Miracle-dz/UniFAR-FTUs huggingface dataset:
A Systems-Wide Analysis of Proteolytic and Lipolytic Pathways Uncovers The Flavor-Forming Potential of The Gram-Positive Bacterium Macrococcus caseolyticus subsp. caseolyticus

Macrococcus caseolyticus subsp. caseolyticus is a Gram-positive, commensal organism documented to be present as a component of the secondary microflora in fermented foods such as Ragusano and Fontina cheeses and Cantonese sausage. In these products, the organism appears to play a role in ripening and the development of the final organoleptic qualities. However, the role of this organism in flavor generation is not well understood. Therefore, the objective of this study was to investigate the role of M. caseolyticus subsp. caseolyticus in flavor compound formation through an examination of enzymatic, metabolomic and genomic data. A bank of M. caseolyticus subsp. caseolyticus strains derived from a variety of niches were examined. Enzyme activities analyzed comprised those of the proteolytic and lipolytic cascades including cell-envelope proteinase (CEP), peptidases, esterases, lipases, aminotransferases and glutamate dehydrogenase (GDH). Strain to strain variation was observed, often associated with niche. All strains, except those isolated from non-dairy sources, demonstrated high CEP activity. Such high CEP activity associated with dairy strains implies the importance of this characteristic in the adaptation of these strains to a dairy-specific niche. However, limited downstream peptidolytic activity, in addition to a limited ability to generate free amino acids (FAA) was observed across all strains, indicating weak ability of this organism to generate amino-acid derived flavor compounds. Interestingly, the strains with high CEP activity also demonstrated high esterase activity and gas chromatography-mass spectrometry (GC-MS) analysis of the volatile compounds produced when these strains were grown in lactose-free milk demonstrated differences in the range and types of volatiles produced. In contrast to this metabolic versatility, comparative genome analysis revealed the distribution of components of the proteolytic and lipolytic system in these strains to be conserved. Overall, this study demonstrates the potential of M. caseolyticus subsp. caseolyticus to generate diverse volatile flavor compounds. Additionally, the identification of the highly active strain-specific cell wall bound caseolytic proteases deriving extensive casein hydrolysis, serves as a promising avenue which can be potentially harnessed in the future to produce greater and more diverse flavor compounds.
How Effective Is Iron Supplementation During Pregnancy and Childhood in Reducing Anemia Among 6–59 Months Old Children in India?

Objectives: The study sought to identify whether iron and folic acid supplementation of pregnant women and preschool children is associated with child's anemia status and the predictors of anemia among children in India. Design: Secondary data analysis was performed using the National Family Health Survey 4 data. Multivariable logistic regression was used to identify the adjusted associations between child's anemia status and iron supplementation, both during pregnancy and childhood. Also, a model of significant predictors of anemia among children was fitted. Setting: India. Participants: Youngest children (6-59 months) in families. Results: The adjusted association between supplementation during pregnancy and child's anemia status was significant (p = 0.010), whereas the adjusted association between supplementation during childhood and child's anemia status was insignificant (p = 0.16). The variables independently associated with anemia status of the child included younger age (95% CI 2.67–2.86), child's recent diarrhea (95% CI 1.02–1.14), low birth weight (95% CI 1.17–1.27), current underweight (95% CI 1.14–1.28), diet diversity score (95% CI 0.96–0.98), higher birth order (95% CI 1.01–1.05), mother's current anemia (95% CI 1.68–1.81), months of breastfeeding (95% CI 0.99–1.00), no/primary education (95% CI 1.23–1.35), family's low wealth index (95% CI 1.11–1.23), and backward caste (95% CI 1.04–1.14). Conclusions: The National Iron Plus Initiative strategy of child's iron supplementation should be evaluated to identify the reasons of its ineffectiveness in anemia reduction. In addition, vulnerable groups of children, i.e., children from poor and less educated families and those with low birth weight, higher birth order, and poor nutritional status, should be targeted first with anemia reduction interventions.
The MADS-Box Gene MdDAM1 Controls Growth Cessation and Bud Dormancy in Apple

