Increasing the accuracy of single-molecule data analysis using tMAVEN.

Time-dependent single-molecule experiments contain rich kinetic information about the functional dynamics of biomolecules. A key step in extracting this information is the application of kinetic models, such as hidden Markov models (HMMs), which characterize the molecular mechanism governing the experimental system. Unfortunately, researchers rarely know the physicochemical details of this molecular mechanism a priori, which raises questions about how to select the most appropriate kinetic model for a given single-molecule data set and what consequences arise if the wrong model is chosen. To address these questions, we have developed and used time-series modeling, analysis, and visualization environment (tMAVEN), a comprehensive, open-source, and extensible software platform. tMAVEN can perform each step of the single-molecule analysis pipeline, from preprocessing to kinetic modeling to plotting, and has been designed to enable the analysis of a single-molecule data set with multiple types of kinetic models. Using tMAVEN, we have systematically investigated mismatches between kinetic models and molecular mechanisms by analyzing simulated examples of prototypical single-molecule data sets exhibiting common experimental complications, such as molecular heterogeneity, with a series of different types of HMMs. Our results show that no single kinetic modeling strategy is mathematically appropriate for all experimental contexts. Indeed, HMMs only correctly capture the underlying molecular mechanism in the simplest of cases. As such, researchers must modify HMMs using physicochemical principles to avoid the risk of missing the significant biological and biophysical insights into molecular heterogeneity that their experiments provide. By enabling the facile, side-by-side application of multiple types of kinetic models to individual single-molecule data sets, tMAVEN allows researchers to carefully tailor their modeling approach to match the complexity of the underlying biomolecular dynamics and increase the accuracy of their single-molecule data analyses.

Plasma Virome of HIV-infected Subjects on Suppressive Antiretroviral Therapy Reveals Association of Differentially Abundant Viruses with Distinct T-cell Phenotypes and Inflammation.

Background: The plasma virome represents the overall composition of viral sequences present in it. Alteration in plasma virome has been reported in treatment naïve and immunocompromised (CD4 count < 200) people with HIV (PWH). However, the effect of ART on virome composition in PWH on ART with preserved CD4 counts is poorly understood. Objectives: We aimed to assess the alterations in plasma virome in PWH on ART in comparison to HIV-negative uninfected controls and to further investigate possible associations of plasma viruses with inflammation and immune dysfunction, namely, immunosenescence and immune exhaustion. Methods: Plasma viral DNA from PWH on ART and controls was used for sequencing on the Illumina Nextseq500 platform, followed by the identification of viral sequences using an automated pipeline, VIROMATCH. Multiplex cytokine assay was performed to measure the concentrations of various cytokines in plasma. Immunophenotyping was performed on PBMCs to identify T cell markers of immunosenescence and immune exhaustion. Results: In our observational, cross-sectional pilot study, chronically infected PWH on ART had significantly different viral species compositions compared to controls. The plasma virome of PWH showed a significantly high relative abundance of species Human gammaherpesvirus 4, also known as Epstein-Barr virus (EBV). Moreover, EBV emerged as a significant viral taxon differentially enriched in PWH on ART, which further correlated positively with the exhaustion phenotype of T cells and significantly increased TNF-α in PWH on ART. Additionally, a significantly increased proportion of senescent T cells and IL-8 cytokine was detected in PWH on ART. Conclusion: Altered plasma virome influenced the inflammatory response and T-cell phenotype in PWH on ART.

Exploring the Human Virome: Composition, Dynamics, and Implications for Health and Disease.

Humans are colonized by large number of microorganisms-bacteria, fungi, and viruses. The overall genome of entire viruses that either lives on or inside the human body makes up the human virome and is indeed an essential fraction of the human metagenome. Humans are constantly exposed to viruses as they are ubiquitously present on earth. The human virobiota encompasses eukaryotic viruses, bacteriophages, retroviruses, and even giant viruses. With the advent of Next-generation sequencing (NGS) and ongoing development of numerous bioinformatic softwares, identification and taxonomic characterization of viruses have become easier. The viruses are abundantly present in humans; these can be pathogenic or commensal. The viral communities occupy various niches in the human body. The viruses start colonizing the infant gut soon after birth in a stepwise fashion and the viral composition diversify according to their feeding habits. Various factors such as diet, age, medications, etc. influence and shape the human virome. The viruses interact with the host immune system and these interactions have beneficial or detrimental effects on their host. The virome composition and abundance change during the course of disease and these alterations impact the immune system. Hence, the virome population in healthy and disease conditions influences the human host in numerous ways. This review presents an overview of assembly and composition of the human virome in healthy asymptomatic individuals, changes in the virome profiles, and host-virome interactions in various disease states.

