Miracle-dz/UniFAR-FTUs huggingface dataset:
Variable habitat conditions drive species covariation in the human microbiota

Two species with similar resource requirements respond in a characteristic way to variations in their habitat—their abundances rise and fall in concert. We use this idea to learn how bacterial populations in the microbiota respond to habitat conditions that vary from person-to-person across the human population. Our mathematical framework shows that habitat fluctuations are sufficient for explaining intra-bodysite correlations in relative species abundances from the Human Microbiome Project. We explicitly show that the relative abundances of closely related species are positively correlated and can be predicted from taxonomic relationships. We identify a small set of functional pathways related to metabolism and maintenance of the cell wall that form the basis of a common resource sharing niche space of the human microbiota.
Questions regarding the optimal use of bevacizumab in glioblastoma: a moving target.

The saga of bevacizumab in brain tumors has been ongoing for many years. Despite encouraging initial reports targeting the vascular endothelial growth factor (VEGF) pathway by a neutralizing monoclonal antibody (bevacizumab) or a receptor tyrosine kinase inhibitor (cediranib), the few subsequent controlled studies were largely disappointing. Opportunities for adequate clinical investigation with bevacizumab were missed or delayed for many years. Nevertheless, these agents undoubtedly have a clinically meaningful benefit in selected patients. However, we lackclinical or biomarkers allowing identification of specific patients that benefit from these therapies. The highly variable clinical practice reflects the contradictory reports and the paucity of prospective and controlled trials. The absence of adequate data also prevented regulatory approval in many countries, especially in the European Union, thus preventing access to bevacizumab for patients. Numerous basic questions remain unresolved years after the drug has entered routine clinical use. 1 Two reports analyzing retrospectively large institutional databases on management of recurrent glioblastoma appear in this issue of Neuro-Oncology, 2,3 and two pivotal prospective randomized trials on the use of bevacizumab in newly diagnosed patients were recently reported. 4,5 Thus, it is timely to briefly review some of the available data and discuss their limitations.
Surface tension, adhesive wettability, and bondability of artificially weathered CCA-treated southern pine

The surface tension, adhesive wettability, and bondability of chromated copper arsenate (CCA)-treated southern pine, exposed to artificial accelerated weathering, was evaluated to examine the recycling potential of weathered CCA-treated wood in composite materials. Accelerated weathering was carried out in a QUV-Accelerated Weathering Tester. Surface tension of the CCA-treated and untreated artificially weathered southern pine wood was determined by means of static contact angle analysis using the Lifshitz-van der Waals/acid-base approach. Adhesive wettability was assessed by static contact angle analysis using resorcinol-formaldehyde (RF) adhesive. The surface tension of both the CCA-treated and untreated southern pine increased as a result of exposure to artificial accelerated weathering. There was no statistically significant difference in RF wettability or wood/RF interfacial adhesive shear strength as the result of the accelerated cyclic weathering examined in this study. The percent wood failure data were not normally distributed, and only showed minor decreases as the result of the accelerated weathering. The percent wood failure was greater for the CCA-treated wood than the untreated wood. From the adhesive wetting and shear strength results, it appears that the accelerated-weathering conditions examined in this study do not severely influence the bondability of CCA-treated southern pine.
Attentional Biases and Vulnerability to Depression

