A nuclear redox sensor modulates gene activation and var switching in Plasmodium falciparum.

The virulence of Plasmodium falciparum, which causes the deadliest form of human malaria, is attributed to its ability to evade the human immune response. These parasites "choose" to express a single variant from a repertoire of surface antigens called PfEMP1, which are placed on the surface of the infected red cell. Immune evasion is achieved by switches in expression between var genes, each encoding a different PfEMP1 variant. While the mechanisms that regulate mutually exclusive expression of var genes are still elusive, antisense long-noncoding RNAs (lncRNAs) transcribed from the intron of the active var gene were implicated in the "choice" of the single active var gene. Here, we show that this lncRNA colocalizes with the site of var mRNA transcription and is anchored to the var locus via DNA:RNA interactions. We define the var lncRNA interactome and identify a redox sensor, P. falciparum thioredoxin peroxidase I (PfTPx-1), as one of the proteins associated with the var antisense lncRNA. We show that PfTPx-1 localizes to a nuclear subcompartment associated with active transcription on the nuclear periphery, in ring-stage parasite, when var transcription occurs. In addition, PfTPx-1 colocalizes with S-adenosylmethionine synthetase (PfSAMS) in the nucleus, and its overexpression leads to activation of var2csa, similar to overexpression of PfSAMS. Furthermore, we show that PfTPx-1 knockdown alters the var switch rate as well as activation of additional gene subsets. Taken together, our data indicate that nuclear PfTPx-1 plays a role in gene activation possibly by providing a redox-controlled nuclear microenvironment ideal for active transcription.

Emerging biology of noncoding RNAs in malaria parasites.

In eukaryotic organisms, noncoding RNAs (ncRNAs) have been implicated as important regulators of multifaceted biological processes, including transcriptional, posttranscriptional, and epigenetic regulation of gene expression. In recent years, it is becoming clear that protozoan parasites encode diverse ncRNA transcripts; however, little is known about their cellular functions. Recent advances in high-throughput "omic" studies identified many novel long ncRNAs (lncRNAs) in apicomplexan parasites, some of which undergo splicing, polyadenylation, and encode small proteins. To date, only a few of them are characterized, leaving a big gap in our understanding regarding their origin, mode of action, and functions in parasite biology. In this review, we focus on lncRNAs of the human malaria parasite Plasmodium falciparum and highlight their cellular functions and possible mechanisms of action.

Characterizing the spatio-temporal distribution, detection, and prediction of aerosol atmospheric rivers on a global scale.

Aerosol Atmospheric Rivers (AARs) are elongated and narrow regions that carry high concentrations of aerosols (tiny particles suspended in the atmosphere) across large distances, exerting effects on both air quality and human health (Chakraborty et al., 2021, 2022). Monitoring and modeling these aerosols present distinct challenges due to their dynamic nature and complex interactions within the atmosphere. In this context, the present study detects and predicts the AARs using MERRA-2 reanalysis datasets with their seasonal climatology of key aerosol species, including Black Carbon (BC), Dust (DU), Organic Carbon (OC), Sea Salt (SS), and Sulphates (SU). The study employs an innovative Integrated Aerosol Transport (IAT) based AAR algorithm from 2015 to 2022. A total count of 44,020 BC AARs, 13,280 DU AARs, 21,599 OC AARs, 17,925 SS AARs, and 31,437 SU AARs were detected globally. The seasonal climatology of BC and OC AARs intensifies in areas such as the Amazon rainforest and Congo during AMJJAS (April-September) due to forest fires. Similarly, DU AARs are more frequent in regions near the Saharan desert, primarily around the equator during AMJJAS. SS AARs tend to predominate over the oceans, while SU AARs are predominantly found in the northern hemisphere, primarily due to higher anthropogenic emissions. Furthermore, convolutional autoencoder-based models were developed for key aerosol species, strengthening predictive accuracy by effectively capturing complex data relationships and delivering precise predictions for the last 5-time frames. During validation, the model evaluation parameters for image prediction such as the Structural Similarity Index ranged from 0.86 to 0.94, Peak Signal-to-Noise Ratio fluctuated between 1.14 and 42.25 dB, Root Mean Square Error varied from 2.39 to 296.4 mg/(m-sec), and Mean Square Error fell within the range of 1.55-17.22 mg/(m-sec). These collectively reflect image closeness, quality, dissimilarity, and accuracy in AAR prediction. This study demonstrates the effectiveness of advanced machine and deep learning models in predicting AARs, offering the potential for advanced forecasting and enhancing resilience in high-aerosol concentration regions.

