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Germline genomic sequencing is increasingly integrated into pediatric cancer care, with pathogenic cancer-predisposing variants identified among 5–18% of affected children and variants of uncertain significance (VUS) in up to 70%. Given the potential medical implications for children and their families, parents' psychosocial responses to learning results are important to understand. Parents of children with cancer who learned their children's germline pathogenic or VUS results following paired tumor and germline genomic sequencing described their cognitive and affective responses to results in an open-ended write-in question after disclosure (M = 10 months post-disclosure; range = 1–28). Responses were coded and categorized using content analysis, then compared across results using chi-square and Fisher's exact test. Parents of children with pathogenic (n = 9), VUS (n = 52), and pathogenic plus VUS results (n = 9) described negative emotions, positive reactions, mixed emotions (i.e., positive and negative emotions), and neutral reactions. Negative emotions were described significantly more frequently with pathogenic results than VUS only (χ2 = 5.19; p =.02), with peace of mind and empowerment only described for those with VUS. Parents also described approach(es) to coping (e.g., faith, plan of action) and reactions specific to the uncertainty of VUS (e.g., disappointment at no explanation for cancer etiology). A subset with VUS described decreasing worry/distress with increased understanding of results, whereas others displayed misconceptions regarding VUS. Screening for emotional adjustment is warranted for parents of children with cancer receiving pathogenic germline results, and screening for understanding is warranted with VUS. Findings highlight the importance of pre-and posttest genetic counseling. [ABSTRACT FROM AUTHOR]

Purpose: In type 2 Diabetes, β-cell failure is caused by loss of cell mass, mostly by apoptosis, but also by simple dysfunction (dedifferentiation, decline of glucose-stimulated insulin secretion). Apoptosis and dysfunction are caused, at least in part, by glucotoxicity, in which increased flux of glucose in the hexosamine biosynthetic pathway plays a role. In this study, we sought to clarify whether increased hexosamine biosynthetic pathway flux affects another important aspect of β-cell physiology, that is β-cell–β-cell homotypic interactions. Methods: We used INS-1E cells and murine islets. The expression and cellular distribution of E-cadherin and β-catenin was evaluated by immunofluorescence, immunohistochemistry and western blot. Cell–cell adhesion was examined by the hanging-drop aggregation assay, islet architecture by isolation and microscopic observation. Results: E-cadherin expression was not changed by increased hexosamine biosynthetic pathway flux, however, there was a decrease of cell surface, and an increase in intracellular E-cadherin. Moreover, intracellular E-cadherin delocalized, at least in part, from the Golgi complex to the endoplasmic reticulum. Beta-catenin was found to parallel the E-cadherin redistribution, showing a dislocation from the plasmamembrane to the cytosol. These changes had as a phenotypic consequence a decreased ability of INS-1E to aggregate. Finally, in ex vivo experiments, glucosamine was able to alter islet structure and to decrease surface abundandance of E-cadherin and β-catenin. Conclusion: Increased hexosamine biosynthetic pathway flux alters E-cadherin cellular localization both in INS-1E cells and murine islets and affects cell–cell adhesion and islet morphology. These changes are likely caused by alterations of E-cadherin function, highlighting a new potential target to counteract the consequences of glucotoxicity on β-cells. [ABSTRACT FROM AUTHOR]

This paper focuses on the gut–lung axis in the context of Inflammatory Bowel Disease (IBD) and Chronic Obstructive Pulmonary Disease (COPD), highlighting the key role played by microbial dysbiosis and the impact of environmental and genetic factors on the innate and acquired immune system and on chronic inflammation in the intestinal and pulmonary tracts. Recent evidence indicates that Antigen-Presenting Cells (APCs) perform regulatory activity influencing the composition of the microbiota. APCs (macrophages, dendritic cells, B cells) possess membrane receptors known as Pattern Recognition Receptors (PRRs), a category of toll-like receptors (TLRs). PRRs recognise distinct microbial structures and microbial metabolites called Signals, which modulate the saprophytic microbial equilibrium of the healthy microbiota by recognising molecular profiles associated with commensal microbes (Microbe-Associated Molecular Patterns, MAMPs). During dysbiosis, pathogenic bacteria can prompt an inflammatory response, producing PAMPs (Pathogen-Associated Molecular Patterns) thereby activating the proliferation of inflammatory response cells, both local and systemic. This series of regulatory and immune-response events is responsible (together with chronic infection, incorrect diet, obesity, etc.) for the systemic chronic inflammation (SCI) known as "low-grade inflammation" typical of COPD and IBD. This review looks at immunological research and explores the role of the microbiota, looking at two recent clinical studies, SPIROMICS and AERIS. There is a need for further clinical studies to characterize the pulmonary microbiota and to obtain new information about the pathogenesis of lung disease to improve our knowledge and treatment strategies and identify new therapeutic targets. [ABSTRACT FROM AUTHOR]

Dedekind domains and their class groups are notions in commutative algebra that are essential in algebraic number theory. We formalized these structures and several fundamental properties, including number-theoretic finiteness results for class groups, in the Lean prover as part of the mathlib mathematical library. This paper describes the formalization process, noting the idioms we found useful in our development and mathlib's decentralized collaboration processes involved in this project. [ABSTRACT FROM AUTHOR]

Anemone-like animals belonging to the order Zoantharia are common anthozoans widely distributed from shallow to deep tropical and subtropical waters. Some species are well-known because of their high toxicity due to the presence of palytoxin (PLTX) in their tissues. PLTX is a large polyhydroxylated compound and one of the most potent toxins known. Currently, the PLTX biosynthetic pathway in zoantharians and the role of the host or the putative symbiotic organism(s) involved in this pathway are entirely unknown. To better understand the presence of PLTX in some Zoantharia, twenty-nine zoantharian colonies were analysed in this study. All zoantharian samples and their endosymbiotic dinoflagellates (Symbiodiniaceae = Zooxanthellae) were identified using DNA barcoding and phylogenetic reconstructions. Quantification of PLTX and its analogues showed that the yields contained in Palythoa heliodiscus, Palythoa aff. clavata and one potentially undescribed species of Palythoa are among the highest ever found (up to > 2 mg/g of wet zoantharian). Mass spectrometry imaging was used for the first time on Palythoa samples and revealed that in situ distribution of PLTX is mainly located in ectodermal tissues such as the epidermis of the body wall and the pharynx. Moreover, high levels of PLTX have been detected in histological regions where few or no Symbiodiniaceae cells could be observed. Finally, issues such as host‐specificity and environmental variables driving biogeographical patterns of hosted Symbiodiniaceae in zoantharian lineages were discussed in light of our phylogenetic results as well as the patterns of PLTX distribution. It was concluded that (1) the variability of Symbiodiniaceae diversity may be related to ecological divergence in Zoantharia, (2) all Palythoa species hosted Cladocopium Symbiodiniaceae (formerly clade C), (3) the sole presence of Cladocopium is not sufficient to explain the presence of high concentrations of PLTX and/or its analogues, and (4) the ability to produce high levels of PLTX and/or its analogues highlighted in some Palythoa species could be a plesiomorphic character inherited from their last common ancestor and subsequently lost in several lineages. [ABSTRACT FROM AUTHOR]

