Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterisation of a modified rotating disk reactor for the cultivation of Staphylococcus epidermidis biofilm

23 Aims : The purpose of this study was to develop a system that would allow biofilms to be 24 cultivated under strictly defined conditions in terms of dissolved oxygen, fluid shear and 25 to assess if the method was suitable for detection of respiratory activity stratification in 26 biofilm samples. 27 Methods : The system is a modified version a commercially available laboratory biofilm 28 reactor and incorporates a number of features such as provision of defined levels of 29 dissolved oxygen, constant average shear, enhanced gas-liquid mass transfer, aseptic 30 operation and the ability to remove biofilm for ex-situ analysis during or after continuous 31 cultivation. 32 Conclusions : The system was shown to be effective for the characterisation of the effects 33 of dissolved oxygen on a pure culture of Staphylococcus epidermidis . The versatility of 34 the system offers the potential for cultivating pure culture biofilm in defined, controlled 35 conditions and facilitates a range of analyses that can be performed ex situ. 36 Significant and impact of study : The ability to provide strict regulation of environmental 37 conditions and enhanced transfer of oxygen to the biofilm during cultivation are 38 important, firstly because oxygen is known to regulate biofilm development in several 39 microorganisms and secondly because many conventional biofilm cultivation systems 40 may not provide adequate oxygen supply to the biofilm. 41
Congenital disorders of glycosylation: The Saudi experience

We retrospectively reviewed Saudi patients who had a congenital disorder of glycosylation (CDG). Twenty‐seven Saudi patients (14 males, 13 females) from 13 unrelated families were identified. Based on molecular studies, the 27 CDG patients were classified into different subtypes: ALG9‐CDG (8 patients, 29.5%), ALG3‐CDG (7 patients, 26%), COG6‐CDG (7 patients, 26%), MGAT2‐CDG (3 patients, 11%), SLC35A2‐CDG (1 patient), and PMM2‐CDG (1 patient). All the patients had homozygous gene mutations. The combined carrier frequency of CDG for the encountered founder mutations in the Saudi population is 11.5 per 10,000, which translates to a minimum disease burden of 14 patients per 1,000,000. Our study provides comprehensive epidemiologic information and prevalence figures for each of these CDG in a large cohort of congenital disorder of glycosylation patients.
Structure, function and regulation of the DNA‐binding protein Dps and its role in acid and oxidative stress resistance in Escherichia coli: a review

Dps, the DNA‐binding protein from starved cells, is capable of providing protection to cells during exposure to severe environmental assaults; including oxidative stress and nutritional deprivation. The structure and function of Dps have been the subject of numerous studies and have been examined in several bacteria that possess Dps or a structural/functional homologue of the protein. Additionally, the involvement of Dps in stress resistance has been researched extensively as well. The ability of Dps to provide multifaceted protection is based on three intrinsic properties of the protein: DNA binding, iron sequestration, and its ferroxidase activity. These properties also make Dps extremely important in iron and hydrogen peroxide detoxification and acid resistance as well. Regulation of Dps expression in E. coli is complex and partially dependent on the physiological state of the cell. Furthermore, it is proposed that Dps itself plays a role in gene regulation during starvation, ultimately making the cell more resistant to cytotoxic assaults by controlling the expression of genes necessary for (or deleterious to) stress resistance. The current review focuses on the aforementioned properties of Dps in E. coli, its prototypic organism. The consequences of elucidating the protective mechanisms of this protein are far‐reaching, as Dps homologues have been identified in over 1000 distantly related bacteria and Archaea. Moreover, the prevalence of Dps and Dps‐like proteins in bacteria suggests that protection involving DNA and iron sequestration is crucial and widespread in prokaryotes.
Cross-sectional Study of Glutamate in the Anterior Cingulate and Hippocampus in Schizophrenia.

