Phenotypic, genomic, and transcriptomic heterogeneity in a pancreatic cancer cell line.

OBJECTIVES: To evaluate the suitability of the MIA PaCa-2 cell line for studying pancreatic cancer intratumor heterogeneity, we aim to further characterize the nature of MIA PaCa-2 cells' phenotypic, genomic, and transcriptomic heterogeneity. METHODS: MIA PaCa-2 single-cell clones were established through flow cytometry. For the phenotypic study, we quantified the cellular morphology, proliferation rate, migration potential, and drug sensitivity of the clones. The chromosome copy number and transcriptomic profiles were quantified using SNPa and RNA-seq, respectively. RESULTS: Four MIA PaCa-2 clones showed distinctive phenotypes, with differences in cellular morphology, proliferation rate, migration potential, and drug sensitivity. We also observed a degree of genomic variations between these clones in form of chromosome copy number alterations and single nucleotide variations, suggesting the genomic heterogeneity of the population, and the intrinsic genomic instability of MIA PaCa-2 cells. Lastly, transcriptomic analysis of the clones also revealed gene expression profile differences between the clones, including the uniquely regulated ITGAV, which dictates the morphology of MIA PaCa-2 clones. CONCLUSIONS: MIA PaCa-2 is comprised of cells with distinctive phenotypes, heterogeneous genomes, and differential transcriptomic profiles, suggesting its suitability as a model to study the underlying mechanisms behind pancreatic cancer heterogeneity.

What is the role of out of programme clinical fellowships in the era of Shape of Training? A single-centre cohort study.

BACKGROUND: The updated Shape of Training curriculum has shortened the duration of specialty training. We present the potential role of out of programme clinical fellowships. METHOD: An electronic online survey was sent to all current fellows to understand their experiences, training opportunities and motivations.Data were collected on fellows' endoscopic experiences and publications using PubMed for all previous doctors who have completed the Sheffield Fellowship Programme. RESULTS: Since 2004, 39 doctors have completed the Sheffield Fellowship.Endoscopic experience: current fellows completed a median average of 350 (IQR 150-500) gastroscopies and 150 (IQR 106-251) colonoscopies per year. Fellows with special interests completed either 428 hepato-pancreato-biliary procedures or 70 endoscopic mucosal resections per year.Medline publications: Median average 9 publications(IQR 4-17). They have also received multiple national or international awards and 91% achieved a doctoral degree.The seven current fellows in the new Shape of Training era (57% male, 29% Caucasian, aged 31-40 years) report high levels of enjoyment due to their research projects, supervisory teams and social aspects. The most cited reasons for undertaking the fellowship were to develop a subspecialty interest, take time off the on-call rota and develop endoscopic skills. The most reported drawback was a reduced income.All current fellows feel that the fellowship has enhanced their clinical confidence and prepared them to become consultants. CONCLUSION: Out of programme clinical fellowships offer the opportunity to develop the required training competencies, subspecialty expertise and research skills in a supportive environment.

A Case of Gastrointestinal Stromal Tumour (GIST) in the Duodenum in a Young Adult.

Gastrointestinal stromal tumours (GISTs) are rare gastrointestinal (GI) malignancies, but the most prevalent mesenchymal tumours of the GI tract arise from the interstitial cells of Cajal. They account for 1-3% of all GI malignancies, and only 3-5% of all cases of GIST are located at the duodenal. We present a case of a young adult who presented to the ED with symptoms of GI bleeding.

Genome-Wide Mapping of Quantitative Trait Loci for Yield-Attributing Traits of Peanut.

