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The (co)variance components and corresponding phenotypic and genetic parameters for growth traits and wool traits of economic importance were estimated in the Alpine Merino sheep population maintained at Gansu Provincial Sheep Breeding Technology Extension Station in northwestern China. Data from a maximum of 49,474 animals sired by 526 rams and born from 22,531 ewes over 20 years from 2000 to 2019 were used in this study. Birth type, age of dam, birth year, sex and/or management group, and age at measurement were initially fitted as fixed effects in an animal model with various random effects. Genetic groups were defined for all animals by the sire breed and breed genotype interacted with dam-strain flocks and were fitted as one of the random effects. Analyses were conducted using a residual maximum likelihood procedure (ASReml). Seven different animal models were fitted for all traits, and the most appropriate model with relevant random effects was selected through log-likelihood ratio testing. After identifying the appropriate model through single-trait analysis, bivariate analyses were used to obtain the phenotypic and genetic correlations among the traits. The estimates of additive direct heritability for birth weight (BWT), weaning weight (WWT), preweaning growth rate (prwADG), postweaning growth rate (powADG), yearling body weight (YWT), average fibre diameter (AFD), greasy fleece weight (GFW), clean fleece weight (CFW), yield (YLD), yearling wool staple length (YSL), coefficient of variation of average fibre diameter (FDcv) and wool visual fineness counts (VFC) were 0.30, 0.18, 0.18, 0.20, 0.29, 0.20, 0.19, 0.20, 0.35, 0.19, 0.16 and 0.13, respectively, with standard errors ranging from 0.02 to 0.05. The corresponding ratios of genetic group variance to additive genetic variance were significant and, respectively, 0.35, 0.80, 0.62, 0.26, 0.13, 1.06, 0.38, 0.64, 0.09, 0.12, 0.06 and 0.58. These results suggest for these traits that there is potential to exploit both the additive genetic variation and between genetic group variation although for most traits the between group variation was smaller than the variation within groups. Favourable genetic correlations were found among the growth traits, and between growth traits and fleece production traits, and among wool traits GFW, CFW, YSL and YLD. This study provides the required estimates of genetic parameters of both growth and wool traits of the new breed for the design of more effective breeding programmes.

PURPOSE This study evaluated risk factors predicting unplanned 30-day acute service utilization among adults subsequent to hospitalization for a new diagnosis of leukemia, lymphoma, or myeloma. This study explored the prevalence of medical complications (aligned with OP-35 measure specifications from the Centers for Medicare & Medicaid Services [CMS] Hospital Outpatient Quality Reporting Program) and the potential impact of psychosocial factors on unplanned acute care utilization. METHODS This study included 933 unique patients admitted to three acute care inpatient facilities within a nonprofit community-based health care system in southern California from 2012 to 2017. Integrated comprehensive data elements from electronic medical records and facility oncology registries were leveraged for univariate statistics, predictive models constructed using multivariable logistic regression, and further exploratory data mining, with predictive accuracy of the models measured with c-statistics. RESULTS The mean age of study participants was 65 years, and 55.1% were male. Specific diagnoses were lymphoma (48.7%), leukemia (35.2%), myeloma (14.0%), and mixed types (2.1%). Approximately one fifth of patients received unplanned acute care services within 30 days postdischarge, and over half of these patients presented with one or more symptoms associated with the CMS medical complication measure. The predictive models, with c-statistics ranging from 0.7 and above for each type of hematologic malignancy, indicated good predictive qualities with the impact of psychosocial functioning on the use of acute care services ( P values < .05), including lack of consult for social work during initial admission (lymphoma or myeloma), history of counseling or use of psychotropic medications (lymphoma), and past substance use (myeloma). CONCLUSION This study provides insights into patient-related factors that may inform a proactive approach to improve health outcomes, such as enhanced care transition, monitoring, and support interventions.

