Lung adenocarcinoma originates from retrovirus infection of proliferating type 2 pneumocytes during pulmonary post-natal development or tissue repair

Jaagsiekte sheep retrovirus (JSRV) is a unique oncogenic virus with distinctive biological properties. JSRV is the only virus causing a naturally occurring lung cancer (ovine pulmonary adenocarcinoma, OPA) and possessing a major structural protein that functions as a dominant oncoprotein. Lung cancer is the major cause of death among cancer patients. OPA can be an extremely useful animal model in order to identify the cells originating lung adenocarcinoma and to study the early events of pulmonary carcinogenesis. In this study, we demonstrated that lung adenocarcinoma in sheep originates from infection and transformation of proliferating type 2 pneumocytes (termed here lung alveolar proliferating cells, LAPCs). We excluded that OPA originates from a bronchioalveolar stem cell, or from mature post-mitotic type 2 pneumocytes or from either proliferating or non-proliferating Clara cells. We show that young animals possess abundant LAPCs and are highly susceptible to JSRV infection and transformation. On the contrary, healthy adult sheep, which are normally resistant to experimental OPA induction, exhibit a relatively low number of LAPCs and are resistant to JSRV infection of the respiratory epithelium. Importantly, induction of lung injury increased dramatically the number of LAPCs in adult sheep and rendered these animals fully susceptible to JSRV infection and transformation. Furthermore, we show that JSRV preferentially infects actively dividing cell in vitro. Overall, our study provides unique insights into pulmonary biology and carcinogenesis and suggests that JSRV and its host have reached an evolutionary equilibrium in which productive infection (and transformation) can occur only in cells that are scarce for most of the lifespan of the sheep. Our data also indicate that, at least in this model, inflammation can predispose to retroviral infection and cancer

Recognition of Handwriting from Electromyography

Handwriting – one of the most important developments in human culture – is also a methodological tool in several scientific disciplines, most importantly handwriting recognition methods, graphology and medical diagnostics. Previous studies have relied largely on the analyses of handwritten traces or kinematic analysis of handwriting; whereas electromyographic (EMG) signals associated with handwriting have received little attention. Here we show for the first time, a method in which EMG signals generated by hand and forearm muscles during handwriting activity are reliably translated into both algorithm-generated handwriting traces and font characters using decoding algorithms. Our results demonstrate the feasibility of recreating handwriting solely from EMG signals – the finding that can be utilized in computer peripherals and myoelectric prosthetic devices. Moreover, this approach may provide a rapid and sensitive method for diagnosing a variety of neurogenerative diseases before other symptoms become clear

End of Green Sahara amplified mid- to late Holocene megadroughts in mainland Southeast Asia

Between 5 and 4 thousand years ago, crippling megadroughts led to the disruption of ancient civilizations across parts of Africa and Asia, yet the extent of these climate extremes in mainland Southeast Asia (MSEA) has never been defined. This is despite archeological evidence showing a shift in human settlement patterns across the region during this period. We report evidence from stalagmite climate records indicating a major decrease of monsoon rainfall in MSEA during the mid- to late Holocene, coincident with African monsoon failure during the end of the Green Sahara. Through a set of modeling experiments, we show that reduced vegetation and increased dust loads during the Green Sahara termination shifted the Walker circulation eastward and cooled the Indian Ocean, causing a reduction in monsoon rainfall in MSEA. Our results indicate that vegetation-dust climate feedbacks from Sahara drying may have been the catalyst for societal shifts in MSEA via ocean-atmospheric teleconnections

International genomic definition of pneumococcal lineages, to contextualise disease, antibiotic resistance and vaccine impact

Background: Pneumococcal conjugate vaccines have reduced the incidence of invasive pneumococcal disease, caused by vaccine serotypes, but non-vaccine-serotypes remain a concern. We used whole genome sequencing to study pneumococcal serotype, antibiotic resistance and invasiveness, in the context of genetic background. / Methods: Our dataset of 13,454 genomes, combined with four published genomic datasets, represented Africa (40%), Asia (25%), Europe (19%), North America (12%), and South America (5%). These 20,027 pneumococcal genomes were clustered into lineages using PopPUNK, and named Global Pneumococcal Sequence Clusters (GPSCs). From our dataset, we additionally derived serotype and sequence type, and predicted antibiotic sensitivity. We then measured invasiveness using odds ratios that relating prevalence in invasive pneumococcal disease to carriage. / Findings: The combined collections (n = 20,027) were clustered into 621 GPSCs. Thirty-five GPSCs observed in our dataset were represented by >100 isolates, and subsequently classed as dominant-GPSCs. In 22/35 (63%) of dominant-GPSCs both non-vaccine serotypes and vaccine serotypes were observed in the years up until, and including, the first year of pneumococcal conjugate vaccine introduction. Penicillin and multidrug resistance were higher (p < .05) in a subset dominant-GPSCs (14/35, 9/35 respectively), and resistance to an increasing number of antibiotic classes was associated with increased recombination (R2 = 0.27 p < .0001). In 28/35 dominant-GPSCs, the country of isolation was a significant predictor (p < .05) of its antibiogram (mean misclassification error 0.28, SD ± 0.13). We detected increased invasiveness of six genetic backgrounds, when compared to other genetic backgrounds expressing the same serotype. Up to 1.6-fold changes in invasiveness odds ratio were observed. / Interpretation: We define GPSCs that can be assigned to any pneumococcal genomic dataset, to aid international comparisons. Existing non-vaccine-serotypes in most GPSCs preclude the removal of these lineages by pneumococcal conjugate vaccines; leaving potential for serotype replacement. A subset of GPSCs have increased resistance, and/or serotype-independent invasiveness

