Miracle-dz/UniFAR-FTUs huggingface dataset:
TRANSLATIONAL IMPACT OF DROSOPHILA The calcineurin inhibitor Sarah ( Nebula ) exacerbates A β 42 phenotypes in a Drosophila model of Alzheimer ’ s disease

Expression of the Down syndrome critical region 1 (DSCR1) protein, an inhibitor of the Ca-dependent phosphatase calcineurin, is elevated in the brains of individuals with Down syndrome (DS) or Alzheimer’s disease (AD). Although increased levels of DSCR1 were often observed to be deleterious to neuronal health, its beneficial effects against AD neuropathology have also been reported, and the roles of DSCR1 on the pathogenesis of AD remain controversial. Here, we investigated the role of sarah (sra; also known as nebula), a Drosophila DSCR1 ortholog, in amyloid-β42 (Aβ42)-induced neurological phenotypes in Drosophila. We detected sra expression in the mushroom bodies of the fly brain, which are a center for learning and memory in flies. Moreover, similar to humans with AD, Aβ42-expressing flies showed increased Sra levels in the brain, demonstrating that the expression pattern of DSCR1 with regard to AD pathogenesis is conserved in Drosophila. Interestingly, overexpression of sra using the UAS-GAL4 system exacerbated the rough-eye phenotype, decreased survival rates and increased neuronal cell death in Aβ42-expressing flies, without modulating Aβ42 expression. Moreover, neuronal overexpression of sra in combination with Aβ42 dramatically reduced both locomotor activity and the adult lifespan of flies, whereas flies with overexpression of sra alone showed normal climbing ability, albeit with a slightly reduced lifespan. Similarly, treatment with chemical inhibitors of calcineurin, such as FK506 and cyclosporin A, or knockdown of calcineurin expression by RNA interference (RNAi), exacerbated the Aβ42-induced rough-eye phenotype. Furthermore, sra-overexpressing flies displayed significantly decreased mitochondrial DNA and ATP levels, as well as increased susceptibility to oxidative stress compared to that of control flies. Taken together, our results demonstrating that sra overexpression augments Aβ42 cytotoxicity in Drosophila suggest that DSCR1 upregulation or calcineurin downregulation in the brain might exacerbate Aβ42-associated neuropathogenesis in AD
Novel technologies uncover novel ‘anti’-microbial peptides in Hydra shaping the species-specific microbiome

The freshwater polyp Hydra uses an elaborate innate immune machinery to maintain its specific microbiome. Major components of this toolkit are conserved Toll-like receptor (TLR)-mediated immune pathways and species-specific antimicrobial peptides (AMPs). Our study harnesses advanced technologies, such as high-throughput sequencing and machine learning, to uncover a high complexity of the Hydra's AMPs repertoire. Functional analysis reveals that these AMPs are specific against diverse members of the Hydra microbiome and expressed in a spatially controlled pattern. Notably, in the outer epithelial layer, AMPs are produced mainly in the neurons. The neuron-derived AMPs are secreted directly into the glycocalyx, the habitat for symbiotic bacteria, and display high selectivity and spatial restriction of expression. In the endodermal layer, in contrast, endodermal epithelial cells produce an abundance of different AMPs including members of the arminin and hydramacin families, while gland cells secrete kazal-type protease inhibitors. Since the endodermal layer lines the gastric cavity devoid of symbiotic bacteria, we assume that endodermally secreted AMPs protect the gastric cavity from intruding pathogens. In conclusion, Hydra employs a complex set of AMPs expressed in distinct tissue layers and cell types to combat pathogens and to maintain a stable spatially organized microbiome. This article is part of the theme issue ‘Sculpting the microbiome: how host factors determine and respond to microbial colonization’.
Biochemical and immunocytochemical characterization and distribution of phosphorylated and nonphosphorylated subunits of neurofilaments in squid giant axon and stellate ganglion

