Auditory hemispheric asymmetry for actions and objects.

What is the function of auditory hemispheric asymmetry? We propose that the identification of sound sources relies on the asymmetric processing of two complementary and perceptually relevant acoustic invariants: actions and objects. In a large dataset of environmental sounds, we observed that temporal and spectral modulations display only weak covariation. We then synthesized auditory stimuli by simulating various actions (frictions) occurring on different objects (solid surfaces). Behaviorally, discrimination of actions relies on temporal modulations, while discrimination of objects relies on spectral modulations. Functional magnetic resonance imaging data showed that actions and objects are decoded in the left and right hemispheres, respectively, in bilateral superior temporal and left inferior frontal regions. This asymmetry reflects a generic differential processing-through differential neural sensitivity to temporal and spectral modulations present in environmental sounds-that supports the efficient categorization of actions and objects. These results support an ecologically valid framework of the functional role of auditory brain asymmetry.

Evaluation of supplemented protein-L-isoaspartate-O-methyltransferase (PIMT) gene of Carica papaya and Ricinus communis in stress survival of Escherichia coli BL21(DE3) cells.

In growing plant population, effect of stress is a perturb issue affecting its physiological, biochemical, yield loss and developmental growth. Protein-L-isoaspartate-O-methyltransferase (PIMT) is a broadly distributed protein repair enzyme which actuate under stressful environment or aging. Stress can mediate damage converting protein bound aspartate (Asp) residues to isoaspartate (iso-Asp). This spontaneous and deleterious conversion occurs at an elevated state of stress and aging. Iso-Asp formation is associated with protein inactivation and compromised cellular survival. PIMT can convert iso-Asp back to Asp, thus repairing and contributing to cellular survival. The present work describes the isolation, cloning, sequencing and expression of PIMT genes of Carica papaya (Cp pimt) and Ricinus communis (Rc pimt) Using gene specific primers, both the pimts were amplified from their respective cDNAs and subsequently cloned in prokaryotic expression vector pProEXHTa. BL21(DE3) strain of E. coli cells were used as expression host. The expression kinetics of both the PIMTs were studied with various concentrations of IPTG and at different time points. Finally, the PIMT supplemented BL21(DE3) cells were evaluated against different stresses in comparison to their counterparts with the empty vector control.

A simple and efficient pathway for the total synthesis of marine natural products: bengamide E and 5-epi-bengamide E.

Total synthesis of the marine natural product bengamide E and 5-epi-bengamide E has been accomplished using two routes: (i) via a polyhydroxy acid precursor involving a total of 16 steps with an overall yield of 17.0% and (ii) via a cyclic lactone precursor with a total of 12 steps and overall 23.0% yield. The key steps involve (1) regioselective p-methoxybenzylidine ring opening, (2) a stereoselective Grignard reaction and (3) olefin cross-metathesis. The total synthesis could provide significant quantities of bengamide E and 5-epi-bengamide E as all the reaction processes were very efficient and the raw materials were inexpensive and highly abundant. The protocol has an advantage over previously reported methods as it provides ready access to the C-5 hydroxy group for further modification and its future structure-activity relationship studies for anti-tumor activity.

Sensitivity of agricultural crops to tropospheric ozone: a review of Indian researches.

Tropospheric ozone (O3) is a long-range transboundary secondary air pollutant, causing significant damage to agricultural crops worldwide. There are substantial spatial variations in O3 concentration in different areas of India due to seasonal and geographical variations. The Indo-Gangetic Plain (IGP) region is one of the most crop productive and air-polluted regions in India. The concentration of tropospheric O3 over the IGP is increasing by 6-7.2% per decade. The annual trend of increase is 0.4 ± 0.25% year-1 over the Northeastern IGP. High O3 concentrations were reported during the summer, while they were at their minimum during the monsoon months. To explore future potential impacts of O3 on major crop plants, the responses of different crops grown under ambient and elevated O3 concentrations were compared. The studies clearly showed that O3 is an important stress factor, negatively affecting the yield of crops. In this review, we have discussed yield losses in agricultural crops due to rising O3 pollution and variations in O3 sensitivity among cultivars and species. The use of ethylene diurea (EDU) as a research tool in assessing the losses in yield under ambient and elevated O3 levels also discussed. Besides, an overview of interactive effects of O3 and nitrogen on crop productivity has been included. Several recommendations are made for future research and policy development on rising concentration of O3 in India.

