Miracle-dz/UniFAR-FTUs huggingface dataset:
Loss of O-GlcNAcylation on MeCP2 Thr 203 Leads to Neurodevelopmental Disorders

Mutations of the X-linked methyl-CpG-binding protein 2 (MECP2) gene in humans are responsible for most cases of Rett syndrome (RTT), an X-linked progressive neurological disorder. While genome-wide screens in clinical trials reveal several putative RTT-associated mutations on MECP2, their causative relevance regarding the functional regulation of MeCP2 on the etiologic sites at the protein level require more evidence. In this study, we demonstrate that MeCP2 is dynamically modified by O-linked-β-N-acetylglucosamine (O-GlcNAc) at threonine 203 (T203), an etiologic site in RTT patients. Disruption of the O-GlcNAcylation of MeCP2 specifically at T203 impairs dendrite development and spine maturation in cultured hippocampal neurons, and disrupts neuronal migration, dendritic spine morphogenesis and dysfunction of synaptic transmission in the developing and juvenile mouse cerebral cortex. Mechanistically, genetic disruption of O-GlcNAcylation at T203 on MeCP2 decreases neuronal activity-induced induction of Bdnf transcription. Our study highlights the critical role of MeCP2 T203 O-GlcNAcylation in neural development and synaptic transmission potentially via BDNF.
A model-based analysis of the mechanical cost of walking on uneven terrain

Human walking on uneven terrain is energetically more expensive than on flat, even ground. This is in part due to increases in, and redistribution of positive work among lower limb joints. To improve understanding of the mechanical adaptations, we performed analytical and computational analyses of simple mechanical models walking over uneven terrain comprised of alternating up and down steps of equal height. We simulated dynamic walking models using trailing leg push-off and/or hip torque to power gait, and quantified the compensatory work costs vs. terrain height. We also examined the effect of swing leg dynamics by including and excluding them from the model. We found that greater work, increasing approximately quadratically with uneven terrain height variations, was necessary to maintain a prescribed average forward speed. Greatest economy was achieved by modulating precisely-timed push-offs for each step height. Least economy was achieved with hip power, which did not require as precise timing. This compares well with observations of humans on uneven terrain, showing similar near-normal push-off but with more variable step timing, and considerably more hip work. These analyses suggest how mechanical work and timing could be adjusted to compensate for real world environments.
Optimisation of brain states and behavioural strategies when learning complex tasks

We designed two self-ordered switching (SOS) fMRI paradigms to investigate how people optimise their behaviour whilst managing competing demands. SOS was performed with feedback and minimal training (study 1) or without feedback but with extensive training (study 2). We hypothesised that behavioural performance would improve with practise and that this would be reflected in an optimisation of the brain states associated with the task events. As expected, response speed was slower in study 1, but increased with practise at a greater rate than in study 2. Furthermore, individuals who established more structured routines benefited from superior task performance. This behavioural optimisation was reflected by an ongoing redeployment of the neural resources supporting routine and task-switching trials. Specifically, as structured behaviour developed, there was increased activation of dorsal frontoparietal regions to switching events but decreased activation for routine trials. Conversely, the default mode network showed increased activation to routine trials with learning. Notably, the optimisation of behavioural performance corresponded with increases in frontoparietal and subcortical connectivity. These results demonstrate that a fundamental property of human behaviour is the establishment of structured task schemas that enable neurocognitive resources to be selectively focused on key executive events.
A Comprehensive Study on Antioxidant Properties of Crude Extracts from Fruits of Berberis vulgaris L., Cornus mas L. and Mahonia aquifolium Nutt.

