Miracle-dz/UniFAR-FTUs huggingface dataset:
The HtrA/DegP family protease MamE is a bifunctional protein with roles in magnetosome protein localization and magnetite biomineralization

Magnetotactic bacteria contain nanometre‐sized, membrane‐bound organelles, called magnetosomes, which are tasked with the biomineralization of small crystals of the iron oxide magnetite allowing the organism to use geomagnetic field lines for navigation. A key player in this process is the HtrA/DegP family protease MamE. In its absence, Magnetospirillum magneticum str AMB‐1 is able to form magnetosome membranes but not magnetite crystals, a defect previously linked to the mislocalization of magnetosome proteins. In this work we use a directed genetic approach to find that MamE, and another predicted magnetosome‐associated protease, MamO, likely function as proteases in vivo. However, as opposed to the complete loss of mamE where no biomineralization is observed, the protease‐deficient variant of this protein still supports the initiation and formation of small, 20 nm‐sized crystals of magnetite, too small to hold a permanent magnetic dipole moment. This analysis also reveals that MamE is a bifunctional protein with a protease‐independent role in magnetosome protein localization and a protease‐dependent role in maturation of small magnetite crystals. Together, these results imply the existence of a previously unrecognized ‘checkpoint’ in biomineralization where MamE moderates the completion of magnetite formation and thus committal to magneto‐aerotaxis as the organism's dominant mode of navigating the environment.
Ulcerative Typhlocolitis Associated With Helicobacter mastomyrinus in Telomerase-Deficient Mice

Telomerase deficiency induces early senescence and defects in proliferating cell populations, but in mice it has not been associated with inflammatory bowel disease. Genetically engineered mice lacking either telomerase reverse transcriptase (TERT) or telomerase RNA were examined for chronic diarrhea and wasting. Affected mice had pasty stools, thickened nondistensible colon walls, and contracted ceca. Histologically, the cecal mucosa was largely replaced by inflammatory infiltrate consisting of plasma cells, neutrophils, lymphocytes, and macrophages with marked widespread fibrosis and ulceration. Remaining epithelium was disorganized and hyperplastic, with multifocal dysplasia. Colonic mucosa was markedly hyperplastic with similar inflammation and epithelial dysplasia. Multifocal adenomatous hyperplasia, but no inflammation, was present in the small intestine. Microaerophilic spiral bacteria with 16S rRNA gene sequences identical to Helicobacter mastomyrinus were isolated from the colon and cecum. Severe granulomatous typhlocolitis without epithelial dysplasia developed in germ-free recombination-activating gene (RAG) knockout (KO) recipients of CD4+ T cells and inoculated with cecal contents from affected TERT KO mice and in specific pathogen-free recipient RAG KO mice and interleukin-10 KO mice inoculated with H mastomyrinus. Typhlocolitis in mice given H mastomyrinus was more severe than in mice given Helicobacter hepaticus. Telomerase-deficient mice are susceptible to helicobacter-associated typhlocolitis. H mastomyrinus causes severe disease in susceptible mouse strains.
Cytogenetic and Molecular Characterization of Heterochromatin Gene Models in Drosophila melanogaster

In the past decade, genome-sequencing projects have yielded a great amount of information on DNA sequences in several organisms. The release of the Drosophila melanogaster heterochromatin sequence by the Drosophila Heterochromatin Genome Project (DHGP) has greatly facilitated studies of mapping, molecular organization, and function of genes located in pericentromeric heterochromatin. Surprisingly, genome annotation has predicted at least 450 heterochromatic gene models, a figure 10-fold above that defined by genetic analysis. To gain further insight into the locations and functions of D. melanogaster heterochromatic genes and genome organization, we have FISH mapped 41 gene models relative to the stained bands of mitotic chromosomes and the proximal divisions of polytene chromosomes. These genes are contained in eight large scaffolds, which together account for ∼1.4 Mb of heterochromatic DNA sequence. Moreover, developmental Northern analysis showed that the expression of 15 heterochromatic gene models tested is similar to that of the vital heterochromatic gene Nipped-A, in that it is not limited to specific stages, but is present throughout all development, despite its location in a supposedly “silent” region of the genome. This result is consistent with the idea that genes resident in heterochromatin can encode essential functions.
A novel SIX3 mutation segregates with holoprosencephaly in a large family