Assessment of rosacea symptom severity by genome-wide association study and expression analysis highlights immuno-inflammatory and skin pigmentation genes.

Rosacea is a common, chronic skin disease of variable severity with limited treatment options. The cause of rosacea is unknown, but it is believed to be due to a combination of hereditary and environmental factors. Little is known about the genetics of the disease. We performed a genome-wide association study (GWAS) of rosacea symptom severity with data from 73 265 research participants of European ancestry from the 23andMe customer base. Seven loci had variants associated with rosacea at the genome-wide significance level (P < 5 × 10-8). Further analyses highlighted likely gene regions or effector genes including IRF4 (P = 1.5 × 10-17), a human leukocyte antigen (HLA) region flanked by PSMB9 and HLA-DMB (P = 2.2 × 10-15), HERC2-OCA2 (P = 4.2 × 10-12), SLC45A2 (P = 1.7 × 10-10), IL13 (P = 2.8 × 10-9), a region flanked by NRXN3 and DIO2 (P = 4.1 × 10-9), and a region flanked by OVOL1and SNX32 (P = 1.2 × 10-8). All associations with rosacea were novel except for the HLA locus. Two of these loci (HERC-OCA2 and SLC45A2) and another precedented variant (rs1805007 in melanocortin 1 receptor) with an association P value just below the significance threshold (P = 1.3 × 10-7) have been previously associated with skin phenotypes and pigmentation, two of these loci are linked to immuno-inflammation phenotypes (IL13 and PSMB9-HLA-DMA) and one has been associated with both categories (IRF4). Genes within three loci (PSMB9-HLA-DMA, HERC-OCA2 and NRX3-DIO2) were differentially expressed in a previously published clinical rosacea transcriptomics study that compared lesional to non-lesional samples. The identified loci provide specificity of inflammatory mechanisms in rosacea, and identify potential pathways for therapeutic intervention.

Same-day discharge in selected patients undergoing atrial fibrillation ablation.

BACKGROUND: Atrial fibrillation (AF) ablation is a complex procedure, generally requiring at least one overnight hospital stay. We investigated the safety and feasibility of early mobilization and same-day discharge following streamlined peri-ablation management for AF. METHODS: From 2014, we offered same-day discharge to selected patients who underwent uncomplicated AF ablation on the morning lists, with ultrasound-guided femoral access, uninterrupted warfarin or minimal interruption in novel oral anticoagulants, and reversal of intraprocedural heparin with protamine. Patients were discharged 6-8 h postprocedure and offered access to a dedicated nurse helpline. RESULTS: Of 1599 AF ablation cases performed from April 2014 to March 2017, 811 (50.7%) were performed on the morning lists and 169/811 (20.8%) were discharged on the same day. Excluding 26 research cases, 1/143 (0.7%) had transient right phrenic nerve palsy and five (3.5%) cases experienced minor problems that did not preclude same-day discharge; three (2.1%) needed rehospitalization postdischarge: one for pericarditic chest pain and two for nausea/vomiting. Compared to 642 overnight cases, day-case procedures were shorter, more likely to be redos, to be performed under sedation rather than general anesthesia, and less likely to involve linear lesions and electrical cardioversion. There were no significant differences in patient age, gender, body mass index, CHA2 DS2 -VASc, in preprocedural anticoagulation regimen (warfarin vs novel anticoagulants vs no anticoagulation) and in choice of ablation method (cryoballoon vs radiofrequency). CONCLUSIONS: Selective same-day discharge after AF ablation is safe and feasible using a streamlined peri-procedural care protocol. Wider adoption can potentially reduce health-care costs while improving patient experience.

Knowledge and attitude of women attending Subharti Medical College towards Pap smear.

