This pdf is about the Schizophrenia.
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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.
Deep Behavioral Phenotyping in Systems Neuroscience for Functional Atlasing a...Ana Luísa Pinho
Functional Magnetic Resonance Imaging (fMRI) provides means to characterize brain activations in response to behavior. However, cognitive neuroscience has been limited to group-level effects referring to the performance of specific tasks. To obtain the functional profile of elementary cognitive mechanisms, the combination of brain responses to many tasks is required. Yet, to date, both structural atlases and parcellation-based activations do not fully account for cognitive function and still present several limitations. Further, they do not adapt overall to individual characteristics. In this talk, I will give an account of deep-behavioral phenotyping strategies, namely data-driven methods in large task-fMRI datasets, to optimize functional brain-data collection and improve inference of effects-of-interest related to mental processes. Key to this approach is the employment of fast multi-functional paradigms rich on features that can be well parametrized and, consequently, facilitate the creation of psycho-physiological constructs to be modelled with imaging data. Particular emphasis will be given to music stimuli when studying high-order cognitive mechanisms, due to their ecological nature and quality to enable complex behavior compounded by discrete entities. I will also discuss how deep-behavioral phenotyping and individualized models applied to neuroimaging data can better account for the subject-specific organization of domain-general cognitive systems in the human brain. Finally, the accumulation of functional brain signatures brings the possibility to clarify relationships among tasks and create a univocal link between brain systems and mental functions through: (1) the development of ontologies proposing an organization of cognitive processes; and (2) brain-network taxonomies describing functional specialization. To this end, tools to improve commensurability in cognitive science are necessary, such as public repositories, ontology-based platforms and automated meta-analysis tools. I will thus discuss some brain-atlasing resources currently under development, and their applicability in cognitive as well as clinical neuroscience.
This presentation explores a brief idea about the structural and functional attributes of nucleotides, the structure and function of genetic materials along with the impact of UV rays and pH upon them.
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 .
Seminar of U.V. Spectroscopy by SAMIR PANDASAMIR PANDA
Spectroscopy is a branch of science dealing the study of interaction of electromagnetic radiation with matter.
Ultraviolet-visible spectroscopy refers to absorption spectroscopy or reflect spectroscopy in the UV-VIS spectral region.
Ultraviolet-visible spectroscopy is an analytical method that can measure the amount of light received by the analyte.
Observation of Io’s Resurfacing via Plume Deposition Using Ground-based Adapt...Sérgio Sacani
Since volcanic activity was first discovered on Io from Voyager images in 1979, changes
on Io’s surface have been monitored from both spacecraft and ground-based telescopes.
Here, we present the highest spatial resolution images of Io ever obtained from a groundbased telescope. These images, acquired by the SHARK-VIS instrument on the Large
Binocular Telescope, show evidence of a major resurfacing event on Io’s trailing hemisphere. When compared to the most recent spacecraft images, the SHARK-VIS images
show that a plume deposit from a powerful eruption at Pillan Patera has covered part
of the long-lived Pele plume deposit. Although this type of resurfacing event may be common on Io, few have been detected due to the rarity of spacecraft visits and the previously low spatial resolution available from Earth-based telescopes. The SHARK-VIS instrument ushers in a new era of high resolution imaging of Io’s surface using adaptive
optics at visible wavelengths.
(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.
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.
Cancer cell metabolism: special Reference to Lactate PathwayAADYARAJPANDEY1
Normal Cell Metabolism:
Cellular respiration describes the series of steps that cells use to break down sugar and other chemicals to get the energy we need to function.
Energy is stored in the bonds of glucose and when glucose is broken down, much of that energy is released.
Cell utilize energy in the form of ATP.
The first step of respiration is called glycolysis. In a series of steps, glycolysis breaks glucose into two smaller molecules - a chemical called pyruvate. A small amount of ATP is formed during this process.
Most healthy cells continue the breakdown in a second process, called the Kreb's cycle. The Kreb's cycle allows cells to “burn” the pyruvates made in glycolysis to get more ATP.
The last step in the breakdown of glucose is called oxidative phosphorylation (Ox-Phos).
It takes place in specialized cell structures called mitochondria. This process produces a large amount of ATP. Importantly, cells need oxygen to complete oxidative phosphorylation.
If a cell completes only glycolysis, only 2 molecules of ATP are made per glucose. However, if the cell completes the entire respiration process (glycolysis - Kreb's - oxidative phosphorylation), about 36 molecules of ATP are created, giving it much more energy to use.
IN CANCER CELL:
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
introduction to WARBERG PHENOMENA:
WARBURG EFFECT Usually, cancer cells are highly glycolytic (glucose addiction) and take up more glucose than do normal cells from outside.
Otto Heinrich Warburg (; 8 October 1883 – 1 August 1970) In 1931 was awarded the Nobel Prize in Physiology for his "discovery of the nature and mode of action of the respiratory enzyme.
WARNBURG EFFECT : cancer cells under aerobic (well-oxygenated) conditions to metabolize glucose to lactate (aerobic glycolysis) is known as the Warburg effect. Warburg made the observation that tumor slices consume glucose and secrete lactate at a higher rate than normal tissues.
