A common founding clone with TP53 and PTEN mutations gives rise to a concurrent germ cell tumor and acute megakaryoblastic leukemia

We report the findings from a patient who presented with a concurrent mediastinal germ cell tumor (GCT) and acute myeloid leukemia (AML). Bone marrow pathology was consistent with a diagnosis of acute megakaryoblastic leukemia (AML M7), and biopsy of an anterior mediastinal mass was consistent with a nonseminomatous GCT. Prior studies have described associations between hematological malignancies, including AML M7 and nonseminomatous GCTs, and it was recently suggested that a common founding clone initiated both cancers. We performed enhanced exome sequencing on the GCT and the AML M7 from our patient to define the clonal relationship between the two cancers. We found that both samples contained somatic mutations in PTEN (C136R missense) and TP53 (R213 frameshift). The mutations in PTEN and TP53 were present at ∼100% variant allele frequency (VAF) in both tumors. In addition, we detected and validated five other shared somatic mutations. The copy-number analysis of the AML exome data revealed an amplification of Chromosome 12p. We also identified a heterozygous germline variant in FANCA (S858R), which is known to be associated with Fanconi anemia but is of uncertain significance here. In summary, our data not only support a common founding clone for these cancers but also suggest that a specific set of distinct genomic alterations (in PTEN and TP53) underlies the rare association between GCT and AML. This association is likely linked to the treatment resistance and extremely poor outcome of these patients. We cannot resolve the clonal evolution of these tumors given limitations of our data

Richer but Resented: What do Cash Transfers do to Social Relations?

Cash transfers are an increasingly important component of social protection systems in most countries. Usually, cash transfers are evaluated against their effects on poverty or human capital, with their impact on social relations within and between households relegated to discrete comments on ‘stigma’, ‘resentment’ and sharing, including reduction of remittances and other support. Using evidence from Oxford Policy Management's evaluations of cash transfer programmes in Malawi and Zimbabwe, we suggest reconceptualising cash transfers as ongoing processes of intervention in a complex system of social relations. Cash transfer interventions operate through and affect this system at each stage: awareness?raising, targeting, payment, case management and monitoring and evaluation. We conclude that the impact of cash transfers on social relations is large and often negative. We argue that this is intrinsically important for wellbeing, but can also have negative consequences for material aspects of wellbeing, such as livelihoods

Voting 'against all' in postcommunist Russia

Since the early 1990s voters in Russia (and most of the other post-Soviet republics) have been offered the opportunity to vote ‘against all’ parties and candidates. Increasing numbers have done so. The evidence of two post-election surveys indicates that ‘against all’ voters are younger than other voters, more urban and more highly educated. They do not reject liberal democracy, but are critical of the contemporary practice of Russian politics and find no parties that adequately reflect their views. With the ending of the ‘against all’ facility in 2006 and other changes in the Russian electoral system under the Putin presidency, levels of turnout are likely to fall further and the protest vote will seek other outlets within or outside the parliamentary system

Statement of the Third International Exercise-Associated Hyponatremia Consensus Development Conference, Carlsbad, California, 2015

The third International Exercise-Associated Hyponatremia (EAH) Consensus Development Conference convened in Carlsbad, California in February 2015 with a panel of 17 international experts. The delegates represented 4 countries and 9 medical and scientific sub-specialties pertaining to athletic training, exercise physiology, sports medicine, water/sodium metabolism, and body fluid homeostasis. The primary goal of the panel was to review the existing data on EAH and update the 2008 Consensus Statement.1 This document serves to replace the second International EAH Consensus Development Conference Statement and launch an educational campaign designed to address the morbidity and mortality associated with a preventable and treatable fluid imbalance. The following statement is a summary of the data synthesized by the 2015 EAH Consensus Panel and represents an evolution of the most current knowledge on EAH. This document will summarize the most current information on the prevalence, etiology, diagnosis, treatment and prevention of EAH for medical personnel, athletes, athletic trainers, and the greater public. The EAH Consensus Panel strove to clearly articulate what we agreed upon, did not agree upon, and did not know, including minority viewpoints that were supported by clinical experience and experimental data. Further updates will be necessary to both: (1) remain current with our understanding and (2) critically assess the effectiveness of our present recommendations. Suggestions for future research and educational strategies to reduce the incidence and prevalence of EAH are provided at the end of the document as well as areas of controversy that remain in this topic. [excerpt

