Miracle-dz/UniFAR-FTUs huggingface dataset:
Temperature Modulates Coccolithophorid Sensitivity of Growth, Photosynthesis and Calcification to Increasing Seawater pCO2

Increasing atmospheric CO2 concentrations are expected to impact pelagic ecosystem functioning in the near future by driving ocean warming and acidification. While numerous studies have investigated impacts of rising temperature and seawater acidification on planktonic organisms separately, little is presently known on their combined effects. To test for possible synergistic effects we exposed two coccolithophore species, Emiliania huxleyi and Gephyrocapsa oceanica, to a CO2 gradient ranging from ∼0.5–250 µmol kg−1 (i.e. ∼20–6000 µatm pCO2) at three different temperatures (i.e. 10, 15, 20°C for E. huxleyi and 15, 20, 25°C for G. oceanica). Both species showed CO2-dependent optimum-curve responses for growth, photosynthesis and calcification rates at all temperatures. Increased temperature generally enhanced growth and production rates and modified sensitivities of metabolic processes to increasing CO2. CO2 optimum concentrations for growth, calcification, and organic carbon fixation rates were only marginally influenced from low to intermediate temperatures. However, there was a clear optimum shift towards higher CO2 concentrations from intermediate to high temperatures in both species. Our results demonstrate that the CO2 concentration where optimum growth, calcification and carbon fixation rates occur is modulated by temperature. Thus, the response of a coccolithophore strain to ocean acidification at a given temperature can be negative, neutral or positive depending on that strain's temperature optimum. This emphasizes that the cellular responses of coccolithophores to ocean acidification can only be judged accurately when interpreted in the proper eco-physiological context of a given strain or species. Addressing the synergistic effects of changing carbonate chemistry and temperature is an essential step when assessing the success of coccolithophores in the future ocean.
Molecular dynamic modeling of CYP51B in complex with azole inhibitors

Cytochrome P450 14α-sterol demethylase (CYP51), the key enzyme in sterol biosynthesis pathway, is an important target protein of cholesterol-lowering agents, antifungal drugs, and herbicides. CYP51B enzyme is one of the CYP51 family members. In the present study, we have chosen four representative inhibitors of CYP51B: diniconazole (Din), fluconazole (Flu), tebuconazole (Teb), and voriconazole (Vor), and launched to investigate the binding features of CYP51B-inhibitor and gating characteristics via molecular docking and molecular dynamics (MD) simulations. The results show that the ranking of binding affinities among these inhibitors is Din > Teb > Vor > Flu. Din shows the strongest binding affinity, whereas Flu shows the weakest binding affinity. More importantly, based on the calculated binding free energy results, we hypothesize that the nonpolar interactions are the most important contributors, and three key residues (Thr77, Ala258, and Lys454) play crucial role in protein-inhibitor binding. Besides, residue Phe180 may play a molecular switch role in the process of the CYP51B-Teb and CYP51B-Vor binding. Additionally, Tunnel analysis results show that the major tunnel of Din, Flu, and Teb is located between helix K, FG loop, and β4 hairpin (Tunnel II). The top ranked possible tunnel (Tunnel II) corresponds to Vor exits through helix K, F and helix J. This study further revealed the CYP51B relevant structural characteristics at the atomic level as well as provided a basis for rational design of new and more efficacious antifungal agents.
Peroxidase and Polyphenol Oxidase Activity in Moderate Resistant and Susceptible Vicia faba Induced by Aphis craccivora (Hemiptera: Aphididae) Infestation

