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METTL3 is the catalytic subunit of the methyltransferase complex, which mediates m6A modification to regulate gene expression. In addition, METTL3 regulates transcription in an enzymatic activity-independent manner by driving changes in high-order chromatin structure. However, how these functions of the methyltransferase complex are coordinated remains unknown. Here we show that the methyltransferase complex coordinates its enzymatic activity-dependent and independent functions to regulate cellular senescence, a state of stable cell growth arrest. Specifically, METTL3-mediated chromatin loops induce Hexokinase 2 expression through the three-dimensional chromatin organization during senescence. Elevated Hexokinase 2 expression subsequently promotes liquid-liquid phase separation, manifesting as stress granule phase separation, by driving metabolic reprogramming. This correlates with an impairment of translation of cell-cycle related mRNAs harboring polymethylated m6A sites. In summary, our results report a coordination of m6A-dependent and -independent function of the methyltransferase complex in regulating senescence through phase separation driven by metabolic reprogramming. Here, the authors report that METTL3 orchestrates cellular senescence by coordinating its enzymatic activity-dependent and independent functions. METTL3-mediated chromatin loops induce phase separation via metabolic reprogramming. [ABSTRACT FROM AUTHOR]

Senescence is a cellular state linked to ageing and age-onset disease across many mammalian species1,2. Acutely, senescent cells promote wound healing3,4 and prevent tumour formation5; but they are also pro-inflammatory, thus chronically exacerbate tissue decline. Whereas senescent cells are active targets for anti-ageing therapy6–11, why these cells form in vivo, how they affect tissue ageing and the effect of their elimination remain unclear12,13. Here we identify naturally occurring senescent glia in ageing Drosophila brains and decipher their origin and influence. Using Activator protein 1 (AP1) activity to screen for senescence14,15, we determine that senescent glia can appear in response to neuronal mitochondrial dysfunction. In turn, senescent glia promote lipid accumulation in non-senescent glia; similar effects are seen in senescent human fibroblasts in culture. Targeting AP1 activity in senescent glia mitigates senescence biomarkers, extends fly lifespan and health span, and prevents lipid accumulation. However, these benefits come at the cost of increased oxidative damage in the brain, and neuronal mitochondrial function remains poor. Altogether, our results map the trajectory of naturally occurring senescent glia in vivo and indicate that these cells link key ageing phenomena: mitochondrial dysfunction and lipid accumulation.The authors identify naturally occurring senescent glia in aged Drosophila brains and decipher their origin and influence, determining that they can appear in response to neuronal mitochondrial dysfunction and that they promote lipid accumulation, indicating that these cells link key ageing phenomena. [ABSTRACT FROM AUTHOR]

Collective motivational interviewing (CMI) breaks new ground by extending the theory of motivational interviewing (MI) beyond the individual to include the social network. We explain the core concepts of the six-process model of CMI, which involves multiple parties in the motivational process in embodying a spirit of "neutrality." The semi-structured manual-guided CMI was trialed in persons with substance use with the support of concerned significant others (CSOs), which demonstrated positive outcomes on motivation, social support, frequency of drug use, and adherence to long-term drug treatments. Our developed CMI approach makes a clear contribution to the theory of MI and can potentially benefit people with substance use problems with complex needs. Presently, we are refining CMI and have been applying this approach to additional clients and CSOs. We call for more studies to monitor its fidelity and wider application in populations of individuals affected by substance use disorders. [ABSTRACT FROM AUTHOR]

