Miracle-dz/UniFAR-FTUs huggingface dataset:
A general principle of dendritic constancy – a neuron’s size and shape invariant excitability

Reducing neuronal size results in less cell membrane and therefore lower input conductance. Smaller neurons are thus more excitable as seen in their voltage responses to current injections in the soma. However, the impact of a neuron’s size and shape on its voltage responses to synaptic activation in dendrites is much less understood. Here we use analytical cable theory to predict voltage responses to distributed synaptic inputs and show that these are entirely independent of dendritic length. For a given synaptic density, a neuron’s response depends only on the average dendritic diameter and its intrinsic conductivity. These results remain true for the entire range of possible dendritic morphologies irrespective of any particular arborisation complexity. Also, spiking models result in morphology invariant numbers of action potentials that encode the percentage of active synapses. Interestingly, in contrast to spike rate, spike times do depend on dendrite morphology. In summary, a neuron’s excitability in response to synaptic inputs is not affected by total dendrite length. It rather provides a homeostatic input-output relation that specialised synapse distributions, local non-linearities in the dendrites and synaptic plasticity can modulate. Our work reveals a new fundamental principle of dendritic constancy that has consequences for the overall computation in neural circuits. In brief We show that realistic neuron models essentially collapse to point neurons when stimulated by randomly distributed inputs instead of by single synapses or current injection in the soma. Highlights A simple equation that predicts voltage in response to distributed synaptic inputs. Responses to distributed and clustered inputs are largely independent of dendritic length. Spike rates in various Hodgkin Huxley (HH) like or Leaky Integrate-and-Fire (LIF) models are largely independent of morphology. Precise spike timing (firing pattern) depends on dendritic morphology. NeuroMorpho.Org database-wide analysis of the relation between dendritic morphology and electrophysiology. Our equations set precise input-output relations in realistic dendrite models.
Step-wise Hydration of Magnesium by Four Water Molecules Precedes Phosphate Release in a Myosin Motor

Molecular motors, such as myosin, kinesin, and dynein, convert the energy released by the hydrolysis of ATP into mechanical work, which allows them to undergo directional motion on cytoskeletal tracks. This process is achieved through synchronization between the catalytic activity of the motor and the associated changes in its conformation. A pivotal step in the chemomechanical transduction in myosin motors occurs after they bind to the actin filament, which triggers the release of phosphate (Pi, product of ATP hydrolysis) and the rotation of the lever arm. Here, we investigate the mechanism of phosphate release in myosin VI, which has been debated for over two decades, using extensive molecular dynamics simulations involving multiple trajectories each several μs long. Because the escape of phosphate is expected to occur on time-scales on the order of milliseconds in myosin VI, we observed Pi release only if the trajectories were initiated with a rotated phosphate inside the nucleotide binding pocket. The rotation provided the needed perturbation that enabled successful expulsions of Pi in several trajectories. Analyses of these trajectories lead to a robust mechanism of Pi release in the class of motors belonging to the myosin super family. We discovered that although Pi populates the traditional “back door” route, phosphate exits through various other gateways, thus establishing the heterogeneity in the escape routes. Remarkably, we observe that the release of phosphate is preceded by a step-wise hydration of the ADP-bound magnesium ion. In particular, the release of the anion occurred only after four water molecules hydrate the cation (Mg2+). By performing comparative structural analyses, we suggest that the hydration of magnesium is the key step in the phosphate release in a number of ATPases and GTPases that share a similar structure in the nucleotide binding pocket. Thus, nature may have evolved hydration of Mg2+ by discrete water molecules as a general molecular switch for Pi release, which is a universal step in the catalytic cycle of many machines which share little sequence or structural similarity.
Atypical neurogenesis in induced pluripotent stem cell (iPSC) from autistic individuals

Autism is a heterogenous collection of disorders with a complex molecular underpinning. Evidence from post mortem studies using adult brains have identified atypical co-expression of genes which may occur during the prenatal period. Recent studies using induced pluripotent stem cells (iPSCs) generated from autistic individuals have suggested that prenatal development is a critical period for the emergence of pathophysiology associated with this condition. However, how early during development these differences emerge and whether such alterations can be seen across the development of multiple brain regions is unclear. In this study we investigated whether early prenatal stages of neurodevelopment differ between iPSCs generated from typically developing and autistic individuals. We specifically selected autistic individuals unrelated to each other with a heterogeneous genetic background and no known comorbidities, to probe for common molecular phenotypes. Differentiation of iPSCs towards a cortical lineage revealed abnormal cell fate acquisition from an early stage of development. Interestingly, abnormal differentiation occurred in the absence of alteration in cell proliferation during cortical differentiation, differing from previous studies. Moreover, these effects appeared specific for the acquisition of a cortical fate, as differentiation of iPSCs towards a midbrain lineage was not accompanied by differences in neurogenesis between typically developing and autism iPSC lines. RNA-sequencing on a subset of our cohort further revealed autism-specific signatures during cortical differentiation similar to that observed in post mortem studies, indicating a potential common biological mechanism. Together, these data suggest unique developmental differences associated with autism may establish at an early prenatal stage.
Protective effect of Kumquat fruits and carrot seeds extracts against brain aging in rats

