Search

During the lamp event in phase-1 (P1) of the first wave of the COVID-19 pandemic, the concentration of air pollutants over the Indo Gangetic Plain (IGP) increased substantially. Analyses show an association of benzene and toluene with PM2.5 due to oil-based emissions.

Identification of interacting protein partners of DENV in the insect vector Aedes aegypti is crucial for designing vector control-based strategies and for understanding the molecular mechanism DENV uses to modulate the host, gain entry, and survive successfully. Similar proteins can be used in generating transmission-blocking vaccines.

Hepatitis B virus (HBV) is the leading cause of liver disease ranging from acute and chronic hepatitis to liver cirrhosis and hepatocellular carcinoma (HCC). Studies have revealed that HBV infection broadly reprogrammes the host cellular metabolic processes for viral pathogenesis. Previous reports have shown that glycolysis and gluconeogenesis are among the most deregulated pathways during HBV infection. We noted that despite being one of the rate-limiting enzymes of gluconeogenesis, the role and regulation of Fructose-1,6-bisphosphatase 1 (FBP1) during HBV infection is not much explored. In this study, we report FBP1 upregulation upon HBV infection and unravel a novel mechanism of epigenetic reprogramming of FBP1 by HBV via utilizing host factor Speckled 110 kDa (Sp110). Here, we identified acetylated lysine 18 of histone H3 (H3K18Ac) as a selective interactor of Sp110 Bromodomain. Furthermore, we found that Sp110 gets recruited on H3K18Ac-enriched FBP1 promoter, and facilitates recruitment of deacetylase Sirtuin 2 (SIRT2) on that site in the presence of HBV. SIRT2 in turn brings its interactor and transcriptional activator Hepatocyte nuclear factor 4-alpha to the promoter, which ultimately leads to a loss of DNA methylation near the cognate site. Interestingly, this Sp110 driven FBP1 regulation during infection was found to promote viral-borne HCC progression. Moreover, Sp110 can be used as a prognostic marker for the hepatitis-mediated HCC patients, where high Sp110 expression significantly lowered their survival. Thus, the epigenetic reader protein Sp110 has potential to be a therapeutic target to challenge HBV-induced HCCs.

Shwitra or Shwet-Kushtha can be correlated with skin disease “Vitiligo”.[1] Vata and Bhrajaka pitta reside in skin. An imbalance in those may cause skin diseases. Shwitra is of two types, that is kilas and varuna.[2] Shwitra differs from other skin disorders by the normal functioning of all but the skin tissue (twak)[3] resulting in discoloration of the skin (twakvaivarnyata), without discharge (aparisarav stravi). [4,5] There are many theories regarding the cause of vitiligo. The main cause is autoimmune, genetic, psychological, endocrine disorder, chemical contact and adverse drug interaction.[6,7] In Ayurveda, the real causes as Nidan-causative factors are considered as untruthfulness, ungratefulness, disrespect for the Gods, insult of the preceptors, sinful acts, misdeeds of past lives and intake of contradictory food.[8] In Ayurveda, Shwitra is considered in Kushta. Though, it is not painful but in society, it is a hating state and dreadful condition, many people are suffering from this condition. It creates mental discomforts in a person due to stigma. A 9-year-old boy had been suffering from white patches over both elbows, both knees, ankles with mild itching over affected area. In this case, we used Shaman and Shodhan therapy which included snehapan, vaman, virechan, prachan, jaloka and external ointment advised to apply on the affected area in the morning at 9am and evening at 4 pm with exposure to sunlight for 2 months daily. Multiple lines of treatment were used which enhanced the proliferation of melanocytes. The colour of the affected skin area became red and size diminished to some extent. We wanted to study about Shwitra, its pathological manifestations, symptoms in detail and to assess the effect of individual panchkarma therapies in Shwitra.

