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Background: Small non-coding microRNAs (miRNAs) are important modulators at post-transcriptional levels. Single-nucleotide polymorphisms (SNPs) located in miRNA genes can alter the secondary structure of pre-miRNA to either impair or promote the miRNA maturation processes. Furthermore, SNPs located in the miRNA seed regions can stabilize or disturb miRNA-target interactions, thereby, quantitatively influence the expression of target genes. Therefore, the main objective of this study was to detect SNPs in bovine miRNAs using the whole-genome re-sequencing datasets of 1632 cattle of five breeds from the 1000 bull genomes project. Results: In total, our study identified 1109, 334, and 130 SNPs in the miRNA precursor, mature, and seed regions, respectively. The heterozygosity values were generally less than 0.3, and the minor allele frequencies (MAFs) were mainly less than 0.1. Most SNPs were in Hardy-Weinberg equilibrium (HWE) (HWE-P > 0.05). Furthermore, we found that the majority of SNPs (MAF > 0.1 and HWE-P > 0.05) in the miRNA seed regions altered the repertoire of target genes, which in turn were enriched in different KEGG pathways or GO terms. Thus target prediction for bta-miR-2888 revealed loss of 309 target genes and gain of 691 target genes. The 691 gained target genes were significantly enriched in 60 KEGG pathways and 21 GO terms. Conclusion: In summary, our study identified candidate SNPs in miRNA precursor, mature, and seed regions that are likely to affect target RNA interactions, thereby potentially influencing cattle phenotypic traits.

Introduction After over 20 years of war in the Middle East, orthopedic injuries have been among the most prevalent combat-related injuries, accounting for 14% of all surgical procedures at Role 2/3 (R2/R3) facilities according to the DoD Trauma Registry. To further delineate the role of the deployed orthopedic surgeon on the modern battlefield, a retrospective review was performed highlighting both quantitative and qualitative analysis factors associated with orthopedic surgical care during the war in the Middle East. Methods A retrospective review was conducted of orthopedic surgeons in the Middle East from 2001 to 2021. A comprehensive literature search was conducted using the PubMed and Embase databases using a two-reviewer strategy. Articles were compiled and reviewed using Covidence. Inclusion criteria included journal articles focusing on orthopedic injuries sustained during the Global War on Terror (GWoT) in an adult U.S. Military population. In the event of a conflict, a third author would determine the relevance of the article. For the remaining articles, a full-text review was conducted to extract relevant predetermined quantitative data, and the Delphi consensus method was then utilized to highlight relevant qualitative themes. Results The initial search yielded 1,226 potentially relevant articles. In all, 40 studies ultimately met the eligibility criteria. With the consultation of previously deployed orthopedic surgeons at the Walter Reed National Military Medical Center, a retrospective thematic analysis of the 40 studies revealed five themes encompassing the orthopedic surgeons experience throughout GWoT. These themes include unique mechanisms of orthopedic injury compared to previous war injuries due to novel weaponry, differences in interventions depending on R2 versus R3 locations, differences in injuries from those seen in civilian settings, the maintained emphasis on humanitarian aspect of an orthopedic surgeon’s mission, and lastly relation of pre-deployment training to perceived deployed success of the orthopedic surgeons. From this extensive review, we found that explosive mechanisms of injury were greatly increased when compared to previous conflicts and were the etiology for the majority of orthopedic injuries sustained. With the increase of complex explosive injuries in the setting of improved body armor and overall survival, R2/3 facilities showed an increased demand for orthopedic intervention including debridement, amputations, and external fixation. Combat injuries sustained during the GWoT differ in the complications, management, and complexity when compared to civilian trauma. “Humanitarian” cases made up a significant number of operative cases for the deployed orthopedic surgeon. Lastly, heterogeneous training opportunities were available prior to deployment (fellowship, combat extremity surgical courses, and dedicated pre-deployment training), and the most commonly identified useful training was learning additional soft-tissue coverage techniques. Conclusion These major themes indicate an emphasis on pre-deployment training and the strategic positioning of orthopedic surgeons to reflect the changing landscape of musculoskeletal trauma care. Moving forward, these authors recommend analyzing the comfort and perceived capability of orthopedic surgeons in these unique military environments to best prepare for a changing operational format and the possibility of future peer–peer conflicts that will likely lead to a lack of medical evacuation and prolonged field care.

