Case Report: Pheochromocytoma and Synchronous Neuroblastoma in a Family With Hereditary Pheochromocytoma Associated With a MAX Deleterious Variant

Introduction: Pheochromocytomas are rare catecholamine-producing neuroendocrine tumours arising from chromaffin cells of the adrenal medulla or extra-adrenal sympathetic paraganglia. Recent studies have indicated that up to 40% of pheochromocytomas could be attributable to an inherited germline variant in an increasing list of susceptibility genes. Germline variants of the MYC-associated factor (MAX) gene have been associated with familial pheochromocytomas and paragangliomas with an autosomal dominant pattern of inheritance, a median age at onset of 33 years and an overall frequency estimated at 1.9%. We describe a deleterious MAX variant associated with hereditary pheochromocytoma in a family with four affected individuals. Case presentation: The first patient presented with bilateral pheochromocytoma in 1995; genetic testing was proposed to his oldest son, when he was diagnosed with a bilateral pheochromocytoma with a synchronous neuroblastoma. Upon the identification of the MAX variant c.97C>T, p.(Arg33Ter), in the latter individual, his two siblings and their father were tested and the same variant was identified in all of them. Both siblings were subsequently diagnosed with pheochromocytoma (one of them bilateral) and choose to remain on active surveillance before they were submitted to adrenalectomy. All the tumours secreted predominantly norepinephrine, accordingly to the typical biochemical phenotype ascribed to variants in the MAX gene. Conclusion: This case series is, to our knowledge, the one with the largest number of individuals with hereditary pheochromocytoma with a deleterious MAX variant in the same family. It is also the first case with a synchronous pheochromocytoma and neuroblastoma in carriers of a MAX deleterious variant. This report draws attention to some ill-defined features of pheochromocytoma and other malignancies associated with a MAX variant and highlights the importance of understanding the genotype-phenotype correlation in hereditary pheochromocytoma and the impact of oriented genetic testing to detect, survey and treat patients and kindreds at risk

Genome variations: Effects on the robustness of neuroevolved control for swarm robotics systems

Manual design of self-organized behavioral control for swarms of robots is a complex task. Neuroevolution has proved a viable alternative given its capacity to automatically synthesize controllers. In this paper, we introduce the concept of Genome Variations (GV) in the neuroevolution of behavioral control for robotic swarms. In an evolutionary setup with GV, a slight mutation is applied to the evolving neural network parameters before they are copied to the robots in a swarm. The genome variation is individual to each robot, thereby generating a slightly heterogeneous swarm. GV represents a novel approach to the evolution of robust behaviors, expected to generate more stable and robust individual controllers, and bene t swarm behaviors that can deal with small heterogeneities in the behavior of other members in the swarm. We conduct experiments using an aggregation task, and compare the evolved solutions to solutions evolved under ideal, noise-free conditions, and to solutions evolved with traditional sensor noise.info:eu-repo/semantics/acceptedVersio

Multicenter study of the natural history and therapeutic responses of patients with chikungunya, focusing on acute and chronic musculoskeletal manifestations - a study protocol from the clinical and applied research in Chikungunya (REPLICK network)

BACKGROUND: Chikungunya is associated with high morbidity and the natural history of symptomatic infection has been divided into three phases (acute, post-acute, and chronic) according to the duration of musculoskeletal symptoms. Although this classification has been designed to help guide therapeutic decisions, it does not encompass the complexity of the clinical expression of the disease and does not assist in the evaluation of the prognosis of severity nor chronic disease. Thus, the current challenge is to identify and diagnose musculoskeletal disorders and to provide the optimal treatment in order to prevent perpetuation or progression to a potentially destructive disease course. METHODS: The study is the first product of the Clinical and Applied Research Network in Chikungunya (REPLICK). This is a prospective, outpatient department-based, multicenter cohort study in Brazil. Four work packages were defined: i. Clinical research; ii) Translational Science - comprising immunology and virology streams; iii) Epidemiology and Economics; iv) Therapeutic Response and clinical trials design. Scheduled appointments on days 21 (D21) ± 7 after enrollment, D90 ± 15, D120 ± 30, D180 ± 30; D360 ± 30; D720 ± 60, and D1080 ± 60 days. On these visits a panel of blood tests are collected in addition to the clinical report forms to obtain data on socio-demographic, medical history, physical examination and questionnaires devoted to the evaluation of musculoskeletal manifestations and overall health are performed. Participants are asked to consent for their specimens to be maintained in a biobank. Aliquots of blood, serum, saliva, PAXgene, and when clinically indicated to be examined, synovial fluid, are stored at -80° C. The study protocol was submitted and approved to the National IRB and local IRB at each study site. DISCUSSION: Standardized and harmonized patient cohorts are needed to provide better estimates of chronic arthralgia development, the clinical spectra of acute and chronic disease and investigation of associated risk factors. This study is the largest evaluation of the long-term sequelae of individuals infected with CHIKV in the Brazilian population focusing on musculoskeletal manifestations, mental health, quality of life, and chronic pain. This information will both define disease burden and costs associated with CHIKV infection, and better inform therapeutic guidelines