Abstract The antioxidant capacity of methanolic crude extracts of Berberis vulgaris L. , Cornus mas L. and Mahonia aquifolium Nutt. was tested with the thiobarbituric acid reactive substances formation assay, the ferric reducing power (FRAP) and 2,2-diphenyl-2-picrylhydrazyl (DPPH•) radical scavenging assay. The content of antioxidant components in the extracts, their partition coefficient on 1-octanol:water and affinity to liposome membranes were determined as well. The results show that the IC50 parameter connected with the antioxidant activity on phosphatidylcholine liposome membrane decreased as follows: B. vulgaris (0.14±0.01 mg/mL) > M. aquifolium (0.34±0.03 mg/mL) > C. mas (1.13±0.01 mg/mL) for AAPH-induced oxidation and M. aquifolium (0.29±0.03 mg/mL) > C. mas (1.24±0.07 mg/mL) > B. vulgaris (1.50±0.05 mg/mL) for Fe(II)/ascorbic acid-induced oxidation, and M. aquifolium (2.35±0.10 mg/mL) > B. vulgaris (2.69±0.04 mg/mL) > C. mas (6.17±0.06 mg/mL) for UVC irradiation. All the extracts exhibited the ability to quench DPPH• and to reduce Fe(III) ions to Fe(II) via redox reaction. The content of active components in the extracts, the partition coefficient and extracts affinity to membranes correlated well with their antioxidant activities. This study has shown that fruits of B. vulgaris, M. aquifolium and C. mas, from which the extracts were obtained, are attractive for consumption and can potentially be used in production of new processed fruit.
Temperature-dependent development of the predator, Scolothrips sexmaculatus (Pergande) (Thysanoptera:Thripidae).

The temperature is an important factor that affects the efficacy of biological control agents. Effect of the temperature on life table, parameters of Scolothrips sexmaculatus (Pergande) (Thysanoptera: Thripidae), the predator of the two-spotted spider mite Tetranychus urticae Koch (Acari: Tetranychidae) was studied under laboratory conditions at three constant temperatures (20, 25 and 30°C). These experiments were conducted at the General Commission for Scientific Agricultural Research (GCSAR), Damascus countryside, Syria. The durations of development of egg, 1 st and2 nd larval instars, pupa, and adult at the three tested constant temperatures were measured. The total developmental period from egg to adult’s emergence was estimated by 23.2, 13.3 and 10.8 days, respectively. The developmental period decreased significantly with increasing the temperature from 20 to 30°C. Survival rate was the highest at temperature (30°C) in comparison with the other temperatures (20 and 25°C). Egg stage of S. sexmaculatus showed highest mortality levels at all temperatures. Generation period, as well as the ovipositional period decreased significantly at the temperatures ranged from 25.1 to 11.54 days, 52.8 to 41.2 days between the two temperature extremes, respectively. The maximum total fecundity (229.3 eggs/ female) and the minimum (94.1 eggs/female) were recorded at 30 and 20°C, respectively. The mean number of fertile eggs, laid per female per day, was highest at 30◦C (4.9 eggs) and lowest (2.7 eggs) at 20◦C. Thermal requirements for developmental thresholds and thermal constant of S. sexmaculatus were estimated as 10.8°C and 200 degree-days (DD), using the common linear model. 30°C was the optimum temperature for development. The results showed that the population of S. sexmaculatus was able to develop at a broad range of temperatures; therefore it is well adapted to the temperatures of the Mediterranean region.
The digestion of two diets of differing protein content but with similar capacities to sustain wool growth.

Measurements were made of the digestion in sheep of two diets of differing protein content but known to support similar levels of wool growth. When offered to the sheep at 500 g/day, the high protein (HP) diet provided 13.8 g nitrogen (N), while the low protein (LP) diet provided 5.5 g. With the HP diet, approximately 8.8 g N in forms other than ammonia passed daily through the pylorus; 6.8 g of this N was apparently digested in the intestines. The corresponding values for the LP diet were 8.1 and 6.2. The similarity in wool growth recorded with these diets, despite large differences in dietary protein intake, is consistent with the hypothesis that wool growth is limited by the quantity of amino acid N absorbed from the alimentary tract. The stomach was the site of 72–73 % of the organic matter digestion and more than 90% of the cellulose digestion that occurred in the whole alimentary tract. In addition, approximately 90% of the dietary soluble carbohydrate was apparently digested in the stomach. It was calculated, by making several assumptions, that the quantity of microbial crude protein synthesized in the rumen did not exceed 44–49 g/day, equivalent to 15–16 g/100 g organic matter digested in the rumen. The implications of this calculation in the protein nutrition of ruminants are discussed. The retention time of a soluble marker in the rumen was 15–18 hr, and rates of flow of digesta from the rumen and abomasum were comparatively low.
Neofusicoccum eucalyptorum, a Eucalyptus pathogen, on native Myrtaceae in Uruguay

