Search

Myofibroblasts were first detected in the granulation tissue and low-grade myofibroblastic sarcoma has now been recognized as a distinct entity. It has an indolent clinical course and distant metastasis is very rare. Hence surgical excision is the mainstay of the treatment. However, this tumor morphologically mimics other relatively high-grade soft tissue sarcomas, so distinguishing them is of utmost importance. Here we report, a 22-year-old young girl presented with neck pain and a slowly growing mass in the cervical paraspinal region. The patient was managed by wide local excision and the specimen was examined thoroughly. After considering all the features diagnosis of low-grade myofibroblastic sarcoma was offered.

The ionization state of amino acids on the outer surface of a virus regulates its physicochemical properties toward the sorbent surface. Serologically different strain of dengue virus (DENV) shows different extents of infectivity depending upon their interactions with a receptor on the host cell. To understand the structural dependence of E-protein protonation over its sequence dependence, we have followed E-protein titration kinetics both experimentally and theoretically for two differentially infected dengue serotypes, namely DENV-2 and DENV-4. We have performed an E-protein protonation titration-induced single particle chemical force spectroscopy using an atomic force microscope (AFM) to measure the surface chemistry of DENV in physiological aqueous solutions not only to understand the charge distribution dynamics on virus surface but also to estimate the isoelectric point (pI) accurately for infectious dengue viruses. Cryo-EM structure-based theoretical pI calculations of DENV-2 surface protein were shown to be consistent with the evaluated pI value from force spectroscopy measurements. This is a comprehensive study to understand how the cumulative charge distribution on the outer surface of a specific serotype of DENV regulates a prominent role of infectivity over minute changes at the genetic level.

Scaling and root planning (SRP) is essential for preventing bacterial infection, it is always the first step of periodontal treatment. The treatment of periodontal pockets with excisional new attachment procedure (ENAP) and gingival curettage as an adjunct to SRP in the treatment of periodontitis represents yet another novel causative therapy

The evaluation of speech outcomes after resection and reconstruction of the oral tongue remains largely unsystematic. A cross-sectional study was performed to analyse the speech outcomes of patients who underwent curative treatment with appropriate reconstruction. Sixty-nine patients were assessed for speech intelligibility and phonetics using a validated speech intelligibility assessment tool in the local language. Volume defects were classified as class I (less than one third), II (one third to half), III (half to two-thirds), or IV (two-thirds to total glossectomy). Defect location was defined as lateral, tip, or sulcus. The χ2 test and Kruskal-Wallis test were used to test volume and location as predictors. Twenty-six patients had class I defects, 29 had class II defects, seven had class III defects, and seven had class IV defects. Twenty-two patients (31.9%) received adjuvant radiotherapy. Mean vowel, consonant, word, and paragraph intelligibility were 99.27%, 86.86%, 85.52%, and 88.72%, respectively. The incremental volume of the glossectomy defect was significantly correlated with speech intelligibility scores and phonatory alterations. In classes II and III, tip resection significantly affected interdental sounds. All patients in class III had affected alveolar and alveo-palatal sounds. The results positively corroborated the volume and location of the glossectomy defect to a classification system.

Acute febrile neutrophilic dermatosis (Sweet syndrome) is a potentially fatal multiorgan inflammatory disease characterized by fever, leukocytosis, and a rash with a neutrophilic infiltrate. Disease pathophysiology remains elusive, and current dogma suggests Sweet syndrome is a "reactive" process to an unknown antigen. Corticosteroids and steroid-sparing agents remain front-line therapies, but refractory cases pose a clinical challenge.A 51-year-old woman with multiorgan Sweet syndrome developed serious corticosteroid-related side effects and was refractory to steroid-sparing agents. Blood counts, liver enzymes, and skin histopathology supported the diagnosis. Whole genome sequencing, transcriptomic profiling, and cellular assays of patient's skin and neutrophils were performed.We identified elevated IL-1 signaling in lesional Sweet syndrome skin caused by a PIK3R1 gain-of-function mutation specifically found in neutrophils. This mutation increased neutrophil migration towards IL-1β and neutrophil respiratory burst. Targeted treatment with an IL-1R1 antagonist in the patient resulted in a dramatic therapeutic response and enabled tapering of corticosteroids.Dysregulated PI3K-AKT signaling is the first signaling pathway linked to Sweet syndrome and suggests Sweet syndrome may be caused by acquired mutations that modulate neutrophil function. Moreover, integration of molecular data across multiple levels identified a distinct subtype within a heterogenous disease that resulted in a rational and successful clinical intervention. Future cases will benefit from efforts to identify potential mutations. The ability to directly interrogate diseased skin allows this method to be generalizable to other inflammatory diseases and demonstrates a potential personalized medicine approach for challenging patients.FUNDING Berstein Foundation, NIH, VA, Moseley Foundation, and H.T. Leung Foundation.