Introduction: Protection of brain against accelerated aging helps avoiding the occurrence of neurodegenerative diseases. So, the current work was conducted to evaluate the rescuing role of kumquat fruits crude ethanol extract, carrot seeds ethanol and petroleum ether extracts against the brain aging induced by D-galactose in rats. Methods: Forty male Sprague Dawley rats were divided equally into five groups. Group I was served as normal control, rats of group II were daily injected intraperitoneally (i.p.) with 150 mg/kg BW of D-galactose. Rats of group III, IV and V were daily injected i.p. with the same dose of D-galactose and administered orally with 250 mg/kg BW/day of kumquat fruits crude ethanol extract, carrot seeds ethanol extract and carrot seeds petroleum ether extract, respectively. After 6 weeks the rats were scarified, brain tissues were analyzed for malondialdehyde (MDA), catalase (CAT) as well as histological examination. Also, the plasma was analyzed for MDA, tumor necrosis factor-α (TNF-α), creatinine and urea levels, as well as CAT, butyrylcholinesterase (BChE), aspartate transaminase (AST) and alanine transaminase (ALT) activities. Results: From the results, it was elucidated that the tested extracts suppressed both the reduction in CAT and the elevation in MDA either in brain or plasma and the increase in plasma TNF-α, BChE as well as liver and kidney parameters. Conclusion: The tested extracts can be served as potent protective agents against the accelerated aging parameters which may be due to anti-oxidant and anti-inflammatory activities.
Plant trichomes and the biomechanics of defense in various systems, with Solanaceae as a model

Plant trichomes are epidermal outgrowths of varying size and form. While the chemical defensive function of the secretory trichomes is well established, the biomechanical function of the non-glandular trichomes emerges as another major defensive strategy of plants. In particular, trichomes impede the locomotion of insect herbivores both by serving as a physical barrier and by wounding them. Solanaceous trichomes are often viewed as a model for the trichome development and defensive function. In particular, trichomes in tomato and relative species have been extensively examined, with different trichome types being precisely described. This review attempts to summarize the knowledge on trichomal defense and biomechanics, with a special emphasis on Solanaceae species, and suggests several avenues for future research.
NEMO: A phase 3 trial of binimetinib (MEK162) versus dacarbazine in patients with untreated or progressed after first-line immunotherapy unresectable or metastatic NRAS-mutant cutaneous melanoma.

TPS9102 Background: Melanoma tumors often harbor mutations in the mitogen-activated protein kinase-signaling pathway family members BRAF or NRAS. NRAS mutations, observed in about 15% of patients with melanoma, are associated with higher tumor proliferation and poorer prognoses. A large retrospective analysis (n = 677) demonstrated that NRAS mutations are independently predictive of poor survival in patients with cutaneous melanoma (Jakob et al., 2011). With no approved targeted therapies for melanoma patients with NRAS-mutant tumors, treatments are currently limited to chemotherapy and/or immunotherapy. Binimetinib (MEK162), a potent and selective inhibitor of MEK1/2, has demonstrated promising phase 2 clinical activity in this patient subset. Here we describe the “NRAS mElanoma and MEK inhibitOr” (NEMO) trial, an ongoing phase 3 study designed to compare the efficacy of binimetinib vs dacarbazine in patients with metastatic NRAS-mutant cutaneous melanoma (NCT01763164). Methods: NEMO is a 2-arm, open-lab.
Great ape mutation spectra vary across the phylogeny and the genome due to distinct mutational processes that evolve at different rates

Recent studies of hominoid variation have shown that mutation rates and spectra can evolve rapidly, contradicting the fixed molecular clock model. The relative mutation rates of three-base-pair motifs differ significantly among great ape species, suggesting the action of unknown modifiers of DNA replication fidelity. To illuminate the footprints of these hypothetical mutators, we measured mutation spectra of several functional compartments (such as late-replicating regions) that are likely targeted by localized mutational processes. Using genetic diversity from 88 great apes, we find that compartment-specific mutational signatures appear largely conserved between species. These signatures layer with species-specific signatures to create rich mutational portraits: for example, late-replicating regions in gorillas contain an identifiable mixture of a replication timing signature and a gorilla-specific signature. Our results suggest that cis-acting mutational modifiers are highly conserved between species and transacting modifiers are driving rapid mutation spectrum evolution.
Recent trends in bovine reproductive biotechnologies.

