Miracle-dz/UniFAR-FTUs huggingface dataset:
High-throughput SSR marker development and its application in a centipedegrass (Eremochloa ophiuroides (Munro) Hack.) genetic diversity analysis

Centipedegrass (Eremochloa ophiuroides (Munro) Hack. ) is a perennial, warm-season C4 grass species that shows great potential for use as a low-maintenance turfgrass species in tropical and subtropical regions. However, limited genetic and genomic information is available for this species, which has impeded systematic studies on the enhancement of its turf quality and resistance against biotic and abiotic stress. In this study, Illumina HiSeq high-throughput sequencing technology was performed to generate centipedegrass transcriptome sequences. A total of 352,513 assembled sequences were used to search for simple sequence repeat (SSR) loci, and 64,470 SSR loci were detected in 47,638 SSR containing sequences. The tri-nucleotides were the most frequent repeat motif, followed by di-nucleotides, tetra-nucleotides hexnucleotides, and pentanucleotides. A total of 48,061 primer pairs were successfully designed in the flanking sequences of the SSRs, and 100 sets of primers were randomly selected for the initial validation in four centipedegrass accessions. In total, 56 (56.0%) of the 100 primer pairs tested successfully amplified alleles from all four centipedegrass accessions, while 50 were identified as polymorphic markers and were then used to assess the level of genetic diversity among 43 centipedegrass core collections. The genetic diversity analysis exhibited that the number of alleles (Na) per locus ranged from 3 to 13, and the observed heterozygosity (Ho) ranged from 0.17 to 0.83. The polymorphism information content (PIC) value of the markers ranged from 0.15 to 0.78, and the genetic distances (coefficient Nei72) between the accessions varied from 0.07 to 0.48. The UPGMA-based dendrogram clustered all 43 core collections into two main groups and six subgroups, which further validated the effectiveness of these newly developed SSR markers. Hence, these newly developed SSR markers will be valuable and potentially useful for future genetic and genomic studies of E. ophiuroides.
Neo-Domestication of an Interspecific Tetraploid Helianthus annuus × Helianthus tuberous Population That Segregates for Perennial Habit

Perennial agriculture has been proposed as an option to improve the sustainability of cropping systems, by increasing the efficiency of resource use, while also providing ecosystem services. Neo-domestication, the contemporary domestication of plants that have not previously been used in agriculture, can be used to generate new crops for these systems. Here we explore the potential of a tetraploid (2n = 4x = 68) interspecific hybrid sunflower as a perennial oilseed for use in multifunctional agricultural systems. A population of this novel tetraploid was obtained from crosses between the annual diploid oilseed crop Helianthus annuus (2n = 2x = 34) and the perennial hexaploid tuber crop Helianthus tuberosus (2n = 6x = 102). We selected for classic domestication syndrome traits for three generations. Substantial phenotypic gains were made, in some cases approaching 320%. We also analyzed the genetic basis of tuber production (i.e., perenniality), with the goal of obtaining molecular markers that could be used to facilitate future breeding in this system. Results from quantitative trait locus (QTL) mapping suggest that tuber production has an oligogenic genetic basis. Overall, this study indicates that substantial gains towards domestication goals can be achieved over contemporary time scales.
Effect of a multicomponent behavioural PMTCT cluster randomised controlled trial on HIV stigma reduction among perinatal HIV positive women in Mpumalanga province, South Africa