Neofusicoccum eucalyptorum is a canker-associated fungus apparently highly specialized on Eucalyptus. However, in surveys of the microbial population inhabiting native Myrtaceae in Uruguay, fungal cultures resembling N. eucalyptorum were isolated. The possible occurrence of N. eucalyptorum on hosts other than Eucalyptus prompted further investigation. Several surveys were conducted throughout Uruguay to obtain samples from native forests, focusing primarily on species in the Myrtaceae. Fungal identification was based on morphology and confirmed using comparison sequences for the internal transcribed spacer (ITS) of the rDNA operon. Pathogenicity was evaluated by inoculating plants of a Eucalyptus grandis clone. Morphological and molecular identification confirmed the occurrence of N. eucalyptorum on Blepharocalyx salicifolius, Myrceugenia glaucescens and Myrrhinium atropurpureum var. octandrum. This is the first report of N. eucalyptorum occurring in hosts other than Eucalyptus. Pathogenicity tests confirmed the ability of this species to produce cankers on E. grandis. This study provides information that will assist breeding programmes in attempts to obtain disease-resistant Eucalyptus plantations and it also suggests that a Eucalyptus pathogen could have moved to native trees in Uruguay.
Limited genetic parallels underlie convergent evolution of quantitative pattern variation in mimetic butterflies

Mimetic systems allow us to address the question of whether the same genes control similar phenotypes in different species. Although widespread parallels have been found for major effect loci, much less is known about genes that control quantitative trait variation. In this study, we identify and compare the loci that control subtle changes in the size and shape of forewing pattern elements in two Heliconius butterfly co-mimics. We use quantitative trait locus (QTL) analysis with a multivariate phenotyping approach to map the variation in red pattern elements across the whole forewing surface of Heliconius erato and Heliconius melpomene. These results are compared to a QTL analysis of univariate trait changes, and show that our resolution for identifying small effect loci is improved with the multivariate approach. QTL likely corresponding to the known patterning gene optix were found in both species but otherwise, a remarkably low level of genetic parallelism was found. This lack of similarity indicates that the genetic basis of convergent traits may not be as predictable as assumed from studies that focus solely on Mendelian traits.
Hyalotrichopteris is Indeed a Campyloneurum (Polypodiaceae)

ABSTRACT The relationships of the rare Mesoamerican fern Campyloneurum anetioides are inferred by comparing sequences of trnLUAA-trnFGAA intergenic spacer of the plastid genome. In the past, this taxon was either treated as the single member of the genus Hyalotrichopteris or as part of the diverse Neotropical genus Campyloneurum. Analyses of the cpDNA give unambiguous support to the taxonomic placement of this species within Campyloneurum. The closest relatives within the genus Campyloneurum are currently unknown because limited taxon sampling and variation of the cpDNA sequences do not allow to elucidate this question. However, we can conclude that C. anetioides is unlikely the derivative of an early separation within Campyloneurum.
A model of listening engagement (MoLE)

Hearing impairment in older adulthood puts people at risk of communication difficulties, disengagement from listening, and social withdrawal. Here, we develop a model of listening engagement (MoLE) that provides a conceptual foundation to understand when people engage in listening and why some people disengage. We use the term "listening engagement" to describe the recruitment of executive and other cognitive resources in the service of a valued communication goal. Listening engagement, listening motivation, and listening experiences are closely interconnected: motivation and other factors determine the degree to which resources are recruited during listening, which in turn influences subjective listening experiences such as enjoyment, effort, frustration, and boredom. We anticipate that this model will help researchers assess more accurately whether a person with hearing difficulties is at risk of disengagement and social withdrawal. It is further useful to more comprehensively characterize a person's listening experiences in laboratory settings when rich, engaging stimulus materials, such as spoken stories, are used. We hope this model will allow new questions in applied and basic hearing science and auditory cognitive neuroscience to be asked and answered.
Performance and nutritional evaluation of beef cattle raised on pasture, castrated at different ages, with and without supplementation