Abstract Two faba bean, Vicia faba L. , cultivars, Gazira2 and Misr1, representing cultivars moderately resistant and susceptible to aphids, were analyzed for peroxidase (POD) and polyphenol oxidase (PPO) activities induced by cowpea aphid, Aphis craccivora Koch. infestation. Two tissue types (whole plant [WP] and detached leaf [DL]), two infestation status (infested and uninfested), and three aphid infestation durations (1, 3, and 5 d) were considered in POD and PPO data analysis. Factorial analysis showed that only cultivar factor has a significant effect on both POD and PPO activity, especially on the first day after aphid infestation ( P: 0.0003 and 0.001, respectively). Tissue type has no significant effect, indicating either DL or WP can be used for measuring POD and PPO activities. While the unsignificant different of infestation status reflecting a constitutive resistant character in Gazira2. Mann–Whitney U -test showed that POD and PPO activities in Gazira2 were higher significantly when compared with Misr1 with P value 0.0006 and 0.0015 for POD and PPO, respectively. Repeated measures analysis indicates that the POD and PPO activities on Gazira2 were significantly higher when compared with Misr1. Additionally, POD activity changed significantly over the time in 1, 3, and 5 d after aphid infestation. We concluded that higher activity of POD and PPO in cultivar Gazira2 is strongly associated with their resistant characters.
Morphological Change to Birds over 120 Years Is Not Explained by Thermal Adaptation to Climate Change

Changes in morphology have been postulated as one of the responses of animals to global warming, with increasing ambient temperatures leading to decreasing body size. However, the results of previous studies are inconsistent. Problems related to the analyses of trends in body size may be related to the short-term nature of data sets, to the selection of surrogates for body size, to the appropriate models for data analyses, and to the interpretation as morphology may change in response to ecological drivers other than climate and irrespective of size. Using generalized additive models, we analysed trends in three morphological traits of 4529 specimens of eleven bird species collected between 1889 and 2010 in southern Germany and adjacent areas. Changes and trends in morphology over time were not consistent when all species and traits were considered. Six of the eleven species displayed a significant association of tarsus length with time but the direction of the association varied. Wing length decreased in the majority of species but there were few significant trends in wing pointedness. Few of the traits were significantly associated with mean ambient temperatures. We argue that although there are significant changes in morphology over time there is no consistent trend for decreasing body size and therefore no support for the hypothesis of decreasing body size because of climate change. Non-consistent trends of change in surrogates for size within species indicate that fluctuations are influenced by factors other than temperature, and that not all surrogates may represent size appropriately. Future analyses should carefully select measures of body size and consider alternative hypotheses for change.
Expressions Profiles of the Proteins Associated with Carbohydrate Metabolism in Rat Liver Regeneration

Liver has a very amazing ability to regenerate from the remnant liver after injury or partial hepatectomy (PH). Carbohydrate metabolism plays a critical role in regeneration. Many signaling pathways are involved in the metabolism process. We analyzed the changes of proteins at 0–36 h after PH in rats using isobaric tags for relative and absolute quantitation (iTRAQ) coupled with LC-MS/MS-based quantitative proteomics strategy. The results showed that 110 proteins and 5 signaling pathways related to carbohydrate metabolism in rat LR changed significantly. Based on a motif discovery method performed by iRegulon, we identified for the first time that the transcription factor SPIB whose motif was enriched among the differentiated genes associated with carbohydrate metabolism may play an important role in liver regeneration for the first time. The findings of this research provide a molecular basis for further unrevealing the mechanism of regeneration at priming stage (0–6 h) and proliferation stage (6–36 h) of LR in rats. At the same time, our studies provide more novel evidence for the signaling pathways which regulate carbohydrate metabolism from proteomics level. This study can provide some new thinking of liver regeneration and treatment of diseases associated with glucose metabolism.
Granulocyte transfusions in the management of invasive fungal infections

Granulocyte transfusions have a long history of being used in patients with neutropenia or neutrophil dysfunction to prevent and treat invasive fungal infections. However, there are limited and conflicting data concerning its clinical effectiveness, considerable variations in current granulocyte transfusion practices, and uncertainties about its benefit as an adjunct to modern antifungal therapy. In this review, we provide an overview on granulocyte transfusions and summarize the evidence on their role in the prevention and treatment of invasive fungal infections.
Hyposmia, symptoms of rapid eye movement sleep behavior disorder, and parkinsonian motor signs suggest prodromal neurodegeneration in 22q11 deletion syndrome