Apple trees require a long exposure to chilling temperature during winter to acquire competency to flower and grow in the following spring. Climate change or adverse meteorological conditions can impair release of dormancy and delay bud break, hence jeopardizing fruit production and causing substantial economic losses. In order to characterize the molecular mechanisms controlling bud dormancy in apple we focused our work on the MADS-box transcription factor gene MdDAM1. We show that MdDAM1 silencing is required for the release of dormancy and bud break in spring. MdDAM1 transcript levels are drastically reduced in the low-chill varieties ‘Anna’ and ‘Dorsett Golden’ compared to ‘Golden Delicious’ corroborating its role as a key genetic factor controlling the release of bud dormancy in Malus species. The functional characterization of MdDAM1 using RNA silencing resulted in trees unable to cease growth in winter and that displayed an evergrowing, or evergreen, phenotype several years after transgenesis. These trees lost their capacity to enter in dormancy and produced leaves and shoots regardless of the season. A transcriptome study revealed that apple evergrowing lines are a genocopy of ‘Golden Delicious’ trees at the onset of the bud break with the significant gene repression of the related MADS-box gene MdDAM4 as a major feature. We provide the first functional evidence that MADS-box transcriptional factors are key regulators of bud dormancy in pome fruit trees and demonstrate that their silencing results in a defect of growth cessation in autumn. Our findings will help producing low-chill apple variants from the elite commercial cultivars that will withstand climate change.
cyclic AMP Regulation and Its Command in the Pacemaker Channel HCN4

Direct regulation of the pacemaker “funny” current (If) by cyclic AMP (cAMP) underlies heart rate modulation by the autonomic nervous system. At the molecular level, cAMP activates hyperpolarization-activated cyclic nucleotide-gated (HCN) channels that drive If in sinoatrial node (SAN) myocytes. Even though HCN channel genes were identified more than 20 years ago, the understanding of how cAMP regulates their gating is still fragmented. Here we summarize present understanding on how the cAMP signal is transmitted from the cytosolic to the transmembrane (TM) domain in HCN4. We further discuss how detailed structural knowledge prompted the development of pharmacological/genetic tools for the control of cAMP regulation in these channels.
A controlled thermoalgesic stimulation device to identify novel pain perception biomarkers

Objective To develop a new device that will help identify physiological markers of pain perception by reading the brain’s electrical activity and the bodies hemodynamic interactions while applying thermoalgesic stimulation. Methods: We designed a compact prototype that generates well-controlled thermal stimuli using a computer driven Peltier cell while simultaneously capturing electroencephalography (EEG) and photoplethysmography (PPG) signals as the stimuli are varied. The study was performed on 35 healthy subjects (mean age 30.46 years, SD 4.93 years; 20 males, 15 females) and to account for the inter-subject variability in the tolerance to thermal pain, we first determined the heat pain threshold (HPT) for each subject, defined as the maximum temperature that the subject can withstand when the Peltier cell gradually increases the temperature. Subsequently, we defined the pain parameters associated with a stimulation temperature equivalent to 90% of the HPT, comparing this to the no-pain state (control) in the absence of thermoalgesic stimulation. Results: Both the one-dimensional and the two-dimensional spectral entropy (SE) obtained from both the EEG and PPG signals could differentiate the condition of pain. In particular, the PPG SE was significantly reduced in association with pain, while the SE for EEG increased slightly. Moreover, significant discrimination occurred within a specific range of frequencies, 26-30 Hz for EEG and about 5-10 Hz for PPG. Conclusion: Hemodynamics, brain dynamics and their interactions can discriminate thermal pain perception. Significance: The possibility of monitoring on-line variations in thermal pain perception using a similar device and algorithms may be of interest to study different pathologies that affect the peripheral nervous system, such as small fiber neuropathies, fibromyalgia or painful diabetic neuropathy.
Ultra-Fast Homomorphic Encryption Models enable Secure Outsourcing of Genotype Imputation