An SR protein is essential for activating DNA repair in malaria parasites.

Plasmodium falciparum, the parasite responsible for the deadliest form of human malaria, replicates within the erythrocytes of its host, where it encounters numerous pressures that cause extensive DNA damage, which must be repaired efficiently to ensure parasite survival. Malaria parasites, which have lost the non-homologous end joining (NHEJ) pathway for repairing DNA double-strand breaks, have evolved unique mechanisms that enable them to robustly maintain genome integrity under such harsh conditions. However, the nature of these adaptations is unknown. We show that a highly conserved RNA splicing factor, P. falciparum (Pf)SR1, plays an unexpected and crucial role in DNA repair in malaria parasites. Using an inducible and reversible system to manipulate PfSR1 expression, we demonstrate that this protein is recruited to foci of DNA damage. Although loss of PfSR1 does not impair parasite viability, the protein is essential for their recovery from DNA-damaging agents or exposure to artemisinin, the first-line antimalarial drug, demonstrating its necessity for DNA repair. These findings provide key insights into the evolution of DNA repair pathways in malaria parasites as well as the ability of the parasite to recover from antimalarial treatment.

Exaggerated response to pattern reversal visual evoked potential among migraineurs.

OBJECTIVE: Visual evoked potential recording has reported ambiguous results among migraineurs, thus the present study explored the association of check-size and reversal rates on the latency and amplitude of pattern reversal VEP among migraineurs. METHOD AND MATERIAL: Monocular VEP responses for both eyes were recorded in 133 migraineurs and 111 controls. Checkerboard pattern with phase reversal frequency of 0.5, 1, 2 and 4 Hz and check-size of 16 × 16, 32 × 32, 64 × 64 and 128 × 128, i.e. spatial frequency of 0.475, 1.029, 2.056 and 4.112 cycle per degree (cpd) were used to record 100 responses each. Three-minutes gap was given after change of reversal frequency to a higher rate for next cycle of 4 check-size records. RESULT: A linear increase in latencies was observed with decreasing check-size in both groups, but migraineurs had significantly higher latencies at a given reversal rate. Amplitudes A1 and A2 were higher among migraineurs and amplitude A2 showed an inverted 'U' shaped trend with maximum amplitude at 32 × 32 check size (1.029 cpd) in both groups, with an exaggerated response among migraineurs. Check-size 32 × 32 i.e. spatial frequency of 1.029 behaves differently than other larger or smaller check-sizes. CONCLUSION: Variable VEP response for different visual stimuli may be due to differential activation of respective retinocortical pathways and cortical areas. The highest amplitude at modest check-size suggests a contributory role of foveal-parafoveal fibres in migraineurs. Exaggerated physiological response to visual stimuli may be responsible for higher amplitudes and prolonged latencies among migraineurs.

Exaggerated physiological VEP response as higher amplitudes and prolonged latencies, among migraineurs may be due to differential activation of respective retinocortical pathways and cortical areas.

Hemodynamic changes in pregnancy: does central blood pressure have any role?

Pregnancy is associated with alteration in the hemodynamic state. In clinical practice, only peripheral blood pressure is measured; however, central blood pressure is a better predictor of cardiovascular events. We have investigated variations in peripheral blood pressure, central blood pressure, and augmentation index in healthy non-pregnant and pregnant women. This was a cross-sectional study of 107 pregnant women (I trimester n = 19, II trimester n = 39, and III trimester n = 49) and age-matched 53 non-pregnant women (Follicular phase n = 25 and luteal phase n = 28). The augmentation index showed a significant decrease with the progression of pregnancy. Central systolic blood pressure showed a decreasing trend (non-significant) with the progression of pregnancy. Heart rate shows a significant increase from follicular to luteal phase in non-pregnant women, which further increases with the progression of pregnancy. Longitudinal studies involving larger sample sizes might provide some insights into the significance of including central blood pressure and augmentation index for routine checkups in both non-pregnant and pregnant women.

Intermittent hypoxia and sleep disruption in obstructive sleep apnea increase serum tau and amyloid-beta levels.