Abstract The establishment of non-invasive and low-cost reproductive techniques are key interest currently. Although, numerous reproductive techniques have been invented during the last few decades, the procedures adopted require further refinement Artificial insemination is a unique and simple reproductive technique offering substantial and rapid genetic transfer. Use of fresh semen has given good results, but success and reach of frozen semen technology is controversial in developing countries. Optimal use of sexed semen requires precise accuracy in ovulation to obtain satisfactory pregnancy rates. Further modification of the sperm sorter technique is necessary to obtain the maximum number of sexed sperm within a limited time. Embryo transfer technology has been well developed for dairy animals, but currently the main focus is on in-vitro embryo production. Its importance is further magnified for animals with good genetics and species near to extinction. Although cloning has been successfully carried out in many species, its cost, neonatal abnormalities and ethical use require further discussion. Transgenesis and stem cells have revolutionized the world through the production of transgenic animals and disease management through mesenchymal stem cells. These technologies are the advanced reproductive technologies which need further research, especially in bovines. In conclusion, modern reproductive techniques are a basic requirement of a modern dairy farming system but their use must be rationalized in an ethical and cost-effective manner.
The potency of chitosan-based Pinus merkusii bark extract nanoparticles as anti-cancer on HeLa cell lines

Background and Aim: Cervical cancer accounts for the fourth as a cause of death from cancer in women worldwide, with more than 85% of events and deaths occurring in developing countries. The main problems of chemotherapy are the lack of selectivity and drug resistance. This study aimed to investigate the signal transduction of chitosan-based Pinus merkusii bark extract nanoparticles (Nano-PMBE) as an anticancer on HeLa cell line. Materials and Methods: Nano-PMBE was prepared based on the ionic gelation method. Its anticancer activities in HeLa cells were investigated through cytotoxicity test, cell cycle, and apoptosis analysis. The expression of p53 and caspase-9 was also observed. Results: The results showed that Nano-PMBE has a size of 394.3 nm. Meanwhile, the Nano-PMBE was cytotoxic to HeLa cells (IC50 of 384.10 µg/ml), caused G0/G1 phase arrest and cell apoptosis in HeLa cells. Besides, the expression of p53 and caspase-9 has increased. Conclusion: The results showed a notable anticancer effect of Nano-PMBE by arresting the cell cycle and inducing apoptosis in HeLa cells, suggesting that it might have therapeutic potential for cervical cancer. Further research is needed to find out more about the anticancer mechanism of Nano-PMBE in HeLa cells to in vivo and clinical studies.
Characterization of the Human Cytomegalovirus UL75 Late Gene Promoter

CHARACTERIZATION OF THE HUMAN CYTOMEGALOVIRUS UL75 LATE GENE PROMOTER Bernard J.P. McWatters Old Dominion University, 2001 Chair: Dr. Julie A. Kerry Gene expression during productive infection by the human cytomegalovirus (HCMV) occurs in an ordered and sequential manner, beginning with immediate early (IE), then early (E) and finally late (L) gene expression. Significant work has addressed the regulation of EE and E gene expression while relatively little work has addressed the control of late gene expression. In order to further address HCMV late gene expression, the promoter of the HCMV UL75 (glycoprotein H, gH) late gene was characterized. The data obtained in this study were combined with observations made in two other studies that have addressed HCMV late gene expression to develop a model of the regulation of HCMV late gene expression. The gH promoter and numerous promoter mutants were cloned into a reporter vector to address sequences responsible for the regulation of gene expression. These gH promoter constructs were transfected into human fibroblasts and subsequently infected with HCMV. Our data revealed that viral infection was necessary to activate expression from the gH promoter, confirming observations made in other HCMV late gene studies. Deletion analysis of promoter sequences revealed that sequences upstream of the TATA element in the gH promoter are not necessary for wild type levels of gene expression. Further deletion of sequences downstream of the mRNA cap site (+1) revealed the presence of upstream control elements that were masked by the dominant downstream activation domain. Mutational analysis demonstrated that a PEA3 element present in this Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. downstream domain is important for promoter activation. In addition, gel shift analysis revealed direct protein binding to the PEA3 element. Deletion and mutational analysis also revealed that multiple sequence elements between -38 and +14 are responsible for gH promoter activation. Gel shift analysis using promoter sequences from this region as probes and competitors revealed protein binding to a DAS element at +1 to +6. Despite direct protein binding, transfection analysis in fibroblasts revealed that the DAS element was not important for promoter activation, however it may be important in other cell types. Gel shift analysis also demonstrated a protein binding to promoter sequences between +1 and +35 at late times of infection that is likely involved in activation. This analysis reveals the complexity of gH promoter regulation as well as demonstrating similarities between all three HCMV late gene promoters characterized thus far. Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Copyright, 2001, by Bernard J.P. McWatters, All Rights Reserved. Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
Behavioral genetics in Cattle- a review