Genotype imputation is a fundamental step in genomic data analysis such as GWAS, where missing variant genotypes are predicted using the existing genotypes of nearby ‘tag’ variants. Imputation greatly decreases the genotyping cost and provides high-quality estimates of common variant genotypes. As population panels increase, e.g., the TOPMED Project, genotype imputation is becoming more accurate, but it requires high computational power. Although researchers can outsource genotype imputation, privacy concerns may prohibit genetic data sharing with an untrusted imputation service. To address this problem, we developed the first fully secure genotype imputation by utilizing ultra-fast homomorphic encryption (HE) techniques that can evaluate millions of imputation models in seconds. In HE-based methods, the genotype data is end-to-end encrypted, i.e., encrypted in transit, at rest, and, most importantly, in analysis, and can be decrypted only by the data owner. We compared secure imputation with three other state-of-the-art non-secure methods under different settings. We found that HE-based methods provide full genetic data security with comparable or slightly lower accuracy. In addition, HE-based methods have time and memory requirements that are comparable and even lower than the non-secure methods. We provide five different implementations and workflows that make use of three cutting-edge HE schemes (BFV, CKKS, TFHE) developed by the top contestants of the iDASH19 Genome Privacy Challenge. Our results provide strong evidence that HE-based methods can practically perform resource-intensive computations for high throughput genetic data analysis. In addition, the publicly available codebases provide a reference for the development of secure genomic data analysis methods.
Anti-predator Strategies in Relation to Diurnal Refuge Usage and Exploration in the Australian Freshwater Prawn, Macrobrachium australiense

Abstract This study examined 24 hour activity patterns of a diurnally refuge seeking palaemonid, Macrobrachium australiense. The results obtained improve our understanding of the mechanistic processes that are likely to underlie observed patterns of anti-predatory refuge usage, and diurnal inactivity, in a wide range of crustaceans. When introduced to a novel environment M. australiense altered their searching behaviours in response to changes in available refugia. These behaviours were consistent with attempts to reduce exposure to predation. They altered in response to variation in stalk density of a vegetated refuge, environmental conditions, and individual body size. When settled in the environment all vegetated refuges were attractive to the test species, though higher stalk densities were preferred. M. australiense demonstrated both an active and a passive strategy of mediating exposure to predation. Like numerous other prawn species they substantially reduced activity during periods of high light. The underlying preferences and behavioural mechanisms displayed by the test animals were consistent with the theory that diurnal inactivity is a form of antipredator behaviour, even in the absence of predators. Upon subsequent exposure to predation, refuge seeking behaviour altered depending on the current activity level of the individual: during periods of low activity there was no significant change in behaviour. The presence of a predator had no significant impact upon the occurrence of periods of high activity. However, during these periods the presence of the predator caused an increase in the time prawns spent within the refuge, and decreased the number of transitions between the refuge and the open area.
Deficits in Auditory and Visual Sensory Discrimination Reflect a Genetic Liability for Psychosis and Predict Disruptions in Global Cognitive Functioning

Sensory discrimination thresholds (i.e., the briefest stimulus that can be accurately perceived) can be measured using tablet-based auditory and visual sweep paradigms. These basic sensory functions have been found to be diminished in patients with psychosis. However, the extent to which worse sensory discrimination characterizes genetic liability for psychosis, and whether it is related to clinical symptomatology and community functioning remains unknown. In the current study we compared patients with psychosis (PSY; N=76), their first-degree biological relatives (REL; N=44), and groups of healthy controls (CON; N=13 auditory and visual/N=275 auditory/N=267 visual) on measures of auditory and visual sensory discrimination, and examined relationships with a battery of symptom, cognitive, and functioning measures. Sound sweep thresholds differed among the PSY, REL, and CON groups, driven by higher thresholds in the PSY compared to CON group, with the REL group showing intermediate thresholds. Visual thresholds also differed among the three groups, driven by higher thresholds in the REL versus CON group, and no significant differences between the REL and PSY groups. Across groups and among patients, higher thresholds (poorer discrimination) for both sound and visual sweeps strongly correlated with lower global cognitive scores. We conclude that low-level auditory and visual sensory discrimination deficits in psychosis may reflect genetic liability for psychotic illness. Critically, these deficits relate to global cognitive disruptions that are a hallmark of psychotic illnesses such as schizophrenia.
Gene action and standard heterosis over environments in rice (Oryza sativa L.).

