Miracle-dz/UniFAR-FTUs huggingface dataset:
ALS‐Associated Endoplasmic Reticulum Proteins in Denervated Skeletal Muscle: Implications for Motor Neuron Disease Pathology

Alpha‐motoneurons and muscle fibres are structurally and functionally interdependent. Both cell types particularly rely on endoplasmic reticulum (ER/SR) functions. Mutations of the ER proteins VAPB, SigR1 and HSP27 lead to hereditary motor neuron diseases (MNDs). Here, we determined the expression profile and localization of these ER proteins/chaperons by immunohistochemistry and immunoblotting in biopsy and autopsy muscle tissue of patients with amyotrophic lateral sclerosis (ALS) and other neurogenic muscular atrophies (NMAs) and compared these patterns to mouse models of neurogenic muscular atrophy. Postsynaptic neuromuscular junction staining for VAPB was intense in normal human and mouse muscle and decreased in denervated Nmd2J mouse muscle fibres. In contrast, VAPB levels together with other chaperones and autophagy markers were increased in extrasynaptic regions of denervated muscle fibres of patients with MNDs and other NMAs, especially at sites of focal myofibrillar disintegration (targets). These findings did not differ between NMAs due to ALS and other causes. G93A‐SOD1 mouse muscle fibres showed a similar pattern of protein level increases in denervated muscle fibres. In addition, they showed globular VAPB‐immunoreactive structures together with misfolded SOD1 protein accumulations, suggesting a primary myopathic change. Our findings indicate that altered expression and localization of these ER proteins and autophagy markers are part of the dynamic response of muscle fibres to denervation. The ER is particularly prominent and vulnerable in both muscle fibres and alpha‐motoneurons. Thus, ER pathology could contribute to the selective build‐up of degenerative changes in the neuromuscular axis in MNDs.
Clines Arc through Multivariate Morphospace

Evolutionary biologists typically represent clines as spatial gradients in a univariate character (or a principal-component axis) whose mean changes as a function of location along a transect spanning an environmental gradient or ecotone. This univariate approach may obscure the multivariate nature of phenotypic evolution across a landscape. Clines might instead be plotted as a series of vectors in multidimensional morphospace, connecting sequential geographic sites. We present a model showing that clines may trace nonlinear paths that arc through morphospace rather than elongating along a single major trajectory. Arcing clines arise because different characters diverge at different rates or locations along a geographic transect. We empirically confirm that some clines arc through morphospace, using morphological data from threespine stickleback sampled along eight independent transects from lakes down their respective outlet streams. In all eight clines, successive vectors of lake-stream divergence fluctuate in direction and magnitude in trait space, rather than pointing along a single phenotypic axis. Most clines exhibit surprisingly irregular directions of divergence as one moves downstream, although a few clines exhibit more directional arcs through morphospace. Our results highlight the multivariate complexity of clines that cannot be captured with the traditional graphical framework. We discuss hypotheses regarding the causes, and implications, of such arcing multivariate clines.
Still no convincing evidence for cognitive map use by honeybees

the view from each release point is compared with the view from the feeder toward the hive (i.e., B ). In both cases, the minimum is near the hive direction (dashed lines). These comparisons show that a remembered direction can be obtained by matching a view stored at a location to the currently perceived view at that location ( B ) and, further, that homing directions can be obtained by comparing the stored view with the current view from other locations in the neighborhood ( C and D ). The general point that the terrain supplies visual information for view-based guidance is independent of the accuracy of this particular reconstruction. Indeed, bees will have a more complex set of stored views gathered during their exploration and orientation flights, including information below the horizon. These extra views would enhance the robustness of their view-based navigation.
Building access tree for attribute-based encryption schemes over multidimensional data objects

Multidimensional data objects are widely used in online analytical processing and data mining technologies. Many security problems arise in building applications on top of multidimensional databases. Attribute-Based Encryption schemes can be effectively used to ensure privacy and security of multidimensional data objects. In order to use such schemes we propose attribute management scheme and access policies. In our paper, it is shown how to convert any access policy to a set of binary trees enabling use of Attribute-Based Encryption for stored multidimensional data cubes. Moreover, we demonstrate that such transformation can be done in a unique way. We argue that our access control technique can be integrated with query processing over encrypted data to increase the security level of multidimensional databases.
Views of Japanese medical students on the work-life balance of female physicians

