Miracle-dz/UniFAR-FTUs huggingface dataset:
The synthesis of OspD3 (ShET2) in Shigella flexneri is independent of OspC1

ABSTRACT Shigella flexneri is a Gram-negative pathogen that invades the colonic epithelium and causes millions of cases of watery diarrhea or bacillary dysentery predominately in children under the age of 5 years in developing countries. The effector Shigella enterotoxin 2 (ShET2), or OspD3, is encoded by the sen or ospD3 gene on the virulence plasmid. Previous literature has suggested that ospD3 is in an operon downstream of the ospC1 gene, and expression of both genes is controlled by a promoter upstream of ospC1. Since the intergenic region is 328 bases in length and contains several putative promoter regions, we hypothesized the genes are independently expressed. Here we provide data that ospD3 and ospC1 are not co-transcribed and that OspC1 is not required for OspD3/ShET2 function. Most importantly, we identified strong promoter activity in the intergenic region and demonstrate that OspD3/ShET2 can be expressed and secreted independently of OspC1. This work increases our understanding of the synthesis of a unique virulence factor and provides further insights into Shigella pathogenesis.
Effect of vitamin D treatments on plasma metabolism and immune parameters of healthy dairy cows

ABSTRACT The objective of this study was to investigate the possible beneficial effect of vitamin D repletion on certain immune parameters of vitamin D insufficient dairy cows. Twenty dairy cows in late lactation were treated daily with vitamin D in five different ways: sunlight exposure (SUN), D2 supplementation combined with sunlight exposure (D2SUN), D2 supplementation (D2), D3 supplementation (D3), and D2 and D3 supplementation combined (D2D3). The cows had very low vitamin D levels at d 0 because of the vitamin D deprivation before the study. After 1 month of vitamin D repletion, all cows had plasma 25(OH)D levels within the normal range. Total 25(OH)D concentration was significantly higher in SUN, D2SUN and D2D3 than D2 or D3 at the end of the study. However, milk yield, as well as protein and fat content of the milk, was not influenced by vitamin D treatments. There was no difference obtained in the measured immune parameters: Leucocyte populations, somatic cell count, immunoglobulin concentrations in plasma and milk, and antigen-stimulated cytokine productions did not change in response to vitamin D repletion or difference in vitamin D sources, and no relations to plasma 25(OH)D levels were identified. Despite the fact that plasma 25(OH)D increased from a very low level to normal range, the present study did not show any effect of vitamin D repletion on the tested immune parameters of healthy dairy cows. Therefore, in this study, it was concluded that repletion to physiologically normal plasma 25-hydroxyvitamin D levels of vitamin D-depleted healthy dairy cows had no influence on immune parameters.
Exploring the impact of living with dyslexia: The perspectives of children and their parents

Abstract Purpose: A small but growing body of literature indicates that children with dyslexia are at elevated risk of internalising and externalising mental health problems. However, little research addresses why this might be the case, particularly from the point of view of the children or their parents. This study therefore aimed to explore the lived experiences of children with dyslexia, and their parents. Method: Drawing on a phenomenological approach, 13 children with dyslexia and 21 parents were interviewed. The semi-structured interviews were analysed thematically. Result: Dyslexia was seen to impact at the individual, family and community level. Children’s accounts of their experiences were ecologically situated at both the micro and mesosystem levels of Bronfenbrenner’s ecological model, while parent’s accounts extended to include the exosystem. Both also reflected on “difference”, a theme related to cultural and attitudinal views at the level of the macrosystem. Conclusion: Presentation of the themes contrasts the experiences of children and parents, illustrating that the experience of dyslexia is indicative of broader challenges associated with societal values and attitudes that privilege perceived ability and shame difference. This study provides information that could be used to inform and educate families and teachers about the impact of living with dyslexia.
Adult Brainstem Gliomas With H3K27M Mutation: Radiology, Pathology, and Prognosis

Adult brainstem gliomas are difficult to classify based on radiologic and histologic features. A K27M mutation in histone 3 has been described to identify high-grade midline gliomas associated with a particularly unfavorable prognosis. While initially considered a pediatric entity, it is now known that H3K27M-mutant brainstem gliomas occur in all age groups, but they are less well understood in adults. We studied clinical, radiologic, and pathologic features of 25 brainstem gliomas diagnosed at our institution between 1994 and 2017 in subjects at least 18 years old. Seven tumors (28%) were positive for the H3K27M mutation, and their median overall survival was significantly shorter than in the H3-wildtype group (p = 0.004). Although the mutation was invariably associated with a poor prognosis, our study also illustrates the radiologic and pathologic heterogeneity in this molecular tumor subtype. The results showed that H3K27M-mutant status and clinically aggressive course cannot be ruled out based on low-grade histology on the initial biopsy, exophytic growth, only focal or minimal enhancement or an extrapontine location, such as midbrain or medulla. These results favor an integrated approach employing a combination of clinical, radiologic, histologic features as well as H3K27M immunohistochemistry for the diagnostic subclassification of adult brainstem gliomas.
lncRNA Chronos is an aging-induced inhibitor of muscle hypertrophy

