cardiovascular disease risk among middle-aged men in an international population-based study. Specifically, it compares the prevalence of carotid plaque between men in the US, Japan and South Korea, finding plaque to be significantly lower in Eastern Asia. It also shows brachial-ankle pulse wave velocity, a measure of arterial stiffness, to be associated with higher coronary artery calcification. Finally, it reports that Japanese men who are able to convert the soy isoflavone daidzein into equol have lower coronary artery calcification than non-converters, suggesting a protective effect of equol against atherosclerosis.
Paget's disease is a condition that causes abnormal bone growth and remodeling. While the exact cause is unclear, studies have implicated viral and genetic factors. Around 20% of cases are familial and linked to mutations in genes involved in osteoclast regulation. The disease predominantly affects older individuals of European descent. Symptoms can resemble mental illnesses like bipolar disorder or psychosis due to bone changes affecting the brain. Paget's disease and cancer share some similarities like new blood vessel formation, but Paget's primarily affects bone cells and is usually not lethal. Cranial bone changes in Paget's can cause hearing loss or neurological issues. Increased bone remodeling leads to high cardiac output and potential heart failure over time.
Mad Cow Disease, also known as Bovine Spongiform Encephalopathy (BSE), is a fatal neurodegenerative disease affecting cattle. It belongs to a group of diseases called Transmissible Spongiform Encephalopathies (TSEs) that can affect both animals and humans. A related human disease is variant Creutzfeldt-Jakob disease (vCJD), which is believed to be caused by eating beef infected with BSE. Both diseases are caused by an abnormal prion protein that changes the shape of normal prion proteins in the brain, causing neurodegeneration. There is currently no treatment for either disease, so prevention focuses on restricting animal feed and meat imports.
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and
offering a wide range of dental certified courses in different formats.
A SURVEY ON PARKINSON’S DISEASE DETECTION TECHNIQUESIRJET Journal
This document discusses techniques for detecting Parkinson's disease through analysis of voice recordings. It provides an overview of several machine learning and deep learning algorithms that have been applied to classify Parkinson's disease based on voice data, including artificial neural networks, random forest classifiers, convolutional neural networks and adaptive backpropagation neural networks. Accuracy rates between 85-88% were reported. The document also discusses the use of techniques like fuzzy C-means clustering and efficient randomized feature selection algorithms to improve Parkinson's disease detection from voice recordings.
TSE/BSE is a type of disease affected to the animals which may transmit to the humans if any products obtained by the disease caused animal may affect to humans also
The many biologic products are expracted from the animal source so before the extraction the animal should be tested for TSE/BSE organism in their source/Body
Prions are infectious proteins that can cause neurodegenerative diseases such as mad cow disease and CJD in humans. Prions lack nucleic acids and are composed solely of abnormal versions of host-encoded proteins. They propagate by converting normal protein molecules into the abnormal prion form. This causes disease by disrupting normal protein folding in the brain. While prion diseases are generally untreatable and fatal, research on yeast prions has provided insights into prion transmission and conversion mechanisms at the molecular level.
Prions are infectious protein particles that cause fatal neurodegenerative diseases in humans and animals. Prions are composed solely of protein and lack DNA or RNA. They are the cause of transmissible spongiform encephalopathies (TSEs), diseases which destroy brain tissue and cause large vacuoles, giving the brain a spongy appearance. Prions convert normal cellular prion proteins (PrPc) into an abnormal disease-causing form (PrPsc) which aggregates to form plaques that damage brain tissue. Common symptoms of TSEs include dementia, loss of motor coordination, insomnia, and eventually death.
This dissertation examines biomarkers of atherosclerosis and their association with cardiovascular disease risk among middle-aged men in an international population-based study. Specifically, it compares the prevalence of carotid plaque between men in the US, Japan and South Korea, finding plaque to be significantly lower in Eastern Asia. It also shows brachial-ankle pulse wave velocity, a measure of arterial stiffness, to be associated with higher coronary artery calcification. Finally, it reports that Japanese men who are able to convert the soy isoflavone daidzein into equol have lower coronary artery calcification than non-converters, suggesting a protective effect of equol against atherosclerosis.
Paget's disease is a condition that causes abnormal bone growth and remodeling. While the exact cause is unclear, studies have implicated viral and genetic factors. Around 20% of cases are familial and linked to mutations in genes involved in osteoclast regulation. The disease predominantly affects older individuals of European descent. Symptoms can resemble mental illnesses like bipolar disorder or psychosis due to bone changes affecting the brain. Paget's disease and cancer share some similarities like new blood vessel formation, but Paget's primarily affects bone cells and is usually not lethal. Cranial bone changes in Paget's can cause hearing loss or neurological issues. Increased bone remodeling leads to high cardiac output and potential heart failure over time.
A REPORT OF THE STUDENTS INDUSTRIAL WORK EXPERIENCE SCHEME(SIWES)Valerie Felton
The document provides a report on a student's 3-month industrial training at the Benue State University Teaching Hospital (BSUTH) chemical pathology department from April to June 2016. It includes an overview of BSUTH, describing its location, leadership, departments, vision, mission and organizational structure. It also outlines the student's involvement in the phlebotomy, separation, and main laboratory units. The student gained experience in blood collection techniques, urinalysis, pregnancy testing, and quantitative analysis of various analytes using spectrophotometry. Challenges encountered and recommendations are also discussed.
Prion diseases are rare neurodegenerative disorders caused by misfolded prion proteins. They affect both humans and animals. In cattle it is known as bovine spongiform encephalopathy (BSE) or "mad cow disease", and in humans it is known as Creutzfeldt-Jakob disease (CJD). Prion diseases occur when normal prion proteins misfold and induce other prion proteins to also misfold, triggering a chain reaction that causes damage to neural cells. There is no cure for prion diseases and diagnosis is difficult since prion proteins are similar to normal forms.
Prions are abnormal protein particles that can cause neurodegenerative diseases. They have a normal function in the body but can transform into an infectious form. When this happens, they induce other normal prion proteins to adopt the abnormal shape. Common prion diseases include scrapie in sheep, mad cow disease, and Creutzfeldt-Jakob disease in humans. There are currently no effective treatments for prion diseases, so prevention and diagnosis are important.
Insilico analysis of pkd genes in polycystic kidney disease patientsVeeramuthumariPandia1
The power point tells about the gene polymorphism alters the protein structure. Alteration in protein structure leads to malfunction of gene causes disease. PKD gnes-Polycystin 1 and 2 protein - Polycystic kidney disease.
Prions are infectious protein particles that cause neurodegenerative diseases like Creutzfeldt-Jakob disease in humans and bovine spongiform encephalopathy (mad cow disease) in cattle. Prions are composed solely of protein and contain no nucleic acids. They propagate by converting the normal cellular prion protein (PrPC) into an abnormal disease-causing form (PrPSc). The normal prion protein is involved in the replication of the mutated form. Prion diseases are difficult to treat as prions are highly resistant to heat and chemical inactivation.
Annovis Bio (NYSE American: ANVS) is a clinical-stage, drug platform company addressing neurodegeneration, such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and Alzheimer’s in Down Syndrome (AD-DS). Annovis is believed to be the only company developing a drug for AD, PD and AD-DS that inhibits more than one neurotoxic protein and improves the information highway of the nerve cell, known as axonal transport. When this information flow is impaired, the nerve cell gets sick and dies. The company expects its treatment to improve memory loss and dementia associated with AD and AD-DS, as well as body and brain function in PD. Annovis has an ongoing Phase 2a study in AD patients and plans to commence a second Phase 2a study in PD patients. Learn more at ANVSinfo.com.
This thesis investigates the role of large conductance calcium and voltage activated potassium (BK) channels in the neurodegenerative process caused by mutations in the cysteine string protein alpha (CSPα). CSPα is a molecular chaperone important for synaptic maintenance. A mutation in the CSPα gene causes adult onset neuronal ceroid lipofuscinosis (ANCL), a fatal neurodegenerative disease characterized by lysosomal accumulation in neurons. Previous studies found increased expression of BK channels in CSPα knockout mice, but the significance is unknown. This study examines BK channel expression levels at various ages in CSPα wild-type and knockout mice, and the effects of lysosome inhibition on BK channel levels, to better
Kuru was a fatal brain disorder seen among the Fore people of Papua New Guinea in the early 1900s. It was caused by prions and transmitted through ritualistic cannibalism of deceased relatives. Symptoms included tremors, loss of motor control and uncontrollable laughter. An epidemic occurred until the practice of cannibalism was banned in the 1950s. While prions were identified as the infectious agent, there is no cure for prion diseases like Kuru.
Prion Diseases ; An overview .........
Credit goes equally to Dr Siraj Uddin, M.V.Sc Scholar, IVRI and Dr. Gazanfar Abass, M.V.Sc. Scholar, VPH, IVRI.