BackgroundNotch signaling is an evolutionarily conserved pathway that dictates cell fate decisions in mammalian cells including megakaryocytes. Existence of functional Notch signaling in enucleate platelets that are generated as cytoplasmic buds from megakaryocytes still remains elusive.MethodsPlatelets were isolated from human blood by differential centrifugation under informed consent. Expression of transcripts as well as peptides of Notch1 and DLL-4 in platelets was studied by employing RT-qPCR, Western analysis and flow cytometry. Platelet activation responses that include aggregation, secretion of granule contents and platelet-leucocyte interaction were analyzed by Born’s aggregometry, flow cytometry, Western analysis and lumi- aggregometry. Shedding of extracellular vesicles from platelets was documented with Nanoparticle Tracking Analyzer. Platelet adhesion and thrombus growth on immobilized matrix was quantified by employing microfluidics platform. Intracellular free calcium in Fura-2-loaded platelets was monitored from ratiometric fluorescence spectrophotometry. Coagulation parameters in whole blood were studied by thromboelastography. Ferric chloride-induced mesenteric arteriolar thrombosis in murine model was imaged by intravital microscopy.ResultsHere we demonstrate significant expression of Notch1 and its ligand, the Delta-like ligand (DLL)- 4, as well as their respective transcripts, in human platelets. Synthesis and surface translocation of Notch1 and DLL-4 were upregulated when cells were challenged with physiological agonists like thrombin. DLL-4, in turn, instigated neighbouring platelets to switch to ‘activated’ phenotype, associated with cleavage of Notch receptor and generation of its intracellular domain (NICD). DLL-4-mediated pro-thrombotic attributes were averted by pharmacological inhibition of γ-secretase and phosphatidylinositol 3-kinase. Inhibition of Notch signaling, too, restrained agonist-induced platelet activation, and significantly impaired arterial thrombosis in mice, suggestive of synergism between thrombin- and DLL-4-mediated pathways. Strikingly, prevention of DLL-4-Notch1 interaction by a blocking antibody abolished platelet aggregation and extracellular vesicle shedding induced by thrombin.ConclusionsOur study presents compelling evidence in support of non-canonical Notch signaling that propagates in juxtacrine manner within platelet aggregates and synergizes with physiological agonists to generate occlusive intramural thrombi. Thus, targeting Notch signaling can be investigated as a potential anti-platelet/anti-thrombotic therapeutic approach.FundingThis research was supported by J. C. Bose National Fellowship (JCB/2017/000029) and grants received by D. Dash from the Indian Council of Medical Research (ICMR) under CAR (71/4/2018-BMS/CAR), Department of Biotechnology (DBT) (BT/PR-20645/BRB/10/1541/2016) and Science and Engineering Research Board (SERB) (EMR/2015/000583), Government of India. S.N. Chaurasia is a recipient of financial assistance from the ICMR. M. Ekhlak is a recipient of CSIR-SRF and V. Singh is a recipient of UGC-SRF. D. Dash acknowledges assistance from the Humboldt Foundation, Germany. Funders have no role in the design, analysis and reporting of the study.

We introduce a novel method to derandomize the learning with errors (LWE) problem by generating deterministic yet sufficiently independent LWE instances that are constructed by using linear regression models, which are generated via (wireless) communication errors. We also introduce star-specific key-homomorphic (SSKH) pseudorandom functions (PRFs), which are defined by the respective sets of parties that construct them. We use our derandomized variant of LWE to construct a SSKH PRF family. The sets of parties constructing SSKH PRFs are arranged as star graphs with possibly shared vertices, i.e., the pairs of sets may have non-empty intersections. We reduce the security of our SSKH PRF family to the hardness of LWE. To establish the maximum number of SSKH PRFs that can be constructed -- by a set of parties -- in the presence of passive/active and external/internal adversaries, we prove several bounds on the size of maximally cover-free at most $t$-intersecting $k$-uniform family of sets $\mathcal{H}$, where the three properties are defined as: (i) $k$-uniform: $\forall A \in \mathcal{H}: |A| = k$, (ii) at most $t$-intersecting: $\forall A, B \in \mathcal{H}, B \neq A: |A \cap B| \leq t$, (iii) maximally cover-free: $\forall A \in \mathcal{H}: A \not\subseteq \bigcup\limits_{\substack{B \in \mathcal{H} \\ B \neq A}} B$. For the same purpose, we define and compute the mutual information between different linear regression hypotheses that are generated from overlapping training datasets., Preprint

This study describes the role of core decompression and bone marrow grafting in the treatment of early AVN of femoral head. We performed core decompression using multiple drill holes and then the bone marrow graft is taken from iliac crest and inserted into track created by drilling into the femoral head and neck .We included 50 patients, 62 hips of both sex, in the age group between 18-50 years without any comorbidities and followed these cases for 1 year.