Behavioral traits are the main controllable factors for domesticating cattle. The traits profoundly influence on the longevity of cattle and play a remarkable role in animal welfare assessment and animal ethics limitations determination. In the present study, the genetics of cattle behavior is discussed. Current breeding status of cattle behavioral traits is also reviewed, regarding the high individual variation of behavioral traits and almost high correlations between the traits and performance. Moreover, recent findings of characterizing quantitative trait loci (QTL) for behavioral traits of cattle is considered, as well as the most important problems in the breeding of cattle behavioral traits such as a large variety of methods which are used to evaluate the traits.
The complete mitochondrial genome sequence and gene organization of Istigobius campbelli (Perciformes, Gobiidae) with phylogenetic consideration

Abstract The complete mitochondrial genome DNA sequence of Istigobius campbelli was 16,527 bp in length. It consists of 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes, and 1 control region. 28 of the 37 genes were encoded on the heavy strand, and 9 of them were encoded on the light strand. The overall base composition of the genome is 27.84% A, 25.81% T, 29.68% C, and 16.67% G. The phylogenetic tree suggested I. campbelli was genetically closest to Acentrogobius pflaumii and Oxyurichthys formosanus. This study could provide valuable information for further studies on I. campbelli.
Evaluation of commercial products based on Isaria fumosorosea and Verticillium lecanii fungi as an alternative in the biocontrol of Phenacoccus solenopsis Tinsley (Hemiptera: Pseudococcidae)

In the Northwest of Mexico, Phenacoccus solenopsis has been recognized as an aggressively invasive species on cotton plants. Therefore, the aim of the present study was to evaluate the effectiveness of two fungal commercial bioinsecticides (Verticillium lecanii and Isaria fumosorosea) against P. solenopsis under laboratory and semi-fields conditions. Our results showed a high mortality by V. lecanii (100%) followed by I. fumosorosea (40%) and control (0%) after 96 h of exposure. Thirty days after initiating the experiment, we observed a significant reduction of the disease index in cotton plants exposed to I. fumosorosea and V. lecanii (50% and 48%, respectively) compared with control (76%). www.biotaxa. org/RSEA. ISSN 1851-7471 (online) Revista de la Sociedad Entomológica Argentina 78(3): 1-6, 2019 Copyright GONZÁLEZ-MENDOZA, D. et al.This is an open access article distributed under the terms of the Creative Commons Attribution Licence (CC BY 4.0) 1 The use of V. lecanii and I . fumosorosea did not show significant changes in the physiological parameters of plants (chlorophyll, polyphenol contents, anthocyanins and potential photochemical yield values) compared with the control after 30 days of exposure to entomopathogenic fungi. Currently, the available information about mode of action of commercial formulations using I. fumosorosea and V. lecanii for biocontrol of P. solenopsis is scarce in Mexico compared with other countries. Therefore, studies focused on their effectiveness are necessary.
Shifts of the Mean Centers of Potential Vegetation Ecosystems under future climate change in Eurasia

Climate change dominantly controls the spatial distributions of potential vegetation ecosystems; the shift trends in the mean centers of potential vegetation ecosystems could be used to explain their responses to climate change. In terms of the climate observation data of Eurasia for the period from 1981 to 2010 and the climate scenario data for the period from 2011 to 2100 under the three Representative Concentration Pathways (RCPs) scenarios of RCP2.6, RCP4.5 and, RCP8.5, which were released by the Coupled Model Intercomparison Project Phase 5 (CMIP5), the Holdridge Life Zone (HLZ) ecosystem model was improved to quantitatively classify the potential vegetation types, and the shift model of mean center was adopted to compute the trends in the spatiotemporal shifts of potential vegetation types in Eurasia. The results showed that the mean centers of the major potential vegetation ecosystems would be distributed in the central and southern parts of Eurasia. Under the RCP2.6, RCP4.5, and RCP8.5 scenarios, the potential shift distances of the mean centers of the vegetation types under the RCP8.5 scenario would be the largest, and those of the polar/nival area, subpolar/alpine moist tundra, warm temperate dry forest, subtropical moist forest, cool temperate moist forest, cool temperate wet forest, subtropical wet forest, subtropical thorn woodland, warm temperate moist forest and subtropical dry forest would be larger than those in the other potential vegetation types in Eurasia. Moreover, the shift directions of the mean centers of the major potential vegetation types would generally shift northward, and subtropical dry forest, warm temperate moist forest and subpolar/alpine moist tundra would be the most sensitive to change among all vegetation types under the three scenarios for the period from 2011 to 2100.