Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanism and Treatment Related to Oxidative Stress in Neonatal Hypoxic-Ischemic Encephalopathy

Hypoxic ischemic encephalopathy (HIE) is a type of neonatal brain injury, which occurs due to lack of supply and oxygen deprivation to the brain. It is associated with a high morbidity and mortality rate. There are several therapeutic strategies that can be used to improve outcomes in patients with HIE. These include cell therapies such as marrow mesenchymal stem cells (MSCs) and umbilical cord blood stem cells (UCBCs), which are being incorporated into the new protocols for the prevention of ischemic brain damage. The focus of this review is to discuss the mechanism of oxidative stress in HIE and summarize the current available treatments for HIE. We hope that a better understanding of the relationship between oxidative stress and HIE will provide new insights on the potential therapy of this devastating condition.
Prioritising Support for Cost Effective Rare Breed Conservation Using Multi-Criteria Decision Analysis

Farm Animal Genetic Resources (FAnGR) are threatened by breed homogenisation. Rare breeds may carry important genes that allow breeders to respond to global production challenges including climate change and emerging disease risk. Yet, exploration of approaches to improve cost-effectiveness of investments in farm animal genetic diversity has been limited. We employ multi-criteria decision analysis (MCDA) to investigate how rare breed incentive schemes can be rationalised. A performance matrix was used to score assess 19 UK cattle native breeds at risk, in terms of diversity, marketability and endangerment criteria, and an expert workshop was used to assign weights for prioritisation. The workshop participants suggested that criteria pertaining to diversity, marketability and endangerment should be weighted 30%, 20% and 50% respectively. A principal component analysis (PCA) on the criteria suggested that fewer criteria could be used to characterise breed status but that each criteria node contributed effectively in explaining variation in breed scores. Breed scores from the MCDA model were used in a hypothetical exercise to rationalise monetary investments across the case study breeds. TModelling the allocation of thea hypothetical breed improvement fund (BIF) revealed that the greatest variation in the allocation of incentives occurred when marketability was weighted highest, while least variation occurred when endangerment received the highest weight. We suggest MCDA can support more targeted investments in diversity by considering the multiple factors that may be driving extinction risk in addition to the cultural and diversity attributes that compliment conservation.
Archaeal Sources of Intact Membrane Lipid Biomarkers in the Oxygen Deficient Zone of the Eastern Tropical South Pacific

Archaea are ubiquitous in the modern ocean where they are involved in the carbon and nitrogen biogeochemical cycles. However, the majority of Archaea remain uncultured. Archaeal specific membrane intact polar lipids (IPLs) are biomarkers of the presence and abundance of living cells. They comprise archaeol and glycerol dibiphytanyl glycerol tetraethers (GDGTs) attached to various polar headgroups. However, little is known of the IPLs of uncultured marine Archaea, complicating their use as biomarkers. Here, we analyzed suspended particulate matter (SPM) obtained in high depth resolution from a coastal and open ocean site in the eastern tropical South Pacific (ETSP) oxygen deficient zone (ODZ) with the aim of determining possible biological sources of archaeal IPL by comparing their composition by Ultra High Pressure Liquid Chromatography coupled to high resolution mass spectrometry with the archaeal diversity by 16S rRNA gene amplicon sequencing and their abundance by quantitative PCR. Thaumarchaeotal Marine Group I (MGI) closely related to Ca. Nitrosopelagicus and Nitrosopumilus dominated the oxic surface and upper ODZ water together with Marine Euryarchaeota Group II (MGII). High relative abundance of hexose phosphohexose- (HPH) crenarchaeol, the specific biomarker for living Thaumarchaeota, and HPH-GDGT-0, dihexose- (DH) GDGT-3 and -4 were detected in these water masses. Within the ODZ, DPANN (Diapherotrites, Parvarchaeota, Aenigmarchaeota, Nanoarchaeota, and Nanohaloarchaea) of the Woesearchaeota DHVE-6 group and Marine Euryarchaeota Group III (MGIII) were present together with a higher proportion of archaeol-based IPLs, which were likely made by MGIII, since DPANN archaea are supposedly unable to synthesize their own IPLs and possibly have a symbiotic or parasitic partnership with MGIII. Finally, in deep suboxic/oxic waters a different MGI population occurred with HPH-GDGT-1, -2 and DH-GDGT-0 and -crenarchaeol, indicating that here MGI synthesize membranes with IPLs in a different relative abundance which could be attributed to the different detected population or to an environmental adaptation. Our study sheds light on the complex archaeal community of one of the most prominent ODZs and on the IPL biomarkers they potentially synthesize.
Differential Effects of Novel Dopamine Reuptake Inhibitors on Interference With Long-Term Social Memory in Mice

