Of mast and mean: differential‐temperature cue makes mast seeding insensitive to climate change

Mast‐seeding plants often produce high seed crops the year after a warm spring or summer, but the warm‐temperature model has inconsistent predictive ability. Here, we show for 26 long‐term data sets from five plant families that the temperature difference between the two previous summers (ΔT) better predicts seed crops. This discovery explains how masting species tailor their flowering patterns to sites across altitudinal temperature gradients; predicts that masting will be unaffected by increasing mean temperatures under climate change; improves prediction of impacts on seed consumers; demonstrates that strongly masting species are hypersensitive to climate; explains the rarity of consecutive high‐seed years without invoking resource constraints; and generates hypotheses about physiological mechanisms in plants and insect seed predators. For plants, ΔT has many attributes of an ideal cue. This temperature‐difference model clarifies our understanding of mast seeding under environmental change, and could also be applied to other cues, such as rainfall.     

Findings from the Peutz-Jeghers Syndrome Registry of Uruguay

Background

Peutz-Jeghers syndrome (PJS) is characterized by intestinal polyposis, mucocutaneous pigmentation and an increased cancer risk, usually caused by mutations of the STK11 gene. This study collected epidemiological, clinical and genetic data from all Uruguayan PJS patients.

Methods

Clinical data were obtained from public and private medical centers and updated annually. Sequencing of the STK11 gene in one member of each family was performed.

Results and discussion

25 cases in 11 unrelated families were registered (15 males, 10 females). The average age of diagnosis and death was 18 and 41 years respectively. All patients had characteristic PJS pigmentation and gastrointestinal polyps. 72% required urgent surgery due to intestinal obstruction. 3 families had multiple cases of seizure disorder, representing 20% of cases. 28% developed cancer and two patients had more than one cancer. An STK11 mutation was found in 8 of the 9 families analyzed. A unique M136K missense mutation was noted in one family. Comparing annual live births and PJS birth records from 1970 to 2009 yielded an incidence of 1 in 155,000.

Conclusion

The Uruguayan Registry for Peutz-Jeghers patients showed a high chance of emergent surgery, epilepsy, cancer and shortened life expectancy. The M136K missense mutation is a newly reported STK 11 mutation.     

Challenges in Providing Counselling to MSM in Highly Stigmatized Contexts: Results of a Qualitative Study from Kenya

The role of men who have sex with men (MSM) in the African HIV epidemic is gaining recognition yet capacity to address the HIV prevention needs of this group is limited. HIV testing and counselling is not only a critical entry point for biomedical HIV prevention interventions, such as pre-exposure prophylaxis, rectal microbicides and early treatment initiation, but is also an opportunity for focused risk reduction counselling that can support individuals living in difficult circumstances. For prevention efforts to succeed, however, MSM need to access services and they will only do so if these are non-judgmental, informative, focused on their needs, and of clear benefit. This study aimed to understand Kenyan providers'' attitudes towards and experiences with counselling MSM in a research clinic targeting this group for HIV prevention. We used in-depth interviews to explore values, attitudes and cognitive and social constructs of 13 counsellors and 3 clinicians providing services to MSM at this clinic. Service providers felt that despite their growing experience, more targeted training would have been helpful to improve their effectiveness in MSM-specific risk reduction counselling. They wanted greater familiarity with MSM in Kenya to better understand the root causes of MSM risk-taking (e.g., poverty, sex work, substance abuse, misconceptions about transmission, stigma, and sexual desire) and felt frustrated at the perceived intractability of some of their clients'' issues. In addition, they identified training needs on how to question men about specific risk behaviours, improved strategies for negotiating risk reduction with counselling clients, and improved support supervision from senior counsellors. This paper describes the themes arising from these interviews and makes practical recommendations on training and support supervision systems for nascent MSM HIV prevention programmes in Africa.     