Molar incisor hypomineralization (MIH) is a highly prevalent condition associated with increased caries experience, dental pain and treatment need. Aim of this study was to determine the prevalence and severity of MIH in a group of 7–8 years old primary school children living in Rome, Italy; and to assess the association with caries experience and possible perinatal risk factors. A survey has been conducted in the city of Rome, between April 2019 and March 2020 with a total of 49 primary schools and 176 2nd grade primary school classes and a total of 3611 children being involved. Of these, a subset of 346 children of 21 primary schools was selected for the epidemiological investigation. The prevalence of MIH was of 18.2%, with girls showing twice the probability of being subject to a mild-severe condition. Molar location was present in 71.4%, while location on both molar plus incisor was present in 28.6% of cases. The mean DMFT was 0.44 ± 0.78, “D” was 0.17 ± 0.58; the mean dmft was 1.7 ± 2.56, “d” was 1.32 ± 2.21. Female gender, caries experience, insufficient oral hygiene were risk factors. The incidence of MIH is increasing in the pediatric population. Knowledge about diagnosis and treatment options should be disseminated among dental professionals. [ABSTRACT FROM AUTHOR]

We present the novel implementation of a non-differentiable metric approximation and a corresponding loss-scheduling aimed at the search for new particles of unknown mass in high energy physics experiments. We call the loss-scheduling, based on the minimisation of a figure-of-merit related function typical of particle physics, a Punzi-loss function, and the neural network that utilises this loss function a Punzi-net. We show that the Punzi-net outperforms standard multivariate analysis techniques and generalises well to mass hypotheses for which it was not trained. This is achieved by training a single classifier that provides a coherent and optimal classification of all signal hypotheses over the whole search space. Our result constitutes a complementary approach to fully differentiable analyses in particle physics. We implemented this work using PyTorch and provide users full access to a public repository containing all the codes and a training example. [ABSTRACT FROM AUTHOR]

As rock-derived primary minerals weather to form soil, they create reactive, poorly crystalline minerals that bind and store organic carbon. By implication, the abundance of primary minerals in soil might influence the abundance of poorly crystalline minerals, and hence soil organic carbon storage. However, the link between primary mineral weathering, poorly crystalline minerals, and soil carbon has not been fully tested, particularly at large spatial scales. To close this knowledge gap, we designed a model that links primary mineral weathering rates to the geographic distribution of poorly crystalline minerals across the USA, and then used this model to evaluate the effect of rock weathering on soil organic carbon. We found that poorly crystalline minerals are most abundant and most strongly correlated with organic carbon in geographically limited zones that sustain enhanced weathering rates, where humid climate and abundant primary minerals co-occur. This finding confirms that rock weathering alters soil mineralogy to enhance soil organic carbon storage at continental scales, but also indicates that the influence of active weathering on soil carbon storage is limited by low weathering rates across vast areas. [ABSTRACT FROM AUTHOR]

The complete genome sequence of the thermophilic purple sulfur bacterium Thermochromatium tepidum strain MCT (DSM 3771T) is described and contrasted with that of its mesophilic relative Allochromatium vinosum strain D (DSM 180T) and other Chromatiaceae. The Tch. tepidum genome is a single circular chromosome of 2,958,290 base pairs with no plasmids and is substantially smaller than the genome of Alc. vinosum. The Tch. tepidum genome encodes two forms of RuBisCO and contains nifHDK and several other genes encoding a molybdenum nitrogenase but lacks a gene encoding a protein that assembles the Fe–S cluster required to form a functional nitrogenase molybdenum-iron cofactor, leaving the phototroph phenotypically Nif–. Tch. tepidum contains genes necessary for oxidizing sulfide to sulfate as photosynthetic electron donor but is genetically unequipped to either oxidize thiosulfate as an electron donor or carry out assimilative sulfate reduction, both of which are physiological hallmarks of Alc. vinosum. Also unlike Alc. vinosum, Tch. tepidum is obligately phototrophic and unable to grow chemotrophically in darkness by respiration. Several genes present in the Alc. vinosum genome that are absent from the genome of Tch. tepidum likely contribute to the major physiological differences observed between these related purple sulfur bacteria that inhabit distinct ecological niches. [ABSTRACT FROM AUTHOR]

Reindeer (Rangifer tarandus) are semi-domesticated animals adapted to the challenging conditions of northern Eurasia. Adipose tissues play a crucial role in northern animals by altering gene expression in their tissues to regulate energy homoeostasis and thermogenic activity. Here, we perform transcriptome profiling by RNA sequencing of adipose tissues from three different anatomical depots: metacarpal (bone marrow), perirenal, and prescapular fat in Finnish and Even reindeer (in Sakha) during spring and winter. A total of 16,212 genes are expressed in our data. Gene expression profiles in metacarpal tissue are distinct from perirenal and prescapular adipose tissues. Notably, metacarpal adipose tissue appears to have a significant role in the regulation of the energy metabolism of reindeer in spring when their nutritional condition is poor after winter. During spring, genes associated with the immune system are upregulated in the perirenal and prescapular adipose tissue. Blood and tissue parameters reflecting general physiological and metabolic status show less seasonal variation in Even reindeer than in Finnish reindeer. This study identifies candidate genes potentially involved in immune response, fat deposition, and energy metabolism and provides new information on the mechanisms by which reindeer adapt to harsh arctic conditions. Weldenegodguad et al. performed transcriptome profiling of adipose tissues from the bone marrow, perirenal, and prescapular fat in Finnish and Even reindeer (in Sakha) during spring and winter. They identified candidate genes potentially involved in immune responses, fat deposition, and energy metabolism that provide insight into the mechanisms by which reindeer adapt to harsh arctic conditions. [ABSTRACT FROM AUTHOR]

