Miracle-dz/UniFAR-FTUs huggingface dataset:
Kill and cure: genomic phylogeny and bioactivity of a diverse collection of Burkholderia gladioli bacteria capable of pathogenic and beneficial lifestyles

Burkholderia gladioli is one of few bacteria with a broad ecology spanning disease in humans, animals, and plants, and encompassing beneficial interactions with multiple eukaryotic hosts. It is a plant pathogen, a bongkrekic acid toxin producing food-poisoning agent, and a lung pathogen in people with cystic fibrosis (CF). Contrasting beneficial traits include antifungal production exploited by insects to protect their eggs, plant protective abilities and antibiotic biosynthesis. We explored the ecological diversity and specialized metabolite biosynthesis of 206 B. gladioli strains, phylogenomically defining 5 evolutionary clades. Historical disease pathovars (pv) B. gladioli pv. allicola and B. gladioli pv. cocovenenans were phylogenetically distinct, while B. gladioli pv. gladioli and B. gladioli pv. agaricicola were indistinguishable. Soft-rot disease and CF infection pathogenicity traits were conserved across all pathovars. Biosynthetic gene clusters for toxoflavin, caryoynencin and enacyloxin were dispersed across B. gladioli, but bongkrekic acid and gladiolin production were clade specific. Strikingly, 13% of CF-infection strains characterised (n=194) were bongkrekic acid toxin positive, uniquely linking this food-poisoning risk factor to chronic lung disease. Toxin production was suppressed by exposing strains to the antibiotic trimethoprim, providing a potential therapeutic strategy to minimise poisoning risk in CF.
Sperm-specific COX6B2 enhances oxidative phosphorylation, proliferation, and survival in lung adenocarcinoma

Cancer testis antigens (CTAs) are genes whose expression is normally restricted to the testis but anomalously activated in cancer. In sperm, a number of CTAs promote energy generation, however whether these proteins contribute to tumor cell metabolism is not understood. Here we describe COX6B2, a sperm-specific component of cytochrome c oxidase (complex IV). COX6B2 is frequently expressed in human lung adenocarcinoma (LUAD) and expression correlates with reduced survival time in patients. COX6B2, but not its somatic isoform COX6B1, enhances activity of complex IV, increasing mitochondrial oxidative phosphorylation (OXPHOS) and NAD+ generation. Consequently, COX6B2-expressing cells display a proliferative advantage, particularly in low oxygen conditions. Conversely, depletion of COX6B2 attenuates OXPHOS and collapses mitochondrial membrane potential leading to cell death or senescence. Furthermore, COX6B2 is both necessary and sufficient for growth of tumors in vivo. Our findings reveal a previously unappreciated, tumor specific metabolic pathway hijacked from one of the most ATP-intensive processes in the animal kingdom: sperm motility.
Clustering and reverse transcription of HIV‐1 genomes in nuclear niches of macrophages

In order to replicate, the Human Immunodeficiency Virus (HIV-1) reverse transcribes its RNA genome into DNA, which subsequently integrates into host cell chromosomes. These two key events of the viral life cycle are commonly viewed as separate not only in time but also in cellular space, since reverse transcription (RT) is thought to be completed in the cytoplasm before nuclear import and integration. However, the spatiotemporal organization of the early replication cycle in macrophages, natural non-dividing target cells that constitute reservoirs of HIV-1 and an obstacle to curing AIDS, remains unclear. Here, we demonstrate that infected macrophages display large nuclear foci of viral DNA and viral RNA, in which multiple genomes cluster together. These clusters form in the absence of chromosomal integration, sequester the paraspeckle protein CPSF6 and localize to nuclear speckles. Strikingly, we show that viral RNA clusters consist mostly of genomic, incoming RNA, both in cells where RT is pharmacologically suppressed and in untreated cells. We demonstrate that, after temporary inhibition, RT can resume in the nucleus and lead to vDNA accumulation in these clusters. We further show that nuclear RT can result in transcription competent viral DNA. These findings change our understanding of the early HIV-1 replication cycle, and may have implications for understanding HIV-1 persistence.
Treated HIV Infection Alters Phenotype but Not HIV-Specific Function of Peripheral Blood Natural Killer Cells

