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Udder cleft dermatitis (UCD) is a well-known disorder in dairy cows. Veterinary literature about this subject, however, is scarce. The objectives of this study were to define a clinical scoring system for UCD, estimate the within-herd prevalence of UCD, and identify potential risk factors of UCD at cow and herd level. On 20 randomly selected dairy farms in the Netherlands, each lactating cow was photographed from a ventral, lateral, and caudal position. A scoring system with 6 categories of severity of UCD was proposed based on the ventral photographs. Cow measures such as udder width and depth, and front quarter attachment were determined from the lateral and caudal photographs. A questionnaire was conducted on each farm during farm visits. Udder cleft dermatitis, defined as a score 3 or higher, was detected in 5.2% of the 948 cows involved in this study. Within-herd prevalences of UCD ranged between 0 and 15% and UCD was found in 16 (80%) of the participating farms. Cows with a deep udder (relative to the hock), large front quarters, and a small angle between udder and abdominal wall were more likely to develop UCD. Production level and use of a footbath were identified as being positively associated with herd-level UCD prevalence. Herd size and average bulk milk somatic cell count did not seem to be associated with UCD prevalence. Because of the small herd sample size, no firm conclusions were drawn on herd-level risk factors. However, results from this study can be used in designing a future longitudinal UCD study. The prevalences of UCD found in the present study illustrate the current UCD situation in the Netherlands. Our results demonstrate that multiple potential risk factors of UCD could be identified at both the cow and herd level

Ccaat/enhancer-binding protein delta (C/ebpδ): A previously unrecognized tumor suppressor that limits the oncogenic potential of pancreatic ductal adenocarcinoma cells

CCAAT/enhancer-binding protein δ (C/EBPδ) is a transcription factor involved in growth arrest and differentiation, which has consequently been suggested to harbor tumor suppressive activities. However, C/EBPδ over-expression correlates with poor prognosis in glioblastoma and promotes genomic instability in cervical cancer, hinting at an oncogenic role of C/EBPδ in these contexts. Here, we explore the role of C/EBPδ in pancreatic cancer. We determined C/EBPδ expression in biopsies from pancreatic cancer patients using public gene-expression datasets and in-house tissue microarrays. We found that C/EBPδ is highly expressed in healthy pancreatic ductal cells but lost in pancreatic ductal adenocarcinoma. Furthermore, loss of C/EBPδ correlated with increased lymph node involvement and shorter overall survival in pancreatic ductal adenocarcinoma patients. In accordance with this, in vitro experiments showed reduced clonogenic capacity and proliferation of pancreatic ductal adenocarcinoma cells following C/EBPδ re-expression, concurrent with decreased sphere formation capacity in soft agar assays. We thus report a previously unrecognized but important tumor suppressor role of C/EBPδ in pancreatic ductal adenocarcinoma. This is of particular interest since only few tumor suppressors have been identified in the context of pancreatic cancer. Moreover, our findings suggest that restoration of C/EBPδ activity could hold therapeutic value in pancreatic ductal adenocarcinoma, although the latter claim needs to be substantiated in future studies

Declining Orangutan Encounter Rates from Wallace to the Present Suggest the Species Was Once More Abundant

BACKGROUND: Bornean orangutans (Pongo pygmaeus) currently occur at low densities and seeing a wild one is a rare event. Compared to present low encounter rates of orangutans, it is striking how many orangutan each day historic collectors like Alfred Russel Wallace were able to shoot continuously over weeks or even months. Does that indicate that some 150 years ago encounter rates with orangutans, or their densities, were higher than now? METHODOLOGY/PRINCIPAL FINDINGS: We test this hypothesis by quantifying encounter rates obtained from hunting accounts, museum collections, and recent field studies, and analysing whether there is a declining trend over time. Logistic regression analyses of our data support such a decline on Borneo between the mid-19th century and the present. Even when controlled for variation in the size of survey and hunting teams and the durations of expeditions, mean daily encounter rates appear to have declined about 6-fold in areas with little or no forest disturbance. CONCLUSIONS/SIGNIFICANCE: This finding has potential consequences for our understanding of orangutans, because it suggests that Bornean orangutans once occurred at higher densities. We explore potential explanations-habitat loss and degradation, hunting, and disease-and conclude that hunting fits the observed patterns best. This suggests that hunting has been underestimated as a key causal factor of orangutan density and distribution, and that species population declines have been more severe than previously estimated based on habitat loss only. Our findings may require us to rethink the biology of orangutans, with much of our ecological understanding possibly being based on field studies of animals living at lower densities than they did historically. Our approach of quantifying species encounter rates from historic data demonstrates that this method can yield valuable information about the ecology and population density of species in the past, providing new insight into species' conservation needs

