This study found that OLM interneurons in the hippocampus differentially modulate inputs to CA1 neurons from the CA3 region versus the entorhinal cortex. The study identified CHRNA2 as a precise molecular marker for OLM cells. Using transgenic mice and optogenetic tools, the study showed that OLM cells facilitate transmission of intrahippocampal information from CA3 while reducing influence from extrahippocampal entorhinal cortex inputs. The study also found that OLM cells receive direct cholinergic inputs from the medial septum and diagonal band of Broca and are important for gating information flow and synaptic plasticity in CA1.
This document summarizes key concepts about cell membranes and signaling. It discusses how cell membranes act as selective barriers and enclose intracellular compartments. The lipid bilayer structure is described, including how phospholipids can move within the bilayer. Various types of membrane proteins are also outlined, highlighting their functions in transport, structure, and signaling. Different classes of cell surface receptors are introduced, along with general principles of intracellular signaling cascades and their roles in cellular responses. Specific G-protein coupled receptor signaling pathways mediated by cyclic AMP and calcium are then examined in more detail.
This study shows that metformin promotes neurogenesis and enhances spatial memory formation by activating an atypical protein kinase C (aPKC)-CREB binding protein (CBP) pathway. Specifically:
1) The aPKC-CBP pathway is essential for normal neuron genesis from neural precursors.
2) Metformin activates this aPKC-CBP pathway to promote rodent and human neurogenesis in culture.
3) Metformin also enhances neurogenesis in the adult mouse brain in a CBP-dependent manner and improves spatial reversal learning in mice.
Therefore, metformin represents a potential pharmacological approach for recruiting neural stem cells in the adult brain, which could have therapeutic value
Snapin deficiency causes abnormal accumulation of BACE1 and APP at synapses, increasing amyloid beta generation. The study found that deletion of the adaptor protein snapin, which mediates retrograde transport of late endosomes, results in defective transport of late endosomes containing BACE1 from synapses to lysosomes for degradation. This leads to accumulation of BACE1 and APP at nerve terminals, enhancing amyloidogenic processing and amyloid beta production at synapses. The results indicate that snapin-mediated retrograde transport is important for regulating synaptic trafficking of BACE1 and its cleavage of APP.
This document provides an introduction to neurophysiology. It discusses the classification of the nervous system into the central nervous system (CNS) and peripheral nervous system. Within the CNS, it is classified into grey matter and white matter. The basic structural and functional unit of the nervous system, the neuron, is described in detail. The structure and function of the synapse is also explained. Different types of neurons are classified. The composition of the nervous system includes neurons and supporting neuroglia cells. Various receptors and sensory systems are outlined. Important neurotransmitters are identified.
1) The active zone is composed of an evolutionarily conserved protein complex containing RIM, Munc13, RIM-BP, α-liprin, and ELKS proteins as core constituents. This complex docks and primes synaptic vesicles for exocytosis.
2) In addition to transmitting information, synapses transform information encoded in bursts of action potentials through short-term and long-term plasticity mediated by the active zone protein complex.
3) The five core proteins work together to recruit voltage-gated calcium channels to the active zone, position the active zone opposite postsynaptic specializations, and mediate both short-term and long-term presynaptic plasticity.
This document summarizes a study examining the role of vasoactive intestinal polypeptide (VIP) in circadian rhythmicity and synchrony in the suprachiasmatic nucleus (SCN) of mice. Mice lacking either VIP or its receptor VPAC2 exhibited multiple circadian periods in constant darkness and abnormal activity patterns in a skeleton photoperiod, indicating disrupted circadian synchronization. Recordings of SCN neuron firing patterns in these mice showed reduced rhythmic firing and loss of synchrony compared to wild-type mice. Daily application of a VPAC2 agonist restored rhythmic firing and synchrony in VIP-deficient SCN neurons. The findings suggest that VIP is required for rhythmicity in some
1. Vesicles bud off from donor membranes with v-SNAREs and are carried along microtubules by motor proteins to target membranes containing t-SNAREs.
2. Vesicle and target membrane tethering proteins bring the two close together to allow v- and t-SNAREs to associate and fuse the vesicle and target membrane.
3. Rab GTPases regulate vesicle movement and docking by cycling between active GTP-bound and inactive GDP-bound states.
Li, Lisanti, Puszkin - Purification and molecular characterization of NP185Shengwen Calvin Li, PhD
This study further characterized the neuronal protein NP185/AP3 through several experiments:
1) Microsequence analysis of purified native NP185 from bovine brain yielded five peptide fragments that matched sequences of mouse F1-20 and rat AP180 proteins.
2) Recombinant NP185/AP3 purified using genetic methods facilitated the reconstruction of clathrin cages in an established assay.
3) Deletion mutagenesis mapped the epitopes of two monoclonal antibodies that recognize bovine NP185 to a 60 amino acid region of recombinant murine NP185/AP3.
4) Recombinant NP185/AP3 was phosphorylated by purified casein kinase II in vitro.
This document summarizes key concepts about cell membranes and signaling. It discusses how cell membranes act as selective barriers and enclose intracellular compartments. The lipid bilayer structure is described, including how phospholipids can move within the bilayer. Various types of membrane proteins are also outlined, highlighting their functions in transport, structure, and signaling. Different classes of cell surface receptors are introduced, along with general principles of intracellular signaling cascades and their roles in cellular responses. Specific G-protein coupled receptor signaling pathways mediated by cyclic AMP and calcium are then examined in more detail.
This study shows that metformin promotes neurogenesis and enhances spatial memory formation by activating an atypical protein kinase C (aPKC)-CREB binding protein (CBP) pathway. Specifically:
1) The aPKC-CBP pathway is essential for normal neuron genesis from neural precursors.
2) Metformin activates this aPKC-CBP pathway to promote rodent and human neurogenesis in culture.
3) Metformin also enhances neurogenesis in the adult mouse brain in a CBP-dependent manner and improves spatial reversal learning in mice.
