Miracle-dz/UniFAR-FTUs huggingface dataset:
IL-34 Actions on FOXP3+ Tregs and CD14+ Monocytes Control Human Graft Rejection

Cytokines are major players regulating immune responses toward inflammatory and tolerogenic results. In organ and bone marrow transplantation, new reagents are needed to inhibit tissue destructive mechanisms and eventually induce immune tolerance without overall immunosuppression. IL-34 is a cytokine with no significant homology with any other cytokine but that acts preferentially through CSF-1R, as CSF-1 does, and through PTPζ and CD138. Although IL-34 and CSF-1 share actions, a detailed analysis of their effects on immune cells needs further research. We previously showed that both CD4+ and CD8+ FOXP3+ Tregs suppress effector T cells through the production of IL-34, but not CSF-1, and that this action was mediated through antigen-presenting cells. We showed here by single-cell RNAseq and cytofluorimetry that different subsets of human monocytes expressed different levels of CSF-1R, CD138, and PTPζ and that both CD4+ and CD8+ FOXP3+ Tregs expressed higher levels of CSF-1R than conventional T cells. The effects of IL-34 differed in the survival of these different subpopulations of monocytes and RNAseq analysis showed several genes differentially expressed between IL-34, CSF-1, M0, M1, and also M2 macrophages. Acute graft-vs.-host disease (aGVHD) in immunodeficient NSG mice injected with human PBMCs was decreased when treated with IL-34 in combination with an anti-CD45RC mAb that depleted conventional T cells. When IL-34-differentiated monocytes were used to expand Tregs in vitro, both CD4+ and CD8+ FOXP3+ Tregs were highly enriched and this effect was superior to the one obtained with CSF-1. Human CD8+ Tregs expanded in vitro with IL-34-differentiated allogeneic monocytes suppressed human immune responses in an NSG mouse aGVHD model humanized with hPBMCs. Overall, we showed that IL-34 induced the differentiation of human monocytes with a particular transcriptional profile and these cells favored the development of potent suppressor FOXP3+ Tregs.
Role of Microbiota in Pathogenesis and Management of Viral Hepatitis

Hepatitis is a condition that can be self-limiting or can progress to fibrosis (scarring), cirrhosis, or liver cancer. These days, gut microbiota becomes an important part of our immune system, which is important for disease progression or recovery. Translocation of gut microbial and metabolic products causes intestinal inflammation by modulating immune cells leading to impairment of the primary barrier. But there are limited studies discussing pathogenesis and management of hepatitis with gut microbiota. In this review, we have discussed the role of gut microbiota in pathogenesis and management of various hepatitis, especially hepatitis B and C. We have discussed the role of bacterial products, LPS-TLR4 pathway, and unmethylated CpG DNA, which ultimately affects downstream NF-kB signaling in hepatitis. Finally, we have discussed the role of fecal microbiota transplantation in the management of hepatitis.
New Insights Into Cranial Synchondrosis Development: A Mini Review

The synchondroses formed via endochondral ossification in the cranial base are an important growth center for the neurocranium. Abnormalities in the synchondroses affect cranial base elongation and the development of adjacent regions, including the craniofacial bones. In the central region of the cranial base, there are two synchondroses present—the intersphenoid synchondrosis and the spheno-occipital synchondrosis. These synchondroses consist of mirror image bipolar growth plates. The cross-talk of several signaling pathways, including the parathyroid hormone-like hormone (PTHLH)/parathyroid hormone-related protein (PTHrP), Indian hedgehog (Ihh), Wnt/β-catenin, and fibroblast growth factor (FGF) pathways, as well as regulation by cilium assembly and the transcription factors encoded by the RUNX2, SIX1, SIX2, SIX4, and TBX1 genes, play critical roles in synchondrosis development. Deletions or activation of these gene products in mice causes the abnormal ossification of cranial synchondrosis and skeletal elements. Gene disruption leads to both similar and markedly different abnormalities in the development of intersphenoid synchondrosis and spheno-occipital synchondrosis, as well as in the phenotypes of synchondroses and skeletal bones. This paper reviews the development of cranial synchondroses, along with its regulation by the signaling pathways and transcription factors, highlighting the differences between intersphenoid synchondrosis and spheno-occipital synchondrosis.
Role of Pre-operative Inflammatory Markers as Predictors of Lymph Node Positivity and Disease Recurrence in Well-Differentiated Pancreatic Neuroendocrine Tumours: Pancreas2000 Research and Educational Program (Course 9)

