scholarly journals Mammalian splicing divergence is shaped by drift, buffering in trans, and a scaling law

2021 ◽  
Vol 5 (4) ◽  
pp. e202101333
Author(s):  
Xudong Zou ◽  
Bernhard Schaefke ◽  
Yisheng Li ◽  
Fujian Jia ◽  
Wei Sun ◽  
...  
Keyword(s):  
Scaling Law ◽  
Evolutionary Divergence ◽  
F1 Hybrid ◽  
Adaptive Mutations ◽  
Mammalian Tissues ◽  
Mouse Species ◽  
In Trans ◽  
Flanking Regions ◽  
The Brain ◽  
Splicing Site

Alternative splicing is ubiquitous, but the mechanisms underlying its pattern of evolutionary divergence across mammalian tissues are still underexplored. Here, we investigated the cis-regulatory divergences and their relationship with tissue-dependent trans-regulation in multiple tissues of an F1 hybrid between two mouse species. Large splicing changes between tissues are highly conserved and likely reflect functional tissue-dependent regulation. In particular, micro-exons frequently exhibit this pattern with high inclusion levels in the brain. Cis-divergence of splicing appears to be largely non-adaptive. Although divergence is in general associated with higher densities of sequence variants in regulatory regions, events with high usage of the dominant isoform apparently tolerate more mutations, explaining why their exon sequences are highly conserved but their intronic splicing site flanking regions are not. Moreover, we demonstrate that non-adaptive mutations are often masked in tissues where accurate splicing likely is more important, and experimentally attribute such buffering effect to trans-regulatory splicing efficiency.

scholarly journals Trade-offs between burrowing and biting force in fossorial scincid lizards?

2020 ◽  
Vol 130 (2) ◽  
pp. 310-319
Author(s):  
Margot Le Guilloux ◽  
Aurélien Miralles ◽  
John Measey ◽  
Bieke Vanhooydonck ◽  
James C O’Reilly ◽  
...  
Keyword(s):  
Vital Role ◽  
Cranial Morphology ◽  
Energetic Cost ◽  
Evolutionary Divergence ◽  
Trade Offs ◽  
Large Head ◽  
Functional Advantage ◽  
Phenotypic Diversification ◽  
And Performance ◽  
The Brain

Abstract Trade-offs are thought to be important in constraining evolutionary divergence as they may limit phenotypic diversification. The cranial system plays a vital role in many functions including defensive, territorial, predatory and feeding behaviours in addition to housing the brain and sensory systems. Consequently, the morphology of the cranial system is affected by a combination of selective pressures that may induce functional trade-offs. Limbless, head-first burrowers are thought to be constrained in their cranial morphology as narrow heads may provide a functional advantage for burrowing. However, having a wide and large head is likely beneficial in terms of bite performance. We used 15 skink species to test for the existence of trade-offs between maximal push and bite forces, and explored the patterns of covariation between external head and body morphology and performance. Our data show that there is no evidence of a trade-off between bite and burrowing in terms of maximal force. Species that generate high push forces also generate high bite forces. Our data also show that overall head size covaries with both performance traits. However, future studies exploring trade-offs between force and speed or the energetic cost of burrowing may reveal other trade-offs.

scholarly journals Plasma dilution improves cognition and attenuates neuroinflammation in old mice

GeroScience ◽  
2020 ◽  
Author(s):  
Melod Mehdipour ◽  
Taha Mehdipour ◽  
Colin M. Skinner ◽  
Nathan Wong ◽  
Chao Liu ◽  
...  
Keyword(s):  
Hippocampal Neurogenesis ◽  
Brain Health ◽  
Positive Effects ◽  
Blood Exchange ◽  
Mammalian Tissues ◽  
Systemic Factors ◽  
Secretory Phenotype ◽  
And Function ◽  
Old Mice ◽  
The Brain

