Mutational analysis of DAX1 in patients with hypogonadotropic hypogonadism or pubertal delay

Although delayed puberty is relatively common and often familial, its molecular and pathophysiologic basis is poorly understood. In contrast, the molecular mechanisms underlying some forms of hypogonadotropic hypogonadism (HH) are clearer, following the description of mutations in the genes KAL, GNRHR, and PROP1. Mutations in another gene, DAX1 (AHC), cause X-linked adrenal hypoplasia congenita and HH. Affected boys usually present with primary adrenal failure in infancy or childhood and HH at the expected time of puberty.DAX1 mutations have also been reported to occur with a wider spectrum of clinical presentations. These cases include female carriers of DAX1 mutations with marked pubertal delay and a male with incomplete BH and mild adrenal insufficiency in adulthood. Given this emerging phenotypic spectrum of clinical presentation in men and women with DAX1 mutations, we hypothesized that DAX1 might be a candidate gene for mutation in patients with idiopathic sporadic or familial HH or constitutional delay of puberty. Direct sequencing of DAX1 was performed in 106 patients, including 85 (80 men and 5 women) with sporadic HH or constitutional delay of puberty and patients from 21 kindreds with familial forms of these disorders. No DAX1 mutations were found in these groups of patients, although silent single nucleotide polymorphisms were identified (T114C, G498A). This study suggests that mutations in DAX1 are unlikely to be a common cause of HH or pubertal delay in the absence of a concomitant history of adrenal insufficiency

Population mechanics: A mathematical framework to study T cell homeostasis

Unlike other cell types, T cells do not form spatially arranged tissues, but move independently throughout the body. Accordingly, the number of T cells in the organism does not depend on physical constraints imposed by the shape or size of specific organs. Instead, it is determined by competition for interleukins. From the perspective of classical population dynamics, competition for resources seems to be at odds with the observed high clone diversity, leading to the so-called diversity paradox. In this work we make use of population mechanics, a non-standard theoretical approach to T cell homeostasis that accounts for clone diversity as arising from competition for interleukins. The proposed models show that carrying capacities of T cell populations naturally emerge from the balance between interleukins production and consumption. These models also suggest remarkable functional differences in the maintenance of diversity in naïve and memory pools. In particular, the distribution of memory clones would be biased towards clones activated more recently, or responding to more aggressive pathogenic threats. In contrast, permanence of naïve T cell clones would be determined by their affinity for cognate antigens. From this viewpoint, positive and negative selection can be understood as mechanisms to maximize naïve T cell diversity

Genetic Diversity and Population Parameters of Sea Otters, Enhydra lutris, before Fur Trade Extirpation from 1741–1911

All existing sea otter, Enhydra lutris, populations have suffered at least one historic population bottleneck stemming from the fur trade extirpations of the eighteenth and nineteenth centuries. We examined genetic variation, gene flow, and population structure at five microsatellite loci in samples from five pre-fur trade populations throughout the sea otter's historical range: California, Oregon, Washington, Alaska, and Russia. We then compared those values to genetic diversity and population structure found within five modern sea otter populations throughout their current range: California, Prince William Sound, Amchitka Island, Southeast Alaska and Washington. We found twice the genetic diversity in the pre-fur trade populations when compared to modern sea otters, a level of diversity that was similar to levels that are found in other mammal populations that have not experienced population bottlenecks. Even with the significant loss in genetic diversity modern sea otters have retained historical structure. There was greater gene flow before extirpation than that found among modern sea otter populations but the difference was not statistically significant. The most dramatic effect of pre fur trade population extirpation was the loss of genetic diversity. For long term conservation of these populations increasing gene flow and the maintenance of remnant genetic diversity should be encouraged

