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Mechanisms by which electric (E) or magnetic (B) fields might be harnessed to affect tumor cell behavior remain poorly defined, presenting a barrier to translation. We hypothesized in early studies that the glycocalyx of lung cancer cells might play a role in mediating plasma membrane leak by low-frequency pulsed magnetic fields (Lf-PMF) generated on a low-energy solenoid platform. In testing glioblastoma and neuroblastoma cells known to overexpress glycoproteins rich in modifications by the anionic glycan sialic acid (Sia), exposure of brain tumor cells on the same platform to a pulse train that included a 5 min 50Hz Lf-PMF (dB/dt ∼ 2 T/s at 10 ms pulse widths) induced a very modest but significant protease leak above that of control nonexposed cells (with modest but significant reductions in long-term tumor cell viability after the 5 min exposure). Using a markedly higher dB/dt system (80 T/s pulses, 70 μs pulse-width at 5.9 cm from a MagVenture coil source) induced markedly greater leak by the same cells, and eliminating Sia by treating cells with AUS sialidase immediately preexposure abrogated the effect entirely in SH-SY5Y neuroblastoma cells, and partially in T98G glioblastoma cells. The system demonstrated significant leak (including inward leak of propidium iodide), with reduced leak at lower dB/dt in a variety of tumor cells. The ability to abrogate Lf-PMF protease leak by pretreatment with sialidase in SH-SY5Y brain tumor cells or with heparin lyase in A549 lung tumor cells indicated the importance of heavy Sia or heparan sulfate glycosaminoglycan glycocalyx modifications as dominant glycan species mediating Lf-PMF membrane leak in respective tumor cells. This first-physical Lf-PMF tumor glycocalyx event, with downstream cell stress, may represent a critical and tunable transduction mechanism that depends on characteristic anionic glycans overexpressed by distinct malignant tumors.

While recent research points to the importance of glycans in cancer immunity, knowledge on functional mechanisms is lacking. In lung carcinoma among other tumors, anti-tumor immunity is suppressed; and while some recent therapies boost T-cell mediated immunity by targeting immune-checkpoint pathways, robust responses are uncommon. Augmenting tumor antigen-specific immune responses by endogenous dendritic cells (DCs) is appealing from a specificity standpoint, but challenging. Here, we show that restricting a heparan sulfate (HS) loss-of-function mutation in the HS sulfating enzyme Ndst1 to predominantly conventional DCs (Ndst1f/f CD11cCre+ mutation) results in marked inhibition of Lewis lung carcinoma growth along with increased tumor-associated CD8+ T cells. In mice deficient in a major DC HS proteoglycan (syndecan-4), splenic CD8+ T cells showed increased anti-tumor cytotoxic responses relative to controls. Studies examining Ndst1f/f CD11cCre + mutants revealed that mutation was associated with an increase in anti-tumor cytolysis using either splenic CD8+ T cells or tumor-infiltrating (TIL) CD8+ T cells purified ex-vivo, and tested in pooled effector-to-target cytolytic assays against tumor cells from respective animals. On glycan compositional analysis, HS purified from Ndst1f/f CD11cCre + mutant DCs had reduced overall sulfation, including reduced sulfation of a tri-sulfated disaccharide species that was intriguingly abundant on wildtype DC HS. Interestingly, antigen presentation in the context of major histocompatibility complex class-I (MHC-I) was enhanced in mutant DCs, with more striking effects in the setting of HS under-sulfation, pointing to a likely regulatory role by sulfated glycans at the antigen/MHC-I - T-cell interface; and possibly future opportunities to improve antigen-specific T cell responses by immunologic targeting of HS proteoglycans in cancer.

Chemogenetic characterization through in vitro evolution combined with whole-genome analysis can identify antimalarial drug targets and drug-resistance genes. We performed a genome analysis of 262 Plasmodium falciparum parasites resistant to 37 diverse compounds. We found 159 gene amplifications and 148 nonsynonymous changes in 83 genes associated with drug-resistance acquisition, where gene amplifications contributed to one-third of resistance acquisition events. Beyond confirming previously identified multidrug-resistance mechanisms, we discovered hitherto unrecognized drug target-inhibitor pairs, including thymidylate synthase and a benzoquinazolinone, farnesyltransferase and a pyrimidinedione, and a dipeptidylpeptidase and an arylurea. This exploration of the P. falciparum resistome and druggable genome will likely guide drug discovery and structural biology efforts, while also advancing our understanding of resistance mechanisms available to the malaria parasite.