For Further reference contact at gazanfar0966@gmail.com
Prion diseases are fatal neurodegenerative diseases caused by misfolded prion proteins. Some key points:
- Prion diseases affect humans and animals like BSE in cattle and scrapie in sheep. Human forms include CJD and vCJD.
- Prions resist heat and disinfectants and propagate through conversion of normal prion proteins into infectious forms.
- BSE emerged in cattle in the 1980s due to feeding meat and bone meal and had severe economic impacts. It can cause vCJD in humans.
- Diagnosis relies on brain examination, but prion detection tests continue to improve. Control focuses on banning risky animal feeds and removing high-risk tissues from the food chain.
An 80-year-old man presented with symptoms of Alzheimer's disease including memory loss, disorientation, difficulty completing tasks, and mood changes. Brain scans and examination of brain tissue confirmed Alzheimer's disease. Alzheimer's is caused by abnormal accumulation of tau and amyloid-beta proteins in the brain, which form plaques and tangles that damage neurons. It is diagnosed based on symptoms, cognitive tests, and brain imaging, and progresses from mild to severe impairment over time. There are medications to temporarily improve symptoms but no cure for the underlying disease process.
Summary
Neurodevelopment is a complex process governed by both intrinsic and extrinsic signals. While historically studied by researching the brain, inputs from the periphery impact many neurological conditions. Indeed, emerging data suggests communication between the gut and the brain in anxiety,
depression, cognition and autism spectrum disorder (ASD). The development of a healthy, functional brain depends on key pre- and post-natal events that integrate environmental cues, such as molecular signals from the gut. These cues largely originate from the microbiome, the consortium of symbiotic bacteria that reside within all animals. Research over the past few years reveals that the gut microbiome plays a role in basic neurogenerative processes such as the formation of the blood-brainbarrier, myelination, neurogenesis, and microglia maturation, and also modulates many aspects of animal behavior. Herein, we discuss the biological intersection of neurodevelopment and the microbiome, and explore the hypothesis that gut bacteria are integral contributors to development and function of the nervous system, and the balance between mental health and disease.
Annovis Bio (NYSE American: ANVS) is a clinical-stage, drug platform company addressing neurodegeneration, such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and Alzheimer’s in Down Syndrome (AD-DS). Annovis is believed to be the only company developing a drug for AD, PD and AD-DS that inhibits more than one neurotoxic protein and improves the information highway of the nerve cell, known as axonal transport. When this information flow is impaired, the nerve cell gets sick and dies. The company expects its treatment to improve memory loss and dementia associated with AD and AD-DS, as well as body and brain function in PD. Annovis has an ongoing Phase 2a study in AD patients and plans to commence a second Phase 2a study in PD patients. Learn more at ANVSinfo.com.
Uncovering novel candidate genes for pyridoxine-responsive epilepsy in a cons...Golden Helix Inc
This document summarizes Hilal Al Shekaili's work on characterizing the genetic cause of pyridoxine-dependent epilepsy (PDE) in an Omani family. [1] Runs of homozygosity mapping and whole-exome sequencing identified two candidate genes involved in vitamin transport and neuropeptide processing. [2] Further studies are planned to validate the candidate genes and recruit additional families. [3] Identifying new PDE genes could improve treatment and fill knowledge gaps in pyridoxine metabolism.
Genetic Basis of Pyridoxine-Responsive Neonatal Epilepsy in Consanguineous Fa...Delaina Hawkins
Hilal Al-Shekaili is a PhD student at the University of British Columbia who conducts research in rare, autosomal recessive disorders, specifically pyridoxine-responsive epileptic encephalopathies (PREE). PREE is often characterized by recurrent seizures in the prenatal, neonatal, or postnatal period, which are typically resistant to conventional anticonvulsant treatment but are well-controlled by the administration of pyridoxine (vitamin B6). Hilal and his colleagues at UBC are undertaking a research project to identify novel genetic causes in unexplained forms of pyridoxine-dependent epilepsy (PDE), a special type of PREE with an estimated incidence of 1:20,000 to 1:750,000. In most affected infants, PDE is caused by mutations in the antiquitin gene (ALDH7A1) and subsequent inactivation of α-aminoadipic semialdehyde dehydrogenase (antiquitin, ATQ).
Currently, ALDH7A1 is the only gene for which mutations are known to underlie PDE. However, locus heterogeneity has been reported in some families and other genes seem to be involved. Nearly 5% of children with a typical clinical picture of PDE harbor no detectable mutation of ALDH7A1. Identifying causative genes in such families will likely lead to improved treatment for these patients and help unravel much of the unknown about pyridoxine metabolism in the human body.
In this webinar, Hilal will cover how he and his team used whole-genome SNP genotyping, genome-wide runs of homozygosity (RoH) mapping using SVS, and whole-exome sequencing to characterize the genetic defect underlying PREE in a consanguineous Omani Arab family with two affected children who have a PDE-like clinical picture but negative ATQ biomarkers.
This document summarizes a thesis that examined the effects of prenatal exposure to TCDD (dioxin) on cell proliferation, apoptosis, and protein expression in the uterus of Sprague-Dawley rats. Pregnant rats were exposed to TCDD on gestational day 15. Female offspring were sacrificed at 21 and 50 days old and their uteri analyzed. At 21 days, cell proliferation was decreased and no differences in apoptosis or proteins were found. At 50 days, cell proliferation increased in one uterine layer, apoptosis decreased in both layers, and 6 proteins were differentially expressed. The thesis aimed to identify how prenatal TCDD exposure alters the uterus and may increase cancer risk.
Both Drosophila and zebrafish are used as animal models for studying human disease. Drosophila is advantageous for its fast development, easy maintenance, and suitability for genetic analysis. However, zebrafish are more suitable models for studies of heart disease due to their greater genetic similarity to humans as vertebrates and transparent embryos allowing heart observation. While both have high fecundity and are used for drug discovery, zebrafish have shorter generation times as vertebrates and are easier to work with.
This document provides an overview of Parkinson's syndrome, a degenerative nervous disorder. It discusses the anatomy of the brain and division of the brain. Parkinson's disease is defined as a slow progressing movement disorder characterized by slowness in movement initiation and execution. It results from the depletion of dopamine in the substantia nigra, which leads to the development of Lewy bodies. Common clinical manifestations include tremor, rigidity, bradykinesia, and postural instability. Treatment involves the use of dopamine agonists, anticholinergics, MAO inhibitors, and COMT inhibitors. Nursing management is based on assessing mobility, self-care, nutrition, elimination, and communication to establish goals and interventions.
The document discusses prion diseases, which are neurodegenerative disorders caused by abnormal prion proteins. It covers the discovery of prions, the different forms of human and animal prion diseases, and the molecular pathogenesis involving the conversion of normal prion protein (PrPc) to abnormal disease-causing prion protein (PrPsc). Clinical features of various human prion diseases like CJD are described. Diagnosis involves neuroimaging, EEG, CSF analysis and detection of PrPsc in brain tissue. Histopathology shows vacuolation, gliosis and prion plaques. Variant CJD results from eating meat from cows with BSE.
The document discusses the physiology of the nervous system and various topics related to it. It begins by describing a 1848 case study where a patient exhibited altered behaviors after brain damage to the frontal cortex. It then discusses memory-related phenomena like déjà vu. It explains that déjà vu may occur due to conflict resolution in the brain when there is a mismatch between actual and perceived memories. The document also covers topics like the blood-brain barrier, neurotransmitters, neuronal membrane potentials and ion channels, memory formation and diseases like Alzheimer's and Parkinson's. It describes the mechanisms, symptoms and treatment options for these diseases.
A REPORT OF THE STUDENTS INDUSTRIAL WORK EXPERIENCE SCHEME(SIWES)Valerie Felton
The document provides a report on a student's 3-month industrial training at the Benue State University Teaching Hospital (BSUTH) chemical pathology department from April to June 2016. It includes an overview of BSUTH, describing its location, leadership, departments, vision, mission and organizational structure. It also outlines the student's involvement in the phlebotomy, separation, and main laboratory units. The student gained experience in blood collection techniques, urinalysis, pregnancy testing, and quantitative analysis of various analytes using spectrophotometry. Challenges encountered and recommendations are also discussed.
Prion diseases are rare neurodegenerative disorders caused by misfolded prion proteins. They affect both humans and animals. In cattle it is known as bovine spongiform encephalopathy (BSE) or "mad cow disease", and in humans it is known as Creutzfeldt-Jakob disease (CJD). Prion diseases occur when normal prion proteins misfold and induce other prion proteins to also misfold, triggering a chain reaction that causes damage to neural cells. There is no cure for prion diseases and diagnosis is difficult since prion proteins are similar to normal forms.
Prions are abnormal protein particles that can cause neurodegenerative diseases. They have a normal function in the body but can transform into an infectious form. When this happens, they induce other normal prion proteins to adopt the abnormal shape. Common prion diseases include scrapie in sheep, mad cow disease, and Creutzfeldt-Jakob disease in humans. There are currently no effective treatments for prion diseases, so prevention and diagnosis are important.