"Does the Exploration of the Temporomandibular Joint Using a Deep Subfascial Technique Result in a Superior Operative Outcome?"

PURPOSE: The literature is replete with various approaches for the temporomandibular joint (TMJ), each with its own distinct advantages and disadvantages. None of these approaches, however, have been associated with superior operative outcomes. The purpose of this study was to measure the efficacy of three operative approaches to TMJ, namely superficial, subfascial, and deep subfascial approaches. The aim was to contrast selected intraoperative and postoperative outcomes among these surgical approaches. METHODS: This was a prospective randomized clinical trial of subjects presenting to outpatient department. The primary predictor variables were three dissection planes of TMJ: Group-I (superficial), Group-II (subfascial), and Group-III (deep subfascial). The primary outcome variables were quality of surgical field employing fromme scale, dissection time in minutes, amount of blood loss in milliliters, and facial nerve function (FNF) using House-Brackmann scale. The secondary outcome variables were postoperative pain using visual-analog scale and swelling in millimeters measured on 1st, 3rd, and 7th postoperative days and quality of life using facial clinimetric evaluation questionnaire at 6-month follow-up. Age, gender, side, diagnosis, and type of surgery were the covariates. The data were analyzed using descriptive, comparative, and regression analysis. A P value of less than .05 was considered statistically significant. RESULT: The study included thirty subjects (8 males and 22 females) with various TMJ disorders ranging in age from 8 years to 65 years (mean 27.83 ± 10.52). On evaluation of intraoperative parameters, subfascial approach had statistically significant superior quality of surgical field (Group-I: 1.90 ± 0.57; Group-II: 1.10 ± 0.32; Group-III: 1.40 ± 0.52; P value = .006), statistically significant shortest dissection time (Group-I: 18.30 ± 3.74 min; Group-II: 13.240 ± 1.96 min; Group-III: 16.20 ± 1.99 min; with P value = .03), and statistically significant lower amount of blood loss compared with other groups (Group-I: 92.40 ± 4.74 ml: Group-II: 82.30 ± 3.77 ml; Group-III: 84.60 ± 3.06 ml; P value<.001). On assessment of postoperative parameters, only FNF of temporal branch showed statistically significant difference from 24 hours till 3 months with better outcome in deep subfascial approach. Mean scores of FNF at 24 hours and 1-week (Group-I: 4.20 ± 2.39; Group-II: 2.40 ± 2.27; Group-III: 1.50 ± 1.58 P = .02) and 1-month and 3-month (Group-I: 2.70 ± 1.82; Group-II: 1.20 ± 0.63; Group-III: 1.00 ± 0.00 P = .04). CONCLUSIONS: The subfascial approach significantly improved intraoperative outcomes and deep subfascial approach was comparatively safe with fewer incidence of facial nerve injury.

Contrasting ß-ODAP content correlates with stress gene expression in Lathyrus cultivars.

Lathyrus sativus, commonly known as grass pea, is a nutrient-rich pulse crop with remarkable climate-resilient attributes. However, wide use of this nutritious crop is not adopted owing to the presence of a non-protein amino acid ß-N-oxalyl-l-α,ß-diaminopropionic acid (ß-ODAP), which is neurotoxic if consumed in large quantities. We conducted a de novo transcriptomic profiling of two ODAP contrasting cultivars, Pusa-24 and its somaclonal variant Ratan, to understand the genetic changes leading to and associated with ß-ODAP levels. Differential gene expression analysis showed that a variety of genes are downregulated in low ß-ODAP cultivar Ratan and include genes involved in biotic/abiotic stress tolerance, redox metabolism, hormonal metabolism, and sucrose, and starch metabolism. Several genes related to chromatin remodeling are differentially expressed in cultivar Ratan. ß-ODAP biosynthetic genes in these cultivars showed differential upregulation upon stress. ODAP content of these cultivars varied differentially upon stress and development. Physiological experiments indicate reduced relative water content and perturbed abscisic acid levels in the low ODAP cultivar. Altogether, our results suggest that the low ODAP cultivar may have a reduced stress tolerance. The dataset provides insight into the biological role of ODAP and will be helpful for hypothesis-driven experiments to understand ODAP biosynthesis and regulation.

