Modeling X-chromosome inactivation and reactivation during human development

Stem-cell-based embryo models generate much excitement as they offer a window into an early phase of human development that has remained largely inaccessible to scientific investigation. An important epigenetic phenomenon during early embryogenesis is the epigenetic silencing of one of the two X chromosomes in female embryos, which ensures an equal output of X-linked gene expression between the sexes. X-chromosome inactivation (XCI) is thought to be established within the first three weeks of human development, although the inactive X-chromosome is reactivated in primordial germ cells (PGCs) that migrate to the embryonic gonads. Here, we summarize our current understanding of X-chromosome dynamics during human development and comment on the potential of recently established stem-cell-based models to reveal the underlying mechanisms

Diagnosis of Faulty Elements in Array Antenna using Nature Inspired Cuckoo Search Algorithm

Detection and correction of faulty elements in a linear array have great importance in radar, sonar, mobile communications and satellite. Due to single element failure, the whole radiation pattern damage in terms of side lobes level and nulls. Once we have detect the position of defective element, then correction method is applied to achieve the desired pattern. In this work, we introduce a nature inspired meta-heuristic cuckoo search algorithm to diagnose the position of defective elements in a linear array. The nature inspired cuckoo search algorithm is new to the optimization family and is used first time for fault detection in an array antenna. Cuckoo search algorithm is a global search optimization technique. The cost function is used as a fitness function which defines an error between the degraded far field power pattern and the estimated one. The proposed technique is used effectively for the diagnosis of complete, as well as, for partial faulty elements position. Different simulation results are evaluated for 40 elements Taylor pattern to validate and check the performance of the proposed technique

Diagnosis of Faulty Sensors in Antenna Array using Hybrid Differential Evolution based Compressed Sensing Technique

In this work, differential evolution based compressive sensing technique for detection of faulty sensors in linear arrays has been presented. This algorithm starts from taking the linear measurements of the power pattern generated by the array under test. The difference between the collected compressive measurements and measured healthy array field pattern is minimized using a hybrid differential evolution (DE). In the proposed method, the slow convergence of DE based compressed sensing technique is accelerated with the help of parallel coordinate decent algorithm (PCD). The combination of DE with PCD makes the  minimization faster and precise. Simulation results validate the performance to detect faulty sensors from a small number of measurements

PO10.19 clinical spectrum of pseudo seizures at a tertiary care hospital Karachi: a video EEG based study

Background: Nonepileptic seizures are involuntary episodes of movement, sensation, or behaviors (e.g., vocalization, crying and other expressions of emotion), that do not result from abnormal cortical discharges. The events typically occur in teenage patients with anxiety and affective disorders. Psychotherapy, behavioral therapy, drugs, hypnosis and placebo are mainstay of treatment. There is no published data on clinical characteristics of pseudo-seizures from Pakistan. The objective of our study is to describe the clinical characteristics of pseudoseizures in a tertiary care hospital in Karachi, Pakistan. Methods: This is a descriptive study. Patients with pseudo-seizures were identified from departmental Video EEG monitoring register, over a period of three years (2004 2006). Their neurophysiologic and video recording data was reviewed and their demographic, clinical and neurophysiologic data was recorded and analyzed. SPSS version 15.0 was used for analysis. Results: A total of 132 patients underwent video EEG during the period and 51 (38%) had pseudo-seizures. Their mean age was 26.7±15.3 years. Thirty-two (63%) were female and 19 (37%) were male. Twelve (23.5%) patients were known epileptics. Median recording time was 24 (range; 0.33 55) hours and median number of events was 3 (range; 1 14). Limb movements were most common manifestation (67%) followed by muteness with no response to verbal commands (49%), behavioral symptoms (35.5%), ocular findings i.e. eye blinking and closure (25.5%), depressed conscious level (13.7%), headache (10%) and GI symptoms (10%). Six (11.8%) patients experienced epileptic seizures, in addition to pseudo-seizures. Conclusions: Pseudo-seizures are common in patients referred for video EEG monitoring. It is more common in young women. Limb movements, muteness and behavioral symptoms are most common manifestations. The pseudo-seizures and epileptic seizures may coexist in the same patient