In the laboratory, long-term social recognition memory (SRM) in mice is highly susceptible to proactive and retroactive interference. Here, we investigate the ability of novel designed dopamine (DA) re-uptake inhibitors (rac-CE-123 and S-CE-123) to block retroactive and proactive interference, respectively. Our data show that administration of rac-CE-123 30 min before learning blocks retroactive interference that has been experimentally induced at 3 h, but not at 6 h, post-learning. In contrast, S-CE-123 treatment 30 min before learning blocked the induction of retroactive interference at 6 h, but not 3 h, post-learning. Administration of S-CE-123 failed to interfere with proactive interference at both 3 h and 6 h. Analysis of additional behavioral parameters collected during the memory task implies that the effects of the new DA re-uptake inhibitors on retroactive and proactive interference cannot easily be explained by non-specific effects on the animals’ general social behavior. Furthermore, we assessed the mechanisms of action of drugs using intracerebral in vivo-microdialysis technique. The results revealed that administration of rac-CE-123 and S-CE-123 dose-dependently increased DA release within the nucleus accumbens of freely behaving mice. Thus, the data from the present study suggests that the DA re-uptake inhibitors tested protect the consolidation of long-term social memory against interference for defined durations after learning. In addition, the data implies that DA signaling in distinct brain areas including the nucleus accumbens is involved in the consolidation of SRM in laboratory mice.
Long-Term Behavioral Effects of Post-weaning Social Isolation in Males and Females

Adolescence is a developmental period associated with vast neural and behavioral changes which are accompanied by altered sensitivity to stimuli, both stressful and rewarding. Perturbations, especially stressful stimuli, during this period have been shown to alter behavior in adulthood. Social isolation rearing is one such perturbation. This review highlights the long-term behavioral consequences of adolescent social isolation rearing in rodents with a specific focus on anxiety- and addiction-related behaviors. Sex-specific effects are discussed where data are available. We then consider changes in monoaminergic neurotransmission as one possible mechanism for the behavioral effects described. This research on both normative and perturbed adolescent development is crucial to understanding and treating the increased vulnerability to psychiatric disorders seen in humans during this life stage.
Piperine: A Savor Inducer and a Cancer Reducer

Spices have been used for many decades, and although new and improved culinary spices have been developed, black pepper (Piper nigrum) continues to retain its distinguished title as the “King of spices” due to its particular pungent taste. An alkaloid called piperine is the main component in black pepper that, besides generating the well-known taste, imparts well-documented immunomodulatory, anti-inflammatory, antimicrobial, antioxidant, and even anti-cancer properties; these properties have led to rigorous research on black pepper. Studies conducted on cancer cell lines and in animal models with tumors revealed that piperine might influence tumor development and metastasis via various pathways, some of which are quite common for most types of malignant processes, while others are associated with a specific type of cancer. In this review, we summarized the effect of piperine on various types of cancer and the mechanism by which it acts as a carcinopreventive agent.
Confidence resets reveal hierarchical adaptive learning in humans