The aim of this prospective study was to assess the knowledge and attitude of women towards the Pap smear. It was carried out on the women coming to the Department of Obstetrics and Gynaecology at our University, with the help of a pre-formed questionnaire. We found that only 33% of the women were aware of the Pap smear, and of these hardly (10%) had the correct information. Sixty-five percent of the women said that they would have gotten the Pap smear done, if they had known about it earlier. Unless this knowledge amongst women is improved and their attitude is changed, the indices of cervical cancer cannot be improved. Impact statement What is already known on this subject? A Pap smear is used as a screening test to detect not only early stages of cervical cancer but also the precancerous conditions. A Pap smear is done every three years for routine screening, or every five years along with an HPV DNA test. What do the results of this study add? Despite the efforts from the medical fraternity and governments, the number of women undergoing this test in Uttar Pradesh is very minimal. This study analysed the knowledge and attitude of women towards the Pap smear. What are the implications of these findings for clinical practice and/or further research? The results have brought into light the many factors hindering an effective cervical cancer screening in India. Further actions need to be directed in the direction to address these issues.

Calcium-induced conformational changes of Thrombospondin-1 signature domain: implications for vascular disease.

CONTEXT: Thrombospondin1 (TSP1) participates in numerous signaling pathways critical for vascular physiology and disease. The conserved signature domain of thrombospondin 1 (TSP1-Sig1) comprises three epidermal growth factor (EGF), 13 calcium-binding type 3 thrombospondin (T3) repeats, and one lectin-like module arranged in a stalk-wire-globe topology. TSP1 is known to be present in both calcium-replete (Holo-) and calcium-depleted (Apo-) state, each with distinct downstream signaling effects. OBJECTIVE: To prepare a homology model of TSP1-Sig1 and investigate the effect of calcium on its dynamic structure and interactions. METHODS: A homology model of Holo-TSP1-Sig1 was prepared with TSP2 as template in Swissmodel workspace. The Apo-form of the model was obtained by omitting the bound calcium ions from the homology model. Molecular dynamics (MD) simulation studies (100 ns) were performed on the Holo- and Apo- forms of TSP1 using Gromacs4.6.5. RESULTS AND DISCUSSION: After simulation, Holo-TSP1-Sig1 showed significant reorientation at the interface of the EGF1-2 and EGF2-3 modules. The T3 wire is predicted to show the maximum mobility and deviation from the initial model. In Apo-TSP1-Sig1 model, the T3 repeats unfolded and formed coils with predicted increase in flexibility. Apo-TSP1-Sig1model also predicted the exposure of the binding sites for neutrophil elastase, integrin and fibroblast growth factor 2. We present a structural model and hypothesis for the role of TSP1-Sig1 interactions in the development of vascular disorders. CONCLUSION: The simulated model of the fully calcium-loaded and calcium-depleted TSP1-Sig1 may enable the development of its interactions as a novel therapeutic target for the treatment of vascular diseases.

Eps15 homology domain containing protein of Plasmodium falciparum (PfEHD) associates with endocytosis and vesicular trafficking towards neutral lipid storage site.

The human malaria parasite, Plasmodium falciparum, takes up numerous host cytosolic components and exogenous nutrients through endocytosis during the intra-erythrocytic stages. Eps15 homology domain-containing proteins (EHDs) are conserved NTPases, which are implicated in membrane remodeling and regulation of specific endocytic transport steps in eukaryotic cells. In the present study, we have characterized the dynamin-like C-terminal Eps15 homology domain containing protein of P. falciparum (PfEHD). Using a GFP-targeting approach, we studied localization and trafficking of PfEHD in the parasite. The PfEHD-GFP fusion protein was found to be a membrane bound protein that associates with vesicular network in the parasite. Time-lapse microscopy studies showed that these vesicles originate at parasite plasma membrane, migrate through the parasite cytosol and culminate into a large multi-vesicular like structure near the food-vacuole. Co-staining of food vacuole membrane showed that the multi-vesicular structure is juxtaposed but outside the food vacuole. Labeling of parasites with neutral lipid specific dye, Nile Red, showed that this large structure is neutral lipid storage site in the parasites. Proteomic analysis identified endocytosis modulators as PfEHD associated proteins in the parasites. Treatment of parasites with endocytosis inhibitors obstructed the development of PfEHD-labeled vesicles and blocked their targeting to the lipid storage site. Overall, our data suggests that the PfEHD is involved in endocytosis and plays a role in the generation of endocytic vesicles at the parasite plasma membrane, that are subsequently targeted to the neutral lipid generation/storage site localized near the food vacuole.