Insilico analysis of pkd genes in polycystic kidney disease patientsVeeramuthumariPandia1
The power point tells about the gene polymorphism alters the protein structure. Alteration in protein structure leads to malfunction of gene causes disease. PKD gnes-Polycystin 1 and 2 protein - Polycystic kidney disease.
Prions are infectious protein particles that cause neurodegenerative diseases like Creutzfeldt-Jakob disease in humans and bovine spongiform encephalopathy (mad cow disease) in cattle. Prions are composed solely of protein and contain no nucleic acids. They propagate by converting the normal cellular prion protein (PrPC) into an abnormal disease-causing form (PrPSc). The normal prion protein is involved in the replication of the mutated form. Prion diseases are difficult to treat as prions are highly resistant to heat and chemical inactivation.
Annovis Bio (NYSE American: ANVS) is a clinical-stage, drug platform company addressing neurodegeneration, such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and Alzheimer’s in Down Syndrome (AD-DS). Annovis is believed to be the only company developing a drug for AD, PD and AD-DS that inhibits more than one neurotoxic protein and improves the information highway of the nerve cell, known as axonal transport. When this information flow is impaired, the nerve cell gets sick and dies. The company expects its treatment to improve memory loss and dementia associated with AD and AD-DS, as well as body and brain function in PD. Annovis has an ongoing Phase 2a study in AD patients and plans to commence a second Phase 2a study in PD patients. Learn more at ANVSinfo.com.
This thesis investigates the role of large conductance calcium and voltage activated potassium (BK) channels in the neurodegenerative process caused by mutations in the cysteine string protein alpha (CSPα). CSPα is a molecular chaperone important for synaptic maintenance. A mutation in the CSPα gene causes adult onset neuronal ceroid lipofuscinosis (ANCL), a fatal neurodegenerative disease characterized by lysosomal accumulation in neurons. Previous studies found increased expression of BK channels in CSPα knockout mice, but the significance is unknown. This study examines BK channel expression levels at various ages in CSPα wild-type and knockout mice, and the effects of lysosome inhibition on BK channel levels, to better
Kuru was a fatal brain disorder seen among the Fore people of Papua New Guinea in the early 1900s. It was caused by prions and transmitted through ritualistic cannibalism of deceased relatives. Symptoms included tremors, loss of motor control and uncontrollable laughter. An epidemic occurred until the practice of cannibalism was banned in the 1950s. While prions were identified as the infectious agent, there is no cure for prion diseases like Kuru.
Prion Diseases ; An overview .........
Credit goes equally to Dr Siraj Uddin, M.V.Sc Scholar, IVRI and Dr. Gazanfar Abass, M.V.Sc. Scholar, VPH, IVRI.
For Further reference contact at gazanfar0966@gmail.com
Prion diseases are fatal neurodegenerative diseases caused by misfolded prion proteins. Some key points:
- Prion diseases affect humans and animals like BSE in cattle and scrapie in sheep. Human forms include CJD and vCJD.
- Prions resist heat and disinfectants and propagate through conversion of normal prion proteins into infectious forms.
- BSE emerged in cattle in the 1980s due to feeding meat and bone meal and had severe economic impacts. It can cause vCJD in humans.
- Diagnosis relies on brain examination, but prion detection tests continue to improve. Control focuses on banning risky animal feeds and removing high-risk tissues from the food chain.
An 80-year-old man presented with symptoms of Alzheimer's disease including memory loss, disorientation, difficulty completing tasks, and mood changes. Brain scans and examination of brain tissue confirmed Alzheimer's disease. Alzheimer's is caused by abnormal accumulation of tau and amyloid-beta proteins in the brain, which form plaques and tangles that damage neurons. It is diagnosed based on symptoms, cognitive tests, and brain imaging, and progresses from mild to severe impairment over time. There are medications to temporarily improve symptoms but no cure for the underlying disease process.
Summary
Neurodevelopment is a complex process governed by both intrinsic and extrinsic signals. While historically studied by researching the brain, inputs from the periphery impact many neurological conditions. Indeed, emerging data suggests communication between the gut and the brain in anxiety,
depression, cognition and autism spectrum disorder (ASD). The development of a healthy, functional brain depends on key pre- and post-natal events that integrate environmental cues, such as molecular signals from the gut. These cues largely originate from the microbiome, the consortium of symbiotic bacteria that reside within all animals. Research over the past few years reveals that the gut microbiome plays a role in basic neurogenerative processes such as the formation of the blood-brainbarrier, myelination, neurogenesis, and microglia maturation, and also modulates many aspects of animal behavior. Herein, we discuss the biological intersection of neurodevelopment and the microbiome, and explore the hypothesis that gut bacteria are integral contributors to development and function of the nervous system, and the balance between mental health and disease.
Annovis Bio (NYSE American: ANVS) is a clinical-stage, drug platform company addressing neurodegeneration, such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and Alzheimer’s in Down Syndrome (AD-DS). Annovis is believed to be the only company developing a drug for AD, PD and AD-DS that inhibits more than one neurotoxic protein and improves the information highway of the nerve cell, known as axonal transport. When this information flow is impaired, the nerve cell gets sick and dies. The company expects its treatment to improve memory loss and dementia associated with AD and AD-DS, as well as body and brain function in PD. Annovis has an ongoing Phase 2a study in AD patients and plans to commence a second Phase 2a study in PD patients. Learn more at ANVSinfo.com.
Uncovering novel candidate genes for pyridoxine-responsive epilepsy in a cons...Golden Helix Inc
This document summarizes Hilal Al Shekaili's work on characterizing the genetic cause of pyridoxine-dependent epilepsy (PDE) in an Omani family. [1] Runs of homozygosity mapping and whole-exome sequencing identified two candidate genes involved in vitamin transport and neuropeptide processing. [2] Further studies are planned to validate the candidate genes and recruit additional families. [3] Identifying new PDE genes could improve treatment and fill knowledge gaps in pyridoxine metabolism.
Genetic Basis of Pyridoxine-Responsive Neonatal Epilepsy in Consanguineous Fa...Delaina Hawkins
Hilal Al-Shekaili is a PhD student at the University of British Columbia who conducts research in rare, autosomal recessive disorders, specifically pyridoxine-responsive epileptic encephalopathies (PREE). PREE is often characterized by recurrent seizures in the prenatal, neonatal, or postnatal period, which are typically resistant to conventional anticonvulsant treatment but are well-controlled by the administration of pyridoxine (vitamin B6). Hilal and his colleagues at UBC are undertaking a research project to identify novel genetic causes in unexplained forms of pyridoxine-dependent epilepsy (PDE), a special type of PREE with an estimated incidence of 1:20,000 to 1:750,000. In most affected infants, PDE is caused by mutations in the antiquitin gene (ALDH7A1) and subsequent inactivation of α-aminoadipic semialdehyde dehydrogenase (antiquitin, ATQ).
Currently, ALDH7A1 is the only gene for which mutations are known to underlie PDE. However, locus heterogeneity has been reported in some families and other genes seem to be involved. Nearly 5% of children with a typical clinical picture of PDE harbor no detectable mutation of ALDH7A1. Identifying causative genes in such families will likely lead to improved treatment for these patients and help unravel much of the unknown about pyridoxine metabolism in the human body.
In this webinar, Hilal will cover how he and his team used whole-genome SNP genotyping, genome-wide runs of homozygosity (RoH) mapping using SVS, and whole-exome sequencing to characterize the genetic defect underlying PREE in a consanguineous Omani Arab family with two affected children who have a PDE-like clinical picture but negative ATQ biomarkers.
This document summarizes a thesis that examined the effects of prenatal exposure to TCDD (dioxin) on cell proliferation, apoptosis, and protein expression in the uterus of Sprague-Dawley rats. Pregnant rats were exposed to TCDD on gestational day 15. Female offspring were sacrificed at 21 and 50 days old and their uteri analyzed. At 21 days, cell proliferation was decreased and no differences in apoptosis or proteins were found. At 50 days, cell proliferation increased in one uterine layer, apoptosis decreased in both layers, and 6 proteins were differentially expressed. The thesis aimed to identify how prenatal TCDD exposure alters the uterus and may increase cancer risk.
Both Drosophila and zebrafish are used as animal models for studying human disease. Drosophila is advantageous for its fast development, easy maintenance, and suitability for genetic analysis. However, zebrafish are more suitable models for studies of heart disease due to their greater genetic similarity to humans as vertebrates and transparent embryos allowing heart observation. While both have high fecundity and are used for drug discovery, zebrafish have shorter generation times as vertebrates and are easier to work with.