The Göttingen minipig is a large animal with a gyrencephalic brain that expresses complex behaviour, making it an attractive model for Parkinson's disease research. Here, we investigate the temporal evolution of presynaptic dopaminergic function for 14 months after injections of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into the minipig using a multi-tracer longitudinal positron emission tomography (PET) design. We injected seven sedated minipigs with 1-2mg/kg of MPTP, and two with saline, three times a week over four weeks. We monitored behavioral deficits using a validated motor scale and walking mat. Brains were imaged with (+)-⍺-[ 11C]-dihydrotetrabenazine ([ 11C]-DTBZ) and [ 18F]-dihydroxyphenylalanine ([ 18F]-FDOPA) PET at baseline and 1, 3, 10 and 14 months after MPTP injection, and immunohistochemistry was used to assess nigral cell loss. The minipigs showed mild bradykinesia and impaired coordination at early timepoints after MPTP. PET revealed decreases of striatal [ 11C]-DTBZ and [ 18F]-FDOPA uptake post-MPTP with partial spontaneous recovery of [ 18F]-FDOPA after 10 months. Postmortem analysis estimated an MPTP-induced nigral loss of 57% tyrosine hydroxylase+ and 43% Nissl-stained cells. Normal motor function despite substantial damage to the dopaminergic system is consistent with prodromal Parkinson's disease, and offers an opportunity for testing disease-modifying therapies. However, partial spontaneous recovery of dopamine terminal function must be taken into account in future studies.

Resveratrol (RSV) has been confirmed to benefit human health. Resveratrol supplemented in the feeds of animals improved pork, chicken, and duck meat qualities. In this study, we identified differentially expressed (DE) messenger RNAs (mRNAs) (n = 3,856) and microRNAs (miRNAs) (n = 93) for the weighted gene co-expression network analysis (WGCNA) to investigate the co-expressed DE mRNAs and DE miRNAs in the primary bovine myoblasts after RSV treatment. The mRNA results indicated that RSV treatments had high correlations with turquoise module (0.91, P-value = 0.01) and blue module (0.93, P-value < 0.01), while only the turquoise module (0.96, P-value < 0.01) was highly correlated with the treatment status using miRNA data. After biological enrichment analysis, the 2,579 DE genes in the turquoise module were significantly enriched in the Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The top two GO terms were actin filament-based process (GO:0030029) and actin cytoskeleton organization (GO:0030036). The top two KEGG pathways were regulation of actin cytoskeleton (bta04810) and tight junction (bta04530). Then, we constructed the DE mRNA co-expression and DE miRNA co-expression networks in the turquoise module and the mRNA–miRNA targeting networks based on their co-expressions in the key module. In summary, the RSV-induced miRNAs participated in the co-expression networks that could affect mRNA expressions to regulate the primary myoblast differentiation. Our study provided a better understanding of the roles of RSV in inducing miRNA and of the characteristics of DE miRNAs in the key co-expressed module in regulation of mRNAs and revealed new candidate regulatory miRNAs and genes for the beef quality traits.

Several genetic variants have been shown to affect the mean number of offspring in different sheep breeds. Here, we analyzed samples from Icelandic sheep with the aim of identifying the genetic cause of the Icelandic Loa phenotype using three previously identified prolificacy genes as candidates. We demonstrate that a 4-bp frameshift deletion positioned in the mature region of the GDF9 protein in the Loa animals is a likely causal mutation for the observed increase in prolificacy; however, sequencing showed that not all ewes with a high number of offspring carried the deletion, suggesting the presence of a second mutation segregating within this group of animals.