Defining the mechanisms safeguarding cell fate identity in differentiated cells is crucial to improve 1) - our understanding of how differentiation is maintained in healthy tissues or altered in a disease state, and 2) - our ability to use cell fate reprogramming for regenerative purposes. Here, using a genome-wide transcription factor screen followed by validation steps in a variety of reprogramming assays (cardiac, neural and iPSC in fibroblasts and endothelial cells), we identified a set of four transcription factors (ATF7IP, JUNB, SP7, and ZNF207 [AJSZ]) that robustly opposes cell fate reprogramming in both lineage and cell type independent manners. Mechanistically, our integrated multi-omics approach (ChIP, ATAC and RNA-seq) revealed that AJSZ oppose cell fate reprogramming by 1) - maintaining chromatin enriched for reprogramming TF motifs in a closed state and 2) - downregulating genes required for reprogramming. Finally, KD of AJSZ in combination with MGT overexpression, significantly reduced scar size and improved heart function by 50%, as compared to MGT alone post-myocardial infarction. Collectively, our study suggests that inhibition of barrier to reprogramming mechanisms represents a promising therapeutic avenue to improve adult organ function post-injury. Transdifferentiation has been proposed as an approach for regenerative medicine, but the mechanisms that safeguard cell identity are not well established. Here they identify transcription factors that oppose transdifferentiation and show that knockdown of these genes improves recovery after myocardial infarction. [ABSTRACT FROM AUTHOR]

Epigenetic modifications are known to be crucial for hematopoietic stem cell (HSC) differentiation, with the BET family member BRD4 playing a vital role in this as an epigenetic reader. In this issue of EMBO reports, Yang et al (2023) demonstrate that the absence of BRD4 leads to senescence in HSCs and hematopoietic progenitor cells (HPCs), affecting the expression of crucial genes involved in myeloid and erythroid development. These data suggest that BRD4 has a protective role in preserving histone tails, thereby sustaining normal HSC/HPC functions. [ABSTRACT FROM AUTHOR]

The red fox (Vulpes vulpes) is one of the most adaptable carnivorans, thriving in cities across the globe. We used GPS-tracking of five suburban foxes across high-density residential suburbs of Perth, Western Australia to quantify (1) their habitat selection and (2) home range area. All five foxes showed statistically significant avoidance of residential locations (p < 0.001) and preference for parkland (p < 0.001), with native vegetation reserves, golf courses, and water reserves showing disproportionately greater use. Landuse category also influenced their movements, with foxes moving quickest (i.e., commuting) in proximity to roads and slowest (i.e., foraging) when they were further from roads. Three females had core home ranges (50% autocorrelated-corrected kernel density estimate; AKDEc) averaging 37 ± 20 ha or 95% AKDEc averaging 208 ± 196 ha. One male had a 95 ha core home range and 349 ha 95% AKDEc but the other male covered an area ~ 20 times this: using a 371 ha core home range and 7,368 ha 95% AKDEc. The extensive movement patterns we describe are likely to be common for urban foxes, with half of published home range estimates for urban foxes (principally based on VHF data) excluding data for 'lost' individuals or animals that showed 'excursions'. It is likely that the home range estimates for these urban exploiters have therefore been grossly underestimated to date. Further application of GPS trackers that allow remote download will vastly improve our understanding of habitat preference and exploitation of resources by urban foxes. [ABSTRACT FROM AUTHOR]

The introduction of European red foxes in Australia in the late mid-nineteenth century has resulted in the spread of this invasive species across the continent. The morphological and functional divergence of this relatively recently introduced population has not been explored to date, yet it may provide unique insights into adaptability of this widespread carnivore to very different environments. Here we used three-dimensional geometric morphometric approaches and dissections to explore differences in mandible form and function between two populations: one from France and the other from Western Australia. Bite force was predicted for Australian foxes using partial least squares (PLS) regression models based on the observed covariation between estimated bite force (from muscle dissections) and mandible form in French foxes. Muscle contributions were estimated based on Euclidean distances between landmarks that provide insights into muscle lever arms. Despite the greater sample size, Australian foxes show reduced variability in mandible shape compared with French foxes. The mandibles of adult French foxes tend to be slightly smaller and they also strongly differ in shape from the Australian foxes in functionally important areas of the mandible such as muscle insertion areas. This is accompanied by significant differences in the predicted bite force, even relative to size, and muscle contribution: the bite of Australian foxes is weaker and they show greater use of their temporalis muscle compared to French foxes. The reduced variability suggests a founder effect or stabilizing selection on a specific morphology, which was supported by statistical tests. The corresponding anatomical traits suggest different functional demands likely due to differences in diet or competition. Future studies investigating the drivers of variation in mandible shape in native and invasive populations, including data from the original source of the Australian introductions, are needed to better understand the observed differences. [ABSTRACT FROM AUTHOR]