Certainty, commitment, and communication are essential requirements which seem to be eluding the existing contracting process giving rise to claims and disputes. Contract management practices continue to be manual and traditional despite the digital and technological developments in construction sector. Blockchain technology is increasingly used in different aspects of the business world with its intrinsic qualities of transparency and security. This research conducts systematic literature reviews in three areas aiming to: analyse the chronic problem of construction disputes, investigate recent methods and tools of contractual dispute avoidance, and provide a compelling rationale for the integration of blockchain technology into the contracting process. While the 'contract-related' issues were found to be the leading cause of disputes, a 'centralized' hierarchy-based environment was established as one of the key challenges to dispute avoidance mechanisms. Discussion followed by feedback survey from industry experts further validated the literature review results. Based on the findings, an integrated blockchain-based conceptual framework is proposed illustrating a contracting process that is: (1) efficient and transparent; (2) digitally integrated; and (3) trustworthy and secure in execution. The study reviews the existing practices and challenges in contract management and offers an interdisciplinary and novel approach for future research in this domain. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) printing has shown broad applicability in tissue engineering in the last few years. This additive manufacturing technique has been successful in printing complex biodegradable scaffolds and cellular constructs. Its versatility ranges from the fabrication of the hard bone tissues to the highly soft tissues like skin and kidney using synthetic or natural polymers. Recent research advances focus on developing biomimicking tissues, organoids, or organs to replace or bridge the requirement for synthetic implants, organ transplantation, animal model studies for drug screening and development, and personalized medicine profiling, especially for vital organs like the liver. Liver being the most metabolically active organ, undergoes gradual damage over the years of repetitive insults, resulting in severe chronic illness. Despite several advances, 3D printing technology is yet to prove its potential in translating biomimicking liver constructs with high vasculature, functional efficacy, varying stiffness, and complex architectural properties similar to liver lobules. Hence, this review article describes the advanced 3D printing techniques, their advantages and ongoing challenges employed during the fabrication of functionalized liver constructs. It also discusses the favorable solutions available and futuristic approaches for the construction of heterogeneous liver tissue along with its extracellular matrix for generating a new platform to facilitate liver disease treatment. [ABSTRACT FROM AUTHOR]

Chemogenetic characterization through in vitro evolution combined with whole-genome analysis can identify antimalarial drug targets and drug-resistance genes. We performed a genome analysis of 262 Plasmodium falciparum parasites resistant to 37 diverse compounds. We found 159 gene amplifications and 148 nonsynonymous changes in 83 genes associated with drug-resistance acquisition, where gene amplifications contributed to one-third of resistance acquisition events. Beyond confirming previously identified multidrug-resistance mechanisms, we discovered hitherto unrecognized drug target–inhibitor pairs, including thymidylate synthase and a benzoquinazolinone, farnesyltransferase and a pyrimidinedione, and a dipeptidylpeptidase and an arylurea. This exploration of the P. falciparum resistome and druggable genome will likely guide drug discovery and structural biology efforts, while also advancing our understanding of resistance mechanisms available to the malaria parasite.

About 50% of malaria infections in India are attributed to Plasmodium falciparum but relatively little is known about the genetic structure of the parasite populations. The molecular genotyping of the parasite populations by merozoite surface protein (msp1 and msp2) and glutamate-rich protein (glurp) genes identifies the existing parasite population in the regions which help in understanding the molecular mechanisms involved in the parasite's drive for survival. This study reveals the genetic profile of the parasite population in selected regions across the country with varying degree of endemicity among them. We also report the prevalence of Pfcrt mutations in this parasite population to evaluate the pattern of drug resistance development in them. [ABSTRACT FROM AUTHOR]

Information about several papers discussed at a meeting held on November 10, 2016 sponsored by the national research and development organizations including Council of Scientific & Industrial Research (CSIR), National Institute of Science Communication and Information Resources (NISCAIR), and United Schools Organization of India (USO) on account of UNESCO World Science Day for Peace and Development. Topics include teacher-student bond, Indian contributions to science, and science teachers.

About 50% of malaria infections in India are attributed to Plasmodium falciparum but relatively little is known about the genetic structure of the parasite populations. The molecular genotyping of the parasite populations by merozoite surface protein (msp1 and msp2) and glutamate-rich protein (glurp) genes identifies the existing parasite population in the regions which help in understanding the molecular mechanisms involved in the parasite's drive for survival. This study reveals the genetic profile of the parasite population in selected regions across the country with varying degree of endemicity among them. We also report the prevalence of Pfcrt mutations in this parasite population to evaluate the pattern of drug resistance development in them.