This document provides an overview of Parkinson's syndrome, a degenerative nervous disorder. It discusses the anatomy of the brain and division of the brain. Parkinson's disease is defined as a slow progressing movement disorder characterized by slowness in movement initiation and execution. It results from the depletion of dopamine in the substantia nigra, which leads to the development of Lewy bodies. Common clinical manifestations include tremor, rigidity, bradykinesia, and postural instability. Treatment involves the use of dopamine agonists, anticholinergics, MAO inhibitors, and COMT inhibitors. Nursing management is based on assessing mobility, self-care, nutrition, elimination, and communication to establish goals and interventions.
The document discusses prion diseases, which are neurodegenerative disorders caused by abnormal prion proteins. It covers the discovery of prions, the different forms of human and animal prion diseases, and the molecular pathogenesis involving the conversion of normal prion protein (PrPc) to abnormal disease-causing prion protein (PrPsc). Clinical features of various human prion diseases like CJD are described. Diagnosis involves neuroimaging, EEG, CSF analysis and detection of PrPsc in brain tissue. Histopathology shows vacuolation, gliosis and prion plaques. Variant CJD results from eating meat from cows with BSE.
The document discusses the physiology of the nervous system and various topics related to it. It begins by describing a 1848 case study where a patient exhibited altered behaviors after brain damage to the frontal cortex. It then discusses memory-related phenomena like déjà vu. It explains that déjà vu may occur due to conflict resolution in the brain when there is a mismatch between actual and perceived memories. The document also covers topics like the blood-brain barrier, neurotransmitters, neuronal membrane potentials and ion channels, memory formation and diseases like Alzheimer's and Parkinson's. It describes the mechanisms, symptoms and treatment options for these diseases.
Similar to PRION DISEASES; HOW SAFE ARE WE IN AFRICA? (20)
ESR spectroscopy in liquid food and beverages.pptxPRIYANKA PATEL
With increasing population, people need to rely on packaged food stuffs. Packaging of food materials requires the preservation of food. There are various methods for the treatment of food to preserve them and irradiation treatment of food is one of them. It is the most common and the most harmless method for the food preservation as it does not alter the necessary micronutrients of food materials. Although irradiated food doesn’t cause any harm to the human health but still the quality assessment of food is required to provide consumers with necessary information about the food. ESR spectroscopy is the most sophisticated way to investigate the quality of the food and the free radicals induced during the processing of the food. ESR spin trapping technique is useful for the detection of highly unstable radicals in the food. The antioxidant capability of liquid food and beverages in mainly performed by spin trapping technique.
Unlocking the mysteries of reproduction: Exploring fecundity and gonadosomati...AbdullaAlAsif1
The pygmy halfbeak Dermogenys colletei, is known for its viviparous nature, this presents an intriguing case of relatively low fecundity, raising questions about potential compensatory reproductive strategies employed by this species. Our study delves into the examination of fecundity and the Gonadosomatic Index (GSI) in the Pygmy Halfbeak, D. colletei (Meisner, 2001), an intriguing viviparous fish indigenous to Sarawak, Borneo. We hypothesize that the Pygmy halfbeak, D. colletei, may exhibit unique reproductive adaptations to offset its low fecundity, thus enhancing its survival and fitness. To address this, we conducted a comprehensive study utilizing 28 mature female specimens of D. colletei, carefully measuring fecundity and GSI to shed light on the reproductive adaptations of this species. Our findings reveal that D. colletei indeed exhibits low fecundity, with a mean of 16.76 ± 2.01, and a mean GSI of 12.83 ± 1.27, providing crucial insights into the reproductive mechanisms at play in this species. These results underscore the existence of unique reproductive strategies in D. colletei, enabling its adaptation and persistence in Borneo's diverse aquatic ecosystems, and call for further ecological research to elucidate these mechanisms. This study lends to a better understanding of viviparous fish in Borneo and contributes to the broader field of aquatic ecology, enhancing our knowledge of species adaptations to unique ecological challenges.
The debris of the ‘last major merger’ is dynamically youngSérgio Sacani
The Milky Way’s (MW) inner stellar halo contains an [Fe/H]-rich component with highly eccentric orbits, often referred to as the
‘last major merger.’ Hypotheses for the origin of this component include Gaia-Sausage/Enceladus (GSE), where the progenitor
collided with the MW proto-disc 8–11 Gyr ago, and the Virgo Radial Merger (VRM), where the progenitor collided with the
MW disc within the last 3 Gyr. These two scenarios make different predictions about observable structure in local phase space,
because the morphology of debris depends on how long it has had to phase mix. The recently identified phase-space folds in Gaia
DR3 have positive caustic velocities, making them fundamentally different than the phase-mixed chevrons found in simulations
at late times. Roughly 20 per cent of the stars in the prograde local stellar halo are associated with the observed caustics. Based
on a simple phase-mixing model, the observed number of caustics are consistent with a merger that occurred 1–2 Gyr ago.
We also compare the observed phase-space distribution to FIRE-2 Latte simulations of GSE-like mergers, using a quantitative
measurement of phase mixing (2D causticality). The observed local phase-space distribution best matches the simulated data
1–2 Gyr after collision, and certainly not later than 3 Gyr. This is further evidence that the progenitor of the ‘last major merger’
did not collide with the MW proto-disc at early times, as is thought for the GSE, but instead collided with the MW disc within
the last few Gyr, consistent with the body of work surrounding the VRM.
ESPP presentation to EU Waste Water Network, 4th June 2024 “EU policies driving nutrient removal and recycling
and the revised UWWTD (Urban Waste Water Treatment Directive)”
When I was asked to give a companion lecture in support of ‘The Philosophy of Science’ (https://shorturl.at/4pUXz) I decided not to walk through the detail of the many methodologies in order of use. Instead, I chose to employ a long standing, and ongoing, scientific development as an exemplar. And so, I chose the ever evolving story of Thermodynamics as a scientific investigation at its best.
Conducted over a period of >200 years, Thermodynamics R&D, and application, benefitted from the highest levels of professionalism, collaboration, and technical thoroughness. New layers of application, methodology, and practice were made possible by the progressive advance of technology. In turn, this has seen measurement and modelling accuracy continually improved at a micro and macro level.
Perhaps most importantly, Thermodynamics rapidly became a primary tool in the advance of applied science/engineering/technology, spanning micro-tech, to aerospace and cosmology. I can think of no better a story to illustrate the breadth of scientific methodologies and applications at their best.
Current Ms word generated power point presentation covers major details about the micronuclei test. It's significance and assays to conduct it. It is used to detect the micronuclei formation inside the cells of nearly every multicellular organism. It's formation takes place during chromosomal sepration at metaphase.
The ability to recreate computational results with minimal effort and actionable metrics provides a solid foundation for scientific research and software development. When people can replicate an analysis at the touch of a button using open-source software, open data, and methods to assess and compare proposals, it significantly eases verification of results, engagement with a diverse range of contributors, and progress. However, we have yet to fully achieve this; there are still many sociotechnical frictions.
Inspired by David Donoho's vision, this talk aims to revisit the three crucial pillars of frictionless reproducibility (data sharing, code sharing, and competitive challenges) with the perspective of deep software variability.
Our observation is that multiple layers — hardware, operating systems, third-party libraries, software versions, input data, compile-time options, and parameters — are subject to variability that exacerbates frictions but is also essential for achieving robust, generalizable results and fostering innovation. I will first review the literature, providing evidence of how the complex variability interactions across these layers affect qualitative and quantitative software properties, thereby complicating the reproduction and replication of scientific studies in various fields.
I will then present some software engineering and AI techniques that can support the strategic exploration of variability spaces. These include the use of abstractions and models (e.g., feature models), sampling strategies (e.g., uniform, random), cost-effective measurements (e.g., incremental build of software configurations), and dimensionality reduction methods (e.g., transfer learning, feature selection, software debloating).
I will finally argue that deep variability is both the problem and solution of frictionless reproducibility, calling the software science community to develop new methods and tools to manage variability and foster reproducibility in software systems.
Exposé invité Journées Nationales du GDR GPL 2024
The binding of cosmological structures by massless topological defectsSérgio Sacani
Assuming spherical symmetry and weak field, it is shown that if one solves the Poisson equation or the Einstein field
equations sourced by a topological defect, i.e. a singularity of a very specific form, the result is a localized gravitational
field capable of driving flat rotation (i.e. Keplerian circular orbits at a constant speed for all radii) of test masses on a thin
spherical shell without any underlying mass. Moreover, a large-scale structure which exploits this solution by assembling
concentrically a number of such topological defects can establish a flat stellar or galactic rotation curve, and can also deflect
light in the same manner as an equipotential (isothermal) sphere. Thus, the need for dark matter or modified gravity theory is
mitigated, at least in part.
The binding of cosmological structures by massless topological defects
PRION DISEASES; HOW SAFE ARE WE IN AFRICA?
1. PRION DISEASES:
HOW SAFE ARE WE
IN AFRICA?