Background: Integrin αV, encoded by ITGAV gene, is one of the most studied protein subunits, closely associated with liver, pancreatic and stomach cancer progression and metastasis via regulation of angiogenesis. The occurrence of Single Nucleotide Polymorphisms (SNPs) in cancer- associated proteins is a key determinant for varied susceptibility of an individual towards cancer. Methodology: The study investigated the deleterious effects of these cancer-associated SNPs on the protein’s structure, stability and cancer causing potential using an in silico approach. Numerous computational tools were employed that identified the most deleterious cancer-associated SNPs and those to get actively involved in post-translational modifications. The impact of these SNPs on the protein structure, function and stability was also examined. Conclusion and Future Scope: A total 63 non-synonymous SNPs in ITGAV gene were observed to be associated in these three gastrointestinal cancers and among this, 63, 19 were the most deleterious ones. The structural and functional importance of residues altered by most damaging SNPs was analyzed through evolutionary conservation and solvent accessibility. The study also elucidated three-dimensional structures of the 19 most damaging mutants. The analysis of conformational variation identified 5 SNPs (D379Y, G188E, G513V, L950P, and R540L) in integrin αV, which influence the protein’s structure. Three calcium binding sites were predicted at residues: D379, G384 and G408 and a peptide binding site at residue: R369 in integrin αV. Therefore, SNPs D379Y, G384C, G408R and R369W have the potential to alter the binding properties of the protein. Screening and characterization of deleterious SNPs could advance novel biomarker discovery and therapeutic development in the future.

A small heat shock protein, HSP27, encoded by HSPB1 gene strongly favors survival, proliferation and metastasis of cancer cells and its expression is dependent on post-translational modifications like phosphorylation. This study performed an extensive in silico screening of 20 deleterious non-synonymous SNPs in the coding region of HSPB1 gene, among which four were identified to be cancer associated. The SNP variant I181S introduced a new phosphorylation site in position 181, which might elevate the protein's activation potential. Emergence of other post-translational modifications was also observed in SNP variants: L144P and E130K.Significant conformational changes were observed in I181S, L144P and E130K SNP variants with respect to wild-type HSP27. These SNPs appear in one among 105 individuals, making them more susceptible towards cancer. This study would therefore, instigate development of novel biomarkers for cancer risk detection and would provide a detailed understanding towards varied cancer susceptibility of human population.

Implant success is evaluated on the basis of the stability gained at the junction of the bone to the implant. The stability needed for the successful future outcomes are of two types, i.e., primary stability which is acquired while placing the implant and secondary stability acquired by osseointegration. At present a new idea of Osseodensication has been established for the preparing the osteotomy site for the insertion of the implant. It is a bone non-extraction technique for osteotomy site preparation. There is a low plastic deformation of bone caused by rolling plus sliding contact with osteotomes or densifying burs which have utes to densify bone as it drills into it and expand osteotomy site. This technique permits bone preservation along with its condensation by compaction autografting of bone through osteotomy site preparation resulting in enhanced peri-implant bone density, healing and mechanical stability as well as minimised micromotion of the implant. This clinical approach is valuable at the sites where there is anatomic paucity of the bone