Purpose: This feasibility study assessed if the Patient-Reported Outcomes Measurement Information System (PROMIS®) 10-item Global Health Survey (PROMIS-10) could be a reliable and valid patient-reported outcome measure (PROM) for a population of cognitively intact home health (HH) patients. Methods: The Centers for Medicare and Medicaid Services (CMS) along with their measurement contractor, Abt Associates, held a field test (2016–2017) to test the feasibility of the PROMIS-10 in in the Outcome and Assessment Information Set (OASIS). Home Health clinician data collectors (registered nurses and physical therapists) were trained to complete the PROMIS-10 along with procedures to facilitate patient self-administration of PROMIS-10. These clinicians provided feedback about their experiences at a focus group at the end of data collection. Results: 213 HH patients comprised the field test sample, 150 of whom completed PROMIS-10 surveys. Clinicians reported they found the PROMIS-10 relevant and acceptable for their HH patients, and noted the surveys provided insight into patients' views of their health. The PROMIS-10 measured the full range of patient-reported health and was sensitive to change between admission and discharge. Conclusions: The study confirmed that the PROMIS-10 can be implemented in the HH setting, opening the door for consideration for implementing the PROMIS-10 in post-acute care (PAC) settings. This study is a first step toward establishing an assessment that captures the patient's voice and could be reported by the CMS PAC quality reporting programs. [ABSTRACT FROM AUTHOR]

Curcumin is a compound found in the rhizome of Curcuma longa (turmeric) with a large repertoire of pharmacological properties, including anti-inflammatory and neuroprotective activities. The current study aims to assess the effects of this natural compound on oligodendrocyte progenitor (OP) differentiation, particularly in inflammatory conditions. We found that curcumin can promote the differentiation of OPs and to counteract the maturation arrest of OPs induced by TNF-α by a mechanism involving PPAR-γ (peroxisome proliferator activated receptor), a ligand-activated transcription factor with neuroprotective and anti-inflammatory capabilities. Furthermore, curcumin induces the phosphorylation of the protein kinase ERK1/2 known to regulate the transition from OPs to immature oligodendrocytes (OLs), by a mechanism only partially dependent on PPAR-γ. Curcumin is also able to raise the levels of the co-factor PGC1-α and of the cytochrome c oxidase core protein COX1, even when OPs are exposed to TNF-α, through a PPAR-γ-mediated mechanism, in line with the known ability of PPAR-γ to promote mitochondrial integrity and functions, which are crucial for OL differentiation to occur. Altogether, this study provides evidence for a further mechanism of action of curcumin besides its well-known anti-inflammatory properties and supports the suggested therapeutic potential of this nutraceutical in demyelinating diseases. [ABSTRACT FROM AUTHOR]

Since its inception in 2012, CRISPR-Cas technologies have taken the life science community by storm. Maize genetics research is no exception. Investigators around the world have adapted CRISPR tools to advance maize genetics research in many ways. The principle application has been targeted mutagenesis to confirm candidate genes identified using map-based methods. Researchers are also developing tools to more effectively apply CRISPR-Cas technologies to maize because successful application of CRISPR-Cas relies on target gene identification, guide RNA development, vector design and construction, CRISPR-Cas reagent delivery to maize tissues, and plant characterization, each contributing unique challenges to CRISPR-Cas efficacy. Recent advances continue to chip away at major barriers that prevent more widespread use of CRISPR-Cas technologies in maize, including germplasm-independent delivery of CRISPR-Cas reagents and production of high-resolution genomic data in relevant germplasm to facilitate CRISPR-Cas experimental design. This has led to the development of novel breeding tools to advance maize genetics and demonstrations of how CRISPR-Cas technologies might be used to enhance maize germplasm. [ABSTRACT FROM AUTHOR]

Introduction: Age, gender, body mass index percentiles and the adherence to Mediterranean diet were investigated as potential predictor factors in this assessment. Aim: To assess the parental perception of children's weight status. Methods: This cross-sectional observational study was carried out during a corporate wellness program (Ferrari Formula Benessere) implemented by Ferrari S.p.A. and managed by Med-Ex s.r.l. The children's real weight status was assessed through Body Mass Index percentiles (ArthroPlus software—WHO). Results: 328 children (66.4%) were normal-weight, 10 were underweight (2%), 66 were overweight (13.4%) and 90 were obese (18.2%). 289 children (59%) were classified correctly by parents, while 205 children (41%) were not. 64 of 66 overweight children and 90 of 90 children with obesity have been completely underestimated (53 of 90 children with obesity were judged normal weight). The parents' probability to estimate children's weight status correctly decreased increasing body mass index percentiles paradoxically [OR = 0.96 (0.95–0.97)] and was lower in boys [OR = 0.65 (0.44–0.98)]. Although not statistically significant, children with higher adherence to Mediterranean diet seems to have higher probability to be correctly estimated [low adherence: reference, medium adherence: OR = 1.06 (0.61–1.85), high adherence: OR = 1.48 (0.81–2.75)]. Conclusions: A high percentage of children is overweight or obese and almost half of parents classified their weight status incorrectly. Increasing children's body mass index percentiles decreases the probability to be correctly classified. [ABSTRACT FROM AUTHOR]

