Relationship between blood attributes and predicted breeding value for milk yield in calves

International audienc

Network analysis of genes regulated in renal diseases: implications for a molecular-based classification

Abstract Background Chronic renal diseases are currently classified based on morphological similarities such as whether they produce predominantly inflammatory or non-inflammatory responses. However, such classifications do not reliably predict the course of the disease and its response to therapy. In contrast, recent studies in diseases such as breast cancer suggest that a classification which includes molecular information could lead to more accurate diagnoses and prediction of treatment response. This article describes how we extracted gene expression profiles from biopsies of patients with chronic renal diseases, and used network visualizations and associated quantitative measures to rapidly analyze similarities and differences between the diseases. Results The analysis revealed three main regularities: (1) Many genes associated with a single disease, and fewer genes associated with many diseases. (2) Unexpected combinations of renal diseases that share relatively large numbers of genes. (3) Uniform concordance in the regulation of all genes in the network. Conclusion The overall results suggest the need to define a molecular-based classification of renal diseases, in addition to hypotheses for the unexpected patterns of shared genes and the uniformity in gene concordance. Furthermore, the results demonstrate the utility of network analyses to rapidly understand complex relationships between diseases and regulated genes.http://deepblue.lib.umich.edu/bitstream/2027.42/112463/1/12859_2009_Article_3354.pd

Multisystem proteinopathy due to a homozygous p.Arg159His VCP mutation : a tale of the unexpected

ObjectiveTo assess the clinical, radiologic, myopathologic, and proteomic findings in a patient manifesting a multisystem proteinopathy due to a homozygous valosin-containing protein gene (VCP) mutation previously reported to be pathogenic in the heterozygous state.MethodsWe studied a 36-year-old male index patient and his father, both presenting with progressive limb-girdle weakness. Muscle involvement was assessed by MRI and muscle biopsies. We performed whole-exome sequencing and Sanger sequencing for segregation analysis of the identified p.Arg159His VCP mutation. To dissect biological disease signatures, we applied state-of-the-art quantitative proteomics on muscle tissue of the index case, his father, 3 additional patients with VCP-related myopathy, and 3 control individuals.ResultsThe index patient, homozygous for the known p.Arg159His mutation in VCP, manifested a typical VCP-related myopathy phenotype, although with a markedly high creatine kinase value and a relatively early disease onset, and Paget disease of bone. The father exhibited a myopathy phenotype and discrete parkinsonism, and multiple deceased family members on the maternal side of the pedigree displayed a dementia, parkinsonism, or myopathy phenotype. Bioinformatic analysis of quantitative proteomic data revealed the degenerative nature of the disease, with evidence suggesting selective failure of muscle regeneration and stress granule dyshomeostasis.ConclusionWe report a patient showing a multisystem proteinopathy due to a homozygous VCP mutation. The patient manifests a severe phenotype, yet fundamental disease characteristics are preserved. Proteomic findings provide further insights into VCP-related pathomechanisms

The microbial diversity of the Su Bentu cave, Italy and the influence of human exploration.

Introduction: The microbial diversity in the Su Bentu Cave (Sardinia, Italy) was investigated by means of Illumina MiSeq analysis. The hypogean environment is of great interest for astrobiological research as cave conditions may resemble those in extra-terrestrial regions. Furthermore, they hold high potential to identify novel, extremely adapted organisms to severely oligo-trophic habitats. However, the influence of human is not neglectable and in-depth investigations are needed to determine the impact of exploration on an otherwise mostly pristine ecosystem. The cave investigated in this study develops for several kilometres into the mountain, two hundred metres below the topographic surface and is characterized by a strong air circulation. Its structure is composed of huge passages carved in limestone where an ephemeral underground stream creates some lakes, close to which seven samples of visible calcite rafts, manganese deposits and moonmilk (a hydrated calcium carbonate speleothem), were sampled during an expedition in 2014. Other samples were re-trieved from a frequently used campsite and from some dry cave passages leading deeper into the cave

Bio-electrospraying and aerodynamically assisted bio-jetting the model eukaryotic Dictyostelium discoideum: assessing stress and developmental competency post treatment

Bio-electrospraying (BES) and aerodynamically assisted bio-jetting (AABJ) have recently been established as important novel biospray technologies for directly manipulating living cells. To elucidate their potential in medical and clinical sciences, these bio-aerosol techniques have been subjected to increasingly rigorous investigations. In parallel to these studies, we wish to introduce these unique biotechnologies for use in the basic biological sciences, for handling a wide range of cell types and systems, thus increasing the range and the scope of these techniques for modern research. Here, the authors present the analysis of the new use of these biospray techniques for the direct handling of the simple eukaryotic biomedical model organism Dictyostelium discoideum. These cells are widely used as a model for immune cell chemotaxis and as a simple model for development. We demonstrate that AABJ of these cells did not cause cell stress, as defined by the stress-gene induction, nor affect cell development. Furthermore, although BES induced the increased expression of one stress-related gene (gapA), this was not a generalized stress response nor did it affect cell development. These data suggest that these biospray techniques can be used to directly manipulate single cells of this biomedical model without inducing a generalized stress response or perturbing later development

Penetrating Blast Injury to the Knee of a United States Soldier Treated with Allograft Mosaicplasty