The 22q11 deletion syndrome (22q11DS) is one of the most common genomic disorders in humans. There is an increased risk of Parkinson’s disease (PD) in individuals with 22q11DS. The characteristic motor features of PD begin when more than 50% of dopaminergic neurons in the substantia nigra have degenerated. Before this, there is a prodromal period, of up to 20 years, in which nonmotor features such as hyposmia, autonomic dysfunction, rapid eye movement sleep behavior disorder, and subtle motor dysfunction can occur. We used validated clinical tools to investigate the presence of prodromal markers of PD in 50 adults with 22q11DS and 14 matched deletion-negative controls. The median score on the University of Pennsylvania Smell Identification Test was significantly lower in the 22q11 deletion group, and 44% scored in the hyposmic range (P=0.024). Individuals with 22q11DS were significantly more likely to report autonomic symptoms (urinary dysfunction or constipation, P=0.016). Twenty-eight percent of 22q11DS participants scored above the threshold for rapid eye movement sleep behavior disorder on a screening questionnaire (P=0.022). Four 22q11DS participants had parkinsonian motor signs on examination, which did not fulfill the diagnostic criteria for PD. We report prodromal markers of PD in 22q11DS. These may help identify individuals with 22q11 deletion at risk of neurological disease. However, the significance of these signs needs to be confirmed by longitudinal studies of development of PD.
Perceived Effectiveness and Barriers to Physical Therapy Services for Families and Children With Friedreich Ataxia

Purpose: To describe the frequency, type, and perceived effectiveness of physical therapy interventions for children with Friedreich ataxia (FA); identify barriers to therapy; and solicit advice from parents. Method: Parents of 30 children with FA participated in semistructured interviews. Qualitative and quantitative methods were used to analyze the data. Results: Sixty-seven percent of children received direct physical therapy service. Stretching and strengthening exercises were used most frequently, and their perceived usefulness increased as the children aged. Seventy-three percent received home exercise programs; 9% implemented these consistently. External barriers included a lack of expert providers and limited reimbursement. Internal barriers included limited time and energy, lack of awareness of services, and children's preferences not to be treated differently. Parents advised therapists to become experts, advocates, and use approaches based on family and child preferences. Conclusions: Outcomes provide a starting point for developing further research, education, and effective interventions for children with FA.
Adjusting Expected Mortality Rates Using Information From a Control Population: An Example Using Socioeconomic Status

Expected or reference mortality rates are commonly used in the calculation of measures such as relative survival in population-based cancer survival studies and standardized mortality ratios. These expected rates are usually presented according to age, sex, and calendar year. In certain situations, stratification of expected rates by other factors is required to avoid potential bias if interest lies in quantifying measures according to such factors as, for example, socioeconomic status. If data are not available on a population level, information from a control population could be used to adjust expected rates. We have presented two approaches for adjusting expected mortality rates using information from a control population: a Poisson generalized linear model and a flexible parametric survival model. We used a control group from BCBaSe-a register-based, matched breast cancer cohort in Sweden with diagnoses between 1992 and 2012-to illustrate the two methods using socioeconomic status as a risk factor of interest. Results showed that Poisson and flexible parametric survival approaches estimate similar adjusted mortality rates according to socioeconomic status. Additional uncertainty involved in the methods to estimate stratified, expected mortality rates described in this study can be accounted for using a parametric bootstrap, but this might make little difference if using a large control population.
Network meta-analysis in health psychology and behavioural medicine: a primer

ABSTRACT Progress in the science and practice of health psychology depends on the systematic synthesis of quantitative psychological evidence. Meta-analyses of experimental studies have led to important advances in understanding health-related behaviour change interventions. Fundamental questions regarding such interventions have been systematically investigated through synthesising relevant experimental evidence using standard pairwise meta-analytic procedures that provide reliable estimates of the magnitude, homogeneity and potential biases in effects observed. However, these syntheses only provide information about whether particular types of interventions work better than a control condition or specific alternative approaches. To increase the impact of health psychology on health-related policy-making, evidence regarding the comparative efficacy of all relevant intervention approaches – which may include biomedical approaches – is necessary. With the development of network meta-analysis (NMA), such evidence can be synthesised, even when direct head-to-head trials do not exist. However, care must be taken in its application to ensure reliable estimates of the effect sizes between interventions are revealed. This review paper describes the potential importance of NMA to health psychology, how the technique works and important considerations for its appropriate application within health psychology.
Health and the Economy in the United States, from 1750 to the Present

