Metagenomic characterisation of canine skin reveals a core healthy skin microbiome.

Furthering our knowledge of the skin microbiome is essential to understand health and disease in canines. To date, studies into the canine skin microbiome have focused on 16S rRNA high throughput sequencing however, these lack the granularity of species and strain level taxonomic characterisation and their associated functions. The aim of this study was to provide a comprehensive assessment of the skin microbiome by analysing the skin microbiome of 72 healthy adult colony dogs, across four distinct skin sites and four breeds, using metagenomic sequencing.

A theoretical model for host-controlled regulation of symbiont density.

There is growing empirical evidence that animal hosts actively control the density of their mutualistic symbionts according to their requirements. Such active regulation can be facilitated by compartmentalization of symbionts within host tissues, which confers a high degree of control of the symbiosis to the host. Here, we build a general theoretical framework to predict the underlying ecological drivers and evolutionary consequences of host-controlled endosymbiont density regulation for a mutually obligate association between a host and a compartmentalized, vertically transmitted symbiont.

A Novel Bacteriophage with Broad Host Range against Clostridioides difficile Ribotype 078 Supports SlpA as the Likely Phage Receptor.

Bacteriophages represent a promising option for the treatment of Clostridioides difficile (formerly Clostridium difficile) infection (CDI), which at present relies on conventional antibiotic therapy. The specificity of bacteriophages should prevent dysbiosis of the colonic microbiota associated with antibiotic treatment of CDI. While numerous phages have been isolated, none have been characterized with broad host range activity toward PCR ribotype (RT) 078 strains, despite their relevance to medicine and agriculture.

Insect-host control of obligate, intracellular symbiont density.

Many insects rely on intracellular bacterial symbionts to supplement their specialized diets with micronutrients. Using data from diverse and well-studied insect systems, we propose three lines of evidence suggesting that hosts have tight control over the density of their obligate, intracellular bacterial partners. First, empirical studies have demonstrated that the within-host symbiont density varies depending on the nutritional and developmental requirements of the host.

Noninvasive prenatal paternity determination using microhaplotypes: a pilot study.

Background: The use of noninvasive techniques to determine paternity prenatally is increasing because it reduces the risks associated with invasive procedures. Current methods, based on SNPs, use the analysis of at least 148 markers, on average.

Methods: To reduce the number of regions, we used microhaplotypes, which are chromosomal segments smaller than 200 bp containing two or more SNPs.

Cardiovascular, metabolic and kidney disease: crosscutting science and best practice in multimorbidity - a multispecialty conference at the Royal College of Physicians.

Patients with multimorbidity are increasingly encountered, especially with an ageing population and the co-segregation of lifestyle diseases such as diabetes, obesity and hypertension, but the care of these patients is fragmented and research rarely undertaken within this group. Research into genetic biomarkers and the evolution of crosscutting multiorgan science, resulting in collaboration between specialties for the treatment of patients with multimorbidity, should be the next major step change in medicine. Evolving technology is making this possible.

Fibroblasts in Pancreatic Ductal Adenocarcinoma: Biological Mechanisms and Therapeutic Targets.

The desmoplastic reaction of pancreas cancer may begin as a wound healing response to the nascent neoplasm, but it soon creates an insidious shelter that can sustain the growing tumor and rebuff therapy. Among the many cell types subverted by transformed epithelial cells, fibroblasts are recruited and activated to lay a foundation of extracellular matrix proteins and glycosaminoglycans that alter tumor biophysics and signaling. Their near-universal presence in pancreas cancer and ostensible support of disease progression make fibroblasts attractive therapeutic targets.

Intimate Partner Homicide: Themes in Judges' Sentencing Remarks.

The aim of this study was to analyse judges' sentencing remarks in cases of intimate partner homicide. Grounded theory methodology was used to undertake a qualitative analysis of the remarks, and the emanating data identified four key themes, as discussed in this article. These themes are: the sentencing of Aboriginal offenders; offender violence; the use of alcohol and/or drugs; and provocation.

The Use of Alcohol and/or Drugs in Intimate Partner Homicide: Themes in Judges' Sentencing Remarks.

This article presents the results of a major theme arising out of a grounded theory analysis of judges' sentencing remarks for males and females sentenced for intimate partner homicide in Australia between July 2009 and June 2014. Specifically, this article focuses on judges' commentary regarding the use of alcohol and/or drugs as a contributing factor to the offending. The qualitative data indicate that despite the seriousness of the offence, sentencing judges often fail to attribute with clarity a sufficient degree of responsibility to male offenders for their voluntary consumption of alcohol and drugs and their subsequent violent behaviour.

Understanding Disease Biology and Informing the Management of Pancreas Cancer With Preclinical Model Systems.

Recent advances in cytotoxic therapies for pancreatic ductal adenocarcinoma (PDA) are overshadowed by stalled clinical progress of more targeted strategies, the vast majority of which have failed in clinical trials. Inability to translate preclinical promise into clinical efficacy derives, in part, from imperfect disease modeling and mismatches between preclinical and clinical study design and execution. Into these gaps fall our patients who enter the clinical trial landscape expectantly and bear the brunt of its inadequacies.

Runx3 and Cell Fate Decisions in Pancreas Cancer.

The RUNX family transcription factors are critical regulators of development and frequently dysregulated in cancer. RUNX3, the least well characterized of the three family members, has been variously described as a tumor promoter or suppressor, sometimes with conflicting results and opinions in the same cancer and likely reflecting a complex role in oncogenesis. We recently identified RUNX3 expression as a crucial determinant of the predilection for pancreatic ductal adenocarcinoma (PDA) cells to proliferate locally or promulgate throughout the body.