Objective: This is the first report of successful allograft mosaicplasty treatment of a large osteochondral lesion of the knee caused by a blast fragment sustained during combat operations. The patient was able to return to active duty following rehabilitation. Methods: An active-duty infantryman sustained an osteochondral lesion of the medial femoral condyle caused by a metallic fragment of an explosively formed projectile. Initial treatment consisted of removal of the foreign body and primary closure. The patient continued to experience pain, mechanical symptoms, and repeated effusions after initial nonoperative treatment. Allograft mosaicplasty of the lesion utilizing two 18-mm-diameter fresh allograft osteochondral plugs was performed at 6 months post-injury. Results: At 2-year follow-up, the patient remains on active duty with marked improvement in symptoms. Two years postoperatively, his outcome scores are 72 of 100 on the Western Ontario and McMaster University osteoarthritis scoring index (WOMAC) and 60 of 100 on the Knee Injury and Osteoarthritis Outcome Score (KOOS). His follow-up x-rays and MRI demonstrate intact articular cartilage and subchondral bone incorporation. Conclusion: Penetrating injuries to joints are commonplace in the battlefield environment. Combat injuries to the knee are frequently associated with articular cartilage injury. While numerous cartilage restoration techniques have been used with success for the treatment of osteochondral injuries to the femoral condyles, no published reports describe the use of allograft mosaicplasty in this location for open, penetrating injuries with focal cartilage loss. This is the first documented use of allograft mosaicplasty for a traumatic osteochondral defect of the medial femoral condyle caused by a metallic projectile. The patient was able to return to active duty following rehabilitation. We demonstrate a high level of functioning is possible following allograft mosaicplasty of a large osteochondral lesion caused by penetrating ballistic trauma

Clinical trial readiness to solve barriers to drug development in FSHD (ReSolve): protocol of a large, international, multi-center prospective study

Background Facioscapulohumeral muscular dystrophy (FSHD) is a dominantly-inherited progressive muscular dystrophy caused by de-repression of the DUX4 gene, which causes disease by a toxic-gain-of-function. As molecularly targeted drugs move from preclinical testing into human trials, it is essential that we validate clinical trial tools and methodology to facilitate the drug development process. Methods/design The primary goal of this study is to hasten drug development for FSHD by validating two novel clinical outcome assessments (COAs) and refining clinical trial strategies. We will perform an 18-month longitudinal study in 220 genetically confirmed and clinically affected participants using our FSHD Clinical Trial Research Network, comprised of 8 sites in the United States, and 3 collaborating sites in Europe. Visits occur at baseline and months 3, 12, and 18. At each visit we will collect: 1) a novel FSHD functional composite COA made up of 18 evaluator-administered motor tasks in the domains of shoulder/arm, hand, core/abdominal, leg, and balance function; and 2) electrical impedance myography as a novel muscle quality biomarker (US sites). Other COAs include 1) Domain 1 of the Motor Function Measure; 2) Reachable workspace; 3) orofacial strength using the Iowa Oral Performance Instrument; 4) lean muscle mass using dual-energy X-ray absorptiometry (DEXA); 5) strength as measured by quantitative myometry and manual muscle testing; and 6) the FSHD Health Index and other patient-reported outcomes. Plasma, DNA, RNA, and serum will be collected for future biomarker studies. We will use an industry standard multi-site training plan. We will evaluate the test-retest reliability, validity, and sensitivity to disease progression, and minimal clinically important changes of our new COAs. We will assess associations between demographic and genetic factors and the rate of disease progression to inform refinement of eligibility criteria for future clinical trials. Discussion To the best of our knowledge, this is the largest collaborative study of patients with FSHD performed in the US and Europe. The results of this study will enable more efficient clinical trial design. During the conduct of the study, relevant data will be made available for investigators or companies pursuing novel FSHD therapeutics

Microbiome dynamics during the HI-SEAS IV mission, and implications for future crewed missions beyond Earth.

Background: Human health is closely interconnected with its microbiome. Resilient microbiomes in, on, and around the human body will be key for safe and successful long-term space travel. However, longitudinal dynamics of microbiomes inside confined built environments are still poorly understood. Herein, we used the Hawaii Space Exploration Analog and Simulation IV (HI-SEAS IV) mission, a 1 year-long isolation study, to investigate microbial transfer between crew and habitat, in order to understand adverse developments which may occur in a future outpost on the Moon or Mars. Results: Longitudinal 16S rRNA gene profiles, as well as quantitative observations, revealed significant differences in microbial diversity, abundance, and composition between samples of the built environment and its crew. The microbiome composition and diversity associated with abiotic surfaces was found to be rather stable, whereas the microbial skin profiles of individual crew members were highly dynamic, resulting in an increased microbiome diversity at the end of the isolation period. The skin microbiome dynamics were especially pronounced by a regular transfer of the indicator species Methanobrevibacter between crew members within the first 200 days. Quantitative information was used to track the propagation of antimicrobial resistance in the habitat. Together with functional and phenotypic predictions, quantitative and qualitative data supported the observation of a delayed longitudinal microbial homogenization between crew and habitat surfaces which was mainly caused by a malfunctioning sanitary facility. Conclusions: This study highlights main routes of microbial transfer, interaction of the crew, and origins of microbial dynamics in an isolated environment. We identify key targets of microbial monitoring, and emphasize the need for defined baselines of microbiome diversity and abundance on surfaces and crew skin. Targeted manipulation to counteract adverse developments of the microbiome could be a highly important strategy to ensure safety during future space endeavors