I discuss the health transition in the United States, bringing new data to bear on health indicators, and investigating the changing relationship between health, income, and the environment. I argue that scientific advances played an outsize role and that health improvements were largest among the poor. Health improvements were not a precondition for modern economic growth. The gains to health are largest when the economy has moved from "brawn" to "brains" because this is when the wage returns to education are high, leading the healthy to obtain more education. More education may improve use of health knowledge, producing a virtuous cycle.
Cortical Structure of Hallucal Metatarsals and Locomotor Adaptations in Hominoids

Diaphyseal morphology of long bones, in part, reflects in vivo loads experienced during the lifetime of an individual. The first metatarsal, as a cornerstone structure of the foot, presumably expresses diaphyseal morphology that reflects loading history of the foot during stance phase of gait. Human feet differ substantially from those of other apes in terms of loading histories when comparing the path of the center of pressure during stance phase, which reflects different weight transfer mechanisms. Here we use a novel approach for quantifying continuous thickness and cross-sectional geometric properties of long bones in order to test explicit hypotheses about loading histories and diaphyseal structure of adult chimpanzee, gorilla, and human first metatarsals. For each hallucal metatarsal, 17 cross sections were extracted at regularly-spaced intervals (2.5% length) between 25% and 65% length. Cortical thickness in cross sections was measured in one degree radially-arranged increments, while second moments of area were measured about neutral axes also in one degree radially-arranged increments. Standardized thicknesses and second moments of area were visualized using false color maps, while penalized discriminant analyses were used to evaluate quantitative species differences. Humans systematically exhibit the thinnest diaphyseal cortices, yet the greatest diaphyseal rigidities, particularly in dorsoplantar regions. Shifts in orientation of maximum second moments of area along the diaphysis also distinguish human hallucal metatarsals from those of chimpanzees and gorillas. Diaphyseal structure reflects different loading regimes, often in predictable ways, with human versus non-human differences probably resulting both from the use of arboreal substrates by non-human apes and by differing spatial relationships between hallux position and orientation of the substrate reaction resultant during stance. The novel morphological approach employed in this study offers the potential for transformative insights into form-function relationships in additional long bones, including those of extinct organisms (e.g., fossils).
Public Perceptions of Behavioral and Substance Addictions

Most of the research on public perceptions of people with addictive disorders has focused on alcohol and illicit drugs, rather than addiction to behavioral activities. To expand the range of addictive behaviors and types of perceptions studied, we designed the present study to assess the lay public’s definitions of and willingness to affiliate with people described as addicted to 1 of 2 specific behaviors (i.e., pornography or gambling) or 1 of 3 specific substances (i.e., alcohol, marijuana, or heroin). A nationwide convenience sample (N = 612) of American adults completed online questionnaires during the summer of 2015. Participants rated heroin as more addictive than the other drugs and behaviors and, despite differences among the conditions, were generally unwilling to affiliate with an individual addicted to any of the 2 behaviors or 3 substances. When asked to rate different potential indications of addiction, participants endorsed behavioral signs of impaired control and physiological and psychological dependence as more indicative of all 5 types of addiction than desire to use the substance or engage in the addictive behavior. Despite recent efforts to increase public knowledge about addictive disorders, members of the public continue to endorse some attitudes indicative of stigmatization toward people with selected substance and behavioral addictions.
Incidence of Clostridium difficile Infection Among Individuals With Inflammatory Bowel Disease

