The ErbB2ΔEx16 splice variant is a major oncogenic driver in breast cancer that promotes a pro-metastatic tumor microenvironment.

Amplification and overexpression of erbB2/neu proto-oncogene is observed in 20-30% human breast cancer and is inversely correlated with the survival of the patient. Despite this, somatic activating mutations within erbB2 in human breast cancers are rare. However, we have previously reported that a splice isoform of erbB2, containing an in-frame deletion of exon 16 (herein referred to as ErbB2ΔEx16), results in oncogenic activation of erbB2 because of constitutive dimerization of the ErbB2 receptor. Here, we demonstrate that the ErbB2ΔEx16 is a major oncogenic driver in breast cancer that constitutively signals from the cell surface. We further show that inducible expression of the ErbB2ΔEx16 variant in mammary gland of transgenic mice results in the rapid development of metastatic multifocal mammary tumors. Genetic and biochemical characterization of the ErbB2ΔEx16-derived mammary tumors exhibit several unique features that distinguish this model from the conventional ErbB2 ones expressing the erbB2 proto-oncogene in mammary epithelium. Unlike the wild-type ErbB2-derived tumors that express luminal keratins, ErbB2ΔEx16-derived tumors exhibit high degree of intratumoral heterogeneity co-expressing both basal and luminal keratins. Consistent with these distinct pathological features, the ErbB2ΔEx16 tumors exhibit distinct signaling and gene expression profiles that correlate with activation of number of key transcription factors implicated in breast cancer metastasis and cancer stem cell renewal

Classroom Management through Teacher Candidates’ Lenses: Transforming Learning Communities Through a Community of Practice

To better prepare teacher candidates for classroom management through attention to learning communities that affirm and support diverse students, including those effected by trauma, four instructors redesigned a required, undergraduate course. This study describes findings from three teacher candidate co-authors who were enrolled in that course. One semester after completing a course on classroom management and building community, candidates were asked to review their course products and other artifacts to consider what they learned and build upon their prior knowledge. Candidates used stimulated recall to respond to prompts on community building and relationships, gender and racial inclusivity, trauma sensitive practices, and the school to prison pipeline. Their perspectives contribute to understandings about how candidates engage in sense-making regarding classroom communities and classroom management

AnyItem, la creació d'una app mòbil

Aquest projecte tracta sobre la creació d'una l'aplicació mòbil. AnyItem és una app gratuïta que funciona principalment a través d'un scanner de codi de barres per a realitzar donacions. Aquesta agrupa entitats caritatives en una sola plataforma per a realitzar donatius d'una manera fàcil i clara. També crea un vincle més pròxim entre l'usuari i l'empresa benèfica ja que proporciona total transparència deixant escollir a l'usuari quina donació fer i a on fer-la, i conseqüentment et notifica de quan arriba a la seva destinació.Este proyecto trata sobre la creación de una aplicación móvil. AnyItem es una app gratuita que funciona a través de un scanner de código de barras para realizar donaciones. Esta agrupa entidades caritativas en una sola plataforma para realizar donativos de una manera fácil y clara. También crea un vínculo más cercano entre el usuario y la empresa benéfica ya que proporciona total transparencia dejando escoger al usuario qué donación hacer y dónde hacerla, y consecuentemente te notifica de cuando llega a su destino.This project is about the creation of a new mobile app. AnyItem is a free application that works mainly through a barcode scanner to make donations. The app brings together many different charities onto a single platform to make the process of donating easier and clearer. It also brings closer the user and the charity as it provides total transparency on its process letting the user choose what donation to make and where they want to donate it, and consequently it notificates you on when it arrives at its proper destinatio

Epicardial pacemaker placement is associated with low complication rate and improved quality of life in dogs.

ObjectiveTo describe complications and outcomes in dogs undergoing epicardial pacemaker (EP) implantation, identify factors associated with survival, and investigate improvement in clinical signs and health-related quality of life (HRQoL) following surgery.Animals52 client-owned dogs that underwent EP placement.MethodsMedical records of 4 UK-based referral hospitals were searched and data reviewed retrospectively between July 2010 and December 2022. Factors contributing to outcomes after EP placement were assessed.ResultsThe primary reasons for referral included collapsing/syncopal episodes (n = 36), exercise intolerance (15), and significant bradycardia (46). Third-degree atrioventricular block (39/52 [75%]) was the predominant indication for pacemaker placement, and common reasons for EP placement included previous transvenous pacemaker dislodgment/loss of capture (n = 12) and small body size (10). Intra- and postoperative complications were documented in 11% and 23% of dogs, respectively. Overall, 96% of dogs survived to discharge, and median follow-up time was 462 days (range, 31 to 3,139 days). Presence of coexistent myocardial or valvular disease at the time of EP implantation was associated with a reduced survival. Owners reported decreased clinical signs, increased activity levels, and improved HRQoL.Clinical relevanceEpicardial pacemaker implantation is a valuable option for dogs requiring artificial cardiac pacing. Complications were common but did not impact the overall outcome. Dogs with a coexisting cardiac pathology had a shorter life expectancy after EP placement, but their HRQoL appeared to be good, with an improvement in clinical signs and increased activity levels