P L A T E A U S T A T E U N I V E R S I T Y ,
B O K K O S
F A C U L T Y O F N A T U R A L A N D
A P P L I E D S C I E N C E S
D E P A R T M E N T O F B I O C H E M I S T R Y
BENSON, MATTHEW LASSA
PLASU/2013/FNS/0025
2. PRION DISEASES: HOW SAFE ARE WE IN AFRICA?
BY
BENSON MATTHEW LASSA
PLASU/2013/FNS/0025
SUBMITTED TO THE DEPARTMENT OF BIOCHEMISTRY
SCHOOL OF NATURAL AND APPLIED SCIENCES,
PLATEAU STATE UNIVERSITY, BOKKOS
BOKKOS, PLATEAU STATE
IN PARTIAL FULFILMENT FOR THE AWARD OF
BACHELOR OF SCIENCE (B.Sc.) IN BIOCHEMISTRY
MAY, 2017
3. CERTIFICATION
BENSON MATTHEW LASSA, an undergraduate student with Matriculation Number
PLASU/FNS/0025 in the Department of Biochemistry has satisfactorily completed the seminar
in biochemistry literature review under the supervision of Prof. MATHEW C. OKAFOR.
___________________ ____________________
Prof. M. C. OKAFOR DR. F. O. OKONKWO
(Supervisor) (Head of Department)
4. DEDICATION
This tedious work is dedicated to God Almighty for the grace to attempt making a great review
of literature.
5. ACKNOWLEDGEMENT
I genuinely appreciate my parents, Mr. & Mrs. Benson Lassa, for their persisting patience, love
and financial support. My sincere gratitude to the friends who became family: Sheku, RS
Michael, CN and Tungon, RI for helping me source for journals and for being of help always. I
also appreciate my brothers for the tough time they gave which pushed me to work harder, Joel
and Destiny.
My sincere gratitude goes to my supervisor Prof. Mathew C.O. whose meticulous guidance and
direction has seen me thus far.
My gratitude also goes to all lecturers and members of staff of the Biochemistry department,
Plateau State University, Bokkos.
6. TABLE OF CONTENT
Title Page -------------------------------------------------------------------------------------------------------i
Certification ---------------------------------------------------------------------------------------------------ii
Dedication ----------------------------------------------------------------------------------------------------iii
Acknowledgement -------------------------------------------------------------------------------------------iv
Table of Content ----------------------------------------------------------------------------------------------v
Abstract -------------------------------------------------------------------------------------------------------vii
Abbreviation ------------------------------------------------------------------------------------------------viii
CHAPTER ONE
1.0 Introduction -----------------------------------------------------------------------------------------------1
CHAPTER TWO
2.0 Review of Related Literature----------------------------------------------------------------------------3
2.1 Introduction -----------------------------------------------------------------------------------------------3
2.2 Human prion diseases------------------------------------------------------------------------------------3
2.2.1 Creutzfeldt-Jakob disease (CJD) ---------------------------------------------------------------------3
2.2.2 Sporadic CJD -------------------------------------------------------------------------------------------4
2.2.3 Familial CJD --------------------------------------------------------------------------------------------5
2.2.4 Iatrogenic CJD -----------------------------------------------------------------------------------------6
2.2.5 Variant CJD ---------------------------------------------------------------------------------------------7
7. 2.2.6 Kuru -----------------------------------------------------------------------------------------------------7
2.2.7 Gertsmann-straussler-scheinker syndrome (GSS) -------------------------------------------------8
2.3 Animal prion diseases -----------------------------------------------------------------------------------8
2.3.1 Scrapie of sheep ----------------------------------------------------------------------------------------8
2.3.2 Transmissible mink encephalopathy (TME) -------------------------------------------------------9
2.3.3 Chronic wasting disease of cervids ----------------------------------------------------------------10
2.3.4 Bovine spongiform encephalopathy ---------------------------------------------------------------10
2.4 Risk assessment -----------------------------------------------------------------------------------------11
2.5 Natural transmission -----------------------------------------------------------------------------------11
2.6 Species barriers -----------------------------------------------------------------------------------------12
2.7 The concept of prion strains ---------------------------------------------------------------------------13
2.8 Molecular Mechanisms of Prion Disease Pathogenesis -------------------------------------------14
CHAPTER THREE
3.0 Conclusion -----------------------------------------------------------------------------------------------15
References ----------------------------------------------------------------------------------------------------16
8. ABSTRACT
Prion diseases are transmissible, progressive and invariably fatal neurodegenerative
conditions affecting animals and humans alike associated with misfolding and aggregation of
a host-encoded cellular prion protein, PrPC. Human prion diseases include Creutzfeldt–Jakob
desease (CJD), Gerstmann-Straussler–Scheinker disease (GSS), Kuru, and fatal familial
insomnia (FFI). These diseases are caused by transmissible particles that contain a
pathogenic isoform of the prion protein, a normal constituent of cell membranes. They may be
sporadic, infectious, or inherited in origin. Sporadic human prion diseases include
Cruetzfeldt-Jacob disease (CJD), fatal insomnia and variably proteasesensitive prionopathy.
Genetic or familial prion diseases are caused by autosomal dominantly inherited mutations in
the gene encoding for PrPC and include familial or genetic CJD, fatal familial insomnia and
Gerstmann-Sträussler-Scheinker syndrome. Acquired human prion diseases account for only
5% of cases of human prion disease. They include kuru, iatrogenic CJD and a new variant
form of CJD that was transmitted to humans from affected cattle via meat consumption
especially brain.
9. ABBREVIATIONS
BSE - Bovine Spongiform Encephalopathy
CJD - Creutzfeldt-Jakob Disease
CNS – Central Nervous System
CSF – Cerebrospinal Fluid
CWD – Chronic wasting disease
DNA – Deoxyribonucleic Acid
fCJD – Familial CJD
FFI - Fatal Familial Insomnia
FSE – Feline Spongiform Encephalopathy
GSS - Gerstmann-Stra¨ussler-Scheinker syndrome
iCJD – Iatrogenic CJD
MBM – Meat and Bone meal
MRI – Magnetic Resonance Imaging
nvCJD – New Variant CJD
Prion – Proteinous Infections
PRNP – Prion Protein Gene
PrP – Prion Protein
PrPSc – Scrapie Prion Protein
RNA – Ribonucleic Acid
sCJD – Sporadic CJD
10. TME – Transmissible Mink Encephalopathy
TSE - Transmissible Spongiform Encephalopathy
UK – United Kingdom
USA – United States of America
vCJD – Variant CJD
11. CHAPTER ONE
1.0 INTRODUCTION
Prion diseases are a group of progressive neurodegenerative conditions (Rudd et al., 1999).
These illnesses exist in both animals and humans. Prion diseases, also called transmissible
spongiform encephalopathies (TSEs), lead to neurological dysfunction in animals and are fatal
(Lee, Kim, Hwang, Ju, & Woo, 2013). These diseases are fatal neurodegenerative disorders that
include scrapie in sheep and goats, bovine spongiform encephalopathy (BSE) in cattle, chronic
wasting disease (CWD) in deer and elk, and feline spongiform encephalopathy (FSE), albino
tigers, pumas, and cheetahs (Prusiner, 1997). Creutzfeldt-Jakob disease (CJD), Gerstmann-
Sträussler-Scheinker disease (GSS), fatal familial insomnia (FFI), kuru and most recently variant
CJD (vCJD) in humans (Wadsworth, Hill, Beck, & Collinge, 2003).
The word PRION, derived from ‗proteinaceous infectious particle‘; meaning that the infectious
agent consists only of protein with no nucleic acid genome. Prions are the only known example
of infectious pathogens that are devoid of nucleic acid. All other infectious agents, like bacteria,
viruses, fungi possess genomes composed of either DNA or RNA that direct the synthesis of
their progeny (Kalikiri & Sachan, 2003; Aguzzi & Weissmann, 1996; Ironside, 1998).
Abnormal forms of the prion protein (a ubiquitous protein of unknown function) cause these
neurodegenerative diseases. The disease occurs when the normal cellular prion protein undergoes
a conformational change to the abnormal form. This may occur spontaneously at an extremely
low rate or at a higher rate if there is a defect in the gene. The agent can "replicate" when the
abnormal form crosses the path of the normal, cellular prion protein and the abnormal prion
induces the normal form to adopt a similar abnormal form. Prions accumulate in the brain as an
insoluble complex of proteins called an amyloid (Prusiner, 1995; Nair & Johnson, 2011).
The interaction of prions with the normal cellular prion proteins damages the cell and leads to its
slow degeneration and death. This releases prions, which can then induce more prions on the
surface of surrounding cells, causing more degeneration and death of cells. This process of
spreading cell death accounts for the holes in the brain. The current idea is that other tissues are
not much affected because prion protein is mainly produced in nerve cells. Lymphoid cells also
have a lot of prion protein and they are important in spreading the infection to nerve cells.