Obstructive sleep apnea is characterized by intermittent hypoxia and sleep disruption, leading to accelerated neurodegenerative changes and cognitive decline. Serum amyloid-beta and tau proteins, which are markers for Alzheimer's disease, have been reported to increase in patients with obstructive sleep apnea. This study compared the serum levels of amyloid-beta proteins and tau proteins in 46 cognitively normal obstructive sleep apnea patients and 30 healthy controls. Sleep parameters and severity of obstructive sleep apnea were determined using overnight polysomnography. Serum levels of Aß40, Aß42, total tau and phosphorylated-tau were determined by enzyme-linked immunosorbent assay. Patients with obstructive sleep apnea had significantly higher median serum levels of Aß40 (121.0 versus 78.3 pg ml-1 ), Aß42 (105.6 versus 18.6 pg ml-1 ) and total tau (168.5 versus 10.9 pg ml-1 ) than controls. Serum levels of phosphorylated-tau did not differ significantly between the two groups. Serum levels of amyloid and tau proteins correlated with parameters of nocturnal oxygen saturation. Rapid eye movement sleep was negatively correlated with total amyloid-beta proteins. We conclude that serum levels of amyloid-beta and total tau are higher in patients with obstructive sleep apnea and hypoxia as well as changes in sleep architecture associated with their increased levels. Patients with obstructive sleep apnea should be closely monitored for the signs of cognitive impairment. Obstructive sleep apnea is a modifiable risk factor, and its treatment may reverse neurodegenerative changes and prevent cognitive impairment.

Impact of facial components on the attractiveness of face: A perception-based study.

INTRODUCTION: Magazines and television displays are not merely crammed with faces-they are filled with appealing faces, and both men and women are interested in a suitable partner's appearance. This study investigated what makes a face attractive and whether perception-related differences exist between facial attractiveness and facial components. METHODS: In this descriptive-analytical study, frontal and lateral view photographs of 18 young adults (9 male and 9 female) in Class I, II, and III malocclusions were assessed by 90 orthodontists, dentists, models, and laypeople using a 7-point Likert scale in terms of attractiveness. Based on scores, attractive and unattractive groups were formed. Using image analysis software, a range of defined length, angles, perimeter, and area for lips, nose, and chin were measured for the attractive group. For statistical analysis, each group was compared using a 1-way analysis of variance. Logistic regression was performed to analyze the factors of different parameters to the attractiveness of facial components. RESULTS: Overall full-face width, upper lip angle, lip area, and mentolabial angle was significantly different in all the 3 classes (P ≤0.05). In Class I malocclusion, nasolabial angle among orthodontists, nasofrontal angle among dentists, lower lip among models, and full-face width among laypeople were responsible for facial attractiveness variation. In Class II malocclusion, nose to upper lip among orthodontists, Cupid's bow among dentists, wider face among models, and upper lip among layperson were responsible for variation in facial attractiveness. In Class III malocclusion, lower lip angle among orthodontists and dentists, Cupid's bows among models and layperson was responsible for variation in facial attractiveness. CONCLUSIONS: In Class I faces, lips (Cupid's bows, lower lips, lip areas), nose (nasolabial, nasofrontal, and nasomental angles), and chin (lower lip to chin) contributed to the overall attractiveness of the face, while in Class II faces, lips (upper lip length, interbow distance, lower lip angle), nose (full facial convexity), and chin (mentolabial sulcus), as well as a greater full-face width contributed to the overall attractiveness of the face. In Class III faces, lips (lower lip angle, upper lip length), nose (nose tip angle, full facial convexity), and chin (mentolabial sulcus depth) contributed to the overall attractiveness of the face.

Assessment of Impact of Fluoride on Mechanical Properties of NiTi and CuNiTi Orthodontic Archwires: An In Vitro Study.

AIM: The current study was carried out to assess the impact on the mechanical properties of orthodontic wires such as the nickel-titanium (NiTi) and copper-nickel-titanium (CuNiTi) wires by fluoride available in various prophylactic products. MATERIALS AND METHODS: Fifty-six wire specimens were randomly divided into two groups-control group in which deionized water was used as a medium and study group in which Phos-Flur gel was used. Both study group and control group were divided into two subgroups-NiTi wire group: 0.019 × 0.025 inch NiTi archwires (14 specimens) and CuNiTi wire group: 0.019 × 0.025 inch CuNiTi archwires (14 specimens). Testing of all the wires was done under a universal force testing machine. RESULTS: Mean loading force among NiTi wire group and CuNiTi wire group specimens with deionized water as a medium was 682.6 and 397.4 MPa, respectively, while the mean loading force among NiTi wire group and CuNiTi wire group specimens with Phos-Flur gel as a medium was 596.1 and 368.4 MPa, respectively. While comparing between study group and control group among NiTi wires, significant results were obtained. Also, while comparing between study group and control group among CuNiTi wires, significant results were obtained. CONCLUSION: Following exposure to fluoride agents, NiTi wires and CuNiTi wires are significantly associated with reduced mechanical properties. CLINICAL SIGNIFICANCE: Although fluoride acts as a vital adjunct in maintaining oral hygiene, particularly among patients undergoing fixed orthodontic treatment, its influence on the mechanical properties of the wires is an area to be explored further; thereby, its use is to be monitored.