The present study on genetic components of variance carried over individual and pooled environments for thirteen metric traits in rice revealed the greater magnitude of dominance component than corresponding additive component of variance, thereby showing greater role of dominance in genetic control for most of the traits. The net dominance effect (ĥ2) was positively significant for the traits plant height, productive tillers per plant, spikelets per panicle, days to flowering and maturity. The estimate was non-significant for all the traits studied. The proportion of Ĥ2/4Ĥ1 was less than 0.25 for all the traits. The proportion of dominance and recessive alleles (KD/KR) in the parents was greater than one for majority of the traits suggesting preponderance of dominance alleles. The study on genetic ratios revealed that proportion of average degree of dominance measured from genetic components of variance was more than unity. The estimates of ĥ1/Ĥ2 were more than 0.50 for most of the characters. Low narrow sense heritability estimates were recorded for most of the traits. Thirteen cross combinations demonstrated the maximum manifestation of standard heterotic effect for grain yield plant−1 over check varieties Jhelum and Shalimar Rice-1. The magnitude of heterosis over Jhelum and Shalimar Rice-1 ranged from -56.07 to 35.21% and -62.69 to 28.29%, respectively. The most promising cross combinations for grain yield plant−1 in order of merit over standard checks Jhelum and Shalimar Rice-1 included SKAU-389 x K-08-60 (35.21 and 28.29%), Jhelum x K-08-60 (32.22 and 26.20%), SKAU-389 x Pusa Sugandh-5 (30.74 and 24.14%), Jhelum x SKAU-389 (29.07 and 22.58%) and China-988 x Shalimar Rice-1 (27.08 and 22.49%). Further, these crosses revealed high heterosis in desirable direction for other economically important traits.
Metagenome-assembled genomes from Monte Cristo Cave (Diamantina, Brazil) reveal prokaryotic lineages as functional models for life on Mars

Although several studies have explored microbial communities in different terrestrial subsurface ecosystems, little is known about the diversity of their metabolic processes and survival strategies. The advance of bioinformatic tools is allowing the description of novel and not-yet cultivated microbial lineages in different ecosystems, due to the genome reconstruction approach from metagenomic data. The recovery of genomes has the potential of revealing novel lifestyles, metabolic processes and ecological roles of microorganisms, mainly in ecosystems that are largely unknown, and in which cultivation could be not viable. In this study, through shotgun metagenomic data, it was possible to reconstruct several genomes of cultivated and not-yet cultivated prokaryotic lineages from a quartzite cave, located in Minas Gerais state, Brazil, which showed to possess a high diversity of genes involved with different biogeochemical cycles, including reductive and oxidative pathways related to carbon, sulfur, nitrogen and iron. Tree genomes were selected, assigned as Truepera sp. , Ca. Methylomirabilis sp. and Ca. Koribacter sp. based on their lifestyles (radiation resistance, anaerobic methane oxidation and potential iron oxidation) for pangenomic analysis, which exhibited genes involved with different DNA repair strategies, starvation and stress response. Since these groups have few reference genomes deposited in databases, our study adds important genomic information about these lineages. The combination of techniques applied in this study allowed us to unveil the potential relationships between microbial genomes and their ecological processes with the cave mineralogy, as well as to discuss their implications for the search for extant lifeforms outside our planet, in silica- and iron-rich environments, especially on Mars.
Human and rat skeletal muscle single-nuclei multi-omic integrative analyses nominate causal cell types, regulatory elements, and SNPs for complex traits