One of the crucial components of well integrity evaluation in offshore drilling is to determine the cement bond quality assuring proper hydraulic sealing. On the Norwegian Continental Shelf (NCS) an industry standard as informative reference imposes verification of cement length and potential barriers using bonding logs. Traditionally, for the last 50 years, wireline (WL) sonic tools have been extensively used for this purpose. However, the applicability of logging-while-drilling (LWD) sonic tools for quantitative cement evaluation was explored in the recent development drilling campaign on the Dvalin Field in the Norwegian Sea, owing to significant advantages on operational efficiency and tool conveyance in any well trajectory. Cement bond evaluation from conventional peak-to-peak amplitude method has shown robust results up to bond indexes of 0.6 for LWD sonic tools. Above this limit, the casing signal is smaller than the collar signal and the amplitude method loses sensitivity to bonding. This practical challenge in the LWD realm was overcome through the inclusion of attenuation rate measurements, which responds accordingly in higher bonding environments. The two methods are used in a hybrid approach providing a full range quantitative bond index (QBI) introduced by Izuhara et al. (2017). In order to conform with local requirements related to well integrity and to ascertain the QBI potential from LWD monopole sonic, a wireline cement bond log (CBL) was acquired in the first well of the campaign for comparison. This enabled the strategic deployment of LWD QBI service in subsequent wells. LWD sonic monopole data was acquired at a controlled speed of 900ft/h. The high-fidelity waveforms were analyzed in a suitable time window and both amplitude- and attenuation-based bond indexes were derived. The combined hybrid bond index showed an excellent match with the wireline reference CBL, both in zones of high as well as lower cement bonding. The presence of formation arrivals was also in good correlation with zones of proper bonding distinguishable on the QBI results. This established the robustness of the LWD cement logging and ensured its applicability in the rest of the campaign which was carried out successfully. While the results from LWD cement evaluation service are omnidirectional, it comes with a wide range of benefits related to rig cost or conveyance in tough borehole trajectories. Early evaluation of cement quality by LWD sonic tools helps to provide adequate time for taking remedial actions if necessary. The LWD sonic as part of the drilling BHA enables this acquisition and service in non-dedicated runs, with the possibility of multiple passes for observing time-lapse effects. Also, the large sizes of LWD tools relative to the wellbore ensures a lower signal attenuation in the annulus and more effective stabilization, thereby providing a reliable bond index.

The authors have requested that this preprint be removed from Research Square.

Placement of a covered self‐expandable metal stent when primary surgery had failed to close the duodenal ulcer perforation or as a primary modality is a promising procedure when compared to other currently available types of surgical rescue or intervention.

Rennet-induced milk coagulation is an important trait for cheese production. Recent studies have reported an alarming frequency of cows producing poorly coagulating milk unsuitable for cheese production. Several genetic factors are known to affect milk coagulation, including variation in the major milk proteins; however, recent association studies indicate genetic effects from other genomic regions as well. The aim of this study was to detect genetic variation affecting milk coagulation properties, measured as curd-firming rate (CFR) and milk pH. This was achieved by examining allele frequency differences between pooled whole-genome sequences of phenotypically extreme samples (pool-seq).. Curd-firming rate and raw milk pH were measured for 415 Danish Holstein cows, and each animal was sequenced at low coverage. Pools were created containing whole genome sequence reads from samples with "extreme" values (high or low) for both phenotypic traits. A total of 6,992,186 and 5,295,501 SNP were assessed in relation to CFR and milk pH, respectively. Allele frequency differences were calculated between pools and 32 significantly different SNP were detected, 1 for milk pH and 31 for CFR, of which 19 are located on chromosome 6. A total of 9 significant SNP, which were selected based on the possible function of proximal candidate genes, were genotyped in the entire sample set ( = 415) to test for an association. The most significant SNP was located proximal to , explaining 33% of the phenotypic variance. , coding for κ-casein, is the most studied in relation to milk coagulation due to its position on the surface of the casein micelles and the direct involvement in milk coagulation. Three additional SNP located on chromosome 6 showed significant associations explaining 7, 3.6, and 1.3% of the phenotypic variance of CFR. The significant SNP on chromosome 6 were shown to be in linkage disequilibrium with the SNP peaking proximal to ; however, after accounting for the genotype of the peak SNP within this QTL, significant effects (-value < 0.1) could still be detected for 2 of the SNP accounting for 2 and 1% of the phenotypic variance. These 2 interesting SNP were located within introns or proximal to the candidate genes-solute carrier family 4 (sodium bicarbonate cotransporter), member 4 () and LIM and calponin homology domains 1 (), respectively-making them interesting targets for further analysis.