Peanuts (Arachis hypogaea L.) are important high-protein and oil-containing legume crops adapted to arid to semi-arid regions. The yield and quality of peanuts are complex quantitative traits that show high environmental influence. In this study, a recombinant inbred line population (RIL) (Valencia-C × JUG-03) was developed and phenotyped for nine traits under two environments. A genetic map was constructed using 1323 SNP markers spanning a map distance of 2003.13 cM. Quantitative trait loci (QTL) analysis using this genetic map and phenotyping data identified seventeen QTLs for nine traits. Intriguingly, a total of four QTLs, two each for 100-seed weight (HSW) and shelling percentage (SP), showed major and consistent effects, explaining 10.98% to 14.65% phenotypic variation. The major QTLs for HSW and SP harbored genes associated with seed and pod development such as the seed maturation protein-encoding gene, serine-threonine phosphatase gene, TIR-NBS-LRR gene, protein kinase superfamily gene, bHLH transcription factor-encoding gene, isopentyl transferase gene, ethylene-responsive transcription factor-encoding gene and cytochrome P450 superfamily gene. Additionally, the identification of 76 major epistatic QTLs, with PVE ranging from 11.63% to 72.61%, highlighted their significant role in determining the yield- and quality-related traits. The significant G × E interaction revealed the existence of the major role of the environment in determining the phenotype of yield-attributing traits. Notably, the seed maturation protein-coding gene in the vicinity of major QTLs for HSW can be further investigated to develop a diagnostic marker for HSW in peanut breeding. This study provides understanding of the genetic factor governing peanut traits and valuable insights for future breeding efforts aimed at improving yield and quality.

Understanding COVID-19 vaccine hesitancy in Meghalaya, India: Multiple correspondence and agglomerative hierarchical cluster analyses.

Meghalaya, a state in the northeastern region of India, had a markedly low vaccine uptake compared to the other states in the country when COVID-19 vaccines were being rolled out in 2021. This study aimed to characterize the distinct vaccine-hesitant subpopulations in healthcare and community settings in Meghalaya state in the early days of the vaccination program. We used data from a cross-sectional survey that was administered to 200 healthcare workers (HCWs) and 200 community members, who were a priori identified as 'vaccine-eligible' and 'vaccine-hesitant,' in Shillong city, Meghalaya, in May 2021. The questionnaire collected information on participants' sociodemographic characteristics, COVID-19 history, and presence of medical comorbidities. Participants were also asked to provide a dichotomous answer to a set of 19 questions, probing the reasons for their hesitancy towards COVID-19 vaccines. A multiple correspondence analysis, followed by an agglomerative hierarchical cluster analysis, was performed to identify the distinct clusters of vaccine-hesitant participants. We identified seven clusters: indecisive HCWs (n = 71), HCWs skeptical of COVID-19 and COVID-19 vaccines (n = 128), highly educated male tribal/clan leaders concerned about infertility and future pregnancies (n = 14), less educated adults influenced by leaders and family (n = 47), older adults worried about vaccine safety (n = 76), middle-aged adults without young children (n = 56), and highly educated ethnic/religious minorities with misinformation (n = 8). Across all the clusters, perceived logistical challenges associated with receiving the vaccine was identified as a common factor contributing to vaccine hesitancy. Our study findings provide valuable insights for local and state health authorities to effectively target distinct subgroups of vaccine-hesitant populations with tailored health messaging, and also call for a comprehensive approach to address the common drivers of vaccine hesitancy in communities with low vaccination rates.

Aeroplane wing, a new recessive autosomal phenotypic marker in the malaria vector, Anopheles stephensi Liston.

A novel and distinct mutant with a phenotype, aeroplane wing (ae) is reported for the first time in the urban malaria vector Anopheles stephensi. The main aim of this study was to establish the mode of inheritance of the ae gene performing genetic crossings between the mutants and wild types. These mutants show extended open wings that are visible to naked eyes in both the sexes. Mutants were first noticed in a nutritionally stressed isofemale colony. Strategic genetic crosses revealed that the ae gene is a recessive, autosomal, and monogenic trait having full penetrance with uniform expression in its adult stage. Egg morphometric analysis confirmed that these mutants were intermediate variant. No significant differences were observed in the wing venation and size of ae mutants compared to their control parental lines. Further cytogenetic analysis on the ovarian polytene chromosome of ae mutant showed an inversion (3Li) on the 3L arm like its parental line. This ae mutant would be a prominent marker and could be useful to study the functions of related specific genes within its genome.