Monoclonal antibodies to squid neurofilament (aNFP) and intermediate filament (aIFA) proteins were used as probes for the biochemical and immunocytochemical analyses of neurofilament structure and distribution in the squid giant axon and stellate ganglion. On Western blots the aNFP antibody stained exclusively the 220 kDa and high-molecular-weight (HMW) components of neurofilaments in the giant axon, whereas the aIFA antibody primarily labeled the 60 kDa protein in the giant axon and the 60 and 65 kDa proteins in the stellate ganglion. Dephosphorylation of axoplasmic proteins by alkaline phosphatase resulted in a decrease in the molecular weights of both the 220 kDa and HMW neurofilament proteins and a concomitant loss of reactivity with the aNFP antibody on Western blots. This indicated that the aNFP antibody is specific for a phosphorylated epitope in the neurofilament. Increased dephosphorylation of the 220 kDa protein led to an enhanced immunostaining of the resultant 190 kDa polypeptide by the aIFA antibody, suggesting that the phosphorylated epitope may mask the conserved epitope recognized by aIFA. Light and electron microscopic immunocytochemical studies show intense labeling by the aNFP antibody in the giant axon. In contrast, the aIFA antibody labeled the glial cells around the giant axon intensely, while labeling of the giant axon itself was considerably less than that with the aNFP antibody. Since the 60 kDa protein in axoplasm is intensely stained by the aIFA antibody on Western blots, the relatively low amounts of labeling seen on semithin and thin sections of the giant axon by this antibody may be due to the masking of the 60 kDa protein by in situ fixed axoplasmic proteins. However, the aIFA antibody intensely labeled glial cells within the stellate ganglion and “islands” of filaments and nuclear membranes within ganglion cells. No reactivity for either antibody was seen in synapses. The aNFP antibody specifically labeled “beadlike” portions and cross-bridges on the axonal neurofilaments, suggesting that these components consist of the 220 kDa and HMW proteins. In contrast, the aIFA antibody labeled relatively smooth filaments in ganglion and glial cells. These data suggest that the 65 kDa protein represents the squid glial filament protein and that the 60 kDa protein found in axoplasm represents the low-molecular-weight subunit in the axonal neurofilament. The latter appears to be formed and/or organized in “islands” of filaments within ganglion cells. (ABSTRACT TRUNCATED AT 400 WORDS)
MITO Measurements of the Sunyaev-Zeldovich Effect in the Coma Cluster of Galaxies

We have measured the Sunyaev-Zeldovich (SZ) effect toward the Coma Cluster (A1656) with the Millimetre and Infrared Testagrigia Observatory experiment, a 2.6 m telescope equipped with a four-channel 17' (FWHM) photometer. Measurements at frequency bands 143 ± 15, 214 ± 15, 272 ± 16, and 353 ± 13 GHz were made during 120 drift scans of Coma. We describe the observations and data analysis that involved extraction of the SZ signal by employing a spatial and spectral decorrelation scheme to remove a dominant atmospheric component. The deduced values of the thermal SZ effect in the first three bands are ΔT0 = -179 ± 38, -33 ± 81, and 170 ± 35 μK in the cluster center. The corresponding optical depth, τ = (4.1 ± 0.9) × 10-3, is consistent (within errors) with both the value from a previous low-frequency SZ measurement and the value predicted from the X-ray-deduced gas parameters.
Polycystic Ovary Syndrome and Irritable Bowel Syndrome: Is There a Common Pathway?

ABSTRACT Objective Little is known about how polycystic ovary syndrome (PCOS) is linked to irritable bowel syndrome (IBS). This study aimed to review the existing literature regarding the association between PCOS or its symptoms and complications with IBS. Methods In this review, studies that investigated the proposed cross‐link between features of PCOS and IBS were included. This review collectively focused on recent findings on the mechanism and novel insight regarding the association between IBS and PCOS in future clinical practice. An electronic search of PubMed, Scopus, Epistemonikos, Cochrane Library and Google Scholar was performed. We did not restrict the study setting and publication date. Results The existing evidence has not completely answered the question of whether there is an association between PCOS and IBS and vice versa. Six case–control studies (793 women with PCOS and 547 women in the control group) directly assessed the association between PCOS and IBS. The prevalence of IBS among women with PCOS in these studies has ranged from 10% to 52% compared with 5%–50% in control groups. Evidence suggested the common pathways may have contributed to the interaction between IBS and PCOS, including metabolic syndrome, sex hormone fluctuation, dysregulation of neurotransmitters, psychological problems and environmental and lifestyle factors. To date, it is still ambiguous which of the mentioned components largely contributes to the pathogenesis of both. Conclusion Although limited evidence has shown a higher prevalence of IBS in women with PCOS, there are several potential, direct and common indirect pathways contributing to the development of both IBS and PCOS.
Nuclear Plakoglobin Is Essential for Differentiation of Cardiac Progenitor Cells to Adipocytes in Arrhythmogenic Right Ventricular Cardiomyopathy