COVID-19 is one of the fatal pandemic throughout the world. For cellular fusion, its antigenic peptides are presented by major histocompatibility complex (MHC) in humans. Therefore, exploration into residual interaction details of CoV2 with MHCs shall be a promising point for instigating the vaccine development. Envelope (E) protein, the smallest outer surface protein from SARS-CoV2 genome was found to possess the highest antigenicity and is therefore used to identify B-cell and T-cell epitopes. Four novel mutations (T55S, V56F, E69R and G70del) were observed in E-protein of SARS-CoV2 after evolutionary analysis. It showed a coil➔helix transition in the protein conformation. Antigenic variability of the epitopes was also checked to explore the novel mutations in the epitope region. It was found that the interactions were more when SARS-CoV2 E-protein interacted with MHC-I than with MHC-II through several ionic and H-bonds. Tyr42 and Tyr57 played a predominant role upon interaction with MHC-I. The higher ΔG values with lesser dissociation constant values also affirm the stronger and spontaneous interaction by SARS-CoV2 proteins with MHCs. On comparison with the consensus E-protein, SARS-CoV2 E-protein showed stronger interaction with the MHCs with lesser solvent accessibility. E-protein can therefore be targeted as a potential vaccine target against SARS-CoV2.

This study aimed to characterize the swallowing outcomes after glossectomy and analyze factors affecting them. An attempt is made to propose a classification system and corroborate it to the results. This is a cross-sectional study to assess swallowing in carcinoma tongue patients treated surgically with or without reconstruction, followed by adjuvant therapy as indicated. One hundred and six patients were evaluated with videofluoroscopy (VFS). Volume defects were classified as I: less than one-third, II: one-third to half, III: half to two-thirds, IV: two-thirds to total glossectomy. Location was assigned as lateral, tip, and sulcus defects. Predictors were T stage, surgical approach, volume, location, and adjuvant radiotherapy. Chi-square and logistic regression were used for statistical analysis. Defects were Class I, II, III, and IV in 36, 42, 16, and 12 patients, respectively. Adjuvant radiotherapy was given in 40% of cases. Mean evaluation time was 14 months from treatment. On, Functional Oral Intake Scale (FOIS) score, as the Class of the defect increased, the percentage of patients with low scores (poor swallowing outcomes) showed an increasing trend (p

We will present the international effort that led to the first-ever revision of the Sunspot and Group Numbers (let us call them "the Sunspot Series"), a well-known series that had never been put into question since its creation by Rudolf Wolf in 1849. We will review the process and its challenges (ISSI review paper, https://www.issibern.ch/teams/sunspotnoser/). At this point in time, the number of Group Number series available is still based on different techniques that enable the stitching of datasets of various quality over wildly different periods, and although they present an undeniable improvement over the original Group Number from Hayt & Schatten (1998), the resulting series remain to be extensively tested in order to be clearly validated by the scientific community.Since this first revision in 2015 (Solar Physics Topical Issue, 2016), the Sunspot Series have become living datasets that require constant monitoring since more source data are being recovered regularly (Arlt & Vaquero, 2020). With the team from ISSI, we are currently driving a large effort to gather raw data from all around the world. At the Royal Observatory of Belgium, within the WDC-SILSO (https://wwwbis.sidc.be/silso/) where the original Mittheilungen have been digitized (2017-2019) we also have 2 PhD students working on stitching historical and modern sunspot numbers and evaluating the quality of the reconstructed series through advanced statistical techniques.After this review of previous efforts, we will focus more specifically on the reconstruction of the International Sunspot Number from raw sunspot data (Bhattacharya et al., 2021, 2022, FARSUN belgian project) end present the potential impact of these revisions on end users (e.g. F10.7, Clette, 2021).

