RNA-binding proteins play a key role in post-transcriptional regulation of mRNA stability and translation. We have identified that RBM3, a translation regulatory protein, is significantly upregulated ...in human tumors, including a stage-dependent increase in colorectal tumors. Forced RBM3 overexpression in NIH3T3 mouse fibroblasts and SW480 human colon epithelial cells increases cell proliferation and development of compact multicellular spheroids in soft agar suggesting the ability to induce anchorage-independent growth. In contrast, downregulating RBM3 in HCT116 colon cancer cells with specific siRNA decreases cell growth in culture, which was partially overcome when treated with prostaglandin E(2), a product of cyclooxygenase (COX)-2 enzyme activity. Knockdown also resulted in the growth arrest of tumor xenografts. We have also identified that RBM3 knockdown increases caspase-mediated apoptosis coupled with nuclear cyclin B1, and phosphorylated Cdc25c, Chk1 and Chk2 kinases, implying that under conditions of RBM3 downregulation, cells undergo mitotic catastrophe. RBM3 enhances COX-2, IL-8 and VEGF mRNA stability and translation. Conversely, RBM3 knockdown results in loss in the translation of these transcripts. These data demonstrate that the RNA stabilizing and translation regulatory protein RBM3 is a novel proto-oncogene that induces transformation when overexpressed and is essential for cells to progress through mitosis.
Summary Background Sepsis is one of the most common causes of neonatal deaths globally. Most sepsis-related deaths occur in low-income and middle-income countries, where the epidemiology of neonatal ...sepsis remains poorly understood. Most of these countries lack proper surveillance networks, hampering accurate assessment of the burden of sepsis, implementation of preventive measures, and investment in research. We report results of neonates born in hospital from a multicentre collaboration on neonatal sepsis. Methods In this cohort study, dedicated research teams prospectively followed up neonates born in one of three tertiary care centres in Delhi, India (Vardhaman Mahavir Medical College, Maulana Azad Medical College, and All India Institute of Medical Sciences coordinating centre) and subsequently admitted to the intensive care unit. Neonates were followed up daily until discharge or death. On clinical suspicion, neonates underwent sepsis work-up including blood cultures. The isolated organisms were identified and tested for antimicrobial susceptibility. We defined Gram-negative isolates resistant to any three of five antibiotic classes (extended-spectrum cephalosporins, carbapenems, aminoglycosides, fluoroquinolones, and piperacillin-tazobactam) as multidrug resistant. Findings 13 530 neonates of 88 636 livebirths were enrolled between July 18, 2011, and Feb 28, 2014. The incidence of total sepsis was 14·3% (95% CI 13·8–14·9) and of culture-positive sepsis was 6·2% (5·8–6·6). Nearly two-thirds of total episodes occurred at or before 72 h of life (defined as early onset; 1351 83% of 1980). Two-thirds (645 64%) of 1005 isolates were Gram-negative including, Acinetobacter spp (22%), Klebsiella spp (17%), and Escherichia coli (14%). The pathogen mix in early-onset sepsis did not differ from that of late-onset sepsis (ie, after 72 h). High rates of multidrug resistance were observed in Acinetobacter spp (181/222, 82%), Klebsiella spp (91/169, 54%), and Escherichia coli (52/137, 38%) isolates. Meticillin resistance prevailed in 61% (85/140) of coagulase-negative staphylococci and 38% (43/114) of Staphylococcus aureus i solates. Nearly a quarter of the deaths were attributable to sepsis. The population-attributable risks of mortality were 8·6% in culture-negative sepsis, 15·7% in culture-positive sepsis by multidrug-resistant organisms, and 12·0% in culture-positive sepsis by non-multidrug-resistant organisms. Interpretation The high incidence of sepsis and alarming degree of antimicrobial resistance among pathogens in neonates born in tertiary hospitals underscore the need to understand the pathogenesis of early-onset sepsis and to devise measures to prevent it in low-income and middle-income countries. Funding Indian Council of Medical Research.
The objective of our study was to determine the clinical and MRI characteristics of clinically significant prostate cancer (PCA) (Gleason score ≥ 3 + 4) in men with Prostate Imaging Reporting and ...Data System version 2 (PI-RADSv2) category 3 transition zone (TZ) lesions.