Dynamic regulation of chromatin organizer SATB1 via TCR-induced alternative promoter switch during T-cell development.

The chromatin organizer SATB1 is highly enriched in thymocytes and is essential for T-cell development. Although SATB1 regulates a large number of genes important for T-cell development, the mechanism(s) regulating expression of SATB1 during this process remain elusive. Using chromatin immune precipitation-seq-based occupancy profiles of H3K4me3 and H3Kme1 at Satb1 gene locus, we predicted four different alternative promoters of Satb1 in mouse thymocytes and characterized them. The expression of Satb1 transcript variants with distinct 5' UTRs occurs in a stage-specific manner during T-cell development and is dependent on TCR signaling. The observed discrepancy between the expression levels of SATB1 mRNA and protein in developing thymocytes can be explained by the differential translatability of Satb1 transcript variants as confirmed by polysome profiling and in vitro translation assay. We show that Satb1 alternative promoters exhibit lineage-specific chromatin accessibility during T-cell development from progenitors. Furthermore, TCF1 regulates the Satb1 P2 promoter switch during CD4SP development, via direct binding to the Satb1 P2 promoter. CD4SP T cells from TCF1 KO mice exhibit downregulation of P2 transcript variant expression as well as low levels of SATB1 protein. Collectively, these results provide unequivocal evidence toward alternative promoter switch-mediated developmental stage-specific regulation of SATB1 in thymocytes.

Is Modified Condylotomy a Better Surgical Option Compared With High-Condylar Shave With Eminectomy in Improving Symptoms of Internal Derangement of Temporomandibular Joint?

PURPOSE: A proper anatomical disc-condyle position is a prerequisite to prevent progressive deteriorating changes within the temporomandibular joint. Surgery becomes the primary treatment option for patients who do not recover with nonoperative management. The present study aimed to compare the clinical outcome of 2 different surgical procedures in patients with internal derangement of the temporomandibular joint. METHODS: A prospective clinical cohort study was conducted among patients presenting to outpatient department of Oral and Maxillofacial Surgery at Maulana Azad Institute of Dental Sciences. The study sample was alternatively allocated into 2 treatment groups; Group I: modified condylotomy (MC) and Group II: high-condylar shave with eminectomy (HCSE). The primary outcome variables included pain on function, tenderness on palpation, and maximum mouth opening. The secondary outcome variables included joint sounds, jaw deviation on opening, maximum protrusive jaw movement, maximum ipsilateral jaw movement, and maximum contralateral jaw movement. The covariates were age, sex of the patient, duration of illness, the diagnosis based on Wilkes's staging, and the laterality (whether unilateral or bilateral). Descriptive, comparative, and regression analyses were conducted. RESULTS: Twenty-one patients with Wilkes Stage II, III, and IV were included in the study (MC: 10 patients and HCSE: 11 patients). The mean age of the study sample was 32.67 (±11.66) years. Among 21 patients recruited in our study, 18 were females. It was observed that after 1-year follow-up, patients in Group I had significantly lower pain on function (0.30 ± 0.48) compared with Group II (3.00 ± 1.18). (P < .001). Similarly, tenderness on palpation was significantly decreased in Group I (0.80 ± 0.48) compared with Group II (2.45 ± 0.93; P < .001). Joint sounds were significantly lower in Group I (1.20 ± 0.63) compared with Group II (2.27 ± 0.90) after 1 year (P < .001). Maximum protrusive jaw movement and maximum ipsilateral jaw movement were significantly higher in Group I compared with Group II after 1 year. CONCLUSION: MC is a comparatively better surgical procedure than HCSE in patients with internal derangement of the TMJ.

Does Mandibular Condylar Morphology After Fracture Healing Predict Functional Outcomes in Patients Treated With Closed Reduction?