Therefore, metformin represents a potential pharmacological approach for recruiting neural stem cells in the adult brain, which could have therapeutic value
Snapin deficiency causes abnormal accumulation of BACE1 and APP at synapses, increasing amyloid beta generation. The study found that deletion of the adaptor protein snapin, which mediates retrograde transport of late endosomes, results in defective transport of late endosomes containing BACE1 from synapses to lysosomes for degradation. This leads to accumulation of BACE1 and APP at nerve terminals, enhancing amyloidogenic processing and amyloid beta production at synapses. The results indicate that snapin-mediated retrograde transport is important for regulating synaptic trafficking of BACE1 and its cleavage of APP.
This document provides an introduction to neurophysiology. It discusses the classification of the nervous system into the central nervous system (CNS) and peripheral nervous system. Within the CNS, it is classified into grey matter and white matter. The basic structural and functional unit of the nervous system, the neuron, is described in detail. The structure and function of the synapse is also explained. Different types of neurons are classified. The composition of the nervous system includes neurons and supporting neuroglia cells. Various receptors and sensory systems are outlined. Important neurotransmitters are identified.
1) The active zone is composed of an evolutionarily conserved protein complex containing RIM, Munc13, RIM-BP, α-liprin, and ELKS proteins as core constituents. This complex docks and primes synaptic vesicles for exocytosis.
2) In addition to transmitting information, synapses transform information encoded in bursts of action potentials through short-term and long-term plasticity mediated by the active zone protein complex.
3) The five core proteins work together to recruit voltage-gated calcium channels to the active zone, position the active zone opposite postsynaptic specializations, and mediate both short-term and long-term presynaptic plasticity.
This document summarizes a study examining the role of vasoactive intestinal polypeptide (VIP) in circadian rhythmicity and synchrony in the suprachiasmatic nucleus (SCN) of mice. Mice lacking either VIP or its receptor VPAC2 exhibited multiple circadian periods in constant darkness and abnormal activity patterns in a skeleton photoperiod, indicating disrupted circadian synchronization. Recordings of SCN neuron firing patterns in these mice showed reduced rhythmic firing and loss of synchrony compared to wild-type mice. Daily application of a VPAC2 agonist restored rhythmic firing and synchrony in VIP-deficient SCN neurons. The findings suggest that VIP is required for rhythmicity in some
1. Vesicles bud off from donor membranes with v-SNAREs and are carried along microtubules by motor proteins to target membranes containing t-SNAREs.
2. Vesicle and target membrane tethering proteins bring the two close together to allow v- and t-SNAREs to associate and fuse the vesicle and target membrane.
3. Rab GTPases regulate vesicle movement and docking by cycling between active GTP-bound and inactive GDP-bound states.
Li, Lisanti, Puszkin - Purification and molecular characterization of NP185Shengwen Calvin Li, PhD
This study further characterized the neuronal protein NP185/AP3 through several experiments:
1) Microsequence analysis of purified native NP185 from bovine brain yielded five peptide fragments that matched sequences of mouse F1-20 and rat AP180 proteins.
2) Recombinant NP185/AP3 purified using genetic methods facilitated the reconstruction of clathrin cages in an established assay.
3) Deletion mutagenesis mapped the epitopes of two monoclonal antibodies that recognize bovine NP185 to a 60 amino acid region of recombinant murine NP185/AP3.
4) Recombinant NP185/AP3 was phosphorylated by purified casein kinase II in vitro.
1) Lhx2 acts as a classic selector gene that cell-autonomously specifies cortical identity and suppresses alternative fates like the hippocampal organizer fate in the developing mouse brain.
2) Using genetic mosaics and timed inactivations in mice, the study demonstrates that Lhx2 performs this function during a critical period from E8.5-E10.5 when stem cells comprise the cortical neuroepithelium.
3) In the absence of Lhx2, cells laterally adopt an antihem identity and medially become cortical hem cells, which can induce and organize ectopic hippocampal fields, showing that the cortical hem is a hippocampal organizer.
The document discusses the genetic code, which is the language that allows genetic instructions stored in DNA to be translated into proteins. Some key points:
- The genetic code is found within messenger RNA (mRNA), which carries copies of genetic instructions from DNA to cellular structures called ribosomes.
- Ribosomes read the genetic code by recognizing linear sequences of the mRNA nucleotides adenine, uracil, cytosine, and guanine grouped into "words" of three nucleotides each.
- Experiments introducing small mutations into genes helped determine that the genetic code is organized into these three-nucleotide words, with each word specifying a single amino acid or start/stop signal.
Protein synthesis and trafficking involves two main stages - transcription and translation. Transcription occurs in the nucleus and involves copying information from DNA to mRNA. Translation occurs in the cytoplasm and involves using the mRNA code to assemble amino acids into proteins. Proteins are targeted to different locations through signal sequences and trafficking pathways. Newly synthesized proteins enter the endoplasmic reticulum and are modified and sorted in the Golgi apparatus before being targeted to their final destinations inside or outside the cell through secretory vesicles.
The document summarizes the endoplasmic reticulum (ER), an organelle found within eukaryotic cells. It was discovered in 1902 by Emilio Verrati but his work was initially disregarded. In the 1950s, Keith Porter and George Palade used electron microscopy to rediscover and prove the existence of the ER. The ER is a network of tubules and sacs that functions to produce and transport proteins and lipids. It exists in two forms: rough ER with ribosomes on its surface for protein synthesis, and smooth ER involved in lipid and steroid production. Current research explores how ER stress contributes to diseases like Alzheimer's, Parkinson's, and diabetes.
The document summarizes key aspects of protein transport within cells, including:
1) Proteins entering the endoplasmic reticulum (ER) have an N-terminal signal sequence that is recognized by signal recognition particle (SRP) to initiate translocation. Chaperone proteins such as BiP assist with proper folding within the ER lumen.
2) Transmembrane proteins maintain their orientation throughout transport, with alpha helices embedding in membranes. Multiple transmembrane proteins have multiple start and stop sequences recognized by SRP.
