A conserved Plasmodium structural integrity maintenance protein (SIMP) is associated with sporozoite membrane and is essential for maintaining shape and infectivity.

Plasmodium sporozoites are extracellular forms introduced during mosquito bite that selectively invade mammalian hepatocytes. Sporozoites are delimited by a cell membrane that is linked to the underlying acto-myosin molecular motor. While membrane proteins with roles in motility and invasion have been well studied, very little is known about proteins that maintain the sporozoite shape. We demonstrate that in Plasmodium berghei (Pb) a conserved hypothetical gene, PBANKA_1422900 specifies sporozoite structural integrity maintenance protein (SIMP) required for maintaining the sporozoite shape and motility. Sporozoites lacking SIMP exhibited loss of regular shape, extensive membrane blebbing at multiple foci, and membrane detachment. The mutant sporozoites failed to infect hepatocytes, though the altered shape did not affect the organization of cytoskeleton or inner membrane complex (IMC). Interestingly, the components of IMC failed to extend under the membrane blebs likely suggesting that SIMP may assist in anchoring the membrane to IMC. Endogenous C-terminal HA tagging localized SIMP to membrane and revealed the C-terminus of the protein to be extracellular. Since SIMP is highly conserved among Plasmodium species, these findings have important implications for utilizing it as a novel sporozoite-specific vaccine candidate.

Temperature tunable flexible photo absorbers based on near-infrared 1D photonic crystal hybridized W-doped VO2nanostructures.

Vanadium dioxide is a potential candidate for energy efficient smart windows and have crystalline phase transition temperature (Tc) at 68 °C. So far, literatures mainly emphasis on different synthetic strategies of tungsten doped VO2which is a most effective dopant to reduceTcof VO2to near room temperatures. Until now, there is no report shows the incorporation of flexible 1D photonic crystals as spectrally selective, temperature tunable device to control the changes in optical transmission modulations of W-VO2nanostrtcures, especially in the near IR region for smart window application. W-doped VO2with various tungsten contents were synthesized with a facile hydrothermal route. We found that, with 1.1 at% of tungsten doping in intrinsic VO2, the metal to insulator transition temperature is brought down to 37 °C from 68 °C. IR transmission of VO2thin film can be reduced from 70% to 40% around room temperature, after doping. Significant absorption enhancement has been observed for both VO2and W-doped VO2films, deposited over tunable SiO2/Ta2O5based distributed Bragg reflector (DBR) fabricated over flexible PET (poly-ethylene terephthalate) substrates. On depositing VO2over ∼70% reflecting DBR, optical transmission is reduced to ∼15% from 35% while the temperature varies to 380 K from 300 K in IR regime. Number of stacks plays a crucial role for effective IR extinctions. A high quality DBR is fabricated by increasing no. of stacks from 4 to 7, with optical transmission of DBR reduced to nearly 5% in stop band. However, with 1.1 at% of W-VO2over such 95% reflecting flexible DBR, optical transmission vanishes nearly, around room temperature itself in the stop bands of that DBR, which clearly indicates the significant absorption enhancement. W-VO2/DBR hybrid can substantially modulate the solar heat flux and also imbuing DBR over flexible PET substrates offers retrofitting of the existing windows for energy economy. Thus these structures have promising potential applications for optical devices and practical design for smart windows.

Biochemical and physiological investigations on adenosine 5' monophosphate deaminase from Plasmodium spp.

The interplay between ATP generating and utilizing pathways in a cell is responsible for maintaining cellular ATP/energy homeostasis that is reflected by Adenylate Energy Charge (AEC) ratio. Adenylate kinase (AK), that catalyzes inter-conversion of ADP, ATP and AMP, plays a major role in maintaining AEC and is regulated by cellular AMP levels. Hence, the enzymes AMP deaminase (AMPD) and nucleotidases, which catabolize AMP, indirectly regulate AK activity and in-turn affect AEC. Here, we present the first report on AMPD from Plasmodium, the causative agent of malaria. The recombinant enzyme expressed in Saccharomyces cerevisiae was studied using functional complementation assay and residues vital for enzyme activity have been identified. Similarities and differences between Plasmodium falciparum AMPD (PfAMPD) and its homologs from yeast, Arabidopsis and humans are also discussed. The AMPD gene was deleted in the murine malaria parasite P. berghei and was found to be dispensable during all stages of the parasite life cycle. However, when episomal expression was attempted, viable parasites were not obtained, suggesting that perturbing AMP homeostasis by over-expressing AMPD might be lethal. As AMPD is known to be allosterically modulated by ATP, GTP and phosphate, allosteric activators of PfAMPD could be developed as anti-parasitic agents.