Visual sunspot observations form the longest scientific record of solar activity, spanning over four centuries. Long term solar studies are crucial to predict the future evolution of the solar cycles and at improving our understanding of the solar influence on Earth climate change.As an important step for the ongoing sunspot number recalibration throughout the entire solar physics community, (Lefevre et al., 2018), SN Version 2 was released in July, 2015 (Clette et al., 2016), which helped in shedding new light to long-term solar variations and instabilities of the 11-year solar cycle. However, uncertainties remain and errors in past historical data need to be further revised using the data at our disposal for a robust long-term series.In 1843, Professor Rudolf Wolf who coined the term “Sunspot Number”, founded a journal called the "Mittheilungen der Naturforschenden Gesellschaft in Berne" where he published yearbooks with all of his findings, including sunspot observations as far back as Galileo (Wolf, 1861). The journal was maintained from 1848 (Wolf, 1848) until his death (Wolf and Wolfer, 1894). The Sunspot records collected by him from his European colleagues and his auxiliary observers are all tabulated in this journal. The Royal Observatory of Belgium (https://www.astro.oma.be/en/), particularly the WDC-SILSO, conducted a mission between 2017 and 2019 to digitize all the data contained in the published Mittheilungen.In this study we exploit this database along with other available recounts of various observers to identify scale discrepancies or inhomogeneities that happened along the Sunspot number series over time. We also introduce statistical techniques to implement confidence bands or errors on daily Sunspot Numbers, an information that existing versions lack. The long-term aim is a complete reconstruction of the Sunspot Number series from the available raw data instead of a recalibration.

Babesia microti, an emerging human pathogen, is primarily transmitted through a bite of an infected tick and blood transfusions in human. Stable transfection technique has been reported in many protozoan parasites over the past few years. However, in vivo transient and stable transfection method has not been established for Babesia microti. Here, for the first time, we present a method of transient as well as stable transfection of the Babesia microti (B. microti) in the in vivo conditions. We have identified a novel promoter of B. microti. We also demonstrated that Plasmodium berghei DHFR promoter is recognized and functional in B. microti. We show that BM-CTQ41297 promoter control the expression of two genes, which are present on either side and thus represents a bi-functional promoter in B. microti. The predicted promoter activity values using Promoter 2.0 program is higher for BM- CTQ41297 promoter than strong promoters such as β-actin, ef-1β, and many other promoters. Furthermore, we discovered a non-essential locus for the genetic manipulation of the parasite, allowing us to stably integrate foreign genes; GFP, mCherry, into the B. microti. The transfection using an electroporation method and genetic manipulation of B. microti is now achievable and it is possible to obtain transfected viable parasites under in vivo growing conditions. The growth curve analysis of transfected and WT B. microti are similar indicating no defects in the transgenic parasites. This study will enable other researchers in understanding the B. microti biology, host modulation and diverse parasite developmental stages using reverse genetics and holds great potential to identify novel drug targets and vaccine development.

Background: Nipah virus (NiV) and Hendra virus (HeV) of genus Henipavirus are the deadliest zoonotic viruses, which cause severe respiratory ailments and fatal encephalitis in humans and other susceptible animals. The fatality rate for these infections had been alarmingly high with no approved treatment available to date. Viral attachment and fusion with host cell membrane is essential for viral entry and is the most essential event of viral infection. Viral attachment is mediated by interaction of Henipavirus attachment glycoprotein (G) with the host cell receptor: Ephrin B2/B3, while viral fusion and endocytosis are mediated by the combined action of both viral glycoprotein (G) and fusion protein (F). Conclusion: This review highlights the mechanism of viral attachment, fusion and also explains the basic mechanism and pathobiology of this infection in humans. The drugs and therapeutics used either experimentally or clinically against NiV and HeV infection have been documented and classified in detail. Some amino acid residues essential for the functionality of G and F proteins were also emphasized. Therapeutic designing to target and block these residues can serve as a promising approach in future drug development against NiV and HeV.

Aspergillus fumigatus is a ubiquitous mold associated with the development of pulmonary diseases that include invasive pulmonary aspergillosis (IPA), an often fatal opportunistic infection. FIBCD1 is a transmembrane endocytic membrane receptor widely expressed on human epithelium. Although FIBCD1 was previously shown to bind chitin, modulate fungal colonization of the gut, and inhibit intestinal inflammation, the role of FIBCD1 in the context of lung fungal infection remains unknown. In this study, we observed that mortality, fungal burden, and tissue histopathology were decreased in the absence of FIBCD1 in murine IPA. Quantitative RT-PCR analyses demonstrated decreased inflammatory cytokines in the lungs of neutrophil-depleted FIBCD1−/− mice with IPA, when compared with wild-type controls. In contrast, inflammatory cytokines were increased in immune-competent FIBCD1−/− mice after fungal aspiration, suggesting that the presence of neutrophils is associated with cytokine modulation. In contrast to the clear IPA phenotype, FIBCD1−/− mice with systemic infection or bleomycin-induced lung injury exhibited similar morbidity and mortality when compared with their wild-type counterparts. Thus, our study identifies a detrimental role of FIBCD1 in IPA. ImmunoHorizons, 2021, 5: 983–993.