3) Vesicle transport between organelles is mediated by SNARE proteins on transport vesicles (v-SNAREs) and target membranes (t-SNAREs) that facilitate docking and fusion
Protein sorting and targeting involves transporting proteins to the appropriate locations within or outside the cell. There are several pathways for protein targeting, including vesicular transport between organelles like the ER and Golgi, as well as transport of proteins into organelles like mitochondria and peroxisomes. Targeting signals like presequences and internal targeting peptides direct cellular transport machinery to correctly position proteins. Lipidation is another method to target proteins to specific membranes through modifications like glycosyl phosphatidylinositol anchors or myristoylation.
This document summarizes the expression of recombinant β-lactoglobulin (rBLG) in prokaryotic and eukaryotic cells. In Escherichia coli, rBLG was expressed with a pET26 vector and was found predominantly in a denatured form, even when expressed in the periplasm. In eukaryotic cells like COS-7 and mouse tibialis muscle, rBLG was expressed in its native conformation. The authors quantified rBLG expression using immunoassays that distinguish between native and denatured rBLG. They found higher expression levels and native folding of rBLG in eukaryotic systems compared to prokaryotic expression
Protein targeting or protein sorting is the mechanism by which a cell transports to the appropriate positions in the cell or outside of it. Both in prokaryotes and eukaryotes, newly synthesized proteins must be delivered to a specific sub-cellular location or exported from the cell for correct activity. This phenomenon is called protein targeting. Protein targeting is necessary for proteins that are destined to work outside the cytoplasm.This delivery process is carried out based on information contained in the protein itself. Correct sorting is crucial for the cell; errors can lead to diseases. In 1970, Günter Blobel conducted experiments on the translocation of proteins across membranes. He was awarded the 1999 Nobel Prize for his findings. He discovered that many proteins have a signal sequence, that is, a short amino acid sequence at one end that functions like a postal code for the target organelle.
This PowerPoint is applicable for the medical, paramedical, and all the life science students who read the mechanism of gene expression. This is equally useful for teachers as well. This is the comprehensive coverage on the aforementioned topic.
I have tried to make a precise presentation on protein transport, targeting and sorting into organelle's other than nucleus. Hope this might help you. Comments are welcome.
This document summarizes protein targeting mechanisms in cells. It discusses how signal sequences direct proteins to different organelles like the endoplasmic reticulum, mitochondria, chloroplasts and nucleus. The signal sequence is cleaved after the protein reaches its destination. Glycosylation in the ER plays a key role in targeting lysosomal enzymes. Mitochondrial and chloroplast proteins use a different targeting mechanism after full synthesis. Receptor-mediated endocytosis imports some extracellular proteins by binding to receptors and forming clathrin-coated vesicles.
RNA editing is a term associated with structural changes in an RNA strand that alter its coding properties. These enzyme-catalyzed reactions include nucleotide and oligonucleotide insertions and deletions as well as base modifications. The diversity of coding strands created by these reactions contributes to the protein diversity present in cells of higher organisms. In this review, we highlight advances in our understanding of the structure, mechanism, regulation, and biological functions of the ADAR enzymes published in the last five years. The ADARs (adenosine deaminases that act on RNA) are multidomain enzymes capable of converting adenosine to inosine at specific locations in certain RNA substrates. These reactions can change codon meaning in mRNA and lead to changes in the structures of proteins, including ligand-gated and voltage-gated ion channels and G-protein coupled receptors expressed in the central nervous system.
1. The document provides 30 multiple choice questions related to the central nervous system and eyeball. It covers topics like the brainstem, spinal cord, cerebellum, diencephalon, basal ganglia, limbic system, visual pathway, and cranial nerves.
2. The questions test knowledge of neuroanatomy including parts of the brain and spinal cord, tracts, nuclei, blood supply, and functions. Cell types like neurons, glia and their locations are also assessed.
3. In addition, concepts such as sympathetic nervous system, cerebrospinal fluid, meninges, vasculature and white matter structures are evaluated in the multiple choice questions.
Proteins must be properly located within cells to carry out their functions. Protein targeting refers to how cells transport proteins to the correct locations after synthesis. There are several mechanisms for protein targeting. Some proteins diffuse through the cytosol and bind to receptors at their destination site, while others contain targeting sequences like nuclear localization signals that bind nuclear transport receptors to be actively transported into the nucleus. The import and export of proteins between the cytosol and nucleus is directed by gradients of Ran-GTP and Ran-GDP concentrations established by regulatory proteins localized to different cellular compartments. This compartmentalization of Ran states provides directionality to nuclear transport.
The document reports on research investigating circadian rhythms in the nudibranch Melibe leonina. It was found that there are two circadian clocks: one in the brain controlling locomotion and one in the buccal ganglia controlling digestion/swallowing. Preliminary experiments showed clock proteins CRY2 and CLK are present in brain neurons, and the buccal ganglia express their own daily activity rhythm. Further experiments aim to characterize clock protein expression and neuronal activity in the two clock centers.
The document reports on research investigating circadian rhythms in the nudibranch Melibe leonina. It was found that there are two circadian clocks: one in the brain controlling locomotion and one in the buccal ganglia controlling digestion/swallowing. Preliminary experiments showed neurons containing clock proteins CRY2 and CLK in the brain and buccal ganglia expressed independent daily activity rhythms. Future experiments aim to further characterize clock protein expression and activity of clock neurons in these regions.
Direct conversion of neurons to fibroblastssyed shafiq
The document summarizes a research article that was published in Nature in 2010. The study found that fibroblasts could be directly converted into functional neurons by infecting the cells with viruses containing five transcription factor genes (Ascl1, Brn2, Myt1l, Zic1, and Olig2). The resulting induced neuronal (iN) cells displayed neuronal morphology, membrane properties, and ability to form functional synapses similar to primary neurons. Further experiments showed that Ascl1 alone or Ascl1 combined with Brn2 and Myt1l were able to generate iN cells, demonstrating the key factors required for direct neuronal conversion.
1) Lhx2 acts as a classic selector gene that cell-autonomously specifies cortical identity and suppresses alternative fates like the hippocampal organizer fate in the developing mouse brain.