Pancreatic neuroendocrine tumours (PNET) is a rare disease and in the absence of metastases, surgical resection is recommended. Key factors affecting survival in PNETs are the stage and grade of the disease, but there is increasing evidence suggesting lymph node involvement is associated with shorter disease-free and overall survival. Ability to predict the likelihood of lymph node involvement at the time of diagnosis would affect surgical decision making in these patients. A systemic inflammatory index such as neutrophil to lymphocyte ratio or platelet to lymphocyte ratio has been associated with poor prognosis in several cancers. Method: This study is a retrospective multi-centre study. The data including pre-operative inflammatory markers such as haemoglobin, neutrophil, lymphocyte counts and pathological data including number of positive lymph nodes, tumour grade and size, are collected to assess the association between inflammatory index and lymph node involvement. Conclusion: This study aims to assess the value of routinely available pre-operative haematological markers in predicting lymph node involvement in non-functioning PNETs.
Combined Brain-Perfusion SPECT and EEG Measurements Suggest Distinct Strategies for Speech Comprehension in CI Users With Higher and Lower Performance

Cochlear implantation constitutes a successful therapy of inner ear deafness, with the majority of patients showing good outcomes. There is, however, still some unexplained variability in outcomes with a number of cochlear-implant (CI) users, showing major limitations in speech comprehension. The current study used a multimodal diagnostic approach combining single-photon emission computed tomography (SPECT) and electroencephalography (EEG) to examine the mechanisms underlying speech processing in postlingually deafened CI users (N = 21). In one session, the participants performed a speech discrimination task, during which a 96-channel EEG was recorded and the perfusions marker 99mTc-HMPAO was injected intravenously. The SPECT scan was acquired 1.5 h after injection to measure the cortical activity during the speech task. The second session included a SPECT scan after injection without stimulation at rest. Analysis of EEG and SPECT data showed N400 and P600 event-related potentials (ERPs) particularly evoked by semantic violations in the sentences, and enhanced perfusion in a temporo-frontal network during task compared to rest, involving the auditory cortex bilaterally and Broca’s area. Moreover, higher performance in testing for word recognition and verbal intelligence strongly correlated to the activation in this network during the speech task. However, comparing CI users with lower and higher speech intelligibility [median split with cutoff + 7.6 dB signal-to-noise ratio (SNR) in the Göttinger sentence test] revealed for CI users with higher performance additional activations of parietal and occipital regions and for those with lower performance stronger activation of superior frontal areas. Furthermore, SPECT activity was tightly coupled with EEG and cognitive abilities, as indicated by correlations between (1) cortical activation and the amplitudes in EEG, N400 (temporal and occipital areas)/P600 (parietal and occipital areas) and (2) between cortical activation in left-sided temporal and bilateral occipital/parietal areas and working memory capacity. These results suggest the recruitment of a temporo-frontal network in CI users during speech processing and a close connection between ERP effects and cortical activation in CI users. The observed differences in speech-evoked cortical activation patterns for CI users with higher and lower speech intelligibility suggest distinct processing strategies during speech rehabilitation with CI.
Pineal Neurosteroids: Biosynthesis and Physiological Functions