Natural killer (NK) cells are the predominant antiviral cells of the innate immune system, and may play an important role in acquisition and disease progression of HIV. While untreated HIV infection is associated with distinct alterations in the peripheral blood NK cell repertoire, less is known about how NK phenotype is altered in the setting of long-term viral suppression with antiretroviral therapy (ART), as well as how NK memory can impact functional responses. As such, we sought to identify changes in NK cell phenotype and function using high-dimensional mass cytometry to simultaneously analyze both surface and functional marker expression of peripheral blood NK cells in a cohort of ART-suppressed, HIV+ patients and HIV-healthy controls. We found that the NK cell repertoire following IL-2 treatment was altered in individuals with treated HIV infection compared to healthy controls, with increased expression of markers including NKG2C and CD2, and decreased expression of CD244 and NKp30. Using co-culture assays with autologous, in vitro HIV-infected CD4 T cells, we identified a subset of NK cells with enhanced responsiveness to HIV-1-infected cells, but no differences in the magnitude of anti-HIV NK cell responses between the HIV+ and HIV-groups. In addition, by profiling of NK cell receptors on responding cells, we found similar phenotypes of HIV-responsive NK cell subsets in both groups. Lastly, we identified clusters of NK cells that are altered in individuals with treated HIV infection compared to healthy controls, but found that these clusters are distinct from those that respond to HIV in vitro. As such, we conclude that while chronic, treated HIV infection induces a reshaping of the IL-2-stimulated peripheral blood NK cell repertoire, it does so in a way that does not make the repertoire more HIV-specific.
Unsupervised protein embeddings outperform hand-crafted sequence and structure features at predicting molecular function

Motivation Protein function prediction is a difficult bioinformatics problem. Many recent methods use deep neural networks to learn complex sequence representations and predict function from these. Deep supervised models require a lot of labeled training data which are not available for this task. However, a very large amount of protein sequences without functional labels is available. Results We applied an existing deep sequence model that had been pre-trained in an unsupervised setting on the supervised task of protein function prediction. We found that this complex feature representation is effective for this task, outperforming hand-crafted features such as one-hot encoding of amino acids, k-mer counts, secondary structure and backbone angles. Also, it partly negates the need for deep prediction models, as a two-layer perceptron was enough to achieve state-of-the-art performance in the third Critical Assessment of Functional Annotation benchmark. We also show that combining this sequence representation with protein 3D structure information does not lead to performance improvement, hinting that three-dimensional structure is also potentially learned during the unsupervised pre-training. Availability Implementations of all used models can be found at https://github.com/stamakro/GCN-for-Structure-and-Function. Contact ameliavm@ugr.es Supplementary information Supplementary data are available online.
Whales and Men: genetic inferences uncover a detailed history of hunting in bowhead whale

After millennia of hunting and a population collapse, it is still challenging to understand the genetic consequences of whaling on the circumarctic bowhead whale. Here I use published modern mtDNA sequences from the Bering-Chukchi-Beaufort population and a new time calibration to show that late–glacial climate changes and whaling have been the major drivers of population change. Cultures that hunted in the Arctic Seas from as early as 5000 years ago appear to be responsible for successive declines of the population growth, bringing the effective size down to 38% of its pristine population size. The Thules and the Basques (year 1000–1730) who only hunted in the North Atlantic had a major impact on this North Pacific population, indicating that bowhead whale stocks respond to harvesting as a single population unit. Recent positive growth is inferred only after the end of commercial whaling in 1915, and for levels of harvesting that are close to the current annual quota of 67 whales. By unfolding the population history of the bowhead whale, I provide compelling evidence that mtDNA yields critical yet undervalued information for management and conservation of natural populations.
Dynamical effects of dendritic pruning implicated in aging and neurodegeneration: Towards a measure of neuronal reserve