Innate and acquired resistance towards the conventional therapeutic regimen imposes a significant challenge for the successful management of cancer for decades. In patients with advanced carcinomas, acquisition of drug resistance often leads to tumor recurrence and poor prognosis after the first therapeutic cycle. In this context, cancer stem cells (CSCs) are considered as the prime drivers of therapy resistance in cancer due to their ‘non-targetable’ nature. Drug resistance in cancer is immensely influenced by different properties of CSCs such as epithelial-to-mesenchymal transition (EMT), a profound expression of drug efflux pump genes, detoxification genes, quiescence, and evasion of apoptosis, has been highlighted in this review article. The crucial epigenetic alterations that are intricately associated with regulating different mechanisms of drug resistance, have been discussed thoroughly. Additionally, special attention is drawn towards the epigenetic mechanisms behind the interaction between the cancer cells and their microenvironment which assists in tumor progression and therapy resistance. Finally, we have provided a cumulative overview of the alternative treatment strategies and epigenome-modifying therapies that show the potential of sensitizing the resistant cells towards the conventional treatment strategies. Thus, this review summarizes the epigenetic and molecular background behind therapy resistance, the prime hindrance of present day anti-cancer therapies, and provides an account of the novel complementary epi-drug-based therapeutic strategies to combat drug resistance.

A short and efficient multicomponent sequence for synthesizing fused novel polyheterocyclic chromeno spiro-pyrrolidine oxindoles via 1,3-dipolar cycloaddition reaction mediated by reactive azomethine ylides catalyzed by the Graphene Oxide (GO) is reported herein. This approach was utilized for synthesizing fused polyheterocyclic spiro-pyrrolothiazole and spiro-pyrrole oxindoles with yields ranging from good to excellent. A heterogeneous GO catalyst with an ultra-low catalytic loading of 0.05 wt% could proficiently catalyze the reaction without the formation of any side products and can also be visualized by the formation of solid mass in the reaction flask. The methodology is green in nature and the products were isolated by simple filtration without the use of any chromatographic techniques.

Ixodes scapularis ticks transmit multiple pathogens, including Borrelia burgdorferi sensu stricto, and encode many proteins harboring epidermal growth factor (EGF)-like domains. We show that I. scapularis produces multiple orthologs for Bm86, a widely studied tick gut protein considered as a target of an anti-tick vaccine, herein termed as Is86. We show that Is86 antigens feature at least three identifiable regions harboring EGF-like domains (termed as EGF-1, EGF-2, and EGF-3) and are differentially upregulated during B. burgdorferi infection. Although the RNA interference-mediated knockdown of Is86 genes did not show any influences on tick engorgement or B. burgdorferi sensu stricto persistence, the immunization of murine hosts with specific recombinant EGF antigens marginally reduced spirochete loads in the skin, in addition to affecting tick blood meal engorgement and molting. However, given the borderline impact of EGF immunization on tick engorgement and pathogen survival in the vector, it is unlikely that these antigens, at least in their current forms, could be developed as potential vaccines. Further investigations of the biological significance of Is86 (and other tick antigens) would enrich our knowledge of the intricate biology of ticks, including their interactions with resident pathogens, and contribute to the development of anti-tick measures to combat tick-borne illnesses.

