The Fission Yeast Homeodomain Protein Yox1p Binds to MBF and Confines MBF-Dependent Cell-Cycle Transcription to G1-S via Negative Feedback

The regulation of the G1- to S-phase transition is critical for cell-cycle progression. This transition is driven by a transient transcriptional wave regulated by transcription factor complexes termed MBF/SBF in yeast and E2F-DP in mammals. Here we apply genomic, genetic, and biochemical approaches to show that the Yox1p homeodomain protein of fission yeast plays a critical role in confining MBF-dependent transcription to the G1/S transition of the cell cycle. The yox1 gene is an MBF target, and Yox1p accumulates and preferentially binds to MBF-regulated promoters, via the MBF components Res2p and Nrm1p, when they are transcriptionally repressed during the cell cycle. Deletion of yox1 results in constitutively high transcription of MBF target genes and loss of their cell cycle–regulated expression, similar to deletion of nrm1. Genome-wide location analyses of Yox1p and the MBF component Cdc10p reveal dozens of genes whose promoters are bound by both factors, including their own genes and histone genes. In addition, Cdc10p shows promiscuous binding to other sites, most notably close to replication origins. This study establishes Yox1p as a new regulatory MBF component in fission yeast, which is transcriptionally induced by MBF and in turn inhibits MBF-dependent transcription. Yox1p may function together with Nrm1p to confine MBF-dependent transcription to the G1/S transition of the cell cycle via negative feedback. Compared to the orthologous budding yeast Yox1p, which indirectly functions in a negative feedback loop for cell-cycle transcription, similarities but also notable differences in the wiring of the regulatory circuits are evident

Production of He-4 and (4) in Pb-Pb collisions at root(NN)-N-S=2.76 TeV at the LHC

Results on the production of He-4 and (4) nuclei in Pb-Pb collisions at root(NN)-N-S = 2.76 TeV in the rapidity range vertical bar y vertical bar <1, using the ALICE detector, are presented in this paper. The rapidity densities corresponding to 0-10% central events are found to be dN/dy4(He) = (0.8 +/- 0.4 (stat) +/- 0.3 (syst)) x 10(-6) and dN/dy4 = (1.1 +/- 0.4 (stat) +/- 0.2 (syst)) x 10(-6), respectively. This is in agreement with the statistical thermal model expectation assuming the same chemical freeze-out temperature (T-chem = 156 MeV) as for light hadrons. The measured ratio of (4)/He-4 is 1.4 +/- 0.8 (stat) +/- 0.5 (syst). (C) 2018 Published by Elsevier B.V.Peer reviewe

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Capillary-based high-harmonic generation driven by different laser systems

High-harmonic generation (HHG), where a short-pulse high-power laser ionises a gas which upon recombination emits high energy radiation, is an exciting option for table-top sources of coherent X-rays and XUV light for imaging and spectroscopy. Traditionally, the pump lasers have been femtosecond Ti:Sapphire lasers. As more high-power ultrafast pump laser systems are becoming commercially available, for example fibre lasers and wavelength shifted systems based on OPAs, it is important to understand how their different operating regimes (wavelength, pulse length, peak power, repetition rate) affect HHG efficiency and flux

Numerical modelling of pump-wavelength dependence of high harmonic generation efficiency

High harmonic generation (HHG) provides a table-top source of extreme ultraviolet (XUV) and soft x-ray radiation. HHG pump-wavelength dependence is of significant practical interest for laser system design as HHG efficiency scales with pump wavelength to the power of P. First experiments suggested P = -6.5 while theoretical models predict P = -4.7 to -6.0. These investigations exploited single-atom models; insight into efficiencies for full experimental setups will further guide HHG laser designs. We developed a model that simulates the HHG process in full for an argon-filled capillary including all Ti:sapphire pump pulse and XUV propagation effects. With this we compare HHG of two geometries: a thin slice of argon, and an argon-filled capillary. For the thin slice with pump wavelengths 820-1890nm we found P = -4.5 scaling when the harmonic energies were integrated between 16 and 45eV. However, further analysis revealed a dependence of P = -6.4 for longer pump wavelengths (1500-1890nm), but P = -4.0 for shorter wavelengths (820-1500nm). By contrast, HHG in a 7-cm long capillary was found to scale with P = -3.4 (800-1850nm). We attribute this to phase-matching effects over longer propagation distances and nonlinear pump propagation distorting the pulse. Different scaling is observed when the energy of a single harmonic is calculated. In the thin slice the energy in the first harmonic above 20eV yields P = -6.1 (820-1890nm), P = -5.7 (820-1500nm), and P = -7.8 (1500-1890nm). For the whole capillary the corresponding value is P = -4.1 (800-1850nm).High-energy harmonics also exhibit very different scaling with pump wavelength as they cross the classical harmonic cutoff energy. For example, for the first harmonic beyond 41eV no value of P provides a good fit to the simulated HHG efficiencies, neither for the thin slice nor the whole capillary. Our simulations highlight pump-wavelength dependence of HHG efficiency is complex, with many contributing factors such as exact experimental geometry, optical nonlinearity, phase matching, and classical cutoff