Understanding basic mechanisms of aging holds great promise for developing interventions that prevent or delay many age-related declines and diseases simultaneously to increase human healthspan. However, a major confounding factor in aging research is the heterogeneity of the aging process itself. At the organismal level, it is clear that chronological age does not always predict biological age or susceptibility to frailty or pathology. While genetics and environment are major factors driving variable rates of aging, additional complexity arises because different organs, tissues, and cell types are intrinsically heterogeneous and exhibit different aging trajectories normally or in response to the stresses of the aging process (e.g., damage accumulation). Tackling the heterogeneity of aging requires new and specialized tools (e.g., single-cell analyses, mass spectrometry-based approaches, and advanced imaging) to identify novel signatures of aging across scales. Cutting-edge computational approaches are then needed to integrate these disparate datasets and elucidate network interactions between known aging hallmarks. There is also a need for improved, human cell-based models of aging to ensure that basic research findings are relevant to human aging and healthspan interventions. The San Diego Nathan Shock Center (SD-NSC) provides access to cutting-edge scientific resources to facilitate the study of the heterogeneity of aging in general and to promote the use of novel human cell models of aging. The center also has a robust Research Development Core that funds pilot projects on the heterogeneity of aging and organizes innovative training activities, including workshops and a personalized mentoring program, to help investigators new to the aging field succeed. Finally, the SD-NSC participates in outreach activities to educate the general community about the importance of aging research and promote the need for basic biology of aging research in particular. [ABSTRACT FROM AUTHOR]

Background: Recent studies have suggested that fatty acid oxidation (FAO) is a key metabolic pathway for the growth of triple negative breast cancers (TNBCs), particularly those that have high expression of MYC. However, the underlying mechanism by which MYC promotes FAO remains poorly understood.Methods: We used a combination of metabolomics, transcriptomics, bioinformatics, and microscopy to elucidate a potential mechanism by which MYC regulates FAO in TNBC.Results: We propose that MYC induces a multigenic program that involves changes in intracellular calcium signalling and fatty acid metabolism. We determined key roles for fatty acid transporters (CD36), lipases (LPL), and kinases (PDGFRB, CAMKK2, and AMPK) that each contribute to promoting FAO in human mammary epithelial cells that express oncogenic levels of MYC. Bioinformatic analysis further showed that this multigenic program is highly expressed and predicts poor survival in the claudin-low molecular subtype of TNBC, but not other subtypes of TNBCs, suggesting that efforts to target FAO in the clinic may best serve claudin-low TNBC patients.Conclusion: We identified critical pieces of the FAO machinery that have the potential to be targeted for improved treatment of patients with TNBC, especially the claudin-low molecular subtype. [ABSTRACT FROM AUTHOR]