Purpose: To quantify total sweat electrolyte losses at two relative exercise intensities and determine the effect of workload on the relation between regional (REG) and whole body (WB) sweat electrolyte concentrations.Methods: Eleven recreational athletes (7 men, 4 women; 71.5 ± 8.4 kg) completed two randomized trials cycling (30 °C, 44% rh) for 90 min at 45% (LOW) and 65% (MOD) of VO2max in a plastic isolation chamber to determine WB sweat [Na+] and [Cl-] using the washdown technique. REG sweat [Na+] and [Cl-] were measured at 11 REG sites using absorbent patches. Total sweat electrolyte losses were the product of WB sweat loss (WBSL) and WB sweat electrolyte concentrations.Results: WBSL (0.86 ± 0.15 vs. 1.27 ± 0.24 L), WB sweat [Na+] (32.6 ± 14.3 vs. 52.7 ± 14.6 mmol/L), WB sweat [Cl-] (29.8 ± 13.6 vs. 52.5 ± 15.6 mmol/L), total sweat Na+ loss (659 ± 340 vs. 1565 ± 590 mg), and total sweat Cl- loss (931 ± 494 vs. 2378 ± 853 mg) increased significantly (p < 0.05) from LOW to MOD. REG sweat [Na+] and [Cl-] increased from LOW to MOD at all sites except thigh and calf. Intensity had a significant effect on the regression model predicting WB from REG at the ventral wrist, lower back, thigh, and calf for sweat [Na+] and [Cl-].Conclusion: Total sweat Na+ and Cl- losses increased by ~ 150% with increased exercise intensity. Regression equations can be used to predict WB sweat [Na+] and [Cl-] from some REG sites (e.g., dorsal forearm) irrespective of intensity (between 45 and 65% VO2max), but other sites (especially ventral wrist, lower back, thigh, and calf) require separate prediction equations accounting for workload. [ABSTRACT FROM AUTHOR]

In this study, the effects of Radio Electric Asymmetric Conveyer (REAC), a non-invasive physical treatment, on neuroinflammatory responses in a mouse model of parkinsonism induced by intoxication with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), were investigated in vivo. We found that the REAC tissue optimization treatment specific for neuro-regenerative purposes (REAC TO-RGN-N) attenuated the inflammatory picture evoked by MPTP-induced nigro-striatal damage in mice, decreasing the levels of pro-inflammatory molecules and increasing anti-inflammatory mediators. Besides, there was a significant reduction of both astrocyte and microglial activation in MPTP-treated mice exposed to REAC TO-RGN-N. These results indicated that REAC TO-RGN-N treatment modulates the pro-inflammatory responses and reduces neuronal damage in MPTP-induced parkinsonism. [ABSTRACT FROM AUTHOR]

Team sport athletes face a variety of nutritional challenges related to recovery during the competitive season. The purpose of this article is to review nutrition strategies related to muscle regeneration, glycogen restoration, fatigue, physical and immune health, and preparation for subsequent training bouts and competitions. Given the limited opportunities to recover between training bouts and games throughout the competitive season, athletes must be deliberate in their recovery strategy. Foundational components of recovery related to protein, carbohydrates, and fluid have been extensively reviewed and accepted. Micronutrients and supplements that may be efficacious for promoting recovery include vitamin D, omega-3 polyunsaturated fatty acids, creatine, collagen/vitamin C, and antioxidants. Curcumin and bromelain may also provide a recovery benefit during the competitive season but future research is warranted prior to incorporating supplemental dosages into the athlete's diet. Air travel poses nutritional challenges related to nutrient timing and quality. Incorporating strategies to consume efficacious micronutrients and ingredients is necessary to support athlete recovery in season. [ABSTRACT FROM AUTHOR]

Sweat losses in team sports can be significant due to repeated bursts of high-intensity activity, as well as the large body size of athletes, equipment and uniform requirements, and environmental heat stress often present during training and competition. In this paper we aimed to: (1) describe sweat losses and fluid balance changes reported in team sport athletes, (2) review the literature assessing the impact of hypohydration on cognitive, technical, and physical performance in sports-specific studies, (3) briefly review the potential mechanisms by which hypohydration may impact team sport performance, and (4) discuss considerations for future directions. Significant hypohydration (mean body mass loss (BML) >2%) has been reported most consistently in soccer. Although American Football, rugby, basketball, tennis, and ice hockey have reported high sweating rates, fluid balance disturbances have generally been mild (mean BML <2%), suggesting that drinking opportunities were sufficient for most athletes to offset significant fluid losses. The effect of hydration status on team sport performance has been studied mostly in soccer, basketball, cricket, and baseball, with mixed results. Hypohydration typically impaired performance at higher levels of BML (3-4%) and when the method of dehydration involved heat stress. Increased subjective ratings of fatigue and perceived exertion consistently accompanied hypohydration and could explain, in part, the performance impairments reported in some studies. More research is needed to develop valid, reliable, and sensitive sport-specific protocols and should be used in future studies to determine the effects of hypohydration and modifying factors (e.g., age, sex, athlete caliber) on team sport performance. [ABSTRACT FROM AUTHOR]

Objectives In many sub-Saharan African countries, the use of long-acting reversible contraceptives (LARCs) is low while unmet need for family planning (FP) remains high. We evaluated the effectiveness of a LARC access expansion initiative in reaching young, less educated, poor, and rural women. Methods Starting in 2008, Marie Stopes International (MSI) has implemented a cross-country expansion intervention to increase access to LARCs through static clinics, mobile outreach units, and social franchising of private sector providers. We analyzed routine service statistics for 2008-2014 and 2014 client exit interview data. Indicators of effectiveness were the number of LARCs provided and the percentages of LARC clients who had not used a modern contraceptive in the last 3 months ('adopters'); switched from a short-term contraceptive to a LARC ('switchers'); were aged <25; lived in extreme poverty; had not completed primary school; lived in rural areas; and reported satisfaction with their overall experience at the facility/site. Results Our annual LARC service distribution increased 1037 % (from 149,881 to over 1.7 million) over 2008-2014. Of 3816 LARC clients interviewed, 46 % were adopters and 46 % switchers; 37 % were aged 15-24, 42 % had not completed primary education, and 56 % lived in a rural location. Satisfaction with services received was rated 4.46 out of 5. Conclusions The effectiveness of the LARC expansion in these 14 sub-Saharan African FP programs demonstrates vast untapped potential for wider use of LARC methods, and suggests that this service delivery model is a plausible way to support FP 2020 goals of reaching those with an unmet need for FP. [ABSTRACT FROM AUTHOR]