Effect of prey mass and selection on predator carrying capacity estimates

The ability to determine the prey-specific biomass intake of large predators is fundamental to their conservation. In the absence of actual prey data, researchers generally use a “unit mass” method (estimated as 3/4 adult female mass) to calculate the biomass intake of predators. However, differences in prey preference and range across geographic regions are likely to have an influence on biomass calculations. Here we investigate the influence of estimated prey mass on leopard biomass calculations, and subsequent carrying capacity estimates, in an understudied mountain population. Potential leopard feeding sites were identified using global positioning system (GPS) location clusters obtained from GPS collars. We investigated 200 potential leopard feeding sites, of which 96 were actual feeding sites. Jaw bones, horns, hooves, and other indicative bones were used to determine gender and age of prey items, which were subsequently used to calculate mass of each prey item based on previously published values. There were significant differences in the biomass values calculated using the traditional unit mass method and the calculated prey masses obtained from leopard feeding sites. However, there were no considerable differences in the carrying capacity estimates using the preferred prey species model and leopard density estimates calculated using a non-biased spatial approach, which suggests that estimating carnivore carrying capacity based on 3/4 adult female masses is a reliable method also for the mountain population in this study.     

Properties of MHC Class I Presented Peptides That Enhance Immunogenicity

T-cells have to recognize peptides presented on MHC molecules to be activated and elicit their effector functions. Several studies demonstrate that some peptides are more immunogenic than others and therefore more likely to be T-cell epitopes. We set out to determine which properties cause such differences in immunogenicity. To this end, we collected and analyzed a large set of data describing the immunogenicity of peptides presented on various MHC-I molecules. Two main conclusions could be drawn from this analysis: First, in line with previous observations, we showed that positions P4–6 of a presented peptide are more important for immunogenicity. Second, some amino acids, especially those with large and aromatic side chains, are associated with immunogenicity. This information was combined into a simple model that was used to demonstrate that immunogenicity is, to a certain extent, predictable. This model (made available at http://tools.iedb.org/immunogenicity/) was validated with data from two independent epitope discovery studies. Interestingly, with this model we could show that T-cells are equipped to better recognize viral than human (self) peptides. After the past successful elucidation of different steps in the MHC-I presentation pathway, the identification of variables that influence immunogenicity will be an important next step in the investigation of T-cell epitopes and our understanding of cellular immune responses.     

Pathways-Driven Sparse Regression Identifies Pathways and Genes Associated with High-Density Lipoprotein Cholesterol in Two Asian Cohorts

Standard approaches to data analysis in genome-wide association studies (GWAS) ignore any potential functional relationships between gene variants. In contrast gene pathways analysis uses prior information on functional structure within the genome to identify pathways associated with a trait of interest. In a second step, important single nucleotide polymorphisms (SNPs) or genes may be identified within associated pathways. The pathways approach is motivated by the fact that genes do not act alone, but instead have effects that are likely to be mediated through their interaction in gene pathways. Where this is the case, pathways approaches may reveal aspects of a trait''s genetic architecture that would otherwise be missed when considering SNPs in isolation. Most pathways methods begin by testing SNPs one at a time, and so fail to capitalise on the potential advantages inherent in a multi-SNP, joint modelling approach. Here, we describe a dual-level, sparse regression model for the simultaneous identification of pathways and genes associated with a quantitative trait. Our method takes account of various factors specific to the joint modelling of pathways with genome-wide data, including widespread correlation between genetic predictors, and the fact that variants may overlap multiple pathways. We use a resampling strategy that exploits finite sample variability to provide robust rankings for pathways and genes. We test our method through simulation, and use it to perform pathways-driven gene selection in a search for pathways and genes associated with variation in serum high-density lipoprotein cholesterol levels in two separate GWAS cohorts of Asian adults. By comparing results from both cohorts we identify a number of candidate pathways including those associated with cardiomyopathy, and T cell receptor and PPAR signalling. Highlighted genes include those associated with the L-type calcium channel, adenylate cyclase, integrin, laminin, MAPK signalling and immune function.     

A Novel Anti-Tumor Inhibitor Identified by Virtual Screen with PLK1 Structure and Zebrafish Assay

Polo-like kinase 1 (PLK1), one of the key regulators of mitosis, is a target for cancer therapy due to its abnormally high activity in several tumors. Plk1 is highly conserved and shares a nearly identical 3-D structure between zebrafish and humans. The initial 10 mitoses of zebrafish embryonic cleavages occur every∼30 minutes, and therefore provide a rapid assay to evaluate mitosis inhibitors including those targeting Plk1. To increase efficiency and specificity, we first performed a computational virtual screen of∼60000 compounds against the human Plk1 3-D structure docked to both its kinase and Polo box domain. 370 candidates with the top free-energy scores were subjected to zebrafish assay and 3 were shown to inhibit cell division. Compared to general screen for compounds inhibiting zebrafish embryonic cleavage, computation increased the efficiency by 11 folds. One of the 3 compounds, named I2, was further demonstrated to effectively inhibit multiple tumor cell proliferation in vitro and PC3 prostate cancer growth in Xenograft mouse model in vivo. Furthermore, I2 inhibited Plk1 enzyme activity in a dose dependent manner. The IC₅₀ values of I2 in these assays are compatible to those of ON-01910, a Plk1 inhibitor currently in Phase III clinic trials. Our studies demonstrate that zebrafish assays coupled with computational screening significantly improves the efficiency of identifying specific regulators of biological targets. The PLK1 inhibitor I2, and its analogs, may have potential in cancer therapeutics.     