Integrative analysis of ocular complications in atherosclerosis unveils pathway convergence and crosstalk.

Atherosclerosis is a life-threatening disease and a major cause of mortalities worldwide. While many of the atherosclerotic sequelae are reflected as microvascular effects in the eye, the molecular mechanisms of their development is not yet known. In this study, we employed a systems biology approach to unveil the most significant events and key molecular mediators of ophthalmic sequelae caused by atherosclerosis. Literature mining was used to identify the proteins involved in both atherosclerosis and ophthalmic diseases. A protein-protein interaction (PPI) network was prepared using the literature-mined seed nodes. Network topological analysis was carried out using Cytoscape, while network nodes were annotated using database for annotation, visualization and integrated discovery in order to identify the most enriched pathways and processes. Network analysis revealed that mitogen-activated protein kinase 1 (MAPK1) and protein kinase C occur with highest betweenness centrality, degree and closeness centrality, thus reflecting their functional importance to the network. Our analysis shows that atherosclerosis-associated ophthalmic complications are caused by the convergence of neurotrophin signaling pathways, multiple immune response pathways and focal adhesion pathway on the MAPK signaling pathway. The PPI network shares features with vasoregression, a process underlying multiple vascular eye diseases. Our study presents a first clear and composite picture of the components and crosstalk of the main pathways of atherosclerosis-induced ocular diseases. The hub bottleneck nodes highlight the presence of molecules important for mediating the ophthalmic complications of atherosclerosis and contain five established drug targets for future therapeutic modulation efforts.

Management of Aberrant Frenum and Gingival Overgrowth in Orthodontic Patients: A Case Report.

The frenum, a fold of mucous membrane, connects the lip and cheek to the alveolar mucosa, gingiva, and underlying periosteum. When the frenum is positioned excessively near the gingival margin, it has the potential to compromise gingival health, impeding plaque control efforts and inducing muscular stress. A frenectomy is a commonly employed corrective measure for anomalous frenum attachments. In a recent clinical case, a 21-year-old female patient was referred from the Department of Orthodontics to the Department of Periodontics due to a papillary-type aberrant labial frenum attachment and excessive gingival tissue surrounding the upper right and left central incisors. The patient underwent a frenectomy, gingivectomy, and gingivoplasty procedures under local anesthesia to address the abnormal frenum attachment and gingival overgrowth using a scalpel. This approach has been demonstrated to yield optimal outcomes in orthodontic therapy for patients exhibiting elevated frenum attachment and gingival overgrowth. Following the achievement of hemostasis, a periodontal pack was applied to facilitate healing and preserve the soft tissue.

Repair of Iatrogenic Furcal Perforation With Mineral Trioxide Aggregate: A Case Report.

In endodontic and restorative procedures, an accidental perforation of the pulp chamber floor or roots presents a considerable risk, potentially leading to persistent inflammatory responses and ultimately tooth loss. Accidental root canal perforations are primary complications encountered by clinicians, requiring either surgical or non-surgical intervention, depending on the severity of the perforation. Over the years, various materials have been utilized for the treatment of such complications, but mineral trioxide aggregate (MTA) stands out prominently due to its exceptional biocompatibility, remarkable sealing capacity, and potent antibacterial properties. The unique ability of MTA to set in the presence of moisture facilitates the formation of a robust seal, thereby making it highly effective in managing root perforations and fostering tissue regeneration within the affected area. Its versatility and effectiveness have made MTA a cornerstone material in modern endodontic therapy, offering clinicians a reliable solution for enhancing the long-term prognosis of teeth affected by perforations.

Fetomaternal outcomes in pregnant women with congenital heart disease: a comparative analysis from an apex institute.

