ETV6 (TEL1) in blood cell development and malignancy

 The ETV6 (TEL1) gene encodes a member of the ETS family of transcriptional regulators. It represents one of the most frequently disrupted genes in haematological malignancies, with over 50 different translocations described. Moreover, deletion, silencing or truncating mutations have also been reported, suggesting a potential tumor suppressor function. Recent studies have shown that ETV6 plays a broad and complex role in early hematopoiesis, impacting on the development of multiple lineages, providing new insights into how its perturbation contributes to disease

Effect of growth media modifications on cell biomass and polyunsaturated fatty acids (PUFAs) production from Shewanella frigidimarina

Polyunsaturated fatty acids (PUFAs) are chemically present as esters, ethers, glycerides glycolipids, phospholipids, phosphonolipids, glycosphingolipids, sulpholipids and lipoproteins in storage oils andmembranes lipids. Marine microorganisms such as Shewanella frigidimarina are important sources of polyunsaturated fatty acids with promising biomedical applications, commercial value and the potentialability to be used in the bioremediation of environments contaminated with petroleum hydrocarbons. The growth media dependency of S. frigidimarina in terms of its growth behavior in response to modifications made to the media as well as its potential to produce PUFAs was evaluated. S. frigidimarina was cultured in conventional shake-flasks and controlled bioreactors with a batch-type procedure using different media compositions. The media used included artificial sea water, modifiedartificial sea water 1, modified artificial sea water 2, Luria Bertani, modified Luria Bertani, sodium pyruvate-yeast (PYS) and marine broth. The highest cell biomass was obtained from artificial sea water media with an optical density (OD600) value of 0.15 and subsequent studies were carried out using this medium. To evaluate the potential for PUFA production, RNA transcripts of polyketide synthases (PKS) genes were isolated and reverse-transcriptase polymerase chain reaction (RT-PCR) with S. frigidimarina specific primers carried out. The results of the successful RNA extraction and subsequent RT-PCR revealed that modifications made to growth media compositions can affect the potential for PUFA production.Keywords: Polyunsaturated fatty acids, Shewanella frigidimarina, media modificatio

Functional Analysis of a Unique Troponin C Mutation, GLY159ASP, that Causes Familial Dilated Cardiomyopathy, Studied in Explanted Heart Muscle

Background-Familial dilated cardiomyopathy can be caused by mutations in the proteins of the muscle thin filament. In vitro, these mutations decrease Ca2+ sensitivity and cross-bridge turnover rate, but the mutations have not been investigated in human tissue. We studied the Ca2+-regulatory properties of myocytes and troponin extracted from the explanted heart of a patient with inherited dilated cardiomyopathy due to the cTnC G159D mutation.Methods and Results-Mass spectroscopy showed that the mutant cTnC was expressed approximately equimolar with wild-type cTnC. Contraction was compared in skinned ventricular myocytes from the cTnC G159D patient and nonfailing donor heart. Maximal Ca2+-activated force was similar in cTnC G159D and donor myocytes, but the Ca2+ sensitivity of cTnC G159D myocytes was higher (EC50 G159D/donor=0.60). Thin filaments reconstituted with skeletal muscle actin and human cardiac tropomyosin and troponin were studied by in vitro motility assay. Thin filaments containing the mutation had a higher Ca2+ sensitivity (EC(50)G159D/donor=0.55 +/- 0.13), whereas the maximally activated sliding speed was unaltered. In addition, the cTnC G159D mutation blunted the change in Ca2+ sensitivity when TnI was dephosphorylated. With wild-type troponin, Ca2+ sensitivity was increased (EC50 P/unP=4.7 +/- 1.9) but not with cTnC G159D troponin (EC50 P/unP=1.2 +/- 0.1).Conclusions-We propose that uncoupling of the relationship between phosphorylation and Ca2+ sensitivity could be the cause of the dilated cardiomyopathy phenotype. The differences between these data and previous in vitro results show that native phosphorylation of troponin I and troponin T and other posttranslational modifications of sarcomeric proteins strongly influence the functional effects of a mutation. (Circ Heart Fail. 2009;2:456-464.

