Seasonal prediction skill of winter temperature over North India

This document is the Accepted Manuscript version of the following article: Tiwari, P.R., Kar, S.C., Mohanty, U.C. et al. Theor Appl Climatol (2016) 124: 15. The final publication is available at Springer via https://doi.org/10.1007/s00704-015-1397-y. © Springer-Verlag Wien 2015.The climatology, amplitude error, phase error, and mean square skill score (MSSS) of temperature predictions from five different state-of-the-art general circulation models (GCMs) have been examined for the winter (December–January– February) seasons over North India. In this region, temperature variability affects the phenological development processes of wheat crops and the grain yield. The GCM forecasts of temperature for a whole season issued in November from various organizations are compared with observed gridded temperature data obtained from the India Meteorological Department (IMD) for the period 1982–2009. The MSSS indicates that the models have skills of varying degrees. Predictions of maximum and minimum temperature obtained from the National Centers for Environmental Prediction (NCEP) climate forecast system model (NCEP_CFSv2) are compared with station level observations from the Snow and Avalanche Study Establishment (SASE). It has been found that when the model temperatures are corrected to account the bias in the model and actual orography, the predictions are able to delineate the observed trend compared to the trend without orography correction.Peer reviewedFinal Accepted Versio

Regulation of mammary gland branching morphogenesis by the extracellular matrix and its remodeling enzymes.

A considerable body of research indicates that mammary gland branching morphogenesis is dependent, in part, on the extracellular matrix (ECM), ECM-receptors, such as integrins and other ECM receptors, and ECM-degrading enzymes, including matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs). There is some evidence that these ECM cues affect one or more of the following processes: cell survival, polarity, proliferation, differentiation, adhesion, and migration. Both three-dimensional culture models and genetic manipulations of the mouse mammary gland have been used to study the signaling pathways that affect these processes. However, the precise mechanisms of ECM-directed mammary morphogenesis are not well understood. Mammary morphogenesis involves epithelial 'invasion' of adipose tissue, a process akin to invasion by breast cancer cells, although the former is a highly regulated developmental process. How these morphogenic pathways are integrated in the normal gland and how they become dysregulated and subverted in the progression of breast cancer also remain largely unanswered questions

Concurrence of Danish Dementia and Cataract: Insights from the Interactions of Dementia Associated Peptides with Eye Lens α-Crystallin

Familial Danish Dementia (FDD) is an autosomal disease, which is distinguished by gradual loss of vision, deafness, progressive ataxia and dementia. Cataract is the first manifestation of the disease. In this article, we demonstrate a specific correlation between the poisoning of the chaperone activity of the rat eye lens α-crystallins, loss of lens transparency in organ culture by the pathogenic form of the Danish dementia peptide, i.e. the reduced Danish dementia peptide (redADan peptide), by a combination of ex vivo, in vitro, biophysical and biochemical techniques. The interaction of redADan peptide and lens crystallins are very specific when compared with another chaperone, HSP-70, underscoring the specificity of the pathogenic form of Danish dementia peptide, redADan, for the early onset of cataract in this disease

Role of fried foods and oral/pharyngeal and oesophageal cancers

We investigated the role of fried foods on oral-pharyngeal and oesophageal cancers, using data from two case–control studies conducted in Italy and Switzerland between 1992 and 1999, one with a total of 749 (634 men) cases of oral/pharyngeal cancer and 1772 (1252 men) controls, the other with 395 (351 men) cases of oesophageal cancer and 1066 (875 men) controls. Controls were admitted for acute, non-neoplastic conditions, unrelated to alcohol and smoking consumption. After allowance for sex, age, centre, education, body mass index, tobacco smoking, alcohol drinking and nonalcohol energy intake, the multivariate odds ratios (ORs) for an increment of one portion per week of total fried foods were 1.11 (95% confidence interval (CI): 1.05–1.17) for oral-pharyngeal and 1.16 (95% CI: 1.08–1.26) for oesophageal cancer. The ORs were consistent across strata of gender (OR in men only were 1.10 and 1.16, respectively), age, alcohol, tobacco consumption and body mass index

Invasive Salmonellosis among Children Admitted to a Rural Tanzanian Hospital and a Comparison with Previous Studies