LEA (Late Embryogenesis Abundant) proteins are abundant in plants and play a crucial role in abiotic stress tolerance. In our work, we primarily focused on the variations in physiochemical properties, conserved domains, secondary structure, gene ontology and evolutionary relationships among 40 LEA proteins of Triticum aestivum (common wheat). Wheat LEA protein belongs to first 6 classes out of the 13 classes present in LEApdB, the comprehensive database for LEA proteins. Proteins belonging to each LEApdB class have structures and functions distinguished from other classes. The study found three different conserved LEA domains in Triticum aestivum. One important domain was dehydrin, present in wheat proteins of classes 1, 2 and 4, though varied in sequence level, have similar biological processes. The study also found sequence level and phylogenetic similarity between dehydrin domains of class 1 and 4, but distinct from that of LEApdB class 2. This study also demonstrated functional diversity in two class 6 proteins occurred due to many destabilizing mutations in the LEA4 domain that caused alteration of ligand binding and conformational shift from 310-helix → turn within the domain. The LEA4 domains of these proteins also showed functional similarity and evolutionary relatedness with three other proteins of genus Aegilops, denoting that these proteins in Triticum aestivum were derived from its ancestor Aegilops. The study also assigned LEApdB class 4 to an unclassified LEA protein ‘WZY2-1’ based on amino acid composition, conserved domain, motif architecture and phylogenetic relatedness with class 4 proteins. Our study has revealed a detailed analysis of LEA proteins in Triticum aestivum and can serve as a pillar for further investigations and comparative analysis of wheat LEA proteins with other cereal or plant types.

This present study centers hepatocellular adenomas (IHCAs) and its effect due to gp130 mutations based on evolutionary relationship as well as literature survey involving wet-laboratory experiments. Generally, IL6 family of cytokines interacts with their respective IL6 receptors and gp130, which in turn induces JAK/STAT pathway to activate pro-inflammatory STAT3 target genes. The activation of this signaling pathway poses a paramount impact in tumor development. Several mutations in gp130 were studied through evolutionary relatedness which aggravates the tumorigenesis. Mutations in IL6Rα binding domain region (positions: 131–218 of human gp130) from MSA were also studied. A point mutation: A200V in Otolemur garnettii showed the deleterious effect. Further, the deleterious effect upon proteins’ functionality was also examined and seven mutations were responsible for it. V189G showed the highest destabilizing effect. Unstable conformation shifts were also observed in the proteins due to their respective mutations. Change in the transmembrane region, change in gp130s’ ordered interface, loss of sulfation at Y186, lesser relative solvent accessibility, change in protein stability and metal binding properties were also observed in several mutations. These mutations might be responsible for changing the activity of the IL6Rα binding domain region of human gp130 protein triggering hepatocellular adenomas. Therefore, targeting gp130 and its mutations would serve as an important therapeutic target to cause apoptosis of the tumor cells. Interaction studies within the three proteins for the respective mutations could also to be in the future pathway of research. It would also aim to instigate the drug discovery for the same.

The contact hypothesis posits that having diverse neighbours may reduce one’s intergroup prejudice. This hypothesis is difficult to test as individuals self-select into neighbourhoods. Using a slum relocation programme in India that randomly assigned neighbours, I examine the effects of exposure to other-caste neighbours on trust and attitudes towards members of other castes. Combining administrative data on housing assignment with original survey data on attitudes, I find evidence corroborating the contact hypothesis. Exposure to more neighbours of other castes increases inter-caste trust, support for inter-caste marriage, and the belief that caste injustice is growing. I explore the role of friendships in facilitating these favourable attitudes. The findings shed light on the positive effects of exposure to diverse social groups through close proximity in neighbourhoods.