Vector-Control Potential of Unani Medicines: A Review of Classical Unani Texts and Contemporary Scientific Literature.

BACKGROUND OBJECTIVES: Vector-borne diseases pose substantial global health challenges, with a notable impact in India as well. Effective vector control strategies are crucial to mitigating these diseases as there are no effective vaccines available. Synthetic chemicals are widely used but concerns about safety and environmental impact have prompted exploration of alternative, natural solutions. Unani medicine offers a potential source of natural products. This study aims to systematically review classical Unani texts and contemporary scientific literature to evaluate the vector control potential of Unani medicines. METHODS: A comprehensive review of classical Unani texts was carried out to compile data on herbal and mineral substances suggested in Unani Medicine for control of insects. Furthermore, electronic databases like PubMed, Google Scholar, and Science Direct were explored for research studies evaluating the insect-repellent, larvicidal, and insecticidal activities of the Unani medicines recommended in these texts. Time restriction was not imposed to ensure the comprehensive retrieval of pertinent and up-to-date information. RESULTS: From classical Unani texts, 29 drugs were identified for control of insects, primarily of plant origin from diverse botanical families. Recent scientific investigations have confirmed the insect-repellent, insecticidal, and larvicidal activities of 19 of these Unani medicines against various insect species, including mosquitoes. INTERPRETATION CONCLUSION: These findings underscore the potential of Unani medicines as natural source for vector control. However, further research is essential to explore mechanism, delivery methods, and optimal concentrations for developing effective vector-control formulations.

Differential modulation of cellular phenotype and drug sensitivity by extracellular matrix proteins in primary and metastatic pancreatic cancer cells.

Pancreatic ductal adenocarcinoma (PDAC) is reported to be the third highest cause of cancer-related deaths in the United States. PDAC is known for its high proportion of stroma, which accounts for 90% of the tumor mass. The stroma is made up of extracellular matrix (ECM) and nonmalignant cells such as inflammatory cells, cancer-associated fibroblasts, and lymphatic and blood vessels. Here, we decoupled the effects of the ECM on PDAC cell lines by culturing cells on surfaces coated with different ECM proteins. Our data show that the primary tumor-derived cell lines have different morphology depending on the ECM proteins on which they are cultured, while metastatic lesion-derived PDAC lines' morphology does not change with respect to the different ECM proteins. Similarly, ECM proteins modulate the proliferation rate and the gemcitabine sensitivity of the primary tumor PDAC cell lines, but not the metastatic PDAC lines. Lastly, transcriptomics analysis of the primary tumor PDAC cells cultured on different ECM proteins reveals the regulation of various pathways, such as cell cycle, cell-adhesion molecules, and focal adhesion, including the regulation of several integrin genes that are essential for ECM recognition.

A comprehensive survey on the beliefs, perceptions, and clinical manifestations of pre and post Covid-19 vaccinations among physiotherapy students in the United Arab Emirates.

The World Health Organization has defined Coronavirus Disease (COVID-19) as an infectious pandemic, caused by a newly discovered SARS-CoV-2 virus. Students relied heavily on the internet, social media, parents, and friends, in addition to medical advice for information on its presentation, complications, prevention, and management. It is evident from the literature that healthcare professionals including students who play an important role in the healthcare system may be lacking important information on COVID-19 vaccinations. Thus, the study aims to identify and compare the pre-post covid-19 vaccination-related essential information among Physical Therapy university students. A cross-sectional survey was conducted among physiotherapy university students in the United Arab Emirates using a self-administrated structured questionnaire. The questionnaire comprised three sections covering beliefs, perceptions, and clinical manifestations of the pre- and post-COVID- 19 vaccination. The survey was shared with more than 300 students through email and social platforms during the time between January 2022 till December 2022. Most of the physiotherapy students believed the vaccines to be safe (71.3%) due to multiple reasons while others did not believe in the effectiveness of the vaccine (28.7%). Some students did report unusual symptoms (painful periods, hair loss, forgetfulness) after the vaccine (10%). Similar findings were reported for family members as well (14%). Students had a positive perception of the vaccine and reported willingness to take it even if not mandatory (68%). Some students did believe in the safety of the vaccine due to multiple reasons while some did not due to fear of long-term side effects and personal choices. The finding of the study could be useful to create confidence as well as awareness among physiotherapy students as they are often invited to aid during medical pandemics such as Covid 19. Also, higher rates of vaccination among healthcare professionals will impart higher acceptance in the medical organization due to safety guidelines. This could also help to counsel other students against fear and apprehension towards the vaccination of such kind in the future.

