Translin facilitates RNA polymerase II dissociation and suppresses genome instability during RNase H2- and Dicer-deficiency.

The conserved nucleic acid binding protein Translin contributes to numerous facets of mammalian biology and genetic diseases. It was first identified as a binder of cancer-associated chromosomal translocation breakpoint junctions leading to the suggestion that it was involved in genetic recombination. With a paralogous partner protein, Trax, Translin has subsequently been found to form a hetero-octomeric RNase complex that drives some of its functions, including passenger strand removal in RNA interference (RNAi). The Translin-Trax complex also degrades the precursors to tumour suppressing microRNAs in cancers deficient for the RNase III Dicer. This oncogenic activity has resulted in the Translin-Trax complex being explored as a therapeutic target. Additionally, Translin and Trax have been implicated in a wider range of biological functions ranging from sleep regulation to telomere transcript control. Here we reveal a Trax- and RNAi-independent function for Translin in dissociating RNA polymerase II from its genomic template, with loss of Translin function resulting in increased transcription-associated recombination and elevated genome instability. This provides genetic insight into the longstanding question of how Translin might influence chromosomal rearrangements in human genetic diseases and provides important functional understanding of an oncological therapeutic target.

Surveillance for Diabetes in Hospital-Evaluation of Dashboard Effectiveness.

There is a large burden of diabetes in Western Sydney, and this descriptor is also valid for the inpatient population. Optimizing diabetes care in hospital is important to prevent inpatient morbidity. A surveillance system was developed to address this need and a diabetes dashboard was developed around a data model built around the patient journey that integrated key data feeds from the pathology, medication, and patient administration systems. This facilitated the rapid identification and triaging of individuals with diabetes. We evaluated this dashboard using high level clinical and financial indicators. This implementation resulted in an improved time to patient review, and a reduction in 28-day readmission rates but the inpatient length of hospital stay was unchanged. (116 words).

Impact of Socio-demographic Characteristics on Time in Outpatient Cardiology Clinics: A Retrospective Analysis.

Inequitable access to health services influences health outcomes. Some studies have found patients of lower socio-economic status (SES) wait longer for surgery, but little data exist on access to outpatient services. This study analyzed patient-level data from outpatient public cardiology clinics and assessed whether low SES patients spend longer accessing ambulatory services. Retrospective analysis of cardiology clinic encounters across 3 public hospitals between 2014 and 2019 was undertaken. Data were linked to age, gender, Indigenous status, country of birth, language spoken at home, number of comorbidities, and postcode. A cox proportional hazards model was applied adjusting for visit type (new/follow up), clinic, and referral source. Higher hazard ratio (HR) indicates shorter clinic time. Overall, 22 367 patients were included (mean [SD] age 61.4 [15.2], 14 925 (66.7%) male). Only 7823 (35.0%) were born in Australia and 8452 (37.8%) were in the lowest SES quintile. Median total clinic time was 84 min (IQR 58-130). Visit type, clinic, and referral source were associated with clinic time (R2 = 0.23, 0.35, 0.20). After adjusting for these variables, older patients spent longer in clinic (HR 0.94 [0.90-0.97]), though there was no difference according to SES (HR 1.02 [0.99-1.06]) or other variables of interest. Time spent attending an outpatient clinic is substantial, amplifying an already significant time burden faced by patients with chronic health conditions. SES was not associated with longer clinic time in our analysis. Time spent in clinics could be used more productively to optimize care, improve health outcomes and patient experience.

Recombination at DNA replication fork barriers is not universal and is differentially regulated by Swi1.

DNA replication stress has been implicated in the etiology of genetic diseases, including cancers. It has been proposed that genomic sites that inhibit or slow DNA replication fork progression possess recombination hotspot activity and can form potential fragile sites. Here we used the fission yeast, Schizosaccharomyces pombe, to demonstrate that hotspot activity is not a universal feature of replication fork barriers (RFBs), and we propose that most sites within the genome that form RFBs do not have recombination hotspot activity under nonstressed conditions. We further demonstrate that Swi1, the TIMELESS homologue, differentially controls the recombination potential of RFBs, switching between being a suppressor and an activator of recombination in a site-specific fashion.

Investigating the environmental costs of utilizing graphene-based adsorbents and pulsed power oxidation for the removal of emerging contaminants from urban wastewater.