This study was designed to examine selective processing of emotional information in depression. It focuses on possible attentional biases in depression, and whether such biases constitute a cognitive vulnerability factor to suffer from the disorder or, on the contrary, they reflect a feature associated exclusively with the clinical level of depression. 81 participants were included in the study: 15 with a diagnosis of Major Depression; 17 were diagnosed as Dysthymia; 11 participants scored over 18 in the Beck Depression Inventory (Beck, Rush, Shaw, & Emery, 1979); 15 participants, in whom a sad mood state was induced by an experimental mood induction (Velten technique + music, or biographical recall + music); and 23 participants as a normal-control group. All participants were presented with the emotional Stroop task. The data indicated that attentional bias was only present in the group of patients with Major Depression, so it does not seem to be a cognitive vulnerability factor for this disorder. En este trabajo se examina el procesamiento selectivo de la información emocional en depresión. Los objetivos se centran en comprobar, en primer lugar, si existen o no sesgos atencionales en la depresión y, en segundo lugar, si estos sesgos constituyen un factor de vulnerabilidad cognitiva a padecer el trastorno o si, por el contrario, reflejan una característica asociada exclusivamente al nivel clínico de depresión. Los participantes fueron 15 pacientes con diagnóstico de Depresión Mayor, 17 pacientes con diagnóstico de Distimia, 11 personas con una puntuación superior a 18 en el Inventario de Depresión de Beck (Beck, Rush, Shaw y Emery, 1979), 15 personas a las que se indujo un estado de ánimo triste (técnica Velten con música, o recuerdo autobiográfico con música) y 23 personas “controles”. Todos los sujetos cumplimentaron la tarea Stroop emocional. Los datos indicaron que el sesgo atencional sólo se manifestaba en el subgrupo de Depresión Mayor, por lo que no parece constituir un factor de vulnerabilidad cognitiva para la depresión.
The intracellular immune receptor Rx1 regulates the DNA-binding activity of a Golden2-like transcription factor

Plant nucleotide-binding leucine–rich repeat (NLR) proteins enable the immune system to recognize and respond to pathogen attack. An early consequence of immune activation is transcriptional reprogramming, and some NLRs have been shown to act in the nucleus and interact with transcription factors. The Rx1 NLR protein of potato is further able to bind and distort double-stranded DNA. However, Rx1 host targets that support a role for Rx1 in transcriptional reprogramming at DNA are unknown. Here, we report a functional interaction between Rx1 and NbGlk1, a Golden2-like transcription factor. Rx1 binds to NbGlk1 in vitro and in planta. NbGlk1 binds to known Golden2-like consensus DNA sequences. Rx1 reduces the binding affinity of NbGlk1 for DNA in vitro. NbGlk1 activates cellular responses to potato virus X, whereas Rx1 associates with NbGlk1 and prevents its assembly on DNA in planta unless activated by PVX. This study provides new mechanistic insight into how an NLR can coordinate an immune signaling response at DNA following pathogen perceptions.
Urinary Bisphenol A (BPA) Concentrations among Workers in Industries that Manufacture and Use BPA in the USA

Background Bisphenol A (BPA) toxicity and exposure risk to humans has been the subject of considerable scientific debate; however, published occupational exposure data for BPA are limited. Methods In 2013-2014, 77 workers at six US companies making BPA, BPA-based resins, or BPA-filled wax provided seven urine samples over two consecutive work days (151 worker-days, 525 samples). Participant information included industry, job, tasks, personal protective equipment used, hygiene behaviors, and canned food/beverage consumption. Total (free plus conjugated) BPA, quantified in urine by mass spectrometry, was detected in all samples. Results The geometric mean (GM) creatinine-adjusted total BPA (total BPACR) concentration was 88.0 µg g-1 (range 0.78-18900 µg g-1), ~70 times higher than in US adults in 2013-2014 (1.27 µg g-1). GM total BPACR increased during Day 1 (26.6-127 µg g-1), decreased by pre-shift Day 2 (84.4 µg g-1) then increased during Day 2 to 178 µg g-1. By industry, baseline and post-baseline total BPACR was highest in BPA-filled wax manufacturing/reclaim (GM = 111 µg g-1) and lowest in phenolic resin manufacturing (GM = 6.56 µg g-1). By job, total BPACR was highest at baseline in maintenance workers (GM = 157 µg g-1) and post-baseline in those working with molten BPA-filled wax (GM = 441 µg g-1). Workers in the job of flaking a BPA-based resin had the lowest concentrations at baseline (GM = 4.81 µg g-1) and post-baseline (GM = 23.2 µg g-1). In multiple regression models, at baseline, industry significantly predicted increased total BPACR (P = 0.0248); post-baseline, handling BPA containers (P = 0.0035), taking ≥3 process/bulk samples with BPA (P = 0.0002) and wearing a Tyvek® coverall (P = 0.0042) significantly predicted increased total BPACR (after adjusting for total BPACR at baseline, time point, and body mass index). Conclusion Several work-related factors, including industry, job, and certain tasks performed, were associated with increased urinary total BPACR concentrations in this group of manufacturing workers. The potential for BPA-related health effects among these workers is unknown.
Right ventricular pressure response to exercise in adults with isolated ventricular septal defect closed in early childhood