Background & Aims: Studies of Clostridium difficile infections (CDIs) among individuals with inflammatory bowel disease (IBD) h ave used data from single centers or CDI administrative data codes of limited diagnostic ac uracy. We determined the incidence, risk factors, and outcomes after CDI in a population-based cohort of patients with IBD and laboratory confirmation diagnoses of C DI. Methods: We searched the University of Manitoba IBD Epidem iology Database and Manitoba Health CDI databases to identify individua ls with CDI, with or without IBD, from July 1, 2005 through March 31, 2014. Time tren ds of incidence were assessed using joinpoint regression. Multivariable Cox regression analyses were performed to assess differences in CDI incidence rates and mortality af ter CDI between individuals with and without IBD. Conditional logistic regression was pe rformed to determine predictors of CDI among individuals with IBD. Results: Individuals with IBD had a 4.8-fold increase in r sk of CDI than individuals without IBD; we found no difference between individ uals with ulcerative colitis vs Crohn’s disease. There was no increase in CDI incid e ce over the study time period in either group. Among individuals with IBD, exposure to corticosteroids, infliximab or adalimumab, metronidazole, hospitalizations, higher ambulatory care visits, shorter duration of IBD, and higher comorbidities were asso ciated with an increased risk of CDI. Although CDI increased mortality among individuals with and without IBD, there was M AN US CR IP T AC CE PT ED ACCEPTED MANUSCRIPT lower mortality after CDI among individuals with IB D than without IBD (hazard ratio, 0.65; 95% CI, 0.44–0.96). Conclusions: CDI incidence is no longer increasing among indivi duals with IBD. We identified unique risk factors for CDI in patients with IBD. CDI is associated with a greater increase in mortality among individuals wit hout IBD than with IBD.
Structural Transitions of the Conserved and Metastable Hantaviral Glycoprotein Envelope

ABSTRACT Hantaviruses are zoonotic pathogens that cause severe hemorrhagic fever and pulmonary syndrome. The outer membrane of the hantavirus envelope displays a lattice of two glycoproteins, Gn and Gc, which orchestrate host cell recognition and entry. Here, we describe the crystal structure of the Gn glycoprotein ectodomain from the Asiatic Hantaan virus (HTNV), the most prevalent pathogenic hantavirus. Structural overlay analysis reveals that the HTNV Gn fold is highly similar to the Gn of Puumala virus (PUUV), a genetically and geographically distinct and less pathogenic hantavirus found predominantly in northeastern Europe, confirming that the hantaviral Gn fold is architecturally conserved across hantavirus clades. Interestingly, HTNV Gn crystallized at acidic pH, in a compact tetrameric configuration distinct from the organization at neutral pH. Analysis of the Gn, both in solution and in the context of the virion, confirms the pH-sensitive oligomeric nature of the glycoprotein, indicating that the hantaviral Gn undergoes structural transitions during host cell entry. These data allow us to present a structural model for how acidification during endocytic uptake of the virus triggers the dissociation of the metastable Gn-Gc lattice to enable insertion of the Gc-resident hydrophobic fusion loops into the host cell membrane. Together, these data reveal the dynamic plasticity of the structurally conserved hantaviral surface. IMPORTANCE Although outbreaks of Korean hemorrhagic fever were first recognized during the Korean War (1950 to 1953), it was not until 1978 that they were found to be caused by Hantaan virus (HTNV), the most prevalent pathogenic hantavirus. Here, we describe the crystal structure of HTNV envelope glycoprotein Gn, an integral component of the Gn-Gc glycoprotein spike complex responsible for host cell entry. HTNV Gn is structurally conserved with the Gn of a genetically and geographically distal hantavirus, Puumala virus, indicating that the observed α/β fold is well preserved across the Hantaviridae family. The combination of our crystal structure with solution state analysis of recombinant protein and electron cryo-microscopy of acidified hantavirus allows us to propose a model for endosome-induced reorganization of the hantaviral glycoprotein lattice. This provides a molecular-level rationale for the exposure of the hydrophobic fusion loops on the Gc, a process required for fusion of viral and cellular membranes.