Enrichment of phenotype among biological forms of Anopheles stephensi Liston through establishment of isofemale lines.

BACKGROUND: Vector management programs rely on knowledge of the biology and genetic make-up of mosquitoes. Anopheles stephensi is a major invasive urban malaria vector, distributed throughout the Indian subcontinent and Middle East, and has recently been expanding its range in Africa. With the existence of three biological forms, distinctly identifiable based on the number of ridges on eggs and varying vectorial competence, An. stephensi is a perfect species for developing isofemale lines, which can be tested for insecticide susceptibility and vectorial competence of various biological forms. METHODS: We describe key steps involved in establishment and validation of isofemale lines. Isofemale colonies were further used for the characterization of insecticide susceptibility and differential vector competence. The results were statistically evaluated through descriptive and inferential statistics using Vassar Stat and Prism GraphPad software packages. RESULTS: Through a meticulous selection process, we overcame an initial inbreeding depression and found no significant morphometric differences in wings and egg size between the parental and respective isofemale lines in later generations. IndCh and IndInt strains showed variations in resistance to different insecticides belonging to all four major classes. We observed a significant change in vectorial competence between the respective isofemale and parental lines. CONCLUSIONS: Isofemale lines can be a valuable resource for characterizing and enhancing several genotypic and phenotypic traits. This is the first detailed report of the establishment of two isofemale lines of type and intermediate biological forms in Anopheles stephensi. The work encompasses characterization of fitness traits among two lines through a transgenerational study. Furthermore, isofemale colonies were established and used to characterize insecticide susceptibility and vector competence. The study provides valuable insights into differential susceptibility status of the parental and isofemale lines to different insecticides belonging to the same class. Corroborating an earlier hypothesis, we demonstrate the high vector competence of the type form relative to the intermediate form using homozygous lines. Using these lines, it is now possible to study host-parasite interactions and identify factors that might be responsible for altered susceptibility and increased vector competence in An. stephensi biological forms that would also pave the way for developing better vector management strategies.

Optimization of alkali, acid and organic solvent pretreatment on rice husk and its techno economic analysis for efficient sugar production.

Excessive use of fossil fuels has accelerated climate change and global warming necessitates the need for renewable energy sources that have a lower environmental impact. In the recent decade, lignocellulosic biomass has become a prominent alternative to renewable energy resources for the production of bioenergy. The pretreatment procedure is considered a pivotal step for transforming biomass into value-added products such as sugars, biofuels, etc. Therefore, the present work aims to study the effect of different pretreatment approaches on rice husk with acids (H2SO4 and HCl), alkalis (NaOH and KOH), and organic solvents (ethanol and methanol) utilizing different concentrations like (2, 4 and 6% in case of acids), (2,4 and 6% for alkalis) and (50% and 70% for organic solvents) with different residence time (1, 3, 6, and 24 h). The most effective results obtained from the aforementioned steps were further adopted for enzymatic hydrolysis. Further, the changes in structural properties of biomass were assessed in relation to the pretreatment process employing scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier Transform Infrared (FTIR) analyses. This paper also highlights the techno-economic analysis of alkali pretreatment. Additionally, the operational targets for the process were identified by using a modeling software-SuperPro Designer. Results obtained from the study showed a maximum yield of reducing sugar i.e., 1.906 ± 0.2 mg/ml (4% NaOH with 6 h of incubation). This study demonstrates that 4% NaOH pretreatment effectively disintegrates the biomass and yields high sugar recovery which can be used further for the production of biofuels and value-added products.