Climate Change and Citrus

Climate change is the change in the statistical distribution of weather patterns that lasts for an extended period. Climate change and agriculture are interrelated processes and affect in many ways. Citrus fruits are one of the largest fruit crops in the world. Yield loss at a drastic level due to abiotic stress annually in which temperature and water stress are the main environmental factors. These factors cause biochemical, anatomical, physiological, and genetic changes in plant structure and lead to defective growth, development, and reproduction, which ultimately cause a reduction in the economic yield of the crop. An increase in temperature and water stress at critical phenological stages of citrus results in reduced tree fruit set, decrease in fruit growth and size, increase in fruit acidity, low tree yield, reduced fruit peel thickness, and pre-harvest fruit drop. Stomatal conductance and net carbon dioxide assimilation in citrus leaves can be reduced by super optimal leaf temperature. Water deficit reduces the transpiration rate, stomatal conductance by stomatal closure associated with ABA content and causes an abrupt decrease in photosynthesis and CO2 assimilation in citrus which reduce trees overall growth and production. Interventions in agronomic practices, breeding strategies, and biotechnological approaches can mitigate climate change effects on citrus. The groundwork against climate change is compulsory for better global livelihood and food security

Investigation of japanese encephalitis virus as a cause of acute encephalitis in southern Pakistan, april 2015-january 2018

Background: Japanese encephalitis (JE) occurs in fewer than 1% of JE virus (JEV) infections, often with catastrophic sequelae including death and neuropsychiatric disability. JEV transmission in Pakistan was documented in 1980s and 1990s, but recent evidence is lacking. Our objective was to investigate JEV as a cause of acute encephalitis in Pakistan.Methods: Persons aged ≥1 month with possible JE admitted to two acute care hospitals in Karachi, Pakistan from April 2015 to January 2018 were enrolled. Cerebrospinal fluid (CSF) or serum samples were tested for JEV immunoglobulin M (IgM) using the InBios JE DetectTM assay. Positive or equivocal samples had confirmatory testing using plaque reduction neutralization tests.Results: Among 227 patients, testing was performed on CSF in 174 (77%) and on serum in 53 (23%) patients. Six of eight patient samples positive or equivocal for JEV IgM had sufficient volume for confirmatory testing. One patient had evidence of recent West Nile virus (WNV) neurologic infection based on CSF testing. One patient each had recent dengue virus (DENV) infection and WNV infection based on serum results. Recent flavivirus infections were identified in two persons, one each based on CSF and serum results. Specific flaviviruses could not be identified due to serologic cross-reactivity. For the sixth person, JEV neutralizing antibodies were confirmed in CSF but there was insufficient volume for further testing.Conclusions: Hospital-based JE surveillance in Karachi, Pakistan could not confirm or exclude local JEV transmission. Nonetheless, Pakistan remains at risk for JE due to presence of the mosquito vector, amplifying hosts, and rice irrigation. Laboratory surveillance for JE should continue among persons with acute encephalitis. However, in view of serological cross-reactivity, confirmatory testing of JE IgM positive samples at a reference laboratory is essential

Coevolved mutations reveal distinct architectures for two core proteins in the bacterial flagellar motor

Switching of bacterial flagellar rotation is caused by large domain movements of the FliG protein triggered by binding of the signal protein CheY to FliM. FliG and FliM form adjacent multi-subunit arrays within the basal body C-ring. The movements alter the interaction of the FliG C-terminal (FliGC) "torque" helix with the stator complexes. Atomic models based on the Salmonella entrovar C-ring electron microscopy reconstruction have implications for switching, but lack consensus on the relative locations of the FliG armadillo (ARM) domains (amino-terminal (FliGN), middle (FliGM) and FliGC) as well as changes during chemotaxis. The generality of the Salmonella model is challenged by the variation in motor morphology and response between species. We studied coevolved residue mutations to determine the unifying elements of switch architecture. Residue interactions, measured by their coevolution, were formalized as a network, guided by structural data. Our measurements reveal a common design with dedicated switch and motor modules. The FliM middle domain (FliMM) has extensive connectivity most simply explained by conserved intra and inter-subunit contacts. In contrast, FliG has patchy, complex architecture. Conserved structural motifs form interacting nodes in the coevolution network that wire FliMM to the FliGC C-terminal, four-helix motor module (C3-6). FliG C3-6 coevolution is organized around the torque helix, differently from other ARM domains. The nodes form separated, surface-proximal patches that are targeted by deleterious mutations as in other allosteric systems. The dominant node is formed by the EHPQ motif at the FliMMFliGM contact interface and adjacent helix residues at a central location within FliGM. The node interacts with nodes in the N-terminal FliGc α-helix triad (ARM-C) and FliGN. ARM-C, separated from C3-6 by the MFVF motif, has poor intra-network connectivity consistent with its variable orientation revealed by structural data. ARM-C could be the convertor element that provides mechanistic and species diversity.JK was supported by Medical Research Council grant U117581331. SK was supported by seed funds from Lahore University of Managment Sciences (LUMS) and the Molecular Biology Consortium