Aging is a main risk factor for neurodegenerative disorders including Alzheimer’s disease. It is often accompanied by reduced cognitive functions, gray-matter volume, and dendritic integrity. Although age-related brain structural changes have been observed across multiple scales, their functional implications remain largely unknown. Here we simulate the aging effects on neuronal morphology as dendritic pruning and characterize its dynamical implications. Utilizing a minimal computational modeling approach, we simulate the dynamics of detailed digitally reconstructed pyramidal neurons of humans obtained from the online repository Neuromorpho.org. We show that as aging progressively affects neuronal integrity, neuronal firing rate is reduced, which causes a reduction in energy consumption, energy efficiency, and dynamic range. Pruned neurons require less energy but their function is often impaired, which can explain the diminished ability to distinguish between similar experiences (pattern separation) in older people. Our measures indicate that the resilience of neuronal dynamics is neuron-specific, heterogeneous, and strongly affected by dendritic topology and the centrality of the soma. Based on the emergent neuronal dynamics, we propose to classify the effects of dendritic deterioration, and put forward that soma centrality measures neuronal reserve. Moreover, our findings suggest that increasing dendritic excitability could partially mitigate the dynamical effects of aging.
Metabolite Genome-Wide Association Study (mGWAS) and Gene-Metabolite Interaction Network Analysis Reveal Potential Biomarkers for Feed Efficiency in Pigs

Metabolites represent the ultimate response of biological systems, so metabolomics is considered to link the genotypes and phenotypes. Feed efficiency is one of the most important phenotypes in sustainable pig production and is the main breeding goal trait. We utilized metabolic and genomic datasets from a total of 108 pigs from our own previously published studies that involved 59 Duroc and 49 Landrace pigs with data on feed efficiency (residual feed intake or RFI), genotype (PorcineSNP80 BeadChip) data and metabolomic data (45 final metabolite datasets derived from LC-MS system). Utilizing these datasets, our main aim was to identify genetic variants (single-nucleotide polymorphisms or SNPs) that affect 45 different metabolite concentrations in plasma collected at the start and end of the performance testing of pigs categorized as high or low in their feed efficiency (based on RFI values). Genome-wide significant genetic variants could be then used as potential genetic or biomarkers in breeding programs for feed efficiency. The other objective was to reveal the biochemical mechanisms underlying genetic variations for pigs’ feed efficiency. In order to achieve these objectives, we firstly conducted a metabolite genome-wide association study (mGWAS) based on mixed linear models and found 152 genome-wide significant SNPs (P-value < 1.06E-06) in association with 17 metabolites that included 90 significant SNPs annotated to 52 genes. On chromosome one alone, 51 significant SNPs associated with isovalerylcarnitine and propionylcarnitine were found to be in strong linkage disequilibrium (LD). SNPs in strong LD annotated to FBXL4 and CCNC consisted of two haplotype blocks where three SNPs (ALGA0004000, ALGA0004041 and ALGA0004042) were in the intron regions of FBXL4 and CCNC. The interaction network revealed that CCNC and FBXL4 were linked by the hub gene N6AMT1 that was associated with isovalerylcarnitine and propionylcarnitine. Moreover, three metabolites (i.e., isovalerylcarnitine, propionylcarnitine and pyruvic acid) were clustered in one group based on the low-high RFI pigs. This study performed a comprehensive metabolite-based GWAS analysis for pigs with differences in feed efficiency and provided significant metabolites for which there is a significant genetic variation as well as biological interaction networks. The identified metabolite genetic variants, genes and networks in high versus low feed efficient pigs could be considered as potential genetic or biomarkers for feed efficiency.
Disentangling the Independent Contributions of Visual and Conceptual Features to the Spatiotemporal Dynamics of Scene Categorization