2) Using genetic mosaics and timed inactivations in mice, the study demonstrates that Lhx2 performs this function during a critical period from E8.5-E10.5 when stem cells comprise the cortical neuroepithelium.
3) In the absence of Lhx2, cells laterally adopt an antihem identity and medially become cortical hem cells, which can induce and organize ectopic hippocampal fields, showing that the cortical hem is a hippocampal organizer.
The document discusses the genetic code, which is the language that allows genetic instructions stored in DNA to be translated into proteins. Some key points:
- The genetic code is found within messenger RNA (mRNA), which carries copies of genetic instructions from DNA to cellular structures called ribosomes.
- Ribosomes read the genetic code by recognizing linear sequences of the mRNA nucleotides adenine, uracil, cytosine, and guanine grouped into "words" of three nucleotides each.
- Experiments introducing small mutations into genes helped determine that the genetic code is organized into these three-nucleotide words, with each word specifying a single amino acid or start/stop signal.
Protein synthesis and trafficking involves two main stages - transcription and translation. Transcription occurs in the nucleus and involves copying information from DNA to mRNA. Translation occurs in the cytoplasm and involves using the mRNA code to assemble amino acids into proteins. Proteins are targeted to different locations through signal sequences and trafficking pathways. Newly synthesized proteins enter the endoplasmic reticulum and are modified and sorted in the Golgi apparatus before being targeted to their final destinations inside or outside the cell through secretory vesicles.
The document summarizes the endoplasmic reticulum (ER), an organelle found within eukaryotic cells. It was discovered in 1902 by Emilio Verrati but his work was initially disregarded. In the 1950s, Keith Porter and George Palade used electron microscopy to rediscover and prove the existence of the ER. The ER is a network of tubules and sacs that functions to produce and transport proteins and lipids. It exists in two forms: rough ER with ribosomes on its surface for protein synthesis, and smooth ER involved in lipid and steroid production. Current research explores how ER stress contributes to diseases like Alzheimer's, Parkinson's, and diabetes.
The document summarizes key aspects of protein transport within cells, including:
1) Proteins entering the endoplasmic reticulum (ER) have an N-terminal signal sequence that is recognized by signal recognition particle (SRP) to initiate translocation. Chaperone proteins such as BiP assist with proper folding within the ER lumen.
2) Transmembrane proteins maintain their orientation throughout transport, with alpha helices embedding in membranes. Multiple transmembrane proteins have multiple start and stop sequences recognized by SRP.
3) Vesicle transport between organelles is mediated by SNARE proteins on transport vesicles (v-SNAREs) and target membranes (t-SNAREs) that facilitate docking and fusion
Protein sorting and targeting involves transporting proteins to the appropriate locations within or outside the cell. There are several pathways for protein targeting, including vesicular transport between organelles like the ER and Golgi, as well as transport of proteins into organelles like mitochondria and peroxisomes. Targeting signals like presequences and internal targeting peptides direct cellular transport machinery to correctly position proteins. Lipidation is another method to target proteins to specific membranes through modifications like glycosyl phosphatidylinositol anchors or myristoylation.
This document summarizes the expression of recombinant β-lactoglobulin (rBLG) in prokaryotic and eukaryotic cells. In Escherichia coli, rBLG was expressed with a pET26 vector and was found predominantly in a denatured form, even when expressed in the periplasm. In eukaryotic cells like COS-7 and mouse tibialis muscle, rBLG was expressed in its native conformation. The authors quantified rBLG expression using immunoassays that distinguish between native and denatured rBLG. They found higher expression levels and native folding of rBLG in eukaryotic systems compared to prokaryotic expression
Protein targeting or protein sorting is the mechanism by which a cell transports to the appropriate positions in the cell or outside of it. Both in prokaryotes and eukaryotes, newly synthesized proteins must be delivered to a specific sub-cellular location or exported from the cell for correct activity. This phenomenon is called protein targeting. Protein targeting is necessary for proteins that are destined to work outside the cytoplasm.This delivery process is carried out based on information contained in the protein itself. Correct sorting is crucial for the cell; errors can lead to diseases. In 1970, Günter Blobel conducted experiments on the translocation of proteins across membranes. He was awarded the 1999 Nobel Prize for his findings. He discovered that many proteins have a signal sequence, that is, a short amino acid sequence at one end that functions like a postal code for the target organelle.
This PowerPoint is applicable for the medical, paramedical, and all the life science students who read the mechanism of gene expression. This is equally useful for teachers as well. This is the comprehensive coverage on the aforementioned topic.
I have tried to make a precise presentation on protein transport, targeting and sorting into organelle's other than nucleus. Hope this might help you. Comments are welcome.
This document summarizes protein targeting mechanisms in cells. It discusses how signal sequences direct proteins to different organelles like the endoplasmic reticulum, mitochondria, chloroplasts and nucleus. The signal sequence is cleaved after the protein reaches its destination. Glycosylation in the ER plays a key role in targeting lysosomal enzymes. Mitochondrial and chloroplast proteins use a different targeting mechanism after full synthesis. Receptor-mediated endocytosis imports some extracellular proteins by binding to receptors and forming clathrin-coated vesicles.
RNA editing is a term associated with structural changes in an RNA strand that alter its coding properties. These enzyme-catalyzed reactions include nucleotide and oligonucleotide insertions and deletions as well as base modifications. The diversity of coding strands created by these reactions contributes to the protein diversity present in cells of higher organisms. In this review, we highlight advances in our understanding of the structure, mechanism, regulation, and biological functions of the ADAR enzymes published in the last five years. The ADARs (adenosine deaminases that act on RNA) are multidomain enzymes capable of converting adenosine to inosine at specific locations in certain RNA substrates. These reactions can change codon meaning in mRNA and lead to changes in the structures of proteins, including ligand-gated and voltage-gated ion channels and G-protein coupled receptors expressed in the central nervous system.
1. The document provides 30 multiple choice questions related to the central nervous system and eyeball. It covers topics like the brainstem, spinal cord, cerebellum, diencephalon, basal ganglia, limbic system, visual pathway, and cranial nerves.
