Search

Abstract Many efforts have been made by the scientific community to produce gridded datasets with high spatial resolution because they are essential for climate change assessment, impact studies, decision‐making, etc. This study fits into this context and describes the methods used to prepare a 5‐km gridded product of precipitation and minimum and maximum temperatures by merging observed data from meteorological stations, from 1981 to 2016, of Bangladesh, Nepal, and Pakistan with ERA5 reanalysis. The step‐by‐step methods for station data quality control and the development of the 5‐km gridded data are presented. Additionally, we use the 5‐km dataset to show the main climate features of the three countries, which facilitate comparison with other data sources in the literature.

Abstract Background Cyclodextrins offer a range of biomedical applications in the pharmaceutical and biotechnology industries. Cyclodextrins (CDs) are oligosaccharides composed of glucose as repeating units (6–9 repeating units given terms α, β, γ and δ, respectively). Its inner core size varies with the type of CD, and this variation finds its fitness with small- to larger-sized organic drug molecules to resolve its delivery problems. Employment of CDs in drug delivery was conceptualized since its initial development (Year 1891). However, the very first pharmaceutical product was in the market in 1976. CDs not only act as carrier or as self-assembly hydrogel or hybrid gels for delivery of hydrophobic drugs but also reported as a modifier of the gelling temperature of agarose and make it suitable for drug delivery. Main body This review represents the trend of research on CDs with reference to drug delivery. Phase I (1975–1980) CD research trend shows inclination towards β-CD molecules for inclusion complex with a wide range of drugs. Decade of phase II (1981–1990) worked majorly on other natural CDs with a glimpse of its derivative for drug delivery system. Critical literature surveys from the years 1991–2000 (phase III) provide research visualization of CD derivatives supported with animal studies. Phase IV (2001–2010) can be attributed as the golden period of CDs with its extreme exploitation in many novel drug delivery systems (aerosols, microemulsion, polymeric nanoparticles, osmotic pumps, and sustain release), while in most last decade CDs were observed in association with nanoscale systems. Conclusions In the view of its incessant utilization in wider applications including drug carrier, gel, gel modifier and nano-composite modifier properties, its chronicle update in the drug delivery knowledge database would inspire the researchers for multidisciplinary research. To sum up, almost every emerging novel drug delivery system in the near future will make the earnest effort to take advantage of the properties of CDs for their better efficacy, stability, prevention of toxicity and patient acceptability.

Developing highly efficient biocatalyst is a pertinent requirement for biofuels production, in particularly biodiesel/bioethanol. To circumvent the minimal efficiency of conventionally used biocatalysts, nanotechnology paves a way by indulging nanoparticles as carriers of biocatalysts. The nanobiocatalysts so formed are applied as a tool for utilizing wide set of biomass related molecules into biofuels. The disadvantages of conventional biocatalysts such as catalyst deactivation, mass transfer, poisoning, and long reaction time can be outstripped by novel nanobiocatalysts. Nanobiocatalyst increases the catalytic activity; and this higher activity is because of the increased surface to volume ratio and hence it can act as a deoxygenation catalyst too. In recent years, exploiting modern tools for nanoparticles synthesis and characterization yielded high quality optimized and conditioned nanocatalyst systems such as metal oxide nanoparticles, magnetic nanoparticles, and carbon nanotubes to increase the biofuel productivity. Nanomaterial immobilized lipases and cellulases are predictably innovative catalysts having remarkable properties. The present article is critically discussed various nanomaterial immobilized enzyme development and its influence over production of biofuel. Continuous research and development and novel nanobiocatalyst engineering is essential for stabilization of biofuel producing companies.

Global energy demand is increased with the rapidly growing population; and it is fulfilled by fossil fuels. However, it also contributes to the greenhouse gas effect in the environment. In recent years, the rapid consumption of fossil fuels has resulted in its depletion, which raised the questions concerning the environment safety. The lignocellulosic biomass has emerged as an alternative solution for these problems. The lignocellulosic biomass is abundantly present on the earth, which can be transformed into bioethanol and/or biochemical products after some suitable pre-treatment methods include physical, chemical and biological methods. But these approaches have certain limitations as they are expensive and inconvenient. These limitations have been overcome by developing a new alternative novel, cost-effective, efficient and eco-friendly method i.e. nanotechnology which offers promising solution to the existing pre-treatment methods. In this review, various conventional pre-treatment methods and evolving nanobiotechnological routes in lignocellulosic pretreatment methods are critically discussed.