The major challenge in chemotherapy lies in the gain of therapeutic resistance properties of cancer cells. The relatively small fraction of chemo-resistant cancer cells outgrows and are responsible for tumor relapse, with acquired invasiveness and stemness. We demonstrate that zinc-finger MYND type-8 (ZMYND8), a putative chromatin reader, suppresses stemness, drug resistance, and tumor-promoting genes, which are hallmarks of cancer. Reinstating ZMYND8 suppresses chemotherapeutic drug doxorubicin-induced tumorigenic potential (at a sublethal dose) and drug resistance, thereby resetting the transcriptional program of cells to the epithelial state. The ability of ZMYND8 to chemo-sensitize doxorubicin-treated metastatic breast cancer cells by downregulating tumor-associated genes was further confirmed by transcriptome analysis. Interestingly, we observed that ZMYND8 overexpression in doxorubicin-treated cells stimulated those involved in a good prognosis in breast cancer. Consistently, sensitizing the cancer cells with ZMYND8 followed by doxorubicin treatment led to tumor regression in vivo and revert back the phenotypes associated with drug resistance and stemness. Intriguingly, ZMYND8 modulates the bivalent or poised oncogenes through its association with KDM5C and EZH2, thereby chemo-sensitizing the cells to chemotherapy for better disease-free survival. Collectively, our findings indicate that poised chromatin is instrumental for the acquisition of chemo-resistance by cancer cells and propose ZMYND8 as a suitable epigenetic tool that can re-sensitize the chemo-refractory breast carcinoma.

The peritrophic matrix (PM) is an acellular membrane that covers the gut epithelium in arthropods and physically separates it from the lumen. The structure is thought to play an important role in tick biology. The PM is also known to impact the persistence of tick-borne pathogens like Borrelia burgdorferi, although limited information is available about its molecular constituents or their biological significance. Herein, we characterize a novel PM-associated gut protein in Ixodes scapularis ticks, annotated as Peritrophic Membrane Chitin Binding Protein (PM_CBP), for its role in the integrity and function of the matrix. The PM_CBP displays homology to the chitin deacetylase metalloenzyme, shows upregulation during tick feeding, and is localized at the luminal surface of the gut epithelium. The structural integrity of the PM was impaired both by the knock down of PM_CBP expression via RNA interference and by treatment with anti-PM_CBP antibodies, as revealed by its electron microscopic appearance. Additionally, the duration of tick engorgement on mice and the passage of experimentally-inoculated fluorescent dextran molecules across the PM are affected by the knock down of PM_CBP expression. The transfer of anti-PM_CBP antibodies into the tick gut impacted the overall composition of the resident microbiome, and also influenced Borrelia burgdorferi acquisition in ticks and its transmission to mice. Taken together, these data highlight the biological significance of the Ixodes PM and suggest that the targeting of its molecular constituents may contribute to the development of novel interventions against tick-borne infections. This article is protected by copyright. All rights reserved. WOS:000579839300001 33006213 Q2

Anonymity is a desirable feature for vehicle-to-vehicle (V2V) communications, but it conflicts with other requirements such as non-repudiation and revocation. Existing, pseudonym-based V2V communications schemes rely on certificate generation and signature verification. These schemes require cumbersome key management, frequent updating of certificate chains and other costly procedures such as cryptographic pairings. In this paper, we present novel V2V communications schemes, that provide authentication, authorization, anonymity, non-repudiation, replay protection, pseudonym revocation, and forward secrecy without relying on traditional certificate generation and signature verification. Security and privacy of our schemes rely on hard problems in number theory. Furthermore, our schemes guarantee security and privacy in the presence of subsets of colluding malicious parties, provided that the cardinality of such sets is below a fixed threshold., This is the full version of the paper that appeared in 2017 IEEE Vehicular Networking Conference (VNC), pp. 139-146. DOI: 10.1109/VNC.2017.8275624

Tandem conjugate addition, decarboxylation and esterification/amidation of coumarin 3-carboxylic acid derivatives with pyrazolones have been developed. The reactions were performed with coumarin 3-carboxylic acid/esters and pyrazolone in alcohol as a solvent to afford the corresponding pyrazolyl 2-hydroxy phenylpropionate derivatives. Amines and green solvents were employed for amidation in the addition reaction. The methodology has advantages such as excellent yields, a broad substrate scope, catalyst-free, easy purification by simple filtration without any workup, mild conditions and does not require any organic solvents, ligands, base or any additives. This is a green and general synthetic protocol, which could be applicable for the synthesis of substituted pyrazolyl phenyl propionate/amide derivatives. This approach demonstrates the importance of the coumarin 3-carboxylic acid/ester core structure for Michael addition.