Human scene categorization is characterized by its remarkable speed. While many visual and conceptual features have been linked to this ability, significant correlations exist between feature spaces, impeding our ability to determine their relative contributions to scene categorization. Here, we used a whitening transformation to decorrelate a variety of visual and conceptual features and assess the time course of their unique contributions to scene categorization. Participants (both sexes) viewed 2250 full-color scene images drawn from 30 different scene categories while having their brain activity measured through 256-channel EEG. We examined the variance explained at each electrode and time point of visual event-related potential (vERP) data from nine different whitened encoding models. These ranged from low-level features obtained from filter outputs to high-level conceptual features requiring human annotation. The amount of category information in the vERPs was assessed through multivariate decoding methods. Behavioral similarity measures were obtained in separate crowdsourced experiments. We found that all nine models together contributed 78% of the variance of human scene similarity assessments and were within the noise ceiling of the vERP data. Low-level models explained earlier vERP variability (88 ms after image onset), whereas high-level models explained later variance (169 ms). Critically, only high-level models shared vERP variability with behavior. Together, these results suggest that scene categorization is primarily a high-level process, but reliant on previously extracted low-level features. SIGNIFICANCE STATEMENT In a single fixation, we glean enough information to describe a general scene category. Many types of features are associated with scene categories, ranging from low-level properties, such as colors and contours, to high-level properties, such as objects and attributes. Because these properties are correlated, it is difficult to understand each property's unique contributions to scene categorization. This work uses a whitening transformation to remove the correlations between features and examines the extent to which each feature contributes to visual event-related potentials over time. We found that low-level visual features contributed first but were not correlated with categorization behavior. High-level features followed 80 ms later, providing key insights into how the brain makes sense of a complex visual world.
Spontaneous Alpha and Theta Oscillations Are Related to Complementary Aspects of Cognitive Control in Younger and Older Adults

The resting-state human EEG power spectrum is dominated by alpha (8-12 Hz) and theta (4-8Hz) oscillations, and also includes non-oscillatory broadband activity inversely related to frequency (1/f activity). Gratton (2018) proposed that alpha and theta oscillations are both related to cognitive control function, though in a complementary manner. Alpha activity is hypothesized to facilitate the maintenance of representations, such as task sets in preparation for expected task conditions. In contrast, theta activity would facilitate changes in representations, such as the updating of task sets in response to unpredicted task demands. Therefore, theta should be related to reactive control (which may prompt changes in task representations), while alpha may be more relevant to proactive control (which implies the maintenance of current task representations). Less is known about the possible relationship between 1/f activity and cognitive control, which was analyzed here in an exploratory fashion. To investigate these hypothesized relationships, we recorded eyes-open and eyes-closed resting-state EEG from younger and older adults and subsequently tested their performance on a cued flanker task, expected to elicit both proactive and reactive control processes. Results showed that alpha power and 1/f slope were smaller in older than younger adults, whereas theta power did not show age-related reductions. Resting alpha power and 1/f slope were predictive of proactive control processes, whereas theta power was related to reactive control as measured by the cued flanker task. All predictive associations were present over and above the effect of age, suggesting that these resting-state EEG correlates could be indicative of trait-like individual differences in cognitive control performance, which may be already evident in younger adults, and are still similarly present in healthy older adults.
Procalcitonin in Children with Relapsing Steroid- Sensitivenephrotic SyndromeA 14-year Retrospective Study

