Protection of Antarctica's biodiversity and ecosystem values is enshrined in the Protocol on Environmental Protection to the Antarctic Treaty, which provides for the designation of Antarctic Specially Protected Areas (ASPAs) to areas with outstanding values. Concern has been raised that existing ASPAs fail to prioritize areas to maximize the likelihood of ensuring the long-term conservation of Antarctic ecosystems and biodiversity. The absence of systematic and representative protection is particularly acute for inland aquatic ecosystems, which support a disproportionate amount of inland biodiversity. This paper promotes the case for overt inclusion of inland waters as a critical component of a representative protected area framework for Antarctica, thereby addressing their current underrepresentation. We set out a structured approach to enable the selection of representative freshwater systems for inclusion in the ASPA framework that, with modification, could also be applied across other Antarctic habitats. We acknowledge an overall lack of information on the biogeography of inland aquatic diversity and recommend increased use of remote data collection along with classification tools to mitigate this, as well as the need for the consideration of catchment-scale processes. Changes that accompany contemporary and anticipated climate change make the need for the conservation of representative biodiversity increasingly urgent.

ABSTRACT IMPACT: By assessing function of mutant (patient-specific) tp53 in zebrafish embryonal rhabdomyosarcoma will inform clinicians of the severity of mutant tp53 alleles. OBJECTIVES/GOALS: This study aims to define loss- and gain-of-function TP53 mutations by comparing effects in tp53-null and wild-type tumors. In addition, it aims to generate a rapid in vivo analysis platform to assign function to patient specific TP53 mutations in the clinic METHODS/STUDY POPULATION: To define tp53 function in ERMS pathogenesis, we previously generated a new tp53-null mutant (tp53-/-) in zebrafish by deleting the entire tp53 genomic locus using TALEN mutagenesis. tp53-/- zebrafish spontaneously develop a spectrum of tumors including sarcomas, leukemia and germ cell tumors (Ignatius…Baxi et. al., eLife) reminiscent of tumors observed in Trp53-null mice. Using the tp53-/- mutants to generate kRASG12D-induced ERMS, we discovered that tp53 is a potent repressor of metastases but rather surprisingly had no effect on self-renewal (Ignatius…Baxi et. al., eLife). Here, using tp53-/- zebrafish, we assessed effects of wild-type and mutant (patient specific) tp53 on tumor initiation, proliferation and apoptosis. RESULTS/ANTICIPATED RESULTS: ERMS tumor initiation in the tp53-/- background is observed in > 97% of animals whereas only <40% of wild-type animals develop ERMS. Additionally, tp53 is a potent suppressor of ERMS proliferation and its effect on apoptosis is minor. Next, we expressed either WT zebrafish or human TP53 in tp53-/- animals along with kRASG12D and both genes suppressed tumor initiation and growth. We co-expressed TP53C176F (found in two ERMS patients) and TP53P153del (identified in a patient with osteosarcoma in our clinic) in zebrafish ERMS, and find that the TP53C176F allele significantly suppressed tumor initiation with effects predominantly on enhanced apoptosis. However, the TP53P153del allele initiated tumors at similar frequency compared to tp53-/- animals but increased the initiation of tumors in the head musculature. DISCUSSION/SIGNIFICANCE OF FINDINGS: Different TP53 alleles identified in patient tumors have very different effects on tumorigenesis in vivo and can respond differently to potentially therapeutic compounds. Thus, the type of precision modeling demonstrated here promises to help further define patient-specific TP53 biology and improve clinical strategies in the future.

There is increasing evidence of an association between a low maternal vitamin D status and a high risk of adverse pregnancy outcomes. In a cross-sectional study, we investigated the vitamin D status of pregnant women to determine potentially influencing factors. Between December 2010 and February 2012, 261 maternal blood samples and 328 cord blood samples were collected for the analysis of 25-hydroxyvitamin D (25(OH)D), intact parathyroid hormone, alkaline phosphatase and Ca concentrations. Demographical characteristics and clinical data were recorded by a questionnaire and from medical files. The overall median maternal and cord blood 25(OH)D levels were 25·0 (interquartile range 12·6–45·5) nmol/l and 34·1 (interquartile range 17·7–58·6) nmol/l, respectively. During the winter months, 98 % of the maternal blood samples and 94 % of the cord blood samples had 25(OH)D levels < 50 nmol/l. In the summer months, 49 % of the women and 35 % of the cord blood samples were vitamin D deficient. Using logistic regression models, significant risk factors for maternal vitamin D deficiency were found to be physical inactivity (adjusted OR (aOR) 2·67, 95 % CI 1·06, 6·69, P= 0·032) and a non-European country of origin (aOR 3·21, 95 % CI 1·0, 10·28, P= 0·047) after controlling for season and independent risk factors. These results are the first 25(OH)D data for pregnant women in Germany. They indicate the need for urgent implementation of strategies to prevent vitamin D deficiency by healthcare authorities that are in charge of preventing vitamin D deficiency, especially during these sensitive stages of life.

Information for motor learning is likely to be stored by groups of Purkinje cells in the cerebellum as suggested by HOUK et al., though their proposal that Purkinje cells act as bistable elements is open to question. THACH's excellent article breaks new ground on what type of information the cerebellum may store. I have queries on whether the cerebellum can generate “thought” or is likely to engage in the purely mental learning of movements, [HOUK et al.; THACH]

Nutrigenomics is the study of how constituents of the diet interact with genes, and their products, to alter phenotype and, conversely, how genes and their products metabolise these constituents into nutrients, antinutrients, and bioactive compounds. Results from molecular and genetic epidemiological studies indicate that dietary unbalance can alter gene–nutrient interactions in ways that increase the risk of developing chronic disease. The interplay of human genetic variation and environmental factors will make identifying causative genes and nutrients a formidable, but not intractable, challenge. We provide specific recommendations for how to best meet this challenge and discuss the need for new methodologies and the use of comprehensive analyses of nutrient–genotype interactions involving large and diverse populations. The objective of the present paper is to stimulate discourse and collaboration among nutrigenomic researchers and stakeholders, a process that will lead to an increase in global health and wellness by reducing health disparities in developed and developing countries.

Background. Auditory hallucinations in psychosis often contain critical evaluations of the voice-hearer (for example, attacks on self-worth). A voice-hearer's experience with their dominant voice is a mirror of their social relationships in general, with experiences of feeling low in rank to both voices and others being associated with depression. However, the direction of the relationship between psychosis, depression and feeling subordinate is unclear.

Method. Covariance structural equation modelling was used with data from 125 participants diagnosed with schizophrenia to compare three ‘causal’ models: (1) that depression leads to the appraisal of low social rank, voice power and distress; (2) that psychotic illness leads to voice activity (frequency, audibility), which in turn leads to depression and the appraisal of voices' power; (3) our hypothesized model, that perceptions of social rank and social power lead to the appraisal of voice power, distress and depression.

Results. Findings supported model 3, suggesting that the appraisal of social power and rank are primary organizing schema underlying the appraisal of voice power, and the distress of voices.

Conclusions. Voices can be seen to operate like external social relationships. Voice content and experience can mirror a person's social sense of being powerless and controlled by others. These findings suggest important new targets for intervention with cognitive and social therapy.