Cancer cell metabolism: special Reference to Lactate Pathway
JBEI Research Highlight Slides - April 2023
1. Office of Biological and Environmental Research
Expanding Extender Substrate Selection for Unnatural
Polyketide Biosynthesis by Acyltransferase Domain
Exchange within a Modular Polyketide Synthase.
Background/Objective
Scientists have wondered if PKSs could be engineered to produce nearly any
organic molecule by assembling PKS modules in new hybrid synthases.
Englund E., et al. Journal of the American Chemical Society. doi: 10.1021/jacs.2c11027
Significance
These results offer a new toolbox and approach to identify and develop novel
PKSs that can help efficiently produce biomaterials, biofuels, and bioproducts.
Results
• Produced several polyketides that have never been reported before, including
product with phenyl sidechain.
• Modeled 1000+ AT active site pockets to predict approximate AT substrate
range based on active site volumes.
Approach
• Researchers developed a new method that involves replacing AT domains
native to a particular module with AT domains from other PKS.
• Tested in vitro production of 12 AT-exchanged PKSs + WT with 14 extender
substrates.
In vitro reaction of 12 AT-exchanged PKSs with 14 substrates
MS
signal
2. Office of Biological and Environmental Research
Microbial production of high octane
olefinic ester biofuels
Background/Objective
• Advanced spark ignition engines require high performance fuels
with resistance to autoignition.
• High titer bioproduction of esters with favorable blend
characteristics could improve fuel performance while reducing
carbon intensity.
Carruthers, D.N., et al. Biotechnol Biofuels, https://doi.org/10.1186/s13068-023-02301-7
Figure 1: Isoprenyl acetate accumulation by select E. coli DH1 strains
grown in 1-L fed-batch reactor with M9 medium and 100 g glucose feed.
Results
Demonstrated novel bioproduction of isoprenyl and prenyl acetate as
well as isoprenyl and prenyl lactate.
Significance
• Achieved 28 g/L isoprenyl acetate titer on glucose over 120 hours in
minimal medium (75.7% theoretical maximum).
• Isoprenyl acetate is both a promising blend candidate (bOS = 22.9 in
10% RBOB) and a precursor to jet fuel (DMCO).
Approach
Mevalonate pathway derived C5 alcohols and selected acyltransferases
were paired to generate olefinic esters.
3. Office of Biological and Environmental Research
A suite of constitutive promoters for
tuning gene expression in plants
Background/Objective
Current plant synthetic biology efforts are largely limited by the
heavy reliance on a small set of strong promoters, precluding
more nuanced and refined engineering endeavors.
Approach
We characterize a suite of constitutive promoters that span a wide
range of transcriptional levels and develop a GoldenGate-based
plasmid toolkit named PCONS.
Results
We demonstrate how easy access to a stepwise gradient of expression
levels can be used for optimizing synthetic transcriptional systems
and the production of small molecules in planta.
Significance/Impacts
Our findings showcase the advantages of the PCONS library as an
invaluable toolkit for plant synthetic biology.
Zhou, et al. ACS Syn Biol, https://doi.org/10.1021/acssynbio.3c00075
4. Office of Biological and Environmental Research
Elongated galactan mediate cellulose–pectin
interactions in engineered Arabidopsis
Background
• Understanding secondary cell wall nanoarchitecture can be extremely
helpful to predictively redesign the biomass composition of bioenergy crops.
• To do this, we need to develop a realistic, testable model of cell wall
nanoarchitecture.
Approach
Employ multi-dimensional solid-state NMR to investigate the native cell
wall architecture of engineered model plants and DOE flagship bioenergy
crops. Iteratively test cell wall models with engineered material.
Results
The elongated pectic galactan chains in engineered Arabidopsis compete for
cellulose binding sites xyloglucan and pectic backbone, which results in a
loosened SCW architecture.
Significance
This discovery is important for the rational engineering of improved bioenergy
crops that combine excellent growth with improved downstream processing
properties.
Gao, Yu, et al. The Plant Journal, https://doi.org/10.1111/tpj.16242
Figure 1: a) Overlaid T1-compensated proton driven spin diffusion
(PDSD) spectra with mixing times of 200 and 1000 ms; b) Models of
secondary cell wall architecture of wild-type and high galactan
Arabidopsis.
b.
a.
6. Office of Biological and Environmental Research
A dolabralexin-deficient mutant provides insight
into specialized diterpenoid metabolism in maize
Background/Objective
Two major groups of specialized metabolites in maize (Zea mays), termed
kauralexins and dolabralexins, serve as known or predicted diterpenoid defenses
against pathogens, herbivores, and other environmental stressors.
Approach
We examined dolabralexin structural diversity, tissue-specificity, and stress-
elicited production in a defined biosynthetic pathway mutant.
Results
We identified dolabradienol as a previously undetected pathway metabolite and
characterized its enzymatic production.
Significance/Impacts
These results suggest an interactive role of maize dolabralexins in plant vigor
during abiotic stress.
Murphy, et al. Plant Physiol doi: 10.1093/plphys/kiad150