Microglia-mediated neuroinflammation has been described as a common hallmark of Parkinson's disease (PD) and is believed to further exacerbate the progressive degeneration of dopaminergic neurons. Current therapies are unable to prevent the disease progression. A significant association has been demonstrated between PD and low levels of vitamin D in patients serum, and vitamin D supplement appears to have a beneficial clinical effect. Herein, we investigated whether vitamin D administered orally in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced preclinical animal model of PD protects against glia-mediated inflammation and nigrostriatal neurodegeneration. Vitamin D significantly attenuated the MPTP-induced loss of tyrosine hydrlase (TH)-positive neuronal cells, microglial cell activation (Iba1-immunoreactive), inducible nitric oxide synthase (iNOS) and TLR-4 expression, typical hallmarks of the pro-inflammatory (M1) activation of microglia. Additionally, Vitamin D was able to decrease pro-inflammatory cytokines mRNA expression in distinct brain areas of the MPTP mouse. Importantly, we also assessed the anti-inflammatory property of vitamin D in the MPTP mouse, in which it upregulated the anti-inflammatory cytokines (IL-10, IL-4 and TGF-β) mRNA expression as well as increasing the expression of CD163, CD206 and CD204, typical hallmarks of alternative activation of microglia for anti-inflammatory signalling (M2). Collectively, these results demonstrate that vitamin D exhibits substantial neuroprotective effects in this PD animal model, by attenuating pro-inflammatory and up-regulating anti-inflammatory processes. [ABSTRACT FROM AUTHOR]

Sexual reproduction in flowering plants involves double fertilization, the union of two sperm from pollen with two sex cells in the female embryo sac. Modern plant breeders increasingly seek to circumvent this process to produce doubled haploid individuals, which derive from the chromosome-doubled cells of the haploid gametophyte. Doubled haploid production fixes recombinant haploid genomes in inbred lines, shaving years off the breeding process. Costly, genotype-dependent tissue culture methods are used in many crops, while seed-based in vivo doubled haploid systems are rare in nature and difficult to manage in breeding programmes. The multi-billion-dollar maize hybrid seed business, however, is supported by industrial doubled haploid pipelines using intraspecific crosses to in vivo haploid inducer males derived from Stock 6, first reported in 1959 (ref. 5), followed by colchicine treatment. Despite decades of use, the mode of action remains controversial. Here we establish, through fine mapping, genome sequencing, genetic complementation, and gene editing, that haploid induction in maize (Zea mays) is triggered by a frame-shift mutation in MATRILINEAL (MTL), a pollen-specific phospholipase, and that novel edits in MTL lead to a 6.7% haploid induction rate (the percentage of haploid progeny versus total progeny). Wild-type MTL protein localizes exclusively to sperm cytoplasm, and pollen RNA-sequence profiling identifies a suite of pollen-specific genes overexpressed during haploid induction, some of which may mediate the formation of haploid seed. These findings highlight the importance of male gamete cytoplasmic components to reproductive success and male genome transmittance. Given the conservation of MTL in the cereals, this discovery may enable development of in vivo haploid induction systems to accelerate breeding in crop plants. [ABSTRACT FROM AUTHOR]

The Enterobacteriaceae are a family of Gram-negative bacteria that include commensal organisms as well as primary and opportunistic pathogens that are among the leading causes of morbidity and mortality worldwide. Although Enterobacteriaceae often comprise less than 1% of a healthy intestine's microbiota, some of these organisms can bloom in the inflamed gut; expansion of enterobacteria is a hallmark of microbial imbalance known as dysbiosis. Microcins are small secreted proteins that possess antimicrobial activity in vitro, but whose role in vivo has been unclear. Here we demonstrate that microcins enable the probiotic bacterium Escherichia coli Nissle 1917 (EcN) to limit the expansion of competing Enterobacteriaceae (including pathogens and pathobionts) during intestinal inflammation. Microcin-producing EcN limits the growth of competitors in the inflamed intestine, including commensal E. coli, adherent-invasive E. coli and the related pathogen Salmonella enterica. Moreover, only therapeutic administration of the wild-type, microcin-producing EcN to mice previously infected with S. enterica substantially reduced intestinal colonization by the pathogen. Our work provides the first evidence that microcins mediate inter- and intraspecies competition among the Enterobacteriaceae in the inflamed gut. Moreover, we show that microcins can act as narrow-spectrum therapeutics to inhibit enteric pathogens and reduce enterobacterial blooms. [ABSTRACT FROM AUTHOR]

Among the chemical elements and chemical compounds that promote life and its evolution on the earth, there are some which have toxic effects on plant life, animals and human beings. A lot of the chemicals released follow more or less complex cycles of different duration, during the course of which they are transported and disseminated, by means of various interactions, throughout the environment, including the biosphere. Natural processes ascribable to magmatism form a powerful system that discharge a large amount of substances which can contaminate waters and soils, even though there are generally only trace elements. In this paper, some of the main contamination processes linked to magmatism, such as the hydrothermalism of black and white smokers at the bottom of oceans, are described, as are other examples in the Mediterranean area and Italy, including volcanic ash deposition, CO soil saturation and emission of radioactive radon. Furthermore, their toxic effects on the population are also highlighted, bearing in mind their implications and relevance in planning the use and management of both the soils and waters of a given area. [ABSTRACT FROM AUTHOR]

Maize, the highest-yielding cereal crop worldwide, is particularly susceptible to drought during its 2- to 3-week flowering period. Many genetic engineering strategies for drought tolerance impinge on plant development, reduce maximum yield potential or do not translate from laboratory conditions to the field. We overexpressed a gene encoding a rice trehalose-6-phosphate phosphatase (TPP) in developing maize ears using a floral promoter. This reduced the concentration of trehalose-6-phosphate (T6P), a sugar signal that regulates growth and development, and increased the concentration of sucrose in ear spikelets. Overexpression of TPP increased both kernel set and harvest index. Field data at several sites and over multiple seasons showed that the engineered trait improved yields from 9% to 49% under non-drought or mild drought conditions, and from 31% to 123% under more severe drought conditions, relative to yields from nontransgenic controls. [ABSTRACT FROM AUTHOR]