Wheat (Triticum aestivum), having high nutritional values is one of the staple food of most of the countries in the world. The productivity of the crop decreases drastically when it encounters various abiotic stresses, most common of which are heat, drought, flood and salinity. There is a crucial role of stress response proteins for the survival of the crops in stress conditions. So the study of wheat stress response proteins is of great importance to raise wheat production in different stress conditions. In this study, we analysed 14-3-3 protein, a stress response protein that is expressed in three major stresses, for example heat, drought and salinity and helps the plants to survive in those conditions. Effect of mutations in the 14-3-3 sequence was predicted using its domain, secondary structure and multiple sequence alignment of amino acid sequences from wheat and its related species. The functional diversity of the protein in different species was correlated with mutations, change in secondary structure and the evolutionary relatedness of the protein in different species. This is the first novel work for analysing the mutational effect on the structure and function of a stress response protein (14-3-3) from Triticum aestivum and its related species.

Nasogastric tube (NGT) insertion is routinely performed in oral cancer surgeries. Although it is not uncommon for the tube to coil around in the pharynx during blind insertion, we came across a patient with trismus where the malpositioned NGT had coiled around the nasotracheal tube (NTT). We hereby describe this uncommon complication and its management in this scenario.

Epidermal homeostasis relies on a well-defined transcriptional control of keratinocyte proliferation and differentiation, which is critical to prevent skin diseases such as atopic dermatitis, psoriasis or cancer. We have recently shown that the homeobox transcription factor DLX3 and the tumor suppressor p53 co-regulate cell cycle-related signaling and that this mechanism is functionally involved in cutaneous squamous cell carcinoma development. Here we show that DLX3 expression and its downstream signaling depend on protein kinase C α (PKCα) activity in skin. We found that following 12-O-tetradecanoyl-phorbol-13-acetate (TPA) topical treatment, DLX3 expression is significantly upregulated in the epidermis and keratinocytes from mice overexpressing PKCα by transgenic targeting (K5-PKCα), resulting in cell cycle block and terminal differentiation. Epidermis lacking DLX3 (DLX3cKO), which is linked to the development of a DLX3-dependent epidermal hyperplasia with hyperkeratosis and dermal leukocyte recruitment, displays enhanced PKCα activation, suggesting a feedback regulation of DLX3 and PKCα. Of particular significance, transcriptional activation of epidermal barrier, antimicrobial peptide and cytokine genes is significantly increased in DLX3cKO skin and further increased by TPA-dependent PKC activation. Furthermore, when inhibiting PKC activity, we show that epidermal thickness, keratinocyte proliferation and inflammatory cell infiltration are reduced and the PKC-DLX3-dependent gene expression signature is normalized. Independently of PKC, DLX3 expression specifically modulates regulatory networks such as Wnt signaling, phosphatase activity and cell adhesion. Chromatin immunoprecipitation sequencing analysis of primary suprabasal keratinocytes showed binding of DLX3 to the proximal promoter regions of genes associated with cell cycle regulation, and of structural proteins and transcription factors involved in epidermal differentiation. These results indicate that Dlx3 potentially regulates a set of crucial genes necessary during the epidermal differentiation process. Altogether, we demonstrate the existence of a robust DLX3–PKCα signaling pathway in keratinocytes that is crucial to epidermal differentiation control and cutaneous homeostasis.

