A neuronal network of mitochondrial dynamics regulates metastasis.

The role of mitochondria in cancer is controversial. Using a genome-wide shRNA screen, we now show that tumours reprogram a network of mitochondrial dynamics operative in neurons, including syntaphilin (SNPH), kinesin KIF5B and GTPase Miro1/2 to localize mitochondria to the cortical cytoskeleton and power the membrane machinery of cell movements. When expressed in tumours, SNPH inhibits the speed and distance travelled by individual mitochondria, suppresses organelle dynamics, and blocks chemotaxis and metastasis, in vivo. Tumour progression in humans is associated with downregulation or loss of SNPH, which correlates with shortened patient survival, increased mitochondrial trafficking to the cortical cytoskeleton, greater membrane dynamics and heightened cell invasion. Therefore, a SNPH network regulates metastatic competence and may provide a therapeutic target in cancer

Improved Measurement of the Positive Muon Lifetime and Determination of the Fermi Constant

The mean life of the positive muon has been measured to a precision of 11 ppm using a low-energy, pulsed muon beam stopped in a ferromagnetic target, which was surrounded by a scintillator detector array. The result, tau_mu = 2.197013(24) us, is in excellent agreement with the previous world average. The new world average tau_mu = 2.197019(21) us determines the Fermi constant G_F = 1.166371(6) x 10^-5 GeV^-2 (5 ppm). Additionally, the precision measurement of the positive muon lifetime is needed to determine the nucleon pseudoscalar coupling g_P.Comment: As published version (PRL, July 2007

Divergent water requirements partition exposure risk to parasites in wild equids

For grazing herbivores, dung density in feeding areas is an important determinant of exposure risk to fecal- orally transmitted parasites. When host species share the same parasite species, a nonrandom distribution of their cumulative dung density and/or nonrandom ranging and feeding behavior may skew exposure risk and the relative selection pressure parasites impose on each host. The arid-adapted Grevy\u27s zebra ( Equus grevyi ) can range more widely than the water-dependent plains zebra ( Equus quagga ), with which it shares the same species of gastrointestinal nematodes. We studied how the spatial distribution of zebra dung relates to ranging and feeding behavior to assess parasite exposure risk in Grevy\u27s and plains zebras at a site inhabited by both zebra species. We found that zebra dung density declined with distance from water, Grevy\u27s zebra home ranges (excluding those of territorial males) were farther from water than those of plains zebras, and plains zebra grazing areas had higher dung density than random points while Grevy\u27s zebra grazing areas did not, suggest - ing a greater exposure risk in plains zebras associated with their water dependence. Fecal egg counts increased with home range proximity to water for both species, but the response was stronger in plains zebras, indicating that this host species may be particularly vulnerable to the elevated exposure risk close to water. We further ran experiments on microclimatic effects on dung infectivity and showed that fewer nematode eggs embryonated in dung in the sun than in the shade. However, only 5% of the zebra dung on the landscape was in shade, indicating that the microclimatic effects of shade on the density of infective larvae is not a major influence on exposure risk dynamics. Ranging constraints based on water requirements appear to be key mediators of nematode parasite exposure in free-ranging equids

Revival of the magnetar PSR J1622-4950: observations with MeerKAT, Parkes, XMM-Newton, Swift, Chandra, and NuSTAR