Implications of Behavioral Architecture for the Evolution of Self-Organized Division of Labor

Division of labor has been studied separately from a proximate self-organization and an ultimate evolutionary perspective. We aim to bring together these two perspectives. So far this has been done by choosing a behavioral mechanism a priori and considering the evolution of the properties of this mechanism. Here we use artificial neural networks to allow for a more open architecture. We study whether emergent division of labor can evolve in two different network architectures; a simple feedforward network, and a more complex network that includes the possibility of self-feedback from previous experiences. We focus on two aspects of division of labor; worker specialization and the ratio of work performed for each task. Colony fitness is maximized by both reducing idleness and achieving a predefined optimal work ratio. Our results indicate that architectural constraints play an important role for the outcome of evolution. With the simplest network, only genetically determined specialization is possible. This imposes several limitations on worker specialization. Moreover, in order to minimize idleness, networks evolve a biased work ratio, even when an unbiased work ratio would be optimal. By adding self-feedback to the network we increase the network's flexibility and worker specialization evolves under a wider parameter range. Optimal work ratios are more easily achieved with the self-feedback network, but still provide a challenge when combined with worker specialization

Ecological Implications of Extreme Events: Footprints of the 2010 Earthquake along the Chilean Coast

Deciphering ecological effects of major catastrophic events such as earthquakes, tsunamis, volcanic eruptions, storms and fires, requires rapid interdisciplinary efforts often hampered by a lack of pre-event data. Using results of intertidal surveys conducted shortly before and immediately after Chile's 2010 Mw 8.8 earthquake along the entire rupture zone (ca. 34–38°S), we provide the first quantification of earthquake and tsunami effects on sandy beach ecosystems. Our study incorporated anthropogenic coastal development as a key design factor. Ecological responses of beach ecosystems were strongly affected by the magnitude of land-level change. Subsidence along the northern rupture segment combined with tsunami-associated disturbance and drowned beaches. In contrast, along the co-seismically uplifted southern rupture, beaches widened and flattened increasing habitat availability. Post-event changes in abundance and distribution of mobile intertidal invertebrates were not uniform, varying with land-level change, tsunami height and coastal development. On beaches where subsidence occurred, intertidal zones and their associated species disappeared. On some beaches, uplift of rocky sub-tidal substrate eliminated low intertidal sand beach habitat for ecologically important species. On others, unexpected interactions of uplift with man-made coastal armouring included restoration of upper and mid-intertidal habitat seaward of armouring followed by rapid colonization of mobile crustaceans typical of these zones formerly excluded by constraints imposed by the armouring structures. Responses of coastal ecosystems to major earthquakes appear to vary strongly with land-level change, the mobility of the biota and shore type. Our results show that interactions of extreme events with human-altered shorelines can produce surprising ecological outcomes, and suggest these complex responses to landscape alteration can leave lasting footprints in coastal ecosystems

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Krill Excretion Boosts Microbial Activity in the Southern Ocean

Antarctic krill are known to release large amounts of inorganic and organic nutrients to the water column. Here we test the role of krill excretion of dissolved products in stimulating heterotrophic bacteria on the basis of three experiments where ammonium and organic excretory products released by krill were added to bacterial assemblages, free of grazers. Our results demonstrate that the addition of krill excretion products (but not of ammonium alone), at levels expected in krill swarms, greatly stimulates bacteria resulting in an order-of-magnitude increase in growth and production. Furthermore, they suggest that bacterial growth rate in the Southern Ocean is suppressed well below their potential by resource limitation. Enhanced bacterial activity in the presence of krill, which are major sources of DOC in the Southern Ocean, would further increase recycling processes associated with krill activity, resulting in highly efficient krill-bacterial recycling that should be conducive to stimulating periods of high primary productivity in the Southern Ocean.This research is a contribution to projects ICEPOS (REN2002-04165-CO3-O2) and ATOS (POL2006-00550/CTM), funded by the Spanish Ministry of Science and Innovation