Modulation of host cell SUMOylation facilitates efficient development of Plasmodium berghei and Toxoplasma gondii.

SUMOylation is a reversible post translational modification of proteins that regulates protein stabilization, nucleocytoplasmic transport, and protein-protein interactions. Several viruses and bacteria modulate host SUMOylation machinery for efficient infection. Plasmodium sporozoites are infective forms of malaria parasite that invade mammalian hepatocytes and transforms into exoerythrocytic forms (EEFs). Here, we show that during EEF development, the distribution of SUMOylated proteins in host cell nuclei was significantly reduced and expression of the SUMOylation enzymes was downregulated. Plasmodium EEFs destabilized the host cytoplasmic protein SMAD4 by inhibiting its SUMOylation. SUMO1 overexpression was detrimental to EEF growth, and insufficiency of the only conjugating enzyme Ubc9/E2 promoted EEF growth. The expression of genes involved in suppression of host cell defense pathways during infection was reversed during SUMO1 overexpression, as revealed by transcriptomic analysis. The inhibition of host cell SUMOylation was also observed during Toxoplasma infection. We provide a hitherto unknown mechanism of regulating host gene expression by Apicomplexan parasites through altering host SUMOylation.

Psychological Distress in Low-Income and Economically Marginalized Populations in India: Protective and Risk Factors.

Studies at the juncture of development economics and public health take on considerable responsibility in addressing inequality and related mental health distress. Mental healthcare in economically marginalized populations requires depicting the linkages between socioeconomic status and psychological distress. In the present work, a sequential mixed-methods design was used to study 190 people in such communities in India. Gender-dependent psychological distress was found according to the Kessler Psychological Distress Scale (K-10) with moderate distress in women (M = 26.30, SD = 9.15) and mild distress in men (M = 21.04, SD = 8.35). Regression analysis indicated that gender significantly predicted psychological distress, followed by age, marital status, and the level of education of the head of the family. The Interpretative Phenomenological Analysis of semi-structured interviews of the six women who scored the highest on the distress scale unveiled three master themes: (1) manifestation of psychological distress, (2) contextual challenges, and (3) sources of strength and resilience. Overall, participants reported a lack of resources, community violence, gender discrimination, and widespread substance use as major contributors to the ongoing distress. These findings can pave the way for future studies to expand beyond independent economic indicators and curate clinical interventions for culturally competent mental healthcare.

Management of excessive gingival display with mucosal coronally positioned flap.

OBJECTIVE: Current methods of managing excessive gingival display, an aesthetic concern, with gingivectomy, orthodontic intrusion, restorative dentistry and even botulinum toxin, have often been unsatisfactory. This study evaluates the efficacy of mucosal coronally positioned flap (MCPF) for reduction of gingival display. MATERIAL AND METHODS: Eight healthy patients, above 18 years, with either short or hyperactive upper lip, gingival display ≥4 mm during smiling or vertical maxillary excess, were recruited into the study. The smile line, upper lip length, upper lip vermillion length, distance between the lips and amount of gingival display along with clinical indices were assessed. The patients then underwent MCPF procedure and were re-evaluated for healing of the surgical site after 15 days and at 3 months. Patients also provided their perceptions of outcome of treatment, through a questionnaire. Paired t test and Repeated measures ANOVA were used for data analysis. RESULTS: Significant improvement in the gingival display was noted 3 months after the procedure, while no concomitant changes were observed in other parameters like upper lip length, vermillion length and distance between the lips post operatively. CONCLUSION: The results of the study suggest that the MCPF procedure provides satisfactory results in terms of reduction of gingival display. Simplicity of the surgical procedure makes it an attractive option for patients without any gross skeletal abnormalities.

Withania somnifera (L.) Dunal (Ashwagandha) for the possible therapeutics and clinical management of SARS-CoV-2 infection: Plant-based drug discovery and targeted therapy.

