scholarly journals The testis-specific serine proteases PRSS44, PRSS46, and PRSS54 are dispensable for male mouse fertility†

2019 ◽  
Author(s):  
Richard J Holcomb ◽  
Seiya Oura ◽  
Kaori Nozawa ◽  
Katarzyna Kent ◽  
Zhifeng Yu ◽  
...  
Keyword(s):  
Serine Proteases ◽  
Sperm Morphology ◽  
Homozygous Deletion ◽  
Developmental Expression ◽  
Sperm Function ◽  
Deletion Mutants ◽  
Es Cell ◽  
Functional Roles ◽  
Functional Genetics ◽  
The Individual

Abstract High-throughput transcriptomics and proteomics approaches have recently identified a large number of germ cell–specific genes with many that remain to be studied through functional genetics approaches. Serine proteases (PRSS) constitute nearly one-third of all proteases, and, in our bioinformatics screens, we identified many that are testis specific. In this study, we chose to focus on Prss44, Prss46, and Prss54, which we confirmed as testis specific in mouse and human. Based on the analysis of developmental expression in the mouse, expression of all four genes is restricted to the late stage of spermatogenesis concomitant with a potential functional role in spermiogenesis, spermiation, or sperm function. To best understand the male reproductive requirement and functional roles of these serine proteases, each gene was individually ablated by CRISPR/Cas9-mediated ES cell or zygote approach. Homozygous deletion mutants for each gene were obtained and analyzed for phenotypic changes. Analyses of testis weights, testis and epididymis histology, sperm morphology, and fertility revealed no significant differences in Prss44, Prss46, and Prss54 knockout mice in comparison to controls. Our results thereby demonstrate that these genes are not required for normal fertility in mice, although do not preclude the possibility that these genes may function in a redundant manner. Elucidating the individual functional requirement or lack thereof of these novel genes is necessary to build a better understanding of the factors underlying spermatogenesis and sperm maturation, which has implications in understanding the etiology of male infertility and the development of male contraceptives.

Expression of an inwardly rectifying K+ channel, Kir4.1, in satellite cells of rat cochlear ganglia

1999 ◽  
Vol 277 (4) ◽  
pp. C638-C644 ◽  
Author(s):  
Hiroshi Hibino ◽  
Yoshiyuki Horio ◽  
Akikazu Fujita ◽  
Atsushi Inanobe ◽  
Katsumi Doi ◽  
...  
Keyword(s):  
Electrical Properties ◽  
Satellite Cells ◽  
Auditory Nerve ◽  
Developmental Expression ◽  
K Channel ◽  
Autonomic Ganglion ◽  
Functional Roles ◽  
Myelin Sheaths ◽  
Ganglion Neurons ◽  
Inwardly Rectifying

Satellite cells are glial cells wrapped around somata of sensory and autonomic ganglion neurons. Neither their functional roles nor electrical properties have been fully clarified so far. Using immunohistochemistry, we found that inwardly rectifying K+ channel subunit Kir4.1 (also called Kir1.2 or KAB-2) was expressed prominently in the satellite cells of cochlear ganglia. The Kir4.1 immunoreactivity was localized specifically at the myelin sheaths of satellite cells wrapping the somata of the ganglion neurons. Developmental expression of Kir4.1 in satellite cells paralleled development of the action potential in the auditory nerve. These results suggest that this channel in satellite cells may be responsible for the regulation of K+ extruded from the ganglion neurons during excitation.

scholarly journals Individual-Level and Population-Level Lateralization: Two Sides of the Same Coin

Symmetry ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 739 ◽  
Author(s):  
Elisa Frasnelli ◽  
Giorgio Vallortigara
Keyword(s):  
Evolutionarily Stable Strategy ◽  
Population Level ◽  
Point Of View ◽  
Theoretical Point ◽  
Evolutionarily Stable Strategies ◽  
Functional Roles ◽  
Individual Level ◽  
Social Species ◽  
The Individual ◽  
Evolutionarily Stable

Lateralization, i.e., the different functional roles played by the left and right sides of the brain, is expressed in two main ways: (1) in single individuals, regardless of a common direction (bias) in the population (aka individual-level lateralization); or (2) in single individuals and in the same direction in most of them, so that the population is biased (aka population-level lateralization). Indeed, lateralization often occurs at the population-level, with 60–90% of individuals showing the same direction (right or left) of bias, depending on species and tasks. It is usually maintained that lateralization can increase the brain’s efficiency. However, this may explain individual-level lateralization, but not population-level lateralization, for individual brain efficiency is unrelated to the direction of the asymmetry in other individuals. From a theoretical point of view, a possible explanation for population-level lateralization is that it may reflect an evolutionarily stable strategy (ESS) that can develop when individually asymmetrical organisms are under specific selective pressures to coordinate their behavior with that of other asymmetrical organisms. This prediction has been sometimes misunderstood as it is equated with the idea that population-level lateralization should only be present in social species. However, population-level asymmetries have been observed in aggressive and mating displays in so-called “solitary” insects, suggesting that engagement in specific inter-individual interactions rather than “sociality” per se may promote population-level lateralization. Here, we clarify that the nature of inter-individuals interaction can generate evolutionarily stable strategies of lateralization at the individual- or population-level, depending on ecological contexts, showing that individual-level and population-level lateralization should be considered as two aspects of the same continuum.