ABSTRACT Background: We evaluate the impact a multicomponent, behavioural, prevention of mother to child transmission (PMTCT), cluster randomised controlled trial on HIV stigma reduction among perinatal HIV infected women in rural South Africa. Methods: In a cluster randomised controlled trial, twelve community health centres (CHCs) in Mpumalanga Province, South Africa, were randomised; pregnant women living with HIV enrolled received either: A Standard Care (SC) condition plus time-equivalent attention-control on disease prevention (SC; 6 CHCs; n =357), or an Enhanced Intervention (EI) condition of SC PMTCT plus the ‘Protect Your Family’ intervention (EI; 6 CHCs; n =342). HIV-infected pregnant women in the SC attended four antenatal and two postnatal video sessions; those in the EI, four antenatal and two postnatal group PMTCT sessions, including stigma reduction, led by trained lay health workers. Maternal PMTCT, HIV knowledge and HIV related stigma were assessed. The impact of the EI was ascertained on stigma reduction (baseline, 12 months postnatally). A series of logistic regression and latent growth curve models were developed to test the impact of the intervention. Results: In all, 699 women living with HIV were recruited during pregnancy (8–24 weeks), and assessments were completed prenatally at baseline and at 12 months (59.5%) postnatally. Baseline scores of overall HIV related stigma and the four scale factors (personalised stigma, disclosure concerns, negative self-image, and concern public attitudes) decreased at follow-up in the intervention group, while baseline scores of overall stigma and three scale factors (personalised stigma, negative self-image, and concern public attitudes) increased at follow-up in the control group. Using longitudinal analyses, Model 1, which included time-invariant predictors of stigma assessed over the two time periods of baseline and 12 months, increases in stigma from baseline to 12 months were associated with being unemployed, having been diagnosed with HIV before the current pregnancy, and alcohol use. In Model 2, which included time-varying predictors, lower stigma scores were associated with participation in the intervention, greater male partner involvement, and consistent condom use. Conclusion: The enhanced PMTCT intervention, including stigma reduction, administered by trained lay health workers had a significant effect on the reduction of HIV related stigma. Trial registration: clinicaltrials.gov: number NCT02085356
Test behaviour detection as a test refactoring safety

When refactoring production code, software developers rely on an automated test suite as a safeguard. However, when refactoring the test suite itself, there is no such safeguard. Therefore, there is a need for tool support that can verify if a refactored test suite preserves its behaviour pre- and post-refactoring. In this work we present T-CORE (Test COde REfactoring tool); a tool that captures the behaviour of Java tests in the form of a Test Behaviour Tree. T-CORE allows developers to verify that the refactoring of a test suite has preserved the behaviour of the test.
Genetic Variants in pre-miR-146a, pre-miR-499, pre-miR-125a, pre-miR-605, and pri-miR-182 Are Associated with Breast Cancer Susceptibility in a South American Population

Breast cancer (BC) is one of the most frequent tumors affecting women worldwide. microRNAs (miRNAs) single-nucleotide polymorphisms (SNPs) likely contribute to BC susceptibility. We evaluated the association of five SNPs with BC risk in non-carriers of the BRCA1/2-mutation from a South American population. The SNPs were genotyped in 440 Chilean BRCA1/2-negative BC cases and 1048 controls. Our data do not support an association between rs2910164:G>C or rs3746444:A>G and BC risk. The rs12975333:G>T is monomorphic in the Chilean population. The pre-miR-605 rs2043556-C allele was associated with a decreased risk of BC, both in patients with a strong family history of BC and in early-onset non-familial BC (Odds ratio (OR) = 0.5 [95% confidence interval (CI) 0.4–0.9] p = 0.006 and OR = 0.6 [95% CI 0.5–0.9] p = 0.02, respectively). The rs4541843-T allele is associated with increased risk of familial BC. This is the first association study on rs4541843 and BC risk. Previously, we showed that the TOX3-rs3803662:C>T was significantly associated with increased risk of familial BC. Given that TOX3 mRNA is a target of miR-182, and that both the TOX3 rs3803662-T and pri-miR-182 rs4541843-T alleles are associated with increased BC risk, we evaluated their combined effect. Risk of familial BC increased in a dose-dependent manner with the number of risk alleles (p-trend = 0.0005), indicating an additive effect.
Epigenetic Effects Induced by Methamphetamine and Methamphetamine-Dependent Oxidative Stress

