Miracle-dz/UniFAR-FTUs huggingface dataset:
Channel Capacity Computations for Unregulated and Autoregulated Gene Expression

How living cells can reliably process biochemical cues in the presence of molecular noise is not fully understood. Here we investigate the fidelity of information transfer in the expression of a single gene. We use the established model of gene expression to examine how precisely the protein levels can be controlled by two distinct mechanisms: (i) the transcription rate of the gene, or (ii) the translation rate for the corresponding mRNA. The fidelity of gene expression is quantified with the information-theoretic notion of information capacity. Derived information capacity formulae reveal that transcriptional control generally provides a tangibly higher capacity as compared to the translational control. We next introduce negative feedback regulation in gene expression, where the protein directly inhibits its own transcription. While negative feedback reduces noise in the level of the protein for a given input signal, it also decreases the input-to-output sensitivity. Our results show that the combined effect of these two opposing forces is a reduced capacity in the presence of feedback. In summary, our analysis presents the first analytical quantification of information transfer in simple gene expression models, which provides insight into the fidelity of basic gene expression control mechanisms.
Prototypic SNARE Proteins Are Encoded in the Genomes of Heimdallarchaeota, Potentially Bridging the Gap between the Prokaryotes and Eukaryotes

A defining feature of eukaryotic cells is the presence of numerous membrane-bound organelles that subdivide the intracellular space into distinct compartments. How the eukaryotic cell acquired its internal complexity is still poorly understood. Material exchange among most organelles occurs via vesicles that bud off from a source and specifically fuse with a target compartment. Central players in the vesicle fusion process are the Soluble N-ethylmaleimide-sensitive factor Attachment protein REceptor (SNARE) proteins. These small tail-anchored (TA) membrane proteins zipper into elongated four-helix bundles that pull membranes together1–3. SNARE proteins are highly conserved among eukaryotes but are thought to be absent in prokaryotes. Here, we identified SNARE-like factors in the genomes of uncultured organisms of Asgard archaea of the Heimdallarchaeota clade4,5, which are thought to be the closest living relatives of eukaryotes. Biochemical experiments show that the archaeal SNARE-like proteins can interact with eukaryotic SNARE proteins. We did not detect SNAREs in α-proteobacteria, the closest relatives of mitochondria, but identified several genes encoding for SNARE proteins in γ-proteobacteria of the order Legionellales, pathogens that live inside eukaryotic cells. Very probably, their SNAREs stem from lateral gene transfer from eukaryotes. Together, this suggests that the diverse set of eukaryotic SNAREs evolved from an archaeal precursor. However, whether Heimdallarchaeota actually have a simplified endomembrane system will only be seen when we succeed studying these organisms under the microscope.
Reorganization of the Primate Dorsal Horn in Response to a Deafferentation Lesion Affecting Hand Function

The loss of sensory input following a spinal deafferentation injury can be debilitating, and this is especially true in primates when the hand is involved. Although significant recovery of function occurs, little is currently understood about the reorganization of the neuronal circuitry, particularly within the dorsal horn. The loss of sensory input following a spinal deafferentation injury can be debilitating, and this is especially true in primates when the hand is involved. Although significant recovery of function occurs, little is currently understood about the reorganization of the neuronal circuitry, particularly within the dorsal horn. This region receives primary afferent input from the periphery, and cortical input via the somatosensory subcomponent of the corticospinal tract (S1 CST), and is critically important in modulating sensory transmission, both in normal and lesioned states. To determine how dorsal horn circuitry alters to facilitate recovery post-injury, we used an established deafferentation lesion model (dorsal root/dorsal column) in male monkeys to remove sensory input from just the opposing digits (digits 1–3) of one hand. This results in a deficit in fine dexterity that recovers over several months. Electrophysiological mapping, tract tracing, and immunolabeling techniques were combined to delineate specific changes to dorsal horn input circuitry. Our main findings show that (1) there is complementary sprouting of the primary afferent and S1 CST populations into an overlapping region of the reorganizing dorsal horn; (2) S1 CST and primary afferent inputs connect in different ways within this region to facilitate sensory integration; and (3) there is a loss of larger S1 CST terminal boutons in the affected dorsal horn, but no change in the size profile of the spared/sprouted primary afferent terminal boutons post-lesion. Understanding such changes helps to inform new and targeted therapies that best promote recovery. SIGNIFICANCE STATEMENT Spinal injuries that remove sensation from the hand, can be debilitating, though functional recovery does occur. We examined changes to the neuronal circuitry of the dorsal horn in monkeys following a lesion that deafferented three digits of one hand. Little is understood about dorsal horn circuitry, despite the fact that this region loses most of its normal input after such an injury, and is clearly a major focus of reorganization. We found that both the spared primary afferents and somatosensory corticospinal efferents sprouted in an overlapping region of the dorsal horn after injury, and that larger (presumably faster) corticospinal terminals are lost, suggesting a significantly altered cortical modulation of primary afferents. Understanding this changing circuitry is important for designing targeted therapies.
Selection gain and interrelations between agronomic traits in wheat F5 genotypes

