Additive prognostic value of preoperative plasma glucose concentrations in calves undergoing abdominal surgery.

Surgical abdominal emergencies in calves are associated with a guarded prognosis, especially if neonates are affected. Because hypoglycemia has been associated with sepsis and endotoxemia, this study aimed to assess the prognostic relevance of preoperative plasma glucose concentrations (GLUC) in calves requiring surgery for an acute abdominal disorder. For this purpose, data from retrospective and prospective case series were analyzed, consisting of 586 and 83 hospitalized calves, respectively. The outcomes of calves were evaluated until hospital discharge (both study populations) and for 3 mo following discharge by a phone call to the farmer (prospective study population). For the retrospective study population, the overall survival rate was 31.2%. Calves with a negative outcome (NO) had significantly lower median GLUC (4.3 mmol/L) than calves with a positive outcome (PO; 5.0 mmol/L). The survival rates of calves with GLUC 8.84 mmol/L), and GLUC <4.4 mmol/L (age 7-20 d) and <3.3 mmol/L (age ≥21 d), respectively. The area under the receiver operating characteristic curve of this model was 0.79 (95% confidence interval: 0.76-0.83) and the resulting sensitivity and specificity for NO at the optimal probability cut-point of 0.69 were 66.7 and 85.8%, respectively. For the prospective study population, the established model had sensitivity and specificity for predicting NO after 3 mo (proportion 24%) of 61.9 and 85%, respectively. In both study populations, hypoglycemia was significantly associated with intraoperative evidence of a septic process within the abdominal cavity. The present analyses show that hypoglycemia was highly indicative of a poor prognosis and serious intraoperative findings such as peritonitis. Determination of GLUC should therefore be part of the diagnostic work-up in calves suffering from an acute abdominal emergency

Let your maps be fuzzy!—Class probabilities and floristic gradients as alternatives to crisp mapping for remote sensing of vegetation

Mapping vegetation as hard classes based on remote sensing data is a frequently applied approach, even though this crisp, categorical representation is not in line with nature\u27s fuzziness. Gradual transitions in plant species composition in ecotones and faint compositional differences across different patches are thus poorly described in the resulting maps. Several concepts promise to provide better vegetation maps. These include (1) fuzzy classification (a.k.a. soft classification) that takes the probability of an image pixel\u27s class membership into account and (2) gradient mapping based on ordination, which describes plant species composition as a floristic continuum and avoids a categorical description of vegetation patterns. A systematic and comprehensive comparison of these approaches is missing to date. This paper hence gives an overview of the state of the art in fuzzy classification and gradient mapping and compares the approaches in a case study. The advantages and disadvantages of the approaches are discussed and their performance is compared to hard classification (a.k.a. crisp or boolean classification). Gradient mapping best conserves the information in the original data and does not require an a priori categorization. Fuzzy classification comes close in terms of information loss and likewise preserves the continuous nature of vegetation, however, still relying on a priori classification. The need for a priori classification may be a disadvantage or, in other cases, an advantage because it allows using categorical input data instead of the detailed vegetation records required for ordination. Both approaches support spatially explicit accuracy analyses, which further improves the usefulness of the output maps. Gradient mapping and fuzzy classification offer various advantages over hard classification, can always be transformed into a crisp map and are generally applicable to various data structures. We thus recommend the use of these approaches over hard classification for applications in ecological research

Microdeletion of target sites for insulator protein CTCF in a chromosome 11p15 imprinting center in Beckwith-Wiedemann syndrome and Wilms' tumor

We have analyzed several cases of Beckwith-Wiedemann syndrome (BWS) with Wilms' tumor in a familial setting, which give insight into the complex controls of imprinting and gene expression in the chromosome 11p15 region. We describe a 2.2-kbp microdeletion in the H19/insulin-like growth factor 2 (IGF2)-imprinting center eliminating three target sites of the chromatin insulator protein CTCF that we believe here is necessary, but not sufficient, to cause BWS and Wilms' tumor. Maternal inheritance of the deletion is associated with IGF2 loss of imprinting and up-regulation of IGF2 mRNA. However, in at least one affected family member a second genetic lesion (a duplication of maternal 11p15) was identified and accompanied by a further increase in IGF2 rnRNA levels 35-fold higher than control values. Our results suggest that the combined effects of the H19//GF2-imprinting center microdeletion and 11p15 chromosome duplication were necessary for manifestation of BWS

A founder CEP120 mutation in Jeune asphyxiating thoracic dystrophy expands the role of centriolar proteins in skeletal ciliopathies.