Methamphetamine is a widely abused drug, which possesses neurotoxic activity and powerful addictive effects. Understanding methamphetamine toxicity is key beyond the field of drug abuse since it allows getting an insight into the molecular mechanisms which operate in a variety of neuropsychiatric disorders. In fact, key alterations produced by methamphetamine involve dopamine neurotransmission in a way, which is reminiscent of spontaneous neurodegeneration and psychiatric schizophrenia. Thus, understanding the molecular mechanisms operated by methamphetamine represents a wide window to understand both the addicted brain and a variety of neuropsychiatric disorders. This overlapping, which is already present when looking at the molecular and cellular events promoted immediately after methamphetamine intake, becomes impressive when plastic changes induced in the brain of methamphetamine-addicted patients are considered. Thus, the present manuscript is an attempt to encompass all the molecular events starting at the presynaptic dopamine terminals to reach the nucleus of postsynaptic neurons to explain how specific neurotransmitters and signaling cascades produce persistent genetic modifications, which shift neuronal phenotype and induce behavioral alterations. A special emphasis is posed on disclosing those early and delayed molecular events, which translate an altered neurotransmitter function into epigenetic events, which are derived from the translation of postsynaptic noncanonical signaling into altered gene regulation. All epigenetic effects are considered in light of their persistent changes induced in the postsynaptic neurons including sensitization and desensitization, priming, and shift of neuronal phenotype.
Infrastructuring in PD: what does infrastructuring look like? when does it look like that?

In1 this hands-on workshop we invite the PD community to take stock of empirical insights and conceptual developments around the notions of infrastructure and infrastructuring. We propose that by leveraging the original relational nature of these concepts, we can revitalize the political soul of PD and better characterize the politics of participation in digitalization phenomena and processes ongoing in all walks of life. With a hands-on approach we will collectively and critically map, disentangle assumptions, identify blind spots and outline new research opportunities charting the possibilities and limitations of an infrastructuring approach in PD at large.
Selection for Protein Stability Enriches for Epistatic Interactions

A now classical argument for the marginal thermodynamic stability of proteins explains the distribution of observed protein stabilities as a consequence of an entropic pull in protein sequence space. In particular, most sequences that are sufficiently stable to fold will have stabilities near the folding threshold. Here we extend this argument to consider its predictions for epistatic interactions for the effects of mutations on the free energy of folding. Although there is abundant evidence to indicate that the effects of mutations on the free energy of folding are nearly additive and conserved over evolutionary time, we show that these observations are compatible with the hypothesis that a non-additive contribution to the folding free energy is essential for observed proteins to maintain their native structure. In particular through both simulations and analytical results, we show that even very small departures from additivity are sufficient to drive this effect.
Investigating the effects of cesarean delivery and antibiotic use in early childhood on risk of later attention deficit hyperactivity disorder.

BACKGROUND Increasing attention deficit hyperactivity disorder (ADHD) incidence has been proposed to be caused by factors influencing microbiota in early life. We investigated the potential causality between ADHD and two surrogate markers for changes in children's microbiota: birth delivery mode and early childhood antibiotic use. METHOD This population-based, prospective cohort study linked nationwide registers of data for native Danish singleton live births in Denmark from 1997 to 2010. Exposure variables were delivery mode and antibiotic use during the first 2 years of life. The main outcome measure was ADHD diagnosis or redeemed ADHD medication prescriptions. For statistical analysis, we used both advanced sibling models and a more traditional approach. RESULTS We included 671,592 children, followed from their second birthday in the period 1999-2014 for 7,300,522 person-years. ADHD was diagnosed in 17,971. In total, 17.5% were born by cesarean delivery, and 72% received antibiotic treatment within their first 2 years of life. In the adjusted between-within sibling survival model, mode of delivery or antibiotics had no effect on ADHD when compared with vaginal delivery or no antibiotic treatment as hazard ratios were 1.09 (95% confidence interval 0.97-1.24) for intrapartum cesarean, 1.03 (0.91-1.16) for prelabor cesarean, 0.98 (0.90-1.07) for penicillin, and 0.99 (0.92-1.06) for broader spectrum antibiotics. In a sibling-stratified Cox regression, intrapartum cesarean was associated with increased ADHD risk, but other exposures were not. In a descriptive, nonstratified Cox model, we found increased risk for ADHD for all exposures. CONCLUSIONS Detailed family confounder control using the superior between-within model indicates that cesarean delivery or use of antibiotics during the first 2 years of life does not increase ADHD risk. Therefore, our study suggests that changes in children's microbiota related to cesarean delivery or antibiotic use, do not cause ADHD.
The Free Radical Diseases of Prematurity: From Cellular Mechanisms to Bedside