Introduction: A neurological consultation is needed in nearly 45% of patients suffering from cancer. The present study was planned to evaluate the clinical, radiological and histopathological spectrum of patients with an underlying malignancy and presenting with a neurological complaint. Materials and Methods: We prospectively evaluated all patients provisionally diagnosed either with a primary or secondary malignancy of the brain on the basis of clinical, radiological and/or histopathological features. Results: A total of 155 patients were enrolled from a total of 4893 admissions done from January 2015 to July 2016. The common presenting symptoms were headache, back pain and paraparesis. Around 26% of patients presented with an altered sensorium, 19.4% with seizures and 21% had at least one cranial nerve involvement. The most common site of involvement was the brain noted in 49.7% of patients. Primary malignancies constituted 78 cases (50.7%) while secondary malignancies included 77 cases (49.3%). Magnetic resonance imaging (MRI) revealed 92 (59.4%) intra-axial lesions and 59 (38.1%) extra-axial lesions, with five cases having both. The most common diagnoses were intra-cerebral metastases and glioblastoma (intra-axial), and vertebral metastases and meningioma (extra-axial). Histopathological confirmation was obtained in 59 patients (38.1%) with 12 primary and 47 secondary lesions. Ten (6.45%) patients had an unknown primary with secondary metastases. The three most common histopathologically confirmed diagnoses were adenocarcinoma lung, plasma cell dyscrasia and adenocarcinoma prostate. Conclusion: Primary neurological consultations with an unknown primary are common hence a high index of suspicion can prevent an inadvertent delay in the diagnosis and appropriate treatment of a malignant lesion. Developing a neuro-oncology register may help us in gaining more insight into such situations.

Aims: The aim was to study the effect of family history of type 2 diabetes mellitus (T2DM) on insulin sensitivity and b-cell function in normoglycemic offspring. Material and Methods: Offspring of T2DM patients (cases) and individuals without family history of T2DM (controls) were the subjects for this cross-sectional study. All participants underwent 75 g OGTT and samples were collected for plasma insulin, C-peptide, and proinsulin at 0, 30, 60, and 120 minutes. Results: A total of 271 cases (age 22 ± 10 years; 53% males) and 259 controls (28 ± 10 years, 66% males) were enrolled for the study. BMI, plasma insulin, C-peptide, proinsulin, HOMA-IR, and insulinogenic index (0-120) were significantly higher and whole-body insulin sensitivity (WBISI) and disposition index (0-120) [DI 120] were lower in cases compared to controls. After adjusting for BMI, proinsulin at 120 minutes, area under the curve (AUC) of proinsulin (during OGTT) and AUC proinsulin/AUC C-peptide were significantly higher in cases. Cases were subdivided into four groups according to inheritance pattern; paternal DM (PDM), maternal DM (MDM), grandparental DM (GPDM), and both parents DM (BPDM). The magnitude of differences varied with relationship (greater when both parents and grandparents were affected). Mean HOMA-IR was higher by 127% and 50% and DI 120 was lower by 33% and 18% (adjusted for age and gender) in the BPDM and GPDM groups respectively compared to controls. Conclusions: We observed higher BMI, plasma insulin, C-peptide, and proinsulin and lower insulin sensitivity and b-cell compensation in normoglycemic offspring of T2DM subjects compared to controls. Differences were greater when both parents and grandparents had T2DM.