Abstract We previously demonstrated an abnormally high right ventricular systolic pressure response to exercise in 50% of adolescents operated on for isolated ventricular septal defect. The present study investigated the prevalence of abnormal right ventricular systolic pressure response in 20 adult (age 30–45 years) patients who underwent surgery for early ventricular septal defect closure and its association with impaired ventricular function, pulmonary function, or exercise capacity. The patients underwent cardiopulmonary tests, including exercise stress echocardiography. Five of 19 patients (26%) presented an abnormal right ventricular systolic pressure response to exercise ⩾ 52 mmHg. Right ventricular systolic function was mixed, with normal tricuspid annular plane systolic excursion and fractional area change, but abnormal tricuspid annular systolic motion velocity (median 6.7 cm/second) and isovolumetric acceleration (median 0.8 m/second2). Left ventricular systolic and diastolic function was normal at rest as measured by the peak systolic velocity of the lateral wall and isovolumic acceleration, early diastolic velocity, and ratio of early diastolic flow to tissue velocity, except for ejection fraction (median 53%). The myocardial performance index was abnormal for both the left and right ventricle. Peak oxygen uptake was normal (mean z score −0.4, 95% CI −2.8–0.3). There was no association between an abnormal right ventricular systolic pressure response during exercise and right or left ventricular function, pulmonary function, or exercise capacity. Abnormal right ventricular pressure response is not more frequent in adult patients compared with adolescents. This does not support the theory of progressive pulmonary vascular disease following closure of left-to-right shunts.
An Intracellular Peptidyl-Prolyl cis/trans Isomerase Is Required for Folding and Activity of the Staphylococcus aureus Secreted Virulence Factor Nuclease

ABSTRACT Staphylococcus aureus is an important human pathogen that relies on a large repertoire of secreted and cell wall-associated proteins for pathogenesis. Consequently, the ability of the organism to cause disease is absolutely dependent on its ability to synthesize and successfully secrete these proteins. In this study, we investigate the role of peptidyl-prolyl cis/trans isomerases (PPIases) on the activity of the S. aureus secreted virulence factor nuclease (Nuc). We identify a staphylococcal cyclophilin-type PPIase (PpiB) that is required for optimal activity of Nuc. Disruption of ppiB results in decreased nuclease activity in culture supernatants; however, the levels of Nuc protein are not altered, suggesting that the decrease in activity results from misfolding of Nuc in the absence of PpiB. We go on to demonstrate that PpiB exhibits PPIase activity in vitro, is localized to the bacterial cytosol, and directly interacts with Nuc in vitro to accelerate the rate of Nuc refolding. Finally, we demonstrate an additional role for PpiB in S. aureus hemolysis and demonstrate that the S. aureus parvulin-type PPIase PrsA also plays a role in the activity of secreted virulence factors. The deletion of prsA leads to a decrease in secreted protease and phospholipase activity, similar to that observed in other Gram-positive pathogens. Together, these results demonstrate, for the first time to our knowledge, that PPIases play an important role in the secretion of virulence factors in S. aureus. IMPORTANCE Staphylococcus aureus is a highly dangerous bacterial pathogen capable of causing a variety of infections throughout the human body. The ability of S. aureus to cause disease is largely due to an extensive repertoire of secreted and cell wall-associated proteins, including adhesins, toxins, exoenzymes, and superantigens. These virulence factors, once produced, are typically transported across the cell membrane by the secretory (Sec) system in a denatured state. Consequently, once outside the cell, they must refold into their active form. This step often requires the assistance of bacterial folding proteins, such as PPIases. In this work, we investigate the role of PPIases in S. aureus and uncover a cyclophilin-type enzyme that assists in the folding/refolding of staphylococcal nuclease.
The Molecular Chaperone HSP90 Promotes Notch Signaling in the Germline of Caenorhabditis elegans