The need for a holistic approach toward pandemic control: lessons from a cross-sectional study on COVID-19 in Meghalaya, India.

We conducted a community-based cross-sectional survey of 416 participants from Meghalaya, India to assess knowledge, perceptions, and practices toward recommended COVID-19 preventive measures, and to explore health-seeking behavior and stigma during early phase of the pandemic. Most participants had knowledge of the signs and symptoms of COVID-19 (94%) and its spread (96%), and reported positive behavior change such as handwashing ≥ 6 times/day (41% pre-COVID-19 vs. 81% during COVID-19, P < 0.001), sneezing or coughing into sleeves (65% pre-COVID-19 vs. 89% during COVID-19, P < 0.001) and staying home if having flu-like symptoms (44% pre-COVID-19 vs. 94% during COVID-19, P < 0.001). We found delayed healthcare seeking for non-COVID-19 illnesses (16%). Fear of losing life was reported by 26% participants, as was discrimination toward migrant returnees, with 35% blaming returnees for the spread of COVID-19. We highlight the need for a holistic approach toward pandemic control, including social and mental health interventions, in public health strategies.

Identification of a TNF-TNFR-like system in malaria vectors (Anopheles stephensi) likely to influence Plasmodium resistance.

Identification of Plasmodium-resistance genes in malaria vectors remains an elusive goal despite the recent availability of high-quality genomes of several mosquito vectors. Anopheles stephensi, with its three distinctly-identifiable forms at the egg stage, correlating with varying vector competence, offers an ideal species to discover functional mosquito genes implicated in Plasmodium resistance. Recently, the genomes of several strains of An. stephensi of the type-form, known to display high vectorial capacity, were reported. Here, we report a chromosomal-level assembly of an intermediate-form of An. stephensi strain (IndInt), shown to have reduced vectorial capacity relative to a strain of type-form (IndCh). The contig level assembly with a L50 of 4 was scaffolded into chromosomes by using the genome of IndCh as the reference. The final assembly shows a heterozygous paracentric inversion, 3Li, involving 8 Mbp, which is syntenic to the extensively-studied 2La inversion implicated in Plasmodium resistance in An. gambiae involving 21 Mbp. Deep annotation of genes within the 3Li region in the IndInt assembly using the state-of-the-art protein-fold prediction and other annotation tools reveals the presence of a tumor necrosis factor-alpha (TNF-alpha) like gene, which is the homolog of the Eiger gene in Drosophila. Subsequent chromosome-wide searches revealed homologs of Wengen (Wgn) and Grindelwald (Grnd) genes, which are known to be the receptors for Eiger in Drosophila. We have identified all the genes in IndInt required for Eiger-mediated signaling by analogy to the TNF-alpha system, suggesting the presence of a functionally-active Eiger signaling pathway in IndInt. Comparative genomics of the three type-forms with that of IndInt, reveals structurally disruptive mutations in Eiger gene in all three strains of the type-form, suggesting compromised innate immunity in the type-form as the likely cause of high vectorial capacity in these strains. This is the first report of the presence of a homolog of Eiger in malaria vectors, known to be involved in cell death in Drosophila, within an inversion region in IndInt syntenic to an inversion associated with Plasmodium resistance in An. gambiae.

Customized Pen for Patients With Arthritis.

Patients with arthritis present with pain, stiffness and limited movement of fingers and hands. Performing tasks independently lead to a lot of anxiety and emotional trauma. Holding simple things like a toothbrush or pen is a cumbersome task. This article describes a simple technique to customize a pen for arthritis patients. The pen holder is customized to the patient's fingers making it easier to write.