Hierdie boek is ’n geskiedkundige en kultuurhistoriese juweeltjie. Baie selde kom handwerkers by skryf uit, en gevolglik word baie van die kundigheid en vaardigheid van hele praktiese beroepe en ondernemings nooit geboekstaaf nie. As dit nie vir die enkele dagboek van Louis Trichard was nie, het ons min geweet van die lewe op die Groot Trek. Die togryer-era en bedryf waarby honderde duisende betrokke was het nie ’n enkele eerstehandse verslag nagelaat nie, net die geromantiseerde en erg verwronge “Jock of the Bushveld.” Onder die omstandighede is ’n dokument soos hierdie ’n rare aanwins.

peer-reviewed H.D.D., A.J.C., P.J.B. and B.J.H. would like to acknowledge the Dairy Futures Cooperative Research Centre for funding. H.P. and R.F. acknowledge funding from the German Federal Ministry of Education and Research (BMBF) within the AgroClustEr ‘Synbreed—Synergistic Plant and Animal Breeding’ (grant 0315527B). H.P., R.F., R.E. and K.-U.G. acknowledge the Arbeitsgemeinschaft Süddeutscher Rinderzüchter, the Arbeitsgemeinschaft Österreichischer Fleckviehzüchter and ZuchtData EDV Dienstleistungen for providing genotype data. A. Bagnato acknowledges the European Union (EU) Collaborative Project LowInputBreeds (grant agreement 222623) for providing Brown Swiss genotypes. Braunvieh Schweiz is acknowledged for providing Brown Swiss phenotypes. H.P. and R.F. acknowledge the German Holstein Association (DHV) and the Confederación de Asociaciones de Frisona Española (CONCAFE) for sharing genotype data. H.P. was financially supported by a postdoctoral fellowship from the Deutsche Forschungsgemeinschaft (DFG) (grant PA 2789/1-1). D.B. and D.C.P. acknowledge funding from the Research Stimulus Fund (11/S/112) and Science Foundation Ireland (14/IA/2576). M.S. and F.S.S. acknowledge the Canadian Dairy Network (CDN) for providing the Holstein genotypes. P.S. acknowledges funding from the Genome Canada project entitled ‘Whole Genome Selection through Genome Wide Imputation in Beef Cattle’ and acknowledges WestGrid and Compute/Calcul Canada for providing computing resources. J.F.T. was supported by the National Institute of Food and Agriculture, US Department of Agriculture, under awards 2013-68004-20364 and 2015-67015-23183. A. Bagnato, F.P., M.D. and J.W. acknowledge EU Collaborative Project Quantomics (grant 516 agreement 222664) for providing Brown Swiss and Finnish Ayrshire sequences and genotypes. A.C.B. and R.F.V. acknowledge funding from the public–private partnership ‘Breed4Food’ (code BO-22.04-011- 001-ASG-LR) and EU FP7 IRSES SEQSEL (grant 317697). A.C.B. and R.F.V. acknowledge CRV (Arnhem, the Netherlands) for providing data on Dutch and New Zealand Holstein and Jersey bulls. Stature is affected by many polymorphisms of small effect in humans1. In contrast, variation in dogs, even within breeds, has been suggested to be largely due to variants in a small number of genes2,3. Here we use data from cattle to compare the genetic architecture of stature to those in humans and dogs. We conducted a meta-analysis for stature using 58,265 cattle from 17 populations with 25.4 million imputed whole-genome sequence variants. Results showed that the genetic architecture of stature in cattle is similar to that in humans, as the lead variants in 163 significantly associated genomic regions (P < 5 × 10−8) explained at most 13.8% of the phenotypic variance. Most of these variants were noncoding, including variants that were also expression quantitative trait loci (eQTLs) and in ChIP–seq peaks. There was significant overlap in loci for stature with humans and dogs, suggesting that a set of common genes regulates body size in mammals.