Макрофагальная активность в коже больных псориазом при NB-UVB (311 нм) терапии

Досліджено 55 пацієнтів хворих на псоріаз. Пацієнти були розділені на 2 групи. Група 1 – 27 пацієнтів, які отримували тільки стандартне лікування і група 2 – 28 пацієнтів, які отримували стандартну і NB-UVB терапію. NB-UVB призначалась 3 рази в тиждень, при цьому використовували стартову дозу 0,1-0,3 J/cm2 , середня кумулятивна доза від 30 до 60 J/cm2 . Рівень макрофагальної активності в біоптатах шкіри досліджували за допомогою імуногістохімічного методу на 1 і 21 добу. NB-UVB терапія призовдить до зниження рівня експресії CD68 – маркера макрофагів, більшою часткою якої є функціонально-активні клітини, що свідчить про адекватність імуної відповіді і зниження запальної реакції.There were researched 55 psoriasis patients. Patients were divided in two groups. Group 1 – 27 patients who received only standard therapy and Group 2 – 28 patients who received standard and NB-UVB therapy. NB-UVB treatment was applied three times weekly. Starting UVB dose 0.1-0.3 J/cm2 , the mean cumulative UVB dose was 42.0 J/cm2 . The level of macrophage activity in skin biopsy was investigated by an immunohistochemical method on 1 and 21 days. NB-UVB therapy is linked to decline of level of CD68 expression with predominant of functionally active cells which testifies to adequacy of immune reactions and decline of inflammatory reaction

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Migrants’ decision-process shaping work destination choice: the case of long-term care work in the United Kingdom and Norway

Escalating demands for formal long-term care (LTC) result in the reliance on migrant workers in many developed countries. Within Europe, this is currently framed by progressive European immigration policies favouring inter-European mobility. Using the UK and Norway as case studies, this article has two main aims: (1) to document changes in the contribution of European Union (EU) migrants to the LTC sectors in Western Europe, and (2) to gain further understanding of migrants’ decision-processes relating to destination and work choices. The UK and Norway provide examples of two European countries with different immigration histories, welfare regimes, labour market characteristics and cultural values, offering a rich comparison platform. The analysis utilizes national workforce datasets and data obtained from migrants working in the LTC sector in the UK and Norway (n = 248) and other stakeholders (n = 136). The analysis establishes a significant increase in the contribution of EU migrants (particularly from Eastern Europe) to the LTC sector in both the UK and Norway despite their different welfare regimes. The findings also highlight how migrant care workers develop rational decision-processes influenced by subjective perspectives of investments and returns within a context of wider structural migration barriers. The latter includes welfare and social care policies framing the conditions for migrants’ individual actions

Landscape of somatic mutations in 560 breast cancer whole-genome sequences.

We analysed whole-genome sequences of 560 breast cancers to advance understanding of the driver mutations conferring clonal advantage and the mutational processes generating somatic mutations. We found that 93 protein-coding cancer genes carried probable driver mutations. Some non-coding regions exhibited high mutation frequencies, but most have distinctive structural features probably causing elevated mutation rates and do not contain driver mutations. Mutational signature analysis was extended to genome rearrangements and revealed twelve base substitution and six rearrangement signatures. Three rearrangement signatures, characterized by tandem duplications or deletions, appear associated with defective homologous-recombination-based DNA repair: one with deficient BRCA1 function, another with deficient BRCA1 or BRCA2 function, the cause of the third is unknown. This analysis of all classes of somatic mutation across exons, introns and intergenic regions highlights the repertoire of cancer genes and mutational processes operating, and progresses towards a comprehensive account of the somatic genetic basis of breast cancer

The effects of ditch dams on water‐level dynamics in tropical peatlands

A significant proportion of tropical peatlands has been drained for agricultural purposes, resulting in severe degradation. Hydrological restoration, which usually involves blocking ditches, is therefore a priority. Nevertheless, the influence of ditch blocking on tropical peatland hydrological functioning is still poorly understood. We studied water-level dynamics using a combination of automated and manual dipwells, and also meteorological data during dry and wet seasons over 6 months at three locations in Sebangau National Park, Kalimantan, Indonesia. The locations were a forested peatland (Forested), a drained peatland with ditch dams (Blocked), and a drained peatland without ditch dams (Drained). In the dry season, water tables at all sites were deeper than the Indonesian regulatory requirement of 40 cm from the peat surface. In the dry season, the ditches were dry and water did not flow to them. The dry season water-table drawdown rates — solely due to evapotranspiration — were 9.3 mm day−1 at Forested, 9.6 mm day−1 at Blocked, but 12.7 mm day−1 at Drained. In the wet season, the proportion of time during which water tables in the wells were deeper than the 40 cm limit ranged between 16% and 87% at Forested, 0% at Blocked, and between 0% and 38% at Drained. In the wet season, water flowed from the peatland to ditches at Blocked and Drained. The interquartile range of hydraulic gradients between the lowest ditch outlet and the farthest well from ditches at Blocked was 3.7 × 10−4 to 7.8 × 10−4 m m−1, but 1.9 × 10−3 to 2.6 × 10−3 m m−1 at Drained. Given the results from Forested, a water-table depth limit policy based on field data may be required, to reflect natural seasonal dynamics in tropical peatlands. Revised spatial designs of dams or bunds are also required, to ensure effective water-table management as part of tropical peatland restoration