Effects of peripartal rumen-derived direct-fed microbial supplementation on lactation performance, metabolism, ruminal fermentation, and microbial abundance in dairy cows.

The objective of this study was to evaluate the effects of a rumen-derived direct-fed microbial (DFM) product on performance, blood biomarkers, ruminal fermentation, and bacterial abundance in dairy cows during the transition period until 100 DIM. Fifty-six Holstein cows were enrolled in a randomized complete block design from -21 to 100 DIM. Cows were blocked based on expected calving date, parity, and previous lactation milk yield for multiparous cows or genetic merit for primiparous cows.

Exploring switch II pocket conformation of KRAS(G12D) with mutant-selective monobody inhibitors.

The G12D mutation is among the most common KRAS mutations associated with cancer, in particular, pancreatic cancer. Here, we have developed monobodies, small synthetic binding proteins, that are selective to KRAS(G12D) over KRAS(wild type) and other oncogenic KRAS mutations, as well as over the G12D mutation in HRAS and NRAS. Crystallographic studies revealed that, similar to other KRAS mutant-selective inhibitors, the initial monobody bound to the S-II pocket, the groove between switch II and α3 helix, and captured this pocket in the most widely open form reported to date.

The effect of supplementing native rumen microbes on milk production of dairy cows.

We evaluated the effects of 2 direct-fed microbial (DFM) supplements containing 4 native rumen microorganisms on the production of dairy cows. Ninety Holstein cows (43% primiparous) were fed a common diet. Mean days in milk, milk yield, and body weight at the beginning of the study (mean ± standard deviation) were 92 ± 23 d, 45 ± 10 kg/d, and 659 ± 86 kg, respectively.

The splanchnic mesenchyme is the tissue of origin for pancreatic fibroblasts during homeostasis and tumorigenesis.

Pancreatic cancer is characterized by abundant desmoplasia, a dense stroma composed of extra-cellular and cellular components, with cancer associated fibroblasts (CAFs) being the major cellular component. However, the tissue(s) of origin for CAFs remains controversial. Here we determine the tissue origin of pancreatic CAFs through comprehensive lineage tracing studies in mice.

STAT3 in tumor fibroblasts promotes an immunosuppressive microenvironment in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is associated with an incredibly dense stroma, which contributes to its recalcitrance to therapy. Cancer-associated fibroblasts (CAFs) are one of the most abundant cell types within the PDAC stroma and have context-dependent regulation of tumor progression in the tumor microenvironment (TME). Therefore, understanding tumor-promoting pathways in CAFs is essential for developing better stromal targeting therapies.

PTEN in cancer associated fibroblasts.

Decades of research have concluded that disruptions to Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) have profound effects on cancer progression. However, as our understanding of the tumor stroma has evolved, we can appreciate that disruptions to tumor suppressors such as PTEN should not be studied solely in an epithelial context. Inactivation of PTEN in the stroma is associated with worse outcomes in human cancers, therefore, it is important to understand activities regulated downstream of PTEN in stromal compartments.

Defining the Tumor Microenvironment by Integration of Immunohistochemistry and Extracellular Matrix Targeted Imaging Mass Spectrometry.

Breast stroma plays a significant role in breast cancer risk and progression yet remains poorly understood. In breast stroma, collagen is the most abundantly expressed protein and its increased deposition and alignment contributes to progression and poor prognosis. Collagen post-translation modifications such as hydroxylated-proline (HYP) control deposition and stromal organization.

The political economy of COVID-19.

We assess the economic and health costs of COVID and policy responses to COVID. Based on initial estimates of health and economic costs, social distancing policies were justified, but these estimates now seem too high because of learning by doing. Significant differences in mortality rates across US states and countries can be explained by population density, climate, exposure, and policy.

Targeting the KRAS α4-α5 allosteric interface inhibits pancreatic cancer tumorigenesis.

is the most frequently mutated oncogene in human cancer with nearly ~20% of cancer patients possessing mutations in one of three genes ( or ). However, is mutated in nearly 90% of pancreatic ductal carcinomas (PDAC). Although pharmacological inhibition of RAS has been challenging, KRAS(G12C)-specific inhibitors have recently entered the clinic.

Effects of dietary microbial feed supplement on production efficacy in lactating dairy cows.

This study evaluated the effects of a microbial feed supplement (MFS; Galaxis, Ascus Biosciences Inc.) comprising 2 native rumen microbes on performance parameters in mid-lactation dairy cows. Forty-six lactating primiparous and multiparous Holstein cows [629 ± 62 kg of body weight, mean ± standard deviation (SD); parity 1.

Estimating long-term pollution exposure effects through inverse probability weighting methods with Cox proportional hazards models.