Molecular Docking and Dynamics Simulation Revealed Ivermectin as Potential Drug against Schistosoma-Associated Bladder Cancer Targeting Protein Signaling: Computational Drug Repositioning Approach.

Urogenital schistosomiasis is caused by Schistosoma haematobium (S. haematobium) infection, which has been linked to the development of bladder cancer. In this study, three repurposing drugs, ivermectin, arteether and praziquantel, were screened to find the potent drug-repurposing candidate against the Schistosoma-associated bladder cancer (SABC) in humans by using computational methods. The biology of most glutathione S-transferases (GSTs) proteins and vascular endothelial growth factor (VEGF) is complex and multifaceted, according to recent evidence, and these proteins actively participate in many tumorigenic processes such as cell proliferation, cell survival and drug resistance. The VEGF and GSTs are now widely acknowledged as an important target for antitumor therapy. Thus, in this present study, ivermectin displayed promising inhibition of bladder cancer cells via targeting VEGF and GSTs signaling. Moreover, molecular docking and molecular dynamics (MD) simulation analysis revealed that ivermectin efficiently targeted the binding pockets of VEGF receptor proteins and possessed stable dynamics behavior at binding sites. Therefore, we proposed here that these compounds must be tested experimentally against VEGF and GST signaling in order to control SABC. Our study lies within the idea of discovering repurposing drugs as inhibitors against the different types of human cancers by targeting essential pathways in order to accelerate the drug development cycle.

A novel analysis of COVID 19 risk in India incorporating climatic and socioeconomic Factors.

This study investigates the influence of climate variables (pressure, relative humidity, temperature and wind speed) in inducing risk due to COVID 19 at rural, urban and total (rural and urban) population scale in 623 pandemic affected districts of India incorporating the socioeconomic vulnerability factors. We employed nonstationary extreme value analysis to model the different quantiles of cumulative COVID 19 cases in the districts by using climatic factors as covariates. Wind speed was the most dominating climatic factor followed by relative humidity, pressure, and temperature in the evolution of the cases. The results reveal that stationarity, i.e., the COVID 19 cases which are independent of pressure, relative humidity, temperature and wind speed, existed only in 148 (23.7%) out of 623 districts. Whereas, strong nonstationarity, i.e., climate dependence, was detected in the cases of 474 (76.08%) districts. 334 (53.6%), 200 (32.1%) and 336 (53.9%) districts out of 623 districts were at high risk (or above) at rural, urban and total population scales respectively. 19 out of 35 states were observed to be under high (or above) Kerala, Maharashtra, Goa and Delhi being the most risked ones. The study provides high-risk maps of COVID 19 pandemic at the district level and is aimed at supporting the decision-makers to identify climatic and socioeconomic factors in augmenting the risks.

Progressive Muscle Relaxation and Guided Imagery in Breast Cancer: A Systematic Review and Meta-analysis of Randomised Controlled Trials.

Breast cancer affects the mental well-being of patients who may need psychological support. The combined practice of progressive muscle relaxation (PMR) and guided imagery (GI) is known to improve psychological health. Its effect has been studied in patients with breast cancer. We need to systematically review and analyse the available data to outline its role in various stages of disease management. We wanted to evaluate the effect of the combined practice of PMR and GI on stress, anxiety, depression and mood. We also wanted to study the impact on quality of life and chemotherapy-related adverse effects. A systematic search and evaluation of the literature was performed. Five randomised controlled trials were selected for data extraction and construction of forest plots. The intervention was effective for stress and anxiety. It positively improved the quality of life but saw no significant improvement in chemotherapy-related adverse effects.

Analysis of stress distribution in lingual orthodontics system for effective en-masse retraction using various combinations of lever arm and mini-implants: A finite element method study.