MPA in Labor: Securing the Pearl Cays of Nicaragua

Implementation of Marine Protected Areas (MPAs) has always a step-zero, i.e., an initial phase when the idea is incepted, communicated and negotiated among stakeholders. What happens during this phase is likely to have an impact later on. If not done right, the management of the MPA may encounter problems at later stage that will be difficult to correct. Inspired by this working theory, this article describes the effort to establish the Pearl Cays off the Caribbean coast of Nicaragua as a protected area. This case-study illustrates the critical actions to be taken during step-zero, i.e., what needs to be considered and done before an MPA is formally declared. The area investigated consists of a number of small islands (cays) and coral reefs, fishing grounds and marine turtle nesting areas. Throughout history, the cays have played an important role in sustaining livelihoods of nearby communities. Although the idea of an MPA was originally conservation, the communities saw it as an opportunity to regain ownership and control of the cays. By Nicaraguan law, in order to establish protected areas, consultation and approval from local people is required. In the case of the Pearl Cays, this has proved difficult. The article demonstrates how MPA initiatives must sometimes relate to already ongoing complex social processes in the area where they are to be instigated

Mechanism of cellular rejection in transplantation

The explosion of new discoveries in the field of immunology has provided new insights into mechanisms that promote an immune response directed against a transplanted organ. Central to the allograft response are T lymphocytes. This review summarizes the current literature on allorecognition, costimulation, memory T cells, T cell migration, and their role in both acute and chronic graft destruction. An in depth understanding of the cellular mechanisms that result in both acute and chronic allograft rejection will provide new strategies and targeted therapeutics capable of inducing long-lasting, allograft-specific tolerance

The behaviour of giant clams (Bivalvia: Cardiidae: Tridacninae)

Giant clams, the largest living bivalves, live in close association with coral reefs throughout the Indo-Pacific. These iconic invertebrates perform numerous important ecological roles as well as serve as flagship species—drawing attention to the ongoing destruction of coral reefs and their associated biodiversity. To date, no review of giant clams has focussed on their behaviour, yet this component of their autecology is critical to their life history and hence conservation. Almost 100 articles published between 1865 and 2014 include behavioural observations, and these have been collated and synthesised into five sections: spawning, locomotion, feeding, anti-predation, and stress responses. Even though the exact cues for spawning in the wild have yet to be elucidated, giant clams appear to display diel and lunar periodicities in reproduction, and for some species, peak breeding seasons have been established. Perhaps surprisingly, giant clams have considerable mobility, ranging from swimming and gliding as larvae to crawling in juveniles and adults. Chemotaxis and geotaxis have been established, but giant clams are not phototactic. At least one species exhibits clumping behaviour, which may enhance physical stabilisation, facilitate reproduction, or provide protection from predators. Giant clams undergo several shifts in their mode of acquiring nutrition; starting with a lecithotrophic and planktotrophic diet as larvae, switching to pedal feeding after metamorphosis followed by the transition to a dual mode of filter feeding and phototrophy once symbiosis with zooxanthellae (Symbiodinium spp.) is established. Because of their shell weight and/or byssal attachment, adult giant clams are unable to escape rapidly from threats using locomotion. Instead, they exhibit a suite of visually mediated anti-predation behaviours that include sudden contraction of the mantle, valve adduction, and squirting of water. Knowledge on the behaviour of giant clams will benefit conservation and restocking efforts and help fine-tune mariculture techniques. Understanding the repertoire of giant clam behaviours will also facilitate the prediction of threshold levels for sustainable exploitation as well as recovery rates of depleted clam populations

A Novel Protein Kinase-Like Domain in a Selenoprotein, Widespread in the Tree of Life

Selenoproteins serve important functions in many organisms, usually providing essential oxidoreductase enzymatic activity, often for defense against toxic xenobiotic substances. Most eukaryotic genomes possess a small number of these proteins, usually not more than 20. Selenoproteins belong to various structural classes, often related to oxidoreductase function, yet a few of them are completely uncharacterised

Spatial access priority mapping (SAPM) with fishers : a quantitative GIS method for participatory planning