Submitted on May 29 , 2019 and accepted on August 22 , 019. 1 Universidade Federal de Santa Maria, Departamento de Ciências Agronômicas e Ambientais, Frederico Westphalen, Rio Grande do Sul, Brazil. meiercarine5@gmail.com; volmir@marchioro.eng.br; luis.antonio. klein@hotmail.com 2 Universidade Tecnológica Federal do Paraná, Pato Branco, Paraná, Brazil. dmdanielameira94@gmail.com 3 Universidade Federal de Santa Maria, Santa Maria, Rio Grande do Sul, Brazil. tiagoolivoto@gmail.com 4Universidade Federal do Pampa, Dom Pedrito, Rio Grande do Sul, Brazil. velciq@gmail.com *Corresponding author: meiercarine5@gmail.com Selection gain and interrelations between agronomic traits in wheat F5 genotypes
Origins of Afrotropical freshwater fishes

The Afrotropics house a diverse freshwater ichthyofauna with > 3000 species, almost all of which are endemic. Recent progress in dated phylogenetics and palaeontology of several groups of Afrotropical freshwater fishes (AFFs) has allowed the testing of palaeoecology- and palaeogeography-based hypotheses explaining their early presence in Africa. Seven hypotheses were tested for 37 most-inclusive monophyletic groups of AFFs. Results indicated that ten lineages originated from direct, but asynchronous, marine-to-freshwater shifts. These lineages contribute < 2% to the current AFF species richness. Eleven lineages colonized the Afrotropics from the Orient after the Afro-Arabian plate collided with Eurasia in the early Oligocene. These lineages contribute ~20% to the total diversity. There are seven sister relationships between Afrotropical and Neotropical taxa. For only three of them (4% of the species diversity), the continental drift vicariance hypothesis was not rejected. Distributions of the other four younger trans-Atlantic lineages are better explained by post-drifting long-distance dispersal. In those cases, I discuss the possibility of dispersal through the Northern Hemisphere as an alternative to direct trans-Atlantic dispersal. The origins of ten AFF lineages, including the most species-rich Pseudocrenilabrinae (> 1100 species), are not yet established with confidence.
The effects of education on breast self-examination knowledge,attitude, and practice among the female employees of Birjand University

Background and Aim: Breast cancer is the most common cancer among women. Early diagnosis of breast cancer is extremely effective in its treatment. The aim of this study was to investigate the impacts of education on breast selfexamination knowledge, attitude, and practice among female employees of Birjand University, Birjand, Iran. Methods: This one-group pretest-posttest quasi-experimental study was conducted in 2012 on 89 female employees of Birjand University who agreed to participate in the study. A three-part researcher-made questionnaire was used for data collection. The first part was a demographic questionnaire containing items such as age, marital status, and education, history of common breast problems, history of breast self-examination, and history of breast cancer among first-degree relatives. The second and the third parts were related to breast self-examination knowledge (20 items) and attitude (ten items). An educational program was implemented for the participants by a pathologist. Educations were provided in a 90-minute session through presenting a lecture, distributing pamphlets, showing a video clip, and using the question-andanswer method. The knowledge and the attitude questionnaires were completed by the participants both before and two months after the study intervention. The data were analyzed by using the SPSS software (v. 15.0) and through performing the Wilcoxon, the Kruskal-Wallis, the Man-Whitney U, and the McNemar’s tests. P values of less than 0.05 were considered as significant. Results: Among 89 participating women, 81 (91%) were married. Participants’ average age was 39.2±7.3 years. Compared with the pretest readings, the means of women’s breast self-examination knowledge and attitude significantly increased after the intervention (P<0.001). Moreover, after the study, there was a significant difference among women with different educational status regarding the mean scores of knowledge and attitude. However, the differences among different age and gender groups were not significant. The pretest-posttest mean differences of knowledge and attitude were also not significantly related with women’s other demographic characteristics Conclusion: Based on the findings of the present study, education can be effective in improving women’s knowledge and attitude about breast cancer screening methods. Consequently, running educational programs is recommended for effective prevention and prompt treatment of breast cancer.
Does Daylight Saving Time Really Make Us Sick?

This paper comprehensively studies the health effects of Daylight Saving Time (DST) regulation. Relying on up to 3.4 million BRFSS respondents from the US and the universe of 160 million hospital admissions from Germany over one decade, we do not find much evidence that population health significantly decreases when clocks are set forth by one hour in spring. However, when clocks are set back by one hour in fall, effectively extending sleep duration for the sleep deprived by one hour, population health slightly improves for about four days. The most likely explanation for the asymmetric effects are behavioral adjustments by marginal people in spring.
Nonsense suppression position effect implicates poly(A)-binding protein in the regulation of translation termination

Readthrough of translation termination codons, also known as nonsense suppression, is a relatively inefficient process mediated by ribosomal A site recognition and insertion of near-cognate tRNAs. Multiple factors influence readthrough efficiency, including nonsense codon specificity and context. To determine whether nonsense codon position in a gene influences the extent of readthrough, we generated a series of LUC nonsense alleles and quantitated both readthrough and termination efficiencies at each nonsense codon in yeast cells lacking nonsense-mediated mRNA decay (NMD) activity. Readthrough efficiency for premature termination codons (PTCs) manifested a marked dependence on PTC proximity to the mRNA 3’-end, decreasing progressively across the LUC ORF but increasing with 3’-UTR lengthening. These effects were eliminated, and translation termination efficiency decreased considerably, in cells harboring pab1 mutations. Our results support a critical role for poly(A)-binding protein in the regulation of translation termination and suggest that inefficient termination is the trigger for NMD.
Mesenchymal stem cell-derived exosomes improve diabetes mellitus-induced myocardial injury and fibrosis via inhibition of TGF-β1/Smad2 signaling pathway.