The objective of this study was to evaluate performance and nutritional traits of beef cattle raised on pastures, castrated at different ages, with and without supplementation. Forty-four crossbred young bulls with predominance of Zebu breed at initial average age of 120±30 days were used in the experiment. Animals were distributed in a completely randomized design in a factorial arrangement with four ages of castration and two supplementation systems. The animals were distributed into four groups and placed on Brachiaria decumbens Stapf pastures, where they were fed concentrate supplementation or mineral salt ad libtum (control). Animals were castrated at 120, 240 and 360 days of age with average body weight of 115, 175 and 276 kg, castrated or not, in each supplementation group. Concentrate supplement composition and the amount supplied to the animals varied according to the time of the year and development phase of the animals. Trials were carried out to evaluate nutritional variables in each of the following phases: suckling, growth in the dry season and growth in the dry/rainy transition season. Concentrate supplementation improved the use of pasture, although it may have caused substitutive effect in all seasons evaluated. Castration of the animals before the dry season impaired animal development until the following dry/rainy transition season, especially when carried out during weaning. Concentrate supply may reduce some effects of this stress.
Polymorphism and Selection Pressure of SARS-CoV-2 Vaccine and Diagnostic Antigens: Implications for Immune Evasion and Serologic Diagnostic Performance

The ongoing SARS-CoV-2 pandemic has triggered multiple efforts for serological tests and vaccine development. Most of these tests and vaccines are based on the Spike glycoprotein (S) or the Nucleocapsid (N) viral protein. Conservation of these antigens among viral strains is critical to ensure optimum diagnostic test performance and broad protective efficacy, respectively. We assessed N and S antigen diversity from 17,853 SARS-CoV-2 genome sequences and evaluated selection pressure. Up to 6-7 incipient phylogenetic clades were identified for both antigens, confirming early variants of the S antigen and identifying new ones. Significant diversifying selection was detected at multiple sites for both antigens. Some sequence variants have already spread in multiple regions, in spite of their low frequency. In conclusion, the N and S antigens of SARS-CoV-2 are well conserved antigens, but new clades are emerging and may need to be included in future diagnostic and vaccine formulations.
Neuronal leak within recurrent neuronal networks prevents the generation of high frequency spurious signals

Elements of recurrent excitatory synaptic loops are present within sensorimotor control loops in the brain. Such positive feedback loops can cause self-amplification, which is potentially dangerous for the brain (as in epilepsy) or which may cause disruptive effects on of the information passed within the neuronal circuitry. Here we introduce a simplified non-spiking neuron model, whose output accurately reflects summated synaptic inputs, with which we performed simulations of highly connected networks composed of excitatory and inhibitory neurons in equal proportions. The neuron model could be optionally equipped with a dynamic leak, i.e. dynamic short-circuit to the resting membrane potential, equivalent to a membrane time constant. Synaptic weights were randomly assigned across the network according to a range of different types and ranges of distribution. Networks were provided with random and semi-structured sensory inputs and we studied the spread of activity through the network. We find that in neurons without dynamic leak, recurrent networks produced high frequency noise components that were not present in the input signal, across all synaptic weight distributions. The addition of dynamic leak consistently removed such high frequency noise. Conduction delays between neurons, when explicitly included, tended to worsen the high frequency noise, which was rescued by dynamic leak also in this case. Our findings suggest that neuronal dynamic short circuit of voltage deviations towards the resting potential serve the beneficial function of protecting recurrent neuronal circuitry from inducing itself into spurious high frequency signal generation, thereby permitting the brain to utilize this architectural circuitry component.
In silico multi-epitope vaccine against covid19 showing effective interaction with HLA-B*15:03