New radio (MeerKAT and Parkes) and X-ray (XMM-Newton, Swift, Chandra, and NuSTAR) observations of PSR J1622-4950 indicate that the magnetar, in a quiescent state since at least early 2015, reactivated between 2017 March 19 and April 5. The radio flux density, while variable, is approximately 100x larger than during its dormant state. The X-ray flux one month after reactivation was at least 800x larger than during quiescence, and has been decaying exponentially on a 111+/-19 day timescale. This high-flux state, together with a radio-derived rotational ephemeris, enabled for the first time the detection of X-ray pulsations for this magnetar. At 5%, the 0.3-6 keV pulsed fraction is comparable to the smallest observed for magnetars. The overall pulsar geometry inferred from polarized radio emission appears to be broadly consistent with that determined 6-8 years earlier. However, rotating vector model fits suggest that we are now seeing radio emission from a different location in the magnetosphere than previously. This indicates a novel way in which radio emission from magnetars can differ from that of ordinary pulsars. The torque on the neutron star is varying rapidly and unsteadily, as is common for magnetars following outburst, having changed by a factor of 7 within six months of reactivation.Comment: Published in ApJ (2018 April 5); 13 pages, 4 figure

Accurate Whole-Genome Sequencing and Haplotyping from 10 to 20 Human Cells

Recent advances in whole genome sequencing have brought the vision of personal genomics and genomic medicine closer to reality. However, current methods lack clinical accuracy and the ability to describe the context (haplotypes) in which genome variants co-occur in a cost-effective manner. Here we describe a low-cost DNA sequencing and haplotyping process, Long Fragment Read (LFR) technology, similar to sequencing long single DNA molecules without cloning or separation of metaphase chromosomes. In this study, ten LFR libraries were made using only ~100 pg of human DNA per sample. Up to 97% of the heterozygous single nucleotide variants (SNVs) were assembled into long haplotype contigs. Removal of false positive SNVs not phased by multiple LFR haplotypes resulted in a final genome error rate of 1 in 10 Mb. Cost-effective and accurate genome sequencing and haplotyping from 10-20 human cells, as demonstrated here, will enable comprehensive genetic studies and diverse clinical applications

Ventilatory muscle strength, diaphragm thickness and pulmonary function in world-class powerlifters.

Resistance training activates the ventilatory muscles providing a stimulus similar to ventilatory muscle training. We examined the effects of elite powerlifting training upon ventilatory muscle strength, pulmonary function and diaphragm thickness in world-class powerlifters (POWER) and a control group (CON) with no history of endurance or resistance training, matched for age, height and body mass

Mammography-based screening program: preliminary results from a first 2-year round in a Brazilian region using mobile and fixed units

RLH, TBS and ALF made substantial contributions to the conception and design of the article, the acquisition, analysis and interpretation of the data, and drafting of the article. ECM, JSCM and NB made substantial contributions to the conception and design of the study.Background: Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer deaths among women worldwide. The use of mobile mammography units to offer screening to women living in remote areas is a rational strategy to increase the number of women examined. This study aimed to evaluate results from the first 2 years of a government-organized mammography screening program implemented with a mobile unit (MU) and a fixed unit (FU) in a rural county in Brazil. The program offered breast cancer screening to women living in Barretos and the surrounding area. Methods: Based on epidemiologic data, 54 238 women, aged 40 to 69 years, were eligible for breast cancer screening. The study included women examined from April 1, 2003 to March 31, 2005. The chi-square test and Bonferroni correction analyses were used to evaluate the frequencies of tumors and the importance of clinical parameters and tumor characteristics. Significance was set at p < 0.05. Results: Overall, 17 964 women underwent mammography. This represented 33.1% of eligible women in the area. A mean of 18.6 and 26.3 women per day were examined in the FU and MU, respectively. Seventy six patients were diagnosed with breast cancer (41 (54%) in the MU). This represented 4.2 cases of breast cancer per 1000 examinations. The number of cancers detected was significantly higher in women aged 60 to 69 years than in those aged 50 to 59 years (p < 0.001) or 40 to 49 years (p < 0.001). No difference was observed between women aged 40 to 49 years and those aged 50 to 59 years (p = 0.164). The proportion of tumors in the early (EC 0 and EC I) and advanced (CS III and CS IV) stages of development were 43.4% and 15.8%, respectively. Conclusions: Preliminary results indicate that this mammography screening program is feasible for implementation in a rural Brazilian territory and favor program continuation