The aim of this study is to investigate the effect of mesenchymal stem cell (MSC)-derived exosomes on diabetes mellitus-induced myocardial injury, and the underlying mechanism. Thirty adult male Sprague Dawley rats were randomly assigned to three groups of ten rats each: normal control group, diabetic control group and MSC exosomes group. Exosomes were isolated from MSCs through gradient ultracentrifugation. With the exception of normal control, diabetes mellitus (DM) was induced in the rats with a single intraperitoneal injection of 30 mg/kg body weight streptozotocin (STZ) in 0.1 mol/L sodium citrate buffer. Rats in MSC exosomes group were intravenously injected with MSC-derived exosomes once a week for 12 weeks. Left ventricular collagen (LVC) level was measured using acid hydrolysis method. Fatty acid transporters (FATPs) and fatty acid beta oxidase (FA-β-oxidase) were determined using enzyme-linked immunosorbent assay (ELISA). Gene and protein expressions of TGF-β and Smad2 were determined using real-time quantitative polymerase chain reaction (qRT-PCR) and Western blotting. Flow cytometric analysis and Western blotting revealed positive expression of exosomal specific marker, CD63. The level of LVC was significantly higher in diabetic control group than in normal control group, but was significantly reduced after treatment with MSC-derived exosomes (p < 0.05). The levels of FATPs and FA-β-oxidase were significantly lower in diabetic control group than in normal control group (p < 0.05). However, treatment with MSC-derived exosomes significantly increased the levels of these proteins (p < 0.05). The levels of expression of TGF-β1 and Smad2 mRNAs were significantly higher in the diabetic control group than in normal control group, but were significantly reduced after treatment with MSC-derived exosomes (p < 0.05). The expressions of TGF-β1 and Smad2 proteins were also significantly upregulated in diabetic control group, when compared with normal control group (p < 0.05). However, treatment with MSC-derived exosomes significantly down-regulated the expression of these proteins (p < 0.05). The results obtained in this study indicate that MSC-derived exosomes improve DM-induced myocardial injury and fibrosis via inhibition of TGF-β1/Smad2 signaling pathway.
HOX13-dependent chromatin accessibility modulates the target repertoires of the HOX factors

Hox genes encode essential transcription factors that control patterning during embryonic development. Distinct combinations of nested Hox expression domains establish cell and tissue identities1–3. Consequently, spatial or temporal de-regulation of Hox genes can cause severe alterations of the body plan3. While HOX factors have very similar DNA binding motifs, their binding specificity is, in part, mediated by co-factors4–6. Yet, the interplay between HOX binding specificities and the cellular context remains largely elusive. To gain insight into this question, we took advantage of developing limbs for which the differential expression of Hox genes is well-characterized7. We show that the transcription factors HOXA13 and HOXD13 (hereafter referred as HOX13) allow another HOX factor, HOXA11, to bind loci initially assumed to be HOX13-specific. Importantly, HOXA11 is unable to bind these loci in distal limbs lacking HOX13 function indicating that HOX13 modulates HOXA11 target repertoire. In addition, we find that the HOX13 factors implement the distal limb developmental program by triggering chromatin opening, a defining property of pioneer factors8,9. Finally, single cell analysis of chromatin accessibility reveals that HOX13 factors pioneer chromatin opening in a lineage specific manner. Together, our data uncover a new mechanism underlying HOX binding specificity, whereby tissue-specific variations in the target repertoire of HOX factors rely, at least in part, on HOX13-dependent chromatin accessibility.
Mapping the brain-wide network effects by optogenetic activation of the corpus callosum

The optogenetically driven manipulation of circuit-specific activity enabled functional causality studies in animals, but its global effect on the brain is rarely reported. Here, we applied simultaneous fMRI with calcium recording to map brain-wide activity by optogenetic activation of fibers running in one orientation along the corpus callosum(CC) connecting the barrel cortex(BC). Robust positive BOLD signals were detected in the ipsilateral BC due to antidromic activity, which spread to ipsilateral motor cortex(MC) and posterior thalamus(PO). In the orthodromic target (contralateral barrel cortex), positive BOLD signals were reliably evoked by 2Hz light pulses, whereas 40Hz light pulses led to a reversed sign of BOLD - indicative of CC-mediated inhibition. This presumed optogenetic CC-mediated inhibition was further elucidated by pairing light with peripheral whisker stimulation at varied inter-stimulus intervals. Whisker induced positive BOLD, and calcium signals were reduced at inter-stimulus intervals of 50/100ms. The calcium-amplitude modulation (AM)-based correlation with whole-brain fMRI signal revealed that the inhibitory effects spread to contralateral BC as well as ipsilateral MC and PO. This work raises the need of fMRI to elucidate the brain-wide network activation in response to projection-specific optogenetic stimulation.
Effects of light intensity in different stocking densities on tibial measurements and incidence of lesions in broilers

