Genome sequence of Silicibacter pomeroyi reveals adaptations to the marine environment

Since the recognition of prokaryotes as essential components of the oceanic food web, bacterioplankton have been acknowledged as catalysts of most major biogeochemical processes in the sea. Studying heterotrophic bacterioplankton has been challenging, however, as most major clades have never been cultured or have only been grown to low densities in sea water. Here we describe the genome sequence of Silicibacter pomeroyi, a member of the marine Roseobacter clade (Fig. 1), the relatives of which comprise approximately 10-20% of coastal and oceanic mixed-layer bacterioplankton. This first genome sequence from any major heterotrophic clade consists of a chromosome (4,109,442 base pairs) and megaplasmid (491,611 base pairs). Genome analysis indicates that this organism relies upon a lithoheterotrophic strategy that uses inorganic compounds (carbon monoxide and sulphide) to supplement heterotrophy. Silicibacter pomeroyi also has genes advantageous for associations with plankton and suspended particles, including genes for uptake of algal-derived compounds, use of metabolites from reducing microzones, rapid growth and cell-density-dependent regulation. This bacterium has a physiology distinct from that of marine oligotrophs, adding a new strategy to the recognized repertoire for coping with a nutrient-poor ocean.     

ATM phosphorylation of Nijmegen breakage syndrome protein is required in a DNA damage response

Nijmegen breakage syndrome (NBS) is characterized by extreme radiation sensitivity, chromosomal instability and cancer. The phenotypes are similar to those of ataxia telangiectasia mutated (ATM) disease, where there is a deficiency in a protein kinase that is activated by DNA damage, indicating that the Nbs and Atm proteins may participate in common pathways. Here we report that Nbs is specifically phosphorylated in response to gamma-radiation, ultraviolet light and exposure to hydroxyurea. Phosphorylation of Nbs mediated by gamma-radiation, but not that induced by hydroxyurea or ultraviolet light, was markedly reduced in ATM cells. In vivo, Nbs was phosphorylated on many serine residues, of which S343, S397 and S615 were phosphorylated by Atm in vitro. At least two of these sites were underphosphorylated in ATM cells. Inactivation of these serines by mutation partially abrogated Atm-dependent phosphorylation. Reconstituting NBS cells with a mutant form of Nbs that cannot be phosphorylated at selected, ATM-dependent serine residues led to a specific reduction in clonogenic survival after gamma-radiation. Thus, phosphorylation of Nbs by Atm is critical for certain responses of human cells to DNA damage.     

Two new species of Xironogiton (Clitellata: Branchiobdellida) from western North America

Xironogiton, a genus of crayfish worm (order Branchiobdellida), is historically endemic to North America. To date, six species of Xironogiton have been described, including five and one from areas west and east of the Continental Divide, respectively. Recent collections of the crayfishes Pacifastacus connectens and Pacifastacus leniusculus from the endorheic Harney Basin in south-eastern Oregon, USA, revealed the presence of two previously unknown Xironogiton species, which we describe herein. Discovery and characterisation of Xironogiton bibendumi sp. nov. and Xironogiton malheurensis sp. nov. suggests that much work remains to understand branchiobdellidan diversity in western North America, and additional targeted sampling is needed to determine intra- and interspecific variation, and thus define species limits.http://www.zoobank.org/urn:lsid:zoobank.org:pub:B24AA844-4A73-48F2-B269-7CD08DC8389A http://www.zoobank.org/urn:lsid:zoobank.org:pub:F1787846-BF04-44A6-949B-551EE3453F26     

The intestinal epithelium tuft cells: specification and function

The intestinal epithelium, composed of at least seven differentiated cell types, represents an extraordinary model to understand the details of multi-lineage differentiation, a question that is highly relevant in developmental biology as well as for clinical applications. This review focuses on intestinal epithelial tuft cells that have been acknowledged as a separate entity for more than 60?years but whose function remains a mystery. We discuss what is currently known about the molecular basis of tuft cell fate and differentiation and why elucidating tuft cell function has been so difficult. Finally, we summarize the current hypotheses on their potential involvement in diseases of the gastro-intestinal tract.     

Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids

Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is an autosomal-dominant central nervous system white-matter disease with variable clinical presentations, including personality and behavioral changes, dementia, depression, parkinsonism, seizures and other phenotypes. We combined genome-wide linkage analysis with exome sequencing and identified 14 different mutations affecting the tyrosine kinase domain of the colony stimulating factor 1 receptor (encoded by CSF1R) in 14 families with HDLS. In one kindred, we confirmed the de novo occurrence of the mutation. Follow-up sequencing identified an additional CSF1R mutation in an individual diagnosed with corticobasal syndrome. In vitro, CSF-1 stimulation resulted in rapid autophosphorylation of selected tyrosine residues in the kinase domain of wild-type but not mutant CSF1R, suggesting that HDLS may result from partial loss of CSF1R function. As CSF1R is a crucial mediator of microglial proliferation and differentiation in the brain, our findings suggest an important role for microglial dysfunction in HDLS pathogenesis.     

TGFB2 mutations cause familial thoracic aortic aneurysms and dissections associated with mild systemic features of Marfan syndrome

A predisposition for thoracic aortic aneurysms leading to acute aortic dissections can be inherited in families in an autosomal dominant manner. Genome-wide linkage analysis of two large unrelated families with thoracic aortic disease followed by whole-exome sequencing of affected relatives identified causative mutations in TGFB2. These mutations-a frameshift mutation in exon 6 and a nonsense mutation in exon 4-segregated with disease with a combined logarithm of odds (LOD) score of 7.7. Sanger sequencing of 276 probands from families with inherited thoracic aortic disease identified 2 additional TGFB2 mutations. TGFB2 encodes transforming growth factor (TGF)-β2, and the mutations are predicted to cause haploinsufficiency for TGFB2; however, aortic tissue from cases paradoxically shows increased TGF-β2 expression and immunostaining. Thus, haploinsufficiency for TGFB2 predisposes to thoracic aortic disease, suggesting that the initial pathway driving disease is decreased cellular TGF-β2 levels leading to a secondary increase in TGF-β2 production in the diseased aorta.     

A Systemic Exploration of Lesotho’s Basic Education through Interactive Management

Lesotho is an inland country striving to improve its economy. Accessible education is perceived as an effective approach to economic growth. Over the years, various projects were commenced to improve Lesotho’s basic education provision. However, the progress is not satisfactory or stable. This paper argues for systemic thinking and adopts Warfield’s interactive management to identify the difficulties in Lesotho’s education projects. Interactive management can help stakeholders to identify system elements, structure the relationship between systems elements and produce a diagraph representing the system in question. The core mechanism of interactive management is a binary matrix which can infer the existence of a relationship between system elements, provided that the relationship is transitive. Four root problems were identified through the interactive management process: ‘board members not educated’, ‘poor service delivery by the Ministry of Education and Training to teachers’, ‘food insecurity’ and ‘reduced and standardisation of school fees at post primary schools’. The developed model demonstrates how system elements are interconnected. The model has potential to be used as a starting point for the Lesotho government to manage on its basic education problems through the identified root causes.     

A giant impact origin for Pluto's small moons and satellite multiplicity in the Kuiper belt

The two newly discovered satellites of Pluto (P1 and P2) have masses that are small compared to both Pluto and Charon-that is, between 5 x 10(-4) and 1 x 10(-5) of Pluto's mass, and between 5 x 10(-3) and 1 x 10(-4) of Charon's mass. This discovery, combined with the constraints on the absence of more distant satellites of Pluto, reveal that Pluto and its moons comprise an unusual, highly compact, quadruple system. These facts naturally raise the question of how this puzzling satellite system came to be. Here we show that P1 and P2's proximity to Pluto and Charon, the fact that P1 and P2 are on near-circular orbits in the same plane as Pluto's large satellite Charon, along with their apparent locations in or near high-order mean-motion resonances, all probably result from their being constructed from collisional ejecta that originated from the Pluto-Charon formation event. We also argue that dust-ice rings of variable optical depths form sporadically in the Pluto system, and that rich satellite systems may be found--perhaps frequently--around other large Kuiper belt objects.