From 2014 to 2016, 865 men underwent prostate MRI and MRI/ultrasound (US) fusion biopsy (FB). A subset of 90 FB-naïve men with 96 PI-RADSv2 category 3 TZ lesions was identified. Patients were imaged at 3 T using a body coil. Images were assigned a PI-RADSv2 category by an experienced radiologist. Using clinical data and imaging features, we performed univariate and multivariate analyses to identify predictors of clinically significant PCA.
The mean patient age was 66 years, and the mean prostate-specific antigen density (PSAD) was 0.13 ng/mL
. PCA was detected in 34 of 96 (35%) lesions, 14 of which (15%) harbored clinically significant PCA. In univariate analysis, DWI score, prostate volume, and PSAD were significant predictors (p < 0.05) of clinically significant PCA with a suggested significance for apparent diffusion coefficient (ADC) and prostate-specific antigen value (p < 0.10). On multivariate analysis, PSAD and lesion ADC were the most important covariates. The combination of both PSAD of 0.15 ng/mL
or greater and an ADC value of less than 1000 mm
/s yielded an AUC of 0.91 for clinically significant PCA (p < 0.001). If FB had been restricted to these criteria, only 10 of 90 men would have undergone biopsy, resulting in diagnosis of clinically significant PCA in 60% with eight men (9%) misdiagnosed (false-negative).
The yield of FB in men with PI-RADSv2 category 3 TZ lesions for clinically significant PCA is 15% but significantly improves to 60% (AUC > 0.9) among men with PSAD of 0.15 ng/mL
or greater and lesion ADC value of less than 1000 mm
/s.
Tremendous benefits have been derived from the use of fungicides but excessive use of chemical fungicides not only posing threat to human and animal life but also contaminates the prevailing ...environment. Damage by pathogenic fungi alone causes significant damage to crops like maize, rice, wheat, soybeans, and potatoes. Therefore, it becomes imperative that these diseases are checked and controlled, for which chemical pesticides are being sprayed on plants extensively. Considering the devastating damage and toxicity, the global focus has taken a drift from synthetic chemicals to nature-friendly biological control agents. The present study focuses on the use of biological control agents particularly
Trichoderma
in sugarcane during Pokkah boeng infection. In the present experiment, twenty promising
Trichoderma
strains were evaluated for plant growth promotion, lytic enzymes, and physiological and biocontrol activity. Out of the twenty, four potential
Trichoderma
strains were assessed in the pot experiment viz.
T. harzianum
strain T28, T41 and T49 and
T. aureoviride
strain T38. The
T. harzianum
(T28) showed efficient plant growth-promoting traits as it produced IAA (20.67 µg/ml), phosphorus solubilization (18.57 µg/ml), and cell wall degrading enzymes such as chitinase (24.98 µg/ml) and β-glucanase (29.98 µg/ml). The interference of biocontrol agent
T. harzianum
(T28) controlled the disease by 73.55%. Apart from this, the inoculation of
Trichoderma
(T28) enhanced growth attributes including germination percentage (26.61%), mean tiller number (8.28 tiller/pot), individual cane length (241.5 cm), single cane weight (1.13 kg) and the number of milleable canes (6.00 cane/pot). Improvements in physiological activities at different growth stages of the sugarcane crop were observed based on the photosynthetically active radiation (PAR) on the leaf surface, transpiration rate, stomatal conductance, and photosynthetic rate. Further, improvement in juice quality parameters was also observed as it recorded the highest
0
brix, sucrose, and commercial cane sugar by 21.26%, 19.28%, and 13.50%, respectively, by applying
T. harzianum
strain T28. Thus, results proved that
T. harzianum
strain T28 may be an effective eco-friendly biocontrol tool for managing Pokkah boeng disease in sugarcane. This is the first report of the biocontrol potential of
Trichoderma
spp. against
Fusarium proliferatum
causing Pokkah boeng disease in sugarcane.