Hierarchical processing is pervasive in the brain, but its computational significance for learning under uncertainty is disputed. On the one hand, hierarchical models provide an optimal framework and are becoming increasingly popular to study cognition. On the other hand, non-hierarchical (flat) models remain influential and can learn efficiently, even in uncertain and changing environments. Here, we show that previously proposed hallmarks of hierarchical learning, which relied on reports of learned quantities or choices in simple experiments, are insufficient to categorically distinguish hierarchical from flat models. Instead, we present a novel test which leverages a more complex task, whose hierarchical structure allows generalization between different statistics tracked in parallel. We use reports of confidence to quantitatively and qualitatively arbitrate between the two accounts of learning. Our results support the hierarchical learning framework, and demonstrate how confidence can be a useful metric in learning theory.
Gene copy number variations as signatures of adaptive evolution in the parthenogenetic, plant‐parasitic nematode Meloidogyne incognita

Adaptation to changing environmental conditions represents a challenge to parthenogenetic organisms, and until now, how phenotypic variants are generated in clones in response to the selection pressure of their environment remains poorly known. The obligatory parthenogenetic root‐knot nematode species Meloidogyne incognita has a worldwide distribution and is the most devastating plant‐parasitic nematode. Despite its asexual reproduction, this species exhibits an unexpected capacity of adaptation to environmental constraints, for example, resistant hosts. Here, we used a genomewide comparative hybridization strategy to evaluate variations in gene copy numbers between genotypes of M. incognita resulting from two parallel experimental evolution assays on a susceptible vs. resistant host plant. We detected gene copy number variations (CNVs) associated with the ability of the nematodes to overcome resistance of the host plant, and this genetic variation may reflect an adaptive response to host resistance in this parthenogenetic species. The CNV distribution throughout the nematode genome is not random and suggests the occurrence of genomic regions more prone to undergo duplications and losses in response to the selection pressure of the host resistance. Furthermore, our analysis revealed an outstanding level of gene loss events in nematode genotypes that have overcome the resistance. Overall, our results support the view that gene loss could be a common class of adaptive genetic mechanism in response to a challenging new biotic environment in clonal animals.
Patterns and causes of hospital maternal mortality in Tanzania: A 10-year retrospective analysis

Background Maternal mortality is among the most important public health concerns in Sub-Saharan Africa. There is limited data on hospital-based maternal mortality in Tanzania. The objective of this study was to determine the causes and maternal mortality trends in public hospitals of Tanzania from 2006–2015. Methods and findings This retrospective study was conducted between July and December 2016 and involved 34 public hospitals in Tanzania. Information on causes of deaths due to pregnancy and delivery complications among women of child-bearing age (15–49 years old) recorded for the period of 2006–2015 was extracted. Data sources included inpatient and death registers and International Classification of Disease (ICD)-10 report forms. Maternal deaths were classified based on case definition by ICD 10 and categorized as direct and indirect causes. A total of 40,052 deaths of women of child-bearing age were recorded. There were 1,987 maternal deaths representing 5·0% of deaths of all women aged 15–49 years. The median age-at-death was 27 years (interquartile range: 22, 33). The average age-at-death increased from 25 years in 2006 to 29 years in 2015. Two thirds (67.1%) of the deaths affected women aged 20–34 years old. The number of deaths associated with teenage pregnancy (15–19 years) declined significantly (p-value<0·001) from 17.8% in 2006–2010 to 11.1% in 2011–2015. The proportion of deaths among 30–34 and 35–39 years old (all together) increased from 13% in 2006–2010 to 15·3% in 2011–2015 (p-value = 0.081). Hospital-based maternal mortality ratio increased from 40.24 (2006) to 57.94/100000 births in 2015. Of the 1,987 deaths, 83.8% were due to direct causes and 16.2% were due to indirect causes. Major direct causes were eclampsia (34.0%), obstetric haemorrhage (24.6%) and maternal sepsis (16.7%). Anaemia (14.9%) and cardiovascular disorders (14.0%) were the main indirect causes. Causes of maternal deaths were highly related; being attributed to up to three direct causes (0.12%). Cardiovascular disorders and anaemia had strong linkage with haemorrhage. While there was a decline in the number of deaths due to eclampsia and abortion, those due to haemorrhage and cardiovascular disoders increased during the period. Conclusions During the ten year period (2006–2015) there was an increase in the number of hospital maternal deaths in public hospitals in Tanzania. Maternal deaths accounted for 5% of all women of child-bearing age in-hospital mortalities. Most maternal deaths were due to direct causes including eclampsia, haemorrhage and sepsis. The findings of this study provide evidence for better planning and policy formulation for reproductive health programmes to reduce maternal deaths in Tanzania.
The Role of the Plant Antioxidant System in Drought Tolerance

