This document discusses copper deficiency in ruminants and its pathogenesis. It notes that molybdenum and sulfur can interact with copper to form complexes that are not absorbed. This can lead to secondary copper deficiency even with adequate dietary copper intake. The phases of copper deficiency are outlined, from initial depletion to eventual disease. Clinical signs include anemia, diarrhea, bone and neurological disorders, and coat color changes. Diagnosis involves assessing copper levels in tissues and diet. Treatment involves removing causes of interference, oral or injectable copper supplementation, and adding copper to feed or mineral mixes.
Lecturer notes for metabolic diseases in Cattle.which is benificial for student of BVSc& AH/DVM and MVsc student. It is My first presentation need your feedback for more presentation like this.
Lecturer notes for metabolic diseases in Cattle.which is benificial for student of BVSc& AH/DVM and MVsc student. It is My first presentation need your feedback for more presentation like this.
Copper- sources, daily requirement, absorption, transportation, storage, excretion, role in enzymatic action, role in iron metabolism, role in elastin maturation, role in bone formation, copper deficiency, copper toxicity, Wilson disease, Menkes disease.
(May 29th, 2024) Advancements in Intravital Microscopy- Insights for Preclini...Scintica Instrumentation
Intravital microscopy (IVM) is a powerful tool utilized to study cellular behavior over time and space in vivo. Much of our understanding of cell biology has been accomplished using various in vitro and ex vivo methods; however, these studies do not necessarily reflect the natural dynamics of biological processes. Unlike traditional cell culture or fixed tissue imaging, IVM allows for the ultra-fast high-resolution imaging of cellular processes over time and space and were studied in its natural environment. Real-time visualization of biological processes in the context of an intact organism helps maintain physiological relevance and provide insights into the progression of disease, response to treatments or developmental processes.
In this webinar we give an overview of advanced applications of the IVM system in preclinical research. IVIM technology is a provider of all-in-one intravital microscopy systems and solutions optimized for in vivo imaging of live animal models at sub-micron resolution. The system’s unique features and user-friendly software enables researchers to probe fast dynamic biological processes such as immune cell tracking, cell-cell interaction as well as vascularization and tumor metastasis with exceptional detail. This webinar will also give an overview of IVM being utilized in drug development, offering a view into the intricate interaction between drugs/nanoparticles and tissues in vivo and allows for the evaluation of therapeutic intervention in a variety of tissues and organs. This interdisciplinary collaboration continues to drive the advancements of novel therapeutic strategies.
This pdf is about the Schizophrenia.
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Introduction:
RNA interference (RNAi) or Post-Transcriptional Gene Silencing (PTGS) is an important biological process for modulating eukaryotic gene expression.
It is highly conserved process of posttranscriptional gene silencing by which double stranded RNA (dsRNA) causes sequence-specific degradation of mRNA sequences.
dsRNA-induced gene silencing (RNAi) is reported in a wide range of eukaryotes ranging from worms, insects, mammals and plants.
This process mediates resistance to both endogenous parasitic and exogenous pathogenic nucleic acids, and regulates the expression of protein-coding genes.
What are small ncRNAs?
micro RNA (miRNA)
short interfering RNA (siRNA)
Properties of small non-coding RNA:
Involved in silencing mRNA transcripts.
Called “small” because they are usually only about 21-24 nucleotides long.
Synthesized by first cutting up longer precursor sequences (like the 61nt one that Lee discovered).
Silence an mRNA by base pairing with some sequence on the mRNA.
Discovery of siRNA?
The first small RNA:
In 1993 Rosalind Lee (Victor Ambros lab) was studying a non- coding gene in C. elegans, lin-4, that was involved in silencing of another gene, lin-14, at the appropriate time in the
development of the worm C. elegans.
Two small transcripts of lin-4 (22nt and 61nt) were found to be complementary to a sequence in the 3' UTR of lin-14.
Because lin-4 encoded no protein, she deduced that it must be these transcripts that are causing the silencing by RNA-RNA interactions.
Types of RNAi ( non coding RNA)
MiRNA
Length (23-25 nt)
Trans acting
Binds with target MRNA in mismatch
Translation inhibition
Si RNA
Length 21 nt.
Cis acting
Bind with target Mrna in perfect complementary sequence
Piwi-RNA
Length ; 25 to 36 nt.