Holoprosencephaly is the most common structural malformation of the forebrain in humans and has a complex etiology including chromosomal aberrations, single gene mutations and environmental components. Here we present the pertinent clinical findings among members of an unusually large kindred ascertained over 15 years ago following the evaluation and subsequent genetic work‐up of a female infant with congenital anomalies. A genome‐wide scan and linkage analysis showed only suggestive evidence of linkage to markers on chromosome 2 among the most likely of several pedigree interpretations. We now report that a novel missense mutation in the SIX3 holoprosencephaly gene is the likely cause in this family. Molecular genetic analysis and/or clinical characterization now show that at least 15 members of this family are presumed SIX3 mutation gene carriers, with clinical manifestations ranging from phenotypically normal adults (non‐penetrance) to alobar holoprosencephaly incompatible with postnatal life. This particular family represents a seminal example of the variable manifestations of gene mutations in holoprosencephaly and difficulties encountered in their elucidation. Published 2009 Wiley‐Liss, Inc.
Immunoglobulin E Antibodies to Rocuronium: A New Diagnostic Tool

Background: Diagnosis of allergy from neuromuscular blocking agents is not always straightforward. The objectives of the current study were to investigate the value of quantification of immunoglobulin E (IgE) by ImmunoCAP (Phadia AB, Uppsala, Sweden) in the diagnosis of rocuronium allergy and to study whether IgE inhibition tests can predict clinical cross-reactivity between neuromuscular blocking agents. Methods: Twenty-five rocuronium-allergic patients and 30 control individuals exposed to rocuronium during uneventful anesthesia were included. Thirty-two sera (total IgE > 1,500 kU/l) were analyzed for potential interference of elevated total IgE titers. Results were compared with quantification of IgE for suxamethonium, morphine, and pholcodine. Cross-reactivity between drugs was assessed by IgE inhibition and skin tests. Results: Sensitivity of IgE for rocuronium, suxamethonium, morphine, and pholcodine was 68, 60, 88, and 86%, respectively. Specificity was 100% for suxamethonium, morphine, and pholcodine IgE and 93% for rocuronium IgE. ROC analysis between patients and control individuals changed the threshold to 0.13 kUa/l for rocuronium, 0.11 kUa/l for suxamethonium, 0.36 kUa/l for morphine, and 0.43 kUa/l for pholcodine. Corresponding sensitivity was 92, 72, 88, and 86%, respectively. Specificity was unaltered. Interference of elevated total IgE with quantification of IgE was demonstrated by the analysis in sera with a total IgE greater than 1,500 kU/l. IgE inhibition did not predict clinical relevant cross-reactivity. Conclusions: The rocuronium ImmunoCAP constitutes a reliable technique to diagnose rocuronium allergy, provided an assay-specific decision threshold is applied. IgE assays based on compounds bearing ammonium epitopes are confirmed to represent reliable tools to diagnose rocuronium allergy. High total IgE titers were observed to affect specificity of the assays.
Impact of Diabetes on Homocysteine Levels and Its Relationship with Coronary Artery Disease: A Single-Centre Cohort Study

