Miracle-dz/UniFAR-FTUs huggingface dataset:
Six Novel Susceptibility Loci for Early-Onset Androgenetic Alopecia and Their Unexpected Association with Common Diseases

Androgenetic alopecia (AGA) is a highly heritable condition and the most common form of hair loss in humans. Susceptibility loci have been described on the X chromosome and chromosome 20, but these loci explain a minority of its heritable variance. We conducted a large-scale meta-analysis of seven genome-wide association studies for early-onset AGA in 12,806 individuals of European ancestry. While replicating the two AGA loci on the X chromosome and chromosome 20, six novel susceptibility loci reached genome-wide significance (p = 2.62×10−9–1.01×10−12). Unexpectedly, we identified a risk allele at 17q21.31 that was recently associated with Parkinson's disease (PD) at a genome-wide significant level. We then tested the association between early-onset AGA and the risk of PD in a cross-sectional analysis of 568 PD cases and 7,664 controls. Early-onset AGA cases had significantly increased odds of subsequent PD (OR = 1.28, 95% confidence interval: 1.06–1.55, p = 8.9×10−3). Further, the AGA susceptibility alleles at the 17q21.31 locus are on the H1 haplotype, which is under negative selection in Europeans and has been linked to decreased fertility. Combining the risk alleles of six novel and two established susceptibility loci, we created a genotype risk score and tested its association with AGA in an additional sample. Individuals in the highest risk quartile of a genotype score had an approximately six-fold increased risk of early-onset AGA [odds ratio (OR) = 5.78, p = 1.4×10−88]. Our results highlight unexpected associations between early-onset AGA, Parkinson's disease, and decreased fertility, providing important insights into the pathophysiology of these conditions.
A Possible Link between Food and Mood: Dietary Impact on Gut Microbiota and Behavior in BALB/c Mice

Major depressive disorder is a debilitating disease in the Western World. A western diet high in saturated fat and refined sugar seems to play an important part in disease development. Therefore, this study is aimed at investigating whether saturated fat or sucrose predisposes mice to develop behavioral symptoms which can be interpreted as depression-like, and the possible influence of the gut microbiota (GM) in this. Fourty-two mice were randomly assigned to one of three experimental diets, a high-fat, a high-sucrose or a control diet for thirteen weeks. Mice on high-fat diet gained more weight (p = 0.00009), displayed significantly less burrowing behavior than the control mice (p = 0.034), and showed decreased memory in the Morris water maze test compared to mice on high-sucrose diet (p = 0.031). Mice on high-sucrose diet burrowed less goal-oriented, showed greater latency to first bout of immobility in the forced swim test when compared to control mice (p = 0.039) and high-fat fed mice (p = 0.013), and displayed less anxiety than mice on high-fat diet in the triple test (p = 0.009). Behavioral changes were accompanied by a significant change in GM composition of mice fed a high-fat diet, while no difference between diet groups was observed for sucrose preferences, LPS, cholesterol, HbA1c, BDNF and the cytokines IL-1α, IL-1β, IL-6, IL-10, IL-12(p70), IL-17 and TNF-α. A series of correlations was found between GM, behavior, BDNF and inflammatory mediators. In conclusion, the study shows that dietary fat and sucrose affect behavior, sometimes in opposite directions, and suggests a possible association between GM and behavior.
The RAVEN Toolbox and Its Use for Generating a Genome-scale Metabolic Model for Penicillium chrysogenum