Background: Early discharge after laparoscopic sleeve gastrectomy (SG) is common and safe, but two-thirds of patients are still hospitalized longer than 1 day. The purpose of this study was to evaluate factors associated with early discharge at a single institution with intention to discharge on postoperative day 1. Methods: Retrospective review of preoperative, intraoperative, and postoperative factors was performed for all patients undergoing SG at an academic hospital between 2010 and 2016. The primary outcome measure was length of stay (LOS). Multivariate logistic regression was used to identify independent predictors of prolonged LOS. Results: A total of 367 patients undergoing SG were included. Two hundred eighty-seven (78%) were women and 294 (80%) were Caucasian. Mean age was 45.5 years and mean body mass index (BMI) was 48.7 kg/m2. One hundred twenty-three patients (33.5%) had a LOS ≤ 1 day. Compared to patients staying ≥ 2 days, early discharge patients had significantly lower BMI, creatinine, and American Society of Anesthesiologists class, were more likely to be White, married, have private insurance, and were more likely to have a morning start and no postoperative upper gastrointestinal (UGI) swallow study. Regression analysis demonstrated several independent predictors of prolonged LOS including institutional experience (OR 0.5, p < 0.001), case start time (OR 0.6, p = 0.04), and routine UGI swallow (OR 8.8, p < 0.0001) postoperatively. Conclusions: LOS after SG is affected by multiple factors, including patient health, socioeconomic status, case order, and postoperative management. Optimization of these may allow for improvement in preoperative education and streamlined postoperative pathways, resulting in reduced LOS. [ABSTRACT FROM AUTHOR]

Workplace harassment in higher education adversely impacts workforce productivity and has deleterious health effects on victims. The aim of this study was to review the literature pertaining to workplace harassment in higher education. This systematic literature search was conducted in December 2013 and completed in January 2014. Refereed journal publications from 1994 to 2013 inclusive were identified. The strategy was conducted on seven major databases. A total of 3278 articles were initially screened, and after review 51 refereed journal articles were included in the final analysis. A thematic analysis identified six themes: causation, types, employee roles, measurement, consequences and interventions. The published evidence, mainly from North America, suggests that workplace harassment is prevalent in higher education, such as gender harassment, workplace bullying, and mobbing. This review highlighted issues associated with: (1) confirming direct causation of harassment due to the high prevalence of correlational research in this area; (2) establishing and standardising measures of harassment that would have cross-cultural applicability and validity; (3) the demand for more comparative research to cater for the globally mobile workforce; (4) the requirement for greater monitoring and evaluation of the efficacy of policies and programmes purporting to be effective in dealing with harassment in the higher education workplace; and (5) the need for more contextually laden research to examine the unique nuances operating in countries, such as those in the Asia Pacific region, not well represented in the literature. [ABSTRACT FROM AUTHOR]

The concept of addiction is complex and shaped by a range of understandings including how the recipient of an addiction is interpreted. This paper examines how concepts of self and concepts of addiction interact. Two fundamentally different understandings of self are considered: one which focuses on the self as a bio-psychological individual, the 'particle' self, and another that focuses on the self as a nexus of relationships, the 'social' self. The effect these have on understandings of addiction is examined along with implications for service interventions. Particle-informed understandings of addiction are seen as dominating services and leading to intervention responses that focus on the individual and de-emphasize the role of family, community and culture. The absence of social understandings limits both the range and quality of services offered. Particle and social approaches to addiction could operate side-by-side in offering a broader range of effective service responses to addiction. [ABSTRACT FROM AUTHOR]

Macroautophagy (hereafter referred to as autophagy) is a catabolic membrane trafficking process that degrades a variety of cellular constituents and is associated with human diseases. Although extensive studies have focused on autophagic turnover of cytoplasmic materials, little is known about the role of autophagy in degrading nuclear components. Here we report that the autophagy machinery mediates degradation of nuclear lamina components in mammals. The autophagy protein LC3/Atg8, which is involved in autophagy membrane trafficking and substrate delivery, is present in the nucleus and directly interacts with the nuclear lamina protein lamin B1, and binds to lamin-associated domains on chromatin. This LC3-lamin B1 interaction does not downregulate lamin B1 during starvation, but mediates its degradation upon oncogenic insults, such as by activated RAS. Lamin B1 degradation is achieved by nucleus-to-cytoplasm transport that delivers lamin B1 to the lysosome. Inhibiting autophagy or the LC3-lamin B1 interaction prevents activated RAS-induced lamin B1 loss and attenuates oncogene-induced senescence in primary human cells. Our study suggests that this new function of autophagy acts as a guarding mechanism protecting cells from tumorigenesis. [ABSTRACT FROM AUTHOR]