BACKGROUND There has been growing support for dysfunctions of the excitatory glutamatergic system and its implications for the psychophysiology of schizophrenia. However, previous studies reported mixed results regarding glutamate concentrations in schizophrenia with varying deviations across brain regions. METHODS We used an optimized proton magnetic resonance spectroscopy procedure to measure absolute glutamate concentrations in the left hippocampal region and the anterior cingulate cortex (ACC) in 29 medicated patients with schizophrenia and in 29 control participants without mental disorder. RESULTS The glutamate concentrations were significantly lower in the ACC but higher in the hippocampus of patients compared to controls. ACC and hippocampal glutamate concentrations correlated positively in patients but not in controls. ACC glutamate was weakly associated with Clinical Global Impression score and duration of illness in patients. CONCLUSION Glutamate concentrations in schizophrenia deviate from controls and show associations with disease severity. A higher concentration of hippocampal glutamate in schizophrenia compared to controls is shown. The association between ACC and hippocampus glutamate concentrations in patients with schizophrenia suggests an abnormal coupling of excitatory systems compared to controls as predicted by previous glutamate models of schizophrenia.
Beyond Down syndrome phenotype: Paternally derived isodicentric chromosome 21 with partial monosomy 21q22.3

Inverted isodicentric chromosome 21 is a rare form of chromosomal rearrangement that may result in trisomy 21; sometimes this rearrangement may also lead to segmental monosomy of the terminal long arm of chromosome 21. In this report, we describe the prenatal diagnosis and neonatal follow‐up of a child with a paternally derived, de novo isodicentric chromosome 21 and a concurrent ∼1.2 Mb deletion of the 21q22.3 region [46,XX,idic(21)(q22.3)]. This child presented with unusual phenotype of Down syndrome and additional defects including esophageal atresia and tethered cord syndrome. The resulting phenotype in this infant might be a coalescence of the partial trisomy and monosomy 21, as well as homozygosity for idic (21). The utilization of chromosomal microarray in this case enabled accurate characterization of a rare chromosome abnormality, potentially contributes to future phenotype–genotype correlation and produced evidence for a molecular mechanism underlying this rearrangement.
Molecular Plasticity Regulates Oligomerization and Cytotoxicity of the Multipeptide-length Amyloid-β Peptide Pool*

Background: Aβ peptide, implicated in Alzheimer disease, occurs in various lengths. Results: Non-abundant Aβ1–38 and Aβ1–43 affect oligomerization, cytotoxicity, and aggregation of Aβ1–40 and Aβ1–42. Conclusion: Small amounts of Aβ lengths other than Aβ1–40 or Aβ1–42 significantly alter the behavior of the total Aβ pool. Significance: Drug strategies targeting APP processing to affect Aβ1–38 levels need careful consideration. Current therapeutic approaches under development for Alzheimer disease, including γ-secretase modulating therapy, aim at increasing the production of Aβ1–38 and Aβ1–40 at the cost of longer Aβ peptides. Here, we consider the aggregation of Aβ1–38 and Aβ1–43 in addition to Aβ1–40 and Aβ1–42, in particular their behavior in mixtures representing the complex in vivo Aβ pool. We demonstrate that Aβ1–38 and Aβ1–43 aggregate similar to Aβ1–40 and Aβ1–42, respectively, but display a variation in the kinetics of assembly and toxicity due to differences in short timescale conformational plasticity. In biologically relevant mixtures of Aβ, Aβ1–38 and Aβ1–43 significantly affect the behaviors of Aβ1–40 and Aβ1–42. The short timescale conformational flexibility of Aβ1–38 is suggested to be responsible for enhancing toxicity of Aβ1–40 while exerting a cyto-protective effect on Aβ1–42. Our results indicate that the complex in vivo Aβ peptide array and variations thereof is critical in Alzheimer disease, which can influence the selection of current and new therapeutic strategies.
Characterization of Conformation-dependent Prion Protein Epitopes*

Background: Despite structural reorganization during disease, conformational prion protein epitopes remain undefined. Results: We identify specific amino acids constituting novel conformational monoclonal antibody epitopes. Conclusion: Immunoreactivities of globular domain epitopes depend on maintenance of regional tertiary structure. Significance: Our studies address how denatured conformational epitopes remain functional, provide insights into normal and disease-related prion protein, and expand epitope tagging options. Whereas prion replication involves structural rearrangement of cellular prion protein (PrPC), the existence of conformational epitopes remains speculative and controversial, and PrP transformation is monitored by immunoblot detection of PrP(27–30), a protease-resistant counterpart of the pathogenic scrapie form (PrPSc) of PrP. We now describe the involvement of specific amino acids in conformational determinants of novel monoclonal antibodies (mAbs) raised against randomly chimeric PrP. Epitope recognition of two mAbs depended on polymorphisms controlling disease susceptibility. Detection by one, referred to as PRC5, required alanine and asparagine at discontinuous mouse PrP residues 132 and 158, which acquire proximity when residues 126–218 form a structured globular domain. The discontinuous epitope of glycosylation-dependent mAb PRC7 also mapped within this domain at residues 154 and 185. In accordance with their conformational dependence, tertiary structure perturbations compromised recognition by PRC5, PRC7, as well as previously characterized mAbs whose epitopes also reside in the globular domain, whereas conformation-independent epitopes proximal or distal to this region were refractory to such destabilizing treatments. Our studies also address the paradox of how conformational epitopes remain functional following denaturing treatments and indicate that cellular PrP and PrP(27–30) both renature to a common structure that reconstitutes the globular domain.
Interactions with WNK (With No Lysine) Family Members Regulate Oxidative Stress Response 1 and Ion Co-transporter Activity*