AbstractOur recent study has established that young blood factors are not causal, nor necessary, for the systemic rejuvenation of mammalian tissues. Instead, a procedure referred to as neutral blood exchange (NBE) that resets signaling milieu to a pro-regenerative state through dilution of old plasma, enhanced the health and repair of the muscle and liver, and promoted better hippocampal neurogenesis in 2-year-old mice (Mehdipour et al., Aging 12:8790–8819, 2020). Here we expand the rejuvenative phenotypes of NBE, focusing on the brain. Namely, our results demonstrate that old mice perform much better in novel object and novel texture (whisker discrimination) tests after a single NBE, which is accompanied by reduced neuroinflammation (less-activated CD68+ microglia). Evidence against attenuation/dilution of peripheral senescence-associated secretory phenotype (SASP) as the main mechanism behind NBE was that the senolytic ABT 263 had limited effects on neuroinflammation and did not enhance hippocampal neurogenesis in the old mice. Interestingly, peripherally acting ABT 263 and NBE both diminished SA-βGal signal in the old brain, demonstrating that peripheral senescence propagates to the brain, but NBE was more robustly rejuvenative than ABT 263, suggesting that rejuvenation was not simply by reducing senescence. Explaining the mechanism of the positive effects of NBE on the brain, our comparative proteomics analysis demonstrated that dilution of old blood plasma yields an increase in the determinants of brain maintenance and repair in mice and in people. These findings confirm the paradigm of rejuvenation through dilution of age-elevated systemic factors and extrapolate it to brain health and function.

scholarly journals Conservation law for self-paced movements

2016 ◽  
Vol 113 (31) ◽  
pp. 8831-8836 ◽  
Author(s):  
Dongsung Huh ◽  
Terrence J. Sejnowski
Keyword(s):  
Optimal Control ◽  
Scaling Law ◽  
Control Variable ◽  
Level Control ◽  
Internal Motivation ◽  
Internal States ◽  
Motivation Level ◽  
High Level ◽  
The Brain ◽  
Biological Motor

Optimal control models of biological movements introduce external task factors to specify the pace of movements. Here, we present the dual to the principle of optimality based on a conserved quantity, called “drive,” that represents the influence of internal motivation level on movement pace. Optimal control and drive conservation provide equivalent descriptions for the regularities observed within individual movements. For regularities across movements, drive conservation predicts a previously unidentified scaling law between the overall size and speed of various self-paced hand movements in the absence of any external tasks, which we confirmed with psychophysical experiments. Drive can be interpreted as a high-level control variable that sets the overall pace of movements and may be represented in the brain as the tonic levels of neuromodulators that control the level of internal motivation, thus providing insights into how internal states affect biological motor control.

scholarly journals Cloning, sequencing, and evolutionary analysis of the mouse erythropoietin gene.

1986 ◽  
Vol 6 (3) ◽  
pp. 842-848 ◽  
Author(s):  
J D McDonald ◽  
F K Lin ◽  
E Goldwasser
Keyword(s):  
Preliminary Analysis ◽  
Genomic Organization ◽  
Functional Constraint ◽  
Evolutionary Divergence ◽  
Evolutionary Analysis ◽  
The Third ◽  
Different Types ◽  
Flanking Regions

The gene for mouse erythropoietin was cloned and sequenced. We present here a preliminary analysis of the overall genomic organization of the coding portions and the two flanking regions of the gene. This is the third mammalian erythropoietin for which the sequence is available, but it represents the first from a nonprimate species. We investigated the evolutionary divergence of sequence and structure of the three erythropoietins and identified specific regions of the molecules that are apparently under various degrees, and perhaps different types, of functional constraint.

scholarly journals Bimodal sequence composition underlies functional duality of transcribed enhancers

2020 ◽  
Author(s):  
Mario Flores ◽  
Ivan Ovcharenko
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Regulatory Elements ◽  
Mechanisms Of Action ◽  
Sequence Composition ◽  
Helix Formation ◽  
Evolutionarily Conserved ◽  
Triple Helix Formation ◽  
In Trans ◽  
Flanking Regions