Rationale: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disease of desmosome proteins characterized by fibroadipogenesis in the myocardium. We have implicated signaling properties of junction protein plakoglobin (PG) in the pathogenesis of ARVC. Objective: To delineate the pathogenic role of PG in adipogenesis in ARVC. Methods and Results: We generated mice overexpressing PG, either a wildtype (PGWT) or a truncated (PGTR), known to cause ARVC, in the heart; and PG null (PG−/−) embryos. PGWT and PGTR mice exhibited fibro-adiposis, cardiac dysfunction, and premature death. Subcellular protein fractionation and immunofluorescence showed nuclear localization of PGWT and PGTR and reduced membrane localization of PGTR. Coimmunoprecipitation showed reduced binding of PGTR but not PGWT to desmosome proteins DSP and DSG2. Transgene PGWT and PGTR were expressed in c-Kit+:Sca1+ cardiac progenitor cells (CPCs) isolated from the hearts of PGWT and PGTR by fluorescence activated cell sorting. CPCs isolated from the transgenic hearts showed enhanced adipogenesis, increased levels of adipogenic factors KLF15, C/EBP-&agr; and noncanonical Wnt5b, and reduced level of CTGF, an inhibitor of adipogenesis. Treatment with BIO activated the canonical Wnt signaling, reversed the proadipogenic transcriptional switch and prevented adipogenesis in a dose-dependent manner. Moreover, c-Kit+ CPCs, isolated from PG−/− embryos, were resistant to adipogenesis, expressed high mRNA levels of CTGF and other canonical Wnt signaling targets. Conclusions: Nuclear PG provokes adipogenesis in c-Kit+ CPCs by repressing the canonical Wnt signaling and inducing a proadipogenic gene expression. The findings suggest that adipocytes in ARVC, at least in part, originate from c-Kit+ CPCs.
Real-time patient experience surveys of hospitalized medical patients.

BACKGROUND Real-time feedback about patients' perceptions of the quality of the care they are receiving could provide physicians the opportunity to address concerns and improve these perceptions as they occur, but physicians rarely if ever receive feedback from patients in real time. OBJECTIVE To evaluate if real-time patient feedback to physicians improves patient experience. DESIGN Prospective, randomized, quality-improvement initiative. SETTING University-affiliated, public safety net hospital. PARTICIPANTS Patients and hospitalist physicians on general internal medicine units. INTERVENTION Real-time daily patient feedback to providers along with provider coaching and revisits of patients not reporting optimal satisfaction with their care. MEASUREMENTS Patient experience scores on 3 provider-specific questions from daily surveys on all patients and Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) scores and percentiles on randomly selected patients. RESULTS Changes in HCAHPS percentile ranks were substantial (communication from doctors: 60th percentile versus 39th, courtesy and respect of doctors: 88th percentile versus 23rd, doctors listening carefully to patients: 95th percentile versus 57th, and overall hospital rating: 87th percentile versus 6th (P = 0.02 for overall differences in percentiles), but we found no statistically significant difference in the top box proportions for the daily surveys or the HCAHPS survey. The median [interquartile range] top box score for the overall hospital rating question on the HCAHPS survey was higher in the intervention group than in the control group (10 [9, 10] vs 9 [8, 10], P = 0.04). CONCLUSIONS Real-time feedback, followed by coaching and patient revisits, seem to improve patient experience.
Dialysis modality decision-making for older adults with chronic kidney disease.