Low-cost, Transportable Hydrogen Fueling Station for Early FCEV Adoption

Thousands of public hydrogen fueling stations are needed to support the early Fuel Cell Electric Vehicle (FCEV) market in the U.S.; there are currently 12. The California state government has been the largest investor of the hydrogen fueling infrastructure funding 9 permanent stations currently open to the public with 48 more in development costing anywhere from $1.8M-$5.5M each. To attract private investors and decrease dependence on government funding, a low-cost, mobile hydrogen dispensing system must be developed. This paper describes a transportable hydrogen fueling station that has been designed for $423,000 using off-the-shelf components, less than 23$9.62/kg. This paper presents the mechanical design and operation of the fueling station. A complete report including an economic analysis and safety features is available at: http://hydrogencontest.org/pdf/2014/WSU_2014_HEF_CONTEST.pdf

Structure of the first representative of Pfam family PF04016 (DUF364) reveals enolase and Rossmann-like folds that combine to form a unique active site with a possible role in heavy-metal chelation.

The crystal structure of Dhaf4260 from Desulfitobacterium hafniense DCB-2 was determined by single-wavelength anomalous diffraction (SAD) to a resolution of 2.01 Å using the semi-automated high-throughput pipeline of the Joint Center for Structural Genomics (JCSG) as part of the NIGMS Protein Structure Initiative (PSI). This protein structure is the first representative of the PF04016 (DUF364) Pfam family and reveals a novel combination of two well known domains (an enolase N-terminal-like fold followed by a Rossmann-like domain). Structural and bioinformatic analyses reveal partial similarities to Rossmann-like methyltransferases, with residues from the enolase-like fold combining to form a unique active site that is likely to be involved in the condensation or hydrolysis of molecules implicated in the synthesis of flavins, pterins or other siderophores. The genome context of Dhaf4260 and homologs additionally supports a role in heavy-metal chelation

Structure of a putative NTP pyrophosphohydrolase: YP_001813558.1 from Exiguobacterium sibiricum 255-15.

The crystal structure of a putative NTPase, YP_001813558.1 from Exiguobacterium sibiricum 255-15 (PF09934, DUF2166) was determined to 1.78 Å resolution. YP_001813558.1 and its homologs (dimeric dUTPases, MazG proteins and HisE-encoded phosphoribosyl ATP pyrophosphohydrolases) form a superfamily of all-α-helical NTP pyrophosphatases. In dimeric dUTPase-like proteins, a central four-helix bundle forms the active site. However, in YP_001813558.1, an unexpected intertwined swapping of two of the helices that compose the conserved helix bundle results in a `linked dimer' that has not previously been observed for this family. Interestingly, despite this novel mode of dimerization, the metal-binding site for divalent cations, such as magnesium, that are essential for NTPase activity is still conserved. Furthermore, the active-site residues that are involved in sugar binding of the NTPs are also conserved when compared with other α-helical NTPases, but those that recognize the nucleotide bases are not conserved, suggesting a different substrate specificity

Роман Э. М. Форстера «Поездка в Индию» сквозь призму аналитической психологии К. Г. Юнга

По мнению большинства критиков и исследователей творчества английского прозаика Эдуарда Моргана Форстера (Edward Morgan Forster, 1879-1970), роман «Поездка в Индию» (“A Passage to India”, 1924) считается его наиболее значительным произведением, которое и по сей день вызывает многочисленные интерпретации. В силу известных причин в советском литературоведении роман изучался преимущественно в свете общественно-политической проблематики; магистральными мотивами выделялись политические и антиколониальные. Безусловно, не стоит преуменьшать социально-политическое значение романа – политическая проблематика занимает важное место в произведении, однако, вряд ли стоит ее и преувеличивать