Bone sialoprotein (BSP) is a multifunctional extracellular matrix protein found in mineralized tissues, including bone, cartilage, tooth root cementum (both acellular and cellular types), and dentin. In order to define the role BSP plays in the process of biomineralization of these tissues, we analyzed cementogenesis, dentinogenesis, and osteogenesis (intramembranous and endochondral) in craniofacial bone in Bsp null mice and wild-type (WT) controls over a developmental period (1-60 days post natal; dpn) by histology, immunohistochemistry, undecalcified histochemistry, microcomputed tomography (microCT), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and quantitative PCR (qPCR). Regions of intramembranous ossification in the alveolus, mandible, and calvaria presented delayed mineralization and osteoid accumulation, assessed by von Kossa and Goldner's trichrome stains at 1 and 14 dpn. Moreover, Bsp(-/-) mice featured increased cranial suture size at the early time point, 1 dpn. Immunostaining and PCR demonstrated that osteoblast markers, osterix, alkaline phosphatase, and osteopontin were unchanged in Bsp null mandibles compared to WT. Bsp(-/-) mouse molars featured a lack of functional acellular cementum formation by histology, SEM, and TEM, and subsequent loss of Sharpey's collagen fiber insertion into the tooth root structure. Bsp(-/-) mouse alveolar and mandibular bone featured equivalent or fewer osteoclasts at early ages (1 and 14 dpn), however, increased RANKL immunostaining and mRNA, and significantly increased number of osteoclast-like cells (2-5 fold) were found at later ages (26 and 60 dpn), corresponding to periodontal breakdown and severe alveolar bone resorption observed following molar teeth entering occlusion. Dentin formation was unperturbed in Bsp(-/-) mouse molars, with no delay in mineralization, no alteration in dentin dimensions, and no differences in odontoblast markers analyzed. No defects were identified in endochondral ossification in the cranial base, and craniofacial morphology was unaffected in Bsp(-/-) mice. These analyses confirm a critical role for BSP in processes of cementogenesis and intramembranous ossification of craniofacial bone, whereas endochondral ossification in the cranial base was minimally affected and dentinogenesis was normal in Bsp(-/-) molar teeth. Dissimilar effects of loss of BSP on mineralization of dental and craniofacial tissues suggest local differences in the role of BSP and/or yet to be defined interactions with site-specific factors.

