Appropriate dairy calf feeding from birth to weaning: “it’s an investment for the future”

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Dairy calves must be fed appropriately to meet their nutritional needs, supporting optimal growth and development to achieve the recommended target age at first calving (AFC) of 24 months. Traditional restricted milk feeding practices suppress growth, contribute to negative welfare states and may result in malnutrition and immunosuppression. Despite more recent recommendations to increase milk allowances for pre-weaned calves, restricted feeding remains a common practice. This study explored the rationales behind the calf feeding protocols used by dairy farmers in England. Forty qualitative interviews (26 farmers, 14 advisors) were conducted between May 2016 and June 2017, transcribed in full, then coded into themes. Results indicate that a variety of calf feeding regimes are used on farms, largely determined by farmers’ attitudes regarding ease of management and the wellbeing of calves. Advisors were concerned about widespread underfeeding of calves, which may be partially due to insufficiently clear recommendations for calf milk replacer (CMR) feeding rates. There was also evidence of uncertainty regarding best practices for weaning calves. Collaboration between academic research and industry is essential to establish a consensus on calf feeding standards which support physiological function, facilitate weaning, support growth targets and ensure calf health and welfare is protected

Cell-cell communication enhances the capacity of cell ensembles to sense shallow gradients during morphogenesis

Collective cell responses to exogenous cues depend on cell-cell interactions. In principle, these can result in enhanced sensitivity to weak and noisy stimuli. However, this has not yet been shown experimentally, and, little is known about how multicellular signal processing modulates single cell sensitivity to extracellular signaling inputs, including those guiding complex changes in the tissue form and function. Here we explored if cell-cell communication can enhance the ability of cell ensembles to sense and respond to weak gradients of chemotactic cues. Using a combination of experiments with mammary epithelial cells and mathematical modeling, we find that multicellular sensing enables detection of and response to shallow Epidermal Growth Factor (EGF) gradients that are undetectable by single cells. However, the advantage of this type of gradient sensing is limited by the noisiness of the signaling relay, necessary to integrate spatially distributed ligand concentration information. We calculate the fundamental sensory limits imposed by this communication noise and combine them with the experimental data to estimate the effective size of multicellular sensory groups involved in gradient sensing. Functional experiments strongly implicated intercellular communication through gap junctions and calcium release from intracellular stores as mediators of collective gradient sensing. The resulting integrative analysis provides a framework for understanding the advantages and limitations of sensory information processing by relays of chemically coupled cells.Comment: paper + supporting information, total 35 pages, 15 figure

Assessment for Active Living

Robert Wood Johnson Foundation’s Active Living by Design (ALbD) grant program funded 25 communities across the U.S. The ALbD National Program Office (NPO) supported grantee community partnerships with technical assistance for assessment, planning, and implementation activities intended to increase population levels of physical activity

Norovirus Epidemiology and Duration of Shedding in Michigan, 2007-2008

Background: In the United States, an estimated 23 million cases of norovirus (NoV) are reported each year, and although mortality is low, the morbidity and economic impact are substantial. Methods: RT-PCR and sequencing were used for identification of NoV genotypes obtained from outbreak and sporadic cases. RT Quant PCR was used to determine the viral load in fecal specimens. In order to rule out bacterial infection as the cause for acute gastroenteritis (AGE), bacterial culture for Salmonella, E.coli O157, Shigella, Campylobacter and Clostridium difficile was performed by standard laboratory procedures. The duration of NV shedding was investigated with longitudinal sampling in the sporadic cases and an evaluation of the association between viral load and days since clinical onset in the outbreak-associated cases. Results: We describe the epidemiology and strain identification for NoV circulating in Michigan during 2007-8 in concurrent sporadic and outbreak-associated cases. In 2007- 8, 138 norovirus outbreaks (3,437 cases) were reported to the MDCH. Among the 47 outbreak specimens sequenced, GI was identified in 14 (29.8%) and GII in 33 (70.2%). The predominant type was GII.4, found in 23 of the 33 (69.6%) GII specimens. The statistical analysis of outbreak-associated cases showed that neither NoV type nor number of days post-onset were associated with NoV log concentration. Among the sporadic cases, the repeated measures analysis of variance showed that NoV type (I or II) was not associated with log titer (P = 0.90), but that the number of weeks post-onset was statistically associated with declining log titer at p = 0.0005. Conclusion: We found no predominant strain difference between concurrent sporadic and outbreak-associated cases. Prevalent strains of NoV were shed in high concentration for at least two weeks past disease onset, suggesting that current public health recommendations for 2-3 days home isolation following clinical recovery may need to be lengthened

Band offsets of metal oxide contacts on TlBr radiation detectors

Metal oxides are investigated as an alternative to metal contacts on thallium bromide (TlBr) radiation detectors. X-ray photoelectron spectroscopy studies of SnO 2/TlBr and ITO/TlBr devices indicate that a type-II staggered heterojunction forms between TlBr and metal oxides upon contacting. By using the Kraut method of valence band offset (VBO) determination, the VBOs of SnO 2/TlBr and ITO/TlBr heterojunctions are determined to be 1.05 ± 0.17 and 0.70 ± 0.17 eV, respectively. The corresponding conduction band offsets are then found to be 0.13 ± 0.17 and 0.45 ± 0.17 eV, respectively. The I-V response of symmetric In/SnO 2/TlBr and In/ITO/TlBr planar devices is almost Ohmic with a leakage current of less than 2.5 nA at 100 V

Protein aggregation mediates stoichiometry of protein complexes in aneuploid cells