Emerging contaminants continue to pose a threat to environmental quality that warrant mitigation. Novel technologies are being investigated that offer promise in their removal, yet it is important that the environmental costs of these treatments do not overshadow their benefits. With sustainability a key priority in global infrastructure development, insights into the environmental impact of new technologies is necessitated. In the present work, the environmental burden of three novel GBM (graphene-based material) filters (porous graphene, graphene oxide-based foam and hybrid combination) are quantified and compared at a flow rate of 1 m3/d by way of life cycle impact assessment with an alternative solution, an AOP-PPT (advanced oxidation process by pulsed power treatment). Initial results demonstrated negligible differences in overall environmental impact between the three GBM filter formats (7.7-7.9 pt), while significant asymmetry was observed with the AOP-PPT that incurred a total impact score of 67.9 pt. This disparity was attributed to the high energy demand of the AOP-PPT that was a key predictor of environmental cost in an India context due to the high proportion of non-renewable energy sourced. The GBM filters were also considered at a range of breakthrough times and contrasted against the AOP-PPT. Results showed that differences between GBM filters were negligible at all breakthrough periods and that multiple breakthroughs a day would be required before the AOP-PPT became environmentally favourable. Finally, due to the AOP-PPT affording inclusive disinfection, the environmental burden of a GBM filter was compared under different scenarios of incorporated disinfection. The total impact of the AOP-PPT achieving full disinfection was found to be 242.5 pt compared to only 26.8 pt for the GBM filter coupled with UV254 (ultraviolet 254 nm) treatment and 13.9 pt when incorporating chlorination/de-chlorination. These findings should support sustainable development goals when combating prevailing emerging contaminants in municipal wastewater.

Home telecare study for patients with chronic lung disease in the Sydney West Area Health Service.

Information and communication technologies may be used to provide health care services to people living at home. The term "home telecare" has been coined for this service. The elderly and patients with chronic pulmonary conditions, heart disease and diabetes have been thought to be obvious beneficiaries. The evidence base supporting home telecare is growing; however, there is a need for studies of long-term deployment and integration with existing health system processes. We discuss the experiences gained from one such pilot conducted in the Sydney West Area Health Service, which examines the integration of home telecare within the framework of an existing respiratory ambulatory care service. Interim results demonstrate high levels of reliability and positive patient attitude towards use of home monitoring. Clinical staff acceptance levels appeared lower. Effects on health burden, such as hospital admissions and nurse workload, were not significantly altered. The study results have been essential in developing local telecare knowledge within the health care community.

Functional characterisation of the Schizosaccharomyces pombe homologue of the leukaemia-associated translocation breakpoint binding protein translin and its binding partner, TRAX.

Translin is a conserved protein which associates with the breakpoint junctions of chromosomal translocations linked with the development of some human cancers. It binds to both DNA and RNA and has been implicated in mRNA metabolism and regulation of genome stability. It has a binding partner, translin-associated protein X (TRAX), levels of which are regulated by the translin protein in higher eukaryotes. In this study we find that this regulatory function is conserved in the lower eukaryotes, suggesting that translin and TRAX have important functions which provide a selective advantage to both unicellular and multi-cellular eukaryotes, indicating that this function may not be tissue-specific in nature. However, to date, the biological importance of translin and TRAX remains unclear. Here we systematically investigate proposals that suggest translin and TRAX play roles in controlling mitotic cell proliferation, DNA damage responses, genome stability, meiotic/mitotic recombination and stability of GT-rich repeat sequences. We find no evidence for translin and/or TRAX primary function in these pathways, indicating that the conserved biochemical function of translin is not implicated in primary pathways for regulating genome stability and/or segregation.

Climate structuring of Batrachochytrium dendrobatidis infection in the threatened amphibians of the northern Western Ghats, India.

Batrachochytrium dendrobatidis (Bd) is a pathogen killing amphibians worldwide. Its impact across much of Asia is poorly characterized. This study systematically surveyed amphibians for Bd across rocky plateaus in the northern section of the Western Ghats biodiversity hotspot, India, including the first surveys of the plateaus in the coastal region. These ecosystems offer an epidemiological model system since they are characterized by differing levels of connectivity, edaphic and climatic conditions, and anthropogenic stressors. One hundred and eighteen individuals of 21 species of Anura and Apoda on 13 plateaus ranging from 67 to 1179 m above sea level and 15.89 to 17.92° North latitude were sampled. Using qPCR protocols, 79% of species and 27% of individuals tested were positive for Bd. This is the first record of Bd in caecilians in India, the Critically Endangered Xanthophryne tigerina and Endangered Fejervarya cf. sahyadris. Mean site prevalence was 28.15%. Prevalence below the escarpment was 31.2% and 25.4% above. The intensity of infection (GE) showed the reverse pattern. Infection may be related to elevational temperature changes, thermal exclusion, inter-site connectivity and anthropogenic disturbance. Coastal plateaus may be thermal refuges from Bd. Infected amphibians represented a wide range of ecological traits posing interesting questions about transmission routes.