Sensitive-Steroid Nephrotic Syndrome (SSNS) is the most common chronic glomerular disease in children with high incidence of relapse. Infections were statistically significant risk factors for recurrence in SSNS. Current findings suggest that procalcitonin (PCT) may not only be a valid marker for infection and inflammation but also a pro-inflammatory cytokine-like mediator. To identify the relationship betweenprocalcitonin and relapse in childhood SSNS. A crosssectional study was conducted from February 2017 to February 2018. Complete blood count, procalcitonin, and urinalysiswere obtained. Data wasanalyzed by chi-square test with P-value <0.05 considered significant. Of all 55 samples, the percentage of relapsing SSNS in this study is 72.7%. On Receiver Operating Characteristic(ROC) curve, the total Area Under Curve (AUC) was 73.6% with P = 0.007. There was a statistically significant correlation between procalcitonin level cut off 0.065 ng / dL with relapse occurrence (P value = 0.002), with a prevalence ratio of8.308 (CI :95% range: 1.993-34.636). Procalcitonin with cut off value > 0.065 ng / dl gave the best accuracy (70.9%), which predicted relapse with sensitivity 67.5%, specificity 80%. The occurrence of relapsingnephrotic syndrome is influenced only with procalcitonin in this study. Keywords—procalcitonin, minimal change nephropathy, steroid-sensitive nephrotic syndrome, children, relapse
Frequency and Characteristics of Types of Trauma in Sexual Assault Victims Aged 15 Years and Less Referred to Legal Medicine Centers of Fars Province, Iran

Background: This study aimed to investigate the prevalence and characteristics of trauma in sexual assault victims aged 15 years and less referred to legal medicine centers of Fars Province, Iran. Methods: This descriptive cross-sectional was carried out on all female victims of sexual assault aged 15 years old and less referred to legal medicine centers of Fars, Iran, during 2006 2012. The study population consisted of 3140 victims that was reduced to 2113 due to incomplete records of some cases. To analyze the data, descriptive statistics and Chi-square test were used in SPSS, version 16. Results: The prevalence of teenage victims was 32.01%. The highest frequency was reported in 2006 and the next highest rate was reported in 2011. The ordinal place of the victims in family was between 4 and 6 in 79% of the cases. All the crimes happened in cities. In 6.4% of the cases, victims had experienced sexual assault. In 90.1% of the cases, criminals were aged 16 25 years old, and in 40.3% of the cases, they were familiar and had familial relationship with the victim. Sexual traumas in 57.1% of the cases were hymen tear and in 11.8% cases anal tear. Conclusions: Most adolescent sexual assaults remain hidden from the law because of fear of exclusion from the family and society. Therefore, community awareness regarding the prevalence of rape should be raised, and the necessary steps should be taken by the authorities and families to control this crime. Enforcing severe punishments for offenders can be considered as a preventive measure.
A virus that has gone viral: amino acid mutation in S protein of Indian isolate of Coronavirus COVID-19 might impact receptor binding, and thus, infectivity

Since 2002, beta coronaviruses (CoV) have caused three zoonotic outbreaks, SARS-CoV in 2002, MERS-CoV in 2012, and the recent outbreak of SARS-CoV-2 late in 2019 (also named as COVID-19 or novel coronavirus 2019 or nCoV2019. Spike(S) protein, one of the structural proteins of this virus plays key role in receptor (ACE2) binding and thus virus entry. Thus, this protein has attracted scientists for detailed study and therapeutic targeting. As the 2019 novel coronavirus takes its course throughout the world, more and more sequence analyses are been done and genome sequences getting deposited in various databases. From India two clinical isolates have been sequenced and the full genome deposited in GenBank. We have performed sequence analyses of the spike protein of the Indian isolates and compared with that of the Wuhan, China (where the outbreak was first reported). While all the sequences of Wuhan isolates are identical, we found point mutations in the Indian isolates. Out of the two isolates one was found to harbour a mutation in its Receptor binding domain (RBD) at position 407. At this site arginine (a positively charged amino acid) was replaced by isoleucine (a hydrophobic amino acid that is also a C-beta branched amino acid). This mutation has been seen to change the secondary structure of the protein at that region and this can potentially alter receptor ding of the virus. Although this finding needs further validation and more sequencing, the information might be useful in rational drug designing and vaccine engineering.