Aneuploidy, a condition characterized by chromosome gains and losses, causes reduced fitness and numerous cellular stresses, including increased protein aggregation. Here, we identify protein complex stoichiometry imbalances as a major cause of protein aggregation in aneuploid cells. Subunits of protein complexes encoded on excess chromosomes aggregate in aneuploid cells, which is suppressed when expression of other subunits is coordinately altered. We further show that excess subunits are either degraded or aggregate and that protein aggregation is nearly as effective as protein degradation at lowering levels of excess proteins. Our study explains why proteotoxic stress is a universal feature of the aneuploid state and reveals protein aggregation as a form of dosage compensation to cope with disproportionate expression of protein complex subunits

Band offsets of metal oxide contacts on TlBr radiation detectors

Metal oxides are investigated as an alternative to metal contacts on thallium bromide (TlBr) radiation detectors. X-ray photoelectron spectroscopy studies of SnO 2/TlBr and ITO/TlBr devices indicate that a type-II staggered heterojunction forms between TlBr and metal oxides upon contacting. By using the Kraut method of valence band offset (VBO) determination, the VBOs of SnO 2/TlBr and ITO/TlBr heterojunctions are determined to be 1.05 ± 0.17 and 0.70 ± 0.17 eV, respectively. The corresponding conduction band offsets are then found to be 0.13 ± 0.17 and 0.45 ± 0.17 eV, respectively. The I-V response of symmetric In/SnO 2/TlBr and In/ITO/TlBr planar devices is almost Ohmic with a leakage current of less than 2.5 nA at 100 V

Cytoplasmic p53 couples oncogene-driven glucose metabolism to apoptosis and is a therapeutic target in glioblastoma.

Cross-talk among oncogenic signaling and metabolic pathways may create opportunities for new therapeutic strategies in cancer. Here we show that although acute inhibition of EGFR-driven glucose metabolism induces only minimal cell death, it lowers the apoptotic threshold in a subset of patient-derived glioblastoma (GBM) cells. Mechanistic studies revealed that after attenuated glucose consumption, Bcl-xL blocks cytoplasmic p53 from triggering intrinsic apoptosis. Consequently, targeting of EGFR-driven glucose metabolism in combination with pharmacological stabilization of p53 with the brain-penetrant small molecule idasanutlin resulted in synthetic lethality in orthotopic glioblastoma xenograft models. Notably, neither the degree of EGFR-signaling inhibition nor genetic analysis of EGFR was sufficient to predict sensitivity to this therapeutic combination. However, detection of rapid inhibitory effects on [18F]fluorodeoxyglucose uptake, assessed through noninvasive positron emission tomography, was an effective predictive biomarker of response in vivo. Together, these studies identify a crucial link among oncogene signaling, glucose metabolism, and cytoplasmic p53, which may potentially be exploited for combination therapy in GBM and possibly other malignancies

Promoting Evidence-based Veterinary Medicine through the online resource ‘EBVM Learning’: User feedback

‘EBVM Learning’ is a freely available resource created in 2015 by an international team with the support of RCVS Knowledge. The resource comprises a series of online modules teaching the fundamental concepts of evidence-based veterinary medicine (EBVM) (Ask, Acquire, Appraise, Apply & Assess) supported by case studies, exercises, worked examples and quizzes. The aim of the current study (undertaken in 2019) was to review ‘EBVM Learning’ to ensure its ongoing relevance and usefulness to the range of learners engaged in EBVM. Feedback was gathered from stakeholder groups using website statistics and feedback forms, a survey and semi-structured interviews to provide a combination of quantitative and qualitative data.Website statistics revealed an international audience and a steady increase in visitors exceeding 1,000 per month in August 2020. Feedback via the online form (n=35) and survey (n=71) indicated that the resource was well structured, with an appropriate level and amount of content, useful examples and quizzes and the majority of respondents would use it again. Semi-structured interviews of educators (n=5) and veterinarians (n=8) identified three themes: features of the ‘EBVM Learning’ resource (strengths, suggestions for improvement), embedding the resource in education (undergraduate, postgraduate) and promoting EBVM (challenges, motivation for engagement). At a project team workshop the results were used to plan updates to the existing content and to identify new ways to promote learning and engagement. An updated version of ‘EBVM Learning’ was developed.‘EBVM Learning’ is helping to produce the next generation of evidence-based practitioners and enabling to engage in the concepts of EBVM as part of their clinical practice

Conformational adaptation of Asian macaque TRIMCyp directs lineage specific antiviral activity

TRIMCyps are anti-retroviral proteins that have arisen independently in New World and Old World primates. All TRIMCyps comprise a CypA domain fused to the tripartite domains of TRIM5α but they have distinct lentiviral specificities, conferring HIV-1 restriction in New World owl monkeys and HIV-2 restriction in Old World rhesus macaques. Here we provide evidence that Asian macaque TRIMCyps have acquired changes that switch restriction specificity between different lentiviral lineages, resulting in species-specific alleles that target different viruses. Structural, thermodynamic and viral restriction analysis suggests that a single mutation in the Cyp domain, R69H, occurred early in macaque TRIMCyp evolution, expanding restriction specificity to the lentiviral lineages found in African green monkeys, sooty mangabeys and chimpanzees. Subsequent mutations have enhanced restriction to particular viruses but at the cost of broad specificity. We reveal how specificity is altered by a scaffold mutation, E143K, that modifies surface electrostatics and propagates conformational changes into the active site. Our results suggest that lentiviruses may have been important pathogens in Asian macaques despite the fact that there are no reported lentiviral infections in current macaque populations