Cdc25A phosphatase: a key cell cycle protein that regulates neuron death in disease and development

Cell cycle molecules are mostly dormant in differentiated neurons that are post-mitotic and in the G0 state of the cell cycle. However, a wealth of evidence strongly suggests that in response to a wide variety of apoptotic stimuli, including trophic factor deprivation, exposure to β-amyloid (Aβ) and DNA damage, neurons emerge from theG0 state with aberrant expression/activation of cell cycle proteins.1 This emergence is characterized by a consistent set of events related to the cell cycle that culminate in neuron death. Initial responses include activation of G1/S cyclin-dependent kinases (Cdks), such as Cdk4 that in turn phosphorylate retinoblastoma (pRb) family proteins and lead to dissociation of repressor complexes comprising E2F and pRb proteins, so that E2F-binding genes are de-repressed. Among genes that are de-repressed by loss of E2F-Rb family complexes are the B- and C-myb transcription factors that in turn transactivate Bim, a pro-apoptotic protein that promotes caspase activation and subsequent neuron death.1–4 This set of events has been termed the ‘apoptotic cell cycle pathway’.Cell division cycle 25A (Cdc25A), a member of a family comprising Cdc25A, B and C, is a dual specificity phosphatase that dephosphorylates inhibitory phosphates on adjacent threonine and tyrosine residues of Cdks such as Cdk4.5 This step is essential for initiation of cell cycle in proliferating cells. However, it was not known whether in the non-dividing neurons, the same events would activate the apoptotic cell cycle pathway. In our recent paper published in Cell Death Discovery,6 we report several novel findings regarding the potential role of Cdc25A in neuron death. First, Cdc25A is required for activation of the apoptotic cell cycle pathway and neuron death in response to nerve growth factor (NGF) deprivation and Aβ treatment. Second, Cdc25A acts upstream of Cdk-mediated Rb phosphorylation and caspase-3 cleavage. Third, NGF deprivation and Aβ lead to rapid increases in Cdc25A mRNA and protein levels. NGF withdrawal causes an increase in Cdc25A activity as well. These events occur at about the same time that apoptotic insults lead to Cdk4 activation and Rb phosphorylation in our experimental systems and well precede evident signs of neuron death

Community-Led Total Sanitation: A Mixed-Methods Systematic Review of Evidence and Its Quality

Background: Community-led total sanitation (CLTS) is a widely applied rural behavior change approach for ending open defecation. However, evidence of its impact is unclear. Objectives: We conducted a systematic review of journal-published and gray literature to a) assess evidence quality, b) summarize CLTS impacts, and c) identify factors affecting implementation and effectiveness. Methods: Eligible studies were systematically screened and selected for analysis from searches of seven databases and 16 websites. We developed a framework to appraise literature quality. We qualitatively analyzed factors enabling or constraining CLTS, and summarized results from quantitative evaluations. Discussion: We included 200 studies (14 quantitative evaluations, 29 qualitative studies, and 157 case studies). Journal-published literature was generally of higher quality than gray literature. Fourteen quantitative evaluations reported decreases in open defecation, but did not corroborate the widespread claims of open defecation–free (ODF) villages found in case studies. Over one-fourth of the literature overstated conclusions, attributing outcomes and impacts to interventions without an appropriate study design. We identified 43 implementation- and community-related factors reportedly affecting CLTS. This analysis revealed the importance of adaptability, structured posttriggering activities, appropriate community selection, and further research on combining and sequencing CLTS with other interventions. Conclusions: The evidence base on CLTS effectiveness available to practitioners, policy makers, and program managers to inform their actions is weak. Our results highlight the need for more rigorous research on CLTS impacts as well as applied research initiatives that bring researchers and practitioners together to address implementation challenges to improve rural sanitation efforts

Enhanced UV photosensitivity from rapid thermal annealed vertically aligned ZnO nanowires