Expressed in Germ Cells
Regulates trnasposomes activity
MECHANISM OF RNAI:
First the double-stranded RNA teams up with a protein complex named Dicer, which cuts the long RNA into short pieces.
Then another protein complex called RISC (RNA-induced silencing complex) discards one of the two RNA strands.
The RISC-docked, single-stranded RNA then pairs with the homologous mRNA and destroys it.
THE RISC COMPLEX:
RISC is large(>500kD) RNA multi- protein Binding complex which triggers MRNA degradation in response to MRNA
Unwinding of double stranded Si RNA by ATP independent Helicase
Active component of RISC is Ago proteins( ENDONUCLEASE) which cleave target MRNA.
DICER: endonuclease (RNase Family III)
Argonaute: Central Component of the RNA-Induced Silencing Complex (RISC)
One strand of the dsRNA produced by Dicer is retained in the RISC complex in association with Argonaute
ARGONAUTE PROTEIN :
1.PAZ(PIWI/Argonaute/ Zwille)- Recognition of target MRNA
2.PIWI (p-element induced wimpy Testis)- breaks Phosphodiester bond of mRNA.)RNAse H activity.
MiRNA:
The Double-stranded RNAs are naturally produced in eukaryotic cells during development, and they have a key role in regulating gene expression .
A brief information about the SCOP protein database used in bioinformatics.
The Structural Classification of Proteins (SCOP) database is a comprehensive and authoritative resource for the structural and evolutionary relationships of proteins. It provides a detailed and curated classification of protein structures, grouping them into families, superfamilies, and folds based on their structural and sequence similarities.
The increased availability of biomedical data, particularly in the public domain, offers the opportunity to better understand human health and to develop effective therapeutics for a wide range of unmet medical needs. However, data scientists remain stymied by the fact that data remain hard to find and to productively reuse because data and their metadata i) are wholly inaccessible, ii) are in non-standard or incompatible representations, iii) do not conform to community standards, and iv) have unclear or highly restricted terms and conditions that preclude legitimate reuse. These limitations require a rethink on data can be made machine and AI-ready - the key motivation behind the FAIR Guiding Principles. Concurrently, while recent efforts have explored the use of deep learning to fuse disparate data into predictive models for a wide range of biomedical applications, these models often fail even when the correct answer is already known, and fail to explain individual predictions in terms that data scientists can appreciate. These limitations suggest that new methods to produce practical artificial intelligence are still needed.
In this talk, I will discuss our work in (1) building an integrative knowledge infrastructure to prepare FAIR and "AI-ready" data and services along with (2) neurosymbolic AI methods to improve the quality of predictions and to generate plausible explanations. Attention is given to standards, platforms, and methods to wrangle knowledge into simple, but effective semantic and latent representations, and to make these available into standards-compliant and discoverable interfaces that can be used in model building, validation, and explanation. Our work, and those of others in the field, creates a baseline for building trustworthy and easy to deploy AI models in biomedicine.
Bio
Dr. Michel Dumontier is the Distinguished Professor of Data Science at Maastricht University, founder and executive director of the Institute of Data Science, and co-founder of the FAIR (Findable, Accessible, Interoperable and Reusable) data principles. His research explores socio-technological approaches for responsible discovery science, which includes collaborative multi-modal knowledge graphs, privacy-preserving distributed data mining, and AI methods for drug discovery and personalized medicine. His work is supported through the Dutch National Research Agenda, the Netherlands Organisation for Scientific Research, Horizon Europe, the European Open Science Cloud, the US National Institutes of Health, and a Marie-Curie Innovative Training Network. He is the editor-in-chief for the journal Data Science and is internationally recognized for his contributions in bioinformatics, biomedical informatics, and semantic technologies including ontologies and linked data.
Nutraceutical market, scope and growth: Herbal drug technologyLokesh Patil
As consumer awareness of health and wellness rises, the nutraceutical market—which includes goods like functional meals, drinks, and dietary supplements that provide health advantages beyond basic nutrition—is growing significantly. As healthcare expenses rise, the population ages, and people want natural and preventative health solutions more and more, this industry is increasing quickly. Further driving market expansion are product formulation innovations and the use of cutting-edge technology for customized nutrition. With its worldwide reach, the nutraceutical industry is expected to keep growing and provide significant chances for research and investment in a number of categories, including vitamins, minerals, probiotics, and herbal supplements.