Abstract Background:Recent studies have drawn attention to transcribed enhancers (trEs) as important regulatory elements of gene expression; however, their characteristics and mechanisms of action remain poorly understood. Results:We profiled the characteristics of trEs and obtained insights into their mechanisms of action. We found that trEs harbor functional duality related to bimodal sequence composition. TrEs are composed of nonoverlapping cores and flanking regions (flanks): cores function as regular enhancers, while flanks transcribe enhancer RNAs (eRNAs) that can potentially regulate the expression of their target genes in trans. Cores are evolutionarily conserved and compact, while flanks are significantly longer. We observed that approximately 25% of eRNAs transcribed from the flanks likely contribute to trans DNA:RNA triple helix formation, while another 10% likely employ classical mechanisms of RNA-based regulation. We found that the majority of human enhancers are not transcribed, and trEs are strikingly different from regular enhancers in their functional characteristics. In addition, we found evidence for trEs exhibiting functional duality in regulatory locus encapsulation (RLE), effectively providing localized control over the spread of gene expression upregulation by trE cores and other locus enhancers. Conclusions:In summary, our results advocate for enhancer transcription being an uncommon mechanism of gene regulation, and the duality of transcribed enhancer function being a product of additive, not overlapping, DNA sequence encryption.

scholarly journals Latrophilin GPCR Signaling Mediates Synapse Formation

2021 ◽  
Author(s):  
Richard Sando ◽  
Thomas C. Südhof
Keyword(s):  
Synapse Formation ◽  
Neural Circuit ◽  
Gpcr Signaling ◽  
Synapse Loss ◽  
Ca1 Region ◽  
In Trans ◽  
Synaptic Complexes ◽  
Camp Levels ◽  
The Brain

ABSTRACTNeural circuit assembly in the brain requires precise establishment of synaptic connections, but the mechanisms of synapse assembly remain incompletely understood. Latrophilins are postsynaptic adhesion-GPCRs that engage in trans-synaptic complexes with presynaptic teneurins and FLRTs. In CA1-region neurons, Latrophilin-2 and Latrophilin-3 are essential for formation of entorhinal-cortex-derived and Schaffer-collateral-derived synapses, respectively. However, it is unknown whether latrophilins function as GPCRs in synapse formation. Here, we show that Latrophilin-2 and Latrophilin-3 exhibit constitutive GPCR activity that increases cAMP levels, which was blocked by a mutation interfering with G-protein and arrestin interactions of GPCRs. The same mutation impaired the ability of Latrophilin-2 and Latrophilin-3 to rescue the synapse-loss phenotype in Latrophilin-2 and Latrophilin-3 knockout neurons in vivo. Our results suggest that Latrophilin-2 and Latrophilin-3 require GPCR signaling in synapse formation, indicating that latrophilins promote synapse formation in the hippocampus by activating a classical GPCR-signaling pathway.

scholarly journals Species-specific differences in synaptic transmission and plasticity

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Prateep Beed ◽  
Saikat Ray ◽  
Laura Moreno Velasquez ◽  
Alexander Stumpf ◽  
Daniel Parthier ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Synaptic Transmission ◽  
Mossy Fiber ◽  
Mossy Fibers ◽  
Evolutionary Divergence ◽  
Short Term Plasticity ◽  
Species Specific ◽  
The Brain ◽  
Lower Expression

Abstract Synaptic transmission and plasticity in the hippocampus are integral factors in learning and memory. While there has been intense investigation of these critical mechanisms in the brain of rodents, we lack a broader understanding of the generality of these processes across species. We investigated one of the smallest animals with conserved hippocampal macroanatomy—the Etruscan shrew, and found that while synaptic properties and plasticity in CA1 Schaffer collateral synapses were similar to mice, CA3 mossy fiber synapses showed striking differences in synaptic plasticity between shrews and mice. Shrew mossy fibers have lower long term plasticity compared to mice. Short term plasticity and the expression of a key protein involved in it, synaptotagmin 7 were also markedly lower at the mossy fibers in shrews than in mice. We also observed similar lower expression of synaptotagmin 7 in the mossy fibers of bats that are evolutionarily closer to shrews than mice. Species specific differences in synaptic plasticity and the key molecules regulating it, highlight the evolutionary divergence of neuronal circuit functions.