Coronavirus disease 2019 (COVID-19) pandemic has killed huge populations throughout the world and acts as a high-risk factor for elderly and young immune-suppressed patients. There is a critical need to build up secure, reliable, and efficient drugs against to the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Bioactive compounds of Ashwagandha [Withania somnifera (L.) Dunal] may implicate as herbal medicine for the management and treatment of patients infected by SARS-CoV-2 infection. The aim of the current work is to update the knowledge of SARS-CoV-2 infection and information about the implication of various compounds of medicinal plant Withania somnifera with minimum side effects on the patients' organs. The herbal medicine Withania somnifera has an excellent antiviral activity that could be implicated in the management and treatment of flu and flu-like diseases connected with SARS-CoV-2. The analysis was performed by systematically re-evaluating the published articles related to the infection of SARS-CoV-2 and the herbal medicine Withania somnifera. In the current review, we have provided the important information and data of various bioactive compounds of Withania somnifera such as Withanoside V, Withanone, Somniferine, and some other compounds, which can possibly help in the management and treatment of SARS-CoV-2 infection. Withania somnifera has proved its potential for maintaining immune homeostasis of the body, inflammation regulation, pro-inflammatory cytokines suppression, protection of multiple organs, anti-viral, anti-stress, and anti-hypertensive properties. Withanoside V has the potential to inhibit the main proteases (Mpro) of SARS-CoV-2. At present, synthetic adjuvant vaccines are used against COVID-19. Available information showed the antiviral activity in Withanoside V of Withania somnifera, which may explore as herbal medicine against to SARS-CoV-2 infection after standardization of parameters of drug development and formulation in near future.

Foliar application of elicitors enhanced the yield of withanolide contents in Withania somnifera (L.) Dunal (variety, Poshita).

This study involves a detailed investigation about the effect of three elicitors, such as chitosan, jasmonic acid and salicylic acid (SA) on withaferin A and withanolide A contents of Withania somnifera (L.) Dunal (Poshita variety). Moreover, the different environmental regimes were also studied to assess and optimise the accumulation of withaferin A and Withanolide A contents. In an open environment, the total withaferin A content was found to be increased 6.3 and 5.8 times when sprayed with chitosan, 10 ppm and 50 ppm, respectively, as compared to control. Similarly, the total withanolide A content was found to be increased 4.5 and 3.6 times when sprayed with jasmonic acid (400 ppm and 200 ppm, respectively) with respect to control. In a controlled condition, the total withaferin A content was found to be increased 6 and 4.5 times when sprayed with jasmonic acid (400 ppm and 200 ppm, respectively) as compared to control. On the other hand, the total withanolide A content was found to be enhanced by 7 and 4.3 times when sprayed with jasmonic acid (400 ppm) and SA (1 ppm), respectively, as compared to control. Therefore, this study was focussed on the optimisation of enhanced accumulation of withaferin A and withanolide A contents in the aerial parts of the plant in open and controlled environment by foliar application of elicitors in minimal concentrations.

Role of 0.5 M mannitol as an adjuvant with lidocaine with or without epinephrine for inferior alveolar nerve block: A randomized control trial.

BACKGROUND: The most commonly used local anesthetic in dentistry is lidocaine. For decades, mannitol is the most widely used agent in the management of raised intracranial pressure and as prophylaxis against acute renal failure surgeries. MATERIAL AND METHODS: 120 patients were randomly divided into four groups, 30 patients in each group. Group A was administered 2% lidocaine with 1:80000 epinephrine; group B, 2% lidocaine with 1:80000 epinephrine and 0.5 M mannitol; group C, 2% lidocaine and 0.5 M mannitol; and group D (control group), 2% lidocaine for achieving local anesthesia. Extraction of lower erupted tooth was done under inferior alveolar nerve block. Parameters taken were onset of anesthesia, duration of anesthesia and pain. Heft-Parker visual analogue scale was taken to evaluate the pain response during procedure after every 10 minutes until complete return of sensation by probing. The Chi-square test was used to compare the pain among the groups. The continuous variables were compared among the groups by one way analysis of variance (ANOVA) followed by Tukey's post-hoc comparison tests. The p-value <0.05 was considered significant. RESULTS: The onset of tingling sensation was higher among the patients of group C (1.53±0.57) than group B (1.50±0.58), group D (1.48±0.51) and group A (1.45±0.62) but difference among the groups was statistically insignificant (p >0.05). The total time in return of sensation was higher among the patients of group C (70.30±4.34) than group A (65.94±3.45), group B (62.23±7.47) and group D (47.70±8.04) but difference among the groups was found to be statistically significant (p=0.0001). There was no significant (p >0.05) difference in the pain at baseline and at start. No pain was found among all the patients from 10 minutes to subsequent time intervals. CONCLUSIONS: Mannitol was effective in increasing the efficacy of lidocaine as an adjuvant to local anesthetic solution in inferior alveolar nerve block. Key words:Inferior alveolar nerve block, lidocaine, local anesthesia, mannitol.