Spatial management tools, such as marine spatial planning and marine protected areas, are playing an increasingly important role in attempts to improve marine management and accommodate conflicting needs. Robust data are needed to inform decisions among different planning options, and early inclusion of stakeholder involvement is widely regarded as vital for success. One of the biggest stakeholder groups, and the most likely to be adversely impacted by spatial restrictions, is the fishing community. In order to take their priorities into account, planners need to understand spatial variation in their perceived value of the sea. Here a readily accessible, novel method for quantitatively mapping fishers’ spatial access priorities is presented. Spatial access priority mapping, or SAPM, uses only basic functions of standard spreadsheet and GIS software. Unlike the use of remote-sensing data, SAPM actively engages fishers in participatory mapping, documenting rather than inferring their priorities. By so doing, SAPM also facilitates the gathering of other useful data, such as local ecological knowledge. The method was tested and validated in Northern Ireland, where over 100 fishers participated in a semi-structured questionnaire and mapping exercise. The response rate was excellent, 97%, demonstrating fishers’ willingness to be involved. The resultant maps are easily accessible and instantly informative, providing a very clear visual indication of which areas are most important for the fishers. The maps also provide quantitative data, which can be used to analyse the relative impact of different management options on the fishing industry and can be incorporated into planning software, such as MARXAN, to ensure that conservation goals can be met at minimum negative impact to the industry. This research shows how spatial access priority mapping can facilitate the early engagement of fishers and the ready incorporation of their priorities into the decision-making process in a transparent, quantitative way

Genome-Wide Association Scan Meta-Analysis Identifies Three Loci Influencing Adiposity and Fat Distribution

Major project or personal funding for the work described in this paper comes from the Academy of Finland (104781, 124243), ADA Smith Family Foundation Pinnacle Program, the American Diabetes Association, Arthritis Research Campaign, AstraZeneca AB, The Barts and The London Charity, Biocentrum Helsinki, Biotechnology and Biological Sciences Research Council (UK), British Heart Foundation, Camstrad, Cancer Research UK, CIDR (NIH Contract Number N01-HG- 65403), Diabetes UK, the European Commission (Framework VI: LSHG-CT-2004-518153 [EURODIA]; LSHG-CT-2004-512066 [MolPAGE]; LSHM-CT-2006-037197; LSHMCT-2003-503041; QL46-CT-2002-02629 [GENOMOS]; LSHM-CT-2007-037273; Framework VII: HEALTH-F4-2007- 201413 [ENGAGE]), the Faculty of Biology and Medicine of Lausanne, Switzerland, the Swiss National Science Foundation (Grant 33CSCO-122661, the Finnish Heart Association, the Finnish Cultural Foundation, Folkha¨lsan Research Foundation, the German National Genome Research Net, GlaxoSmithKline, the Sigrid Juselius Foundation, the Karolinska Institute, Kings College London, the Knut and Alice Wallenberg Foundation, the Medical Research Council UK (G0000934, G0000649, G0601261, G0500539, G9521010D, G0600705), MedStar Research Institute, Munich Center of Health Sciences, National Institutes of Health (US: intramural programs (1Z01-HG000024), National Institute on Aging; NHLBI (HL087679 [STAMPEED], HL084729), NIDDK (DK062370; DK072193; DK075787; DK079466; DK080145; DK067288; DK07191), NHGRI (HG02651), the Netherlands Organization for Scientific Research, the Netherlands Center of Medical Systems Biology, the Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) (050-060-810), Novartis, Peninsula Medical School, Scottish Executive Chief Scientist’s Office, Stockholm County Council (560183), Support for Science Funding (UK); Swedish Heart-Lung Foundation, the Swedish Medical Research Council (8691), UK National Institute of Health Research, UK Department of Health Policy Research Programme, University of Oxford, Vandervell Foundation and Wellcome Trust (068545/Z/02, GR072960, GR076113, GR069224, 086596/Z/08/Z)

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS