Evaluation of molecular makers for species phylogeny of genus Acropora (Cnidaria; Scleractinia; Acroporidae)

Acropora is the most speciose genus in coral reef with 113 species currently described. Diversified morphology and potential of cross-species hybridization have drawn our attention in defining the species boundary, constructing species-level phylogeny, and inferring mechanism of speciation for this genus. Although endeavours have been taking in developing molecular markers in the last decade, several unique features such as slow evolution of mitochondrial genome and abundant ribosomal pseudogenes of Acropora neither provide little resolution for phylogenetic inference, nor equivocal conclusions in contrast to phylogenies based on fossil records and morphological characters. In this study, we evaluated 4 molecular markers, including mitochondrial cytochrome b gene (Cytb), mitochondrial intergenic spacer spanning between Cytb and ND gene (mtigs), mini-collagen intron 2 (mci2), and nuclear histone 2a and 2b gene (H2ab), for constructing species phylogeny of genus Acropora. All the 4 loci supported the two subgenera, lsopora and Acropora, as two distinct evolutionary lineages, and relocated Acropora togianensis as the fifth species in the• subgenus lsopora. However, Cytb, mtigs, and mci2 suffering from either low variability or sharing unsorted polymorphisms between the Caribbean and Indo-Pacific species provided no further resolution in resolving phylogeny in subgenus Acropora. In contrast, phylogeny constructed based on h2ab gene using Bayesian approach supported, in part, to Wallace (1999), that A. humilis group and A. austera form the basal clades of morphological phylogeny. The utility of nuclear coding genes in. resolving. species phylogeny of Acropora is highlighted

The TiM system: developing a novel telehealth service to improve access to specialist care in motor neurone disease using user-centered design

Objectives: Attendance at a specialist multidisciplinary motor neurone disease (MND) clinic is associated with improved survival and may also improve quality of life and reduce hospital admissions. However, patients struggle to travel to clinic and may experience difficulties between clinic visits that may not be addressed in a timely manner. We wanted to explore how we could improve access to specialist MND care. Methods: We adopted an iterative, user-centered co-design approach, collaborating with those with experience of providing and receiving MND care including patients, carers, clinicians, and technology developers. We explored the unmet needs of those living with MND, how they might be met through service redesign and through the use of digital technologies. We developed a new digital solution and performed initial testing with potential users including clinicians, patients, and carers. Results: We used these findings to develop a telehealth system (TiM) using an Android app into which patients and carers answer a series of questions about their condition on a weekly basis. The questions aim to capture all the physical, emotional, and social difficulties associated with MND. This information is immediately uploaded to the internet for review by the MND team. The data undergoes analysis in order to alert clinicians to any changes in a patient or carer’s condition. Conclusions: We describe the benefits of developing a novel digitally enabled service underpinned by participatory design. Future trials must evaluate the feasibility and acceptability of the TiM system within a clinical environment

Being Warm Being Happy: fuel poverty and adults with intellectual disabilities

Self-determination has been acknowledged as a criticalconstruct for people with intellectual disability (ID), given the benefits itspromotion entails towards an enhanced quality of life..

Who pays and who benefits? How different models of shared responsibilities between formal and informal carers influence projections of costs of dementia management

<p>Abstract</p> <p>Background</p> <p>The few studies that have attempted to estimate the future cost of caring for people with dementia in Australia are typically based on total prevalence and the cost per patient over the average duration of illness. However, costs associated with dementia care also vary according to the length of the disease, severity of symptoms and type of care provided. This study aimed to determine more accurately the future costs of dementia management by taking these factors into consideration.</p> <p>Methods</p> <p>The current study estimated the prevalence of dementia in Australia (2010-2040). Data from a variety of sources was recalculated to distribute this prevalence according to the location (home/institution), care requirements (informal/formal), and dementia severity. The cost of care was attributed to redistributed prevalences and used in prediction of future costs of dementia.</p> <p>Results</p> <p>Our computer modeling indicates that the ratio between the prevalence of people with mild/moderate/severe dementia will change over the three decades from 2010 to 2040 from 50/30/20 to 44/32/24.</p> <p>Taking into account the severity of symptoms, location of care and cost of care per hour, the current study estimates that the informal cost of care in 2010 is AU$3.2 billion and formal care at AU$5.0 billion per annum. By 2040 informal care is estimated to cost AU$11.6 billion and formal care$AU16.7 billion per annum. Interventions to slow disease progression will result in relative savings of 5% (AU$1.5 billion) per annum and interventions to delay disease onset will result in relative savings of 14$4 billion) of the cost per annum.</p> <p>With no intervention, the projected combined annual cost of formal and informal care for a person with dementia in 2040 will be around AU$38,000 (in 2010 dollars). An intervention to delay progression by 2 years will see this reduced to AU$35,000.</p> <p>Conclusions</p> <p>These findings highlight the need to account for more than total prevalence when estimating the costs of dementia care. While the absolute values of cost of care estimates are subject to the validity and reliability of currently available data, dynamic systems modeling allows for future trends to be estimated.</p

Annotation of two large contiguous regions from the Haemonchus contortus genome using RNA-seq and comparative analysis with Caenorhabditis elegans

The genomes of numerous parasitic nematodes are currently being sequenced, but their complexity and size, together with high levels of intra-specific sequence variation and a lack of reference genomes, makes their assembly and annotation a challenging task. Haemonchus contortus is an economically significant parasite of livestock that is widely used for basic research as well as for vaccine development and drug discovery. It is one of many medically and economically important parasites within the strongylid nematode group. This group of parasites has the closest phylogenetic relationship with the model organism Caenorhabditis elegans, making comparative analysis a potentially powerful tool for genome annotation and functional studies. To investigate this hypothesis, we sequenced two contiguous fragments from the H. contortus genome and undertook detailed annotation and comparative analysis with C. elegans. The adult H. contortus transcriptome was sequenced using an Illumina platform and RNA-seq was used to annotate a 409 kb overlapping BAC tiling path relating to the X chromosome and a 181 kb BAC insert relating to chromosome I. In total, 40 genes and 12 putative transposable elements were identified. 97.5% of the annotated genes had detectable homologues in C. elegans of which 60% had putative orthologues, significantly higher than previous analyses based on EST analysis. Gene density appears to be less in H. contortus than in C. elegans, with annotated H. contortus genes being an average of two-to-three times larger than their putative C. elegans orthologues due to a greater intron number and size. Synteny appears high but gene order is generally poorly conserved, although areas of conserved microsynteny are apparent. C. elegans operons appear to be partially conserved in H. contortus. Our findings suggest that a combination of RNA-seq and comparative analysis with C. elegans is a powerful approach for the annotation and analysis of strongylid nematode genomes

A proteomic approach for the rapid, multi-informative and reliable identification of blood

Blood evidence is frequently encountered at the scene of violent crimes and can provide valuable intelligence in the forensic investigation of serious offences. Because many of the current enhancement methods used by crime scene investigators are presumptive, the visualisation of blood is not always reliable nor does it bear additional information. In the work presented here, two methods employing a shotgun bottom up proteomic approach for the detection of blood are reported; the developed protocols employ both an in solution digestion method and a recently proposed procedure involving immobilization of trypsin on hydrophobin Vmh2 coated MALDI sample plate. The methods are complementary as whilst one yields more identifiable proteins (as biomolecular signatures), the other is extremely rapid (5 minutes). Additionally, data demonstrate the opportunity to discriminate blood provenance even when two different blood sources are present in a mixture. This approach is also suitable for old bloodstains which had been previously chemically enhanced, as experiments conducted on a 9-year-old bloodstain deposited on a ceramic tile demonstrate

Author Correction:C16orf72/HAPSTR1/TAPR1 functions with BRCA1/Senataxin to modulate replication-associated R-loops and confer resistance to PARP disruption

Correction to: Nature Communications https://doi.org/10.1038/s41467-023-40779-9, published online 17 August 2023

Intratumoral Hydrogen Peroxide With Radiation Therapy in Locally Advanced Breast Cancer: Results From a Phase 1 Clinical Trial.

Purpose Hydrogen peroxide (H2O2) plays a vital role in normal cellular processes but at supraphysiological concentrations causes oxidative stress and cytotoxicity, a property that is potentially exploitable for the treatment of cancer in combination with radiation therapy (RT). We report the first phase 1 trial testing the safety and tolerability of intratumoral H2O2 + external beam RT as a novel combination in patients with breast cancer and exploratory plasma marker analyses investigating possible mechanisms of action.Methods and materials Twelve patients with breast tumors ≥3 cm (surgically or medically inoperable) received intratumoral H2O2 with either 36 Gy in 6 twice-weekly fractions (n = 6) or 49.5 Gy in 18 daily fractions (n = 6) to the whole breast ± locoregional lymph nodes in a single-center, nonrandomized study. H2O2 was mixed in 1% sodium hyaluronate gel (final H2O2 concentration 0.5%) before administration to slow drug release and minimize local discomfort. The mixture was injected intratumorally under ultrasound guidance twice weekly 1 hour before RT. The primary endpoint was patient-reported maximum intratumoral pain intensity before and 24 hours postinjection. Secondary endpoints included grade ≥3 skin toxicity and tumor response by ultrasound. Blood samples were collected before, during, and at the end of treatment for cell-death and immune marker analysis.Results Compliance with H2O2 and RT was 100%. Five of 12 patients reported moderate pain after injection (grade 2 Common Terminology Criteria for Adverse Events v4.02) with median duration 60 minutes (interquartile range, 20-120 minutes). Skin toxicity was comparable to RT alone, with maintained partial/complete tumor response relative to baseline in 11 of 12 patients at last follow-up (median 12 months). Blood marker analysis highlighted significant associations of TRAIL, IL-1β, IL-4, and MIP-1α with tumor response.Conclusions Intratumoral H2O2 with RT is well tolerated with no additional toxicity compared with RT alone. If efficacy is confirmed in a randomized phase 2 trial, the approach has potential as a cost-effective radiation response enhancer in multiple cancer types in which locoregional control after RT alone remains poor

Glutamate-Gated Chloride Channels of Haemonchus contortus Restore Drug Sensitivity to Ivermectin Resistant Caenorhabditis elegans

Anthelmintic resistance is a major problem in livestock farming, especially of small ruminants, but our understanding of it has been limited by the difficulty in carrying out functional genetic studies on parasitic nematodes. An important nematode infecting sheep and goats is Haemonchus contortus; in many parts of the world this species is resistant to almost all the currently available drugs, including ivermectin. It is extremely polymorphic and to date it has proved impossible to relate any sequence polymorphisms to its ivermectin resistance status. Expression of candidate drug-resistance genes in Caenorhabditis elegans could provide a convenient means to study the effects of polymorphisms found in resistant parasites, but may be complicated by differences between the gene families of target and model organisms. We tested this using the glutamate-gated chloride channel (GluCl) gene family, which forms the ivermectin drug target and are candidate resistance genes. We expressed GluCl subunits from C. elegans and H. contortus in a highly resistant triple mutant C. elegans strain (DA1316) under the control of the avr-14 promoter; expression of GFP behind this promoter recapitulated the pattern previously reported for avr-14. Expression of ivermectin-sensitive subunits from both species restored drug sensitivity to transgenic worms, though some quantitative differences were noted between lines. Expression of an ivermectin-insensitive subunit, Hco-GLC-2, had no effect on drug sensitivity. Expression of a previously uncharacterised parasite-specific subunit, Hco-GLC-6, caused the transgenic worms to become ivermectin sensitive, suggesting that this subunit also encodes a GluCl that responds to the drug. These results demonstrate that both orthologous and paralogous subunits from C. elegans and H. contortus are able to rescue the ivermectin sensitivity of mutant C. elegans, though some quantitative differences were observed between transgenic lines in some assays. C. elegans is a suitable system for studying parasitic nematode genes that may be involved in drug resistance