2. The questions test knowledge of neuroanatomy including parts of the brain and spinal cord, tracts, nuclei, blood supply, and functions. Cell types like neurons, glia and their locations are also assessed.
3. In addition, concepts such as sympathetic nervous system, cerebrospinal fluid, meninges, vasculature and white matter structures are evaluated in the multiple choice questions.
Proteins must be properly located within cells to carry out their functions. Protein targeting refers to how cells transport proteins to the correct locations after synthesis. There are several mechanisms for protein targeting. Some proteins diffuse through the cytosol and bind to receptors at their destination site, while others contain targeting sequences like nuclear localization signals that bind nuclear transport receptors to be actively transported into the nucleus. The import and export of proteins between the cytosol and nucleus is directed by gradients of Ran-GTP and Ran-GDP concentrations established by regulatory proteins localized to different cellular compartments. This compartmentalization of Ran states provides directionality to nuclear transport.
The document reports on research investigating circadian rhythms in the nudibranch Melibe leonina. It was found that there are two circadian clocks: one in the brain controlling locomotion and one in the buccal ganglia controlling digestion/swallowing. Preliminary experiments showed clock proteins CRY2 and CLK are present in brain neurons, and the buccal ganglia express their own daily activity rhythm. Further experiments aim to characterize clock protein expression and neuronal activity in the two clock centers.
The document reports on research investigating circadian rhythms in the nudibranch Melibe leonina. It was found that there are two circadian clocks: one in the brain controlling locomotion and one in the buccal ganglia controlling digestion/swallowing. Preliminary experiments showed neurons containing clock proteins CRY2 and CLK in the brain and buccal ganglia expressed independent daily activity rhythms. Future experiments aim to further characterize clock protein expression and activity of clock neurons in these regions.
Direct conversion of neurons to fibroblastssyed shafiq
The document summarizes a research article that was published in Nature in 2010. The study found that fibroblasts could be directly converted into functional neurons by infecting the cells with viruses containing five transcription factor genes (Ascl1, Brn2, Myt1l, Zic1, and Olig2). The resulting induced neuronal (iN) cells displayed neuronal morphology, membrane properties, and ability to form functional synapses similar to primary neurons. Further experiments showed that Ascl1 alone or Ascl1 combined with Brn2 and Myt1l were able to generate iN cells, demonstrating the key factors required for direct neuronal conversion.
Multifunctional nucleolus in Plant cell growth and development.Bhawna Mishra
This document provides an overview of the nucleolus in plant cells. It discusses that the nucleolus is made up of fibrillar centers, dense fibrillar compartments, and granular centers, and its main function is ribosome biosynthesis. It also notes that the nucleolus is involved in other processes like RNA regulation, cell cycle progression, genome maintenance, and stress response. Specific proteins and pathways in each of these functions are outlined. Recent research topics discussed include the nucleolus's role in DNA repair, links to the proteasome, and effects of nucleolar protein deficiencies on plant growth and development.
Abnormal Neural Oscillations And Synchrony In SchizophreniaKyongsik Yun
This document summarizes research on abnormal neural oscillations and synchrony in schizophrenia. It finds that patients show dysfunctional phase synchrony and reduced gamma oscillations, associated with reduced parvalbumin expression and inhibitory function. Animal models replicating anatomical and behavioral deficits in schizophrenia also show impaired gamma oscillations. The transition from adolescence to adulthood involves increased gamma oscillations and cortical network reorganization, associated with changes in GABAA receptor-mediated inhibition.
The role of vasopressin in light-induced c-Fos expression in the SCNJane Chapman
- Light exposure at night causes rapid induction of the immediate early gene c-Fos in the suprachiasmatic nucleus (SCN), which is implicated in shifting circadian rhythms.
- A population of retinal projections to the SCN express the neuropeptide vasopressin (VP), but the physiological significance is unknown.
- This study investigated whether VP released from retinal neurons mediates light-induced c-Fos expression in the SCN. Rats pre-treated with a VP antagonist before light exposure still showed c-Fos expression in the SCN, with no significant decrease. This suggests VP is not essential for generating light-induced c-Fos expression in the SCN.
This document summarizes research on lysosomal membrane permeability (LMP) and its implications for neurodegenerative diseases like neuronal ceroid lipofuscinoses (NCLs). The researchers found evidence that LMP occurs in mouse models of two forms of NCL, CLN2 and CLN3, resulting in the formation of protein aggregates. Normally, LMP triggers a response to sequester damaged lysosomes, but this "lysophagy" response is impaired in NCL models. As a result, aggregates containing lysosomal contents accumulate and may contribute to neurodegeneration. The researchers are testing the drug arimoclomol, which could prevent LMP, in hopes of reducing neurodegeneration in CL
This document discusses long non-coding RNAs (lncRNAs), which are RNA transcripts longer than 200 nucleotides that do not code for proteins. It provides background on lncRNAs, describing how they are classified and can function as signals, decoys, guides, or scaffolds. The document also examines the roles of lncRNAs in several human diseases like cancer, cardiovascular disease, Alzheimer's, and diabetes. It concludes that lncRNAs play significant roles in disease pathogenesis and could serve as biomarkers or therapeutic targets, and that further research is needed to fully understand lncRNA functions in vivo.
Ikrar Et Al (Cell Type Specific Regulation Of Cortical Excitability Through T...Taruna Ikrar
This study investigated using the allatostatin receptor (AlstR) system to selectively inhibit neuronal activity in specific cell types in the cortex. The researchers expressed AlstRs in either excitatory or inhibitory neurons in mouse brain slices using Cre-driven expression. They found that applying the allatostatin peptide ligand strongly reduced spiking in AlstR-expressing neurons but not others. When targeting excitatory neurons, it constrained activity propagation, but enhancing it when targeting inhibitory neurons. Expressing AlstRs in excitatory neurons also effectively suppressed induced seizure activity. This work demonstrates the AlstR system can regulate cortical excitability in a cell-type specific manner.