Dendrobium bigibbum Lindl. has a long confused history, with taxa variously described as separate species, subspecies, varieties and forms. This paper records morphological variation in 160 representative plants in north Queensland and Torres Strait. The distribution range is delineated. ITS-DNA results did not show significant differences between populations. The evidence supports a single species D. bigibbum Lindl. with three intergrading varieties: vars bigibbum, superbum and compactum. Some types have uncertain provenance, particularly D. phalaenopsis, which is reduced to synonymy under D. bigibbum var. superbum. A combination of characters can be used to identify varieties. A new combination of D. bigibbum var. compactum reduces D. phalaenopsis var. compactum to synonymy. [ABSTRACT FROM AUTHOR]

The Coastal Storm Modeling System (CoSMoS) applies a predominantly deterministic framework to make detailed predictions (meter scale) of storm-induced coastal flooding, erosion, and cliff failures over large geographic scales (100s of kilometers). CoSMoS was developed for hindcast studies, operational applications (i.e., nowcasts and multiday forecasts), and future climate scenarios (i.e., sea-level rise + storms) to provide emergency responders and coastal planners with critical storm hazards information that may be used to increase public safety, mitigate physical damages, and more effectively manage and allocate resources within complex coastal settings. The prototype system, developed for the California coast, uses the global WAVEWATCH III wave model, the TOPEX/Poseidon satellite altimetry-based global tide model, and atmospheric-forcing data from either the US National Weather Service (operational mode) or Global Climate Models (future climate mode), to determine regional wave and water-level boundary conditions. These physical processes are dynamically downscaled using a series of nested Delft3D-WAVE (SWAN) and Delft3D-FLOW (FLOW) models and linked at the coast to tightly spaced XBeach (eXtreme Beach) cross-shore profile models and a Bayesian probabilistic cliff failure model. Hindcast testing demonstrates that, despite uncertainties in preexisting beach morphology over the ~500 km alongshore extent of the pilot study area, CoSMoS effectively identifies discrete sections of the coast (100s of meters) that are vulnerable to coastal hazards under a range of current and future oceanographic forcing conditions, and is therefore an effective tool for operational and future climate scenario planning. [ABSTRACT FROM AUTHOR]

Cellular senescence is a stable proliferation arrest associated with an altered secretory pathway, the senescence-associated secretory phenotype. However, cellular senescence is initiated by diverse molecular triggers, such as activated oncogenes and shortened telomeres, and is associated with varied and complex physiological endpoints, such as tumor suppression and tissue aging. The extent to which distinct triggers activate divergent modes of senescence that might be associated with different physiological endpoints is largely unknown. To begin to address this, we performed gene expression profiling to compare the senescence programs associated with two different modes of senescence, oncogene-induced senescence (OIS) and replicative senescence (RS [in part caused by shortened telomeres]). While both OIS and RS are associated with many common changes in gene expression compared to control proliferating cells, they also exhibit substantial differences. These results are discussed in light of potential physiological consequences, tumor suppression and aging. [ABSTRACT FROM AUTHOR]