A novel type of phosphorus doped Ti3C2Tx MXene nanosheets (P-Ti3C2Tx) is synthesized via a facile and controllable strategy of annealing MXene nanosheets with the presence of sodium hypophosphite. A combination of theoretical density functional theory calculation and experimental X-ray photoelectron spectroscopy discloses that the doped P atoms are prone to fill into Ti vacancies first due to their lowest formation free energy (ΔGP* = −0.028 eV·A−2) and next to bond with surface terminals on MXene layers (ΔGP* = 0.013 eV·A−2), forming P-C and P-O species, respectively. More importantly, the as-obtained P-Ti3C2Tx is, for the first time, investigated as the electrode material for supercapacitors, demonstrating a significantly boosted electrochemical performance by P doping. As a result, P-Ti3C2Tx electrode delivers a high specific capacitance of 320 F·g−1 at a current density of 0.5 A·g−1 (much higher than 131 F·g−1 for undoped MXene), an ultrahigh rate retention of 83.8% capacitance at 30 A·g−1, and a high cycling stability over continuous 5000 cycles.

A novel type of phosphorus doped Ti

312 Background: Improving the ability to predict which patients are at increased risk for acute care services subsequent to hospitalization can lead to more effective interventions and quality care. This study evaluated the performance of risk models to predict 30-day acute service utilization among adult inpatients with newly diagnosed hematologic malignancies. The study explored the impact of medical complications on potentially preventable service utilization, aligned with specifications for proposed measure OP-35 from the CMS Hospital Outpatient Quality Reporting Program. Methods: The study included 933 unique adult patients admitted to four acute care inpatient facilities within a non-profit community based healthcare system during calendar years 2012 to 2017. Risk models integrated a comprehensive set of data elements using clinical information from electronic medical records and facility oncology registries. Predictive models were constructed using a multivariable logistic regression, with calculation of standardized coefficients to rank order variables with the greatest impact on unplanned readmissions. Exploratory data mining techniques were conducted to augment classification of at-risk patients. Results: The mean age of study participants was 65 years and 55.1% were male. In order of prevalence, the types of hematologic malignancy were lymphoma (48.7%), leukemia (35.2%), myeloma (14.0%), and mixed types (2.1%). Approximately one fifth of patients received unplanned acute care services within 30 days after the index hospitalization (lymphoma = 23.1%, myeloma = 22.1%, leukemia = 18.6%). Among the risk models, the most influential predictors included initial length of stay, severity of illness, and consult for social work. Overall, 56.6% of patients who were readmitted within 30 days of hospitalization presented with one or more symptoms associated with the CMS medical complication measure, including cytopenia, infection, negative hydration, and/or pain. Conclusions: Optimizing quality care in a value-based health care environment requires proactive approaches such as risk prediction models for identifying patients who can benefit most from care transition interventions.

We analyzed the roles of the three domains of a Drosophila hnRNP A1 homolog by expression of wild-type and mutant versions of HRB87F/hrp36 in Drosophila melanogaster. HRB87F/hrp36 is one of two Drosophila proteins that is most similar to mammalian A1 hnRNP, and like A1, consists of two copies of the RNA-binding domain (RBD) motif followed by a glycine-rich domain (GRD). The role of the domains in nuclear localization and RNA binding to polytene chromosomal sites was determined. RBD-1 and the GRD were largely responsible for both the cellular location of the protein and for the typical chromosomal distribution pattern of the protein at sites of PolII transcription. RBD-1 also provided a role in the exon-skipping activity of the protein that was not provided by RBD-2. On the other hand, RBD-2 and the GRD were responsible for the very limited chromosomal distribution pattern seen upon heat shock, when HRB87F/hrp36 is sequestered at heat-shock puff 93D, which encodes a long nucleus-restricted RNA. Thus, these studies indicate that the two RBDs function independently of each other but in concert with the GRD. In addition, the self-association property of the GRD was strikingly evident in these overexpressed proteins.

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are abundant RNA-binding proteins that are implicated in splicing regulation. Here we investigate the role of a Drosophila hnRNP in splicing regulation in living animals. We find that overexpression of the Drosophila hnRNP HRB98DE leads to skipping of all internal exons in the Drosophila dopa decarboxylase (Ddc) pre-mRNA in vivo. These results indicate that HRB98DE has a splicing activity that promotes use of terminal splice sites. The effect of excess HRB98DE on Ddc splicing is transient, even though high levels of HRB98DE persist for at least 24 hr. This suggests that Drosophila larvae can induce a compensating mechanism to counteract the effects of excess HRB98DE.