Water deficiency compromises plant performance and yield in many habitats and in agriculture. In addition to survival of the acute drought stress period which depends on plant-genotype-specific characteristics, stress intensity and duration, also the speed and efficiency of recovery determine plant performance. Drought-induced deregulation of metabolism enhances generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) which in turn affect the redox regulatory state of the cell. Strong correlative and analytical evidence assigns a major role in drought tolerance to the redox regulatory and antioxidant system. This review compiles current knowledge on the response and function of superoxide, hydrogen peroxide and nitric oxide under drought stress in various species and drought stress regimes. The meta-analysis of reported changes in transcript and protein amounts, and activities of components of the antioxidant and redox network support the tentative conclusion that drought tolerance is more tightly linked to up-regulated ascorbate-dependent antioxidant activity than to the response of the thiol-redox regulatory network. The significance of the antioxidant system in surviving severe phases of dehydration is further supported by the strong antioxidant system usually encountered in resurrection plants.
Proteomic and Isotopic Response of Desulfovibrio vulgaris to DsrC Perturbation

Dissimilatory sulfate reduction is a microbial energy metabolism that can produce sulfur isotopic fractionations over a large range in magnitude. Calibrating sulfur isotopic fractionation in laboratory experiments allows for better interpretations of sulfur isotopes in modern sediments and ancient sedimentary rocks. The proteins involved in sulfate reduction are expressed in response to environmental conditions, and are collectively responsible for the net isotopic fractionation between sulfate and sulfide. We examined the role of DsrC, a key component of the sulfate reduction pathway, by comparing wildtype Desulfovibrio vulgaris DSM 644T to strain IPFG07, a mutant deficient in DsrC production. Both strains were cultivated in parallel chemostat reactors at identical turnover times and cell specific sulfate reduction rates. Under these conditions, sulfur isotopic fractionations between sulfate and sulfide of 17.3 ± 0.5‰ or 12.6 ± 0.5‰ were recorded for the wildtype or mutant, respectively. The enzymatic machinery that produced these different fractionations was revealed by quantitative proteomics. Results are consistent with a cellular-level response that throttled the supply of electrons and sulfur supply through the sulfate reduction pathway more in the mutant relative to the wildtype, independent of rate. We conclude that the smaller fractionation observed in the mutant strain is a consequence of sulfate reduction that proceeded at a rate that consumed a greater proportion of the strains overall capacity for sulfate reduction. These observations have consequences for models of sulfate reducer metabolism and how it yields different isotopic fractionations, notably, the role of DsrC in central energy metabolism.
Characterization and Transcriptome Studies of Autoinducer Synthase Gene from Multidrug Resistant Acinetobacter baumannii Strain 863

Quorum sensing (QS) is a cell-to-cell communication system that uses autoinducers as signaling molecules to enable inter-species and intra-species interactions in response to external stimuli according to the population density. QS allows bacteria such as Acinetobacter baumannii to react rapidly in response to environmental changes and hence, increase the chances of survival. A. baumannii is one of the causative agents in hospital-acquired infections and the number of cases has increased remarkably in the past decade. In this study, A. baumannii strain 863, a multidrug-resistant pathogen, was found to exhibit QS activity by producing N-acyl homoserine lactone. We identified the autoinducer synthase gene, which we named abaI, by performing whole genome sequencing analysis of A. baumannii strain 863. Using high resolution tandem triple quadrupole mass spectrometry, we reported that abaI of A. baumannii strain 863 produced 3-hydroxy-dodecanoyl-homoserine lactone. A gene deletion mutant was constructed, which confirmed the functionality of abaI. A growth defect was observed in the QS-deficient mutant strain. Transcriptome profiling was performed to determine the possible genes regulated by QS. Four groups of genes that showed differential expression were discovered, namely those involved in carbon source metabolism, energy production, stress response and the translation process.
Explanation in mathematical conversations: an empirical investigation