The recent outbreak of severe acute respiratory syndrome (SARS) coronavirus (CoV)-2 (SARS-CoV-2) causing coronavirus disease (covid19) has posed a great threat to human health. Previous outbreaks of SARS-CoV and Middle East respiratory Syndrome CoV (MERS-CoV) from the same CoV family had posed similar threat to human health and economic growth. To date, not even a single drug specific to any of these CoVs has been developed nor any anti-viral vaccine is available for the treatment of diseases caused by CoVs. Subunits present in spike glycoproteins of SARS-CoV and SARS-CoV-2 are involved in binding to human ACE2 Receptor which is the primary method of viral invasion. As it has been observed in the previous studies that there are very minor differences in the spike glycoproteins of SARS-CoV and SARS-CoV-2. SARS-CoV-2 has an additional furin cleavage site that makes it different from SARS-CoV (Walls et al., 2020). In this study, we have analyzed spike glycoproteins of SARS-CoV-2 and SARS-CoV phylogenetically and subjected them to selection pressure analysis. Selection pressure analysis has revealed some important sites in SARS-CoV-2 and SARS-CoV spike glycoproteins that might be involved in their pathogenicity. Further, we have developed a potential multi-epitope vaccine candidate against SARS-CoV-2 by analyzing its interactions with HLA-B*15:03 subtype. This vaccine consists of multiple T-helper (TH) cells, B-cells, and Cytotoxic T-cells (CTL) epitopes joined by linkers and an adjuvant to increase its immunogenicity. Conservation of selected epitopes in SARS, MERS, and human hosts, suggests that the designed vaccine could provide cross-protection. The vaccine is designed in silico by following a reverse vaccinology method acknowledging its antigenicity, immunogenicity, toxicity, and allergenicity. The vaccine candidate that we have designed as a result of this work shows promising result indicating its potential capability of simulating an immune response.
Activation of p38 Mitogen-Activated Protein Kinase by Sodium Salicylate Leads to Inhibition of Tumor Necrosis Factor-Induced IκBα Phosphorylation and Degradation

ABSTRACT Many actions of the proinflammatory cytokines tumor necrosis factor (TNF) and interleukin-1 (IL-1) on gene expression are mediated by the transcription factor NF-κB. Activation of NF-κB by TNF and IL-1 is initiated by the phosphorylation of the inhibitory subunit, IκB, which targets IκB for degradation and leads to the release of active NF-κB. The nonsteroidal anti-inflammatory drug sodium salicylate (NaSal) interferes with TNF-induced NF-κB activation by inhibiting phosphorylation and subsequent degradation of the IκBα protein. Recent evidence indicated that NaSal activates the p38 mitogen-activated protein kinase (MAPK), raising the possibility that inhibition of NF-κB activation by NaSal is mediated by p38 MAPK. We now show that inhibition of TNF-induced IκBα phosphorylation and degradation by NaSal is prevented by treatment of cells with SB203580, a highly specific p38 MAPK inhibitor. Both p38 activation and inhibition of TNF-induced IκBα degradation were seen after only 30 s to 1 min of NaSal treatment. Induction of p38 MAPK activation and inhibition of TNF-induced IκBα degradation were demonstrated with pharmacologically achievable doses of NaSal. These findings provide evidence for a role of NaSal-induced p38 MAPK activation in the inhibition of TNF signaling and suggest a possible role for the p38 MAPK in the anti-inflammatory actions of salicylates. In addition, these results implicate the p38 MAPK as a possible negative regulator of TNF signaling that leads to NF-κB activation.
Multiple information carried by RNAs: total eclipse or a light at the end of the tunnel?

ABSTRACT The findings that an RNA is not necessarily either coding or non-coding, or that a precursor RNA can produce different types of mature RNAs, whether coding or non-coding, long or short, have challenged the dichotomous view of the RNA world almost 15 years ago. Since then, and despite an increasing number of studies, the diversity of information that can be conveyed by RNAs is rarely searched for, and when it is known, it remains largely overlooked in further functional studies. Here, we provide an update with prominent examples of multiple functions that are carried by the same RNA or are produced by the same precursor RNA, to emphasize their biological relevance in most living organisms. An important consequence is that the overall function of their locus of origin results from the balance between various RNA species with distinct functions and fates. The consideration of the molecular basis of this multiplicity of information is obviously crucial for downstream functional studies when the targeted functional molecule is often not the one that is believed.