African penguins as predators and prey — coping (or not) with change

African penguins Spheniscus demersus live in the Benguela and western Agulhas ecosystems off southern Africa. Their numbers decreased throughout the 20th century from at least 1.5 million to about 0.18 million adults, although different regional trends were apparent. They feed to a large extent on shoaling epipelagic fish, notably anchovy Engraulis capensis and sardine Sardinops sagax, and regional trends in the abundance of penguins are associated with trends in the abundance and distribution of these prey fish. Many first-time breeders emigrate from colonies where feeding or other conditions at the time are unfavourable to more favourable breeding localities. This has led to both the extinction and formation of colonies. Food now may limit colonies at relatively small sizes, a fact attributable to industrial fisheries reducing the densities of forage fish. African penguins share their habitat with several other predators, with which they compete for food and breeding space. One of these, the Cape fur seal Arctocephalus p. pusillus, increased through the 20th century to 1.5–2 million animals at its close. Reported observations of predation by fur seals on seabirds have increased in recent decades and threaten the continued existence of small colonies of penguins. Stochastic modelling suggests that colonies of 10 000 pairs have a 9% probability of extinction in 100 years, so smaller populations should be regarded as “Vulnerable”. However, in a period of prolonged food scarcity off southern Namibia, the regional population decreased from more than 40 000 pairs in 1956 to about 1 000 pairs in 2000, and many colonies numbering less than 1 000 pairs became extinct. The minimum viable population for African penguins is currently considered to be >40 000 pairs, likely of the order of 50 000 pairs, a figure equivalent to its level in 2000. The chance of survival of the species through the 21st century is tenuous.African Journal of Marine Science 2001, 23: 435–44

Differential genomic imprinting regulates paracrine and autocrine roles of IGF2 in mouse adult neurogenesis.

Genomic imprinting is implicated in the control of gene dosage in neurogenic niches. Here we address the importance of Igf2 imprinting for murine adult neurogenesis in the subventricular zone (SVZ) and in the subgranular zone (SGZ) of the hippocampus in vivo. In the SVZ, paracrine IGF2 is a cerebrospinal fluid and endothelial-derived neurogenic factor requiring biallelic expression, with mutants having reduced activation of the stem cell pool and impaired olfactory bulb neurogenesis. In contrast, Igf2 is imprinted in the hippocampus acting as an autocrine factor expressed in neural stem cells (NSCs) solely from the paternal allele. Conditional mutagenesis of Igf2 in blood vessels confirms that endothelial-derived IGF2 contributes to NSC maintenance in SVZ but not in the SGZ, and that this is regulated by the biallelic expression of IGF2 in the vascular compartment. Our findings indicate that a regulatory decision to imprint or not is a functionally important mechanism of transcriptional dosage control in adult neurogenesis.This work was supported by grants from Ministerio de Economía y Competitividad (SAF2012-40107), Generalitat Valenciana (Programa ACOMP2014-258) and Fundación BBVA to SRF and grants from the MRC, Wellcome Trust and EU FP7 Ingenium Training Network to AFS. AW and TRM were supported by the Association for International Cancer Research and Medical Research Council, UK.SRF was a recipient of a Herchel-Smith fellowship and currently is a Ramón y Cajal investigator. ADM is funded by a Spanish FPU fellowship program of the Ministerio de Educación, Cultura y Deporte. AR was from the Erasmus Placement Program.This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/ncomms926

Using BOX-PCR to exclude a clonal outbreak of melioidosis

Background Although melioidosis in endemic regions is usually caused by a diverse range of Burkholderia pseudomallei strains, clonal outbreaks from contaminated potable water have been described. Furthermore B. pseudomallei is classified as a CDC Group B bioterrorism agent. Ribotyping, pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) have been used to identify genetically related B. pseudomallei isolates, but they are time consuming and technically challenging for many laboratories. Methods We have adapted repetitive sequence typing using a BOX A1R primer for typing B. pseudomallei and compared BOX-PCR fingerprinting results on a wide range of well-characterized B. pseudomallei isolates with MLST and PFGE performed on the same isolates. Results BOX-PCR typing compared favourably with MLST and PFGE performed on the same isolates, both discriminating between the majority of multilocus sequence types and showing relatedness between epidemiologically linked isolates from various outbreak clusters. Conclusion Our results suggest that BOX-PCR can be used to exclude a clonal outbreak of melioidosis within 10 hours of receiving the bacterial strains