Earliest Galaxies in the JADES Origins Field: Luminosity Function and Cosmic ...Sérgio Sacani
We characterize the earliest galaxy population in the JADES Origins Field (JOF), the deepest
imaging field observed with JWST. We make use of the ancillary Hubble optical images (5 filters
spanning 0.4−0.9µm) and novel JWST images with 14 filters spanning 0.8−5µm, including 7 mediumband filters, and reaching total exposure times of up to 46 hours per filter. We combine all our data
at > 2.3µm to construct an ultradeep image, reaching as deep as ≈ 31.4 AB mag in the stack and
30.3-31.0 AB mag (5σ, r = 0.1” circular aperture) in individual filters. We measure photometric
redshifts and use robust selection criteria to identify a sample of eight galaxy candidates at redshifts
z = 11.5 − 15. These objects show compact half-light radii of R1/2 ∼ 50 − 200pc, stellar masses of
M⋆ ∼ 107−108M⊙, and star-formation rates of SFR ∼ 0.1−1 M⊙ yr−1
. Our search finds no candidates
at 15 < z < 20, placing upper limits at these redshifts. We develop a forward modeling approach to
infer the properties of the evolving luminosity function without binning in redshift or luminosity that
marginalizes over the photometric redshift uncertainty of our candidate galaxies and incorporates the
impact of non-detections. We find a z = 12 luminosity function in good agreement with prior results,
and that the luminosity function normalization and UV luminosity density decline by a factor of ∼ 2.5
from z = 12 to z = 14. We discuss the possible implications of our results in the context of theoretical
models for evolution of the dark matter halo mass function.
Multi-source connectivity as the driver of solar wind variability in the heli...Sérgio Sacani
The ambient solar wind that flls the heliosphere originates from multiple
sources in the solar corona and is highly structured. It is often described
as high-speed, relatively homogeneous, plasma streams from coronal
holes and slow-speed, highly variable, streams whose source regions are
under debate. A key goal of ESA/NASA’s Solar Orbiter mission is to identify
solar wind sources and understand what drives the complexity seen in the
heliosphere. By combining magnetic feld modelling and spectroscopic
techniques with high-resolution observations and measurements, we show
that the solar wind variability detected in situ by Solar Orbiter in March
2022 is driven by spatio-temporal changes in the magnetic connectivity to
multiple sources in the solar atmosphere. The magnetic feld footpoints
connected to the spacecraft moved from the boundaries of a coronal hole
to one active region (12961) and then across to another region (12957). This
is refected in the in situ measurements, which show the transition from fast
to highly Alfvénic then to slow solar wind that is disrupted by the arrival of
a coronal mass ejection. Our results describe solar wind variability at 0.5 au
but are applicable to near-Earth observatories.
9. Copper-molybdenum-sulfate relationship
•The interaction between copper, molybdenum, and sulfur
in ruminant nutrition is unique in its effects on health and
production.
•Copper, molybdenum, and sulfur from organic or inorganic
sources can combine in the rumen to from an
unabsorbable triple complex, copper tetrathiomolybdate
and deplete the host tissues of copper.
•Secondary or conditioned copper deficiency occurs when
the dietary intake of copper is adequate, but absorption
and utilization of the copper are inadequate because of
the presence of interfering substances in the diet.
10. •Molybdenum and sulfate alone or in combination can
affect copper metabolism.This effect also operates in
the fetus and interferes with copper storage in the
fetal liver.
•Besides the relationship with molybdenum, an
interaction between the absorption of copper and
selenium has been demonstrated the administration of
selenium to sheep on copper-deficient pastures
causing an improvement in copper absorption.
•The toxicity of any level of dietary molybdenum is
affected by the ratio of the dietary molybdenum to
dietary copper.
11. •The critical copper:molybdenum ratio in animal
feeds is 2 and feeds or pasture with a lower ratio
may result in conditioned copper deficiency.
• In some regions of Canada, the copper:
molybdenum ratio will vary from 0.1 to 52.7.
•Higher critical ratios closer to 4.1-5 . 1 have been
recommended for safety.