Objectives To survey medical students on their ideas of future work-life balance and discuss topics for next-generation medical education. Methods First-year (n=372, 34.9% female) and sixth-year medical students (n=311, 44.1% female) responded to a questionnaire on future self, marriage and childcare, and gender differences at the workplace. Responses were compared between academic years and gender. Responses were evaluated by gender and academic year using the Mann-Whitney U test. Significance was set at p<0.01. Results The first-year and sixth-year students, regardless of gender, had different views on gender-related favorable treatment at workplaces {U=13464, p=0.000 (first-year), U=10407, p=0.000 (sixth-year)}. A greater percentage of female students would choose career options based on the possibility of marriage and childbirth {U=10689, p=0.000 (first-year), U=10930, p=0.000 (sixth-year)}. Among first-year students, a greater percentage of female students expected to work part-time. Also among first-year students, greater percentages of female students expected to work part-time or leave their jobs temporarily while raising their children. Compared with first-year male students, first-year female students expected to undertake larger portions of the childcare and housework burden than their partners. However, gender differences in work-life balance and childcare leave vanished in the sixth-year students. Conclusions Female medical students accepted childcare and housework burdens as inevitable; the work environment they choose might affect their career development. While support from male partners and institutions must be increased, voluntary actions and change in mentality of female students need to be promoted through medical education to prevent them from waiting passively for the situation to change.
Previous antibiotic exposure and antibiotic resistance of commensal Staphylococcus aureus in Spanish primary care

Abstract Introduction: Commensal flora of healthy people is becoming an important reservoir of resistant bacteria. Objectives: To evaluate the relationship of previous antibiotic-dispensed and resistance pattern of strains of Staphylococcus aureus in primary care patients. Methods: A cross-sectional study was carried out in seven primary care centres in Catalonia, Spain, from October 2010 to May 2011, as part of the APRES (The appropriateness of prescribing antibiotics in primary care in Europe concerning antibiotic resistance) study. Outpatients aged 4 or more who did not present an infectious disease and had not taken antibiotic or had not been hospitalised in the previous 3 months were invited to participate. Nasal swabs were collected for S. aureus culture, and antimicrobial susceptibility testing was carried out. Antibiotics dispensed boxes in the previous 4 years were extracted from Information System for Research in Primary Care. Results: A total of 4,001 nasal swabs were collected, and 3,969 were tested for identification, 765 S. aureus were tested for resistance. Resistance rates to penicillin, azithromycin and methicillin were 87.1%, 11.6% and 1.3%, respectively, and a total of 10 MRSA strains were isolated (1.3%). Penicillin-resistant staphylococci were statistically significantly associated with the previous number of packages of penicillin dispensed (OR, 1.18; 95% CI, 1.04–1.35). Conclusion: Although no causal inference is possible, an association was observed between previous antibiotic dispensation and isolation of resistant organisms in community-dwelling individuals, mainly between packages of penicillin and penicillin-resistant staphylococci.
Residual thermal stresses around bonded fibre metal laminate repair patches on an aircraft fuselage

Residual stresses are present after elevated temperature cure of adhesively bonded patches to cracked aircraft structures. These residual stresses will affect the performance and the durability of the repair. Strain and temperature measurements were taken on a real aircraft fuselage section during and after repair at three locations. Thermal buckling of the skin was observed and therefore a precuring at a lower temperature was employed. Also at a lower temperature a significant outward bending of the skin was observed which influences the residual stresses. The measured temperature field corresponded weil with the theoretical model of Rose.
Risk assessment in emergency general surgery.

Patients with emergency general surgery (EGS) diseases display variable severity. The extent of disease can be amplified by comorbidity or dramatic changes in presenting physiology. Estimating the extent of disease severity in order to adequately provide prognosis, determine optimal operative or non-operative management, and plan for potential outcomes is difficult. A variety of risk factors have been studied for specific diseases but these criteria may not be universally applied. This limits the generalizability of prior work. The American Association for the Surgery of Trauma (AAST) created a grading system wherein uniform definitions could be applied to begin to measure disease severity in a granular manner. This review presents some of the initial work focused on the validation and incorporation of the AAST EGS grading system. The authors evaluate several diseases wherein the AAST EGS grade has been applied. Finally the work concludes with a review of several inclusive risk estimation tools. Taken together, the ability to measure disease severity - whether by anatomic changes, physiologic disturbance, or patient comorbidity status - will provide a better method to appraise, research, and improve patient care for several EGS conditions.
Genome-Wide Analysis of DNA Methylation and Fine Particulate Matter Air Pollution in Three Study Populations: KORA F3, KORA F4, and the Normative Aging Study