Micro-habitat distribution drives patch quality for sub-tropical rocky plateau amphibians in the northern Western Ghats, India.

The importance of patch quality for amphibians is frequently overlooked in distribution models. Here we demonstrate that it is highly important for the persistence of endemic and endangered amphibians found in the threatened and fragile ecosystems that are the rocky plateaus in Western Maharashtra, India. These plateaus are ferricretes of laterite and characterise the northern section of the Western Ghats/Sri Lanka Biodiversity Hotspot, the eighth most important global hotspot and one of the three most threatened by population growth. We present statistically supported habitat associations for endangered and data-deficient Indian amphibians, demonstrating significant relationships between individual species and their microhabitats. Data were collected during early monsoon across two seasons. Twenty-one amphibian taxa were identified from 14 lateritic plateaus between 67 and 1179m above sea level. Twelve of the study taxa had significant associations with microhabitats using a stepwise analysis of the AICc subroutine (distLM, Primer-e, v7). Generalist taxa were associated with increased numbers of microhabitat types. Non-significant associations are reported for the remaining 9 taxa. Microhabitat distribution was spatially structured and driven by climate and human activity. Woody plants were associated with 44% of high-elevation taxa. Of the 8 low-elevation taxa 63% related to water bodies and 60% of those were associated with pools. Rock size and abundance were important for 33% of high elevation specialists. Three of the 4 caecilians were associated with rocks in addition to soil and stream presence. We conclude the plateaus are individualistic patches whose habitat quality is defined by their microhabitats within climatic zones.

Linear element-independent meiotic recombination in Schizosaccharomyces pombe.

Most organisms form protein-rich, linear, ladder-like structures associated with chromosomes during early meiosis, the synaptonemal complex. In Schizosaccharomyces pombe, linear elements (LinEs) are thread-like, proteinacious chromosome-associated structures that form during early meiosis. LinEs are related to axial elements, the synaptonemal complex precursors of other organisms. Previous studies have led to the suggestion that axial structures are essential to mediate meiotic recombination. Rec10 protein is a major component of S. pombe LinEs and is required for their development. In this report we study recombination in a number of rec10 mutants, one of which (rec10-155) does not form LinEs, but is predicted to encode a truncated Rec10 protein. This mutant has levels of crossing over and gene conversion substantially higher than a rec10 null mutant (rec10-175) and forms cytologically detectable Rad51 foci indicative of meiotic recombination intermediates. These data demonstrate that while Rec10 is required for meiotic recombination, substantial meiotic recombination can occur in rec10 mutants that do not form LinEs, indicating that LinEs per se are not essential for all meiotic recombination.

A small-scale randomised controlled trial of home telemonitoring in patients with severe chronic obstructive pulmonary disease.

Introduction This was a pilot study to examine the effects of home telemonitoring (TM) of patients with severe chronic obstructive pulmonary disease (COPD). Methods A randomised controlled 12-month trial of 42 patients with severe COPD was conducted. Home TM of oximetry, temperature, pulse, electrocardiogram, blood pressure, spirometry, and weight with telephone support and home visits was tested against a control group receiving only identical telephone support and home visits. Results The results suggest that TM had a reduction in COPD-related admissions, emergency department presentations, and hospital bed days. TM also seemed to increase the interval between COPD-related exacerbations requiring a hospital visit and prolonged the time to the first admission. The interval between hospital visits was significantly different between the study arms, while the other findings did not reach significance and only suggest a trend. There was a reduction in hospital admission costs. TM was adopted well by most patients and eventually, also by the nursing staff, though it did not seem to change patients' psychological well-being. Discussion Ability to draw firm conclusions is limited due to the small sample size. However the trends of reducing hospital visits warrant a larger study of a similar design. When designing such a trial, one should consider the potential impact of the high quality of care already made available to this patient cohort.

Differential activation of M26-containing meiotic recombination hot spots in Schizosaccharomyces pombe.