Feral pigs have long been implicated as potential vectors in the spread of the devastating plant pathogen Phytophthora cinnamomi due to their rooting and wallowing activities which may predispose them as vectors of infested soil. In this study, we aim to determine whether feral pigs have the potential to act as vectors of plant pathogens such as P. cinnamomi through their feeding activity. The typically omnivorous diet of feral pigs may also lead to the passage of P. cinnamomi infected plant material through their digestive system. This study investigates the potential for feral pigs to pass viable P. cinnamomi in their faeces following the ingestion of millet seeds, pine plugs and Banksia leptophilia roots inoculated with P. cinnamomi. Recovery rates of P. cinnamomi from the millet seeds, pine plugs and B. leptophilia roots following a single ingested bolus were 33.2, 94.9 and 10.4 %, respectively supported by quantitative PCR analysis. These results demonstrate that P. cinnamomi remain viable within infected plant material following passage through the pig digestive tract, although the digestive processes reduce the pathogen's viability. An inverse relationship was observed between the viability of infected material and passage time, suggesting that partially digested plant material provides protection for P. cinnamomi against the adverse environmental conditions of the pig digestive tract. Phytophthora cinnamomi remained viable for up to 7 days in larger pieces of colonised woody plant material such as the pine plugs. A plant infection trial using passaged P. cinnamomi colonised pine plugs showed that even material that remained in the digestive tract for 7 days was capable of infecting and killing healthy plants, susceptible to P. cinnamomi. This study provides compelling evidence that feral pigs have the ability to transport viable P. cinnamomi in their digestive tract. [ABSTRACT FROM AUTHOR]

Macroautophagy (hereafter referred to as autophagy) is a process in which organelles termed autophagosomes deliver cytoplasmic constituents to lysosomes for degradation. Autophagy has a major role in cellular homeostasis and has been implicated in various forms of human disease. The role of autophagy in cancer seems to be complex, with reports indicating both pro-tumorigenic and tumour-suppressive roles. Here we show, in a humanized genetically-modified mouse model of pancreatic ductal adenocarcinoma (PDAC), that autophagy's role in tumour development is intrinsically connected to the status of the tumour suppressor p53. Mice with pancreases containing an activated oncogenic allele of Kras (also called Ki-Ras)-the most common mutational event in PDAC-develop a small number of pre-cancerous lesions that stochastically develop into PDAC over time. However, mice also lacking the essential autophagy genes Atg5 or Atg7 accumulate low-grade, pre-malignant pancreatic intraepithelial neoplasia lesions, but progression to high-grade pancreatic intraepithelial neoplasias and PDAC is blocked. In marked contrast, in mice containing oncogenic Kras and lacking p53, loss of autophagy no longer blocks tumour progression, but actually accelerates tumour onset, with metabolic analysis revealing enhanced glucose uptake and enrichment of anabolic pathways, which can fuel tumour growth. These findings provide considerable insight into the role of autophagy in cancer and have important implications for autophagy inhibition in cancer therapy. In this regard, we also show that treatment of mice with the autophagy inhibitor hydroxychloroquine, which is currently being used in several clinical trials, significantly accelerates tumour formation in mice containing oncogenic Kras but lacking p53. [ABSTRACT FROM AUTHOR]

Altered DNA methylation and associated destabilization of genome integrity and function is a hallmark of cancer. Replicative senescence is a tumour suppressor process that imposes a limit on the proliferative potential of normal cells that all cancer cells must bypass. Here we show by whole-genome single-nucleotide bisulfite sequencing that replicative senescent human cells exhibit widespread DNA hypomethylation and focal hypermethylation. Hypomethylation occurs preferentially at gene-poor, late-replicating, lamin-associated domains and is linked to mislocalization of the maintenance DNA methyltransferase (DNMT1) in cells approaching senescence. Low-level gains of methylation are enriched in CpG islands, including at genes whose methylation and silencing is thought to promote cancer. Gains and losses of methylation in replicative senescence are thus qualitatively similar to those in cancer, and this 'reprogrammed' methylation landscape is largely retained when cells bypass senescence. Consequently, the DNA methylome of senescent cells might promote malignancy, if these cells escape the proliferative barrier. [ABSTRACT FROM AUTHOR]