Identification and Distribution of β-Phenylethylamine in the Rat

1973 ◽  
Vol 51 (7) ◽  
pp. 995-1002 ◽  
Author(s):  
D. A. Durden ◽  
S. R. Philips ◽  
Alan A. Boulton
Keyword(s):  
Wistar Rats ◽  
Internal Standard ◽  
Ion Exchange Chromatography ◽  
Exchange Chromatography ◽  
Mass Spectrometric ◽  
Ion Current ◽  
Mammalian Tissues ◽  
Male Wistar Rats ◽  
Dansyl Derivatives ◽  
The Brain

A procedure for the quantitative evaluation of some amines present in mammalian tissues has been developed. It includes isolation of the amines by ion exchange chromatography followed by conversion to dansyl derivatives, chromatographic separation, and quantitation by the mass spectrometric integrated ion current technique. The use of an isotopically labelled internal standard improves the precision and sensitivity of the analysis.The concentrations of β-phenylethylamine in some tissues of male Wistar rats were (ng/g); brain 1.8 ± 0.4, heart 5.7 ± 3.1, kidney 20.5 ± 2.2, liver 2.0 ± 0.7, lung 4.0 ± 1.4, and spleen 4.7 ± 2.7. In the brain the hypothalamus contained 25.3 ± 5.0, the cerebellum 3.4 ± 0.5, the stem 2.2 ± 0.9, the caudate nucleus 8.0 ± 0.3, and the 'rest' 1.1 ± 0.2 ng/g, respectively.

scholarly journals Nitric Oxide Inactivation Mechanisms in the Brain: Role in Bioenergetics and Neurodegeneration

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Ricardo M. Santos ◽  
Cátia F. Lourenço ◽  
Ana Ledo ◽  
Rui M. Barbosa ◽  
João Laranjinha
Keyword(s):  
Nitric Oxide ◽  
Direct Reaction ◽  
Tyrosine Residues ◽  
Mammalian Tissues ◽  
Temporal Measurement ◽  
The Brain ◽  
And Diffusion ◽  
Key Questions ◽  
Lack Of Knowledge

During the last decades nitric oxide (•NO) has emerged as a critical physiological signaling molecule in mammalian tissues, notably in the brain.•NO may modify the activity of regulatory proteins via direct reaction with the heme moiety, or indirectly, via S-nitrosylation of thiol groups or nitration of tyrosine residues. However, a conceptual understanding of how•NO bioactivity is carried out in biological systems is hampered by the lack of knowledge on its dynamicsin vivo. Key questions still lacking concrete and definitive answers include those related with quantitative issues of its concentration dynamics and diffusion, summarized in the how much, how long, and how far trilogy. For instance, a major problem is the lack of knowledge of what constitutes a physiological•NO concentration and what constitutes a pathological one and how is•NO concentration regulated. The ambient•NO concentration reflects the balance between the rate of synthesis and the rate of breakdown. Much has been learnt about the mechanism of•NO synthesis, but the inactivation pathways of•NO has been almost completely ignored. We have recently addressed these issuesin vivoon basis of microelectrode technology that allows a fine-tuned spatial and temporal measurement•NO concentration dynamics in the brain.

Cluster decay half-lives in trans-tin and transition metal region using RMF theory

2021 ◽  
Author(s):  
Ajeet Singh ◽  
A Shukla ◽  
M K Gaidarov
Keyword(s):  
Transition Metal ◽  
Scaling Law ◽  
Mean Field ◽  
Magic Number ◽  
Neutron Number ◽  
Cluster Decay ◽  
Relativistic Mean Field ◽  
Empirical Relations ◽  
In Trans ◽  
Rmf Model

Abstract In the present work, we have studied the alpha-like clusters (8Be, 12C, 16O, 20Ne, and 24Mg) decay half-lives in the trans-tin region for (106-116Xe, 108-122Ba, 114-124Ce, and 118-128Nd) and in transition metal region for (156-166Hf, 158-172W, 160-174Os, 166-180Pt, and 170-182Hg) nuclei. These half-lives have been calculated using the shape parametrization model of cluster decay in conjunction with the relativistic mean-field (RMF) model with the NL3* parameter set. Thus calculated cluster decay half-lives are also compared with the half-lives computed using the latest empirical relations, namely Universal decay law (UDL) and the Scaling Law given by Horoi et al.. From the calculated results, it has been observed that in the trans-tin region, the minimum cluster decay half-lives are found at nearly doubly magic or doubly magic daughter 100Sn (Nd = 50, Nd is the neutron number of the daughter nuclei) shell effect at Nd = 50 and in transition metal region, half-lives are minimum at Nd = 82, which is a magic number. Further, the Geiger-Nuttal plots of half-lives showing Q dependence for different alpha-like clusters from various CR emitters that have been plotted are found to vary linearly.

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