Background: Fine particulate matter (PM) is associated with negative health outcomes in both the short and long term. However, the cohort studies that have produced many of the estimates of long-term exposure associations may fail to account for selection bias in pollution exposure as well as covariate imbalance in the study population; therefore, causal modeling techniques may be beneficial.

Methods: Twenty-nine years of data from the National Health Interview Survey (NHIS) was compiled and linked to modeled annual average outdoor PM concentration and restricted-use mortality data.

Complete Genome Sequence of Strains FMAS_KW1, FMAS_KW2 and FMAS_AW1 Isolated from Leptospirosis Patients from Karawanalla and Awissawella, Sri Lanka.

Leptospirosis is an important cause of acute undifferentiated fever and complex multisystem febrile diseases in the tropics and subtropics. Understanding the evolution of especially as related to the clinical pathogenesis of leptospirosis is facilitated by systematic comparative genomic analysis of human-infecting isolates. Here, we announce the complete genome sequences of three strains that were isolated from blood of humans with undifferentiated fever in Sri Lanka.

Cancer mortality risk, fine particulate air pollution, and smoking in a large, representative cohort of US adults.

Purpose: Air pollution and smoking are associated with various types of mortality, including cancer. The current study utilizes a publicly accessible, nationally representative cohort to explore relationships between fine particulate matter (PM) exposure, smoking, and cancer mortality.

Methods: National Health Interview Survey and mortality follow-up data were combined to create a study population of 635,539 individuals surveyed from 1987 to 2014.

Air pollution and mortality in a large, representative U.S. cohort: multiple-pollutant analyses, and spatial and temporal decompositions.

Background: Cohort studies have documented associations between fine particulate matter air pollution (PM) and mortality risk. However, there remains uncertainty regarding the contribution of co-pollutants and the stability of pollution-mortality associations in models that include multiple air pollutants. Furthermore, it is unclear whether the PM-mortality relationship varies spatially, when exposures are decomposed according to scale of spatial variability, or temporally, when effect estimates are allowed to change between years.

PTEN in the Stroma.

Although tremendous progress has been made in understanding the functions of (PTEN) in tumor cells, only recently have tumor cell-non-autonomous actions within the tumor microenvironment (TME) been appreciated. While it is accepted that the TME actively communicates with cancer cells to influence disease progression, our understanding of the genes and pathways responsible is still evolving. Given that inactivation of PTEN in the stroma is correlated with worse outcomes in human cancers, determining the unique functions and mechanisms of PTEN regulation in various TME cell compartments is essential.

Mortality Risk and Fine Particulate Air Pollution in a Large, Representative Cohort of U.S. Adults.

Background: Evidence indicates that air pollution contributes to cardiopulmonary mortality. There is ongoing debate regarding the size and shape of the pollution–mortality exposure–response relationship. There are also growing appeals for estimates of pollution–mortality relationships that use public data and are based on large, representative study cohorts.

Temporal Stability of the Ruminal Bacterial Communities in Beef Steers.

Nutritional studies involving ruminants have traditionally relied on relatively short transition or wash-out periods between dietary treatments, typically two to four weeks. However, little is known about adequate adaptation periods required to reach stabilization of the rumen microbiome that could provide more accurate results from nutritional studies in ruminants. This study determined the rumen bacterial communities and rumen environment parameters over ten weeks following transition from a forage-based to concentrate-based diet.

Short-Term Elevation of Fine Particulate Matter Air Pollution and Acute Lower Respiratory Infection.

Rationale: Nearly 60% of U.S. children live in counties with particulate matter less than or equal to 2.

A communal catalogue reveals Earth's multiscale microbial diversity.

Our growing awareness of the microbial world's importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project.

Pinus ponderosa: A checkered past obscured four species.

Premise Of The Study: Molecular genetic evidence can help delineate taxa in species complexes that lack diagnostic morphological characters. Pinus ponderosa (Pinaceae; subsection Ponderosae) is recognized as a problematic taxon: plastid phylogenies of exemplars were paraphyletic, and mitochondrial phylogeography suggested at least four subdivisions of P. ponderosa.

Complex nanomineral formation utilizing kinetic control by PLAL.

We used pulsed-laser ablation in liquids (PLAL) of Cu or Zn foil targets in water or in aqueous Cu or Zn salt solutions. PLAL in neat water generated mixtures of metal and (thermodynamically preferred) metal oxide nanomaterials, whereas the availability of select dissolved anions predictably led to the fabrication of more complex phase-pure nanominerals. PLAL of Cu foil in aqueous CuCl solution produced nano-paratacamite, CuCl(OH), whereas nano-rouaite, Cu(NO)(OH), was formed in aqueous Cu(NO) and NHOH solution.