We present the RAVEN (Reconstruction, Analysis and Visualization of Metabolic Networks) Toolbox: a software suite that allows for semi-automated reconstruction of genome-scale models. It makes use of published models and/or the KEGG database, coupled with extensive gap-filling and quality control features. The software suite also contains methods for visualizing simulation results and omics data, as well as a range of methods for performing simulations and analyzing the results. The software is a useful tool for system-wide data analysis in a metabolic context and for streamlined reconstruction of metabolic networks based on protein homology. The RAVEN Toolbox workflow was applied in order to reconstruct a genome-scale metabolic model for the important microbial cell factory Penicillium chrysogenum Wisconsin54-1255. The model was validated in a bibliomic study of in total 440 references, and it comprises 1471 unique biochemical reactions and 1006 ORFs. It was then used to study the roles of ATP and NADPH in the biosynthesis of penicillin, and to identify potential metabolic engineering targets for maximization of penicillin production.
Evidence on the Human Health Effects of Low-Level Methylmercury Exposure

Background: Methylmercury (MeHg) is a known neuro-toxicant. Emerging evidence indicates it may have adverse effects on the neuro-logic and other body systems at common low levels of exposure. Impacts of MeHg exposure could vary by individual susceptibility or be confounded by bene-ficial nutrients in fish containing MeHg. Despite its global relevance, synthesis of the available literature on low-level MeHg exposure has been limited. Objectives: We undertook a synthesis of the current knowledge on the human health effects of low-level MeHg exposure to provide a basis for future research efforts, risk assessment, and exposure remediation policies worldwide. Data sources and extraction: We reviewed the published literature for original human epidemio-logic research articles that reported a direct biomarker of mercury exposure. To focus on high-quality studies and those specifically on low mercury exposure, we excluded case series, as well as studies of populations with unusually high fish consumption (e.g., the Seychelles), marine mammal consumption (e.g., the Faroe Islands, circumpolar, and other indigenous populations), or consumption of highly contaminated fish (e.g., gold-mining regions in the Amazon). Data synthesis: Recent evidence raises the possibility of effects of low-level MeHg exposure on fetal growth among susceptible subgroups and on infant growth in the first 2 years of life. Low-level effects of MeHg on neuro-logic outcomes may differ by age, sex, and timing of exposure. No clear pattern has been observed for cardio-vascular disease (CVD) risk across populations or for specific CVD end points. For the few studies evaluating immunologic effects associated with MeHg, results have been inconsistent. Conclusions: Studies targeted at identifying potential mechanisms of low-level MeHg effects and characterizing individual susceptibility, sexual dimorphism, and non-linearity in dose response would help guide future prevention, policy, and regulatory efforts surrounding MeHg exposure.
Survival of red blood cells after transfusion: processes and consequences

The currently available data suggest that efforts toward improving the quality of red blood cell (RBC) blood bank products should concentrate on: (1) preventing the removal of a considerable fraction of the transfused RBCs that takes place within the first hours after transfusion; (2) minimizing the interaction of the transfused RBCs with the patient's immune system. These issues are important in reducing the number and extent of the damaging side effects of transfusions, such as generation of alloantibodies and autoantibodies and iron accumulation, especially in transfusion-dependent patients. Thus, it becomes important for blood bank research not only to assess the classical RBC parameters for quality control during storage, but even more so to identify the parameters that predict RBC survival, function and behavior in the patient after transfusion. These parameters are likely to result from elucidation of the mechanisms that underly physiological RBC aging in vivo, and that lead to the generation of senescent cell antigens and the accumulation of damaged molecules in vesicles. Also, study of RBC pathology-related mechanisms, such as encountered in various hemoglobinopathies and membranopathies, may help to elucidate the mechanisms underlying a storage-associated increase in susceptibility to physiological stress conditions. Recent data indicate that a combination of new approaches in vitro to mimick RBC behavior in vivo, the growing knowledge of the signaling networks that regulate RBC structure and function, and the rapidly expanding set of proteomic and metabolomic data, will be instrumental to identify the storage-associated processes that control RBC survival after transfusion.
A novel taxonomic marker that discriminates between morphologically complex actinomycetes