Changes in deep-water wave climate drive coastal morphologic change according to unique shoaling transformation patterns of waves over local shelf bathymetry. The Southern California Bight has a particularly complex shelf configuration, of tectonic origin, which poses a challenge to predictions of wave driven, morphologic coastal change. Northward shifts in cyclonic activity in the central Pacific Ocean, which may arise due to global climate change, will significantly alter the heights, periods, and directions of waves approaching the California coasts. In this paper, we present the results of a series of numerical experiments that explore the sensitivity of longshore sediment transport patterns to changes in deep water wave direction, for several wave height and period scenarios. We outline a numerical modeling procedure, which links a spectral wave transformation model (SWAN) with a calculation of gradients in potential longshore sediment transport rate (CGEM), to project magnitudes of potential coastal erosion and accretion, under proscribed deep water wave conditions. The sediment transport model employs two significant assumptions: (1) quantity of sediment movement is calculated for the transport-limited case, as opposed to supply-limited case, and (2) nearshore wave conditions used to evaluate transport are calculated at the 5-meter isobath, as opposed to the wave break point. To illustrate the sensitivity of the sedimentary system to changes in deep-water wave direction, we apply this modeling procedure to two sites that represent two different coastal exposures and bathymetric configurations. The Santa Barbara site, oriented with a roughly west-to-east trending coastline, provides an example where the behavior of the coastal erosional/accretional character is exacerbated by deep-water wave climate intensification. Where sheltered, an increase in wave height enhances accretion, and where exposed, increases in wave height and period enhance erosion. In contrast, all simulations run for the Torrey Pines site, oriented with a north-to-south trending coastline, resulted in erosion, the magnitude of which was strongly influenced by wave height and less so by wave period. At both sites, the absolute value of coastal accretion or erosion strongly increases with a shift from northwesterly to westerly waves. These results provide some examples of the potential outcomes, which may result from increases in cyclonic activity, El Niño frequency, or other changes in ocean storminess that may accompany global climate change. [ABSTRACT FROM AUTHOR]

Climate change could substantially alter the width of beaches in Southern California. Climate-driven sea level rise will have at least two important impacts on beaches: (1) higher sea level will cause all beaches to become more narrow, all things being held constant, and (2) sea level rise may affect patterns of beach erosion and accretion when severe storms combine with higher high tides. To understand the potential economic impacts of these two outcomes, this study examined the physical and economic effects of permanent beach loss caused by inundation due to sea level rise of one meter and of erosion and accretion caused by a single, extremely stormy year (using a model of beach change based on the wave climate conditions of the El Niño year of 1982/1983.) We use a random utility model of beach attendance in Southern California that estimates the impacts of changes on beach width for different types of beach user visiting public beaches in Los Angeles and Orange Counties. The model allows beachgoers to have different preferences for beach width change depending on beach size. We find that the effect of climate-driven beach change differs for users that participate in bike path activities, sand-based activities, and water-based activities. We simulate the effects of climate-related beach loss on attendance patterns at 51 public beaches, beach-related expenditures at those beaches, and the non-market (consumer surplus) value of beach going to those beaches. We estimate that increasing sea level will cause an overall reduction of economic value in beach going, with some beaches experiencing increasing attendance and beach-related earnings while attendance and earnings at other beaches would be lower. We also estimate that the potential annual economic impacts from a single stormy year may be as large as those caused by permanent inundation that would result from a rise in sea level of one meter. The economic impacts of both permanent inundation and storm-related erosion are distributed unevenly across the region. To put the economic impacts of these changes in beach width in perspective, the paper provides simple estimates of the cost of mitigating beach loss by nourishing beaches with sand. [ABSTRACT FROM AUTHOR]