Skeletal muscle exhibits remarkable plasticity in its ability to modulate its mass in response to the physiologic changes associated with functional use, systemic disease, and aging. Although a gradual loss of muscle mass normally occurs with advancing age, its increasingly rapid progression results in sarcopenia in a subset of individuals. The identities of muscle-enriched, long noncoding RNAs that regulate this process are unknown. Here, we identify a long noncoding RNA, named Chronos, whose expression in muscle is positively regulated with advancing age and negatively regulated during Akt1-mediated growth. Inhibition of Chronos induces myofiber hypertrophy both in vitro and in vivo, in part, through the epigenetic modulation of Bmp7 signaling.
Psychological Stress and Mitochondria: A Systematic Review

Objective Mitochondria are multifunctional life-sustaining organelles that represent a potential intersection point between psychosocial experiences and biological stress responses. This article provides a systematic review of the effects of psychological stress on mitochondrial structure and function. Methods A systematic review of the literature investigating the effects of psychological stress on mitochondrial function was conducted. The review focused on experimentally controlled studies allowing us to draw causal inference about the effect of induced psychological stress on mitochondria. Results A total of 23 studies met the inclusion criteria. All studies involved male laboratory animals, and most demonstrated that acute and chronic stressors influenced specific facets of mitochondrial function, particularly within the brain. Nineteen studies showed significant adverse effects of psychological stress on mitochondria and four found increases in function or size after stress. In humans, only six observational studies were available, none with experimental designs, and most only measured biological markers that do not directly reflect mitochondrial function, such as mitochondrial DNA copy number. Conclusons Overall, evidence supports the notion that acute and chronic stressors influence various aspects of mitochondrial biology, and that chronic stress exposure can lead to molecular and functional recalibrations among mitochondria. Limitations of current animal and human studies are discussed. Maladaptive mitochondrial changes that characterize this subcellular state of stress are termed mitochondrial allostatic load. Prospective studies with sensitive measures of specific mitochondrial outcomes will be needed to establish the link between psychosocial stressors, emotional states, the resulting neuroendocrine and immune processes, and mitochondrial energetics relevant to mind-body research in humans.
A Memristive Chaotic Oscillator With Increasing Amplitude and Frequency

A chaotic oscillator utilizing a flux-controlled memristor to produce a signal that grows in amplitude and frequency over time is introduced in this paper. It was found that the initial condition can be used to change the starting oscillation as well as the amplitude and frequency. From this, a new regime of homogenous multistability was found, where various attractors with different initial conditions are of the same type but have different amplitudes and frequencies.
Predictive accuracy of combined genetic and environmental risk scores

The substantial heritability of most complex diseases suggests that genetic data could provide useful risk prediction. To date the performance of genetic risk scores has fallen short of the potential implied by heritability, but this can be explained by insufficient sample sizes for estimating highly polygenic models. When risk predictors already exist based on environment or lifestyle, two key questions are to what extent can they be improved by adding genetic information, and what is the ultimate potential of combined genetic and environmental risk scores? Here, we extend previous work on the predictive accuracy of polygenic scores to allow for an environmental score that may be correlated with the polygenic score, for example when the environmental factors mediate the genetic risk. We derive common measures of predictive accuracy and improvement as functions of the training sample size, chip heritabilities of disease and environmental score, and genetic correlation between disease and environmental risk factors. We consider simple addition of the two scores and a weighted sum that accounts for their correlation. Using examples from studies of cardiovascular disease and breast cancer, we show that improvements in discrimination are generally small but reasonable degrees of reclassification could be obtained with current sample sizes. Correlation between genetic and environmental scores has only minor effects on numerical results in realistic scenarios. In the longer term, as the accuracy of polygenic scores improves they will come to dominate the predictive accuracy compared to environmental scores.
Influence of feed provisioning prior to digesta sampling on precaecal amino acid digestibility in broiler chickens