Expression and spatial heterogeneity of dipeptidyl peptidases in endothelial cells of conduct vessels and capillaries

2011 ◽  
Vol 392 (3) ◽  
Author(s):  
Veerle Matheeussen ◽  
Lesley Baerts ◽  
Guido De Meyer ◽  
Gilles De Keulenaer ◽  
Pieter Van der Veken ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Spatial Heterogeneity ◽  
Serine Proteases ◽  
Published Data ◽  
Microvascular Endothelium ◽  
Dipeptidyl Peptidases ◽  
The Individual ◽  
Immunohistochemical Studies

AbstractDipeptidyl peptidase IV (DPPIV)/CD26 is by far the most extensively studied member of the prolyl oligopeptidase family of serine proteases. The discovery of the related enzymes DPP8 and DPP9 necessitates a (re-)evaluation of the DPPIV-like enzymatic activity in cells and organs. In this study, we aimed (1) to investigate the expression of the individual dipeptidyl peptidases in different types of endothelial cells (ECs) and (2) to reconsider published data in relation to our findings. Examination of DPP expression in rat primary ECs of aortic, endocardial and cardiac microvascular origin revealed the presence of DPPIV-like activity in all cell lysates. More than half of this activity could be attributed to DPP8/9. Western blot analysis revealed an abundance of the DPP8 protein as compared to DPP9. The expression of DPPIV and DPP8 was significantly higher in the cardiac microvascular endothelium than in the other ECs, suggesting a more pronounced role of these DPPs in the microvasculature.In situ, DPP activity in ventricular microvasculature was completely inhibited by sitagliptin, indicating that DPPIV is the predominant DPPIV-like enzyme in this organ. By contrast, immunohistochemical studies indicated DPP9 as the predominant DPP in human carotid artery ECs. In conclusion, our results support a highly regulated expression of individual DPPs in ECs, with a spatial heterogeneity in the cardiovascular tree.

scholarly journals mTFE3, an X-linked transcriptional activator containing basic helix-loop-helix and zipper domains, utilizes the zipper to stabilize both DNA binding and multimerization.

1992 ◽  
Vol 12 (2) ◽  
pp. 817-827 ◽  
Author(s):  
C Roman ◽  
A G Matera ◽  
C Cooper ◽  
S Artandi ◽  
S Blain ◽  
...  
Keyword(s):  
Dna Binding ◽  
Heavy Chain ◽  
Leucine Zipper ◽  
Immunoglobulin Heavy Chain ◽  
Functional Roles ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
The Individual ◽  
Bhlh Proteins ◽  
High Degree

Southwestern (DNA-protein) screening of a murine L-cell cDNA library by using a probe for the microE3 site in the immunoglobulin heavy-chain enhancer yielded a clone, mTFE3, which is a member of the subset of basic helix-loop-helix (BHLH) proteins that also contain a leucine zipper (ZIP). Since the individual contribution of these domains is not well understood for proteins which contain them both, mutational analyses were performed to assess the functional roles of the HLH and ZIP regions for DNA binding and multimerization. The HLH region is stringently required for DNA binding but not for multimerization. The ZIP region is not stringently required for binding or multimerization, but stabilizes both multimer formation and DNA binding. A high degree of conservation at both the amino acid and nucleotide levels between the human transcription factor TFE3 and mTFE3 suggests that mTFE3 is the murine homolog of human TFE3. By using fluorescent in situ hybridization, mTFE3 was mapped to mouse chromosome X in band A2, which is just below the centromere. We show that in addition to the immunoglobulin heavy-chain microE3 site, mTFE3 binds to transcriptional elements important for lymphoid-specific, muscle-specific, and ubiquitously expressed genes. Binding of mTFE3 to DNA induces DNA bending.