Medicinal chemists synthesize arrays of molecules by attaching functional groups to scaffolds. There is evidence suggesting that some scaffolds yield biologically active molecules more than others, these are termed privileged substructures. One role of the scaffold is to present its side-chains for molecular recognition, and biologically relevant scaffolds may present side-chains in biologically relevant geometries or shapes. Since drug discovery is primarily focused on the discovery of compounds that bind to proteinaceous targets, we have been deciphering the scaffold shapes that are used for binding proteins as they reflect biologically relevant shapes. To decipher the scaffold architecture that is important for binding protein surfaces, we have analyzed the scaffold architecture of protein loops, which are defined in this context as continuous four residue segments of a protein chain that are not part of an α-helix or β-strand secondary structure. Loops are an important molecular recognition motif of proteins. We have found that 39 clusters reflect the scaffold architecture of 89% of the 23,331 loops in the dataset, with average intra-cluster and inter-cluster RMSD of 0.47 and 1.91, respectively. These protein loop scaffolds all have distinct shapes. We have used these 39 clusters that reflect the scaffold architecture of protein loops as biological descriptors. This involved generation of a small dataset of scaffold-based peptidomimetics. We found that peptidomimetic scaffolds with reported biological activities matched loop scaffold geometries and those peptidomimetic scaffolds with no reported biologically activities did not. This preliminary evidence suggests that organic scaffolds with tight matches to the preferred loop scaffolds of proteins, implies the likelihood of the scaffold to be biologically relevant. [ABSTRACT FROM AUTHOR]

Let ( X, C) be a k-cycle system of order n, with vertex set X (of cardinality n) and collection of k-cycles C. Suppose n= kq+ r where r< k. An almost parallel class of C is a collection of q=( n−r)/ k pairwise vertex-disjoint k-cycles of C. Each almost parallel class thus will miss r of the n vertices in X. The k-cycle system ( X,C) is said to be almost resolvable if C can be partitioned into almost parallel classes such that the remaining k-cycles are vertex disjoint. (These remaining k-cycles are referred to as a short parallel class.) In this paper we (a) construct an almost resolvable 10-cycle system of every order congruent to 5 (mod 20), and (b) construct an almost resolvable 10-cycle system of order 41, thus completing the result that the spectrum for almost resolvable 10-cycle systems consists of all orders congruent to 1 or 5 (mod 20). [ABSTRACT FROM AUTHOR]

This paper examines the post-treatment support practices, attitudes and preferences of outpatient alcohol and other drug (AOD) treatment staff as well as perceived barriers to implementing a post-treatment support service in an outpatient AOD treatment context. Data were collected via semi-structured interview and group discussion ( n = 23). Findings suggest that post-treatment support was rarely provided by participating AOD treatment staff or their respective services. However, there was widespread support for implementing such services, and it was generally believed that implementation would be most successful if: multiple post-treatment support options were made available; if one or more of these options were based on the maintenance of an established client/clinician relationship; and if one of the options involved proactive (service-led) telephone support. A number of barriers to possible implementation were identified, although none were considered insurmountable. [ABSTRACT FROM AUTHOR]

This paper presents findings from a survey that sought the post-treatment support preferences of a group of outpatient alcohol and other drug treatment clients. The client group ( n = 83) were presented with six possible models of post-treatment support and were asked to express their level of interest in using or receiving each model and, if interested, by what means they could best be provided. The six models included a range of pro-active (service initiated) and passive (client initiated) support services, variously accessible by telephone, mail, text-message, computer or in-person. Participants were also afforded an opportunity to identify alternative approaches. The results suggest pro-active telephone- and mail-based approaches to post-treatment support are favoured over passive in-person approaches and that computer and text-message approaches (whether passive or pro-active) may be least favourable in the contemporary environment. [ABSTRACT FROM AUTHOR]

This paper examines the possibility that clinicians working in an alcohol and other drug (AOD) treatment service may lack appreciation of problem improvement in clients who choose to dropout against clinical advice. Underlying this investigation is the belief that if clinicians are indeed unperceptive of problem improvement amongst this population then this may explain why retention based responses to client dropout continue to be promoted, despite evidence to suggest that they are ineffective and/or unnecessary. Outcome data obtained from a sample of 75 AOD treatment clients and their respective clinicians at baseline and 2-month follow-up are reported. Analysis of these data suggest a client/clinician discrepancy in perceived problem improvement was evident in the study setting: clinicians reported significantly less problem improvement in the first 2 months of service attendance as compared to their clients and this discrepancy was most pronounced if the client had dropped out of treatment. [ABSTRACT FROM AUTHOR]