Secret sharing provides a means to distribute shares of a secret such that any authorized subset of shares, specified by an access structure, can be pooled together to recompute the secret. The standard secret sharing model requires public access structures, which violates privacy and facilitates the adversary by revealing the high-value targets. In this paper, we address this shortcoming by introducing hidden access structures, which remain secret until some authorized subset of parties collaborate. The central piece of this work is the construction of a set-system \(\mathcal {H}\) with strictly greater than \(\exp \left( c \dfrac{1.5 (\log h)^2}{\log \log h}\right) \) subsets of a set of h elements. Our set-system \(\mathcal {H}\) is defined over \(\mathbb {Z}_m\), where m is a non-prime-power, such that the size of each set in \(\mathcal {H}\) is divisible by m but the sizes of their pairwise intersections are not divisible by m, unless one set is a subset of another. We derive a vector family \(\mathcal {V}\) from \(\mathcal {H}\) such that superset-subset relationships in \(\mathcal {H}\) are represented by inner products in \(\mathcal {V}\). We use \(\mathcal {V}\) to “encode” any access structure and thereby develop the first access structure hiding secret sharing scheme. The information rate (secret-size/maximum-share-size) of our scheme is 1/2. For a setting with \(\ell \) parties, our scheme supports \(2^{\ell }\) out of the \(2^{2^{\ell - O(\log \ell )}}\) possible access structures. The scheme assumes semi-honest polynomial-time parties, and its security relies on the Generalized Diffie-Hellman assumption.

Secret sharing allows distributing a secret among several parties such that only authorized subsets, specified by an access structure, can reconstruct the secret. Sehrawat and Desmedt (COCOON 2020) introduced hidden access structures, that remain secret until some authorized subset of parties collaborate. However, their scheme assumes semi-honest parties and supports only restricted access structures. We address these shortcomings by constructing an access structure hiding verifiable secret sharing scheme that supports all monotone access structures. It is the first secret sharing scheme to support cheater identification and share verifiability in malicious-majority settings. The verification procedure of our scheme incurs no communication overhead. As the building blocks of our scheme, we introduce and construct: (i) a set-system with $> \exp\left(c\frac{2(\log h)^2}{(\log\log h)}\right)+2\exp\left(c\frac{(\log h)^2}{(\log\log h)}\right)$ subsets of a set of $h$ elements. Our set-system, $\mathcal{H}$, is defined over $\mathbb{Z}_m$, where $m$ is a non-prime-power. The size of each set in $\mathcal{H}$ is divisible by $m$ but the sizes of their pairwise intersections are not, unless one set is a subset of another, (ii) a new variant of the learning with errors (LWE) problem, called PRIM-LWE, wherein the secret matrix is sampled such that its determinant is a generator of $\mathbb{Z}_q^*$, where $q$ is the LWE modulus. The security of our scheme relies on the hardness of the LWE problem, and its share size is $$(1+ o(1)) \dfrac{2^{\ell}}{\sqrt{\pi \ell/2}}(2 q^{\varrho + 0.5} + \sqrt{q} + \mathrm{\Theta}(h)),$$ where $\varrho \leq 1$ is a constant and $\ell$ is the total number of parties. We also provide directions for future work to reduce the share size to \[\leq \dfrac{1}{3} \left( (1+ o(1)) \dfrac{2^{\ell}}{\sqrt{\pi \ell/2}}(2 q^{\varrho + 0.5} + 2\sqrt{q}) \right).\], Comment: Final version published in Theoretical Computer Science, 2021, volume 886, pp. 106-138