Similar to the adrenal glands, gonads, and placenta, vertebrate brains also produce various steroids, which are known as “neurosteroids. ” Neurosteroids are mainly synthesized in the hippocampus, hypothalamus, and cerebellum; however, it has recently been discovered that in birds, the pineal gland, a photosensitive region in the brain, produces more neurosteroids than other brain regions. A series of experiments using molecular and biochemical techniques have found that the pineal gland produces various neurosteroids, including sex steroids, de novo from cholesterol. For instance, allopregnanolone and 7α-hydroxypregnenolone are actively produced in the pineal gland, unlike in other brain regions. Pineal 7α-hydroxypregnenolone, an up-regulator of locomotion, enhances locomotor activity in response to light stimuli in birds. Additionally, pineal allopregnanolone acts on Purkinje cells in the cerebellum and prevents neuronal apoptosis within the developing cerebellum in juvenile birds. Furthermore, exposure to light during nighttime hours can cause loss of diurnal variations of pineal allopregnanolone synthesis during early posthatch life, eventually leading to cerebellar Purkinje cell death in juvenile birds. In light of these new findings, this review summarizes the biosynthesis and physiological functions of pineal neurosteroids. Given that the circadian rhythms of individuals in modern societies are constantly interrupted by artificial light exposure, these findings in birds, which are excellent model diurnal animals, may have direct implications for addressing problems regarding the mental health and brain development of humans.
TRADITIONAL TURKISH ART MUSIC

This paper presents an automatic music transcription (AMT) system which accepts monophonic instrumental ney (flute-like woodwind instrument) recordings of traditional Turkish art music (shortly Turkish music) as input and outputs transcripti ons in the conventional staff notation format. Therefore, aim of the study is to obtain conventional Turkish staff notation for the use of analysis and performance. In order to obtain an output presented in staff notation from audio recordings the following steps are applied: f0 estimation, automatic makam and tonic detection, segmentation and quantiza tion of the f0 curve, determination of pitch intervals, note labeling, quantization of duration and representation of transcription in a symbolic format (note names and durations). For testing purposes, both automatic and manual transcriptions are compared to the original scores of the pieces. Success rates of the automa tic transcriptions and manual transcriptions are found to be comparatively close.
The laboratory culture and development of Helicoverpa armigera

Techniques for the laboratory rearing of Helicoverpa armigera, an important pest of food crops in the Old World tropics, are described. Methods for rearing all stages of the insect are given, including recepies for artificial diets and recommendations for the recognition and control of disease. The effects of various environmental factors on development in the laboratory are described.
Integrating independent microbial studies to build predictive models of anaerobic digestion inhibition by ammonia and phenol

Anaerobic digestion (AD) is a microbial process that can efficiently degrade organic waste into renewable energies such as methane-rich biogas. However, the underpinning microbial mechanisms are highly vulnerable to a wide range of inhibitory compounds, leading to process failure and economic losses. High-throughput sequencing technologies enable the identification of microbial indicators of digesters inhibition and can provide new insights into the key phylotypes at stake during AD process. But yet, current studies have used different inocula, substrates, geographical sites and types of reactors, resulting in indicators that are not robust or reproducible across independent studies. In addition, such studies focus on the identification of a single microbial indicator that is not reflective of the complexity of AD. Our study proposes the first analysis of its kind that seeks for a robust signature of microbial indicators of phenol and ammonia inhibitions, whilst leveraging on 4 independent in-house and external AD microbial studies. We applied a recent multivariate integrative method on two-in-house studies to identify such signature, then predicted the inhibitory status of samples from two datasets with more than 90% accuracy. Our study demonstrates how we can efficiently analyze existing studies to extract robust microbial community patterns, predict AD inhibition, and deepen our understanding of AD towards better AD microbial management. Highlights Robust biomarkers of AD inhibition were tagged by integrating independent 16S studies Increase of the Clostridiales relative abundance is an early warning of AD inhibition Cloacimonetes is associated with good performance of biomethane production Multivariate model predicts ammonia inhibition with 90% accuracy in external data
Seasonal and Fasting-Related Changes in Circulating Gonadal Steroids and Prolactin in King Penguins, Aptenodytes patagonicus