Certain genomic loci, termed hot spots, are predisposed to undergo genetic recombination during meiosis at higher levels relative to the rest of the genome. The factors that specify hot-spot potential are not well understood. The M26 hot spot of Schizosaccharomyces pombe is dependent on certain trans activators and a specific nucleotide sequence, which can function as a hot spot in a position- and orientation-independent fashion within ade6. In this report we demonstrate that a linear element (LE) component, Rec10, has a function that is required for activation of some, but not all, M26-containing hot spots and from this we propose that, with respect to hot-spot activity, there are three classes of M26-containing sequences. We demonstrate that the localized sequence context in which the M26 heptamer is embedded is a major factor governing whether or not this Rec10 function is required for full hot-spot activation. Furthermore, we show that the rec10-144 mutant, which is defective in full activation of ade6-M26, but proficient for activation of other M26-containing hot spots, is also defective in the formation of LEs, suggesting an intimate link between higher-order chromatin structure and local influences on hot-spot activation.

Homologous chromosome pairing in Schizosaccharomyces pombe.

Homologous chromosome pairing is a central feature of meiosis I, contributing to the correct segregation of chromosomes during meiosis. The fission yeast, Schizosaccharomyces pombe, has been widely used to study meiotic chromosome dynamics, partly because studies in this yeast are simplified due to the lack of post-pairing synaptic structures. Chromosome pairing in Sz. pombe occurs differentially throughout the genome. Telomeres cluster at the spindle pole body (SPB) at the onset of meiosis, imposing a spatial restriction on pairing events. Subsequently, centromeres dissociate from the SPB and pair in a recombination- and heterochromatin (Swi6)-independent fashion. Pairing of telomere distal regions occurs during meiotic prophase, concomitant with a dynamic association/dissociation of homologous regions, with interhomologue associations becoming increasingly stable. The stabilization of paired regions is enhanced by factors required for the initiation of meiotic recombination, suggesting that recombination stabilizes paired regions. However, substantial pairing is initiated in the absence of recombination; this is dependent upon another factor, the conserved Meu13 protein, demonstrating that recombination is not required for initial pairing interactions. During meiotic prophase Sz. pombe exhibits a pronounced dynein-dependent nuclear oscillation, which drives the pairing of centromeric and interstitial regions. Dynein is also required for the significant levels of achiasmate reductional segregation observed in Sz. pombe, possibly implicating the centromere-associated pairing with achiasmate homologue segregation. Whilst Sz. pombe does not form discernable synaptic structures continuously along the meiotic chromosomes, it does form proteinacious, meiosis-specific, linear structures (linear elements). However, the role, if any, of these structures in mediating homologue pairing is unknown.

Psc3 cohesin of Schizosaccharomyces pombe: cell cycle analysis and identification of three distinct isoforms.

Cohesins are a group of proteins that function to mediate correct chromosome segregation, DNA repair and meiotic recombination. This report presents the amino acid sequence for the Schizosaccharomyces pombe cohesin Psc3 based on the translation of the cDNA sequence, showing that the protein is smaller than previously predicted. Interestingly, comparison of the amino acid and DNA coding sequences of Psc3 with fission yeast Rec11 meiotic region-specific recombination activator shows that both intron positioning within the genes and the amino-terminal half of the two proteins are highly conserved. We demonstrate that although the intergenic region upstream of the psc3+ start codon contains a consensus sequence for the cell-cycle regulatory MluI cell-cycle box, psc3+ transcription is not differentially regulated during the mitotic cell cycle. Finally, we demonstrate that an epitope-tagged version of Psc3 undergoes no major changes during the mitotic cell cycle. However, instead we identify at least three distinct isoforms of Psc3, suggesting that post-translational modification of Psc3 contributes to the regulation of cohesion function.

S. pombe meiotic linear elements contain proteins related to synaptonemal complex components.

The fission yeast Schizosaccharomyces pombe does not form synaptonemal complexes (SCs) in meiotic prophase nuclei. Instead, thin threads, the so-called linear elements (LEs), are observed at the corresponding stages by electron microscopy. Here, we demonstrate that S. pombe Rec10 is a protein related to the Saccharomyces cerevisiae SC protein Red1 and that it localizes to LEs. Moreover, a homologue to S. cerevisiae Hop1 does exist in S. pombe and we show by in situ immunostaining that it, and the kinase Mek1 (a homologue of which is also known to be associated with SCs), localizes to LEs. These observations indicate the evolutionary relationship of LEs with the lateral elements of SCs and suggest that these structures might exert similar functions in S. cerevisiae and S. pombe.