Physical activity, smoking, and genetic predisposition to obesity in people from Pakistan:the PROMIS study

Background: Multiple genetic variants have been reliably associated with obesity-related traits in Europeans, but little is known about their associations and interactions with lifestyle factors in South Asians. Methods: In 16,157 Pakistani adults (8232 controls; 7925 diagnosed with myocardial infarction [MI]) enrolled in the PROMIS Study, we tested whether: a) BMI-associated loci, individually or in aggregate (as a genetic risk score - GRS), are associated with BMI; b) physical activity and smoking modify the association of these loci with BMI. Analyses were adjusted for age, age(2), sex, MI (yes/no), and population substructure. Results: Of 95 SNPs studied here, 73 showed directionally consistent effects on BMI as reported in Europeans. Each additional BMI-raising allele of the GRS was associated with 0.04 (SE = 0.01) kg/m(2) higher BMI (P = 4.5 x 10(-14)). We observed nominal evidence of interactions of CLIP1 rs11583200 (P-interaction = 0.014), CADM2 rs13078960 (P-interaction = 0.037) and GALNT10 rs7715256 (P-interaction = 0.048) with physical activity, and PTBP2 rs11165643 (P-interaction = 0.045), HIP1 rs1167827 (P-interaction = 0.015), C6orf106 rs205262 (P-interaction = 0.032) and GRID1 rs7899106 (P-interaction = 0.043) with smoking on BMI. Conclusions: Most BMI-associated loci have directionally consistent effects on BMI in Pakistanis and Europeans. There were suggestive interactions of established BMI-related SNPs with smoking or physical activity

Mapping geographical inequalities in access to drinking water and sanitation facilities in low-income and middle-income countries, 2000-17

Background: Universal access to safe drinking water and sanitation facilities is an essential human right, recognised in the Sustainable Development Goals as crucial for preventing disease and improving human wellbeing. Comprehensive, high-resolution estimates are important to inform progress towards achieving this goal. We aimed to produce high-resolution geospatial estimates of access to drinking water and sanitation facilities. Methods: We used a Bayesian geostatistical model and data from 600 sources across more than 88 low-income and middle-income countries (LMICs) to estimate access to drinking water and sanitation facilities on continuous continent-wide surfaces from 2000 to 2017, and aggregated results to policy-relevant administrative units. We estimated mutually exclusive and collectively exhaustive subcategories of facilities for drinking water (piped water on or off premises, other improved facilities, unimproved, and surface water) and sanitation facilities (septic or sewer sanitation, other improved, unimproved, and open defecation) with use of ordinal regression. We also estimated the number of diarrhoeal deaths in children younger than 5 years attributed to unsafe facilities and estimated deaths that were averted by increased access to safe facilities in 2017, and analysed geographical inequality in access within LMICs. Findings: Across LMICs, access to both piped water and improved water overall increased between 2000 and 2017, with progress varying spatially. For piped water, the safest water facility type, access increased from 40·0% (95% uncertainty interval [UI] 39·4–40·7) to 50·3% (50·0–50·5), but was lowest in sub-Saharan Africa, where access to piped water was mostly concentrated in urban centres. Access to both sewer or septic sanitation and improved sanitation overall also increased across all LMICs during the study period. For sewer or septic sanitation, access was 46·3% (95% UI 46·1–46·5) in 2017, compared with 28·7% (28·5–29·0) in 2000. Although some units improved access to the safest drinking water or sanitation facilities since 2000, a large absolute number of people continued to not have access in several units with high access to such facilities (>80%) in 2017. More than 253 000 people did not have access to sewer or septic sanitation facilities in the city of Harare, Zimbabwe, despite 88·6% (95% UI 87·2–89·7) access overall. Many units were able to transition from the least safe facilities in 2000 to safe facilities by 2017; for units in which populations primarily practised open defecation in 2000, 686 (95% UI 664–711) of the 1830 (1797–1863) units transitioned to the use of improved sanitation. Geographical disparities in access to improved water across units decreased in 76·1% (95% UI 71·6–80·7) of countries from 2000 to 2017, and in 53·9% (50·6–59·6) of countries for access to improved sanitation, but remained evident subnationally in most countries in 2017. Interpretation: Our estimates, combined with geospatial trends in diarrhoeal burden, identify where efforts to increase access to safe drinking water and sanitation facilities are most needed. By highlighting areas with successful approaches or in need of targeted interventions, our estimates can enable precision public health to effectively progress towards universal access to safe water and sanitation