Dominant mutations of the Notch ligand Jagged1 cause peripheral neuropathy

Notch signaling is a highly conserved intercellular pathway with tightly regulated and pleiotropic roles in normal tissue development and homeostasis. Dysregulated Notch signaling has also been implicated in human disease, including multiple forms of cancer, and represents an emerging therapeutic target. Successful development of such therapeutics requires a detailed understanding of potential on-target toxicities. Here, we identify autosomal dominant mutations of the canonical Notch ligand Jagged1 (or JAG1) as a cause of peripheral nerve disease in 2 unrelated families with the hereditary axonal neuropathy Charcot-Marie-Tooth disease type 2 (CMT2). Affected individuals in both families exhibited severe vocal fold paresis, a rare feature of peripheral nerve disease that can be life-threatening. Our studies of mutant protein posttranslational modification and localization indicated that the mutations (p.Ser577Arg, p.Ser650Pro) impair protein glycosylation and reduce JAG1 cell surface expression. Mice harboring heterozygous CMT2-associated mutations exhibited mild peripheral neuropathy, and homozygous expression resulted in embryonic lethality by midgestation. Together, our findings highlight a critical role for JAG1 in maintaining peripheral nerve integrity, particularly in the recurrent laryngeal nerve, and provide a basis for the evaluation of peripheral neuropathy as part of the clinical development of Notch pathway–modulating therapeutics

Wolbachia and DNA barcoding insects: patterns, potential and problems

Wolbachia is a genus of bacterial endosymbionts that impacts the breeding systems of their hosts. Wolbachia can confuse the patterns of mitochondrial variation, including DNA barcodes, because it influences the pathways through which mitochondria are inherited. We examined the extent to which these endosymbionts are detected in routine DNA barcoding, assessed their impact upon the insect sequence divergence and identification accuracy, and considered the variation present in Wolbachia COI. Using both standard PCR assays (Wolbachia surface coding protein – wsp), and bacterial COI fragments we found evidence of Wolbachia in insect total genomic extracts created for DNA barcoding library construction. When >2 million insect COI trace files were examined on the Barcode of Life Datasystem (BOLD) Wolbachia COI was present in 0.16% of the cases. It is possible to generate Wolbachia COI using standard insect primers; however, that amplicon was never confused with the COI of the host. Wolbachia alleles recovered were predominantly Supergroup A and were broadly distributed geographically and phylogenetically. We conclude that the presence of the Wolbachia DNA in total genomic extracts made from insects is unlikely to compromise the accuracy of the DNA barcode library; in fact, the ability to query this DNA library (the database and the extracts) for endosymbionts is one of the ancillary benefits of such a large scale endeavor – for which we provide several examples. It is our conclusion that regular assays for Wolbachia presence and type can, and should, be adopted by large scale insect barcoding initiatives. While COI is one of the five multi-locus sequence typing (MLST) genes used for categorizing Wolbachia, there is limited overlap with the eukaryotic DNA barcode region

Radical genome remodelling accompanied the emergence of a novel host-restricted bacterial pathogen

The emergence of new pathogens is a major threat to public and veterinary health. Changes in bacterial habitat such as a switch in host or disease tropism are typically accompanied by genetic diversification. Staphylococcus aureus is a multi-host bacterial species associated with human and livestock infections. A microaerophilic subspecies, Staphylococcus aureus subsp. anaerobius, is responsible for Morel’s disease, a lymphadenitis restricted to sheep and goats. However, the evolutionary history of S. aureus subsp. anaerobius and its relatedness to S. aureus are unknown. Population genomic analyses of clinical S. aureus subsp. anaerobius isolates revealed a highly conserved clone that descended from a S. aureus progenitor about 1000 years ago before differentiating into distinct lineages that contain African and European isolates. S. aureus subsp. anaerobius has undergone limited clonal expansion, with a restricted population size, and an evolutionary rate 10-fold slower than S. aureus. The transition to its current restricted ecological niche involved acquisition of a pathogenicity island encoding a ruminant host-specific effector of abscess formation, large chromosomal re-arrangements, and the accumulation of at least 205 pseudogenes, resulting in a highly fastidious metabolism. Importantly, expansion of ~87 insertion sequences (IS) located largely in intergenic regions provided distinct mechanisms for the control of expression of flanking genes, including a novel mechanism associated with IS-mediated anti-anti-sense decoupling of ancestral gene repression. Our findings reveal the remarkable evolutionary trajectory of a host-restricted bacterial pathogen that resulted from extensive remodelling of the S. aureus genome through an array of diverse mechanisms in parallel