Purpose: To determine if tear fluid osmolarity (T) can track changes in hydration status during exercise and post-exercise rehydration. Methods: Nineteen male athletes (18-37 years, 74.6 ± 7.9 kg) completed two randomized, counterbalanced trials; cycling (~95 min) with water intake to replace fluid losses or water restriction to progressively dehydrate to 3 % body mass loss (BML). After exercise, subjects drank water to maintain body mass (water intake trials) or progressively rehydrate to pre-exercise body mass (water restriction trials) over a 90-min recovery period. Plasma osmolality (P) and T measurements (mean of right and left eyes) were taken pre-exercise, during rest periods between exercise bouts corresponding to 1, 2, and 3 % BML, and rehydration at 2, 1, and 0 % BML. Results: During exercise mean (± SD) T was significantly higher in water restriction vs. water intake trials at 1 % BML (299 ± 9 vs. 293 ± 9 mmol/L), 2 % BML (301 ± 9 vs. 294 ± 9 mmol/L), and 3 % BML (302 ± 9 vs. 292 ± 8 mmol/L). Mean T progressively decreased during post-exercise rehydration and was not different between trials at 1 % BML (291 ± 8 vs. 290 ± 7 mmol/L) and 0 % BML (288 ± 7 vs. 289 ± 8 mmol/L). Mean T tracked changes in hydration status similar to that of mean P; however, the individual responses in T to water restriction and water intake was considerably more variable than that of P. Conclusion: T is a valid indicator of changes in hydration status when looking at the group mean; however, large differences among subjects in the T response to hydration changes limit its validity for individual recommendations. [ABSTRACT FROM AUTHOR]

This paper discusses the extent to which sociodemographic characteristics of consumers and their past consumption are less effective in explaining the decision of purchasing a cultural good than the characteristics of the product itself, which allow for imitative behaviors and are at the basis of distinction. While the former approaches are well documented in the literature, the latter refers to Bourdieu's idea of objectified cultural capital, which has been revisited and empirically explored. Because the various causal effects interact with each other, this paper tests a theoretical model which matches individual characteristics of the consumer with the properties of the cultural product. Specifically, we discussed the emergence of a new version of a cultural good, which is able to broaden the dimension of the market by gaining rapid success in its audience. This diffusion pattern is a quite rare event, but disruptive for the market and extremely profitable for the producer. The authors label this occurrence a disruptive cultural fad and try to understand the determinants of its adoption. The hypotheses of the model are tested on a unique dataset of microdata of purchasing transactions in Milan in the early nineteenth century, when the music by Gioachino Rossini emerged as a disruptive cultural fad at the dawn of the music industry. Results show that key features of a successful disruptive cultural fad are the role of some specific patterns of personal past consumption, the capabilities of generating positive network externalities in the consumption, and, surprisingly, the lack of negative ones due to any possible hip or snob effect. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnea syndrome (OSAS) is an independent risk factor for atherosclerosis and arterial thrombosis, which are associated with high cardiovascular (CV) morbidity and mortality. In studies performed in clinical populations with elevated CV event risk profiles, the occurrence of moderate to severe OSAS was very often accompanied by a worsened vascular function and increased prevalence of structural abnormalities. Recent investigations of atherosclerosis in OSAS have focused on thrombotic tendency and blood viscosity, providing new insight into mechanisms of the disease. Despite that knowledge about the mechanisms of development of CV disease in patients with OSAS is still incomplete, observations confirm a relationship between sleep-disordered breathing and the rheological properties (flow properties) of blood. While platelet dysfunction and hypercoagulability (PDMPs, PaI-1, and SF) play important roles in the pathogenesis of vascular disease, there are limited studies on the potential role of blood viscosity in the development of vascular disease in OSAS. [ABSTRACT FROM AUTHOR]

Let S be the amalgamated free product of two finite inverse semigroups. We prove that the Schützenberger graph of an element of S with respect to a standard presentation of S is a context-free graph in the sense of Müller and Schupp (Theor. Comput. Sci. 37:51-75, ), showing that the language L recognized by the Schützenberger automaton is context-free. Moreover we construct the grammar generating L proving that L is a deterministic context-free language and we use this fact for solving some algorithmic problems. [ABSTRACT FROM AUTHOR]

Spintronics has shown a remarkable and rapid development, for example from the initial discovery of giant magnetoresistance in spin valves to their ubiquity in hard-disk read heads in a relatively short time. However, the ability to fully harness electron spin as another degree of freedom in semiconductor devices has been slower to take off. One future avenue that may expand the spintronic technology base is to take advantage of the flexibility intrinsic to organic semiconductors (OSCs), where it is possible to engineer and control their electronic properties and tailor them to obtain new device concepts. Here we show that we can control the spin polarization of extracted charge carriers from an OSC by the inclusion of a thin interfacial layer of polar material. The electric dipole moment brought about by this layer shifts the OSC highest occupied molecular orbital with respect to the Fermi energy of the ferromagnetic contact. This approach allows us full control of the spin band appropriate for charge-carrier extraction, opening up new spintronic device concepts for future exploitation. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the time course of body weight, daytime sleepiness, and functional cardiorespiratory parameters in patients with both chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea syndrome (OSA), after institution of domiciliary nasal continuous positive airway pressure (nCPAP). Twelve consecutive obese outpatients (mean age = 61 ± 11 years; four women) were evaluated before (baseline) and after 3, 12, and 24 months of nocturnal nCPAP (4 h per night). At baseline, all patients were hypercapnic and hypoxemic, suffering from night desaturation ( T90 is the percentage of total recording time (TRT) spent with SaO2 ≤ 90% = 38 ± 2%) and sleepy (Epworth sleepiness scale [ESS] = 16.58 ± 0.86). Three months after the implementation of nCPAP, daytime PaCO2 and PaO2 improved up to 45.1 ± 0.9 and 69.0 ± 1 mmHg, respectively; mean pulmonary artery pressure (MPAP) decreased from 24.7 ± 1.1 to 19.2 ± 04 mmHg. All other variables showed progressive improvements up to 12 months. At 3 and 12 months, mean body mass index was slightly decreased (to 31.6 ± 0.2 and 30.7 ± 0.1 kg/m2, respectively); daytime sleepiness, nocturnal O2 desaturation, and maximal inspiratory pressure were also improved and thereafter remained stable. In conclusion, in our patients with both severe OSA and mild-to-moderate COPD, arterial blood gasses and MPAP improved and stabilized after 3 months of nCPAP therapy, with the greatest improvements being in ESS score, T90, and maximal inspiratory force from 3 up to 12 months; these parameters remained stable over the following 12 months. Finally, our data support early treatment with nCPAP in such patients. [ABSTRACT FROM AUTHOR]

