Ecological Effects of Fear: How Spatiotemporal Heterogeneity in Predation Risk Influences Mule Deer Access to Forage in a Sky‐Island System

Forage availability and predation risk interact to affect habitat use of ungulates across many biomes. Within sky‐island habitats of the Mojave Desert, increased availability of diverse forage and cover may provide ungulates with unique opportunities to extend nutrient uptake and/or to mitigate predation risk. We addressed whether habitat use and foraging patterns of female mule deer (Odocoileus hemionus) responded to normalized difference vegetation index (NDVI), NDVI rate of change (green‐up), or the occurrence of cougars (Puma concolor). Female mule deer used available green‐up primarily in spring, although growing vegetation was available during other seasons. Mule deer and cougar shared similar habitat all year, and our models indicated cougars had a consistent, negative effect on mule deer access to growing vegetation, particularly in summer when cougar occurrence became concentrated at higher elevations. A seemingly late parturition date coincided with diminishing NDVI during the lactation period. Sky‐island populations, rarely studied, provide the opportunity to determine how mule deer respond to growing foliage along steep elevation and vegetation gradients when trapped with their predators and seasonally limited by aridity. Our findings indicate that fear of predation may restrict access to the forage resources found in sky islands

Implementation of a quality improvement programme to support advance care planning in five hospitals across a health region.

OBJECTIVES: Advance care planning (ACP) can help patients with a terminal illness to prepare for the end of their lives. This report describes a regional service improvement initiative to increase the identification of hospital inpatients at this stage in their illnesses and to increase the number of such patients who are offered the opportunity to start the process of ACP. METHODS: Data were collected prospectively over a 7 month period from four acute hospital trusts and a specialist cancer centre in the South-West London region. Each unit identified a specific patient population who were screened for eligibility to engage in the process of ACP. Data concerning the reasons for eligibility, the suitability for discussion and the various reasons why patients did not complete the process, were recorded. RESULTS: Over a 7 month period 1980 patients were screened and 559 (28.2%) were found to be potentially eligible for an ACP discussion. Of these 227/559 (40.6%) were deemed suitable for a discussion by medical staff. The majority of these patients (195/227; 86%) were offered the opportunity to undergo ACP discussions and 144/195 (73.8%) agreed to begin the process of ACP. CONCLUSIONS: This report shows that a targeted approach can result in increased uptake in the number of patients who engage in ACP. However, systematic identification of potentially eligible patients requires a significant investment of clinical time and resources

Hematology and serum biochemistry values of free-ranging Iberian wolves (Canis lupus) trapped by leg-hold snares

Hematology and serum biochemistry are important tools in assessing the health and physiological status of wildlife populations. Nevertheless, studies on free-ranging wolves (Canis lupus) are scarce, and no reference values are available neither for Iberian wolves nor for wolves captured with leghold snares. We report 37 hematology and serum biochemistry variables obtained from 26 free-ranging Iberian wolves captured with leg-hold snares between 2007 and 2014, including variables previously not reported in the literature. The values obtained are similar to the published reference intervals for Scandinavian wolves captured by darting from a helicopter, except for higher values for mean corpuscular hemoglobin concentration (MCHC), red blood cell distribution width (RDW), leukocyte count, creatinine kinase (CK), ?-globulins, and total bilirubin (TBIL) and lower values for alkaline phosphatase (ALP). We propose that differences in leukocyte count, CK, and TBIL are related to the method of capture, while differences in RDW, MCHC, ALP, and ?-globulins could reflect physiological adaptations to environmental conditions, sampling, or pre-analytical artifacts. Lymphocyte count was lower and neutrophil/lymphocyte ratio was significantly higher in older, reproductive females, while ALP and phosphorus were higher in juvenile wolves. For the first time, we describe hematology and serum biochemistry values of free-ranging Iberian wolves captured with leg-hold snares. The data reported here is the first published reference for wolves captured with similar methods and for monitoring Iberian wolves populations’ physiological and health status.We thank Nuria Fandos and Carla Ferreira, rangers from Xunta de Galicia and Parque Nacional de los Picos de Europa, and volunteers who helped during the trapping sessions. The wolves were captured under projects financed by Associacao de Conservacao do Habitat do Lobo Iberico (ACHLI) in Portugal and by Picos de Europa National Park, Ministerio de Agricultura, Alimentacion y Medio Ambiente, and Xunta de Galicia in Spain. Sara Roque benefited from grant SFRH/BD/12291/2003 from Fundacao para a Ciencia e a Tecnologia. Jose V. Lopez-Bao was supported by a postdoctoral contract from the Spanish Ministry of Economy and Competitiveness. This is the paper no. 5 from the Iberian Wolf Research Team

