Differences in standing behavior between Jersey and Holstein dairy cows during the periparturient period.

Jerseys are the second most popular breed in the US dairy industry, yet there are few studies that directly compare their behavior with Holsteins. The objective of this observational study was to describe differences in the standing behavior of healthy Jersey and Holstein dairy cows during the periparturient period. A total of 51 Jerseys (11 primiparous [PP] and 40 multiparous [MP]) and 36 Holsteins (8 PP, 28 MP) were used for this analysis.

Mixture Experimentation in Pharmaceutical Formulations: A Tutorial.

Mixture experimentation is commonly seen in pharmaceutical formulation studies, where the relative proportions of the individual components are modeled for effects on product attributes. The requirement that the sum of the component proportions equals 1 has given rise to the class of designs, known as mixture designs. The first mixture designs were published by Quenouille in 1953 but it took nearly 40 years for the earliest mixture design applications to be published in the pharmaceutical sciences literature by Kettaneh-Wold in 1991 and Waaler in 1992.

Targeting NRAS via miR-1304-5p or farnesyltransferase inhibition confers sensitivity to ALK inhibitors in ALK-mutant neuroblastoma.

Targeting Anaplastic lymphoma kinase (ALK) is a promising therapeutic strategy for aberrant ALK-expressing malignancies including neuroblastoma, but resistance to ALK tyrosine kinase inhibitors (ALK TKI) is a distinct possibility necessitating drug combination therapeutic approaches. Using high-throughput, genome-wide CRISPR-Cas9 knockout screens, we identify miR-1304-5p loss as a desensitizer to ALK TKIs in aberrant ALK-expressing neuroblastoma; inhibition of miR-1304-5p decreases, while mimics of this miRNA increase the sensitivity of neuroblastoma cells to ALK TKIs. We show that miR-1304-5p targets NRAS, decreasing cell viability via induction of apoptosis.

STAT3 couples activated tyrosine kinase signaling to the oncogenic core transcriptional regulatory circuitry of anaplastic large cell lymphoma.

Anaplastic large cell lymphoma (ALCL) is an aggressive, CD30 T cell lymphoma of children and adults. ALK fusion transcripts or mutations in the JAK-STAT pathway are observed in most ALCL tumors, but the mechanisms underlying tumorigenesis are not fully understood. Here, we show that dysregulated STAT3 in ALCL cooccupies enhancers with master transcription factors BATF3, IRF4, and IKZF1 to form a core regulatory circuit that establishes and maintains the malignant cell state in ALCL.

Challenging our understanding of B-cell lymphomagenesis and risk: Paediatric high-grade B-cell lymphoma, not otherwise specified with a DDX3X::MLLT10 fusion and an IGH deletion.

We report a unique case of high-grade B-cell lymphoma, not otherwise specified in a 5-year-old child. Whole-genome sequencing revealed a DDX3X::MLLT10 fusion, usually seen in T-cell acute lymphoblastic leukaemia (ALL). This suggests the novel idea that MLLT10 fusions are capable of driving B-cell malignancies.

Using the Colloidal Method to Prepare Au Catalysts for the Alkylation of Aniline by Benzyl Alcohol.

Using the colloidal method, attempts were made to deposit Au NPs on seven different material supports (TiO, α and γ-AlO, HFeO, CeO, C, and SiO). The deposition between 0.8 and 1 wt% of Au NPs can be generally achieved, apart for SiO (no deposition) and α-alumina (0.

Maternal electronic cigarette use during pregnancy affects long-term arterial function in offspring.

Vaping, or electronic cigarette (ecig) use, is prevalent among pregnant women, although little is known about the effects of perinatal ecig use on cardiovascular health of the progeny (even when using nicotine-free e-liquid). Maternal toxicant inhalation may adversely affect vital conduit vessel development. We tested the hypothesis that perinatal exposure to maternal vaping would lead to a dose-dependent dysfunction that would persist into later life of offspring.

Resistance to Targeted Agents Used to Treat Paediatric ALK-Positive ALCL.

Non-Hodgkin lymphoma (NHL) is the third most common malignancy diagnosed in children. The vast majority of paediatric NHL are either Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), anaplastic large cell lymphoma (ALCL), or lymphoblastic lymphoma (LL). Multi-agent chemotherapy is used to treat all of these types of NHL, and survival is over 90% but the chemotherapy regimens are intensive, and outcomes are generally poor if relapse occurs.