In a genetic screen to identify genes that promote GLP-1/Notch signaling in Caenorhabditis elegans germline stem cells, we found a single mutation, om40, defining a gene called ego-3. ego-3(om40) causes several defects in the soma and the germline, including paralysis during larval development, sterility, delayed proliferation of germline stem cells, and ectopic germline stem cell proliferation. Whole genome sequencing identified om40 as an allele of hsp-90, previously known as daf-21, which encodes the C. elegans ortholog of the cytosolic form of HSP90. This protein is a molecular chaperone with a central position in the protein homeostasis network, which is responsible for proper folding, structural maintenance, and degradation of proteins. In addition to its essential role in cellular function, HSP90 plays an important role in stem cell maintenance and renewal. Complementation analysis using a deletion allele of hsp-90 confirmed that ego-3 is the same gene. hsp-90(om40) is an I→N conservative missense mutation of a highly conserved residue in the middle domain of HSP-90. RNA interference-mediated knockdown of hsp-90 expression partially phenocopied hsp-90(om40), confirming the loss-of-function nature of hsp-90(om40). Furthermore, reduced HSP-90 activity enhanced the effect of reduced function of both the GLP-1 receptor and the downstream LAG-1 transcription factor. Taken together, our results provide the first experimental evidence of an essential role for HSP90 in Notch signaling in development.
Reduced expression of the Nodal co-receptor Oep causes loss of mesendodermal competence in zebrafish

ABSTRACT The activation of specific gene expression programs depends on the presence of the appropriate signals and the competence of cells to respond to those signals. Although it is well established that cellular competence is regulated in space and time, the molecular mechanisms underlying the loss of competence remain largely unknown. Here, we determine the time window during which zebrafish prospective ectoderm loses its ability to respond to Nodal signals, and show that this coincides with a decrease in the levels of the Nodal co-receptor One-eyed pinhead (Oep). Bypassing Oep using a photoactivatable receptor, or an Oep-independent ligand, allows activation of Nodal target genes for an extended period of time. These results suggest that the reduced expression of Oep causes the loss of responsiveness to Nodal signals in the prospective ectoderm. Indeed, extending the presence of Oep prolongs the window of competence to respond to Nodal signals. Our findings suggest a simple mechanism in which the decreasing level of one component of the Nodal signaling pathway regulates the loss of mesendodermal competence in the prospective ectoderm. Summary: Zebrafish prospective ectoderm cells lose responsiveness to Nodal between shield stage and 75% epiboly owing to embryo-wide degradation of maternally provided oep mRNA, at least partially mediated by an abundance of destabilizing codons.
Apical closure device for full-percutaneous transapical valve implantation: stress-test in an animal model†.

OBJECTIVES Transapical valve implantation is traditionally performed through a left antero-lateral mini-thoracotomy. A self-expandable apical closure device has recently been developed for full-percutaneous transapical valve implantation. We performed haemodynamics stress-tests on an animal model to evaluate the sealing properties. METHODS Under general anaesthesia 5 pigs (mean weight: 67 ± 6 Kg) received full heparinization (100 IU/Kg; activated clotting time >250 s and, through inferior mini-sternotomies, 21-Fr introducer sheaths for transapical aortic valve implantation (outer diameter: 25-Fr) were placed over-the-wire in the apexes. Delivery-catheters carrying folded occluders (SAFEX TM final design) were inserted in the introducer sheaths and plugs were then deployed under fluoroscopic guidance. Phase 1: after protamine injection, apical bleeding was monitored for 1 h with standard haemodynamics condition. Phase 2: we induced systemic hypertension with adrenaline infusion to test the sealing properties under stress. Animals were sacrificed after Phase 2 and hearts were removed and inspected. RESULTS Five plugs were successfully introduced and deployed in 5 pig hearts. Plugs provided good apical sealing in each animal and a mean of 7 ± 4 ml of blood lost per animal was collected during Phase 1: haemodynamics remained stable and no plug dislodgement was detected (mean blood pressure: 52 ± 9 mmHg). During Phase 2, mean systolic and diastolic peak levels reached 268 ± 24 mmHg and 175 ± 17 mmHg, respectively, without plug dislodgment or bleeding. Post-mortem inspection showed good plug deployment and fixation without myocardial damage. CONCLUSIONS The new apical occluder seals large-sized apical access sites in animal models also during induced systemic hypertension. This pilot study is a further step towards full-percutaneous transapical valve procedures in the clinical setting.
Review of Family-centered Interventions to Enhance the Health Outcomes of Children With Type 1 Diabetes