Narratives for drug design

We explore the role of narratives of complex systems in anti-cancer drug design. We set out the value of narratives relating to cancer in promoting awareness of risky behaviour and in supporting decision-making regarding treatment options. We present cancer as a dysregulated, complex system that has emergent behaviours at multiple scales, and is governed by dynamical spatio-temporal processes. We show that this system changes structure and function in response to anti-cancer drugs, and explain that these changes are sufficiently complex to impede effective drug design. We pose what narrative might offer to support the process of drug design, providing an example of work done to date that might serve as a foundation for narrating complexity. We suggest ways of using this work combined with that of others to begin to consider narrating drug design

Drug Inhibition Profile Prediction for NFκB Pathway in Multiple Myeloma

Nuclear factor κB (NFκB) activation plays a crucial role in anti-apoptotic responses in response to the apoptotic signaling during tumor necrosis factor (TNFα) stimulation in Multiple Myeloma (MM). Although several drugs have been found effective for the treatment of MM by mainly inhibiting NFκB pathway, there are not any quantitative or qualitative results of comparison assessment on inhibition effect between different drugs either used alone or in combinations. Computational modeling is becoming increasingly indispensable for applied biological research mainly because it can provide strong quantitative predicting power. In this study, a novel computational pathway modeling approach is employed to comparably assess the inhibition effects of specific drugs used alone or in combinations on the NFκB pathway in MM and to predict the potential synergistic drug combinations

Drought-induced changes in flow regimes lead to long-term losses in mussel provided ecosystem services

Extreme hydro-meteorological events such as droughts are becoming more frequent, intense, and persistent. This is particularly true in the south central USA, where rapidly growing urban areas are running out of water and human-engineered water storage and management are leading to broad-scale changes in flow regimes. The Kiamichi River in southeastern Oklahoma, USA, has high fish and freshwater mussel biodiversity. However, water from this rural river is desired by multiple urban areas and other entities. Freshwater mussels are large, long-lived filter feeders that provide important ecosystem services. We ask how observed changes in mussel biomass and community composition resulting from drought-induced changes in flow regimes might lead to changes in river ecosystem services. We sampled mussel communities in this river over a 20-year period that included two severe droughts. We then used laboratory-derived physiological rates and river-wide estimates of species-specific mussel biomass to estimate three aggregate ecosystem services provided by mussels over this time period: biofiltration, nutrient recycling (nitrogen and phosphorus), and nutrient storage (nitrogen, phosphorus, and carbon). Mussel populations declined over 60%, and declines were directly linked to drought-induced changes in flow regimes. All ecosystem services declined over time and mirrored biomass losses. Mussel declines were exacerbated by human water management, which has increased the magnitude and frequency of hydrologic drought in downstream reaches of the river. Freshwater mussels are globally imperiled and declining around the world. Summed across multiple streams and rivers, mussel losses similar to those we document here could have considerable consequences for downstream water quality although lost biofiltration and nutrient retention. While we cannot control the frequency and severity of climatological droughts, water releases from reservoirs could be used to augment stream flows and prevent compounded anthropogenic stressors.National Science Foundation (DEB-9870092, DEB-0211010) Oklahoma Department of Wildlife Conservation (Projects E-12, E-59 and T-10) U.S. Geological SurveyYe

Confidence from uncertainty - A multi-target drug screening method from robust control theory