Long-term cerebrovascular dysfunction in the offspring from maternal electronic cigarette use during pregnancy.

Electronic cigarettes (E-cigs) have been promoted as harm-free or less risky than smoking, even for women during pregnancy. These claims are made largely on E-cig aerosol having fewer number of toxic chemicals compared with cigarette smoke. Given that even low levels of smoking are found to produce adverse birth outcomes, we sought to test the hypothesis that vaping during pregnancy (with or without nicotine) would not be harm-free and would result in vascular dysfunction that would be evident in offspring during adolescent and/or adult life.

Type 2 diabetes in general practice - a focus-group study.

Background: The National Diabetes Plan 2017-21 has implemented measures to improve diagnosis and follow-up of persons with type 2 diabetes by the primary health services. The objective of this study was to explore the experiences and thoughts of Norwegian general practitioners (GPs) with regard to diagnosis and follow-up of this patient group.

Material And Method: In this qualitative study, three focus-group interviews were conducted with a total of 17 GPs.

The Role of Spiritual Care and Healing in Health Management.

There is substantial evidence that spiritual well-being is an important determinant of overall health, longevity and quality of life, especially in patients with severe illness. While most physicians would agree that spiritual well-being is an important factor in their patients' health, the spiritual needs and well-being of patients are largely ignored and rarely addressed by healthcare providers, representing a significant gap in care. Physicians often cite a lack of training or comfort in assessing and/or addressing patients' spiritual needs, and a lack of research on the safety and efficacy of spiritual interventions as barriers to care.

Is it justifiable to pool Chironomus species in trace element contamination studies?

Larvae of the insect Chironomus (Chironomidae: Diptera) have great potential for estimating the bioavailability of sedimentary trace elements because they are common in fine sediments and tolerate high concentrations of these contaminants. Their use as biomonitors is limited by the fact that they are difficult to identify as to species, and the species can differ in their trace element concentrations. To determine whether pooling species would compromise their use as trace element biomonitors, we identified species of Chironomus larvae collected from 22 lakes and measured their concentrations of 9 trace elements.

Genetic Link Between Gender Dysphoria and Sex Hormone Signaling.

Context: There is a likely genetic component to gender dysphoria, but association study data have been equivocal.

Objective: We explored the specific hypothesis that gender dysphoria in transgender women is associated with variants in sex hormone-signaling genes responsible for undermasculinization and/or feminization.

Design: Subject-control analysis included 380 transgender women and 344 control male subjects.

Organic selenium, selenate, and selenite accumulation by lake plankton and the alga Chlamydomonas reinhardtii at different pH and sulfate concentrations.

Selenium (Se) concentrations measured in lake planktonic food chains (microplankton <64 μm, copepods, and Chaoborus larvae) were strongly correlated with the concentrations of dissolved organic Se. These correlations were strengthened slightly by adding the concentrations of dissolved selenate to those of organic Se. To better understand the role of Se species and the influence of water chemistry on Se uptake, we exposed the green alga Chlamydomonas reinhardtii to selenite, selenate, or selenomethionine at various H ion and sulfate concentrations under controlled laboratory conditions.

Evaluating Benthic Recovery Decades after a Major Oil Spill in the Laurentian Great Lakes.

The long-term effects of oil spills on freshwater organisms have been little studied. In 1950, a large oil spill (10 million L) covered the harbor area of Parry Sound, Ontario, the deepest port in the Laurentian Great Lakes. Ecological impacts were not studied at the time, but 25 years later three-quarters of the Chironomus cucini larvae (Insecta, Diptera, Chironomidae) living in the harbor area were reported to be deformed.

Hepatic oxidative stress and metal subcellular partitioning are affected by selenium exposure in wild yellow perch (Perca flavescens).