Background/Aims: Coronary artery disease (CAD) is a major cause of mortality worldwide. Hyperhomocysteinemia has been identified as a risk factor for CAD due to increased thrombogenicity, oxidative stress status and endothelial dysfunction. Few data have been provided on the impact of diabetes on homocysteine and its relationship with the prevalence and extent of CAD in this high-risk subset of patients and therefore, this is the aim of this study. Methods: Our population is represented by a consecutive cohort of patients undergoing coronary angiography at Azienda Ospedaliera-Universitaria, ‘Maggiore della Carità', Novara, Italy from March 2007 to October 2012. Results: Diabetes was observed in a total of 1,125 out of 3,534 patients. Diabetes was associated with more advanced age, hypercholesterolemia, arterial hypertension, renal failure, previous myocardial infarction, coronary revascularization (p < 0.001, respectively) and smoking (p = 0.001). Patients with diabetes were more frequently on angiotensin-converting-enzyme inhibitors, angiotensin receptor blockers, beta-blockers, calcium-antagonists, diuretics, statins (p < 0.001, respectively), and acetylsalicylic acid (p = 0.004). Patients with diabetes displayed higher creatinine and triglycerides (p < 0.001), but lower total and high-density lipoprotein-cholesterol (p < 0.001) and haemoglobin (p < 0.001). Diabetes was associated with a significantly higher prevalence and extent of CAD and more complex lesions at angiography, including calcified lesion, total occlusions, in-stent restenosis. No significant difference was found in total homocysteine (tHcy) levels between diabetic and non-diabetic patients (p = 0.2). No difference in the percentage of patients with tHcy above the third tertile (≥18.2 nmol/ml) was observed between patients with or without diabetes (32.8 vs. 35%, p = 0.18; adjusted OR 0.88, 95% CI 0.73-1.05, p = 0.14). Among patients with diabetes, no significant association was found between tHcy, CAD (82.4 vs. 83.6 vs. 78.6%, p = 0.19) or severe CAD (33.2 vs. 33.1 vs. 36.9%, p = 0.18). Same results were observed after correction for baseline differences (adjusted OR 0.78, 95% CI 0.61-1.02, p = 0.11) for CAD and severe CAD (adjusted OR 0.92, 95% CI 0.76-1.13, p = 0.46). Conclusions: In our study, diabetes was not associated with higher tHcy levels. Furthermore, elevated tHcy is not a risk factor for CAD among patients with diabetes.
Violation of the ISNT rule in Nonglaucomatous pediatric optic disc cupping.

PURPOSE To determine whether nonglaucomatous optic disc cupping in children violates the ISNT rule (which states that for normal optic discs the neuroretinal rim width is greatest in the order inferior >or= superior >or= nasal >or= temporal). METHODS Digital ocular fundus photographs from a random cohort of children with large optic disc cups of nonglaucomatous origin were analyzed in masked fashion by using computer graphic software. The diameter and perimeter of each optic disc and optic cup and the width of the neuroretinal rim were drawn and measured. Measurements were compared to a random cohort of normal pediatric optic discs. RESULTS The ISNT rule was intact in 9 (16%) of 55 eyes of nonpremature children with nonglaucomatous cupping, in 6 (21%) of 28 eyes of children with a history of prematurity and nonglaucomatous cupping, and in 35 (73%) of 48 eyes with normal discs. CONCLUSIONS Violation of the ISNT rule occurs with greater frequency in the pediatric population with large optic disc cups of nonglaucomatous origin, compared with the pediatric population with normal optic discs. In discs with small cups, neuroretinal rim width conforms to the overall oval shape of the disc, which is usually greatest in vertical dimension, whereas discs with large cups possess greater variability of relative neuroretinal rim width around the disc, greater relative vertical cup/disc ratio versus horizontal cup/disc ratio, and lower predictability of the ISNT rule.
Renal Expression and Function of Oat1 and Oat3 in Rats with Vascular Calcification

Background/Aims: Calcium overload in vascular smooth muscle is a highly pathogenic event, which progresses with advancing age. Old patients are polymedicated, and several pharmacotherapeutic agents circulate in the plasma as organic anions. The organic anion transporters 1 and 3 (Oat1 and Oat3) are present in renal basolateral membranes, which transport organic anions of pharmacological and physiological interest. This study was designed to evaluate the renal expression and function of Oat1 and Oat3 in rats with vascular calcification. Methods: Vascular calcification was induced by administration of a single dose of vitamin D3 (300,000 UI/ kg b.w., i.m.) to male Wistar rats 10 days before the experiments. Oat1 and Oat3 expression was assessed by immunoblotting, immunohistochemistry and reverse-transcriptase polymerase chain reaction. The renal clearance of p-aminohippurate (PAH, a prototypical organic anion, substrate of Oat1 and Oat3) was measured by conventional clearance techniques. Results: Oat1 and Oat3 protein levels showed an increase in plasma membranes of renal proximal tubules of treated animals, where both transporters are functional. This could explain the increase observed in the renal clearance of PAH in treated rats. Conclusions: These results suggest the relevance of considering the existence of vascular calcification, which is common in ageing, when organic anion drugs are prescribed.
Designing Educational Materials for a Blind Arduino Workshop