Analysis of online mathematics forums can help reveal how explanation is used by mathematicians; we contend that this use of explanation may help to provide an informal conceptualization of simplicity. We extracted six conjectures from recent philosophical work on the occurrence and characteristics of explanation in mathematics. We then tested these conjectures against a corpus derived from online mathematical discussions. To this end, we employed two techniques, one based on indicator terms, the other on a random sample of comments lacking such indicators. Our findings suggest that explanation is widespread in mathematical practice and that it occurs not only in proofs but also in other mathematical contexts. Our work also provides further evidence for the utility of empirical methods in addressing philosophical problems. This article is part of the theme issue ‘The notion of ‘simple proof’ - Hilbert's 24th problem’.
The impact of cuff width and biological sex on cuff preference and the perceived discomfort to blood-flow-restricted arm exercise

Objective: To investigate the influence of cuff width, sex, and applied pressure on the perceived discomfort associated with blood flow restriction at rest and following exercise. Approach: Experiment 1 (n = 96) consisted of four sets of biceps exercise to failure with a narrow and wide cuff inflated to the same relative pressure. Experiment 2 (n = 87) compared two wide cuffs, one of which was inflated to a relative pressure obtained from a narrow cuff. Experiment 3 (n = 50) compared the discomfort of wide and narrow cuffs at rest. Effects are presented as median δ (95% credible interval). Main results: There was no sex effect for any variable of interest. In Experiment 1, the narrow cuff resulted in less discomfort than the wide cuff (39.3 versus 42.5; median δ −0.388 (−0.670, −0.109)). Participants also rated the narrow cuff as more preferable. Experiment 2 found that a wide cuff inflated to a narrow cuffs pressure resulted in greater discomfort than a wide cuff (44 versus 40.9; median δ: 0.420 (0.118, 0.716)). Experiment 3 found no difference between cuff widths. Significance: Blood flow restricted exercise with a narrow cuff results in less discomfort than a wider cuff inflated to the same relative pressure. This effect is not observed at rest and suggests that the wide cuff produces a differential environment compared to a narrow cuff when combined with exercise. Additionally, applying a pressure meant for a narrow cuff to a wide cuff augments the applied pressure and subsequent discomfort to blood flow restricted exercise.
SNP rs2596542G>A in MICA is associated with risk of hepatocellular carcinoma: a meta-analysis

The association of major histocompatibility complex class I chain-related gene A (MICA) single nucleotide polymorphism (SNP) rs2596542G>A and hepatocellular carcinoma (HCC) has been broadly studied, with inconsistent results. Therefore, we conducted the current meta-analysis to better elucidate the roles of SNP rs2596542G>A in HCC. Eligible articles were searched in PubMed, CNKI, Wanfang, Embase, VIP, Web of Science, and CBM databases up to November 2018. Odds ratios (ORs) and 95% CIs were applied. A total of 11 articles, including 4528 HCC patients and 16,625 control subjects, were analyzed. Results revealed that rs2596542G>A was significantly associated with HCC in the heterozygote (G/A versus A/A, P=0.006, OR = 0.854; 95% CI: 0.763–0.956); and dominant (G/G + G/A versus A/A; P=0.021; OR = 0.796; 95% CI: 0.655–0.967) genetic models. Nevertheless, we also detected significant associations between rs2596542G>A and HCV-induced HCC. Additionally, according to our analyses, SNP rs2596542G>A was not correlated with HBV-induced HCC. In conclusion, our findings suggest that MICA SNP rs2596542G>A is associated with HCC susceptibility amongst the Asian, Caucasian, and African ethnicity in certain genetic models. Specifically, MICA SNP rs2396542G>A is associated with risk of HCV-induced HCC, not HBV-induced HCC.