However, lymphoid cells are readily replaced, whereas a process that destroys neurones, even a
slowly progressive one, will lead to disease, since nerve cells cannot normally be replaced.
12. Transmissible spongiform encephalopathies are uniformly fatal and often characterized by a long
incubation period and a multifocal neuropathologic picture of neuronal loss, spongiform
changes, and an abnormal increase in the number of astrocytes due to the destruction of nearby
neurons from CNS trauma, infection, ischemia, stroke, autoimmune responses, and
neurodegenerative disease (Huang, Prusiner & Cohen, 1996; Nair & Johnson, 2011).
13. CHAPTER TWO
2.0 REVIEW OF RELATED LITERATURE
2.1 Introduction
Creutzfeldt-Jakob disease (CJD), the most common human prion disease, is a rare form of adult
dementia; the disease was not widely recognized until the 1960s. In the past years, CJD has
become a prominent consideration in the differential diagnosis of chronic neurological diseases.
The growing interest in the disease is not caused by increasing incidence, which is estimated to
be stable at between 0·5 and 1·5 cases per million people per year. This focus on CJD and other
prion diseases stems from basic biological studies on the nature of the transmissible agents,
which have raised fundamental new questions in biochemistry and microbiology, and from the
emergence of bovine spongiform encephalopathy (BSE) in the United Kingdom. The highly
publicized spreads of BSE outside of the UK and the transmission to human beings have had
major economic and political repercussions all over the globe (Africa exclusive) (Johnson &
Gibbs, 1998).
2.2 HUMAN PRION DISEASES
Prions cause different kinds of diseases in humans as the infection can arise in different regions
of the brain. CJD is the commonest human prion disease (Gambetti et al., 2008) and the sporadic
form of CJD accounts for about 85% of cases; about 10–15% of cases are familial, 1%
iatrogenic, and variant CJD is a regional disease limited largely to the UK and France. Kuru was
the first spongiform encephalopathy of human beings to be experimentally transmitted to non-
human primates. This disease is of importance not only for historical reasons but also because of
lessons learned about modes of transmission and incubation periods associated with transmission
among human beings (Johnson, 2005).
2.2.0 Creutzfeldt-Jakob disease (CJD)
Creutzfeldt-Jakob disease (CJD) is a rare, rapidly progressive fatal central nervous system (CNS)
disorder. Two German neurologists, Hans Gerhard Creutzfeldt and Alfons Maria Jakob, first
described Creutzfeldt-Jakob disease. Some of the clinical findings described their first papers do
not match current criteria for CJD, and it is considered highly likely that at least two of the
14. patients in their initial studies were suffering from a different disorder (Obi & Nwanebu, 2008).
CJD is a very rare and incurable degenerative neurological disorder (brain disease) that is
ultimately fatal. It is the most common of the TSEs (Todd et al., 2005). Typically, onset of
symptoms occurs at about age 60. Three major categories of the disease exist. These are the
sporadic, hereditary and acquired CJDs (Obi & Nwanebu, 2008).
The prion that is believed to cause CJD exhibits at least two stable conformations. One, the
native state, is water-soluble and present in healthy cells. As at 2006, its biological function was
unknown. The other conformational state is very poorly water-soluble and readily forms protein
aggregates (Shmakov & Ghosh, 2001). The CJD prion is dangerous because it promotes
refolding of native proteins into the diseased state. Subsequently the number of misfolded protein
molecules will increase exponentially and the process will lead to a large quantity of insoluble
prions in affected cells. This mass of misfolded proteins disrupts cell functions and cause cell
death. Once the prion is transmitted, the defective proteins invade the brain and get produced in a
self-sustaining feedback loop, causing exponential spread of the prion, and the patient usually
dies within a few months although a few patients have been known to live as long as two years
(McDonnell & Burke 2003).
Although CJD is the most common prion human disease, it is still rare and only occurs about one
out of every one Million people. It usually affects people aged 45-75, most commonly appearing
in people between the ages of 60-65. The exception to this is the more recently recognized
"variant" CJD (vCJD), which occurs in younger people (Obi & Nwanebu, 2008). Some cases of
CJD are clustered in certain families, and the fact that some of these families also have an
apparently higher incidence of Alzheimer's disease has led to the supposition that the two
diseases may be related (Obi & Nwanebu, 2008).
2.2.1 Sporadic CJD
Creutzfeldt-Jakob disease consists of three main catalogues: sporadic, familial and iatrogenic
CJD. The reasons of sporadic CJD are still unclear (Prusiner, Telling, Cohen, & DeArmond,
1996). CJD was first described in the early 1920s. The predominant subtype of human prion
15. diseases, sCJD, occurs equally in both sexes with a peak age of onset between 60 and 69 years
(Gao et al., 2011; Ladogana et al., 2005). sCJD occurs all year round, with no seasonal
specificity. Typical clinical symptoms include progressive dementia, accompanied by visual and
cerebellum function abnormalities (Brown et al., 1994). sCJD, caused by the spontaneous
misfolding of prion-protein in an individual. This accounts for 85% of cases of CJD.
The disease affects men and women equally, average age at onset is 60 years, and it is rare in
people under age 40 years or over age 80 years. The initial symptoms in about a third of cases
are systemic complaints of fatigue, disordered sleep, and decreased appetite; about a third of
patients present with behavioral or cognitive changes; and the final third have focal signs such as
visual loss, cerebellar ataxia, aphasia, or motor deficits. The disease progresses rapidly with
prominent cognitive decline and the development of myoclonus, particularly startlesensitive
myoclonus. The median time to death from onset is only 5 months, and 90% of patients with
sporadic CJD are dead within 1year (Johnson et al., 1998; Brown et al., 1994).
Characteristic patterns on MRI, the synchronized biphasic or triphasic sharp-wave complexes on
the electroencephalogram, and the finding of 14-3-3 protein in CSF all support the diagnosis of
CJD (Tschampa et al., 2005; Steinhoff et al., 2005), but none are 100% sensitive or specific.
MRI and electroencephalogram changes are commonly found only with repeated examination,
and 14-3-3, a normal neural protein released with rapid neuronal loss, is present in CSF after
strokes or during encephalitis. The pathological findings in CJD are limited to the brain and
spinal cord. There is neuronal loss, and vacuolization within cell bodies and dendrites that gives
a spongiform appearance to the cortex and deep nuclei. The pathogenic isoform of prion protein
can be demonstrated in brain by immunocytochemical staining and by western-blot analysis.
The mode of infection is unknown. Exposure to people with the illness, even the intimate
exposure of years of marriage, does not seem to increase the risk, and there has been only one
documented conjugal case pair (Brown et al., 1998).
2.2.2 Familial CJD
Familial CJD, (fCJD), caused by an inherited mutation in the prion-protein gene (Budka & Will,
2015). This accounts for the majority of the other 15% of cases of CJD. Familial CJD cases show
autosomal dominant inheritance of mutations in PRNP. Over 50 different mutations in PRNP
16. have been found in kindred with familial CJD; but four point mutations—at codons 102, 178,
200, and 210—and insertions of five or six octapeptide repeats account for 95% of the familial
cases (Capellari et al., 2005). In addition, a polymorphism (difference) at codon 129 leads to the
protein containing either methionine or valine. This polymorphism influences susceptibility to or
phenotype of CJD (Palmer & Dryden, 1991). For example, over 80% of patients with sporadic
CJD are homozygous at this site compared with 49% of healthy controls (Palmer & Dryden,
1991; Mastrianni, 2005).
In general, familial CJD has earlier age of onset and longer clinical course than sporadic CJD.
The commonest familial form of CJD results from mutation at codon 200, and the phenotype in
patients with this mutation resembles that of sporadic CJD (Mastrianni, 2005). Several other
mutations result in a phenotype sufficiently different from sporadic CJD that distinct names have
been used.
2.2.3 Iatrogenic CJD
Iatrogenic CJD is caused by contamination with tissue from an infected person, usually as the
result of a medical procedure. Medical procedures that are associated with the spread of this form
of CJD include blood transfusion from the infected person, use of human-derived pituitary
growth hormones, gonadotropin hormone therapy, and corneal and meningeal transplants (Budka
& Will, 2015). Sizeable outbreaks of iatrogenic CJD have occurred after distribution of
contaminated dural graft material and human growth hormone. Since 1985, over 100 cases of
CJD have occurred 16 months to 18 years after surgical use of human cadaveric dura mater
(Brown et al., 2000). Over 8000 children and adolescents in the USA had received this
preparation. The product was withdrawn in most countries, and a recombinant human growth
hormone was quickly licensed. Since then, however, over 130 young adults have developed CJD
5–30 years after discontinuing injections (Brown et al., 2000). The long incubation period after
growth hormone injections presumably reflects the peripheral route of inoculation in contrast to
intracerebral placement of contaminated dura mater. In both situations, homozygosity at codon
129 seems to increase susceptibility to iatrogenic disease (Brown et al., 2000).