Abstract.  D. M. Riley proved in [3] that, if A and B are either Lie nilpotent or Lie metabelian algebras, then their tensor product A ⊗ B is Lie soluble and obtained bounds on the Lie derived length of A ⊗ B. The aim of the present note is to improve Riley’s bounds; moreover we consider also the cases in which A and B are either strongly Lie soluble or strongly Lie nilpotent algebras. [ABSTRACT FROM AUTHOR]

This paper describes an innovative integrated micro flow cytometer that presents a new arrangement for the excitation/detection system. The sample liquid, containing the fluorescent marked particles/cells under analysis, is hydrodynamically squeezed into a narrow stream by two sheath flows so that the particles/cells flow individually through a detection region. The detection of the particles/cells emitted fluorescence is carried out by using a collection fiber placed orthogonally to the flow. The device is based on silicon hollow core antiresonant reflecting optical waveguides (ARROWs). ARROW geometry allows one to use the same channel to guide both the sample stream and the fluorescence excitation light, leading to a simplification of the optical configuration and to an increase of the signal-to-noise ratio. The integrated micro flow cytometer has been characterized by using biological samples marked with standard fluorochromes. The experimental investigation confirms the success of the proposed microdevice in the detection of cells. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Brain-resident macrophages (microglia) are key cellular elements in the preservation of tissue integrity. On the other hand, they can also contribute to the development of pathological events by causing an extensive and inappropriate inflammatory response. A growing number of reports indicate the involvement of nucleotides in the control of microglial functions. With this study on P2Y receptors in rat microglia, we want to contribute to the definition of their expression profile and to the characterisation of their signalling mechanisms leading to Ca2+ movements. Endogenous nucleotides, when applied at a concentration of 100 μM, elicited robust Ca2+ transients, thanks to a panel of metabotropic receptors comprising mainly P2Y2, P2Y6 and P2Y12 subtypes. The involvement of P2Y12 receptors in Ca2+ responses induced by adenine nucleotides was confirmed by the pharmacological and pertussis toxin sensitivity of the response induced by adenosine diphosphate (ADP). Beside the G protein involved, Gi and Gq respectively, adenine and uracil nucleotides differed also for induction by the latter of a capacitative Ca2+ plateau. Moreover, when applied at low (sub-micromolar) concentrations with a long-lasting challenge, uracil nucleotides elicited oscillatory Ca2+ changes with low frequency of occurrence (≤ 1 min−), sometimes superimposed to an extracellular Ca2+-dependent sustained Ca2+ rise. We conclude that different patterns of Ca2+ transients are induced by low (i.e., oscillatory Ca2+ activity) compared to high (i.e., fast release followed by sustained raise) concentrations of nucleotides, which can suggest different roles played by receptor stimulation depending not only on the type but also on the concentration of nucleotides. [ABSTRACT FROM AUTHOR]

Rationale: The effects of antidepressant (AD) drugs on sleep in depressed patients and their relationship to AD response have been investigated previously. However, newer AD agents, which appear to have different effects on sleep, have not been evaluated systematically for their usefulness in predicting treatment response. Objectives: To examine the effect of bupropion sustained release (SR) (Wellbutrin SR) on sleep macroarchitecture, and to assess whether the observed electroencephalographic (EEG) sleep changes in response to a single dose of bupropion are associated with treatment response to the AD. Methods: Twenty patients with unipolar major depressive disorder received EEG sleep assessments prior to treatment. Subjects were studied twice for 2 consecutive nights, with each 2-night session approximately 1 week apart. Baseline EEG sleep and the EEG sleep responses to placebo (baseline sleep) and a single dose of bupropion SR (150 mg, PO) were measured using a randomized, double-blind, crossover design. The participants then received open-label treatment with bupropion SR for about 8 weeks. Results: No relationship was observed between baseline EEG sleep measures and response to treatment with bupropion. However, a statistically significant relationship was found between latency to the onset of rapid eye movement (REM) sleep following a single dose of bupropion and clinical response to treatment with bupropion. Responders showed an increase in REM latency following bupropion challenge, whereas non-responders showed a decrease. Moreover, the REM latency change in response to bupropion challenge correlated with change in depression ratings as a result of treatment. Conclusions: These findings suggest that bupropion's effect on REM latency and its AD action might be linked, possibly via dopamine (D[sub 2]) receptor-mediated effects, or by noradrenergic mechanism(s). [ABSTRACT FROM AUTHOR]

Abstract Rationale: Ethnicity can affect the pharmacokinetics and pharmacodynamics of psychopharmacologic drugs. Objectives: Reboxetine disposition differences among Asians, blacks, and Caucasians were examined. Methods: Healthy subjects (12 Asians, 12 blacks, 12 Caucasians) received a single oral dose of one 4-mg reboxetine tablet in an open label, parallel study design. Plasma concentrations of reboxetine enantiomers [R,R(-) reboxetine and predominantly active S,S(+) reboxetine] were quantified using HPLC-MS-MS. Plasma unbound fractions of reboxetine enantiomers were evaluated by equilibrium dialysis. Ethnic group effects on pharmacokinetic parameters were assessed by ANOVA. Results: Mean S,S(+) reboxetine CLPO for blacks was significantly greater, compared to Asians and Caucasians (154+/-82 ml/min, 101+/-19 ml/min and 101+/-18 ml/min, respectively). Mean S,S(+) reboxetine free fractions (fu) were significantly greater for Asians and blacks, compared to Caucasians (3.04+/-1.28%, 2.89+/-0.69%, and 1.99+/-0.58%, respectively). S,S(+) Reboxetine unbound clearance (CLu) was significantly less for Asians, compared to blacks and Caucasians (3742+/-1468 ml/min, 5187+/-2027 ml/min, and 5294+/-1163 ml/min, respectively). S,S(+) Reboxetine mean unbound AUC (AUCu) in these groups were 20.2+/-7.1 ng.h/ml, 14.6+/-5.1 ng.h/ml, and 13.2+/-3.2 ng.h/ml, respectively. AUCu was significantly greater for Asians. CLu and AUCu did not differ significantly between blacks and Caucasians. Ethnic effects of R,R(-) reboxetine were similar to those observed for S,S(+) reboxetine. Conclusions: The AUCu difference between Asian and black and Caucasian subjects was modest. Tolerability differences among groups were not observed. No dosage adjustment is necessary for Asians or blacks. [ABSTRACT FROM AUTHOR]