Context: Congenital adrenal hyperplasia (CAH) is one of the inborn errors of metabolic disorder inherited in an autosomal recessive manner caused by the defects in the steroid 21 hydroxylase CYP21A2 gene. We analyzed the genotype of 62 patients with classic CAH. Aims: To find out the underlying mutations of CYP21A2 gene. Settings and Design: Cohort of CAH patients. Materials and Methods: Sixty-two patients with CAH were recruited from the endocrine clinic at AIIMS. Electrochemiluminiscence method was used for estimating the levels of cortisol. Radioimmunoassay kit-based method was used for estimating the 17 OHP levels. Polymerase chain reaction amplification was done using specific primers to amply the CYP21A2 gene. Statistical Analysis Used: Statistical analysis was done by using Epi Info Version 3.5.1.2008. Results: Out of 62 patients, 50 were simple virilizers (SV) and 12 were salt wasters (SW). Fifty-six were females and six were males. Five 46, XX children were reared as males. Age at presentation varied from 8 months to 38 years. Molecular genetic analysis revealed that the highest number of patients harboured (In 2) IVS2-13 A/C > G (48%), followed by p.P30L (46%), p.Q318X (35%), (D 8 bp) deletion 8 bp (26%), p.I172N (26%), and p. R356W (20%) mutations. Conclusion: This is among the few studies to analyze the mutational spectrum of CYP21A2 gene in a large CAH cohort from India. Molecular diagnosis of CYP21A2 gene should be considered as part of the CAH evaluation to assess the risk of the patients/parents/siblings and to offer genetic counseling.

Background: The pathogenesis of type 1 diabetes mellitus (T1DM) requires a genetic predisposition to particular environmental triggers that may activate mechanisms leading to progressive loss of pancreatic beta cells. Aims: We tried to compare the impact of some demographic and environmental factors and breast-feeding on children (aged < 18 years) with recent onset diabetes mellitus (≤1 year) with that on age, sex, and socioeconomic status-matched controls. Material and Methods: A total of 43 consecutive patients (male, 24, mean age ± SD = 12.58 ± 9.6 years) and equal number of controls without diabetes mellitus or dysglycemia were included in this hospital-based case-control study. Results and Conclusions: A distinct peak in the incidence noted in the early adolescence with segregation in the winter months. Our patients did not differ significantly from the controls with regard to birth order, mode of delivery, parental age, parental education, dietary practices, breast-feeding, and migration in the family. Growth characteristics and nutritional status were also similar. A population study with more power will be better equipped to answer such queries.

The present study was conducted to evaluate the effects of petroleum ether, chloroform, and methanol root extracts of Curcuma zedoaria Rosc (Family: Zingiberaceae) on behavioral and radiology aspects of Freund′s Complete Adjuvant (FCA)-induced monoarthritis in left ankle joint of rats using open-field test. Traditionally, Curcuma zedoaria root has been used as anti-inflammatory and antiarthritic drug. Behavioral aspects include latency time to explore, ambulatory, rearing, grooming, urination, and defecation. Animals were divided into ten groups each of six rats, all the animals were subjected to open-field test before the induction of arthritis at 0 day and thereafter 3, 7, 14 21, 28, 35, and 42 days of postinoculation FCA injection. The rat was placed in an open field and observed all behavioral aspects for 5 minutes and radiography analysis was made on day 42. Selected doses were 10 mg/kg.i.p. Indomethacin 200 mg/kg.p.o. marketed herbal drug Rumalaya forte and 200 and 400 mg/kg.p.o. of each extracts, respectively. The results showed significant decrease in ambulation and rearing; however, increase in latency time to explore and grooming, urination, and defecation in control group, but in contrast, drug-treated groups showed significant recovery in all behavioral aspects except methanol groups. On the basis of radiography examination, control and methanol groups showed highest swelling compared with normal group; however, all drug-treated groups showed significant reduced swelling. Treatments with petroleum ether and chloroform extracts recovery were observed in behavioral and radiological aspects in arthritic rats.