The document provides an overview of cell signaling and signal transduction. It discusses how cells communicate with each other via signaling molecules, both over short and long ranges. The key modes of cell signaling are introduced as autocrine, paracrine, endocrine, and juxtacrine signaling. The document then examines the processes of signal transduction, how signals are transmitted across and within cells to elicit responses. Specific topics covered include the synthesis and release of signaling molecules, signal detection by receptors, and the cellular changes induced by receptor-signal complexes.
Merkel cells (MCs) constitute a very unique population of postmitotic cells scattered along the dermoepidermal
junction. These cells that have synaptic contacts with somatosensory afferents are regarded
to have a pivotal role in sensory discernment. Several concerns exist till date as to their origin,
multiplication, and relevance in skin biology.
Long non coding RNA and Their clinical perspectiveMOHIT GOSWAMI
This document discusses long non-coding RNAs (lncRNAs), which are RNA molecules longer than 200 nucleotides that do not code for proteins but play important regulatory roles. It describes the central dogma of molecular biology and how most of the human genome is transcribed into non-coding RNA. It classifies lncRNAs and explains their potential functions as signals, decoys, guides and scaffolds. The document also discusses the roles of lncRNAs in several human diseases like cancer, Alzheimer's, diabetes and more. It concludes that lncRNAs are important biomarkers and therapeutic targets due to their involvement in complex disease pathogenesis.
The document presents a computational model of episodic memory encoding in the dentate gyrus region of the hippocampus using an ART neural network. The dentate gyrus is proposed to encode episodes in binary patterns in a way that achieves high levels of pattern encoding and separation. The model incorporates a method for encoding episodes as binary patterns that are stored sparsely. Simulation results show that the model achieves good separation of different episodes depending on the vigilance parameter, which is assumed to correlate with attention during episode perception.
Neurons form neural circuits that process sensory information and drive behavior. Glial cells such as astrocytes, oligodendrocytes, microglia, and Schwann cells provide support and insulation to neurons. Neurons communicate with each other at synapses, where neurotransmitters such as glutamate and GABA are released in response to action potentials and bind to receptors on adjacent cells.
The document discusses several factors that may contribute to the vulnerability of dopamine neurons in the substantia nigra pars compacta (SNc) in Parkinson's disease. These include dopamine metabolism, the interaction between dopamine and alpha-synuclein, neuromelanin content, calcium buffering capacity, and reliance on L-type calcium channels. Neurodegeneration may begin in both the SNc and supplementary motor cortex. Over time, Lewy bodies spread from the brainstem to the neocortex in a caudorostral gradient, contributing to non-dopaminergic symptoms and eventual dementia. Both neuronal cell loss and Lewy body accumulation appear to drive disease progression.
This document summarizes key findings about the molecular mechanisms that regulate myelination in the peripheral nervous system (PNS). It discusses how transcription factors such as Sox10, Oct6, Krox20, and Yy1 control myelination by activating myelin genes and suppressing inhibitors of myelination. It also describes the roles of epigenetic regulators like HDAC1/2, microRNAs, and the influence of cholesterol and fatty acid biosynthesis on myelin synthesis. Additionally, the roles of various cell adhesion molecules and signaling pathways in selecting axons for myelination and forming axo-glial junctions are summarized.
Female mammals achieve dosage compensation by inactivating one of their two X chromosomes
during development, a process entirely dependent on Xist, an X-linked long noncoding
RNA (lncRNA). At the onset of X chromosome inactivation (XCI), Xist is up-regulated
and spreads along the future inactive X chromosome. Contextually, it recruits repressive
histone and DNA modifiers that transcriptionally silence the X chromosome. Xist regulation is
tightly coupled to differentiation and its expression is under the control of both pluripotency
and epigenetic factors. Recent evidence has suggested that chromatin remodelers accumulate
at the X Inactivation Center (XIC) and here we demonstrate a new role for Chd8 in Xist
regulation in differentiating ES cells, linked to its control and prevention of spurious
transcription factor interactions occurring within Xist regulatory regions. Our findings have a
broader relevance, in the context of complex, developmentally-regulated gene expression.
Apoptosis, or programmed cell death, is an important physiological process that eliminates unwanted or damaged cells. There are two main pathways that trigger apoptosis - the extrinsic or death receptor pathway, and the intrinsic or mitochondrial pathway. The extrinsic pathway involves death receptors and ligands that activate caspase enzymes. The intrinsic pathway occurs in response to cellular stress and involves mitochondrial outer membrane permeabilization and the release of proteins like cytochrome c. This forms the apoptosome complex and activates caspase-9 and caspase-3, leading to apoptosis. Apoptosis is a highly regulated process involving Bcl-2 family proteins, caspase enzymes, and characteristic morphological changes including cell shrinkage, nuclear fragmentation, and membrane blebbing. Assays to detect
Similar to OLM interneurons differentially modulate CA3 and entorhinal inputs to hippocampal CA1 neurons (20)
Offshore fresh groundwater reserves as a global phenomenonCarlos Bella
There is mounting evidence that vast reserves of fresh and brackish groundwater exist below continental shelves around the world. These offshore fresh groundwater reserves (OFGRs) were formed when sea levels were lower during glacial periods, exposing continental shelf areas that became recharged with precipitation and glacial meltwater. While some OFGRs may still be connected to modern coastal groundwater systems, many appear to be relics of past hydrological conditions and are termed "palaeo-groundwater". The largest documented OFGR is below the New Jersey shelf, where freshwater has been found over 100km offshore. Global occurrences of OFGRs have also been identified through borehole and geophysical data in locations such as the North
Revealing letters in rolled Herculaneum papyri by X-ray phase-contrast imagingCarlos Bella
X-ray phase-contrast tomography was used to read letters hidden inside two unopened Herculaneum papyri without damaging them. In a fragment of one papyrus, two Greek words were identified on a hidden layer. In an intact rolled papyrus, several letter sequences were revealed, including "APN", "HEY", and "KI". This non-destructive technique opens opportunities to read many rolled Herculaneum papyri and enhance knowledge of ancient Greek literature.