Bone sialoprotein (BSP) is an anionic phosphoprotein in the extracellular matrix of mineralized tissues, and a promoter of biomineralization and osteoblast development. Previous studies on the Bsp-deficient mouse (Bsp(-/-)) have demonstrated a significant bone and periodontal tissue phenotype in adulthood. However, the role of BSP during early long bone development is not known. To address this, early endochondral ossification in the Bsp(-/-) mouse was studied. Embryonic day 15.5 (E15.5) wild-type (WT) tibiae showed early stages of ossification that were absent in Bsp(-/-) mice. At E16.5, mineralization had commenced in the Bsp(-/-) mice, but staining for mineral was less intense and more dispersed compared with that in WT controls. Tibiae from Bsp(-/-) mice also demonstrated decreased mineralization and shortened length at postnatal day 0.5 (P0.5) compared to WT bones. There was no detectable difference in the number of tartrate-resistant acid phosphatase-positive foci at P0.5, although the P0.5 Bsp(-/-) tibiae had decreased Vegfα expression compared with WT tissue. Due to the shortened tibiae the growth plates were examined and determined to be of normal overall length. However, the length of the resting zone was increased in P0.5 Bsp(-/-) tibiae whereas that of the proliferative zone was decreased, with no change in the hypertrophic zone length of Bsp(-/-) mice. A reduction in cells positive for Ki-67, an S-phase cell-cycle marker, was noted in the proliferative zone. Decreased numbers of TUNEL-positive hypertrophic chondrocytes were also apparent in the Bsp(-/-) tibial growth plates, suggesting decreased apoptosis. Expression of the osteogenic markers Alp1, Col1a1, Sp7, Runx2, and Bglap was reduced in the endochondral bone of the neonatal Bsp(-/-) compared to WT tibiae. These results suggest that BSP is an important and multifaceted protein that regulates both chondrocyte proliferation and apoptosis as well as transition from cartilage to bone during development of endochondral bone.

Patient: Female, 28 Final Diagnosis: Rupture of the splenic artery aneurysm Symptoms: Hypovolemic shock Medication: — Clinical Procedure: — Specialty: Surgery Objective: Rare disease Background: ATLS principles have become a standard of care for trauma patients. However, there is poor documentation in regard to spontaneous non-traumatic life-threatening bleedings. Case Report: Two women, a 21-year-old and a 28-year-old, presented to the admissions department in hemorrhagic shock. The latter woman was in her 26th week of pregnancy. The trauma alarm was raised and the patients received prompt, complex diagnostics including ultrasonography verifying massive intraabdominal fluid. Massive infusion therapy was initiated. The first patient was intubated in the emergency room and required cardiopulmonary rescue due to cardiopulmonary arrest. The patients were moved to the surgical theatre for life-saving operations at 30 and 60 minutes, respectively, after arrival in the emergency department. Results: In the first case, we found 4 L of intraabdominal blood and a rupture in the lower pole of the splenic capsule. Splenectomy was performed. The patient developed disseminated intravascular coagulation syndrome and was transferred to a first-level trauma centre for further treatment. She survived with slight sequelae in the form of psychosocial maladjustment, and low-grade spasms and myoclonic twitches due to prolonged brain ischemia. She was steadily improving at 17 months of follow-up. Viral mononucleosis was established as the cause of the spontaneous rupture of the spleen. In the second case, we found 2.5 L of intraabdominal blood and persistent bleeding from an aneurism of the splenic artery. A splenectomy was performed. She was transferred to a first-level trauma centre for further treatment. She lost the fetus and underwent autotransplantation of the right kidney after 3 months, due to the finding of an aneurism of the right renal artery on the abdominal CT. We also found an ectasia in the ascending aorta, which will require follow-up. The patient does not have any other sequelae and has made a complete recovery at 12 months of follow-up. Conclusions: ATLS principles and trauma alarm readiness play a major role in lifesaving surgery in patients with non-traumatic hemorrhagic shock.

Bone sialoprotein (BSP) is an extracellular matrix protein found in mineralized tissues of the skeleton and dentition. BSP is multifunctional, affecting cell attachment and signaling through an RGD integrin-binding region, and acting as a positive regulator for mineral precipitation by nucleating hydroxyapatite crystals. BSP is present in cementum, the hard tissue covering the tooth root that anchors periodontal ligament (PDL) attachment. To test our hypothesis that BSP plays an important role in cementogenesis, we analyzed tooth development in a Bsp null (-/-) mouse model. Developmental analysis by histology, histochemistry, and SEM revealed a significant reduction in acellular cementum formation on Bsp-/- mouse molar and incisor roots, and the cementum deposited appeared hypomineralized. Structural defects in cementum-PDL interfaces in Bsp-/- mice caused PDL detachment, likely contributing to the high incidence of incisor malocclusion. Loss of BSP caused progressively disorganized PDL and significantly increased epithelial down-growth with aging. Bsp-/- mice displayed extensive root and alveolar bone resorption, mediated by increased RANKL and the presence of osteoclasts. Results collected here suggest that BSP plays a non-redundant role in acellular cementum formation, likely involved in initiating mineralization on the root surface. Through its importance to cementum integrity, BSP is essential for periodontal function.