EBV-associated post-transplant lymphoproliferative disease (PTLD) following Alemtuzumab-based allo-SCT is a relatively uncommon and challenging clinical problem but has not received detailed study in ...a large cohort. Quantitative-PCR (qPCR) monitoring for EBV reactivation post allo-SCT is now commonplace but its diagnostic and predictive value remains unclear. Sixty-nine patients with PTLD following Alemtuzumab-based allo-SCT were studied. Marked clinicopathological heterogeneity was evident; lymphadenopathy was frequently absent, whereas advanced extranodal disease was common. The median viral load at clinical presentation was 49 300 copies/mL (50-65 200 000 copies/mL) and, notably, 23% and 45% of cases, respectively, had 10 000 and 40 000 copies/mL. The overall response rate to rituximab as first-line therapy was 70%. For rituximab failures, chemotherapy was ineffectual but DLIs were successful. A four-parameter prognostic index predicted response to therapy (OR 0.30 (0.12-0.74); P=0.009 and PTLD mortality (hazard ratio (HR) 1.81 (1.12-2.93) P=0.02) on multivariate analysis. This is the largest detailed series of EBV-associated PTLD after allo-SCT. At clinical presentation, EBV-qPCR values are frequently below customary thresholds for pre-emptive therapy, challenging current paradigms for monitoring and intervention. A four-point score identifies a proportion of patients at risk of rituximab-refractory disease for whom alternative therapy is needed.
Bounds on the hop domination number of a tree AYYASWAMY, S K; KRISHNAKUMARI, B; NATARAJAN, C ...
Proceedings of the Indian Academy of Sciences. Mathematical sciences,
11/2015, Letnik:
125, Številka:
4
Journal Article
Recenzirano
A hop dominating set of a graph
G
is a set
D
of vertices of
G
if for every vertex of
V
(
G
)∖
D
, there exists
u
∈
D
such that
d
(
u
,
v
)=2. The hop domination number of a graph
G
, denoted by
γ
h
(
...G
), is the minimum cardinality of a hop dominating set of
G
. We prove that for every tree
T
of order
n
with
l
leaves and
s
support vertices we have (
n
−
l
−
s
+4)/3≤
γ
h
(
G
)≤
n
/2, and characterize the trees attaining each of the bounds.
Plasma sprayed coatings have been considered as one of the important surface modification processes to improve the tribological properties of materials used in extreme conditions. NiCrBSi composite ...coatings on stainless steel are known to offer good abrasive wear resistance in service conditions. Graphite is the material which has many potential advantages when processed and used in different forms. This paper describes the effect of graphite addition on the microstructure; hardness and abrasive wear behavior of plasma sprayed NiCrBSi coatings. The mechanical and tribological properties of the coatings can be significantly improved by refinement of grain structure of the coatings. The XRD results show that the NiCrBSi–graphite composite coatings are mainly composed of γ-Ni, CrB and Cr7C3. With addition of graphite, phases such as CrB, Cr7C3 emerge in composite coating. The study was conducted, using an abrasive wear test rig according to ASTM G65 on uncoated as well as coated SS304 samples at room temperature. The samples were analyzed for volume loss and wear rate with respect to increasing content of graphite in the coatings. The results suggest that addition of graphite in the coatings resulted in reduction of volume loss and wear rate significantly. The NiCrBSi–8 wt %C composite coating presents excellent abrasion resistance.
•Effect of graphite on microstructure, hardness & abrasive wear of NiCrBSi coatings investigated.•XRD analysis reveals coatings are composed of γ-Ni, CrB & Cr7C3.•Graphite addition in thermal spray coatings improve wear resistance.•NiCrBSi–8 wt % C coating has excellent abrasion resistance.
The interactions of ruthenium(II) complex with Glucose inhibited division protein A (GidA protein) was studied through various spectroscopic techniques with the ultimate goal of preparing adducts ...with good selectivity for cancer cells. In all the cases, formation of a tight metal-protein conjugate was observed. The influence of pH, reducing agents and chelators on the formation of adduct was analysed by UV- visible spectroscopy. While there was no effect on the addition of sodium ascorbate, some alterations on some selected bands were seen on the UV-visible spectra on the addition of EDTA. The adduct was stable in the pH range of 5-8. Addition of ruthenium(II) complex effectively quenched the intrinsic fluorescence of GidA and it occurred through static quenching. The effect of ruthenium(II) complex on the conformation of GidA has been examined by analyzing CD spectrum. Though, there was some conformational changes observed in the presence of ruthenium(II) complex, α- helix in the secondary structure of GidA retained its identity. Molecular docking of ruthenium(II) complex with GidA also indicated that GidA docks through hydrophobic interaction. The stable semisynthetic complex (ruthenium(II) complex with GidA) was checked for topoisomerase II inhibition. Relaxation and decatenation assay proved topoisomerase II inhibition of semisynthetic complex.
Communicated by Ramaswamy H. Sarma
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