BACKGROUND: The importance of invasive salmonellosis in African children is well recognized but there is inadequate information on these infections. We conducted a fever surveillance study in a Tanzanian rural hospital to estimate the case fraction of invasive salmonellosis among pediatric admissions, examine associations with common co-morbidities and describe its clinical features. We compared our main findings with those from previous studies among children in sub-Saharan Africa. METHODOLOGY/PRINCIPAL FINDINGS: From 1 March 2008 to 28 Feb 2009, 1,502 children were enrolled into the study. We collected clinical information and blood for point of care tests, culture, and diagnosis of malaria and HIV. We analyzed the clinical features on admission and outcome by laboratory-confirmed diagnosis. Pathogenic bacteria were isolated from the blood of 156 (10%) children, of which 14 (9%) were S. typhi, 45 (29%) were NTS and 97 (62%) were other pathogenic bacteria. Invasive salmonellosis accounted for 59/156 (38%) bacteremic children. Children with typhoid fever were significantly older and presented with a longer duration of fever. NTS infections were significantly associated with prior antimalarial treatment, malarial complications and with a high risk for death. CONCLUSIONS/SIGNIFICANCE: Invasive salmonellosis, particularly NTS infection, is an important cause of febrile disease among hospitalized children in our rural Tanzanian setting. Previous studies showed considerable variation in the case fraction of S. typhi and NTS infections. Certain suggestive clinical features (such as older age and long duration of fever for typhoid whereas concomitant malaria, anemia, jaundice and hypoglycemia for NTS infection) may be used to distinguish invasive salmonellosis from other severe febrile illness

GX15-070 (obatoclax) overcomes glucocorticoid resistance in acute lymphoblastic leukemia through induction of apoptosis and autophagy

Glucocorticoids (GCs) are common components of many chemotherapeutic regimens for lymphoid malignancies including acute lymphoblastic leukemia (ALL). The BCL-2 family has an essential role in regulating GC-induced cell death. Here we show that downregulation of antiapoptotic BCL-2 family proteins, especially MCL-1, enhances GC-induced cell death. Thus we target MCL-1 by using GX15-070 (obatoclax) in ALL cells. Treatment with GX15-070 in both dexamethasone (Dex)-sensitive and -resistant ALL cells shows effective growth inhibition and cell death. GX15-070 induces caspase-3 cleavage and increases the Annexin V-positive population, which is indicative of apoptosis. Before the onset of apoptosis, GX15-070 induces LC3 conversion as well as p62 degradation, both of which are autophagic cell death markers. A pro-apoptotic molecule BAK is released from the BAK/MCL-1 complex following GX15-070 treatment. Consistently, downregulation of BAK reduces caspase-3 cleavage and cell death, but does not alter LC3 conversion. In contrast, downregulation of ATG5, an autophagy regulator, decreases LC3 conversion and cell death, but does not alter caspase-3 cleavage, suggesting that apoptosis and autophagy induced by GX15-070 are independently regulated. Downregulation of Beclin-1, which is capable of crosstalk between apoptosis and autophagy, affects GX15-070-induced cell death through apoptosis but not autophagy. Taken together, GX15-070 treatment in ALL could be an alternative regimen to overcome glucocorticoid resistance by inducing BAK-dependent apoptosis and ATG5-dependent autophagy

Progressive dry-core-wet-rim hydration trend in a nested-ring topology of protein binding interfaces

<p>Abstract</p> <p>Background</p> <p>Water is an integral part of protein complexes. It shapes protein binding sites by filling cavities and it bridges local contacts by hydrogen bonds. However, water molecules are usually not included in protein interface models in the past, and few distribution profiles of water molecules in protein binding interfaces are known.</p> <p>Results</p> <p>In this work, we use a tripartite protein-water-protein interface model and a nested-ring atom re-organization method to detect hydration trends and patterns from an interface data set which involves immobilized interfacial water molecules. This data set consists of 206 obligate interfaces, 160 non-obligate interfaces, and 522 crystal packing contacts. The two types of biological interfaces are found to be drier than the crystal packing interfaces in our data, agreeable to a hydration pattern reported earlier although the previous definition of immobilized water is pure distance-based. The biological interfaces in our data set are also found to be subject to stronger water exclusion in their formation. To study the overall hydration trend in protein binding interfaces, atoms at the same burial level in each tripartite protein-water-protein interface are organized into a ring. The rings of an interface are then ordered with the core atoms placed at the middle of the structure to form a nested-ring topology. We find that water molecules on the rings of an interface are generally configured in a dry-core-wet-rim pattern with a progressive level-wise solvation towards to the rim of the interface. This solvation trend becomes even sharper when counterexamples are separated.</p> <p>Conclusions</p> <p>Immobilized water molecules are regularly organized in protein binding interfaces and they should be carefully considered in the studies of protein hydration mechanisms.</p