AIMS AND OBJECTIVES To examine the personal and structural facilitators and barriers for home-dialysis decision-making for older adults with chronic kidney disease. BACKGROUND Chronic illness is a global problem. Older adults with chronic kidney disease form a large and growing segment of the dialysis population in many high-income countries but are less likely to uptake home-dialysis despite its benefits. DESIGN This qualitative ethnography framed in social theory took place in Canada and included adults with chronic kidney disease not on dialysis, older than 65 years of age. METHODS Thirteen people (seven men and six women, aged 65-83 years of age) who received care in a team chronic kidney disease clinic took part. Persons with chronic kidney disease were interviewed and group interviews were conducted with four of their chronic kidney disease clinic healthcare professionals. Content analysis was used for data analysis. RESULTS The factors influencing older adults' chronic kidney disease modality decisions are similar to younger adults. However, older adults with chronic kidney disease are in a precarious state with persistent uncertainty. Age imposes some limitations on modality options and transplantation. Modality decisions were influenced by health status, gender, knowledge, values, beliefs, past experience, preferences, lifestyle and resources. Support from family and healthcare professionals was the largest determinant to home-dialysis selection. CONCLUSION The social and contextual factors associated with age influenced home-dialysis decision-making. Adequate social support, functional status and resources enabled home-dialysis selection. RELEVANCE TO CLINICAL PRACTICE Understanding more about the decision-making processes for older adults with chronic kidney disease is important for quality interventions and the economic sustainability of dialysis services.
Oral bacterial community dynamics in paediatric patients with malignancies in relation to chemotherapy-related oral mucositis: a prospective study

The role of oral bacteria in the development of chemotherapy-related oral mucositis has not been fully elucidated. This study aimed to investigate oral bacterial community diversity and dynamics in paediatric patients with malignancies in relation to the occurrence of oral mucositis. Patients with malignancies (n = 37) and reference individuals without known systemic disorders (n = 38) were recruited. For patients, oral bacterial samples were taken from mucosal surfaces both at the time of malignancy diagnosis and during chemotherapy. If oral mucositis occurred, samples were taken from the surface of the mucositis lesions. Oral mucosal bacterial samples were also taken from reference individuals. All samples were assessed using a 16S ribosomal RNA gene 454 pyrosequencing method. A lower microbial diversity (p < 0.01) and a higher intersubject variability (p < 0.001) were found in patients as compared with reference individuals. At the time of malignancy diagnosis (i.e. before chemotherapy) patients that later developed mucositis showed a higher microbial diversity (p < 0.05) and a higher intersubject variability (p < 0.001) compared with those without mucositis. The change of bacterial composition during chemotherapy was more pronounced in patients who later developed mucositis than those without mucositis (p < 0.01). In conclusion, we found a higher microbial diversity at the time of malignancy diagnosis in patients who later develop oral mucositis and that these patients had a more significant modification of the bacterial community by chemotherapy before the occurrence of mucositis. These findings may possibly be of clinical importance in developing better strategies for personalized preventive management.
Neisserial Porin-Induced Dendritic Cell Activation Is MyD88 and TLR2 Dependent1

Neisserial porins have been shown to act as B cell mitogens and immune adjuvants. PorA and PorB are the major outer membrane porin proteins of the human pathogen Neisseria meningitidis. We have shown that the mechanism of the immunopotentiating capability of porin involves up-regulation of the T cell costimulatory ligand, CD86. Due to neisserial porin’s ability to activate B cells and potentiate immune responses, we hypothesized that porin also employs the potent immune stimulatory function of dendritic cells (DC). We examined the ability of purified N. meningitidis PorB to induce maturation of murine splenic and bone marrow-derived DC. PorB treatment induced DC maturation, as demonstrated by increased expression of CD86 and class I and II MHC molecules. In addition, PorB not only enhanced the allostimulatory activity of DC, but also augmented the ability of DC to stimulate T cells in an Ag-specific manner. PorB-matured DC secreted the inflammatory cytokine IL-6, which may have implications for the adjuvant property of porin. Induction of IL-6 by PorB is also significant because IL-6 is one of a number of cytokines produced during infection with N. meningitidis and may be involved in the inflammatory process observed during infection and disease. We previously demonstrated the requirement of MyD88 and TLR2 for PorB-induced B cell activation. In the present study, MyD88 and TLR2 were also essential for PorB-induced DC activation. This work is significant for elucidating the mechanism(s) of neisserial porin’s immune stimulatory activity.
Experimental Investigation of Adaptive Impedance Matching for a MIMO Terminal With CMOS-SOI Tuners