In the era when large whole genome bacterial datasets are generated routinely, rapid and accurate molecular systematics is becoming increasingly important. However, 16S ribosomal RNA sequencing does not always offer sufficient resolution to discriminate between closely related genera. The SsgA-like proteins are developmental regulatory proteins in sporulating actinomycetes, whereby SsgB actively recruits FtsZ during sporulation-specific cell division. Here, we present a novel method to classify actinomycetes, based on the extraordinary way the SsgA and SsgB proteins are conserved. The almost complete conservation of the SsgB amino acid (aa) sequence between members of the same genus and its high divergence between even closely related genera provides high-quality data for the classification of morphologically complex actinomycetes. Our analysis validates Kitasatospora as a sister genus to Streptomyces in the family Streptomycetaceae and suggests that Micromonospora, Salinispora and Verrucosispora may represent different clades of the same genus. It is also apparent that the aa sequence of SsgA is an accurate determinant for the ability of streptomycetes to produce submerged spores, dividing the phylogenetic tree of streptomycetes into liquid-culture sporulation and no liquid-culture sporulation branches. A new phylogenetic tree of industrially relevant actinomycetes is presented and compared with that based on 16S rRNA sequences.
Cortical Network Dynamics of Perceptual Decision-Making in the Human Brain

Goal-directed behavior requires the flexible transformation of sensory evidence about our environment into motor actions. Studies of perceptual decision-making have shown that this transformation is distributed across several widely separated brain regions. Yet, little is known about how decision-making emerges from the dynamic interactions among these regions. Here, we review a series of studies, in which we characterized the cortical network interactions underlying a perceptual decision process in the human brain. We used magnetoencephalography to measure the large-scale cortical population dynamics underlying each of the sub-processes involved in this decision: the encoding of sensory evidence and action plan, the mapping between the two, and the attentional selection of task-relevant evidence. We found that these sub-processes are mediated by neuronal oscillations within specific frequency ranges. Localized gamma-band oscillations in sensory and motor cortices reflect the encoding of the sensory evidence and motor plan. Large-scale oscillations across widespread cortical networks mediate the integrative processes connecting these local networks: Gamma- and beta-band oscillations across frontal, parietal, and sensory cortices serve the selection of relevant sensory evidence and its flexible mapping onto action plans. In sum, our results suggest that perceptual decisions are mediated by oscillatory interactions within overlapping local and large-scale cortical networks.
Characterization of miR-888 expression and regulation in endometrial cancer

Endometrial cancer is the fourth most common cancer in women and the most common gynecological malignancy. While patient outcome has improved for the majority of cancers, the outlook for endometrial cancer has steadily decreased. In order to address this problem, we must better understand the different mechanisms involved in endometrial cancer development and progression. To this end, we quantified expression of 667 miRNAs in four endometrioid adenocarcinoma and four serous adenocarcinoma using Taqman Low Density Arrays (TLDAs). miR-888 was one of the most highly overexpressed miRNAs in both endometrial cancer subtypes. Analysis of miR-888 expression across multiple cancer types using the The Cancer Genome Atlas database revealed that miR-888 was selectively expressed in endometrial cancer, with a significant association to invasive and high grade tumors. In addition, miR-888 was most predominantly expressed in endometrial carcinosarcoma, a rare but deadly form of endometrial cancer. Therefore, we conclude that miR-888 expression marks an aggressive endometrial tumor phenotype. One of the top predicted targets of miR-888 by TargetScan is the progesterone receptor (PR). PR is a potent tumor suppressor of the endometrium whose expression is often lost in advanced endometrial cancers. We quantified PR mRNA expression in a panel of endometrial tumors and found a statistically significant, negative correlation between miR-888 and PR mRNA expression. Furthermore, overexpression of miR-888 in endometrial cancer cell lines was capable of decreasing PR at the protein level. To determine if miR-888 directly targets PR, we cloned each of the four miR-888 binding sites downstream of Renilla luciferase into the psiCHECK2 reporter vector. miR-888
Differential Susceptibility and Response of Primary Human Myeloid BDCA1+ Dendritic Cells to Infection with Different Enteroviruses