Yellow perch (Perca flavescens) collected from 11 lakes in the Canadian mining regions of Sudbury (Ontario) and Rouyn-Noranda (Quebec) display wide ranges in the concentrations of cadmium (Cd), nickel (Ni), selenium (Se), and thallium (Tl) in their livers. To determine if these trace elements, as well as copper (Cu) and zinc (Zn), are causing oxidative stress in these fish, we measured three biochemical indicators (glutathione (GSH), glutathione disulfide (GSSG) and thiobarbituric acid-reactive substances (TBARS)) in their livers. We observed that 44% of the yellow perch that we collected were at risk of cellular oxidative stress and lipid peroxidation.

Metal (Ag, Cd, Cu, Ni, Tl, and Zn) Binding to Cytosolic Biomolecules in Field-Collected Larvae of the Insect Chaoborus.

We characterized the biomolecules involved in handling cytosolic metals in larvae of the phantom midge (Chaoborus) collected from five mining-impacted lakes by determining the distribution of Ag, Cd, Cu, Ni, Tl, and Zn among pools of various molecular weights (HMW: high molecular weight, >670-40 kDa; MMW: medium molecular weight, 40-<1.3 kDa; LMW: low molecular weight, <1.3 kDa).

Trace metals partitioning among different sedimentary mineral phases and the deposit-feeding polychaete Armandia brevis.

Trace metals (Cd, Co, Cu, Fe, Mn, Ni, Pb, Zn) were determined in two operationally defined fractions (HCl and pyrite) in sediments from Ensenada and El Sauzal harbors (Mexico). The HCl fraction had significantly higher metal concentrations relative to the pyrite fraction in both harbors, underlining the weak tendency of most trace metals to associate with pyrite. Exceptionally, Cu was highly pyritized, with degrees of trace metal pyritization (DTMP) >80% in both harbors.

Using Sulfur Stable Isotopes to Understand Feeding Behavior and Selenium Concentrations in Yellow Perch (Perca flavescens).

We measured selenium (Se) concentrations in yellow perch (Perca flavescens) muscle and their prey collected from four Se-contaminated lakes located near metal smelters in the eastern Canadian cities of Sudbury and Rouyn-Noranda. Yellow perch Se concentrations were related to their weight in two of the four lakes. Measurements of sulfur stable isotopes (δ(34)S) in yellow perch muscle and stomach contents showed that larger fish tended to feed less on zooplankton and more on benthic invertebrates than did smaller fish.

Heterozygous expression of the oncogenic Pik3ca(H1047R) mutation during murine development results in fatal embryonic and extraembryonic defects.

The phosphoinositide 3-kinase (PI3K)/AKT signalling pathway regulates many cellular functions including proliferation, migration, survival and protein synthesis. Somatic mutations in PIK3CA, the gene encoding the p110α catalytic subunit of PI3K enzyme, are commonly associated with many human cancers as well as recently being implicated in human overgrowth syndromes. However, it is not clear if such mutations can be inherited through the germline.

Subcellular partitioning of non-essential trace metals (Ag, As, Cd, Ni, Pb, and Tl) in livers of American (Anguilla rostrata) and European (Anguilla anguilla) yellow eels.

We determined the intracellular compartmentalization of the trace metals Ag, As, Cd, Ni, Pb, and Tl in the livers of yellow eels collected from the Saint Lawrence River system in Canada (Anguilla rostrata) and in the area of the Gironde estuary in France (Anguilla anguilla). Differential centrifugation, NaOH digestion and thermal shock were used to separate eel livers into putative "sensitive" fractions (heat-denatured proteins, mitochondria and microsomes+lysosomes) and detoxified metal fractions (heat-stable peptides/proteins and granules). The cytosolic heat-stable fraction (HSP) was consistently involved in the detoxification of all trace metals.

Ubiquitous expression of the Pik3caH1047R mutation promotes hypoglycemia, hypoinsulinemia, and organomegaly.

Mutations in PIK3CA, the gene encoding the p110α catalytic subunit of PI3K, are among the most common mutations found in human cancer and have also recently been implicated in a range of overgrowth syndromes in humans. We have used a novel inducible "exon-switch" approach to knock in the constitutively active Pik3ca(H1047R) mutation into the endogenous Pik3ca gene of the mouse. Ubiquitous expression of the Pik3ca(H1047R) mutation throughout the body resulted in a dramatic increase in body weight within 3 weeks of induction (mutant 150 ± 5%; wild-type 117 ± 3%, mean ± sem), which was associated with increased organ size rather than adiposity.