Intervention to enhance skilled arm and hand movements after stroke: A feasibility study using a new virtual reality system

<p>Abstract</p> <p>Background</p> <p>Rehabilitation programs designed to develop skill in upper extremity (UE) function after stroke require progressive practice that engage and challenge the learner. Virtual realty (VR) provides a unique environment where the presentation of stimuli can be controlled systematically for optimal challenge by adapting task difficulty as performance improves. We describe four VR tasks that were developed and tested to improve arm and hand movement skills for individuals with hemiparesis.</p> <p>Methods</p> <p>Two participants with chronic post-stroke paresis and different levels of motor severity attended 12 training sessions lasting 1 to 2 hours each over a 3-week period. Behavior measures and questionnaires were administered pre-, mid-, and post-training.</p> <p>Results</p> <p>Both participants improved VR task performance across sessions. The less impaired participant averaged more time on task, practiced a greater number of blocks per session, and progressed at a faster rate over sessions than the more impaired participant. Impairment level did not change but both participants improved functional ability after training. The less impaired participant increased the number of blocks moved on the Box & Blocks test while the more impaired participant achieved 4 more items on the Functional Test of the Hemiparetic UE.</p> <p>Conclusion</p> <p>Two participants with differing motor severity were able to engage in VR based practice and improve performance over 12 training sessions. We were able to successfully provide individualized, progressive practice based on each participant's level of movement ability and rate of performance improvement.</p

Measurement of Exclusive B Decays to Final States Containing a Charmed Baryon

Using data collected by the CLEO detector in the Upsilon(4S) region, we report new measurements of the exclusive decays of B mesons into final states of the type Lambda_c^+ p-bar n(pi), where n=0,1,2,3. We find signals in modes with one, two and three pions and an upper limit for the two body decay Lambda_c^+ pbar. We also make the first measurements of exclusive decays of B mesons to Sigma_c p-bar n(pi), where n=0,1,2. We find signals in modes with one and two pions and an upper limit for the two body decay Sigma_c p-bar. Measurements of these modes shed light on the mechanisms involved in B decays to baryons.Comment: 11 pages postscript, also available through http://w4.lns.cornell.edu/public/CLNS, submitted to PR

Measurement of the Masses and Widths of the Sigma_c^++ and Sigma_c^0 Charmed Baryons

Using data recorded by the CLEO II and CLEO II.V detector configurations at CESR, we report new measurements of the masses of the Sigma_c^{++} and Sigma_c^0 charmed baryons, and the first measurements of their intrinsic widths. We find M(Sigma_c^{++}) - M(Lambda_c^+) = 167.4 +- 0.1 +- 0.2 MeV, Gamma(Sigma_c^{++}) = 2.3 +- 0.2 +- 0.3 MeV, and M(Sigma_c^0) - M(Lambda_c^+) = 167.2 +- 0.1 +- 0.2 MeV, Gamma(Sigma_c^0) = 2.5 +- 0.2 +- 0.3 MeV, where the uncertainties are statistical and systematic, respectively.Comment: 9 pages postscript, also available through http://w4.lns.cornell.edu/public/CLNS, submitted to PRD, Rapid Communications. Reference [13] correcte

Hadronic Mass Moments in Inclusive Semileptonic B Meson Decays

We have measured the first and second moments of the hadronic mass-squared distribution in B -> X_c l nu, for P(lepton) > 1.5 GeV/c. We find <M_X^2 - M_D[Bar]^2> = 0.251 +- 0.066 GeV^2, )^2 > = 0.576 +- 0.170 GeV^4, where M_D[Bar] is the spin-averaged D meson mass. From that first moment and the first moment of the photon energy spectrum in b -> s gamma, we find the HQET parameter lambda_1 (MS[Bar], to order 1/M^3 and beta_0 alpha_s^2) to be -0.24 +- 0.11 GeV^2. Using these first moments and the B semileptonic width, and assuming parton-hadron duality, we obtain |V_cb| = 0.0404 +- 0.0013.Comment: 11 pages postscript, also available through http://w4.lns.cornell.edu/public/CLNS, submitted to PR