Coxsackie B viruses (CVBs) and echoviruses (EVs) form the Human Enterovirus-B (HEV-B) species within the family Picornaviridae. HEV-B infections are widespread and generally cause mild disease; however, severe infections occur and HEV-B are associated with various chronic diseases such as cardiomyopathy and type 1 diabetes. Dendritic cells (DCs) are the professional antigen-presenting cells of our immune system and initiate and control immune responses to invading pathogens, yet also maintain tolerance to self-antigens. We previously reported that EVs, but not CVBs, can productively infect in vitro generated monocyte-derived DCs. The interactions between HEV-B and human myeloid DCs (mDCs) freshly isolated from blood, however, remain unknown. Here, we studied the susceptibility and responses of BDCA1(+) mDC to HEV-B species and found that these mDC are susceptible to EV, but not CVB infection. Productive EV7 infection resulted in massive, rapid cell death without DC activation. Contrary, EV1 infection, which resulted in lower virus input at the same MOI, resulted in DC activation as observed by production of type I interferon-stimulated genes (ISGs), upregulation of co-stimulatory and co-inhibitory molecules (CD80, CD86, PDL1) and production of IL-6 and TNF-α, with a relative moderate decrease in cell viability. EV1-induced ISG expression depended on virus replication. CVB infection did not affect DC viability and resulted in poor induction of ISGs and CD80 induction in part of the donors. These data show for the first time the interaction between HEV-B species and BDCA1(+) mDCs isolated freshly from blood. Our data indicate that different HEV-B species can influence DC homeostasis in various ways, possibly contributing to HEV-B associated pathology.
Exploring the Impact of Target Eccentricity and Task Difficulty on Covert Visual Spatial Attention and Its Implications for Brain Computer Interfacing

Objective Covert visual spatial attention is a relatively new task used in brain computer interfaces (BCIs) and little is known about the characteristics which may affect performance in BCI tasks. We investigated whether eccentricity and task difficulty affect alpha lateralization and BCI performance. Approach We conducted a magnetoencephalography study with 14 participants who performed a covert orientation discrimination task at an easy or difficult stimulus contrast at either a near (3.5°) or far (7°) eccentricity. Task difficulty was manipulated block wise and subjects were aware of the difficulty level of each block. Main Results Grand average analyses revealed a significantly larger hemispheric lateralization of posterior alpha power in the difficult condition than in the easy condition, while surprisingly no difference was found for eccentricity. The difference between task difficulty levels was significant in the interval between 1.85 s and 2.25 s after cue onset and originated from a stronger decrease in the contralateral hemisphere. No significant effect of eccentricity was found. Additionally, single-trial classification analysis revealed a higher classification rate in the difficult (65.9%) than in the easy task condition (61.1%). No effect of eccentricity was found in classification rate. Significance Our results indicate that manipulating the difficulty of a task gives rise to variations in alpha lateralization and that using a more difficult task improves covert visual spatial attention BCI performance. The variations in the alpha lateralization could be caused by different factors such as an increased mental effort or a higher visual attentional demand. Further research is necessary to discriminate between them. We did not discover any effect of eccentricity in contrast to results of previous research.
Gntb-A, a Novel Sh2d1a-Associated Surface Molecule Contributing to the Inability of Natural Killer Cells to Kill Epstein-Barr Virus–Infected B Cells in X-Linked Lymphoproliferative Disease