Background Over the last few years, continuous development of high-throughput sequencing platforms and sequence analysis tools has facilitated reliable identification and characterization of genetic variants in many cattle breeds. Deep sequencing of entire genomes within a cattle breed that has not been thoroughly investigated would be imagined to discover functional variants that are underlying phenotypic differences. Here, we sequenced to a high coverage the Danish Holstein cattle breed to detect and characterize single nucleotide polymorphisms (SNPs), insertion/deletions (Indels), and loss-of-function (LoF) variants in protein-coding genes in order to provide a comprehensive resource for subsequent detection of causal variants for recessive traits. Results We sequenced four genetically unrelated Danish Holstein cows with a mean coverage of 27X using an Illumina Hiseq 2000. Multi-sample SNP calling identified 10,796,794 SNPs and 1,295,036 indels whereof 482,835 (4.5 %) SNPs and 231,359 (17.9 %) indels were novel. A comparison between sequencing-derived SNPs and genotyping from the BovineHD BeadChip revealed a concordance rate of 99.6–99.8 % for homozygous SNPs and 93.3–96.5 % for heterozygous SNPs. Annotation of the SNPs discovered 74,886 SNPs and 1937 indels affecting coding sequences with 2145 being LoF mutations. The frequency of LoF variants differed greatly across the genome, a hot spot with a strikingly high density was observed in a 6 Mb region on BTA18. LoF affected genes were enriched for functional categories related to olfactory reception and underrepresented for genes related to key cellular constituents and cellular and biological process regulation. Filtering using sequence derived genotype data for 288 Holstein animals from the 1000 bull genomes project removing variants containing homozygous individuals retained 345 of the LoF variants as putatively deleterious. A substantial number of the putative deleterious LoF variants had a minor allele frequency >0.05 in the 1000 bull genomes data set. Conclusions Deep sequencing of Danish Holstein genomes enabled us to identify 12.1 million variants. An investigation into LoF variants discovered a set of variants predicted to disrupt protein-coding genes. This catalog of variants will be a resource for future studies to understand variation underlying important phenotypes, particularly recessively inherited lethal phenotypes. Electronic supplementary material The online version of this article (doi:10.1186/s12864-015-2249-y) contains supplementary material, which is available to authorized users.

Conservation of the intraspecific genetic diversity of livestock species requires protocols that assess between-breed genetic variability and also take into account differences among individuals within breeds. Here, we focus on variation between breeds. Conservation of neutral genetic variation has been seen as promoting, through linkage processes, the retention of useful and potentially useful variation. Using public information on beef cattle breeds, with a total of 165 data sets each relating to a breed comparison of a performance variable, we have tested this paradigm by calculating the correlations between pairwise breed differences in performance and pairwise genetic distances deduced from biochemical and immunological polymorphisms, microsatellites and single-nucleotide polymorphisms. As already observed in floral and faunal biodiversity, significant positive correlations (n=54) were found, but many correlations were non-significant (n=100) or significantly negative (n=11). This implies that maximizing conserved neutral genetic variation with current techniques may conserve breed-level genetic variation in some traits but not in others and supports the view that genetic distance measurements based on neutral genetic variation are not sufficient as a determinant of conservation priority among breeds.

A glass filled with carbon dioxide gas upside down on a plate of water constitutes an excellent demonstration of the solubility of gases. If the water level on the plate is maintained the CO2 will slowly dissolve and the column of water will rise inside the glass, without quite reaching the ceiling, before an opposite process sets in: the water level will even more slowly begin to sink in a process which will take several years. We followed the process for several months, recording images of the water column with 10 min to 1 h intervals. The physics of the process is discussed and modeled quantitatively.