17. 2.2.4 Variant CJD
In 1994, a new form of human spongiform encephalopathy emerged in the UK. Over the past
decade, the CJD Surveillance Unit in Edinburgh has reported 150 cases of a new variant of CJD
in the UK (Johnson, 2005). Patients have a course and pathology distinctive from other forms of
CJD: young age at onset, prominence of psychiatric and sensory symptoms, and long disease
course. Neuropathological examination shows widespread vacuolisation with many plaques of
abnormal prion protein. All cases tested have been homozygous at codon 129 for methionine
(Will et al., 2000; Peden & Ironside, 2004). Nine cases have been reported in France and there
have been isolated cases in several other countries.
Although the numbers in the UK seem to have subsided since 2000 (Andrews et al., 2003),
concern persists whether the polymorphism at 129 represents a susceptibility determinant to
infection or a determinant of the incubation period; in the latter case a future second wave of
disease would be expected.
The prions from the variant disease seem to be of common origin: they have similar localization
and incubation periods in strains of inbred mice and similar western blot patterns. Prions from
patients with variant CJD share these signatures with those from cattle with BSE, indicating that
they have a common source (Bruce et al.,1997). Cattle were likely infected by feed and people
were probably infected by the consumption of beef. Although this route is probably true, human
beings, like cattle, are exposed directly to products of the rendering industry (Johnson, 2005).
The derived tallow is used in cosmetics that could lead to conjunctival or mucous membrane
exposure, in soap that can come into contact with skin abrasions, and in gelatin that can lead to
oral exposure. Furthermore, bone meal produced by rendering is a component of gardening
products, such as dusting powder for roses, which could lead to olfactory exposure.
2.2.5 Kuru
This disease appeared in the earlier part of the 20th
Century among members of the "Fore" tribe,
in the Eastern Highlands of Papua New Guinea, to the east of the Pacific Ocean. The name
"Kuru" is the local name used by fore people to describe the condition. It means "laughing death"
in their language because it is accompanied by uncontrollable laughter.
Kuru is an invariably fatal disease, and like other TSEs it affects both mental and motor
functions. Its incubation period ranges between 2-40 years, but is usually several years long.
18. However, the clinical course of the disease is relatively short - the patient dies within 3 months to
one year, at the most, after the appearance of symptoms. The symptoms include: in coordination
of movement, stumbling, muscle tremors, difficulty in articulating words, involuntary oscillation
of the eyes (nystagmus), difficulty to swallow, inability to hold things and finally dementia and
death. The disease was associated with cannibalism (eating the brain of dead humans) and spread
between members of the tribe, affecting more women and children than male adults. It is
generally believed that Kuru is now extinct (Nair & Johnson, 2011).
2.2.6 Gertsmann-straussler-scheinker syndrome (GSS)
GSS is a very rare, usually familial, fatal neurodegenerative disease that affects patients from 20-
60 years of age (Prusiner, 1995). This prion disease is caused by the inheritance of a PRNP gene
with a mutation encoding most commonly, leucine instead of proline at position 102 (P102L) or
valine instead of alanine at position 117 (A117V). The disease is strongly associated with
homozygosity for a polymorphism at position 129 (both residues being Methionine). Brain
extracts from patients with GSS can transmit the disease to Monkeys, apes and transgenic mice
containing a portion of the human PRNP gene. Transgenic mice expressing the P102L gene
develop the disease spontaneously (Prusiner, 1997).
GSS occurs typically in the 4th-5th decade, characterized by cerebella ataxia and concomitant
motor. Problems, dementia less common and disease course lasts several years to death. It was
originally thought to be familial, but it is now known to occur sporadically as well (Heaphy,
1998; Obi & Nwanebu, 2008).
2.3 ANIMAL PRION DISEASES
2.3.0 Scrapie of sheep
Scrapie the first TSE to be studied was described in sheep and goats in the 18th century,
precisely in 1732. However it is still found in most parts of the world despite attempts to
eradicate the agent by destroying the infected flock (Prusiner, 1997; Schwartz, 2004). Scrapie is
a fatal, degenerative disease that affects the nervous system of sheep and goats. It is one of
several transmissible spongiform encephalopathies, which are related to bovine spongiform
encephalopathies (BSE) and chronic wasting disease (CWD) of deer and elk. Like other TSEs,
19. scrapie is also caused by prions (Gee, 1996). The name scrapie was derived from one of the
symptoms of the condition, wherein affected animals will compulsively scrape off their fleece
aganist rocks, trees or fences. The disease apparently causes an itching sensation in the animals.
Other symptoms include excessive lip smacking, strange gait and convulsive collapse
(Weissmann, 2004; Johnson, 2005).
Scrapie is infectious and transmissible among similar animals in feed contaminated with nerve
tissue and so one of the most common ways to the disease (since it is incurable) is to quarantine
and destroy those affected. However it tends to persist in flock and can also arise apparently
spontaneously in flocks that have not previously had cases of the disease. The mechanism of
transmission between animals and other aspects of the biology of the disease are only poorly
understood. Recent studies suggest that scrapie agents. Suggest that scrapie agents may be spread
through urine and persist in the environment for decades (Obi & Nwanebu, 2008). Scrapie
agent, in the form of extracts from infected brains, has been passed experimentally to mice,
hamster, ferrets, mink, and monkeys, but apparently is not infectious for humans, chimpanzees
or rabbits (Obi & Nwanebu, 2008). Vertical transmission may occur, but exposure of young
lambs to infected flocks seems to be the major risk factor. The infection crosses species barriers
to goats that share pastures with affected sheep, but no evidence implicates natural spread to
other livestock or to people. The disease has been experimentally transmitted to primates,
rodents, and other species (Johnson, 2005).
2.3.1 Transmissible mink encephalopathy (TME)
Transmissible mink encephalopathy is a rare disease of ranch-raised mink that is caused by
exposure to a scrapie-like agent in feed (prion). Transmission of TME to hamsters resulted in the
identification of two clinically different syndromes, HYPER and DROWSY. Differences in the
physicochemical properties of PrP from these two strains suggests that PrP plays an important
role in defining strains (McKenzie, Bartz & Marsh, 1996)
20. 2.3.2 Chronic wasting disease of cervids
Chronic wasting disease (CWD) is a unique transmissible spongiform encephalopathy (TSE) of
mule deer (Odocoileus hemionus), white-tailed deer (O. virginianus), and Rocky Mountain elk
(Cervus elaphus nelsoni). The natural history of CWD is incompletely understood, but it differs
from scrapie and bovine spongiform encephalopathy (BSE) by virtue of its occurrence in
nondomestic and free-ranging species. CWD has many features in common with scrapie
(Williams, 2005). Chronic wasting disease of deer (cervids) was first found in the 1960s among
captive mule deer in a wildlife research facility in Colorado, USA. The clinical disease occurred
in deer 2·5–4·0 years after entering the facility as fawns or young adults. Animals became
emaciated, and developed behavioural changes, unsteadiness, and excessive salivation. Death
occurred within weeks to months, and pathological examination of brains showed widespread
spongiform changes in grey matter. Elk in contact with mule deer developed the disease, and the
disease was experimentally transmitted to various species, including limited evidence of
transmission to squirrel monkeys and cows (Johnson, 2005).
2.3.3 Bovine spongiform encephalopathy
There are several theories regarding the cause of the first reported case of BSE in the mid-1980s;
some insist that the BSE pathogen (PrPSc) formed naturally and others claim that the disease
was caused by the cow feed made from sheep infected with scrapie. By an extensive
epidemiologic investigation, the main cause for BSE turned out to be a meat and bone meal
(MBM) made from the discarded bones and intestines of slaughtered cows and sheep (Lee, Kim,
Hwang, Ju & Woo, 2013).
In 1985, the first cases of BSE were observed in the UK; in the next decade a massive epidemic
throughout the country led to infection of about 1 million cows (Johnson, 2005).
In the UK, in particular, cow intestines have been used in MBM as a protein supplement since
1972, which accelerated the increase of the occurrence of BSE (Lee, Kim, Hwang, Ju & Woo,
2013) Export of cattle and feed spread the disease to Europe and to scattered countries around
the world. This was apparently an extended common source outbreak, and the source was
evidently the contamination of meat-and bone meal fed to young calves. The initial hypothesis
assumed that scrapie in infected sheep carcasses rendered into bone meal crossed a species
barrier causing infection in calves and disease in cows age 4–5 years. Subsequent rendering of
21. cattle carcasses fuelled the epidemic. An alternative hypothesis is that a sporadic case of BSE in
a cow could have initiated the epidemic.
Hundreds of thousands of infected animals have been eaten by Europeans and particularly the
British over the past years. Research work suggests that the infected meat may pose a threat to
human health, but the significance of that threat may not become apparent for years. The US
Department of Agriculture claims that BSE has not been identified in any US cattle so far12,
hence it is generally considered a British problem (Kalikiri & Sachan, 2003).