Background: Epidemiological studies have reported associations between particulate matter (PM) concentrations and cancer and respiratory and cardiovascular diseases. DNA methylation has been identified as a possible link but so far it has only been analyzed in candidate sites. Objectives: We studied the association between DNA methylation and short- and mid-term air pollution exposure using genome-wide data and identified potential biological pathways for additional investigation. Methods: We collected whole blood samples from three independent studies—KORA F3 (2004–2005) and F4 (2006–2008) in Germany, and the Normative Aging Study (1999–2007) in the United States—and measured genome-wide DNA methylation proportions with the Illumina 450k BeadChip. PM concentration was measured daily at fixed monitoring stations and three different trailing averages were considered and regressed against DNA methylation: 2-day, 7-day and 28-day. Meta-analysis was performed to pool the study-specific results. Results: Random-effect meta-analysis revealed 12 CpG (cytosine-guanine dinucleotide) sites as associated with PM concentration (1 for 2-day average, 1 for 7-day, and 10 for 28-day) at a genome-wide Bonferroni significance level (p ≤ 7.5E-8); 9 out of these 12 sites expressed increased methylation. Through estimation of I2 for homogeneity assessment across the studies, 4 of these sites (annotated in NSMAF, C1orf212, MSGN1, NXN) showed p > 0.05 and I2 < 0.5: the site from the 7-day average results and 3 for the 28-day average. Applying false discovery rate, p-value < 0.05 was observed in 8 and 1,819 additional CpGs at 7- and 28-day average PM2.5 exposure respectively. Conclusion: The PM-related CpG sites found in our study suggest novel plausible systemic pathways linking ambient PM exposure to adverse health effect through variations in DNA methylation. Citation: Panni T, Mehta AJ, Schwartz JD, Baccarelli AA, Just AC, Wolf K, Wahl S, Cyrys J, Kunze S, Strauch K, Waldenberger M, Peters A. 2016. A genome-wide analysis of DNA methylation and fine particulate matter air pollution in three study populations: KORA F3, KORA F4, and the Normative Aging Study. Environ Health Perspect 124:983–990; http://dx.doi. org/10.1289/ehp.1509966
Direct Fitness Correlates and Thermal Consequences of Facultative Aggregation in a Desert Lizard

Social aggregation is a common behavioral phenomenon thought to evolve through adaptive benefits to group living. Comparing fitness differences between aggregated and solitary individuals in nature – necessary to infer an evolutionary benefit to living in groups – has proven difficult because communally-living species tend to be obligately social and behaviorally complex. However, these differences and the mechanisms driving them are critical to understanding how solitary individuals transition to group living, as well as how and why nascent social systems change over time. Here we demonstrate that facultative aggregation in a reptile (the Desert Night Lizard, Xantusia vigilis) confers direct reproductive success and survival advantages and that thermal benefits of winter huddling disproportionately benefit small juveniles, which can favor delayed dispersal of offspring and the formation of kin groups. Using climate projection models, however, we estimate that future aggregation in night lizards could decline more than 50% due to warmer temperatures. Our results support the theory that transitions to group living arise from direct benefits to social individuals and offer a clear mechanism for the origin of kin groups through juvenile philopatry. The temperature dependence of aggregation in this and other taxa suggests that environmental variation may be a powerful but underappreciated force in the rapid transition between social and solitary behavior.
The impact of removing financial incentives from clinical quality indicators: longitudinal analysis of four Kaiser Permanente indicators

Objective To evaluate the effect of financial incentives on four clinical quality indicators common to pay for performance plans in the United Kingdom and at Kaiser Permanente in California. Design Longitudinal analysis. Setting 35 medical facilities of Kaiser Permanente Northern California, 1997-2007. Participants 2 523 659 adult members of Kaiser Permanente Northern California. Main outcomes measures Yearly assessment of patient level glycaemic control (HbA1c <8%), screening for diabetic retinopathy, control of hypertension (systolic blood pressure <140 mm Hg), and screening for cervical cancer. Results Incentives for two indicators—screening for diabetic retinopathy and for cervical cancer—were removed during the study period. During the five consecutive years when financial incentives were attached to screening for diabetic retinopathy (1999-2003), the rate rose from 84.9% to 88.1%. This was followed by four years without incentives when the rate fell year on year to 80.5%. During the two initial years when financial incentives were attached to cervical cancer screening (1999-2000), the screening rate rose slightly, from 77.4% to 78.0%. During the next five years when financial incentives were removed, screening rates fell year on year to 74.3%. Incentives were then reattached for two years (2006-7) and screening rates began to increase. Across the 35 facilities, the removal of incentives was associated with a decrease in performance of about 3% per year on average for screening for diabetic retinopathy and about 1.6% per year for cervical cancer screening. Conclusion Policy makers and clinicians should be aware that removing facility directed financial incentives from clinical indicators may mean that performance levels decline.
Effects of introduced bees on native ecosystems