OBJECTIVE: With advancements in cardiac surgical interventions during infancy and childhood, the incidence of maternal congenital heart disease (CHD) is increasing. This retrospective study compared fetal and cardiac outcomes in women with and without CHD, along with a sub-analysis between cyanotic versus non-cyanotic defects and operated versus non-operated cases. METHODS: A 10-year data were retrospectively collected from pregnant women with CHD and a 1:1 ratio of pregnant women without any heart disease. Adverse fetal and cardiac outcomes were noted in both groups. Statistical significance was set at P<0.05. RESULTS: A total of 86 pregnant women with CHD were studied, with atrial septal defects (29.06%) being the most common. Out of 86 participants, 27 (31.39%) had cyanotic CHD. Around 55% of cases were already operated on for their cardiac defects. Among cardiovascular complications, 5.8% suffered from heart failure, 7.0% had pulmonary arterial hypertension, 8.1% presented in New York Heart Association functional class IV, 9.3% had a need for intensive care unit admission, and one experienced maternal mortality. Adverse fetal outcomes, including operative vaginal delivery, mean duration of hospital stay, fetal growth restriction, preterm birth (<37 weeks), low birth weight (<2,500 g), 5-minute APGAR score <7, and neonatal intensive care unit admissions, were significantly higher in women with CHD than in women without heart disease. CONCLUSION: Women with CHD have a higher risk of adverse fetal and cardiac outcomes. The outcome can be improved with proper pre-conceptional optimization of the cardiac condition, good antenatal care, and multidisciplinary team management.

Synthesis, QSAR study and Pharmacological Evaluation of Novel Triazolidine-2-thione Analogues as Antimicrobial, Anti-inflammatory and Antioxidant agents.

BACKGROUND: The triazole analogues are molecules of immense attraction because of their wide pharmacological applications. METHODS: Present research deals with the synthesis of triazole-2-thione analogues and their QSAR study. The synthesized analogs are also evaluated for their antimicrobial, anti-inflammatory, and antioxidant effect. RESULTS: It was revealed that the benzamide analogues (3a, 3d) and triazolidine analogue (4b) were found to be most active against P. aeruginosa and E. coli with pMIC values of 1.69, 1.69 and 1.72, respectively. The antioxidant study of the derivatives showed that 4b was the most active antioxidant with 79% protein denaturation inhibition. The highest anti-inflammatory activity was shown by 3f, 4a and 4f. CONCLUSION: This study provides certain potent leads for further development of more potential anti-inflammatory, antioxidant and antimicrobial agents.

In Contemporary Reproductive Medicine Human Beings are Not Yet Dispensable.

In the past few years almost every aspect of an IVF cycle has been investigated, including research on sperm, color doppler in follicular studies, prediction of embryo cleavage, prediction of blastocyst formation, scoring blastocyst quality, prediction of euploid blastocysts and live birth from blastocysts, improving the embryo selection process, and for developing deep machine learning (ML) algorithms for optimal IVF stimulation protocols. Also, artificial intelligence (AI)-based methods have been implemented for some clinical aspects of IVF, such as assessing patient reproductive potential and individualizing gonadotropin stimulation protocols. As AI has the inherent capacity to analyze "Big" data, the goal will be to apply AI tools to the analysis of all embryological, clinical, and genetic data to provide patient-tailored individualized treatments. Human skillsets including hand eye coordination to perform an embryo transfer is probably the only step of IVF that is outside the realm of AI & ML today. Embryo transfer success is presently human skill dependent and deep machine learning may one day intrude into this sacred space with the advent of programed humanoid robots. Embryo transfer is arguably the rate limiting step in the sequential events that complete an IVF cycle. Many variables play a role in the success of embryo transfer, including catheter type, atraumatic technique, and the use of sonography guidance before and during the procedure of embryo transfer. In contemporary Reproductive Medicine human beings are not yet dispensable.

Zirconium-Coated ß-Cyclodextrin Nanomaterials for Biofilm Eradication.