12. •Phases of copper deficiency
•The development of a deficiency can be
divided into four phases:
•1. Depletion
•2. Deficiency (marginal)
•3. Dysfunction
•4. Disease
13. •During the depletion phase, there is loss of
copper from any storage site, such as liver, but
the plasma concentrations of copper may remain
constant. With continued dietary deficiency, the
concentrations of copper in the blood decline
during the phase of marginal deficiency.
•However, it may be some time before the
concentrations or activities of copper-containing
enzymes in the tissues begin to decline and it is
not until this happens that the phase of
dysfunction is reached. There may be a further
lag before the changes in cellular function are
manifested as clinical signs of disease.
14. Summary of pathogenesis
The overall effect of these interactions is as
follows.
1. Molybdate reacts with sulfides to produce
thiomolybdates in the rumen. The subsequent
formation of copper thiomolybdate complexes
isolates the copper from being biologically
available. The thiomolybdates reduce the
effectiveness of enzymes containing copper
and there are some significant interactions
between copper, zinc, and iron. The following
is the most important mechanism:
15. (1)Copper is essential for the synthesis of
hemoglobin, reutilization of iron (hemosiderin)
liberated from the normal breakdown of
hemoglobin, enzymatic activities and tissue
oxidation.
(2) Normal copper levels in animals range from
0.5 to 1.5 ug/ml blood, about 90% of copper
remains in plasma as ceruloplasmin.
(3) Liver is the main storage organ of copper.
High level of copper is observed in liver in
number of diseases of man and animals (e.g.
Cirrhosis of liver, hepatocellular degeneration
and tuberculosis).
16. (4) Copper deficiency leads to:
1) Faulty in tissue oxidation because copper is essential for
function and formation of cytochrome oxidase system so
that inadequate keratinization of skin, wool and hair occur
due to inability of follicle cells to convert prekeratin to
keratin.
2) Decrease Hb synthesis resulting in anemic hypoxia
3) Loss of bone collagen as a result of impaired activity of the
copper enzymes (e.g. amine or lysil oxidase causing
osteoporosis.
4) Demyelination of CNS as well as necrosis and neuronal
degeneration of spinal cord and brain stem.
5) Depigmentation of hairs and wools (achromotrichia) so that
blacks hairs turn gray or brown. This occurs because copper
interferes with the formation of melanine from tyrosine.
6) Mucosal atrophy in the small intestine resulting in severe
diarrhea and malabsorption.
17. Clinical signs
(1) Microcytic hypochromic anemia due to
hindrance in the process of hematopoiesis.
(2) Diarrhea (Scouring) in cattle. This diarrhea is
persistent in nature and is defined as ’peat
scours’ and ‘teart’ (Table.9).
(3) Bone deformities: Bones become porous
(osteoporosis) and there is tendency of
spontaneous fracture.
(4) Nervous disorder: Such animal shows
nervous manifestations known as neonatal
ataxia and sway back, later on paralysis may
be occur.
18.
19. (5) Pigmentary disorder: Black hairs turn grey or brown.
There are abnormalities in the growth of hair and
wools. Hair color around the eyes is strikingly altered
giving glasses like appearance (Spectacle disease).
(6) In sheep: the fine wool becomes limp, gloosy and
looses its crimp developing straight and steely wool
appearance. Black wool shows depigmentation to
white.
(7) Partial or complete alopecia may be occurring.
(8) The coat becomes rough. The red and black coat of
cattle changed to a bleached, rusty red.
(9) Myocardial degeneration causing acute heart failure
and sudden death (Falling disease).
(10) Infertility, delayed estrus in cattle, dead fetus and
abortion may be occurs in all animals.
20.
21.
22. Diagnosis
(1) History of diet and clinical
findings.
(2) Estimation of Cu level in soil,
hair, diet, blood and liver.
(3) Low level of copper reduces
hemoglobin level and RBC.
23.
24.
25.
26. •Treatment
(1) Remove the cause.
(2) Oral copper sulphate 2-4 gm for adult
cattle, 1.5 gm for goat and sheep (recovery
occurs within hours), repeated weekly
interval to prevent reappearance.
(3) Add 5 ppm of copper sulphate to the dry
diet or 0.5% copper can be added in
mineral mixture.
(4) Very slowly IV injection of diluted 20 mg
copper for sheep and 50 mg for cattle are
effective for about four months.