It is well known that user proximity introduces absorption and impedance mismatch losses (MLs) that severely degrade multiple-input multiple-output (MIMO) performance of handset antennas. In this work, we experimentally verified the potential of adaptive impedance matching (AIM) to mitigate user interaction effects and identified the main AIM gain mechanism in realistic systems. A practical setup including custom-designed CMOS silicon-on-insulator (SOI) impedance tuners implemented on a MIMO handset was measured in three propagation environments and ten real user scenarios. The results indicate that AIM can improve MIMO capacity by up to 42% equivalent to 3.5 dB of multiplexing efficiency (ME) gain. Taking into account the measured losses of 1 dB in the integrated tuners, the maximum net ME gain is 2.5 dB suggesting applicability in practical systems. Variations in ME gains of up to 1.5 dB for different hand-grip styles were mainly due to differences in impedance mismatch and tuner loss distribution. The study also confirmed earlier results on the significant differences in mismatch and absorption between phantoms and real users in which the phantoms underestimated user effects and, therefore, AIM gains. Finally, propagation environments of different angular spreads were found to give only minor ME gain variations.
Effects of High-Fat High-Sucrose Feeding, Energy Restriction, and trans-10,cis-12 Conjugated Linoleic Acid on Visfatin and Apelin in Hamsters

Objective: To analyze the effects of high-fat high-sucrose (HFHS) feeding, energy restriction, and trans-10,cis-12 conjugated linoleic acid (CLA) on visfatin and apelin. Design: A randomized dietary intervention study. Setting: Free-living individuals studied in metabolic cages. Subjects: Thirty-two male Syrian Golden hamsters (82.6 ± 1.4 g). Interventions: Standard and HFHS feeding for 7 weeks. After that, some hamsters fed the HFHS diet were submitted for 3 weeks to a 25% energy restriction with or without trans-10,cis-12 CLA supplementation (0.5%). Results: Feeding animals an HFHS diet resulted in increased body fat and reduced insulin sensitivity. No changes were observed in the expression and serum levels of visfatin and apelin, or in peroxisome proliferator-activated receptor (PPAR)γ and Sirt1 expression. Energy restriction reduced body fat and normalized insulin sensitivity. Visfatin showed increased serum levels without changes in expression. No modifications were found as far as apelin was concerned. Sirt1 expression was increased, and PPARγ remained unchanged. With regard to trans-10,cis-12 CLA, no changes were induced by its addition to the restricted diet. Conclusions: Insulin function impairment induced by HFHS feeding is not mediated by visfatin and apelin. However, visfatin can play a role in improving insulin sensitivity associated with energy restriction. These results suggest that visfatin may not have evolved as a molecule that reserves the action of insulin when food is widely available, but rather that its function seems to be associated with energy restriction adaptation. In general terms, trans-10,cis-12 CLA did not modify changes induced by energy restriction.
The numbers of individual mitochondrial DNA molecules and mitochondrial DNA nucleoids in yeast are co‐regulated by the general amino acid control pathway

Mitochondrial DNA (mtDNA) is inherited as a protein–DNA complex (the nucleoid). We show that activation of the general amino acid response pathway in ρ+ and ρ− petite cells results in an increased number of nucleoids without an increase in mtDNA copy number. In ρ− cells, activation of the general amino acid response pathway results in increased intramolecular recombination between tandemly repeated sequences of ρ− mtDNA to produce small, circular oligomers that are packaged into individual nucleoids, resulting in an ∼10‐fold increase in nucleoid number. The parsing of mtDNA into nucleoids due to general amino acid control requires Ilv5p, a mitochondrial protein that also functions in branched chain amino acid biosynthesis, and one or more factors required for mtDNA recombination. Two additional proteins known to function in mtDNA recombination, Abf2p and Mgt1p, are also required for parsing mtDNA into a larger number of nucleoids, although expression of these proteins is not under general amino acid control. Increased nucleoid number leads to increased mtDNA transmission, suggesting a mechanism to enhance mtDNA inheritance under amino acid starvation conditions.