Background: WNK1 binds OSR1 via RFXV motifs and is on intracellular puncta. Results: C-terminal WNK1 segments bind OSR1 and localize to puncta like endogenous WNK1; changes in tonicity decrease WNK1 mobility. Conclusion: Complex interplay of protein-protein interactions, changes in tonicity, and localization control the WNK-OSR1 cascade. Significance: WNK function varies because of family member and splice form expression, protein interactions, and localization. Two of the four WNK (with no lysine (K)) protein kinases are associated with a heritable form of ion imbalance culminating in hypertension. WNK1 affects ion transport in part through activation of the closely related Ste20 family protein kinases oxidative stress-responsive 1 (OSR1) and STE20/SPS1-related proline-, alanine-rich kinase (SPAK). Once activated by WNK1, OSR1 and SPAK phosphorylate and stimulate the sodium, potassium, two chloride co-transporters, NKCC1 and NKCC2, and also affect other related ion co-transporters. We find that WNK1 and OSR1 co-localize on cytoplasmic puncta in HeLa and other cell types. We show that the C-terminal region of WNK1 including a coiled coil is sufficient to localize the fragment in a manner similar to the full-length protein, but some other fragments lacking this region are mislocalized. Photobleaching experiments indicate that both hypertonic and hypotonic conditions reduce the mobility of GFP-WNK1 in cells. The four WNK family members can phosphorylate the activation loop of OSR1 to increase its activity with similar kinetic constants. C-terminal fragments of WNK1 that contain three RFXV interaction motifs can bind OSR1, block activation of OSR1 by sorbitol, and prevent the OSR1-induced enhancement of ion co-transporter activity in cells, further supporting the conclusion that association with WNK1 is required for OSR1 activation and function at least in some contexts. C-terminal WNK1 fragments can be phosphorylated by OSR1, suggesting that OSR1 catalyzes feedback phosphorylation of WNK1.
Duchas vaginales y otros riesgos de vaginosis bacteriana

Bacterial vaginosis (BV) is an infection characterized by a change in the micro flora of the vagina. BV has been associated with adverse pregnancy outcomes and increased risk of acquiring sexually transmitted infections (STI). Objective. To identifiy the association of douching and other behavioral risk factors in relation to BV. Material and methods. This cross-sectional study was carried out among 1252 women attending in 3 public hospitals and one specialized institute in Lima, Peru in 1997. A structured questionnaire was used to collect information on socio-demographic and lifestyle characteristics of women. BV was diagnosed by the Nugent’s score. Logistic regression procedures were employed to estimate adjusted odds ratios (OR) and 95% confidence intervals (95% CI). Results. Mean age of participants was 25.1 ± 4.7 and 23.4% had more than 11 years of formal education. The prevalence of BV was 20.1% and significantly associated with a number of behavioral risk factors. Women who practice douching (OR: 2.28; 95% CI: 1.0-5.0), having two or more sexual partners (OR: 2.0; 95% CI: 1.2-3.5) and who started sexual intercourse at a younger age (OR:1.4; 95% CI: 1.0-1.9) have more risk to get BV. Conclusion. Vaginal douching is a risk factor associated with BV among Peruvian women. Programs aimed at women’s health must address the adverse health outcomes associated with douching.
Access to the Nucleus and Functional Association with c-Myc Is Required for the Full Oncogenic Potential of ΔEGFR/EGFRvIII*