Jeune asphyxiating thoracic dystrophy (JATD) is a skeletal dysplasia characterized by a small thoracic cage and a range of skeletal and extra-skeletal anomalies. JATD is genetically heterogeneous with at least nine genes identified, all encoding ciliary proteins, hence the classification of JATD as a skeletal ciliopathy. Consistent with the observation that the heterogeneous molecular basis of JATD has not been fully determined yet, we have identified two consanguineous Saudi families segregating JATD who share a single identical ancestral homozygous haplotype among the affected members. Whole-exome sequencing revealed a single novel variant within the disease haplotype in CEP120, which encodes a core centriolar protein. Subsequent targeted sequencing of CEP120 in Saudi and European JATD cohorts identified two additional families with the same missense mutation. Combining the four families in linkage analysis confirmed a significant genome-wide linkage signal at the CEP120 locus. This missense change alters a highly conserved amino acid within CEP120 (p.Ala199Pro). In addition, we show marked reduction of cilia and abnormal number of centrioles in fibroblasts from one affected individual. Inhibition of the CEP120 ortholog in zebrafish produced pleiotropic phenotypes characteristic of cilia defects including abnormal body curvature, hydrocephalus, otolith defects and abnormal renal, head and craniofacial development. We also demonstrate that in CEP120 morphants, cilia are shortened in the neural tube and disorganized in the pronephros. These results are consistent with aberrant CEP120 being implicated in the pathogenesis of JATD and expand the role of centriolar proteins in skeletal ciliopathies

A founder CEP120 mutation in Jeune asphyxiating thoracic dystrophy expands the role of centriolar proteins in skeletal ciliopathies

Jeune asphyxiating thoracic dystrophy (JATD) is a skeletal dysplasia characterized by a small thoracic cage and a range of skeletal and extra-skeletal anomalies. JATD is genetically heterogeneous with at least nine genes identified, all encoding ciliary proteins, hence the classification of JATD as a skeletal ciliopathy. Consistent with the observation that the heterogeneous molecular basis of JATD has not been fully determined yet, we have identified two consanguineous Saudi families segregating JATD who share a single identical ancestral homozygous haplotype among the affected members. Whole-exome sequencing revealed a single novel variant within the disease haplotype in CEP120, which encodes a core centriolar protein. Subsequent targeted sequencing of CEP120 in Saudi and European JATD cohorts identified two additional families with the same missense mutation. Combining the four families in linkage analysis confirmed a significant genome-wide linkage signal at the CEP120 locus. This missense change alters a highly conserved amino acid within CEP120 (p.Ala199Pro). In addition, we show marked reduction of cilia and abnormal number of centrioles in fibroblasts from one affected individual. Inhibition of the CEP120 ortholog in zebrafish produced pleiotropic phenotypes characteristic of cilia defects including abnormal body curvature, hydrocephalus, otolith defects and abnormal renal, head and craniofacial development. We also demonstrate that in CEP120 morphants, cilia are shortened in the neural tube and disorganized in the pronephros. These results are consistent with aberrant CEP120 being implicated in the pathogenesis of JATD and expand the role of centriolar proteins in skeletal ciliopathie

Understanding forest health with Remote sensing-Part II-A review of approaches and data models

Stress in forest ecosystems (FES) occurs as a result of land-use intensification, disturbances, resource limitations or unsustainable management, causing changes in forest health (FH) at various scales from the local to the global scale. Reactions to such stress depend on the phylogeny of forest species or communities and the characteristics of their impacting drivers and processes. There are many approaches to monitor indicators of FH using in-situ forest inventory and experimental studies, but they are generally limited to sample points or small areas, as well as being time- and labour-inte

Hyaline fibromatosis syndrome inducing mutations in the ectodomain of anthrax toxin receptor 2 can be rescued by proteasome inhibitors.

Hyaline Fibromatosis Syndrome (HFS) is a human genetic disease caused by mutations in the anthrax toxin receptor 2 (or cmg2) gene, which encodes a membrane protein thought to be involved in the homeostasis of the extracellular matrix. Little is known about the structure and function of the protein or the genotype-phenotype relationship of the disease. Through the analysis of four patients, we identify three novel mutants and determine their effects at the cellular level. Altogether, we show that missense mutations that map to the extracellular von Willebrand domain or the here characterized Ig-like domain of CMG2 lead to folding defects and thereby to retention of the mutated protein in the endoplasmic reticulum (ER). Mutations in the Ig-like domain prevent proper disulphide bond formation and are more efficiently targeted to ER-associated degradation. Finally, we show that mutant CMG2 can be rescued in fibroblasts of some patients by treatment with proteasome inhibitors and that CMG2 is then properly transported to the plasma membrane and signalling competent, identifying the ER folding and degradation pathway components as promising drug targets for HFS