Under alkaline treatment, zirconyl chloride (ZrOCl2.8H2O) became a zirconia gel and formed a stable complex with beta-cyclodextrin (ßCD). This complex was highly active in reactive oxygen species (ROS) formation via H2O2 decomposition. Its surface with numerous hydroxyl groups acts as an ionic sponge to capture the charged reaction intermediates, including superoxide (O2-•) and the hydroxyl radical (•OH). ROS, especially •OH radicals, are harmful to living microorganisms because of their kinetic instability, high oxidation potential, and chemical nonselectivity. Therefore, •OH radicals can engage in fast reactions with virtually any adjacent biomolecule. With H2O2, the complex with cationic and hydrophobic moieties interacted with the anionic bacterial membrane of two Gram-positive (Staphylococcus aureus and S. epidermidis) and two Gram-negative (Escherichia coli and Klebsiella pneumoniae) strains. The Zr-ßCD-H2O2 also eradicated more than 99% of the biofilm of these four pathogens. Considering the difficult acquisition of resistance to the oxidation of •OH, the results suggested that this ßCD-based nanomaterial might be a promising agent to target both drug-resistant pathogens with no cytotoxicity and exceptional antimicrobial activity.

Discovery of imeglimin-inspired novel 1,3,5-triazine derivatives as antidiabetic agents in streptozotocin-induced diabetes in Wistar rats via inhibition of DPP-4.

Novel 1,3,5-triazine derivatives bearing oxazine have been synthesized and tested for their ability to inhibit a panel of dipeptidyl peptidase (DPP)-4, 8, and 9 enzymes. In a comparative inhibitory assay, the molecules showed potent inhibition of DPP-4 ranging from IC50 of 4.2 ± 0.30-260.5 ± 0.42 nM, with no activity against DPP-8 and DPP-9. Among the tested series, compound 8c demonstrated the strongest DPP-4 inhibitory activity with an IC50 of 4.2 ± 0.30 nM. It also showed the greatest binding affinity during docking studies with DPP-4 with a docking score of -8.956 and a glide energy of -78.546 kcal mol-1 and was found oriented in the S1 and S2 pockets of the DPP-4 active site, which is composed of the catalytic triad Ser 630, Asp 710, and His 740. The in vivo pharmacological assay revealed that compound 8c in a dose-dependent manner improved the insulin level, body weight, antioxidants, and HDL, and reduced the levels of blood glucose, LDL, and VLDL in streptozotocin-induced diabetes in Wistar rats. Our study demonstrated the discovery and development of novel 1,3,5-triazine derivatives bearing oxazine as a novel class of anti-diabetic agents via inhibition of DPP-4.

Discovery of novel 1,3,5-triazine derivatives as an antidiabetic agent in Wistar rats via inhibition of DPP-4.

Aim: To develop imeglimin-inspired novel 1,3,5-triazine derivatives as antidiabetic agents. Materials & methods: These derivatives were synthesized and tested against DPP enzymes. Compound 8c was tested for in vivo antidiabetic activity in streptozotocin-induced diabetes in Wistar rats by estimating various biochemical parameters. Docking experiments were also performed. Results: Compound 8c was identified as a selective and potent DPP-4 inhibitor. It was proficiently docked into the catalytic triad of Ser 630, Asp 710 and His740 in S1 and S2 pockets of DPP-4. In experimental animals, it also showed dose-dependent improvement in blood glucose, blood insulin, bodyweight, lipid profile and kidney and liver antioxidant profiles. Conclusion: This study demonstrated the discovery of imeglimin-inspired novel 1,3,5-triazines as a potent antidiabetic agent.

Type 2 diabetes mellitus is a complicated heterogeneous and polygenic metabolic disease. Therefore, in search of a potent antidiabetic drug, the authors have synthesized 13 novel 1,3,5-triazine-morpholino-pyrazole derivatives, compounds 8(a­m), and they were subsequently tested for in vitro inhibitory activity against a panel of DPP enzymes (DPP-4, DPP-8 and DPP-9) where they are found active toward DPP-4 while inactive toward DPP-8 and DPP-9. Compound 8c was observed to be the most potent DPP-4 inhibitor and showed excellent interaction with DPP-4 in docking analysis. Furthermore, in high-fat, low-dose streptozotocin-induced diabetes in rats, compound 8c significantly reduced blood glucose, cholesterol, triglyceride, low-density lipoprotein, very low-density lipoprotein and reactive species levels and increased high-density lipoprotein levels, possibly by the potent inhibition of DPP-4. It also showed intense antioxidant activity. The potent DPP-4 inhibition, antidiabetic and antioxidant activity render compound 8c a probable lead for antidiabetic drug discovery.