The compounds 4,4′-bipyridinium(2+) pentachloro-bismuthate(III) ( 1), [4,4′-(C10H8N2)BiCl5] and 2,2′-bipyridinium(2+) pentachloro-bismuthate(III) ( 2), [2,2′-(C10H8N2)Bi2Cl10] have been obtained by reacting bismuthate oxide and 4,4′-bipyridine or 2,2′-bipyridine in HCl acid medium. They have been characterized by single crystal X-ray analysis. ( 1) crystallizes in the triclinic space group $$P\bar 1$$ with a = 9.776(2), b = 11.009(3), c = 8.346(1) Å, α = 101.58(2), β = 98.63(2), and γ = 112.86(2)°. ( 2) crystallizes in the monoclinic space group P21/ c with a = 14.239(2), b = 14.226(2), c = 16.275(3) Å, and β = 110.15(2)°. The crystal structure of ( 1) consists of 4,4′-bipyridinium(2+) cations interacting through hydrogen bonding with [Bi2Cl10]2− dimers giving rise to endless double chains, while that of ( 2) is formed by 2,2′-bipyridinium(2+) cations and [Bi4Cl20]8− tetramers extensively interacting through hydrogen bonding. The different polynuclearity of the anions seems related to the different directions along which each cation can form hydrogen bond interactions. [ABSTRACT FROM AUTHOR]

A modified protocol for differential display of mRNA was used to identify and clone genes expressed in developing Arabidopsis thaliana seeds. Two novel embryo-specific genes designated ATS1 and ATS3 (Arabidopsis thaliana seed gene) were identified. In situ hybridization showed that, spatially, ATS1 is expressed in a pattern similar to the Arabidopsis GEA1 gene and that ATS3 is expressed in a pattern similar to the Arabidopsis seed storage protein genes. Southern analysis of Arabidopsis genomic DNA indicated that ATS1 is a member of a small gene family and that ATS3 is present as a single copy in the diploid genome. Sequence analysis of both genes showed that ATS1 is similar to the rice EFA27 gene and that ATS3 is unique. Western analysis and light level immunocytochemistry using antisera raised against the putative ATS1 and ATS3 translation products verified that ATS1 and ATS3 proteins are seed-specific and accumulate in a spatial pattern similar to their respective transcripts. Taken together, these data show that ATS1 and ATS3 are novel embryo-specific genes in Arabidopsis. [ABSTRACT FROM AUTHOR]

Limited emphasis has been given to the molecular study of apomixis, an asexual method of reproduction where seeds are produced without fertilization. Most buffelgrass ( Pennisetum ciliare (L.) Link syn = Cenchrus ciliaris L.) genotypes reproduce by obligate apomixis (apospory); however, rare sexual plants have been recovered. A modified differential display procedure was used to compare gene expression in unpollinated ovaries containing ovules with either sexual or apomictic female gametophytes. The modification incorporated end-labeled poly(A) anchored primers as the only isotopic source, and was a reliable and consistent approach for detecting differentially displayed transcripts. Using 20 different decamers and two anchor primers, 2268 cDNA fragments between 200 and 600 bp were displayed. From these, eight reproducible differentially displayed cDNAs were identified and cloned. Based on northern analysis, one cDNA was detected in only the sexual ovaries, two cDNAs in only apomictic ovaries and one cDNA was present in both types of ovaries. Three fragments could not be detected and one fragment was detected in ovaries, stems, and leaves. Comparison of gene expression during sexual and apomictic development in buffelgrass represents a new model system and a strategy for investigating female reproductive development in the angiosperms. [ABSTRACT FROM AUTHOR]

The enzyme Δ-desaturase is responsible for the conversion of linoleic acid (18:2) to γ-linolenic acid (18:3γ). A cyanobacterial gene encoding Δ-desaturase was cloned by expression of a Synechocystis genomic cosmid library in Anabaena, a cyanobacterium lacking Δ-desaturase. Expression of the Synechocystis Δ-desaturase gene in Anabaena resulted in the accumulation of γ-linolenic acid (GLA) and octadecatetraenoic acid (18:4). The predicted 359 amino acid sequence of the Synechocystis Δ-desaturase shares limited, but significant, sequence similarity with two other reported desaturases. Analysis of three overlapping cosmids revealed a Δ-desaturase gene linked to the Δ-desaturase gene. Expression of Synechocystis Δ-and Δ-desaturase in Synechococcus, a cyanobacterium deficient in both desaturases, resulted in the production of linoleic acid and γ-linolenic acid. [ABSTRACT FROM AUTHOR]

Abstract The pharmacokinetics and pharmacodynamics of adinazolam and N-demethyladinazolam (NDMAD), its major active metabolite, were compared in 39 healthy male volunteers (13 Asian, 12 Caucasian and 14 African-American). In a four-way, double-blind crossover design, subjects were administered (1) 30 mg oral adinazolam mesylate SR tablets, (2) 10 mg parenteral (IV) adinazolam mesylate, (3) 30 mg IV NDMAD and (4) placebo. Venous blood samples were collected at specific time intervals after drug administration and assayed for adinazolam and NDMAD concentrations. Sedation was rated at the time of each blood draw according to the Nurse-Rated Sedation Scale, and the digit-symbol substitution test was administered to evaluate psychomotor performance. After IV administration of adinazolam, Asians manifested significantly higher C[sub max], larger AUC and lower CL of both adinazolam and NDMAD than their Caucasian and African-American counterparts. Likewise, after IV NDMAD Asians had significantly higher NDMAD C[sub max] and AUC than Caucasians and African-Americans. Most of these differences remained statistically significant after controlling for body surface area. With PO adinazolam, Asians also manifested substantially higher C[sub max], larger AUC and lower CL for both adinazolam and NDMAD; however, with the exception of C[sub max], these differences did not reach statistical significance. These results are in accordance with previous observations for ethnic-related differences in drug pharmacokinetics. In contrast, pharmacodynamic differences were not noted among the three study groups. [ABSTRACT FROM AUTHOR]

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