Enhancer Remodeling during Adaptive Bypass to MEK Inhibition Is Attenuated by Pharmacologic Targeting of the P-TEFb Complex.

Targeting the dysregulated BRAF-MEK-ERK pathway in cancer has increasingly emerged in clinical trial design. Despite clinical responses in specific cancers using inhibitors targeting BRAF and MEK, resistance develops often involving nongenomic adaptive bypass mechanisms. Inhibition of MEK1/2 by trametinib in patients with triple-negative breast cancer (TNBC) induced dramatic transcriptional responses, including upregulation of receptor tyrosine kinases (RTK) comparing tumor samples before and after one week of treatment.

Analysis of uni and bi-parental markers in mixture samples: Lessons from the 22nd GHEP-ISFG Intercomparison Exercise.

Since 1992, the Spanish and Portuguese-Speaking Working Group of the ISFG (GHEP-ISFG) has been organizing annual Intercomparison Exercises (IEs) coordinated by the Quality Service at the National Institute of Toxicology and Forensic Sciences (INTCF) from Madrid, aiming to provide proficiency tests for forensic DNA laboratories. Each annual exercise comprises a Basic (recently accredited under ISO/IEC 17043: 2010) and an Advanced Level, both including a kinship and a forensic module. Here, we show the results for both autosomal and sex-chromosomal STRs, and for mitochondrial DNA (mtDNA) in two samples included in the forensic modules, namely a mixture 2:1 (v/v) saliva/blood (M4) and a mixture 4:1 (v/v) saliva/semen (M8) out of the five items provided in the 2014 GHEP-ISFG IE.

Mutant p53 Together with TGFβ Signaling Influence Organ-Specific Hematogenous Colonization Patterns of Pancreatic Cancer.

TP53 and the TGFβ pathway are major mediators of pancreatic cancer metastasis. The mechanisms by which they cause hematogenous metastasis have not been fully explored. (;; ) mice were generated, and the frequency and morphology of organ-specific hematogenous metastases compared with that seen in and littermates ().

RUNX3 defines disease behavior in pancreatic ductal adenocarcinoma.

Runt-related transcription factor 3 (RUNX3) functions downstream of transforming growth factor beta (TGFβ) and plays dual roles in pancreas cancer by both suppressing (by inhibiting proliferation) and promoting (by enhancing migratory and metastatic capacity) disease progression. Consideration of the contextual regulation of RUNX3 together with its myriad downstream effects may help improve clinical outcomes for pancreas cancer patients.

A laser driven pulsed X-ray backscatter technique for enhanced penetrative imaging.

X-ray backscatter imaging can be used for a wide range of imaging applications, in particular for industrial inspection and portal security. Currently, the application of this imaging technique to the detection of landmines is limited due to the surrounding sand or soil strongly attenuating the 10s to 100s of keV X-rays required for backscatter imaging. Here, we introduce a new approach involving a 140 MeV short-pulse (< 100 fs) electron beam generated by laser wakefield acceleration to probe the sample, which produces Bremsstrahlung X-rays within the sample enabling greater depths to be imaged.

RUNX3 Controls a Metastatic Switch in Pancreatic Ductal Adenocarcinoma.

For the majority of patients with pancreas cancer, the high metastatic proclivity is life limiting. Some patients, however, present with and succumb to locally destructive disease. A molecular understanding of these distinct disease manifestations can critically inform patient management.

A global analysis of Y-chromosomal haplotype diversity for 23 STR loci.

In a worldwide collaborative effort, 19,630 Y-chromosomes were sampled from 129 different populations in 51 countries. These chromosomes were typed for 23 short-tandem repeat (STR) loci (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385ab, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635, GATAH4, DYS481, DYS533, DYS549, DYS570, DYS576, and DYS643) and using the PowerPlex Y23 System (PPY23, Promega Corporation, Madison, WI). Locus-specific allelic spectra of these markers were determined and a consistently high level of allelic diversity was observed.

Pneumococcal polysaccharide vaccine responses are impaired in a subgroup of children with cystic fibrosis.

Background: Pneumococcal immunization is recommended in children with cystic fibrosis (CF). To date, however, there are no published studies on the efficacy of pneumococcal vaccination in this group of patients.

Methods: We carried out a retrospective study of serotype-specific pneumococcal antibody responses to immunization with Prevenar 7 and Pneumovax II in a cohort of children with CF.

GHEP-ISFG collaborative exercise on mixture profiles of autosomal STRs (GHEP-MIX01, GHEP-MIX02 and GHEP-MIX03): results and evaluation.

One of the main objectives of the Spanish and Portuguese-Speaking Group of the International Society for Forensic Genetics (GHEP-ISFG) is to promote and contribute to the development and dissemination of scientific knowledge in the area of forensic genetics. Due to this fact, GHEP-ISFG holds different working commissions that are set up to develop activities in scientific aspects of general interest. One of them, the Mixture Commission of GHEP-ISFG, has organized annually, since 2009, a collaborative exercise on analysis and interpretation of autosomal short tandem repeat (STR) mixture profiles.

Application of multiplexed kinase inhibitor beads to study kinome adaptations in drug-resistant leukemia.

Protein kinases play key roles in oncogenic signaling and are a major focus in the development of targeted cancer therapies. Imatinib, a BCR-Abl tyrosine kinase inhibitor, is a successful front-line treatment for chronic myelogenous leukemia (CML). However, resistance to imatinib may be acquired by BCR-Abl mutations or hyperactivation of Src family kinases such as Lyn.