Aim and Objective: One of the challenges to conventional therapies against Mycobacterium tuberculosis is the development of multi-drug resistant pathogenic strains. This study was undertaken to explore new therapeutic targets for the revolutionary antivirulence therapy utilizing the pathogen’s essential hypothetical proteins, serving as virulence factors, which is the essential first step in novel drug designing. Methods: Functional annotations of essential hypothetical proteins from Mycobacterium tuberculosis (H37Rv strain) were performed through domain annotation, Gene Ontology analysis, physicochemical characterization and prediction of subcellular localization. Virulence factors among the essential hypothetical proteins were predicted, among which pathogen-specific drug target candidates, non-homologous to human and gut microbiota, were identified. This was followed by druggability and spectrum analysis of the identified targets. Results and conclusion: The study successfully assigned functions of 83 essential hypothetical proteins of Mycobacterium tuberculosis, among which 25 were identified as virulence factors. Out of 25, 12 virulence factors were observed as potential pathogen-specific drug target candidates. Nine potential targets had druggable properties and rest three were considered as novel targets. Exploration of these targets will provide new insights into future drug development. Characterization of subcellular localizations revealed that most of the predicted targets were cytoplasmic which could be ideal for intracellular drugs, while two drug targets were membranebound, ideal for vaccines. Spectrum analysis identified one broad-spectrum and 11 narrowspectrum targets. This study would, therefore, instigate designing novel therapeutics for antivirulence therapy, which have the potential to serve as revolutionary treatment instead of conventional antibiotic therapies to overcome the lethality of antibiotic-resistant strains.

Is there always an inherent contradiction between political pragmatismand ethics? This paper explores this through the classical Indian realist politicaltreatise, the Arthashastra, written by Kautilya. He was the key advisor to EmperorChandragupta Maurya (c. 317-293 B.C.E), credited with first consolidating theIndian subcontinent into an empire under centralized control. Kautilya is widelyagreed to be a pioneer in developing a ‘science of politics’- a great departure fromthe hitherto existing moralistic, spiritual, ascetic preoccupations and, religiousspeculations of Indian political philosophy. Kautilya blurred the distinctionbetween morality and political utility. Much of political theory tradition remainsoblivious to Kautilya’s contribution to morality in realpolitik and his continuinginfluence in non-Western societies. His treatise is a significant point of entry intoexploring the dilemmas attached to active pursuance of ethical goals while alsobalancing the imperatives underpinning political pragmatism- a concern whichhas carried on to this day.

While free flap is the standard of care for bony reconstruction of the mandible, complex oro-mandibular defects after oral cancer ablation require adequate skin and soft-tissue replacement for optimum functional results. We report a case of multifaceted oral cavity resection effectively reconstructed in single stage by the three-way pectoralis major osteomyocutaneous flap. The technical aspects, benefits, deficiencies, and literature review are discussed. In the background of multiple recurrences and comorbidities, this flap is a viable alternative and should be given due reconsideration in oral cancer surgery. This gains more relevance in the context of developing countries.

Simultaneous occurrence of oral submucous fibrosis along with carcinoma of the buccal mucosa is common. We report a novel technique of a single dumbbell-shaped, cross-cheek radial forearm free flap to repair bilateral defects caused by oral cancer resection on one side and the release of fibrosis on the other side in two patients. The dumbbell-shaped flap provided tissue for both the buccal mucosa defects and central released soft palate preventing fibrosis and reapproximation. The interincisor distance improved in both the patients.

Salmonella strains are responsible for a huge mortality rate through foodborne ailment in the world that necessitated the discovery of novel drugs and vaccines. Essential hypothetical proteins (EHPs), whose structures and functions were previously unknown, could serve as potential therapeutic and vaccine targets. Antivirulence therapy shall emerge as a superior therapeutic approach that uses virulence factors as drug targets. This study annotated the biological functions of 96 out of total 106 essential hypothetical proteins in five strains of Salmonella and classified into nine important protein categories. 34 virulence factors were predicted among the EHPs, out of which, 11 were identified to be pathogen specific potential drug targets for antivirulence therapy. These targets were non-homologous to both human and gut microbiota proteome to avoid cross-reactivity with them. Seven identified targets had druggable property, while the rest four targets were novel targets. Four identified targets (DEG10320148, DEG10110027, DEG10110040 and DEG10110142) had antigenic properties and were further classified as: two membrane-bound Lipid-binding transmembrane proteins, a Zinc-binding membrane protein and an extracellular glycosylase. These targets could be potentially used for the development of subunit vaccines. The study further identified 11 highly conserved and exposed epitope sequences from these 4 vaccine targets. The three-dimensional structures of the vaccine targets were also elucidated along with highlighting the conformation of the epitopes. This study identified potential therapeutic targets for antivirulence therapy against Salmonella. It would therefore instigate in novel drug designing as well as provide important leads to new Salmonella vaccine development.