BACKGROUND: The aim of this work is to investigate the structure and function of enzymes immobilised on nanomaterials. This work will allow better understanding of enzyme-nanomaterial interactions, as well as designing functional protein-nanomaterial conjugates. METHODOLOGY/PRINCIPAL FINDINGS: Multiwalled carbon nanotubes (MWNTs) were functionalised with amino groups to improve solubility and biocompatibility. The pristine and functionalised forms of MWNTs were characterised with Fourier-transform infrared spectroscopy. Thermogravimetric analysis was done to examine the degree of the functionalisation process. An immobilised biocatalyst was prepared on functionalised nanomaterial by covalent binding. Thermomyces lanuginosus lipase was used as a model enzyme. The structural change of the immobilised and free lipases were characterised with transmission electron Microscopy, X-ray photoelectron spectroscopy, Fourier-transform infrared spectroscopy and Circular dichroism spectroscopy. Biochemical characterisation of immobilised enzyme showed broader pH and thermal optima compared to soluble form. Reusability of the immobilised enzyme for hydrolysis of long chain esters was demonstrated up to ten cycles. CONCLUSION/SIGNIFICANCE: Lipase immobilised on MWNTs has exhibited significantly improved thermal stability. The exploration of advanced nanomaterial for enzyme immobilisation support using sophisticated techniques makes nanobiocatalyst of potential interest for biosensor applications.

Despite extensive research, strategies to effectively combat breast cancer sternness and achieve a definitive cure remains elusive. CD44, a well-defined cancer stem cell (CSC) marker is reported to promote breast cancer tumorigenesis, metastasis, and chemoresis-tance. However, mechanisms leading to its enhanced expression and function is poorly understood. Here, we demonstrate that USP10 positively regulates CD44 protein levels and its downstream actions. While USP10 depletion prominently down-regulates CD44 protein levels and functions, its overexpression significantly enhances CD44 protein levels, leading to enhanced cluster tumor cell formation, stemness, and metastasis in breast cancer cells both in vitro and ex vivo in primary human breast tumor cells. USP10 interacts with CD44 and stabilizes it through deubiquitination both in breast cancer cell lines and human breast cancer-derived primary tumor cells. Stabilized CD44 shows enhanced interaction with cytoskeleton proteins Ezrin/Radixin/Moesin and potently activates PDGFRp/STAT3 signaling which are involved in promoting CSC traits. Using USP10 stably expressing 4T1 cells, we further demonstrate that the USP10-CD44 axis potently promotes tumorigenicity in vivo in mice, while simultaneous depletion of CD44 in these cells renders them ineffective. In line with these findings, we further showed that inhibition of USP10 either through RNAi or the pharmacological inhibitor Spautin-1 significantly mitigated CD44 levels and its downstream function ex vivo in primary breast tumor cells. Finally, we demonstrated that primary breast tumor cells are more susceptible to chemotherapy when co-treated with USP10 inhibitor indicating that the USP10-CD44 axis could be an attractive therapeutic target in combination with chemotherapy in CD44 expressing breast cancers. [ABSTRACT FROM AUTHOR]

CCAAT/enhancer‐binding protein α (C/EBPα), a key myeloid transcription factor, drives myeloid differentiation from blast cells by regulating the expression of granulocyte colony stimulating factor receptor and C/EBPε as required for promoting granulocyte differentiation. Here, we show that serine/threonine‐protein kinase NLK, also known as Nemo‐like kinase, physically associates with C/EBPα and phosphorylates it at multiple sites, including Ser21, Thr226, Thr230 and S234, leading to its ubiquitin‐mediated degradation. Individual phospho‐point mutants of C/EBPα could be phosphorylated by NLK, but a mutant with all phosphorylatable residues replaced by alanine resisted phosphorylation and degradation by NLK, as did the single point mutants. Furthermore, although ectopic expression of NLK enhanced phosphorylation of C/EBPα levels, it markedly inhibited total C/EBPα protein levels. Conversely, NLK depletion inhibited endogenous C/EBPα phosphorylation but enhanced its total protein levels in several acute myeloid leukemia (AML) cell lines and in peripheral blood mononuclear cells isolated from number of AML patient samples. Importantly, NLK depletion in peripheral blood mononuclear cells from primary AML patients not only restored C/EBPα protein levels, but also induced myeloid differentiation, suggesting that NLK could be therapeutically targeted to restore C/EBPα to resolve differentiation arrest in AML. [ABSTRACT FROM AUTHOR]