Background Skeletal muscle accounts for the largest proportion of human body mass, on average, and is a key tissue in complex diseases, mobility, and quality of life. It is composed of several different cell and muscle fiber types. Results Here, we optimize single-nucleus ATAC-seq (snATAC-seq) to map skeletal muscle cell-specific chromatin accessibility landscapes in frozen human and rat samples, and single-nucleus RNA-seq (snRNA-seq) to map cell-specific transcriptomes in human. We capture type I and type II muscle fiber signatures, which are generally missed by existing single-cell RNA-seq methods. We perform cross-modality and cross-species integrative analyses on 30,531 nuclei, representing 11 libraries, profiled in this study, and identify seven distinct cell types ranging in abundance from 63% (type II fibers) to 0.9% (muscle satellite cells) of all nuclei. We introduce a regression-based approach to infer cell types by comparing transcription start site-distal ATAC-seq peaks to reference enhancer maps and show consistency with RNA-based marker gene cell type assignments. We find heterogeneity in enrichment of genetic variants linked to complex phenotypes from the UK Biobank and diabetes genome wide association studies in cell-specific ATAC-seq peaks, with the most striking enrichment patterns in muscle mesenchymal stem cells (∼3% of nuclei). Finally, we overlay these chromatin accessibility maps on GWAS data to nominate causal cell types, SNPs, and transcription factor motifs for creatinine levels and type 2 diabetes signals. Conclusions These chromatin accessibility profiles for human and rat skeletal muscle cell types are a useful resource for investigating specific cell types and nominating causal GWAS SNPs and cell types.
Neural Correlates of Modal Displacement and Discourse-Updating under (Un)Certainty

Abstract A hallmark of human thought is the ability to think about not just the actual world but also about alternative ways the world could be. One way to study this contrast is through language. Language has grammatical devices for expressing possibilities and necessities, such as the words might or must. With these devices, called “modal expressions,” we can study the actual versus possible contrast in a highly controlled way. While factual utterances such as “There is a monster under my bed” update the here-and-now of a discourse model, a modal version of this sentence, “There might be a monster under my bed,” displaces from the here-and-now and merely postulates a possibility. We used magnetoencephalography (MEG) to test whether the processes of discourse updating and modal displacement dissociate in the brain. Factual and modal utterances were embedded in short narratives, and across two experiments, factual expressions increased the measured activity over modal expressions. However, the localization of the increase appeared to depend on perspective: signal localizing in right temporoparietal areas increased when updating the representation of someone else’s beliefs, while frontal medial areas seem sensitive to updating one’s own beliefs. The presence of modal displacement did not elevate MEG signal strength in any of our analyses. In sum, this study identifies potential neural signatures of the process by which facts get added to our mental representation of the world.
Reduced stress and increased immune responses in Nile tilapia kept under self‐feeding conditions

: Stress and immune responses were studied in Nile tilapia Oreochromis niloticus under both conditions of self-feeding and scheduled feeding. Self-feeding fish had a significantly lower cortisol level in their blood plasma than that of scheduled feeding fish. Furthermore, skin color was found to be paler in the self-feeding fish compared with that of the scheduled feeding fish. Thus, the self-feeding fish had a less stressful physiological status than the other experimental fish. Immunological analyses revealed that the self-feeding fish significantly exceeded the scheduled feeding fish in the phagocytic activity of their macrophages, antibody production, and the number of blood-circulating lymphocytes. The higher immune responses of self-feeding fish seem to be attained through a less stressful environment. This self-feeding behavior could be exploited to create reduced stress for disease control in fish farming.
Prior hypotheses or regularization allow inference of diversification histories from extant timetrees

Phylogenies of extant species are widely used to study past diversification dynamics1. The most common approach is to formulate a set of candidate models representing evolutionary hypotheses for how and why speciation and extinction rates in a clade changed over time, and compare those models through their probability to have generated the corresponding empirical tree. Recently, Louca & Pennell2 reported the existence of an infinite number of ‘congruent’ models with potentially markedly different diversification dynamics, but equal likelihood, for any empirical tree (see also Lambert & Stadler3). Here we explore the implications of these results, and conclude that they neither undermine the hypothesis-driven model selection procedure widely used in the field nor show that speciation and extinction dynamics cannot be investigated from extant timetrees using a data-driven procedure.