Latitudinal but not elevational variation in blood glucose level is linked to life history across passerine birds.

Macrophysiological research is vital to our understanding of mechanisms underpinning global life history variation and adaptation to diverse environments. Here, we examined latitudinal and elevational variation in a key substrate of energy metabolism and an emerging physiological component of pace-of-life syndromes, blood glucose concentration. Our data, collected from 61 European temperate and 99 Afrotropical passerine species, revealed that baseline blood glucose increases with both latitude and elevation, whereas blood glucose stress response shows divergent directions, being stronger at low latitudes and high elevations. Low baseline glucose in tropical birds, compared to their temperate counterparts, was mainly explained by their low fecundity, consistent with the slow pace-of-life syndrome in the tropics. In contrast, elevational variation in this trait was decoupled from fecundity, implying a unique montane pace-of-life syndrome combining slow-paced life histories with fast-paced physiology. The observed patterns suggest that pace-of-life syndromes do not evolve along the single fast-slow axis.

An analysis of government-sponsored health insurance enrolment and claims data from Meghalaya: Insights into the provision of health care in North East India.

INTRODUCTION: The Megha Health Insurance Scheme (MHIS) was launched in 2013 in the North-East Indian state of Meghalaya to reduce household out-of-pocket expenditure on health and provide access to high-quality essential healthcare. Despite substantial expansion of the MHIS since the scheme's inception, there is a lack of comprehensive documentation and evaluation of the scheme's performance against its Universal Health Care (UHC) objectives. METHODS: We analysed six years of enrolment and claims data (2013-2018) covering three phases of the scheme to understand the pattern of enrolment, utilisation and care provision under the MHIS during this period. De-identified data files included information on age, sex, district of residence, the district of provider hospital, type of hospital, date of admission, status at discharge, claimed category of care, package codes, and amount claimed. Descriptive statistics were generated to investigate key trends in enrolment, service utilisation, and Government health spending under the MHIS. RESULTS: Approximately 55% of the eligible population are currently enrolled in MHIS. Enrolment increased consistently from phase I through III and remained broadly stable across districts, gender, age group and occupation categories, with a small decline in males 19-60 years. Claims were disproportionately skewed towards private provision; 57% of all claims accrued to the 18 empanelled private hospitals and 39% to the 159 public sector facilities. The package 'General Ward Unspecified' was responsible for the highest volume of claims and highest financial dispensation across all three phases of the scheme. This likely indicates substantial administrative error and is potentially masking both true burden of disease and accurate financial provision for care under the MHIS. Anti-rabies injections for dog/cat bite contributed to 11% of total claims under MHIS III, and 1.6% of all claims under MHIS II. This warrants investigation to better understand the burden of animal bites on the Meghalayan population and inform the implementation of cost-effective strategies to reduce this burden. CONCLUSIONS: This paper describes the first analysis of health insurance enrolment and claims data in the state of Meghalaya. The analysis has generated an important evidence base to inform future MHIS enrolment and care provision policies as the scheme expands to provide Universal Health Coverage to the state's entire population.

The genome trilogy of Anopheles stephensi, an urban malaria vector, reveals structure of a locus associated with adaptation to environmental heterogeneity.

