Inhibition of insulin receptor function by a human,allosteric monoclonal antibody: A potential new approach for the treatment of hyperinsulinemic hypoglycemia

Novel therapies are needed for the treatment of hypoglycemia resulting from both endogenous and exogenous hyperinsulinema. To provide a potential new treatment option, we identified XMetD, an allosteric monoclonal antibody to the insulin receptor (INSR) that was isolated from a human antibody phage display library. To selectively obtain antibodies directed at allosteric sites, panning of the phage display library was conducted using the insulin-INSR complex. Studies indicated that XMetD bound to the INSR with nanomolar affinity. Addition of insulin reduced the affinity of XMetD to the INSR by 3-fold, and XMetD reduced the affinity of the INSR for insulin 3-fold. In addition to inhibiting INSR binding, XMetD also inhibited insulin-induced INSR signaling by 20- to 100-fold. These signaling functions included INSR autophosphorylation, Akt activation and glucose transport. These data indicated that XMetD was an allosteric antagonist of the INSR because, in addition to inhibiting the INSR via modulation of binding affinity, it also inhibited the INSR via modulation of signaling efficacy. Intraperitoneal injection of XMetD at 10 mg/kg twice weekly into normal mice induced insulin resistance. When sustained-release insulin implants were placed into normal mice, they developed fasting hypoglycemia in the range of 50 mg/dl. This hypoglycemia was reversed by XMetD treatment. These studies demonstrate that allosteric monoclonal antibodies, such as XMetD, can antagonize INSR signaling both in vitro and in vivo. They also suggest that this class of allosteric monoclonal antibodies has the potential to treat hyperinsulinemic hypoglycemia resulting from conditions such as insulinoma, congenital hyperinsulinism and insulin overdose.     

Fluidity enhancement: a critical factor for performance of liposomal transdermal drug delivery system

Liposomes are well known lipid carriers for drug delivery of bioactive molecules encapsulated inside their membrane. Liposomes as skin drug delivery systems were initially promoted primarily for localized effects with minimal systemic delivery. Subsequently, a novel vesicular system, transferosomes was reported for transdermal delivery with efficiency similar to subcutaneous injection. The multiple bilayered organizations of lipids applied in these vesicles structure are somewhat similar to complex nature of stratum corneal intercellular lipids domains. The incorporation of novel agents into these lipid vesicles results in the loss of entrapped markers but it is similar to fluidization of stratum corneum lipids on treatment with a penetration enhancer. This approach generated the utility of penetration enhancers/fluidizing agents in lipids vesicular systems for skin delivery. For the transdermal and topical applications of liposomes, fluidity of bilayer lipid membrane is rate limiting which governs the permeation. This article critically reviews the relevance of using different types of vesicles as a model for skin in permeation enhancement studies. This study has also been designed to encompass all enhancement measurements and analytical tools for characterization of permeability in liposomal vesicular system.     

The Rumor of Globalization: Globalism,Counterworks and the Location of Commodity

This article seeks to document the vernacular perceptions of ‘globalization’ in rural Bengal (India) and, in that connection, seeks to rethink some long-held western notions concerning commodity, consumption, representation, the nature of sociality and the politics of democratic empowerment in the third-world. In the subaltern imaginary, images seem to play a crucial role conductive to empowerment. Also, far from resisting globalization and consumption, the rural poor seems to have assimilated these into their vernacular cosmology. In memoriam: Gourkishore Ghosh (1923–2001) Vernacular intellectual, publicist, crusader for free speech and democracy     

Breeding lines of the Indian mega-rice variety,MTU 1010, possessing protein kinase <Emphasis Type="Italic">OsPSTOL</Emphasis> (<Emphasis Type="Italic">Pup1</Emphasis>), show better root system architecture and higher yield in soils with low phosphorus

MTU 1010 is a high-yielding mega-variety of rice grown extensively in India. However, it does not perform well in soils with low phosphorus (P) levels. With an objective to improve MTU 1010 for tolerance to low soil P, we have transferred Pup1, a major quantitative trait locus (QTL) associated with tolerance from another mega-variety, Swarna, through marker-assisted backcross breeding (MABB). Foreground selection of the F₁ and backcross plants was performed with the co-dominant, closely linked CAPS marker, K20-2, while two flanking markers RM28011 and RM28157 were utilized for recombinant selection. At each backcross generation, positive plants were also analyzed with a set of 85 parental polymorphic SSR markers to identify the QTL-positive plants possessing maximum introgression of MTU 1010 genome. At BC₂F₁, the best backcross plant was selfed to generate BC₂F₂s. Among them, the plants homozygous for Pup1 (n?=?22) were reconfirmed using the functional marker for Pup1, viz., K46-1, and they were advanced through pedigree method of selection until BC₂F₆ generation. A total of five elite BC₂F₆ lines, possessing Pup1 and phenotypically similar to MTU 1010, were screened in the low soil P plot and normal plot (with optimum soil P levels) during wet season, 2016. All the selected lines showed better performance under low P soil with more number of productive tillers, better root system architecture, and significantly higher yield (>?390%) as compared to MTU 1010. Further, under normal soil, the lines were observed to be similar to or better than MTU 1010 for most of the agro-morphological traits and yield. This study represents the successful application of marker-assisted selection for improvement of tolerance to low soil P in a high-yielding Indian rice variety.     

PCL-Based Composite Scaffold Matrices for Tissue Engineering Applications

Biomaterial-based scaffolds are important cues in tissue engineering (TE) applications. Recent advances in TE have led to the development of suitable scaffold architecture for various tissue defects. In this narrative review on polycaprolactone (PCL), we have discussed in detail about the synthesis of PCL, various properties and most recent advances of using PCL and PCL blended with either natural or synthetic polymers and ceramic materials for TE applications. Further, various forms of PCL scaffolds such as porous, films and fibrous have been discussed along with the stem cells and their sources employed in various tissue repair strategies. Overall, the present review affords an insight into the properties and applications of PCL in various tissue engineering applications.     