Dataset for Numerical Modelling of Pump-Wavelength Dependence of High Harmonic Generation Efficiency

Dataset to support conference: Samuel M. Senior, William S. Brocklesby, and Peter Horak &quot;Numerical modelling of pump-wavelength dependence of high harmonic generation efficiency&quot;, SPIE Photonics Europe, 6-10 Apr 2020, France; Proc. SPIE 11358, 1135815 (2020). https://doi.org/10.1117/12.2554554 Paper title : &quot;Numerical Modelling of Pump-Wavelength Dependence of High Harmonic Generation Efficiency&quot;. Contained are full capillary simulation and single atom/sheet of atoms datasets for 1 W and 3 W average laser power, with the single atom/sheet of atom datasets being split into a number of sub-datasets. Due to the size of this dataset, approx 47Gb, the files are available on request via the data request web form at https://library.soton.ac.uk/datarequest </span

Ancient retroperitoneal schwannoma imitating seminoma recurrence: A case report

A 28-year-old male with bilateral testicular seminoma underwent bilateral orchiectomy and radiation therapy of the retroperitoneum. After 17 years, he had a retroperitoneal tumor detected, which was removed 7 years later at age 52 because of its progressive enlargement. Due to its partially cystic and partially solid structure, the radiologic findings could not exclude the possibility of regressively altered seminoma metastasis. After radical surgical removal of the tumor, the histopathological and immunohistochemical examination of the tumor revealed ancient schwannoma. These tumors, although unusual, might pose a clinical diagnostic challenge with the risk of undesired overtreatment

Prognostic Value of Apoptosis-Inducing Factor (AIF) in Germ Cell Tumors

Apoptosis is a strictly regulated process essential for preservation of tissue homeostasis. This study aimed to evaluate expression of apoptosis inducing factor (AIF) in testicular germ cell tumors (GCTs) and to correlate expression patterns with clinicopathological variables. Formalin-fixed and paraffin-embedded specimens of non-neoplastic testicular tissue and GCTs obtained from 216 patients were included in the study. AIF expression was detected by immunohistochemistry, scored by the multiplicative quickscore method (QS). Normal testicular tissue exhibits higher cytoplasmic granular expression of AIF compared to GCTs (mean QS = 12.77 vs. 4.80, p p = 0.048). We observed significantly lower AIF expression in GCTs compared to normal testicular tissue, which is an uncommon finding in malignant tumors. AIF downregulation might represent one of the mechanisms of inhibition of apoptosis and promotion of cell survival in GCTs

Functional Reorganization of the Locomotor Network in Parkinson Patients with Freezing of Gait

<div><p>Freezing of gait (FoG) is a transient inability to initiate or maintain stepping that often accompanies advanced Parkinson’s disease (PD) and significantly impairs mobility. The current study uses a multimodal neuroimaging approach to assess differences in the functional and structural locomotor neural network in PD patients with and without FoG and relates these findings to measures of FoG severity. Twenty-six PD patients and fifteen age-matched controls underwent resting-state functional magnetic resonance imaging and diffusion tensor imaging along with self-reported and clinical assessments of FoG. After stringent movement correction, fifteen PD patients and fourteen control participants were available for analysis. We assessed functional connectivity strength between the supplementary motor area (SMA) and the following locomotor hubs: 1) subthalamic nucleus (STN), 2) mesencephalic and 3) cerebellar locomotor region (MLR and CLR, respectively) within each hemisphere. Additionally, we quantified structural connectivity strength between locomotor hubs and assessed relationships with metrics of FoG. FoG+ patients showed greater functional connectivity between the SMA and bilateral MLR and between the SMA and left CLR compared to both FoG− and controls. Importantly, greater functional connectivity between the SMA and MLR was positively correlated with i) clinical, ii) self-reported and iii) objective ratings of freezing severity in FoG+, potentially reflecting a maladaptive neural compensation. The current findings demonstrate a re-organization of functional communication within the locomotor network in FoG+ patients whereby the higher-order motor cortex (SMA) responsible for gait initiation communicates with the MLR and CLR to a greater extent than in FoG− patients and controls. The observed pattern of altered connectivity in FoG+ may indicate a failed attempt by the CNS to compensate for the loss of connectivity between the STN and SMA and may reflect a loss of lower-order, automatic control of gait by the basal ganglia.</p></div