Anopheles stephensi is the most menacing malaria vector to watch for in newly urbanising parts of the world. Its fitness is reported to be a direct consequence of the vector adapting to laying eggs in over-head water tanks with street-side water puddles polluted by oil and sewage. Large frequent inversions in the genome of malaria vectors are implicated in adaptation. We report the genome assembly of a strain of An. stephensi of the type-form, collected from a construction site from Chennai (IndCh) in 2016. The genome reported here with a L50 of 4, completes the trilogy of high-resolution genomes of strains with respect to a 16.5 Mbp 2Rb genotype in An. stephensi known to be associated with adaptation to environmental heterogeneity. Unlike the reported genomes of two other strains, STE2 (2R+b/2Rb) and UCI (2Rb/2Rb), IndCh is found to be homozygous for the standard form (2R+b/2R+b). Comparative genome analysis revealed base-level details of the breakpoints and allowed extraction of 22,650 segregating SNPs for typing this inversion in populations. Whole genome sequencing of 82 individual mosquitoes from diverse geographical locations reveal that one third of both wild and laboratory populations maintain the heterozygous genotype of 2Rb. The large number of SNPs can be tailored to 1740 exonic SNPs enabling genotyping directly from transcriptome sequencing. The genome trilogy approach accelerated the study of fine structure and typing of an important inversion in An. stephensi, putting the genome resources for this understudied species on par with the extensively studied malaria vector, Anopheles gambiae. We argue that the IndCh genome is relevant for field translation work compared to those reported earlier by showing that individuals from diverse geographical locations cluster with IndCh, pointing to significant convergence resulting from travel and commerce between cities, perhaps, contributing to the survival of the fittest strain.

Effect of Strontium Substituted Tetracalcium Phosphate Cement on Proliferation and Mineralization Potential in Human Dental Pulp Stem Cells.

OBJECTIVE: The aim of this study was to comparatively evaluate the proliferation, differentiation and mineralization inducing potential of strontium incorporated tetracalcium phosphate cement (STTCP) and mineral trioxide aggregate (MTA) on human dental pulp stem cells (hDPSCs). METHODS: hDPSCs were cultured from freshly extracted human premolar teeth. Cement discs (5mm×3mm) were prepared using MTA and STTCP. hDPSCs were exposed to the test materials and grouped as follows: 1. MTA; 2. STTCP; 3. NC: Media alone (negative control; 4.PC: hDPSCs with osteogenic medium (positive control); Cell viability and proliferation was evaluated using MTT and trypan blue assays for 0, 7 and 14 day intervals. Odontoblastic differentiation potential were evaluated using ALP assay followed by degree of mineralization using Alizarin Red test and Osteopontin expression on day 7,14 and 21. Quantitative analysis were done by evaluating the absorbance and expressed as optical density. Statistical analysis was performed using Kruskal Wallis test followed by Friedman test (P<0.05). RESULTS: MTA showed higher percentage of cell proliferation than STTCP at day 7 and 14. ALP assay revealed higher significant value for STTCP on day 7 and 14. STTCP exhibited intense staining and similar mineralization potential with MTA at all time periods. Osteopontin expression was exhibited by both MTA and STTCP on all days (P<0.05). CONCLUSION: STTCP promoted cell viability and enhanced mineralization and odontogenic differentiation potential on hDPSCs similar to MTA. STTCP has a potential to be an alternative therapeutic agent for pulp capping procedures.

A Model for Predicting Cation Selectivity and Permeability in AMPA and NMDA Receptors Based on Receptor Subunit Composition.

Glutamatergic AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) and NMDA (N-methyl-D-aspartate) receptors are implicated in diverse functions ranging from synaptic plasticity to cell death. They are heterotetrameric proteins whose subunits are derived from multiple distinct gene families. The subunit composition of these receptors determines their permeability to monovalent and/or divalent cations, but it is not entirely clear how this selectivity arises in native and recombinantly-expressed receptor populations. By analyzing the sequence of amino acids lining the selectivity filters within the pore forming membrane helices (M2) of these subunits and by correlating subunit stoichiometry of these receptors with their ability to permeate Na+ and/or Ca2+, we propose here a mathematical model for predicting cation selectivity and permeability in these receptors. The model proposed is based on principles of charge attractivity and charge neutralization within the pore forming region of these receptors; it accurately predicts and reconciles experimental data across various platforms including Ca2+ permeability of GluA2-lacking AMPARs and ion selectivity within GluN3-containing di- and tri-heteromeric NMDARs. Additionally, the model provides insights into biophysical mechanisms regulating cation selectivity and permeability of these receptors and the role of various subunits in these processes.