ABSTRACT A regression approach was applied to determine the influence of feed provisioning prior to digesta sampling on precaecal (pc) amino acid (AA) digestibility in broiler chickens. Soybean meal was used as an example test ingredient. Five feed-provisioning protocols were investigated, four with restricted provision and one with ad libitum provision. When provision was restricted, feed was provided for 30 min after a withdrawal period of 12 h. Digesta were sampled 1, 2, 4 and 6 h after feeding commenced. A diet containing 300 g maize starch/kg was prepared. Half or all the maize starch was replaced with soybean meal in two other diets. Average pc digestibility of all determined AA in the soybean meal was 86% for the 4 and 6-h protocols and 66% and 60% for the 2 and 1-h protocols, respectively. Average pc AA digestibility of soybean meal was 76% for ad libitum feed provision. Feed provisioning also influenced the determined variance. Variance in digestibility ranked in magnitude 1 h > ad libitum > 2 h > 6 h > 4 h for all AA. Owing to the considerable influence of feed-provisioning protocols found in this study, comparisons of pc AA digestibility between studies applying different protocols prior to digesta sampling must be treated with caution. Digestibility experiments aimed at providing estimates for practical feed formulation should use feed-provisioning procedures similar to those used in practice.
Clay-Water/Cement Ratio is the Prime Parameter for Fine Grained Soil Improvement at High Water Content

The in-situ deep mixing technique has been established as a means to effect columnar inclusions into soft ground to enhance the bearing capacity and reduce settlement. Since the inception of this method, developments in the plant and machinery, as well as associated field techniques, have surpassed the basic understanding of developments of soil strength in high water content clays admixed with cement. In this paper, an attempt is made to identify the factors governing the engineering behavior of cement stabilized soft clays. It helps not only to control the input of cementing agent to attain strength development with curing time, clay type and clay-water content, but also to understand the subsequent geotechnical engineering behavior of stabilized soft clays. The cementation bond strength increases as the clay-water/cement ratio (wc/c) decreases. It is demonstrated by the test results of consolidation, the yield stress in Koconsolidation of samples increases with the decrease in wc/c, and samples having the same wc/c develop practically the same level of yield stress. The stress~strains behavior and strength characteristics in the unconfined compression test are practically the same as long as the wc/c is identical. It is revealed that clay-water/cement ratio wc/c is the prime parameter for such fine grained soil improvement.
A High-Resolution Map of Segmental DNA Copy Number Variation in the Mouse Genome

Submicroscopic (less than 2 Mb) segmental DNA copy number changes are a recently recognized source of genetic variability between individuals. The biological consequences of copy number variants (CNVs) are largely undefined. In some cases, CNVs that cause gene dosage effects have been implicated in phenotypic variation. CNVs have been detected in diverse species, including mice and humans. Published studies in mice have been limited by resolution and strain selection. We chose to study 21 well-characterized inbred mouse strains that are the focus of an international effort to measure, catalog, and disseminate phenotype data. We performed comparative genomic hybridization using long oligomer arrays to characterize CNVs in these strains. This technique increased the resolution of CNV detection by more than an order of magnitude over previous methodologies. The CNVs range in size from 21 to 2,002 kb. Clustering strains by CNV profile recapitulates aspects of the known ancestry of these strains. Most of the CNVs (77.5%) contain annotated genes, and many (47.5%) colocalize with previously mapped segmental duplications in the mouse genome. We demonstrate that this technique can identify copy number differences associated with known polymorphic traits. The phenotype of previously uncharacterized strains can be predicted based on their copy number at these loci. Annotation of CNVs in the mouse genome combined with sequence-based analysis provides an important resource that will help define the genetic basis of complex traits.
Effects of suspended drill cuttings on the coral Lophelia pertusa using pulsed and continuous exposure scenarios

ABSTRACT This study aimed at providing confidence in the predictability of the impacts of drill cuttings (DC) discharge on the cold-water coral Lophelia pertusa. L. pertusa was exposed to DC from offshore exploration in the lab with the goal to assess precautionary thresholds of effects. Two exposure scenarios with DC were tested: a long-term (LT) pulsed exposure (12 weeks, peak concentrations: 2–50 mg/L, mean concentrations: 1–25 mg/L) and a short-term (ST) continuous exposure (2.5 weeks, mean concentrations: 4–42 mg/L). After exposure, a recovery period of 16 and 4 weeks was maintained in LT and ST, respectively. While there was an assumption that DC might result in an increase in respiration, decrease in growth, enhanced mucus production, reduced fatty acid content, only a significant rise was noted in skeleton growth at DC 4 mg/L and a significant increase of mucus particulate organic carbon at 25 mg/L at end of the exposure. DC did not markedly reduce prey capture rate consecutive to DC exposure. However, the effect of DC produced an increase of coral polyp activity during exposure and a return to pre-exposure conditions after cessation of DC, and coenosarc was smothered from DC even after a long recovery period (4 weeks). Overall, a DC concentration of 10 mg/L seems to represent a threshold above which changes in coral conditions were observed however with no apparent physiological consequences for the coral within the experimental time scale.
Effects of Food Availability on Yolk Androgen Deposition in the Black-Legged Kittiwake (Rissa tridactyla), a Seabird with Facultative Brood Reduction