Background: Expression of ΔEGFR, a mutant of EGFR in gliomas, correlates with poor prognosis. Results: Access to the nucleus is required for full oncogenicity of ΔEGFR, and nuclear ΔEGFR regulates transcription of target genes via c-Myc. Conclusion: Functional association of nuclear ΔEGFR with c-Myc is necessary for ΔEGFR-induced oncogenicity. Significance: These data show a novel activity of ΔEGFR and offer new opportunities for therapeutic intervention. ΔEGFR is a potent glioblastoma oncogene which has been studied primarily as a plasma membrane kinase. Using intracranial xenograft studies in mice, we show that blocking ΔEGFR access to the nucleus attenuates its tumorigenicity and, conversely, that promoting nuclear accumulation enhances this, providing the first in vivo evidence that the nuclear actions of ΔEGFR contribute strongly to its oncogenic function. Nuclear actions of ΔEGFR include regulation of gene expression by participation in chromatin-bound complexes, and genome-wide mapping of these sequences by chromatin immunoprecipitation and massively parallel sequencing identified 2294 peaks. Bioinformatic analysis showed enrichment of the E-box motif in the dataset, and c-Myc and ΔEGFR were corecruited to the promoters of and transcriptionally activated a subset of nuclear ΔEGFR chromatin targets. Knockdown of c-Myc decreased the expression of these targets and diminished ΔEGFR-stimulated anchorage-independent colony formation. We conclude that transcriptional regulation of target genes by association with gene regulatory chromatin in cooperation with c-Myc by nuclear ΔEGFR makes a unique contribution to its oncogenicity and propose that this venue provides new targets for therapeutic intervention.
The role of the brain‐derived neurotrophic factor (BDNF) val66met variant in the phenotypic expression of obsessive‐compulsive disorder (OCD)

Evidence suggests that the Val66Met variant of the brain‐derived neurotrophic factor (BDNF) gene may play a role in the etiology of Obsessive‐Compulsive Disorder (OCD). In this study, the role of the BDNF Val66Met variant in the etiology and the phenotypic expression of OCD is investigated. Associations between the BDNF Val66Met variant and OCD, obsessive‐compulsive symptom dimensions, Yale‐Brown Obsessive Compulsive Scale (YBOCS) severity scores, age of onset and family history of obsessive‐compulsive symptoms were assessed. The BDNF Val66Met variant was genotyped in 419 patients with sub‐/clinical OCD and 650 controls. No differences in allele or genotype frequency were observed between cases and controls. In females with OCD, the Met66Met genotype was associated with later age of onset and a trend for a negative family history, whereas the Val66Val genotype was associated with a trend for lower YBOCS severity scores. Item‐level factor analysis revealed six factors: 1) Contamination/cleaning; 2) Aggressive obsessions/checking; 3) Symmetry obsessions, counting, ordering and repeating; 4) Sexual/religious obsessions; 5) Hoarding and 6) Somatic obsessions/checking. A trend was found for a positive association between Factor 4 (Sexual/religious obsessions) and the BDNF Val66Val genotype. The results suggest that BDNF function may be implicated in the mediation of OCD. We found that for the BDNF Met66Met genotype may be associated with a milder phenotype in females and a possible role for the BDNF Val66Val genotype and the BDNF Val66 allele in the sexual/religious obsessions. © 2009 Wiley‐Liss, Inc.
School Opportunity Hoarding? Racial Segregation and Access to High Growth Schools

Abstract Persistent school segregation may allow advantaged groups to hoard educational opportunities and consign minority students to lower-quality educational experiences. Although minority students are concentrated in low-achieving schools, relatively little previous research directly links segregation to measures of school quality based on student achievement growth, which more plausibly reflect learning opportunities. Using a dataset of public elementary schools in California, this study provides the first analysis detailing the distribution of a growth-based measure of school quality using standard inequality indices, allowing disparities to be decomposed across geographic and organizational scales. We find mixed support for the school opportunity hoarding hypothesis. We find small White and Asian advantages in access to high-growth schools, but most of the inequality in exposure to school growth is within racial groups. Growth-based disparities both between and within groups tend to be on a more local scale than disparities in absolute achievement levels, focusing attention on within-district policies to mitigate school-based inequalities in opportunities to learn.
Functional Equilibrium of the KcsA Structure Revealed by NMR*