Animal behaviour: Incipient tradition in wild chimpanzeesCarlos Bella
This study observed the adoption of a new tool use behavior, moss sponging, by chimpanzees at the Sonso community in Uganda's Budongo Forest. The dominant male was first observed using a moss sponge to drink from a small flooded waterhole. Over the next six days, six other chimpanzees began displaying this behavior after observing the dominant male and female. The researchers used a statistical technique called network-based diffusion analysis to show the spread of this innovation was consistent with social learning along social network pathways, providing the first direct evidence of cultural diffusion in wild chimpanzees.
Cohesive forces prevent the rotational breakup of rubble-pile asteroid (29075...Carlos Bella
1) The asteroid (29075) 1950 DA is rotating faster than would be allowed without cohesive forces, with a rotation period of just over 2 hours.
2) Thermal infrared observations and measurements of its orbital drift were used to determine it has a low bulk density of 1.7 g/cm3, indicating it is a rubble pile asteroid made of smaller pieces held together weakly.
3) For it to retain its fine-grained surface and resist breaking up from centrifugal forces at its rate of rotation, cohesive van der Waals forces between the grains comparable to lunar regolith are required, with a minimum cohesive strength of 64 Pa.
Detection of Radio Emission from FireballsCarlos Bella
This document summarizes the detection of radio emissions from fireballs (very bright meteors) using the Long Wavelength Array radio telescope. A search of over 11,000 hours of all-sky radio images found 49 long-duration radio transients. Ten of these transients correlated spatially and temporally with fireballs detected by an optical meteor monitoring network. This provides evidence that fireballs emit previously undiscovered low frequency radio pulses. Further analysis found characteristics inconsistent with expected radio reflections from meteor trails, suggesting a non-thermal radio emission mechanism from the fireballs. This identifies a new class of natural radio transients and provides a new probe to study meteor physics.
This document is the introduction to The Skeptic Encyclopedia of Pseudoscience. It provides an overview of the encyclopedia, which aims to objectively analyze prominent scientific and pseudoscientific claims. The introduction discusses the relationship between facts and theories in science. It notes that observations must be viewed through theoretical lenses, and references Darwin's view that observations are only useful if they are for or against some view. The introduction also discusses how views of science have changed over time between seeing it as progressively approaching truth, and as a relativistic social construct. It argues the field has moved to a more balanced middle view. The goal of the encyclopedia is to explore the borderlands where theory and data intersect, with the aim of achieving a
Preserved flora and organics in impact melt brecciasCarlos Bella
This document discusses the preservation of organic matter and plant remains in impact melt breccias found in Argentina. Analyses found centimeter-scale leaf fragments encapsulated in the impact glass that exhibited remarkable cellular-level preservation. Organic matter was also detected, including polycyclic aromatic hydrocarbons, alkanes, and pigment-like structures similar to chlorophyll. Heating experiments showed temperatures above 1500°C were required to preserve morphology, suggesting the impact process rapidly quenched and encapsulated the organic material. These findings demonstrate the potential for impact events to preserve biomarkers of early life on Mars.
A Sedna-like body with a perihelion of 80 astronomical unitsCarlos Bella
1) The document reports the discovery of 2012 VP113, the second known object after Sedna with an extremely distant perihelion of 80 AU, confirming that Sedna is not isolated.
2) Simulation results suggest there may be few inner Oort cloud objects with perihelia between 50-75 AU, and the population increases with perihelion distances greater than 75 AU.
3) Both Sedna and 2012 VP113 have similar arguments of perihelion, as do all other objects beyond 150 AU, suggesting they were perturbed by a possible unseen super-Earth mass perturber in the outer solar system that could restrict their arguments of perihelion.
Fuel gain exceeding unity in an inertially confined fusion implosionCarlos Bella
The document summarizes key results from experiments achieving fusion fuel gains exceeding unity using a "high-foot" laser pulse shape on the National Ignition Facility. Specifically:
1) Experiments achieved fusion fuel gains over unity for the first time, representing a 10x improvement over past experiments, and showed significant alpha heating and evidence of ignition requirements being met.
2) The "high-foot" pulse shape reduces instability during implosions by increasing ablation velocity and density scale length, improving stability compared to past "low-foot" experiments.
3) Improved performance is attributed to reduced mix from the ablator, with experiments pushing higher velocities through laser power and pattern optimization while maintaining hotspot shape control.
This document summarizes meteor phenomena and bodies. It discusses the different types of interactions that can occur when meteoroids collide with Earth's atmosphere, including meteors, fireballs, bolides, explosive impacts, and meteoric dust particles. It also describes the various stages of a meteoroid's trajectory through the atmosphere, including orbital motion, preheating, ablation, dark flight, and impact. Finally, it provides an overview of the size ranges and velocities associated with different meteor phenomena.
The Origin Of The 1998 June BoöTid Meteor ShowerCarlos Bella
The document analyzes the origin of the 1998 June Boötid meteor shower through comparing orbital elements and simulating particle release from the potential parent comet 7P/Pons–Winnecke. It finds that:
1) 7P/Pons–Winnecke best matches the shower orbit based on the Tisserand invariant and D-discriminant.
2) Simulations show particles released from 7P/Pons–Winnecke in 1819 and 1869 were Earth-crossing in 1998 after Jovian perturbations altered their orbits starting in the 1940s.
3) This identifies 7P/Pons–Winnecke as the parent comet and 1819 and 1869 as the active returns
Physics first spectrum of ball lightningCarlos Bella
Researchers in China measured the first spectrum of ball lightning. They observed ball lightning form after a cloud-to-ground lightning strike about 900 meters away. The spectrum contained emission lines from silicon, iron, and calcium, elements common in soil. This supports the theory that ball lightning is formed when lightning vaporizes soil, producing glowing nanoparticles. It was about 2 meters wide and drifted horizontally for 30 meters before rising a few meters. This is the first direct observation of ball lightning forming from a lightning strike and the first measurement of its emission spectrum.
1) PSR J033711715 is a millisecond pulsar discovered to be in a hierarchical triple system with two white dwarf companions, making it the first known millisecond pulsar triple system.