In humans, natural killer (NK) cell function is regulated by a series of receptors and coreceptors with either triggering or inhibitory activity. Here we describe a novel 60-kD glycoprotein, termed NTB-A, that is expressed by all human NK, T, and B lymphocytes. Monoclonal antibody (mAb)-mediated cross-linking of NTB-A results in the induction of NK-mediated cytotoxicity. Similar to 2B4 (CD244) functioning as a coreceptor in the NK cell activation, NTB-A also triggers cytolytic activity only in NK cells expressing high surface densities of natural cytotoxicity receptors. This suggests that also NTB-A may function as a coreceptor in the process of NK cell activation. Molecular cloning of the cDNA coding for NTB-A molecule revealed a novel member of the immunoglobulin superfamily belonging to the CD2 subfamily. NTB-A is characterized, in its extracellular portion, by a distal V-type and a proximal C2-type domain and by a cytoplasmic portion containing three tyrosine-based motifs. NTB-A undergoes tyrosine phosphorylation and associates with the Src homology 2 domain–containing protein (SH2D1A) as well as with SH2 domain–containing phosphatases (SHPs). Importantly, analysis of NK cells derived from patients with X-linked lymphoproliferative disease (XLP) showed that the lack of SH2D1A protein profoundly affects the function not only of 2B4 but also of NTB-A. Thus, in XLP-NK cells, NTB-A mediates inhibitory rather than activating signals. These inhibitory signals are induced by the interaction of NTB-A with still undefined ligands expressed on Epstein-Barr virus (EBV)-infected target cells. Moreover, mAb-mediated masking of NTB-A can partially revert this inhibitory effect while a maximal recovery of target cell lysis can be obtained when both 2B4 and NTB-A are simultaneously masked. Thus, the altered function of NTB-A appears to play an important role in the inability of XLP-NK cells to kill EBV-infected target cells.
The Collaborative Image of The City: Mapping the Inequality of Urban Perception

A traveler visiting Rio, Manila or Caracas does not need a report to learn that these cities are unequal; she can see it directly from the taxicab window. This is because in most cities inequality is conspicuous, but also, because cities express different forms of inequality that are evident to casual observers. Cities are highly heterogeneous and often unequal with respect to the income of their residents, but also with respect to the cleanliness of their neighborhoods, the beauty of their architecture, and the liveliness of their streets, among many other evaluative dimensions. Until now, however, our ability to understand the effect of a city's built environment on social and economic outcomes has been limited by the lack of quantitative data on urban perception. Here, we build on the intuition that inequality is partly conspicuous to create quantitative measure of a city's contrasts. Using thousands of geo-tagged images, we measure the perception of safety, class and uniqueness; in the cities of Boston and New York in the United States, and Linz and Salzburg in Austria, finding that the range of perceptions elicited by the images of New York and Boston is larger than the range of perceptions elicited by images from Linz and Salzburg. We interpret this as evidence that the cityscapes of Boston and New York are more contrasting, or unequal, than those of Linz and Salzburg. Finally, we validate our measures by exploring the connection between them and homicides, finding a significant correlation between the perceptions of safety and class and the number of homicides in a NYC zip code, after controlling for the effects of income, population, area and age. Our results show that online images can be used to create reproducible quantitative measures of urban perception and characterize the inequality of different cities.
Redundancy and modularity in membrane-associated dissimilatory nitrate reduction in Bacillus

The genomes of two phenotypically denitrifying type strains of the genus Bacillus were sequenced and the pathways for dissimilatory nitrate reduction were reconstructed. Results suggest that denitrification proceeds in the periplasmic space and in an analogous fashion as in Gram-negative organisms, yet with the participation of proteins that tend to be membrane-bound or membrane-associated. A considerable degree of functional redundancy was observed with marked differences between B. azotoformans LMG 9581T and B. bataviensis LMG 21833T. In addition to the already characterized menaquinol/cyt c-dependent nitric oxide reductase (Suharti et al., 2001, 2004) of which the encoding genes could be identified now, evidence for another novel nitric oxide reductase (NOR) was found. Also, our analyses confirm earlier findings on branched electron transfer with both menaquinol and cytochrome c as reductants. Quite unexpectedly, both bacilli have the disposal of two parallel pathways for nitrite reduction enabling a life style as a denitrifier and as an ammonifying bacterium.