p42mapk [mitogen activated protein (MAP) kinase; extracellular signal-regulated protein kinase (ERK)] is a serine/threonine-specific protein kinase that is activated by dual tyrosine and threonine phosphorylation in response to diverse agonists. Both the tyrosine and threonine phosphorylations are necessary for full enzymic activity. A MAP kinase activator recently purified and cloned has been shown to be a protein kinase (MAP kinase kinase) that is able to induce the dual phosphorylation of MAP kinase on both the regulatory tyrosine and threonine sites in vitro. In the present paper we have utilized MAP kinase mutants altered in the sites of regulatory phosphorylation to show, both in vivo and in vitro, that phosphorylation of the tyrosine and the threonine can occur independently of one another, with no required order of phosphorylation. We also utilized kinase-defective variants of MAP kinase with mutations in either the ATP-binding loop or the catalytic loop, and obtained data suggesting that the activity or structure of the catalytic loop of MAP kinase plays an important role in its own dual phosphorylation.

Adenylate cyclase (AC) toxin from Bordetella pertussis inserts into eukaryotic cells, producing intracellular cAMP, as well as hemolysis and cytotoxicity. Concentration dependence of hemolysis suggests oligomers as the functional unit and inactive deletion mutants permit partial restoration of intoxication and/or hemolysis, when added in pairs [M. Iwaki, A. Ullmann, P. Sebo, Mol. Microbiol. 17 (1995) 1015–1024], suggesting dimerization/oligomerization. Using affinity co-precipitation and fluorescence resonance energy transfer (FRET), we demonstrate specific self-association of AC toxin molecules in solution. Flag-tagged AC toxin mixed with biotinylated-AC toxin, followed by streptavidin beads, yields both forms of the toxin. FRET measurements of toxin, labeled with different fluorophores, demonstrate association in solution, requiring post-translational acylation, but not calcium. AC toxin mixed with ΔR, an inactive mutant, results in enhancement of hemolysis over that with wild type alone, suggesting that oligomers are functional. Dimers and perhaps higher molecular mass forms of AC toxin occur in solution in a manner that is relevant to toxin action.

A novel approach to monomeric PNA building blocks by a solution phase Ugi multi component reaction (MCR) is described. The reaction is easily performed in 96 well plates. The products precipitate from the reaction solution and are thus obtained in high yields and purity. Those products are not amenable by another multi step synthesis in such a diversity.

The Drosophila melanogaster genes Hrb87F and Hrb98DE encode the fly proteins HRB87F and HRB98DE (also known as hrp36 and hrp38, respectively) that are most similar in sequence and function to mammalian A/B-type hnRNP proteins. Using overexpression and deletion mutants of Hrb87F, we have tested the hypothesis that the ratio of A/B hnRNP proteins to SR family proteins modulates certain types of alternative splice-site selection. In flies in which HRB87F/hrp36 had been overexpressed 10- to 15-fold above normal levels, aberrant internal exon skipping was induced in at least one endogenous transcript, the dopa decarboxylase (Ddc) pre-mRNA, which previously had been shown to be similarly affected by excess HRB98DE/hrp38. In a second endogenous pre-mRNA, excess HRB87F/hrp36 had no effect on alternative 3' splice-site selection, as expected from mammalian hnRNP studies. Immunolocalization of the excess hnRNP protein showed that it localized correctly to the nucleus, specifically to sites on or near chromosomes, and that the peak of exon-skipping activity in Ddc RNA correlated with the peak of chromosomally associated hnRNP protein. The chromosomal association and level of the SR family of proteins were not significantly affected by the large increase in hnRNP proteins during this time period. Although these results are consistent with a possible role for hnRNP proteins in alternative splicing, the more interesting finding was the failure to detect significant adverse effects on flies with a greatly distorted ratio of hnRNPs to SR proteins. Electron microscopic visualization of the general population of active genes in flies overexpressing hnRNP proteins also indicated that the great majority of genes seemed normal in terms of cotranscriptional RNA processing events, although there were a few abnormalities consistent with rare exon-skipping events. Furthermore, in a Hrb87F null mutant, which is viable, the normal pattern of Ddc alternative splicing was observed, indicating that HRB87F/hrp36 is not required for Ddc splicing regulation. Thus, although splice-site selection can be affected in at least a few genes by gross overexpression of this hnRNP protein, the combined evidence suggests that if it plays a general role in alternative splicing in vivo, the role can be provided by other proteins with redundant functions, and the role is independent of its concentration relative to SR proteins.