Metaphysical Beliefs as Predictors of Death Anxiety

1992 ◽  
Vol 25 (2) ◽  
pp. 95-107 ◽  
Author(s):  
R. K. Naidu ◽  
Ambalika Sinha
Keyword(s):  
Death Anxiety ◽  
The Other ◽  
High Exposure ◽  
Functional Roles ◽  
Significant Relationships ◽  
Attributes Of God ◽  
Low Exposure ◽  
The Individual ◽  
The Impact

The impact of four metaphysical beliefs on death anxiety was investigated. Beliefs about the existence and attributes of God, afterlife, and consequences of suffering were chosen for study. It was hypothesized that any belief which assures the individual a continued existence beyond death would reduce the degree of anxiety felt on encountering death-related stimuli. A test including pictures depicting death and non-death scenes was constructed to measure death anxiety. The sample included 120 householders (60 heads of unsettled and 60 heads of settled families). Half of them lived in high exposure to death sight areas and the other half lived in low exposure areas. Subjects from only low exposure areas revealed significant relationships between beliefs and death anxiety. The results of this study suggest that the beliefs play functional roles that are different for people with different needs.

scholarly journals Sperm morphology, adenosine triphosphate (ATP) concentration and swimming velocity: unexpected relationships in a passerine bird

2016 ◽  
Vol 283 (1837) ◽  
pp. 20161558 ◽  
Author(s):  
Clair Bennison ◽  
Nicola Hemmings ◽  
Lola Brookes ◽  
Jon Slate ◽  
Tim Birkhead
Keyword(s):  
Sperm Morphology ◽  
Passerine Bird ◽  
Negative Association ◽  
Swimming Velocity ◽  
Sperm Function ◽  
Sperm Length ◽  
Atp Content ◽  
Number Of Individuals ◽  
The Relationship ◽  
Sperm Traits

The relationship between sperm energetics and sperm function is poorly known, but is central to our understanding of the evolution of sperm traits. The aim of this study was to examine how sperm morphology and ATP content affect sperm swimming velocity in the zebra finch Taeniopygia guttata . We exploited the high inter-male variation in this species and created extra experimental power by increasing the number of individuals with very long or short sperm through artificial selection. We found a pronounced quadratic relationship between total sperm length and swimming velocity, with velocity increasing with length up to a point, but declining in the very longest sperm. We also found an unexpected negative association between midpiece length and ATP content: sperm with a short midpiece generally contained the highest concentration of ATP. Low intracellular ATP is therefore unlikely to explain reduced swimming velocity among the very longest sperm (which tend to have a shorter midpiece).

scholarly journals Leveraging heterogeneity for neural computation with fading memory in layer 2/3 cortical microcircuits

2017 ◽  
Author(s):  
Renato Duarte ◽  
Abigail Morrison
Keyword(s):  
Large Scale ◽  
Fading Memory ◽  
Multiple Sources ◽  
Biologically Inspired ◽  
Functional Roles ◽  
Layer 2 ◽  
Cortical Microcircuits ◽  
Cortical Models ◽  
The Individual ◽  
And Function

AbstractComplexity and heterogeneity are intrinsic to neurobiological systems, manifest in every process, at every scale, and are inextricably linked to the systems’ emergent collective behaviours and function. However, the majority of studies addressing the dynamics and computational properties of biologically inspired cortical microcircuits tend to assume (often for the sake of analytical tractability) a great degree of homogeneity in both neuronal and synaptic/connectivity parameters. While simplification and reductionism are necessary to understand the brain’s functional principles, disregarding the existence of the multiple heterogeneities in the cortical composition, which may be at the core of its computational proficiency, will inevitably fail to account for important phenomena and limit the scope and generalizability of cortical models. We address these issues by studying the individual and composite functional roles of heterogeneities in neuronal, synaptic and structural properties in a biophysically plausible layer 2/3 microcircuit model, built and constrained by multiple sources of empirical data. This approach was made possible by the emergence of large-scale, well curated databases, as well as the substantial improvements in experimental methodologies achieved over the last few years. Our results show that variability in single neuron parameters is the dominant source of functional specialization, leading to highly proficient microcircuits with much higher computational power than their homogeneous counterparts. We further show that fully heterogeneous circuits, which are closest to the biophysical reality, owe their response properties to the differential contribution of different sources of heterogeneity.

scholarly journals Genome-Wide Analysis of CCT Transcript Factors to Identify Genes Contributing to Photoperiodic Flowering in Oryza rufipogon

2021 ◽  
Vol 12 ◽  
Author(s):  
Xin Peng ◽  
Win Tun ◽  
Shuang-feng Dai ◽  
Jia-yue Li ◽  
Qun-jie Zhang ◽  
...  
Keyword(s):  
Expression Patterns ◽  
Functional Characterization ◽  
Oryza Rufipogon ◽  
Developmental Expression ◽  
Cultivated Rice ◽  
Functional Roles ◽  
Rhythmic Expression ◽  
Photoperiodic Flowering ◽  
In The Wild ◽  
Functional Alleles