Purpose The purpose of this systematic literature review was to examine family-centered interventions that enhance the health outcomes of children with type 1 diabetes. The review summarizes the interventions and outcome measures that consisted of A1Cs, family relationships, and family conflict. Methods Multiple electronic databases were searched from their start date to September 2008 for reports of studies that examined family-centered interventions among children with type 1 diabetes. Results Nine publications, all randomized controlled trials, were located that investigated the effectiveness of family-centered interventions. Findings indicated that family-centered interventions significantly improved A1Cs, enhanced family dynamics, and decreased family conflict. Conclusions Family-centered interventions targeting children diagnosed with type 1 diabetes appear to be effective in enhancing health outcomes. These interventions focused on traditional 2-parent families, and many did not report race or ethnicity. Given the increasing number of single-parent households and divorced parents, a need exists to explore and develop family-centered interventions that target nontraditional family structures as well as addressing cultural differences.
Analysis of Recurrent Stenosis After Carotid Endarterectomy Featuring Primary Plaque Calcification

BACKGROUND The relationship between calcification in primary plaque and restenosis after carotid endarterectomy (CEA) has been seldom investigated. OBJECTIVE To clarify the relationship between characteristics of calcified carotid plaque and recurrent stenosis after CEA, as well as the disease's natural course. METHODS Ninety-four plaques out of 107 consecutive CEAs were retrospectively analyzed with regard to calcification, employing calcium score as well as shape, location, and other characteristics of original plaques. CEA was performed in a standard fashion with primary closure using an internal shunt. Restenosis was assessed by direct measurement of stenosis mainly using multidetector row computed tomography (CT) angiography. RESULTS Univariate analysis revealed that calcium score and calcification circularity score were significantly lower in more than moderate restenosis (≥50%; 422.1 ± 551.6 vs 84.2 ± 92.0, P < .001; 1.8 ± 1.3 vs 1.1 ± 0.3, P < .001, respectively). Receiver operating characteristic analysis demonstrated a calcium score of 80, which was the optimal cutoff value for restenosis over 50% (sensitivity 0.70, specificity 0.68, pseudopositive ratio 0.32, area under curve 0.71, Youden's index 0.38). Low calcium score (OR 2.88, CI 1.06-7.79, P = .04) and low calcification circularity (OR 5.72, CI 1.42-23.1, P = .01) were independent predictors for more than moderate recurrent carotid stenosis 1 year postoperatively. Cases with decreasing tendency of restenosis showed higher calcium scores than those with increasing or unchanged tendency (217.2 ± 245.3 vs 164.5 ± 155.5, P < .001). Lower calcium score cases showed lower restenosis-free survival. CONCLUSION Carotid plaque calcification may be inversely associated with recurrent stenosis 1 year after CEA or later. Preoperative CT assessment for less calcification will benefit restenosis patients by early prediction and close follow-up.
Persistent Hepatitis C Virus Infection In Vitro: Coevolution of Virus andHost

ABSTRACT The virological and cellular consequences of persistent hepatitis C virus (HCV) infection have been elusive due to the absence of the requisite experimental systems. Here, we report the establishment and the characteristics of persistent in vitro infection of human hepatoma-derived cells by a recently described HCV genotype 2a infectious molecular clone. Persistent in vitro infection was characterized by the selection of viral variants that displayed accelerated expansion kinetics, higher peak titers, and increased buoyant densities. Sequencing analysis revealed the selection of a single adaptive mutation in the HCV E2 envelope protein that was largely responsible for the variant phenotype. In parallel, as the virus became more aggressive, cells that were resistant to infection emerged, displaying escape mechanisms operative at the level of viral entry, HCV RNA replication, or both. Collectively, these results reveal the existence of coevolutionary events during persistent HCV infection that favor survival of both virus and host.