Indirect Estimates of Total Fertility Rate Using Child Woman/Ratio: A Comparison with the Bogue-Palmore Method

Indirect estimation methodologies of the total fertility rate (TFR) have a long history within demography and have provided important techniques applied demographers can use when data is sparse or lacking. However new methodologies for approximating the total fertility rate have not been proposed in nearly 30 years. This study presents a novel method for indirectly approximating the total fertility rate using an algebraic rearrangement of the general fertility rate (GFR) through the known relationship between GFR and TFR. It then compares the proposed method to the well-known Bogue-Palmore method. These methods are compared in 196 countries and include overall errors as well as characteristics of the countries that contribute to fertility behavior. Additionally, these methods were compared geographically to find any geographical patterns. We find this novel method is not only simpler than the Bogue-Palmore method, requiring fewer data inputs, but also has reduced algebraic and absolute errors when compared with the Bogue-Palmore method and specifically outperforms the Bogue-Palmore method in developing countries. We find that our novel method may be useful estimation procedure for demographers.     

Outlier detection methods are still effective even using virtual species created with the probabilistic approach

Liu et al. (Journal of Biogeography, 2018, 45 :164–176) presented an approach to detect outliers in species distribution data by developing virtual species created using the threshold approach. Meynard et al. (Journal of biogeography, 2019, 46 :2141–2144) raised concerns about this approach stating that ‘using a probabilistic approach … may significantly change results’. Here we provide a new series of simulations using the two approaches and demonstrate that the outlier detection approach based on pseudo species distribution models was still effective when using the probabilistic approach, although the detection rate was lower than when using the threshold approach.     

Disturbance does not have a significant impact on waders in an estuary close to conurbations: importance of overlap between birds and people in time and space

Disturbance of wildlife is a potential cause of conservation concern, not least to overwintering waders Charadrii inhabiting estuaries close to conurbations where human recreational and economic activities are often concentrated. Disturbance from people on and alongside intertidal foraging areas could make it more difficult for birds to survive until spring in good condition by reducing the time available for foraging, increasing energy requirements and displacing birds to poorer foraging areas. We adopted a two-part approach to testing whether such significant impacts occurred in a Special Protection Area where disturbance risk was high because of its small size and close proximity to conurbations. In part one, we recorded over the whole estuary during stages of the tidal cycle when part or all of the intertidal zone was exposed and so accessible to waders (i.e. on receding, low and advancing tides): (1) the numbers and activities of people on the intertidal flats and on the adjacent land in those places where people were visible to waders in the intertidal zone and (2) the numbers of waders present and disturbed into flight, the flight distance and flight duration in the ‘overlap’ areas where people did disturb waders. People occurred on < 25% of the 938 ha of intertidal flats, but most waders foraged on mudflats, whereas most people were on sandflats. People on land were visible to foraging waders along < 35% of the 16.5 km of shoreline. Waders and people were therefore substantially separated in space. Within overlap areas, people and waders were often frequently separated in time: for example, people on land mostly disturbed waders when only the upper shore levels were exposed. The average overwintering wader spent < 0.1% of its foraging time during daylight flying away from people and the additional energy expenditure was equivalent to < 0.02% of its daily requirements. The comparison made in part two between our study area and two comparable estuaries showed that the number of visits each day to the overlap areas would need to be 29 or 43 times greater for disturbance to have lowered the birds’ body condition and winter survival. Both parts of the study therefore suggested strongly that the amount of disturbance was too trivial to have a significant impact on waders. It is concluded that: (1) to properly assess disturbance risk to waders, both extensive and intensive observations must be made on the behaviour of people and birds to quantify the extent to which they overlap in space and time, and (2) it should not be assumed that an estuary's close proximity to conurbations, and the presence of large numbers of people in the vicinity of the SPA, necessarily implies a significant disturbance risk to waders.