India's E‐Waste Rules and Their Impact on E‐Waste Management Practices: A Case Study

India, like many other developed and developing countries, has adopted an extended producer responsibility (EPR) approach for electronic waste (e‐waste) management under its E‐waste (Management and Handling) Rules, 2011. Under these rules, producers have been made responsible for setting up collection centers of e‐waste and financing and organizing a system for environmentally sound management of e‐waste. In this article, we use the implementation of these rules in Ahmedabad in western India as a case study to conduct a critical analysis of the implementation of India's Rules. Interviews of main stakeholder groups, including a sample of regulated commercial establishments, regulatory agencies enforcing the Rules, informal actors involved in waste collection and handling, as well as publicly available information on the implementation constitute data for our case study. Our results indicate that while there has been an increase in the formal waste processing capacity after the implementation of the Rules, only 5% to 15% of the total waste generated is likely channeled through formal processing facilities. While the EPR regulation forced the producers to take action on a few relatively inexpensive aspects of the Rules, the collection and recycling system has not been made convenient for the consumers to deposit e‐waste in formal collection and recycling centers. Based on our findings, we argue that Indian EPR regulation should go beyond simple take‐back mandates and consider implementing other policy instruments such as a deposit‐refund system. An important implication for developing countries is the need for careful attention to instrument choice and design within EPR regulations.     

A net ecosystem carbon budget for snow dominated forested headwater catchments: linking water and carbon fluxes to critical zone carbon storage

Climate-driven changes in carbon (C) cycling of forested ecosystems have the potential to alter long-term C sequestration and the global C balance. Prior studies have shown that C uptake and partitioning in response to hydrologic variation are system specific, suggesting that a comprehensive assessment is required for distinct ecosystems. Many sub-humid montane forest ecosystems in the US are projected to experience increased water limitation over the next decades and existing water-limited forests can be used as a model for how changes in the hydrologic cycle will impact such ecosystems more broadly. Toward that goal we monitored precipitation, net ecosystem exchange and lateral soil and stream C fluxes in three semi-arid to sub-humid montane forest catchments for several years (WY 2009–2013) to investigate how the amount and timing of water delivery affect C stores and fluxes. The key control on aqueous and gaseous C fluxes was the distribution of water between winter and summer precipitation, affecting ecosystem C uptake versus heterotrophic respiration. We furthermore assessed C stores in soil and above- and below-ground biomass to assess how spatial patterns in water availability influence C stores. Topographically-driven patterns in catchment wetness correlated with modeled soil C stores, reflecting both long-term trends in local C uptake as well as lateral redistribution of C leached from upslope organic soil horizons to convergent landscape positions. The results suggest that changes in the seasonality of precipitation from winter snow to summer rain will influence both the amount and the spatial distribution of soil C stores.     

Improvement of blast resistance of the popular high-yielding,medium slender-grain type,bacterial blight resistant rice variety,Improved Samba Mahsuri by marker-assisted breeding

Improved Samba Mahsuri (ISM) is a popular, high-yielding, bacterial blight resistant rice variety possessing medium-slender grain type. As ISM is highly susceptible to blast disease of rice, through the present study we have transferred two major blast resistance genes, Pi2 and Pi54 into the elite variety by marker-assisted backcross breeding. The two blast resistance genes were transferred to ISM through sets of backcrosses. In every backcross generation, PCR-based markers, specific for the blast resistance genes (Pi2 and Pi54) and bacterial blight resistance genes (Xa21, xa13 and xa5) were utilized for foreground selection, while a set of 144 parental polymorphic SSR markers were used for background selection and backcrossing was carried out until BC₂ generation. A solitary BC₂F₁ plant possessing Pi2 or Pi54 along with Xa21, xa13 and xa5 and >?90% recovery of ISM genome was selected from the two sets of backcrosses were crossed and the intercross F₁s (ICF₁s) thus obtained were selfed to generate ICF₂s. Homozygous ICF₂ plants carrying all the five resistance genes were identified through markers and advanced through selfing till ICF₅ generation by adopting pedigree method of selection. Three best lines at ICF₅, possessing excellent resistance against bacterial blight and blast and closely resembling or superior to ISM in terms of grain quality: yield and agro-morphological traits have been identified and advanced for multi-location trials.     

Responses by the brown planthopper,Nilaparvata lugens,to conspecific density on resistant and susceptible rice varieties

This study examines the nature of intraspecific interactions among Nilaparvata lugens (Stål) (Hemiptera: Delphacidae) planthoppers feeding on resistant and susceptible rice varieties. Planthopper nymphs produced less honeydew and gained less weight when feeding on rice variety IR62 (resistant) compared to susceptible rice varieties. A series of bioassays was conducted that varied N. lugens nymph densities on IR62 and IR22 (susceptible). Increasing nymph density facilitated feeding by conspecifics; however, intraspecific competition increased mortality of nymphs on IR62 (but rarely on IR22). Furthermore, nymph weights declined with increasing conspecific density on IR22, and the effects were weak on IR62. More female nymphs than males survived on IR62 but this was not affected by density. Nitrogenous fertilizer increased competition among N. lugens on young plants of IR22, but not on IR62. Results indicate that nymphs have a low efficiency in accessing resources when feeding on IR62, even where the plants have received fertilizer. Female‐biased survival and biomass compensation for mortality may promote population recovery after development on the resistant plant and accelerate adaptation to the resistant variety.