Background: The selectivity filter of KcsA undergoes an equilibrium between permeable and impermeable conformations under acidic conditions. Results: Truncation of the intracellular region or addition of 2,2,2-trifluoroethanol modulates the equilibrium. Conclusion: Membrane environments affect dynamics of KcsA. Significance: This is the first evidence that a structural equilibrium in the membrane is related to the inactivation of a potassium channel. KcsA is a tetrameric K+ channel that is activated by acidic pH. Under open conditions of the helix bundle crossing, the selectivity filter undergoes an equilibrium between permeable and impermeable conformations. Here we report that the population of the permeable conformation (pperm) positively correlates with the tetrameric stability and that the population in reconstituted high density lipoprotein, where KcsA is surrounded by the lipid bilayer, is lower than that in detergent micelles, indicating that dynamic properties of KcsA are different in these two media. Perturbation of the membrane environment by the addition of 1–3% 2,2,2-trifluoroethanol increases pperm and the open probability, revealed by NMR and single-channel recording analyses. These results demonstrate that KcsA inactivation is determined not only by the protein itself but also by the surrounding membrane environments.
Association of Restless Legs Syndrome With Incident Parkinson's Disease

Study Objectives: The association between restless legs syndrome (RLS) and Parkinson's disease (PD) has been extensively studied with inconclusive results; therefore, we prospectively examined the associations of the presence of RLS with development of incident PD. Methods: From a nationally representative prospective cohort of almost 3.5 million US veterans (age: 60 ± 14 years, 93% male, median follow‐up time of 7.8 years [interquartile range: 6.4‐8.4 years]), we created a propensity‐matched cohort of 100882 PD‐free patients and examined the association between prevalent RLS and incident PD. This association was also assessed in the entire cohort. Associations were examined using Cox models. Results: There were 68 incident PD events (0.13%, incidence rate 1.87 [1.48‐2.37]/10000 patient‐years) in the RLS‐negative group, and 185 incident PD events (0.37%, incidence rate 4.72 [4.09‐5.45]/10000 patient‐years) in the RLS‐positive group in the propensity‐matched cohort. Prevalent RLS was associated with more than twofold higher risk of incident PD (hazard ratio [HR]: 2.57, 95% confidence interval [CI]: 1.95‐3.39) compared to RLS‐negative patients. Qualitatively similar results were found when we examined the entire 3.5 million cohort: Prevalent RLS was associated with more than twofold higher risk of incident PD (multivariable adjusted HR: 2.81, 95%CI: 2.41‐3.27). Conclusion: RLS and PD share common risk factors. In this large cohort of US veterans, we found that prevalent RLS is associated with higher risk of incident PD during 8 years of follow‐up, suggesting that RLS could be an early clinical feature of incident PD.
The Benefit of Directed Forgetting Persists After a Daytime Nap: The Role of Spindles and Rapid Eye Movement Sleep in the Consolidation of Relevant Memories

Study Objectives We aimed to investigate the effect of directed forgetting instruction on memory retention after a 2-hour delay involving a daytime nap or an equivalent amount of time spent awake. We examined the associations between sleep-specific oscillations and the retention of relevant and irrelevant study materials. Methods We applied a list-method directed forgetting paradigm manipulating the perceived relevance of previously encoded lists of words. Participants were randomly assigned to either a nap or an awake group, and to a remember or a forget subgroup. The remember and the forget subgroups were both instructed to study two consecutive lists of words, although, the forget subgroup was manipulated to forget the first list and memorize only the second one. Participants were 112 healthy individuals (44 men; Mage = 21.4 years, SD = 2.4). Results A significant directed forgetting effect emerged after a 2-hour delay both in the awake and sleep conditions; however, the effect was more pronounced within the sleep group. The benefit of directed forgetting, that is, relatively enhanced recall of relevant words in the forget group, was evidenced only in those participants that reached rapid eye movement (REM) phase. Non-rapid eye movement (NREM) sigma power was correlated with memory performance for the relevant (second) list, and sleep spindle amplitude was associated with the retention of both lists. These associations, however, were detected only within the forget subgroup. REM duration correlated with recall performance for the relevant (second) list within the forget subgroup, and with recall performance for the first list within the remember subgroup. Conclusions A directed forgetting effect persists after a 2-hour delay spent awake or asleep. Spindle-related activity and subsequent REM sleep might selectively facilitate the processing of memories that are considered to be relevant for the future.