INTRODUCTION: The aims and objectives of this study were to evaluate the von Mises stress and principal stress distribution and displacement of anterior teeth in a lingual orthodontics system along the periodontal ligament and alveolar bone by various combinations of mini-implants and lever arm during en-masse retraction. Four 3-dimensional finite element (FE) models of the bilateral maxillary first premolar extraction cases were constructed. METHODS: Lingual brackets were (0.018-in slots) positioned over the center of the clinical crown. In all 4 models, 150 g of retraction force was applied with the help of a nickel-titanium closed coil spring with different combinations of mini-implants and lever arm on each side. FE analysis was then performed to evaluate stress distribution, principal stress, von Mises stress, and displacement of the anterior teeth using ANSYS software (version 12.1; Ansys, Canonsburg, Pa). The FE study was enough to validate the analysis results obtained by software tools with FE simulation instead of experimental readings. Thus, statistical analysis was not required. RESULTS: In this study, maximum tensile stresses were observed in the periodontal ligament at the mesial cervical region of the canine with values of 1.84 MPa, 2.02 MPa, 1.88 MPa, and 2.08 MPa for models 1-4, respectively. Maximum von Mises stress in alveolar bone was 8.05 MPa, 8.23 MPa, 8.19 MPa, and 8.37 MPa for models 1-4, respectively, which was within the optimum limit (135 MPa). Variable amounts of displacements like lingual crown tipping, lingual root tipping, and extrusion were observed in all the models. The 15-mm long lever arm models (models 2 and 4) showed a more controlled crown (0.015 mm) and root movement (0.004 mm) compared with 12-mm long lever arm models (models 1 and 3). CONCLUSIONS: In lingual orthodontics, controlled root movement increased as we increased the length of the lever arm. It was also concluded that the amount of increased controlled tipping found with the placement of the mini-implant was toward the palatal slope.

Comparison of Mesiodistal Width of Maxillary Anteriors with Arch Form in Various Malocclusions: A Retrospective Study.

AIM: This study was conducted for evaluating and comparing the mesiodistal width of upper anteriors in different malocclusions and its relation with various arch forms. MATERIALS AND METHODS: In total, 60 subjects with different malocclusions were examined. Mesiodistal width was measured for the anterior teeth using digital vernier caliper. 3M Unitek arch form template and two-dimensional (2D) model were superimposed to find out primarily the relation of arch form in specific malocclusion to the sum the mesiodistal width of the maxillary of anterior teeth and secondarily the relation of sum of the mesiodistal width of the maxillary anterior tooth with different arch forms. RESULTS: The ovoid arch form was common in class I malocclusion with mean mesiodistal width of 50.43 mm. The tapered arch form was the common type in both class II and class III malocclusion with mean mesiodistal width of 49.96 and 45.15 mm, respectively. CONCLUSION: The mean of anterior mesiodistal width for Angle's class III individuals was 45.15 mm considerably less than that of class II subjects and class I subjects, which signifies that the tooth material was more in the anterior region of the subject of class I followed by class II and class III malocclusions. CLINICAL SIGNIFICANCE: The performed study presents various maxillary dental arch forms observed in various malocclusions (Angle's class I, class II, and class III). The ovoid and tapered arch forms exhibited the common occurrence, while the square form was the rarest.

Assessment of ecosystem resilience to hydroclimatic disturbances in India.

Recent studies have shown an increasing trend in hydroclimatic disturbances like droughts, which are anticipated to become more frequent and intense under global warming and climate change. Droughts adversely affect the vegetation growth and crop yield, which enhances the risks to food security for a country like India with over 1.2 billion people to feed. Here, we compared the response of terrestrial net primary productivity (NPP) to hydroclimatic disturbances in India at different scales (i.e., at river basins, land covers, and climate types) to examine the ecosystems' resilience to such adverse conditions. The ecosystem water use efficiency (WUEe : NPP/Evapotranspiration) is an effective indicator of ecosystem productivity, linking carbon (C) and water cycles. We found a significant difference (p < .05) in WUEe across India at different scales. The ecosystem resilience analysis indicated that most of the river basins were not resilient enough to hydroclimatic disturbances. Drastic reduction in WUEe under dry conditions was observed for some basins, which highlighted the cross-biome incapability to withstand such conditions. The ecosystem resilience at land cover and climate type scale did not completely relate to the basin-scale ecosystem resilience, which indicated that ecosystem resilience at basin scale is controlled by some other ecohydrological processes. Our results facilitate the identification of the most sensitive regions in the country for ecosystem management and climate policy making, and highlight the need for taking sufficient adaptation measures to ensure sustainability of ecosystems.