Radioactive 26Al and massive stars in the Galaxy

Gamma-rays from radioactive 26Al (half life ~7.2 10^5 yr) provide a 'snapshot' view of ongoing nucleosynthesis in the Galaxy. The Galaxy is relatively transparent to such gamma-rays, and emission has been found concentrated along the plane of the Galaxy. This led to the conclusion1 that massive stars throughout the Galaxy dominate the production of 26Al. On the other hand, meteoritic data show locally-produced 26Al, perhaps from spallation reactions in the protosolar disk. Furthermore, prominent gamma-ray emission from the Cygnus region suggests that a substantial fraction of Galactic 26Al could originate in localized star-forming regions. Here we report high spectral resolution measurements of 26Al emission at 1808.65 keV, which demonstrate that the 26Al source regions corotate with the Galaxy, supporting its Galaxy-wide origin. We determine a present-day equilibrium mass of 2.8 (+/-0.8) M_sol of 26Al. We use this to estimate that the frequency of core collapse (i.e. type Ib/c and type II) supernovae to be 1.9(+/- 1.1) events per century.Comment: accepted for publication in Nature, 24 pages including Online Supplements, 11 figures, 1 tabl

Current and potential providers of blood pressure self-screening: a mixed methods study in Oxfordshire.

OBJECTIVES: To (1) establish the extent of opportunities for members of the public to check their own blood pressure (BP) outside of healthcare consultations (BP self-screening), (2) investigate the reasons for and against hosting such a service and (3) ascertain how BP self-screening data are used in primary care. DESIGN: A mixed methods, cross-sectional study. SETTING: Primary care and community locations in Oxfordshire, UK. PARTICIPANTS: 325 sites were surveyed to identify where and in what form BP self-screening services were available. 23 semistructured interviews were then completed with current and potential hosts of BP self-screening services. RESULTS: 18/82 (22%) general practices offered BP self-screening and 68/110 (62%) pharmacies offered professional-led BP screening. There was no evidence of permanent BP self-screening activities in other community settings.Healthcare professionals, managers, community workers and leaders were interviewed. Those in primary care generally felt that practice-based BP self-screening was a beneficial activity that increased the attainment of performance targets although there was variation in its perceived usefulness for patient care. The pharmacists interviewed provided BP checking as a service to the community but were unable to develop self-screening services without a clear business plan. Among potential hosts, barriers to providing a BP self-screening service included a perceived lack of healthcare commissioner and public demand, and a weak-if any-link to their core objectives as an organisation. CONCLUSIONS: BP self-screening currently occurs in a minority of general practices. Any future development of community BP self-screening programmes will require (1) public promotion and (2) careful consideration of how best to support-and reward-the community hosts who currently perceive little if any benefit

Using and communicating uncertainty for the effective control of invasive non-native species

Estimates of quantities needed to plan invasive species control, such as population size, are always uncertain; this is an issue that can become a problem when mishandled in ecological science and its communication. The complexities of incorporating uncertainty into sophisticated decision‐support tools may be a barrier to their use by decision makers, leading to decisions being made without due regard to uncertainty and risking misplaced certainty of predicted outcomes. We summarise ways in which uncertainty has been incorporated into and used to advise decisions on the management of invasive non‐native species and other problem species, and offer a simple conceptual model for accommodating and using uncertainty at the planning stage. We also demonstrate how frequently uncertainty has been misused and miscommunicated in the wildlife management literature. We contend that uncertainty in estimates of natural quantities must be acknowledged, can inform decisions and can be made to derive decisions, and should not be ignored if invasive species policy is to be delivered effectively. Uncertainty must be communicated thoroughly and correctly by scientists if decision makers are to understand its consequences for planning and resourcing control programmes