Trypanosoma brucei PUF9 Regulates mRNAs for Proteins Involved in Replicative Processes over the Cell Cycle

Many genes that are required at specific points in the cell cycle exhibit cell cycle–dependent expression. In the early-diverging model eukaryote and important human pathogen Trypanosoma brucei, regulation of gene expression in the cell cycle and other processes is almost entirely post-transcriptional. Here, we show that the T. brucei RNA-binding protein PUF9 stabilizes certain transcripts during S-phase. Target transcripts of PUF9—LIGKA, PNT1 and PNT2—were identified by affinity purification with TAP-tagged PUF9. RNAi against PUF9 caused an accumulation of cells in G2/M phase and unexpectedly destabilized the PUF9 target mRNAs, despite the fact that most known Puf-domain proteins promote degradation of their target mRNAs. The levels of the PUF9-regulated transcripts were cell cycle dependent, peaking in mid- to late- S-phase, and this effect was abolished when PUF9 was targeted by RNAi. The sequence UUGUACC was over-represented in the 3′ UTRs of PUF9 targets; a point mutation in this motif abolished PUF9-dependent stabilization of a reporter transcript carrying the PNT1 3′ UTR. LIGKA is involved in replication of the kinetoplast, and here we show that PNT1 is also kinetoplast-associated and its over-expression causes kinetoplast-related defects, while PNT2 is localized to the nucleus in G1 phase and redistributes to the mitotic spindle during mitosis. PUF9 targets may constitute a post-transcriptional regulon, encoding proteins involved in temporally coordinated replicative processes in early G2 phase

Cost-Effectiveness of Intermittent Preventive Treatment of Malaria in Pregnancy in Southern Mozambique

BACKGROUND: Malaria in pregnancy is a public health problem for endemic countries. Economic evaluations of malaria preventive strategies in pregnancy are needed to guide health policies. METHODS AND FINDINGS: This analysis was carried out in the context of a trial of malaria intermittent preventive treatment in pregnancy with sulphadoxine-pyrimethamine (IPTp-SP), where both intervention groups received an insecticide treated net through the antenatal clinic (ANC) in Mozambique. The cost-effectiveness of IPTp-SP on maternal clinical malaria and neonatal survival was estimated. Correlation and threshold analyses were undertaken to assess the main factors affecting the economic outcomes and the cut-off values beyond which the intervention is no longer cost-effective. In 2007 US$, the incremental cost-effectiveness ratio (ICER) for maternal malaria was 41.46 US$ (95% CI 20.5, 96.7) per disability-adjusted life-year (DALY) averted. The ICER per DALY averted due to the reduction in neonatal mortality was 1.08 US$(95$ (95% CI 0.42, 3.21) per DALY averted. Efficacy was the main factor affecting the economic evaluation of IPTp-SP. The intervention remained cost-effective with an increase in drug cost per dose up to 11 times in the case of maternal malaria and 183 times in the case of neonatal mortality. CONCLUSIONS: IPTp-SP was highly cost-effective for both prevention of maternal malaria and reduction of neonatal mortality in Mozambique. These findings are likely to hold for other settings where IPTp-SP is implemented through ANC visits. The intervention remained cost-effective even with a significant increase in drug and other intervention costs. Improvements in the protective efficacy of the intervention would increase its cost-effectiveness. Provision of IPTp with a more effective, although more expensive drug than SP may still remain a cost-effective public health measure to prevent malaria in pregnancy. TRIAL REGISTRATION: ClinicalTrials.gov NCT00209781