The association between family and community social capital and health risk behaviours in young people: an integrative review

Background: Health risk behaviours known to result in poorer outcomes in adulthood are generally established in late childhood and adolescence. These ‘risky’ behaviours include smoking, alcohol and illicit drug use and sexual risk taking. While the role of social capital in the establishment of health risk behaviours in young people has been explored, to date, no attempt has been made to consolidate the evidence in the form of a review. Thus, this integrative review was undertaken to identify and synthesise research findings on the role and impact of family and community social capital on health risk behaviours in young people and provide a consolidated evidence base to inform multi-sectorial policy and practice.<p></p> Methods: Key electronic databases were searched (i.e. ASSIA, CINAHL, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, Embase, Medline, PsycINFO, Sociological Abstracts) for relevant studies and this was complemented by hand searching. Inclusion/exclusion criteria were applied and data was extracted from the included studies. Heterogeneity in study design and the outcomes assessed precluded meta-analysis/meta-synthesis; the results are therefore presented in narrative form.<p></p> Results: Thirty-four papers satisfied the review inclusion criteria; most were cross-sectional surveys. The majority of the studies were conducted in North America (n=25), with three being conducted in the UK. Sample sizes ranged from 61 to 98,340. The synthesised evidence demonstrates that social capital is an important construct for understanding the establishment of health risk behaviours in young people. The different elements of family and community social capital varied in terms of their saliency within each behavioural domain, with positive parent–child relations, parental monitoring, religiosity and school quality being particularly important in reducing risk.<p></p> Conclusions: This review is the first to systematically synthesise research findings about the association between social capital and health risk behaviours in young people. While providing evidence that may inform the development of interventions framed around social capital, the review also highlights key areas where further research is required to provide a fuller account of the nature and role of social capital in influencing the uptake of health risk behaviours.<p></p&gt

Terminal-instar larval systematics and biology of west European species of Ormyridae associated with insect galls (Hymenoptera, Chalcidoidea)

A systematic study of the genus Ormyrus (Chalcidoidea, Ormyridae) was conducted based on the morphology and biology of the terminal-instar larvae of ten west European species that are parasitoids of gall wasps and gallflies of the families Cynipidae, Eurytomidae and Tephritidae. The first detailed descriptions are provided of the terminal-instar larvae of these ten species using SEM images to illustrate diagnostic characters with systematic values. A key is provided for the identification of ormyrid larvae associated with galls in Europe, which is based particularly on characters of the head, mouthparts and mandibles. Although only limited informative variation in body shape was found, the setation of the head provided several characters of potential taxonomic value. The larval biology of the ten ormyrid species inhabiting different galls is also summarised. Although Ormyrus larvae are usually solitary idiobiont ectoparasitoids of the host larva of various gall-inhabiting insects, evidence of secondary phytophagy was observed in some species.The Spanish Ministry of Education and Science research projects CGL2010-15786/BOS and MINECO/FEDER, UE) CGL2015-66571-P to JLNA provided financial support for this paper.Peer Reviewe

Current concepts in the treatment of intra-articular calcaneal fractures: results of a nationwide survey

The treatment of intra-articular calcaneal fractures is controversial and randomised clinical trials are scarce. Moreover, the socio-economic cost remains unclear. The aim of this study was to estimate the incidence, treatment preferences and socio-economic cost of this complex fracture in the Netherlands. This data may aid in planning future clinical trials and support education. The method of study was of a cross-sectional survey design. A written survey was sent to one representative of both the traumatology and the orthopaedic staff in each hospital in the Netherlands. Data on incidence, treatment modalities, complications and follow-up strategies were recorded. The socio-economic cost was calculated. The average response rate was 70%. Fracture classifications, mostly by Sanders and Essex-Lopresti, were applied by 29%. Annually, 920 intra-articular calcaneal fractures (0.4% incidence rate) were treated, mainly with ORIF (46%), conservative (39%) and percutaneous (10%) treatment. The average non-weight-bearing mobilisation was 9 weeks (SD 2 weeks). An outcome score, mainly AOFAS, was documented by 7%. A secondary arthrodesis was performed in 21% of patients. The socio-economic cost was estimated to be €21.5–30.7 million. Dutch intra-articular calcaneal fracture incidence is at least 0.4% of all fractures presenting to hospitals. Better insight into treatment modalities currently employed and costs in the Netherlands was obtained