During the perinatal period, free radicals (FRs) are involved in several physiological roles such as the cellular responses to noxia, the defense against infectious agents, the regulation of cellular signaling function, and the induction of a mitogenic response. However, the overproduction of FRs and the insufficiency of an antioxidant mechanism result in oxidative stress (OS) which represents a deleterious process and an important mediator of damage to the placenta and the developing fetus. After birth, OS can be magnified by other predisposing conditions such as hypoxia, hyperoxia, ischemia, hypoxia ischemia-reperfusion, inflammation, and high levels of nonprotein-bound iron. Newborns are particularly susceptible to OS and oxidative damage due to the increased generation of FRs and the lack of adequate antioxidant protection. This impairment of the oxidative balance has been thought to be the common factor of the so-called “free radical related diseases of prematurity,” including retinopathy of prematurity, bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, kidney damage, and oxidative hemolysis. In this review, we provide an update focused on the factors influencing these diseases refining the knowledge about the role of OS in their pathogenesis and the current evidences of such relationship. Mechanisms governing FR formation and subsequent OS may represent targets for counteracting tissue damage.
Immuno-Oncology: Emerging Targets and Combination Therapies

Host immunity recognizes and eliminates most early tumor cells, yet immunological checkpoints, exemplified by CTLA-4, PD-1, and PD-L1, pose a significant obstacle to effective antitumor immune responses. T-lymphocyte co-inhibitory pathways influence intensity, inflammation and duration of antitumor immunity. However, tumors and their immunosuppressive microenvironments exploit them to evade immune destruction. Recent PD-1 checkpoint inhibitors yielded unprecedented efficacies and durable responses across advanced-stage melanoma, showcasing potential to replace conventional radiotherapy regimens. Neverthless, many clinical problems remain in terms of efficacy, patient-to-patient variability, and undesirable outcomes and side effects. In this review, we evaluate recent advances in the immuno-oncology field and discuss ways forward. First, we give an overview of current immunotherapy modalities, involving mainy single agents, including inhibitor monoclonal antibodies (mAbs) targeting T-cell checkpoints of PD-1 and CTLA-4. However, neoantigen recognition alone cannot eliminate tumors effectively in vivo given their inherent complex micro-environment, heterogeneous nature and stemness. Then, based mainly upon CTLA-4 and PD-1 checkpoint inhibitors as a “backbone,” we cover a range of emerging (“second-generation”) therapies incorporating other immunotherapies or non-immune based strategies in synergistic combination. These include targeted therapies such as tyrosine kinase inhibitors, co-stimulatory mAbs, bifunctional agents, epigenetic modulators (such as inhibitors of histone deacetylases or DNA methyltransferase), vaccines, adoptive-T-cell therapy, nanoparticles, oncolytic viruses, and even synthetic “gene circuits. ” A number of novel immunotherapy co-targets in pre-clinical development are also introduced. The latter include metabolic components, exosomes and ion channels. We discuss in some detail of the personalization of immunotherapy essential for ultimate maximization of clinical outcomes. Finally, we outline possible future technical and conceptual developments including realistic in vitro and in vivo models and inputs from physics, engineering, and artificial intelligence. We conclude that the breadth and quality of immunotherapeutic approaches and the types of cancers that can be treated will increase significantly in the foreseeable future.
Research on Topology Control Algorithm in Heterogeneous wireless sensor networks Based on the Game Theory