The possibility for use of high light intensity in broiler production management to improve the health of broilers? legs was examined in a study aiming to determine the effect of two levels of light intensity in different stocking densities of broiler chickens. The study was carried out on 1200 Ross 308 broilers according to a random block system with 6 treatments (2 x 3 factorial design) and 4 replicates per treatment. The examined light intensity levels of 150 lx (high light intensity-HLI) and 20 lx (low light intensity-LLI) were applied to 3 stocking densities of broilers: 10, 13 and 15 birds/m2. Scoring of foot pad (FP) and hock burns (HB) was carried out on the 42nd day, on a sample of 240 broilers. Osteometric and biomechanical measurements on tibia were performed after slaughtering and primary processing, on a sample of 72 broilers. The high level intensity of light exerted no significant effect on the development and firmness of the tibia of broilers grown in the densities of 10, 13 and 15 birds/m2. There are indications that in the highest studied stocking density the increased light intensity can improve the individual properties of tibia. The differences in the average assessment of hock burns were concluded to be the result of the stocking density that was observed only in conditions of the increased intensity of light. The average score of foot pad lesions was under the significant main effect of both investigated factors. The differences in the average FP estimation between the light intensity treatments were confirmed in the stocking density of 13 birds/m2.
The silver spoon effect and individual quality in relation to telomere length in blue tits (Cyanistes caeruleus)

Telomeres shorten over time due to internal and external factors. They are linked to factors experienced by an organism throughout its lifetime and may explain variations among individuals in a number of life-history traits. This thesis aims to investigate the silver spoon effect and individual quality in adult blue tits (Cyanistes caeruleus) in relation to relative telomere length. In addition, I analysed the relationship between relative telomere length, morphology and survival, by using cross-sectional and longitudinal data. Field work was conducted at Dæli, near Oslo. Blood samples from 109 individuals collected in 2016 and 2017 were assessed using a qPCR assay to estimate relative telomere length, and correlations between relative telomere length and various variables were performed. There were significant year and collection date effects on telomere length. Furthermore, the results indicate that there is a silver spoon effect on telomere length, because blue tits growing up in larger broods had shorter telomeres as adults than those growing up in smaller broods. In terms of individual quality, adult males with longer telomeres mated with females that laid larger clutches; however, one-year-old males with longer wings had shorter telomeres. I discuss possible explanations for these somewhat inconsistent results.
Breast Cancer: A Lot to be Done!!@@@سرطان الثدي : مازال أمامنا الكثير

One hundred and twenty-one female patients with breast cancer were treated at King Abdulaziz University Hospital over a period of eight years. Early breast cancer (stage 0-1) represented 13.2%, while 73.3% presented with locally advanced disease (stage II-III), and examined metastatic disease at the time of presentation was only present in 5.8%. The majority of our patients were premenopausal (64.5%) and 30.6% were less than 40 years old. Modified radical mastectomy was performed in 71.1%, while only 15.7% had conservative breast surgery. The present situation of this common and serious health problem is less than ideal and indicates that a lot has to be done to detect the disease at an earlier stage. This can be achieved by the introduction of public health education programs, initiation of breast clinics, and encouraging screening mammogram protocols.
Fexofenadine: Assessment of sleepiness potential using objective criteria

To evaluate the sedating effect of fexofenadine by subjective and objective assessment, 28 healthy male subjects were randomized to receive either placebo or fexofenadine 120 mg orally on day 1 or 2. Subjects were subjectively assessed for drowsiness on the basis of Stanford sleepiness scale (SSS) and visual analog scale (VAS). On day 2, multiple sleep latency tests were done at 0930, 1030, 1130, 1230, 1330, 1430, 1530 and 1700 hours. The procedure was repeated on day 3 and 4. Multiple sleep latency test (MSLT) (range) seen with placebo and fexofenadine is 14.36(± 2.83) and 13.5(± 3.66) minutes respectively. There was also no significant difference after fexofenadine and placebo between subjective sleepiness assessed by (VAS) (p=0.05) and (SSS) (p=0.412) respectively.