e19515 Background: Acute Myeloid Leukemia (AML) is a highly heterogeneous disease. High throughput sequencing (HTS) has led to the discovery of a number of recurrently mutated genes in AML & has provided a detailed molecular landscape of the disease. This information is now extensively utilised & interpreted in AML. Methods: Retrospective analysis of 47 patients with newly diagnosed AML for those who had both cytogenetic and targeted HTS information at diagnosis, [median age: 44y (12-80y); 24 females] & treated at Tata Medical Center, India between 2013-2019. HTS was performed using Illumina Trusight myeloid panel and/or Thermo Fisher Scientific Oncomine Myeloid panel, and mutation data from the common 28 genes were used. Patients were stratified by European Leukemia Net (ELN) 2010 and 2017 guidelines. Standard of care clinical outcome data was available for all patients. Results: 45 of 47 patients had mutations. The most frequently mutated gene was FLT3 (n = 13, 28.9%), followed by NPM1 (n = 8, 17.8%), and others [ IDH1, IDH2, TET2, CEBPA, and NRAS; n = 7, 15.6%). ELN-2010 classified 6 patients as Favourable (12.8%), 10 as Intermediate-I (21.3%), 25 as Intermediate-II (53.2%) and 6 as Adverse (12.8%) risk groups. One patient migrated to the adverse group from Intermediate-II when ELN-2017 was applied. ELN 2017 re-classification: Favorable (n = 6, 12.8%), intermediate (n = 34, 72.3%), and adverse risk groups (n = 7, 14.9%). Co-occurrence of driver gene mutations was found in NPM1 and FLT3 (8.2%) frequently. Patients with mutations in epigenetic modifiers ( ASXL1, IDH1, IDH2, DNMT3A) had high Variant Allele Frequency (VAF, 40-50%) while those with signaling pathway gene mutations ( NRAS, KRAS) had low VAF (9-25%). At a median follow up of 3.25 years, median overall survival in the three risk groups (favorable, intermediate, adverse) were 11.25 mons, 7 mons and 8 mons respectively, and relapse rates were 16%, 29% and 42% respectively. Conclusions: Early experience from a middle-income real-world setting suggests feasibility of integration of HTS information in practise, as additional prognostic/ predictive information. The pattern of a high VAF in epigenetic modifier gene mutations, potentially as a result of early acquisition during clonal development, needs further evaluation. This data set has helped us initiate a prospective multimodal omics study at our institution.

Expedition into anti-aggregating proteins present in the plant kingdom led to discovery of Late embryogenesis abundant (LEA) proteins, a group of versatile, hydrophilic, heat stable, low molecular weight proteins that play a significant role in abiotic stress tolerance in plants. In plant, LEA proteins have been detected in various regions such as in roots, stems and seedlings. The expression of LEA proteins has been observed to get highly elevated in stressed conditions, especially drought, temperature fluctuations and salinity. This study identified three different LEA designated domains in Oryza sativa indica (Indian rice), namely LEA3, LEA4 and LEA6, and focused on which other organisms have these LEA domains with >50% sequence identity than that of Oryza sativa indica. Diversity in physiochemical properties, structure and gene ontology were observed among LEA3, LEA4 and LEA6 domain-containing proteins along with their genomic distribution and level of expression. An inverse relationship between disorder and coil content, while a direct relationship between disorder and helix content were observed in these LEA domain-containing proteins. Higher content of helix breakers like proline and glycine and less helix former like alanine, glutamate and lysine resulted in low helix and high coil in LEA6 domain-containing proteins. While the opposite trend was observed in helix-rich LEA4 domain-containing protein with a high content of helix formers and very low content of helix breakers. Phylogenetic study classified the LEA domain containing proteins into two clusters with LEA4 and LEA6 domain-containing proteins in the same group, even though they have significant structural diversity and LEA3 domain-containing proteins in the other cluster. This computational study holds an insight in agricultural biotechnology by highlighting the role of LEA domains in abiotic stress response and would further instigate detailed study and comparative analyses of LEA domains of other cereal crops and advancement in the field of genetic engineering.