Temporal correlations between reproductive endocrinology and the breeding and molt cycle of the king penguin were studied at the Crozet Islands, in the southern Indian Ocean. This species is unique in having a long cycle (14-15 mo), mainly due to a prolonged fledging period (11 mo), which includes the austral winter. Plasma gonadal steroids and prolactin were at their minimum levels during the prebreeding molt. However, circulating testosterone (males) and estradiol and progesterone (females) were already elevated at the time of arrival at the colony to breed, and the levels peaked during copulation. After laying plasma steroids decreased but remained above basal levels during the following months. Prolactin was low during the sexual phase of the reproductive cycle of both males and females. It reached high plasma concentrations in incubating birds and remained elevated during the whole fledging period. Possible roles for sustained high prolactin levels in winter and spring, which involve the care of the single chick and the prevention of a new cycle, are discussed. The effect of nutritional status of birds on plasma reproductive hormones was also investigated in relation to brief (brooding shifts) and prolonged (incubation spells)fasting. No major effect of food deprivation on plasma hormones was found in incubating and brooding king penguins during normal shifts. However, birds with a low body mass (<9 kg), which progressively mobilized their body protein, presented higher progesterone levels and lower plasma testosterone and prolactin. The decrease in plasma prolactin may be involved in the spontaneous abandon of reproduction previously described in penguins that have depleted their fat stores.
When Guiding Principles Don't Guide: The Moderating Effects of Cultural Tightness on Value-Behavior Links.

OBJECTIVE Ample research documented the effects of guiding principles in people's lives, as reflected in personal values, on a variety of behaviors. But do these principles universally guide behaviors across all cultural contexts? To address this question, we investigated the effect of cross-cultural differences in the strength of social norms (i.e., tightness-looseness) on value-behavior relationships. METHOD Using the archival data from the World Value Survey for 24 nations (N = 38924; 51.40% female; Mage = 44.98, SD = 16.87), a multi-level analysis revealed that cultural tightness moderated the effects of individual differences in personal values on behaviors from different life-domains. RESULTS As hypothesized, the relationships between self-transcendence values with civic involvement and pro-environmental behaviors, and between conservation values with religious behavior were significantly stronger in loose cultures that have weak norms and were almost nonexistent in tight cultures that have strong norms, even when controlling for individualism-collectivism or GDP. CONCLUSIONS Thus, despite the common believe that people behave in line with their guiding principles, our findings suggest this might not be the case in cultural contexts that put a strong emphasis on norms.
Development and application of statistical algorithms for the detection of additive and interacting loci underlying quantitative traits

A major goal of today’s biology is to understand the genetic basis of quantitative traits. This can be achieved by statistical methods which evaluate the association between phenotypic observations and molecular markers. The objective of this work was (i) to evaluate different kinds of populations in regard to their suitability for quantitative trait loci (QTLs) mapping; (ii) the development of statistical methods with improved power for association mapping; and (iii) the analysis of the Arabidopsis multi-parental recombinant inbred lines version 2 (AMPRILv2). The examined mating designs differed strongly with respect to the statistical power to detect QTLs. We observed the highest power to detect QTLs for the diallel cross with random mating design. Our results, however, revealed that using designs in which more than two parental genomes are segregated in each subpopulation increases the power even more. The quantitative trait cluster association test (QTCAT) was developed, which allows the joint association of all available single-nucleotide polymorphisms (SNPs) to the phenotype. Furthermore, the test accounts for the correlation among SNPs by integrating a hierarchical clustering structure of the SNPs into the testing procedure. SNPs near to the base of this hierarchy are strongly correlated, so it is therefore not always possible to decide which of them is carrying the causal variant. In these cases it is best to further join these clusters as one and associate them jointly, which is the fundamental idea of the QTCAT approach. This has appealing consequences for cases in which SNP density is high and every causal variant is expected to be highly linked to one of the SNPs, then no further correction of the population structure is needed. In a simulation-based comparison we will show the benefits of QTCAT in comparison to other methods. The AMPRILv2 population is a multi-parental mapping population based on eight founders. 2 million SNPs were accessible and could be used for the analysis with QTCAT. We found 14 genomic regions associated to flowering time. Furthermore, we found epistatic interactions which were able to improve the predictability of flowering time. Our results showed the improved power of QTCAT compared to other methods. Moreover, we found several pairs of regions in the genome with dependency among alleles. For a known hybrid incompatibility we were able to detect an additional modifier locus involved. We were able to show that multi-parental populations are beneficial not only for association studies but also for the detection of hybrid incompatibility. The QTCAT approach is able to improve association testing compared to other methods.
Soybean BARCSoySNP6K: An assay for soybean genetics and breeding research