There is an overall shortage of accessible educational material available for blind and low vision learners. This shortage is especially pronounced in the domain of electronics, where the materials are historically visually-rendered and complex. To address this, we took a qualitative approach to designing and evaluating tactile graphics and textual descriptions when building circuits. To gain an understanding of their efficacy, we provided a circuit description [3], component diagrams (Figure 4), and a tactile schematic [9] as educational materials in a Blind Arduino workshop with eight participants and interviewed these participants about their experience. Our research revealed the complexities of designing these materials: our tactile component diagrams were usable and helpful, whereas our tactile schematics and circuit descriptions presented learning barriers in a microcontroller workshop. We provide recommendations for future research to design accessible materials to teach electronics.
Development of a Dual-Index Sequencing Strategy and Curation Pipeline for Analyzing Amplicon Sequence Data on the MiSeq Illumina Sequencing Platform

ABSTRACT Rapid advances in sequencing technology have changed the experimental landscape of microbial ecology. In the last 10 years, the field has moved from sequencing hundreds of 16S rRNA gene fragments per study using clone libraries to the sequencing of millions of fragments per study using next-generation sequencing technologies from 454 and Illumina. As these technologies advance, it is critical to assess the strengths, weaknesses, and overall suitability of these platforms for the interrogation of microbial communities. Here, we present an improved method for sequencing variable regions within the 16S rRNA gene using Illumina's MiSeq platform, which is currently capable of producing paired 250-nucleotide reads. We evaluated three overlapping regions of the 16S rRNA gene that vary in length (i.e., V34, V4, and V45) by resequencing a mock community and natural samples from human feces, mouse feces, and soil. By titrating the concentration of 16S rRNA gene amplicons applied to the flow cell and using a quality score-based approach to correct discrepancies between reads used to construct contigs, we were able to reduce error rates by as much as two orders of magnitude. Finally, we reprocessed samples from a previous study to demonstrate that large numbers of samples could be multiplexed and sequenced in parallel with shotgun metagenomes. These analyses demonstrate that our approach can provide data that are at least as good as that generated by the 454 platform while providing considerably higher sequencing coverage for a fraction of the cost.
Race, Gender, and Information Technology Use: The New Digital Divide

This research examined race and gender differences in the intensity and nature of IT use and whether IT use predicted academic performance. A sample of 515 children (172 African Americans and 343 Caucasian Americans), average age 12 years old, completed surveys as part of their participation in the Children and Technology Project. Findings indicated race and gender differences in the intensity of IT use; African American males were the least intense users of computers and the Internet, and African American females were the most intense users of the Internet. Males, regardless of race, were the most intense videogame players, and females, regardless of race, were the most intense cell phone users. IT use predicted children's academic performance. Length of time using computers and the Internet was a positive predictor of academic performance, whereas amount of time spent playing videogames was a negative predictor. Implications of the findings for bringing IT to African American males and bringing African American males to IT are discussed.
A feasibility and pilot randomized controlled trial of the “Timing it Right Stroke Family Support Program”