Plasmodium berghei sporozoite specific genes- PbS10 and PbS23/SSP3 are required for the development of exo-erythrocytic forms.

Plasmodium sporozoites are infective forms of the parasite to mammalian hepatocytes. Sporozoite surface or secreted proteins likely play an important role in recognition, invasion and successful establishment of hepatocyte infection. By approaches of reverse genetics, we report the functional analysis of two Plasmodium berghei (Pb) sporozoite specific genes- PbS10 and PbS23/SSP3 that encode for proteins with a putative signal peptide. The expression of both genes was high in oocyst and salivary gland sporozoite stages as compared to other life cycle stages and PbS23/SSP3 protein was detected in salivary gland sporozoites. Both mutants were indistinguishable to wild-type parasites with regard to asexual growth in RBC, ability to complete sexual reproduction and form sporozoites in vector host. While the sporozoite stage of both mutants were able to glide and invade hepatocytes normally in vitro and in vivo, PbS10 mutants suffered growth attenuation at an early stage while PbS23/SSP3 mutants manifested defect during late exo-erythrocytic form maturation. Interestingly, both mutants gave rare breakthrough infections, suggesting that while both were critical for liver stage development, their depletion did not completely abrogate blood stage infection. These findings have important implications for weakening sporozoites by multiple gene attenuation towards the generation of a safe whole organism vaccine.

Angina bullosa haemorrhagica.

Angina bullosa haemorrhagica is the term used to describe benign subepithelial oral mucosal blisters filled with blood that are not attributable to a systemic disorder or haemostatic defect. It is a very rare condition. Elderly patients are usually affected and lesions heal spontaneously without scarring. The pathogenesis is unknown, although it may be a multifactorial phenomenon. Trauma seems to be the major provoking factor and long-term use of steroid inhalers has also been implicated in the disease. We present a 50-year-old patient with angina bullosa haemorrhagica. Trauma by sharp cusp of adjacent tooth and metal crown were identified as aetiological factors in this case. Lesions healed after removal of the metal crown and rounding of the cusp. Therefore, recognition of the lesion is of great importance to dentists, to avoid misdiagnosis.

Non-esterified fatty acids generate distinct low-molecular weight amyloid-ß (Aß42) oligomers along pathway different from fibril formation.

Amyloid-ß (Aß) peptide aggregation is known to play a central role in the etiology of Alzheimer's disease (AD). Among various aggregates, low-molecular weight soluble oligomers of Aß are increasingly believed to be the primary neurotoxic agents responsible for memory impairment. Anionic interfaces are known to influence the Aß aggregation process significantly. Here, we report the effects of interfaces formed by medium-chain (C9-C12), saturated non-esterified fatty acids (NEFAs) on Aß42 aggregation. NEFAs uniquely affected Aß42 aggregation rates that depended on both the ratio of Aß:NEFA as well the critical micelle concentration (CMC) of the NEFAs. More importantly, irrespective of the kind of NEFA used, we observed that two distinct oligomers, 12-18 mers and 4-5 mers were formed via different pathway of aggregation under specific experimental conditions: (i) 12-18 mers were generated near the CMC in which NEFAs augment the rate of Aß42 aggregation towards fibril formation, and, (ii) 4-5 mers were formed above the CMC, where NEFAs inhibit fibril formation. The data indicated that both 12-18 mers and 4-5 mers are formed along an alternate pathway called 'off-pathway' that did not result in fibril formation and yet have subtle structural and morphological differences that distinguish their bulk molecular behavior. These observations, (i) reflect the possible mechanism of Aß aggregation in physiological lipid-rich environments, and (ii) reiterate the fact that all oligomeric forms of Aß need not be obligatory intermediates of the fibril formation pathway.