Photoperiod sensitivity is a dominant determinant for the phase transition in cereal crops. CCT (CONSTANS, CO-like, and TOC1) transcription factors (TFs) are involved in many physiological functions including the regulation of the photoperiodic flowering. However, the functional roles of CCT TFs have not been elucidated in the wild progenitors of crops. In this study, we identified 41 CCT TFs, including 19 CMF, 17 COL, and five PRR TFs in Oryza rufipogon, the presumed wild ancestor of Asian cultivated rice. There are thirty-eight orthologous CCT genes in Oryza sativa, of which ten pairs of duplicated CCT TFs are shared with O. rufipogon. We investigated daily expression patterns, showing that 36 OrCCT genes exhibited circadian rhythmic expression. A total of thirteen OrCCT genes were identified as putative flowering suppressors in O. rufipogon based on rhythmic and developmental expression patterns and transgenic phenotypes. We propose that OrCCT08, OrCCT24, and OrCCT26 are the strong functional alleles of rice DTH2, Ghd7, and OsPRR37, respectively. The SD treatment at 80 DAG stimulated flowering of the LD-grown O. rufipogon plants. Our results further showed that the nine OrCCT genes were significantly downregulated under the treatment. Our findings would provide valuable information for the construction of photoperiodic flowering regulatory network and functional characterization of the CCT TFs in both O. rufipogon and O. sativa.

scholarly journals Computational Methods for Predicting Functions at The mRNA Isoform Level

2020 ◽  
Author(s):  
Sambit Kumar Mishra ◽  
Viraj Muthye ◽  
Gaurav Kandoi
Keyword(s):  
Alternative Splicing ◽  
Computational Methods ◽  
Regulation Of Gene Expression ◽  
Plant Diseases ◽  
Mrna Isoforms ◽  
Stress Regulation ◽  
Functional Roles ◽  
Alternatively Spliced ◽  
The Individual ◽  
Mrna Isoform

Multiple mRNA isoforms of the same gene are produced via alternative splicing, a biological mechanism that regulates protein diversity while maintaining genome size. Alternatively spliced mRNA isoforms of the same gene may sometimes have very similar sequence, but they can have significantly diverse effects on cellular function and regulation. The products of alternative splicing have important and diverse functional roles, such as response to environmental stress, regulation of gene expression, human heritable and plant diseases. The mRNA isoforms of the same gene, such as the apoptosis associated CASP3 gene, can have dramatically different functions. The shorter mRNA isoform product CASP3-S inhibits apoptosis, while the longer CASP3-L mRNA isoform promotes apoptosis. Despite the functional importance of mRNA isoforms, very little has been done to annotate their functions. The recent years have however seen the development of several computational methods aimed at predicting mRNA isoform level biological functions. These methods use a wide array of proteo-genomic data to develop machine learning-based mRNA isoform function prediction tools. In this review, we discuss the computational methods developed for predicting the biological function at the individual mRNA isoform level.

scholarly journals Assembly of infectious enteroviruses depends on multiple, conserved genomic RNA-coat protein contacts

2020 ◽  
Vol 16 (12) ◽  
pp. e1009146
Author(s):  
Rebecca Chandler-Bostock ◽  
Carlos P. Mata ◽  
Richard J. Bingham ◽  
Eric C. Dykeman ◽  
Bo Meng ◽  
...  
Keyword(s):  
Extensive Study ◽  
Genomic Rna ◽  
Rna Packaging ◽  
Viral Pathogens ◽  
Functional Roles ◽  
Cryo Electron Microscopy ◽  
Evolutionarily Conserved ◽  
The Family ◽  
The Individual ◽  
Sequence Similarities

Picornaviruses are important viral pathogens, but despite extensive study, the assembly process of their infectious virions is still incompletely understood, preventing the development of anti-viral strategies targeting this essential part of the life cycle. We report the identification, via RNA SELEX and bioinformatics, of multiple RNA sites across the genome of a typical enterovirus, enterovirus-E (EV-E), that each have affinity for the cognate viral capsid protein (CP) capsomer. Many of these sites are evolutionarily conserved across known EV-E variants, suggesting they play essential functional roles. Cryo-electron microscopy was used to reconstruct the EV-E particle at ~2.2 Å resolution, revealing extensive density for the genomic RNA. Relaxing the imposed symmetry within the reconstructed particles reveals multiple RNA-CP contacts, a first for any picornavirus. Conservative mutagenesis of the individual RNA-contacting amino acid side chains in EV-E, many of which are conserved across the enterovirus family including poliovirus, is lethal but does not interfere with replication or translation. Anti-EV-E and anti-poliovirus aptamers share sequence similarities with sites distributed across the poliovirus genome. These data are consistent with the hypothesis that these RNA-CP contacts are RNA Packaging Signals (PSs) that play vital roles in assembly and suggest that the RNA PSs are evolutionarily conserved between pathogens within the family, augmenting the current protein-only assembly paradigm for this family of viruses.

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