2.4 Risk Assessment
Prion diseases in both animals and humans show great remarkable similarities. They have long
incubation periods; present as progressive fatal neurological diseases with motor, sensory, and
cognitive deficits; cause similar spongiform pathology limited to the CNS; result from
misfolding of a normal membrane glycoprotein; and evoke no immune response due to the fact
that the body recognizes the prion protein as a part of the body component and not a foreign
body (antigen). Despite these shared features predicting risk of acquisition or spread of disease is
complicated by the striking differences in mode and ease of transmission, unpredictable species
barriers, differing distribution of the agent in the body, and strain variations.
2.5 Natural Transmission
Both infectious and genetic transmission can occur in nature. Food-chain infection is paramount
for Kuru, transmissible mink encephalopathy, and BSE. In contrast, these three diseases do not
seem to spread easily in the field, unlike scrapie and chronic wasting disease, although some
horizontal transmission or intrauterine infection of BSE might have occurred but remained
hidden by the food-borne epidemic. Genetic transmission has been documented only with
familial CJD; genetic transmission in animals has not been observed. Vertical transmission with
intrauterine infection has also not been definitely established with any prion disease.
22. Table 1: The Prion diseases (Prusiner, Scott, DeArmond, & Cohen, 1998)
NATURAL TRANSMISSION OF PRION DISEASES
DISEASE MODE OF TRANSMISSION
Scrapie Exposure of lambs to infected sheep
CWD Pasture contamination
Kuru Endocannibalism
BSE Meat-and-bone meal fed to calves
TME Feed and possibly cannibalism
Vcjd Probable consumption of infected cattle
fCJD Mutations in PRNP
sCJD Unknown
GSS Inheritance of a PRNP gene with a mutation
Sporadic CJD remains the oddity in which evidence does not implicate either lateral or genetic
transmission. Judging from the spread of other prion diseases transmission from zoonotic
diseases or other affected humans would seem plausible. The lack of data incriminating contact
transmission has led to the speculation of endogenous generation of prion proteins—reminiscent
of ―spontaneous generation‖.
2.6 Species Barriers
It has been known for many years that transmission of prion strains between species is restricted
by a ―species barrier‖. This is demonstrated by an increase in incubation period, and a decrease
in the percentage of animals succumbing to disease, when prions from one species are inoculated
into another (―first passage‖). This contrasts with the situation when prions are inoculated into
animals of the same species, when these animals are seen to all become sick, with remarkably
consistent incubation periods. If after inoculation into a different species infectious tissue is
taken from the animals that do become sick and transmitted to further animals (―second
passage‖), the pattern of infectivity seen resembles that of the initial species, with most if not all
animals becoming sick after relatively short and consistent incubation periods. This transmission
barrier between species can be quantified by the difference in incubation period and rate of
infection between first and second passages (McKintosh, Tabrizi & Collinge, 2003).
23. Transmission to another species, however, may generate species-specific prions that can no
longer be transmitted to the original species or that can facilitate spread. For example, human
Kuru and CJD brain tissue do not transmit disease to goats or ferrets, but if transmitted to
primates or cats the primate or cat tissue will transmit to goats and ferrets. There are many
examples of this patchwork pattern of species barriers (Brown, Will, Bradley, Asher & Detwiler,
2001).
Some species seem protected whereas others—such as mice, hamsters, and primates—have been
susceptible experimental hosts to various prion diseases of other species. In the UK, the public
was reassured that BSE would not spread to people; an assumption based on hundreds of years of
eating scrapie-infected mutton with no evidence of gastrointestinal transmission of this ruminant
disease across the species barrier to humans. However, BSE did cross a similar species barrier
(Johnson, 2005).
2.7 The concept of prion strains
Prion strains are defined as infectious isolates exhibiting distinct incubation times and prion
disease phenotype in the same host. Strains cannot be encoded by differences in the primary
structure of PrP (Collinge & Clarke, 2007; Kovacs, & Budka, 2009).
In conventional pathogens strains are distinguished by differences in their nucleic acid genome.
In contrast in prion disease, this is most likely related to different conformational states of PrP
that includes also differential proteinase K digestion kinetics. Three principal PrP glycoforms are
associated with prion strains; both PrPC and PrPSc exists in three main glycosylation states:
mono-, di and unglycosylated forms (Parchi et al., 1999). These are widely used as molecular
indicators of prion strain typing. To support the notion of strains and also the ‗protein-only‘
hypothesis, so called synthetic prion strains have been developed and described (Legname et al.,
2004). The question arises whether these are in fact infectious prions or are simply capable of
seeding prion protein production in hosts that have high levels of PrPC and are close to develop a
spontaneous disease. In humans the polymorphism at residue 129 constrains which prion strains
may propagate, although the exact mode needs clarification. Diversity of prion strains has been
demonstrated in several mammals and has been discussed also in relation with the species barrier
(Aguzzi, Heikenwalder, & Polymenidou, 2007). The latter means that prions isolated from one
species may be less infectious to other species.
24. That such isolates could be propagated through multiple passages in mice suggested that the
scrapie pathogen has a nucleic acid genome that is copied and passed on to nascent prions. But
no evidence for scrapie-specific nucleic acid encoding information that specifies the incubation
time and the distribution of neuropathological lesions has emerged from considerable efforts
with a variety of experimental approaches as described above. In striking contrast, mice
expressing PrP transgenes have demonstrated that the level of PrP expression is inversely related
to the incubation time. Furthermore, the distribution of CNS vacuolation and attendant gliosis are
a consequence of a pattern of PrPSc deposition that can be altered by both PrP genes and non-
PrP genes. These observations taken together begin to build an argument for PrPSc as the
information molecule in which prion strain-specific information is encrypted. Deciphering the
mechanism by which PrPSc carries information for prion diversity and passes it on to the nascent
prions is a challenging goal. Whether PrPSc can adopt multiple conformations, each of which
produces prions exhibiting distinct incubation times and patterns of PrPSc deposition, remains to
be determined (DeArmond & Prusiner, 1995).
2.8 Molecular Mechanisms of Prion Disease Pathogenesis
The intracellular accumulation of PrPSc seems to be responsible for the pathogenesis of prion
diseases. Although extracellular deposits of PrPSc are seen as PrP amyloid plaques, they are not
an obligatory feature of the disease. The precise subcellular sites of PrPSc accumulation in brain
are not well defined. Presumably, PrPSc is deposited in neurons, and evidence exists for the
transport of both PrPc and PrPSc along axons. In scrapie-infected cultured cells, PrPSc is found
primarily in secondary lysosomes (Aguzzi, & Heikenwalder, 2006), and some investigators have
suggested that similar sites of PrPSc deposition occur in brain, but the data are less convincing.
The lack of conformation dependent PrPSc-specific antibodies has hampered such studies. The
first link between PrP and the neuropathology of prion diseases came during the characterization
of brain fractions highly enriched for scrapie infectivity.
Such fractions were found to contain one protein, PrP 27-30, and rod-shaped particles that
proved to be indistinguishable from amyloids on the basis of ultrastructural and tinctorial criteria.
This finding was extended to the brains of rodents with a-PrP antiserum, which stained amyloid
plaques. Such findings were initially greeted with great skepticism as amyloids are composed of
proteins found in animals and not of viral proteins (DeArmond, & Prusiner, 1995).
25. CHAPTER THREE
3.0 CONCLUSION
Statistics observed from related literature has proven that prion related diseases are either not
observed or recorded in Africa as in many parts of the world; Kuru, seems to be the only prion
related disease associated with the black continent. Of late, research has suggested that
epidemics of human TSEs may have occurred for thousands of years (McKintosh, Tabrizi, &
Collinge, 2003). Despite these statistics, it is the potential threat of an epidemic of nvCJD in the
UK population that has provided an increased momentum to try to understand these refreshingly
new and dynamic diseases. Animal TSEs are now recognized to occur across all countries,
African countries inclusive (with the exception of Australia and New Zealand), and to occur not
only as scrapie in sheep, but as transmissible mink encephalopathy, BSE in cows, FSE in
domestic cats, and zoo animals, and as chronic wasting disease in American deer and elk herds.
Infectious diseases are not known for their tendency to respect national borders; BSE has already
spread through many European countries and vCJD may therefore still do so. The past few years
have seen major increases in our understanding of the etiology and pathology of prion diseases
but large research challenges still remain, if a major epidemic of vCJD is to be avoided and
suitable treatments are to be found. Not least among these are proof of the exact nature of this
novel infectious agent, further elaboration of the role of PrPc, and the development of reliable
therapeutics. For Africa to stay secured against the fatal neurodegenerative disease, all countries
in the continent most be very careful on importation and consumption of meat of cows, sheep
goats, deer, etc. from other countries especially European countries. Care must be taken on using
MBM to feed other animals and Prion, prion disease and prion associated research laboratories
should be setup to continually investigate this misfolded protein mishap.
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