The aim of the study is two-fold. First, it adds to the existing state-of-the-art housing research by suggesting the implementation of new econometric methodology. Specifically, the study adds to earlier studies of homeownership by adding spatial impacts. It advocates simultaneous adjustment for intra-municipal correlation and heterogeneity as well as spatial spillover patterns between municipalities. It concludes that ignorance of controlling for intra-municipal correlation, heterogeneity and spatial spillover skews conclusions regarding effects of the determinants of homeownership. Furthermore, it finds that endogenous as well as exogenous spatial spillovers are essential parts of specifying demand for homeownership. Specifically, the demand for homeowner- ship spills over and stimulates demand in neighbouring municipalities, and house prices and incomes exert positive effects on demand for homeownership in neighbouring municipalities. Second, as is clear from the above empirical conclusions, the study adds to existing empirical research and knowledge.

Aims Endothelial progenitor cells (EPCs) are circulating pluripotent vascular cells capable of enhancing re-endothelialization and diminishing neointima formation following arterial injury. Glycogen synthase kinase (GSK)-3β is a protein kinase that has been implicated in the regulation of progenitor cell biology. We hypothesized that EPC abundance and function could be enhanced with the use of an inhibitor of GSK-3β (GSKi), thereby resulting in improved arterial repair. Methods and results Human EPCs were expanded e x vivo , treated with a specific GSKi, and then assessed for both yield and functional characteristics by in vitro assays for adherence, apoptosis, and survival. In vivo functionality of treated human EPCs was assessed in immune-tolerant mice subjected to femoral artery wire injury. Re-endothelialization was assessed at 72 h and neointima formation at 7 and 14 days following injury. GSKi treatment resulted in an improvement in the yield of EPCs and a reduction in apoptosis in cells derived from both healthy controls and patients with coronary artery disease. Treatment also increased vascular endothelial growth factor secretion, up-regulated expression of mRNA for the α-4 integrin subunit, and improved adhesion, an effect which could be abrogated with an α-4 integrin blocking antibody. EPCs without or with ex vivo GSKi treatment enhanced re-endothelialization 72 h following injury as well as reduced neointima formation at 7 days (e.g. endothelial coverage: 7.2 ± 1.7% vs. 70.7 ± 5.8% vs. 87.2 ± 4.1%; intima to media ratios: 1.05 ± 0.19 vs. 0.39 ± 0.08 vs. 0.14 ± 0.02; P < 0.05 for all comparisons), an effect that was persistent at 14 days. Conclusion GSKi improves the functional profile of EPCs and is associated with improved re-endothelialization and reduced neointima formation following injury.

Determination of the demand for home ownership is analyzed. Determinants include prices and short—and medium term price changes, public regulation, competition from alternative residence forms, social composition of population, economic ability, and congestion. The study applies a parametric spatially adjusted SUR approach, so that dynamic as well as spatial patterns are controlled for simultaneously and further analyzes the effects of spatial spillover using a non-parametric spatial filtering approach. The importance of adjusting for spatial spillover is confirmed, but we show that parametric and non-parametric approaches may lead to substantially different conclusions regarding explanation of homeownership rate variations.

Dr Holm and Ambassador De Vos van Steenwijk discuss the state of affairs between the West and Russia. They argue that it is much worse and antagonistic than would have been necessary. They blame this largely on mistakes in American and European policies towards the Soviet Union/Russia, but disagree on the causes and motivations of those policies. Holm and De Vos van Steenwijk offer thoughts on how matters could be rectified or at least improved.

Dr Holm and Ambassador De Vos van Steenwijk discuss the state of affairs between the West and Russia. They argue that it is much worse and antagonistic than would have been necessary. They blame this largely on mistakes in American and European policies towards the Soviet Union/Russia, but disagree on the causes and motivations of those policies. Holm and De Vos van Steenwijk offer thoughts on how matters could be rectified or at least improved.