In birds with facultative brood reduction, survival of the junior chick is thought to be regulated primarily by food availability. In black-legged kittiwakes (Rissa tridactyla) where parents and chicks are provided with unlimited access to supplemental food during the breeding season, brood reduction still occurs and varies interannually. Survival of the junior chick is therefore affected by factors in addition to the amount of food directly available to them. Maternally deposited yolk androgens affect competitive dynamics within a brood, and may be one of the mechanisms by which mothers mediate brood reduction in response to a suite of environmental and physiological cues. The goal of this study was to determine whether food supplementation during the pre-lay period affected patterns of yolk androgen deposition in free-living kittiwakes in two years (2003 and 2004) that varied in natural food availability. Chick survival was measured concurrently in other nests where eggs were not collected. In both years, supplemental feeding increased female investment in eggs by increasing egg mass. First-laid (“A”) eggs were heavier but contained less testosterone and androstenedione than second-laid (“B”) eggs across years and treatments. Yolk testosterone was higher in 2003 (the year with higher B chick survival) across treatments. The difference in yolk testosterone levels between eggs within a clutch varied among years and treatments such that it was relatively small when B chick experienced the lowest and the highest survival probabilities, and increased with intermediate B chick survival probabilities. The magnitude of testosterone asymmetry in a clutch may allow females to optimize fitness by either predisposing a brood for reduction or facilitating survival of younger chicks.
Toxicity‐dependent feasibility bounds for the escalation with overdose control approach in phase I cancer trials

Phase I trials of anti‐cancer therapies aim to identify a maximum tolerated dose (MTD), defined as the dose that causes unacceptable toxicity in a target proportion of patients. Both rule‐based and model‐based methods have been proposed for MTD recommendation. The escalation with overdose control (EWOC) approach is a model‐based design where the dose assigned to the next patient is one that, given all available data, has a posterior probability of exceeding the MTD equal to a pre‐specified value known as the feasibility bound. The aim is to conservatively dose‐escalate and approach the MTD, avoiding severe overdosing early on in a trial. The EWOC approach has been applied in practice with the feasibility bound either fixed or varying throughout a trial, yet some of the methods may recommend incoherent dose‐escalation, that is, an increase in dose after observing severe toxicity at the current dose. We present examples where varying feasibility bounds have been used in practice, and propose a toxicity‐dependent feasibility bound approach that guarantees coherent dose‐escalation and incorporates the desirable features of other EWOC approaches. We show via detailed simulation studies that the toxicity‐dependent feasibility bound approach provides improved MTD recommendation properties to the original EWOC approach for both discrete and continuous doses across most dose‐toxicity scenarios, with comparable performance to other approaches without recommending incoherent dose escalation. © 2017 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.
Sudden Collapse of Vacuoles in Saintpaulia sp. Palisade Cells Induced by a Rapid Temperature Decrease

It is well known that saintpaulia leaf is damaged by the rapid temperature decrease when cold water is irrigated onto the leaf surface. We investigated this temperature sensitivity and the mechanisms of leaf damage in saintpaulia (Saintpaulia sp. cv. ‘Iceberg’) and other Gesneriaceae plants. Saintpaulia leaves were damaged and discolored when subjected to a rapid decrease in temperature, but not when the temperature was decreased gradually. Sensitivity to rapid temperature decrease increased within 10 to 20 min during pre-incubation at higher temperature. Injury was restricted to the palisade mesophyll cells, where there was an obvious change in the color of the chloroplasts. During a rapid temperature decrease, chlorophyll fluorescence monitored by a pulse amplitude modulated fluorometer diminished and did not recover even after rewarming to the initial temperature. Isolated chloroplasts were not directly affected by the rapid temperature decrease. Intracellular pH was monitored with a pH-dependent fluorescent dye. In palisade mesophyll cells damaged by rapid temperature decrease, the cytosolic pH decreased and the vacuolar membrane collapsed soon after a temperature decrease. In isolated chloroplasts, chlorophyll fluorescence declined when the pH of the medium was lowered. These results suggest that a rapid temperature decrease directly or indirectly affects the vacuolar membrane, resulting in a pH change in the cytosol that subsequently affects the chloroplasts in palisade mesophyll cells. We further confirmed that the same physiological damage occurs in other Gesneriaceae plants. These results strongly suggested that the vacuoles of palisade mesophyll cells collapsed during the initial phase of leaf injury.