Bees are generally regarded as beneficial insects for their role in pollination, and in the case of the honeybee Apis mellifera, for production of honey. As a result several bee species have been introduced to countries far beyond their home range, including A. mellifera, bumblebees (Bombus sp.), the alfalfa leafcutter bee Megachile rotundata, and various other solitary species. Possible negative consequences of these introductions include: competition with native pollinators for floral resources; competition for nest sites; co-introduction of natural enemies, particularly pathogens that may infect native organisms; pollination of exotic weeds; and disruption of pollination of native plants. For most exotic bee species little or nothing is known of these possible effects. Research to date has focused mainly on A. mellifera, and has largely been concerned with detecting competition with native flower visitors. Considerable circumstantial evidence has accrued that competition does occur, but no experiment has clearly demonstrated long-term reductions in populations of native organisms. Most researchers agree that this probably reflects the difficulty of carrying out convincing studies of competition between such mobile organisms, rather than a genuine absence of competitive effects. Effects on seed set of exotic weeds are easier to demonstrate. Exotic bees often exhibit marked preferences for visiting flowers of exotic plants. For example, in Australia and New Zealand many weeds from Europe are now visited by European honeybees and bumblebees. Introduced bees are primary pollinators of a number of serious weeds. Negative impacts of exotic bees need to be carefully assessed before further introductions are carried out.
Divergence in problem-solving skills is associated with differential expression of glutamate receptors in wild finches

Wild birds that vary in their problem-solving capacity were found to express different neurotransmitter receptor densities. Problem solving and innovation are key components of intelligence. We compare wild-caught individuals from two species that are close relatives of Darwin’s finches, the innovative Loxigilla barbadensis, and its most closely related species in Barbados, the conservative Tiaris bicolor. We found an all-or-none difference in the problem-solving capacity of the two species. Brain RNA sequencing analyses revealed interspecific differences in genes related to neuronal and synaptic plasticity in the intrapallial neural populations (mesopallium and nidopallium), especially in the nidopallium caudolaterale, a structure functionally analogous to the mammalian prefrontal cortex. At a finer scale, we discovered robust differences in glutamate receptor expression between the species. In particular, the GRIN2B/GRIN2A ratio, known to correlate with synaptic plasticity, was higher in the innovative L. barbadensis. These findings suggest that divergence in avian intelligence is associated with similar neuronal mechanisms to that of mammals, including humans.
Understanding Clostridium difficile Colonization

SUMMARY Clostridium difficile is the main causative agent of antibiotic-associated and health care-associated infective diarrhea. Recently, there has been growing interest in alternative sources of C. difficile other than patients with Clostridium difficile infection (CDI) and the hospital environment. Notably, the role of C. difficile-colonized patients as a possible source of transmission has received attention. In this review, we present a comprehensive overview of the current understanding of C. difficile colonization. Findings from gut microbiota studies yield more insights into determinants that are important for acquiring or resisting colonization and progression to CDI. In discussions on the prevalence of C. difficile colonization among populations and its associated risk factors, colonized patients at hospital admission merit more attention, as findings from the literature have pointed to their role in both health care-associated transmission of C. difficile and a higher risk of progression to CDI once admitted. C. difficile colonization among patients at admission may have clinical implications, although further research is needed to identify if interventions are beneficial for preventing transmission or overcoming progression to CDI.
Bordetella holmesii sp. nov., a new gram-negative species associated with septicemia

CDC nonoxidizer group 2 (NO-2) currently consists of 15 gram-negative, rod-shaped, oxidase-negative, asaccharolytic, brown soluble pigment-producing strains isolated from blood cultures, usually from young adults. On the basis of their cellular fatty acid profiles, NO-2 strains formed a single group that was identical with the profile of Bordetella avium. 16S rRNA sequencing of one NO-2 strain and the type strains of B. pertussis, B. parapertussis, B. bronchiseptica, and B. avium showed a high degree of homology (> or = 98% over 1,525 bases). The NO-2 guanine-plus-cytosine content (61.5 to 62.3 mol%) and major ubiquinone analysis (ubiquinone-8) results were both consistent with those for the genus Bordetella. DNA relatedness studies (hydroxyapatite method) confirmed a close relatedness between NO-2 and Bordetella species and demonstrated that NO-2 strains were a single new species. The name B. holmesii sp. nov. is proposed for CDC group NO-2.
Aurora A activation in mitosis promoted by BuGZ

Protein phase separation or coacervation has emerged as a potential mechanism to regulate biological functions. We have shown that coacervation of a mostly unstructured protein, BuGZ, promotes assembly of spindle and its matrix. BuGZ in the spindle matrix binds and concentrates tubulin to promote microtubule (MT) assembly. It remains unclear, however, whether BuGZ could regulate additional proteins to promote spindle assembly. In this study, we report that BuGZ promotes Aurora A (AurA) activation in vitro. Depletion of BuGZ in cells reduces the amount of phosphorylated AurA on spindle MTs. BuGZ also enhances MCAK phosphorylation. The two zinc fingers in BuGZ directly bind to the kinase domain of AurA, which allows AurA to incorporate into the coacervates formed by BuGZ in vitro. Importantly, mutant BuGZ that disrupts the coacervation activity in vitro fails to promote AurA phosphorylation in Xenopus laevis egg extracts. These results suggest that BuGZ coacervation promotes AurA activation in mitosis.