Given that the selfish behavior performed by saving energy when the nodes of heterogeneous sensor network is transmitting data, the decline or even rejection in providing data forward services for the neighbor nodes, and the consequence of decline or even paralysis of network communication capability, we put forward a game theory-based topology control algorithm(GTTCA) of heterogeneous wireless sensor network after making consideration for the effects that nodes' transmission power and residual energy exert on the sensor network topology. We also design a revenue function related to transmission power, residual energy and the degree of participation (the possibility nodes participating in transmitting data services). The constant game between network nodes and the adjustment in transmission power is to select the strategy maximizing the revenue function to construct the optimal path with the neighbor nodes. By theoretical analysis, after a period of time, the function converges to a stable state, namely, Nash equilibrium state. Through stimulation experiment, compared with the existing algorithm, the one in this paper is able to efficiently adjust the transmission power of nodes, balance the network energy consumption, and to some extent, prolong the life cycle of network.
The Responsibility of Veterinarians to Address Companion Animal Obesity

Simple Summary Obesity is a disease of rapidly increasing prevalence in dogs and cats, with significant and often lifelong implications for animal welfare. Veterinarians are expected and mandated to protect animal health and welfare, and provide informed consent. We provide an overview of the causes, risk factors, and consequences of pet obesity; evidence regarding veterinarian compliance in diagnosing and discussing obesity in small animal practice; and outline recommendations to prevent and address overweight and obesity in companion animals. We argue that small-animal veterinarians are not meeting their ethical and professional obligation to speak up about obesity, which is a One-Health problem. Abstract Obesity is a modern-day epidemic in both people and companion animals. A summary of the current research on the causes, risk factors, consequences, and implications of overweight and obesity, and the compliance of small-animal practitioners in recognizing and addressing pet obesity, is provided. Ethical and animal welfare concerns are raised regarding these findings. We argue that a patient advocacy posture compels the veterinary profession to confront this issue more reliably. Evidence is presented to support obesity as a One-Health problem, and discrete and practical recommendations for preventing and addressing companion animal obesity are proposed. The One-Health perspective encourages coordinated action by veterinary healthcare professionals in order to address overweight and obesity in companion animals as a public health concern.
Membrane Active Peptides and Their Biophysical Characterization

In the last 20 years, an increasing number of studies have been reported on membrane active peptides. These peptides exert their biological activity by interacting with the cell membrane, either to disrupt it and lead to cell lysis or to translocate through it to deliver cargos into the cell and reach their target. Membrane active peptides are attractive alternatives to currently used pharmaceuticals and the number of antimicrobial peptides (AMPs) and peptides designed for drug and gene delivery in the drug pipeline is increasing. Here, we focus on two most prominent classes of membrane active peptides; AMPs and cell-penetrating peptides (CPPs). Antimicrobial peptides are a group of membrane active peptides that disrupt the membrane integrity or inhibit the cellular functions of bacteria, virus, and fungi. Cell penetrating peptides are another group of membrane active peptides that mainly function as cargo-carriers even though they may also show antimicrobial activity. Biophysical techniques shed light on peptide–membrane interactions at higher resolution due to the advances in optics, image processing, and computational resources. Structural investigation of membrane active peptides in the presence of the membrane provides important clues on the effect of the membrane environment on peptide conformations. Live imaging techniques allow examination of peptide action at a single cell or single molecule level. In addition to these experimental biophysical techniques, molecular dynamics simulations provide clues on the peptide–lipid interactions and dynamics of the cell entry process at atomic detail. In this review, we summarize the recent advances in experimental and computational investigation of membrane active peptides with particular emphasis on two amphipathic membrane active peptides, the AMP melittin and the CPP pVEC.
Double Tuned 1H-23Na Birdcage Coils for MRI at 7 T : Performance evaluation through electromagnetic simulations

The aim of the present study is the electromagnetic evaluation of a ‘four-ring’ double-tuned (DT) birdcage coil designed for head imaging. The model consists of an inner Low-Pass (LP) birdcage coil and two externally nested High-Pass (HP) birdcage-like coils. LP and HP structures are tuned at the 23Na and 1H Larmor frequency at 7 T, respectively. Dimensional parameters are varied in order to optimize the radio frequency (RF) B 1 + field homogeneity at both Larmor frequencies. Results show that B 1 + field homogeneity at the 1H Larmor frequency can be considerably increased by optimizing the mutual distance between the inner and outer coil structure length. This result is particularly significant in case of MRI at 7 T, to correct for the ‘intrinsically’ inhomogeneous B 1 + field due to the short wavelength.