<p>Abstract</p> <p>Background</p> <p>Robustness is a recognized feature of biological systems that evolved as a defence to environmental variability. Complex diseases such as diabetes, cancer, bacterial and viral infections, exploit the same mechanisms that allow for robust behaviour in healthy conditions to ensure their own continuance. Single drug therapies, while generally potent regulators of their specific protein/gene targets, often fail to counter the robustness of the disease in question. Multi-drug therapies offer a powerful means to restore disrupted biological networks, by targeting the subsystem of interest while preventing the diseased network from reconciling through available, redundant mechanisms. Modelling techniques are needed to manage the high number of combinatorial possibilities arising in multi-drug therapeutic design, and identify synergistic targets that are robust to system uncertainty.</p> <p>Results</p> <p>We present the application of a method from robust control theory, Structured Singular Value or μ- analysis, to identify highly effective multi-drug therapies by using robustness in the face of uncertainty as a new means of target discrimination. We illustrate the method by means of a case study of a negative feedback network motif subject to parametric uncertainty.</p> <p>Conclusions</p> <p>The paper contributes to the development of effective methods for drug screening in the context of network modelling affected by parametric uncertainty. The results have wide applicability for the analysis of different sources of uncertainty like noise experienced in the data, neglected dynamics, or intrinsic biological variability.</p

Temporal and spatial variability in stable isotope ratios of SPM link to local hydrography and longer term SPM averages suggest heavy dependence of mussels on nearshore production

Temporal changes in hydrography affect suspended particulate matter (SPM) composition and distribution in coastal systems, potentially influencing the diets of suspension feeders. Temporal variation in SPM and in the diet of the mussel Perna perna, were investigated using stable isotope analysis. The δ13C and δ15 N ratios of SPM, mussels and macroalgae were determined monthly, with SPM samples collected along a 10 km onshore–offshore transect, over 14 months at Kenton-on-Sea, on the south coast of South Africa. Clear nearshore (0 km) to offshore (10 km) carbon depletion gradients were seen in SPM during all months and extended for 50 km offshore on one occasion. Carbon enrichment of coastal SPM in winter (June–August 2004 and May 2005) indicated temporal changes in the nearshore detrital pool, presumably reflecting changes in macroalgal detritus, linked to local changes in coastal hydrography and algal seasonality. Nitrogen patterns were less clear, with SPM enrichment seen between July and October 2004 from 0 to 10 km. Nearshore SPM demonstrated cyclical patterns in carbon over 24-h periods that correlated closely with tidal cycles and mussel carbon signatures, sampled monthly, demonstrated fluctuations that could not be correlated to seasonal or monthly changes in SPM. Macroalgae showed extreme variability in isotopic signatures, with no discernable patterns. IsoSource mixing models indicated over 50% reliance of mussel tissue on nearshore carbon, highlighting the importance of nearshore SPM in mussel diet. Overall, carbon variation in SPM at both large and small temporal scales can be related to hydrographic processes, but is masked in mussels by long-term isotope integration

Dynamics of extracellular matrix in ovarian follicles and corpora lutea of mice

Despite the mouse being an important laboratory species, little is known about changes in its extracellular matrix (ECM) during follicle and corpora lutea formation and regression. Follicle development was induced in mice (29 days of age/experimental day 0) by injections of pregnant mare’s serum gonadotrophin on days 0 and 1 and ovulation was induced by injection of human chorionic gonadotrophin on day 2. Ovaries were collected for immunohistochemistry (n=10 per group) on days 0, 2 and 5. Another group was mated and ovaries were examined on day 11 (n=7). Collagen type IV α1 and α2, laminin α1, β1 and γ1 chains, nidogens 1 and 2 and perlecan were present in the follicular basal lamina of all developmental stages. Collagen type XVIII was only found in basal lamina of primordial, primary and some preantral follicles, whereas laminin α2 was only detected in some preantral and antral follicles. The focimatrix, a specialised matrix of the membrana granulosa, contained collagen type IV α1 and α2, laminin α1, β1 and γ1 chains, nidogens 1 and 2, perlecan and collagen type XVIII. In the corpora lutea, staining was restricted to capillary sub-endothelial basal laminas containing collagen type IV α1 and α2, laminin α1, β1 and γ1 chains, nidogens 1 and 2, perlecan and collagen type XVIII. Laminins α4 and α5 were not immunolocalised to any structure in the mouse ovary. The ECM composition of the mouse ovary has similarities to, but also major differences from, other species with respect to nidogens 1 and 2 and perlecan