SUMMARY The limited number of recombinant events in recombinant inbred lines suggests that for a biparental population with a limited number of recombinant inbred lines, it is unnecessary to genotype the lines with many markers. For genomic prediction and selection, previous studies have demonstrated that only 1000–2000 genome‐wide common markers across all lines/accessions are needed to reach maximum efficiency of genomic prediction in populations. Evaluation of too many markers will not only increase the cost but also generate redundant information. We developed a soybean (Glycine max) assay, BARCSoySNP6K, containing 6000 markers, which were carefully chosen from the SoySNP50K assay based on their position in the soybean genome and haplotype block, polymorphism among accessions and genotyping quality. The assay includes 5000 single nucleotide polymorphisms (SNPs) from euchromatic and 1000 from heterochromatic regions. The percentage of SNPs with minor allele frequency >0.10 was 95% and 91% in the euchromatic and heterochromatic regions, respectively. Analysis of progeny from two large families genotyped with SoySNP50K versus BARCSoySNP6K showed that the position of the common markers and number of unique bins along linkage maps were consistent based on the SNPs genotyped with the two assays; however, the rate of redundant markers was dramatically reduced with the BARCSoySNP6K. The BARCSoySNP6K assay is proven as an excellent tool for detecting quantitative trait loci, genomic selection and assessing genetic relationships. The assay is commercialized by Illumina Inc. and being used by soybean breeders and geneticists and the list of SNPs in the assay is an ideal resource for SNP genotyping by targeted amplicon sequencing.
The limited spatial scale of dispersal in soil arthropods revealed with whole-community haplotype-level metabarcoding

Soil mesofauna communities are hyperdiverse and critical for ecosystem functioning. However, our knowledge on spatial structure and underlying processes of community assembly for soil arthropods is scarce, hampered by limited empirical data on species diversity and turnover. We implement a high-throughput-sequencing approach to generate comparative data for thousands of arthropods at three hierarchical levels: genetic, species and supra-specific lineages. A joint analysis of the spatial arrangement across these levels can reveal the predominant processes driving the variation in biological assemblages at the local scale. This multi-hierarchical approach was performed using haplotype-level-COI metabarcoding of entire communities of mites, springtails and beetles from three Iberian mountain regions. Tens of thousands of specimens were extracted from deep and superficial soil layers and produced comparative phylogeographic data for >1000 co-distributed species and nearly 3000 haplotypes. Local assemblages were highly distinctive between grasslands and forests, and within each of them showed strong spatial structures and high endemicity at the scale of a few kilometres or less. The local distance-decay patterns were self-similar for the haplotypes and higher hierarchical entities, and this fractal structure was very similar in all three regions, pointing to a significant role of dispersal limitation driving the local-scale community assembly. Our results from whole-community metabarcoding provide unprecedented insight into how dispersal limitations constrain mesofauna community structure within local spatial settings over evolutionary timescales. If generalized across wider areas, the high turnover and endemicity in the soil locally may indicate extremely high richness globally, challenging our current estimations of total arthropod-diversity on Earth.