Objective: Examine feasibility of conducting a randomized controlled trial of the Timing it Right Stroke Family Support Program (TIRSFSP) and collect pilot data. Design: Multi-site mixed method randomized controlled trial. Setting: Acute and community care in three Canadian cities. Subjects: Caregivers were family members or friends providing care to individuals who experienced their first stroke. Intervention: The TIRSFSP offered in two formats, self-directed by the caregiver or stroke support person-directed over time, were compared to standard care. Main measures: Caregivers completed baseline and follow-up measures 1, 3 and 6 months post-stroke including Centre for Epidemiological Studies Depression, Positive Affect, Social Support, and Mastery Scales. We completed in-depth qualitative interviews with caregivers and maintained intervention records describing support provided to each caregiver. Results: Thirty-one caregivers received standard care (n=10), self-directed (n=10), or stroke support person-directed (n=11) interventions. We retained 77% of the sample through 6-months. Key areas of support derived from intervention records (n=11) related to caregiver wellbeing, caregiving strategies, patient wellbeing, community re-integration, and service delivery. Compared to standard care, caregivers receiving the stroke support person-directed intervention reported improvements in perceived support (estimate 3.1, P=.04) and mastery (estimate .35, P=.06). Qualitative caregiver interviews (n=19) reflected the complex interaction between caregiver needs, preferences and available options when reporting on level of satisfaction. Conclusions: Preliminary findings suggest the research design is feasible, caregivers’ needs are complex, and the support intervention may enhance caregivers’ perceived support and mastery. The intervention will be tested further in a large scale trial.
The effect of hemolysis on plasma oxidation and nitration in patients with sickle cell disease

Abstract This study aimed to determine the effect of haemolysis on plasma oxidation and nitration in sickle cell disease (SCD) patients. Blood was collected from haemoglobin (Hb)A volunteers and homozygous HbSS patients who had not received blood transfusions in the last 3 months. Haemolysis was characterised by low levels of haemoglobin and haptoglobin and high levels of reticulocyte, mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), plasma cell-free haemoglobin, bilirubin, total lactate dehydrogenase (LDH) and dominance of LDH-1 isoenzyme. Plasma 8-isoprostane, protein carbonyl and nitrotyrosine levels were measured to evaluate oxidised lipids, oxidised and nitrated proteins, respectively. Plasma nitrite–nitrate levels were also determined to assess nitric oxide (NO) production in both SCD patients and controls. Markers of haemolysis were significantly evident in SCD patients compared to controls. Plasma 8-isoprostane, protein carbonyl and nitrotyrosine levels were markedly elevated in SCD patients compared to controls. Linear regression analysis revealed a significant inverse correlation between haemoglobin and reticulocyte counts and a significant positive correlation of plasma cell-free haemoglobin with protein carbonyl and nitrotyrosine levels. The obtained data shows that increased haemolysis in SCD increases plasma protein oxidation and nitration.
The Recovery Knowledge Inventory for Measurement of Nursing Student Views on Recovery-oriented Mental Health Services

Recovery-oriented services are a goal for policy and practice in the Australian mental health service system. Evidence-based reform requires an instrument to measure knowledge of recovery concepts. The Recovery Knowledge Inventory (RKI) was designed for this purpose, however, its suitability and validity for student health professionals has not been evaluated. The purpose of the current article is to report the psychometric features of the RKI for measuring nursing students’ views on recovery. The RKI, a self-report measure, consists of four scales: (I) Roles and Responsibilities, (II) Non-Linearity of the Recovery Process, (III) Roles of Self-Definition and Peers, and (IV) Expectations Regarding Recovery. Confirmatory and exploratory factor analyses of the baseline data (n = 167) were applied to assess validity and reliability. Exploratory factor analyses generally replicated the item structure suggested by the three main scales, however more stringent analyses (confirmatory factor analysis) did not provide strong support for convergent validity. A refined RKI with 16 items had internal reliabilities of α = . 75 for Roles and Responsibilities, α = . 49 for Roles of Self-Definition and Peers, and α = . 72, for Recovery as Non-Linear Process. If the RKI is to be applied to nursing student populations, the conceptual underpinning of the instrument needs to be reworked, and new items should be generated to evaluate and improve scale validity and reliability.
HER2 gene copy number and breast cancer‐specific survival

HER2 amplification occurs in 10–15% of breast cancers. It is associated with poor breast cancer‐specific survival (BCSS) and is an important prognostic and predictive marker. While it has been accepted that the HER2:chromosome 17 centromere (CEP17) ratio determines HER2 status, recent guidelines acknowledge the significance of HER2 copy number alone. The aims of this study were to assess BCSS according to mean HER2 copy number and HER2 status expressed as a HER2:CEP17 ratio with and without increased CEP17 copy number.