We report on the major improvement in UV photosensitivity and faster photoresponse from vertically aligned ZnO nanowires (NWs) by means of rapid thermal annealing (RTA). The ZnO NWs were grown by vapor-liquid-solid method and subsequently RTA treated at 700°C and 800°C for 120 s. The UV photosensitivity (photo-to-dark current ratio) is 4.5 × 103 for the as-grown NWs and after RTA treatment it is enhanced by a factor of five. The photocurrent (PC) spectra of the as-grown and RTA-treated NWs show a strong peak in the UV region and two other relatively weak peaks in the visible region. The photoresponse measurement shows a bi-exponential growth and bi-exponential decay of the PC from as-grown as well as RTA-treated ZnO NWs. The growth and decay time constants are reduced after the RTA treatment indicating a faster photoresponse. The dark current-voltage characteristics clearly show the presence of surface defects-related trap centers on the as-grown ZnO NWs and after RTA treatment it is significantly reduced. The RTA processing diminishes the surface defect-related trap centers and modifies the surface of the ZnO NWs, resulting in enhanced PC and faster photoresponse. These results demonstrated the effectiveness of RTA processing for achieving improved photosensitivity of ZnO NWs

Granulomatous Reactivation during the Course of a Leprosy Infection: Reaction or Relapse

Leprosy is a serious infectious disease whose treatment still poses some challenges. Patients are usually treated with a combination of antimicrobial drugs called multidrug therapy. Although this treatment is effective against Mycobacterium leprae, the bacillus that causes leprosy, patients may develop severe inflammatory reactions during treatment. These reactions may be either attributed to an improvement in the immunological reactivity of the patient along with the treatment, or to relapse of the disease due to the proliferation of remaining bacilli. In certain patients these two conditions may be difficult to differentiate. The present study addresses the histopathology picture of and the M. leprae bacilli in sequential biopsies taken from lesions of patients who presented such reactions aiming to improve the differentiation of the two conditions. This is important because these reactions are one of the major causes of the disabilities of the patients with leprosy, and should be treated early and appropriately. Our results show that the histopathology picture alone is not sufficient, and that bacilli's counting is necessary

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Measurement of the cross-section of high transverse momentum vector bosons reconstructed as single jets and studies of jet substructure in pp collisions at √s = 7 TeV with the ATLAS detector

This paper presents a measurement of the cross-section for high transverse momentum W and Z bosons produced in pp collisions and decaying to all-hadronic final states. The data used in the analysis were recorded by the ATLAS detector at the CERN Large Hadron Collider at a centre-of-mass energy of √s = 7 TeV;{\rm Te}{\rm V}$and correspond to an integrated luminosity of$4.6\;{\rm f}{{{\rm b}}^{-1}}$. The measurement is performed by reconstructing the boosted W or Z bosons in single jets. The reconstructed jet mass is used to identify the W and Z bosons, and a jet substructure method based on energy cluster information in the jet centre-of-mass frame is used to suppress the large multi-jet background. The cross-section for events with a hadronically decaying W or Z boson, with transverse momentum${{p}_{{\rm T}}}\gt 320\;{\rm Ge}{\rm V}$and pseudorapidity$|\eta |\lt 1.9$, is measured to be${{\sigma }_{W+Z}}=8.5\pm 1.7$ pb and is compared to next-to-leading-order calculations. The selected events are further used to study jet grooming techniques

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Search for the neutral Higgs bosons of the minimal supersymmetric standard model in pp collisions at root s=7 TeV with the ATLAS detector

A search for neutral Higgs bosons of the Minimal Supersymmetric Standard Model (MSSM) is reported. The analysis is based on a sample of proton-proton collisions at a centre-of-mass energy of 7TeV recorded with the ATLAS detector at the Large Hadron Collider. The data were recorded in 2011 and correspond to an integrated luminosity of 4.7 fb-1 to 4.8 fb-1. Higgs boson decays into oppositely-charged muon or τ lepton pairs are considered for final states requiring either the presence or absence of b-jets. No statistically significant excess over the expected background is observed and exclusion limits at the 95% confidence level are derived. The exclusion limits are for the production cross-section of a generic neutral Higgs boson, φ, as a function of the Higgs boson mass and for h/A/H production in the MSSM as a function of the parameters mA and tan β in the mhmax scenario for mA in the range of 90GeV to 500 GeV. Copyright CERN