2) Precise timing observations using multiple radio telescopes determined the masses of the pulsar (1.4378 solar masses), inner white dwarf companion (0.19751 solar masses), and outer white dwarf companion (0.4101 solar masses) to high precision.
3) The unexpectedly coplanar and nearly circular orbits of the system indicate an exotic evolutionary history and provide an opportunity to test theories of general relativity by studying the interactions between the bodies.
Transient Water Vapor at Europa’s South PoleCarlos Bella
1) Hubble Space Telescope images from November and December 2012 of Europa's atmosphere detected statistically significant surpluses of hydrogen Lyman-α and oxygen OI130.4 nm emissions above Europa's southern hemisphere in December 2012.
2) These emissions were observed in the same region over a period of ~7 hours, suggesting an inhomogeneous atmosphere, consistent with two 200-km-high plumes of water vapor with column densities of about 1020 m−2.
3) No plumes were detected in November 2012 images or previous 1999 images, indicating variable plume activity possibly related to Europa's changing orbital phases and surface stresses. The December 2012 plume was seen when Europa was near apocenter.
Solid-state plastic deformation in the dynamic interior of a differentiated a...Carlos Bella
This document summarizes a study that analyzed the microstructural properties of olivine grains in the diogenite meteorite Northwest Africa 5480 using electron backscatter diffraction techniques. The study found evidence of solid-state plastic deformation in the olivine-dominated zones, represented by a well-defined lattice-preferred orientation that is best explained by high-temperature deformation via the pencil-glide slip system, typically seen on Earth in dry ultramafic rocks deformed in the mantle. Numerical modeling indicates this observation in the meteorite can be explained by large-scale downwelling in the asteroid's mantle within the first 50 million years after formation, providing evidence of dynamic planet-like processes occurring in the interior of
Broadband high photoresponse from pure monolayer graphene photodetectorCarlos Bella
This document summarizes a research article that reports on the development of a high-performance photodetector using pure monolayer graphene. The researchers introduced electron trapping centers and created a bandgap in graphene through band structure engineering. This allowed them to achieve a high photoresponsivity of 8.61 A/W, about three orders of magnitude higher than previous graphene photodetectors. Additionally, they demonstrated broadband photoresponse from visible to mid-infrared wavelengths, the broadest reported for a pure graphene photodetector. By introducing defects and quantum confinement effects, they were able to greatly increase the lifetime of photo-generated carriers and achieve carrier multiplication, resulting in high photoresponsivity across a wide spectrum
Formation SiO2 Mass-Independent Oxygen Isotopic Partitioning During Gas-PhaseCarlos Bella
This document summarizes an experimental study that investigated oxygen isotopic partitioning during gas-phase silicon dioxide (SiO2) formation. The experiments involved laser ablation of silicon monoxide (SiO) in the presence of oxygen (O2) with and without hydrogen (H2). SiO2 formed in experiments without H2 showed normal mass-dependent isotopic fractionation, whereas those with H2 exhibited anomalous mass-independent fractionation. The extent of mass-independent fractionation in SiO2 increased with higher H2/O2 ratios. This provides the first experimental evidence that gas-to-particle conversion reactions can produce solids like SiO2 with oxygen isotopic compositions similar to early solar system materials like calcium-
A Complete Skull from Dmanisi, Georgia, and the Evolutionary Biology of Early...Carlos Bella
The article describes a newly discovered complete skull (D4500) from the site of Dmanisi, Georgia dating to 1.8 million years ago. It represents the earliest known completely preserved adult hominin skull. The skull possesses a small braincase of 546 cubic centimeters but also exhibits a large, prognathic face. This combination of features had not been seen before in the human fossil record. Analysis of this new skull and comparison to other remains from Dmanisi provides direct evidence of wide morphological variation within early members of the genus Homo, implying a single evolving lineage across continents.
Minor Planet Evidence for Water in the Rocky Debris of a Disrupted Extrasolar...Carlos Bella
Evidence has been found for water in the debris of a disrupted extrasolar minor planet orbiting a white dwarf star. Spectroscopic analysis of the white dwarf's atmosphere revealed an excess of oxygen that cannot be explained by oxide minerals alone, indicating the parent body was originally composed of about 26% water by mass. This demonstrates that water-bearing planetesimals can form around higher mass stars that eventually become white dwarfs. The disrupted planetesimal is the source of a circumstellar debris disk closely orbiting the white dwarf remnant.
Level 3 NCEA - NZ: A Nation In the Making 1872 - 1900 SML.pptHenry Hollis
The History of NZ 1870-1900.
Making of a Nation.
From the NZ Wars to Liberals,
Richard Seddon, George Grey,
Social Laboratory, New Zealand,
Confiscations, Kotahitanga, Kingitanga, Parliament, Suffrage, Repudiation, Economic Change, Agriculture, Gold Mining, Timber, Flax, Sheep, Dairying,
Andreas Schleicher presents PISA 2022 Volume III - Creative Thinking - 18 Jun...EduSkills OECD
Andreas Schleicher, Director of Education and Skills at the OECD presents at the launch of PISA 2022 Volume III - Creative Minds, Creative Schools on 18 June 2024.
How to Setup Default Value for a Field in Odoo 17Celine George
In Odoo, we can set a default value for a field during the creation of a record for a model. We have many methods in odoo for setting a default value to the field.
Creative Restart 2024: Mike Martin - Finding a way around “no”Taste
Ideas that are good for business and good for the world that we live in, are what I’m passionate about.
Some ideas take a year to make, some take 8 years. I want to share two projects that best illustrate this and why it is never good to stop at “no”.
How to Manage Reception Report in Odoo 17Celine George
A business may deal with both sales and purchases occasionally. They buy things from vendors and then sell them to their customers. Such dealings can be confusing at times. Because multiple clients may inquire about the same product at the same time, after purchasing those products, customers must be assigned to them. Odoo has a tool called Reception Report that can be used to complete this assignment. By enabling this, a reception report comes automatically after confirming a receipt, from which we can assign products to orders.