PURPOSE: The purpose of the study is to assess the healing temporomandibular joint morphology and function after closed treatment of unilateral mandibular condylar fracture. MATERIALS AND METHODS: A prospective interventional cohort study was designed in patients recruited from the outpatient department who underwent closed reduction for unilateral condylar fractures, and mean mouth opening, mean maximum protrusion, laterotrusion, and radiological pattern of healing were noted. RESULTS: Forty patients in the age group of 18-50 years (mean 24.5 years) were included. The difference between the pretreatment mean mouth opening (26.94 mm), mean maximum protrusion (1.22 mm), and laterotrusion (3.82 mm and 1.45 mm) values and the 6-month post-treatment values (46.3 mm, 4.45 mm, and 11.82 mm and 9.82 mm, respectively) was found to be statistically significant (P < .001). Deranged pretreatment occlusion seen in 20 cases was improved in 18 patients (85%) at the 6-month post-treatment visit, with persisting malocclusion in 2 patients (5%). Clinically, cases that had healed with the anatomical pattern (M1) were found to have significantly better clinical outcomes (P value < .05) than that achieved with cases healed with spherical pattern (M2), L-shaped pattern (M3), or detached pattern (M4). On radiographs, the greatest improvement (21.16 mm) in mean mouth opening values was seen in the M1 group (anatomical pattern), followed by similar improvement in groups M2 and M3 (18.39 and 18.66 mm, respectively). Least improvement (7.06 mm) was seen in the single case of the M4 group (detached pattern), although the 6-month post-treatment value was still an acceptable one (34 mm). CONCLUSIONS: Favorable functional outcomes can be achieved after closed treatment, including adequate mouth opening, pain-free jaw excursions, and stable occlusion, with the anatomical healing pattern showing the most superior results and the detached pattern being associated with relatively poorer outcomes compared with other healing patterns.

WheatQTLdb: a QTL database for wheat.

During the last three decades, QTL analysis in wheat has been conducted for a variety of individual traits, so that thousands of QTL along with the linked markers, their genetic positions and contribution to phenotypic variation (PV) for concerned traits are now known. However, no exhaustive database for wheat QTL is currently available at a single platform. Therefore, the present database was prepared which is an exhaustive information resource for wheat QTL data from the published literature till May, 2020. QTL data from both interval mapping and genome-wide association studies (GWAS) have been included for the following classes of traits: (i) morphological traits, (ii) N and P use efficiency, (iii) traits for biofortification (Fe, K, Se, and Zn contents), (iv) tolerance to abiotic stresses including drought, water logging, heat stress, pre-harvest sprouting and salinity, (v) resistance to biotic stresses including those due to bacterial, fungal, nematode and insects, (vi) quality traits, and (vii) a variety of physiological traits, (viii) developmental traits, and (ix) yield and its related traits. For the preparation of the database, literature was searched for data on QTL/marker-trait associations (MTAs), curated and then assembled in the form of WheatQTLdb. The available information on metaQTL, epistatic QTL and candidate genes, wherever available, is also included in the database. Information on QTL in this WheatQTLdb includes QTL names, traits, associated markers, parental genotypes, crosses/mapping populations, association mapping panels and other useful information. To our knowledge, WheatQTLdb prepared by us is the largest collection of QTL (11,552), epistatic QTL (107) and metaQTL (330) data for hexaploid wheat to be used by geneticists and plant breeders for further studies involving fine mapping, cloning, and marker-assisted selection (MAS) during wheat breeding.

Neuroinflammation is associated with infiltration of T cells in Lewy body disease and α-synuclein transgenic models.

BACKGROUND: α-Synuclein (α-syn) is a pre-synaptic protein which progressively accumulates in neuronal and non-neuronal cells in neurodegenerative diseases such as Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy. Recent evidence suggests that aberrant immune activation may be involved in neurodegeneration in PD/DLB. While previous studies have often focused on the microglial responses, less is known about the role of the peripheral immune system in these disorders. METHODS: To understand the involvement of the peripheral immune system in PD/DLB, we evaluated T cell populations in the brains of α-syn transgenic (tg) mice (e.g., Thy1 promoter line 61) and DLB patients. RESULTS: Immunohistochemical analysis showed perivascular and parenchymal infiltration by CD3+/CD4+ helper T cells, but not cytotoxic T cells (CD3+/CD8+) or B cells (CD20+), in the neocortex, hippocampus, and striatum of α-syn tg mice. CD3+ cells were found in close proximity to the processes of activated astroglia, particularly in areas of the brain with significant astrogliosis, microgliosis, and expression of pro-inflammatory cytokines. In addition, a subset of CD3+ cells co-expressed interferon γ. Flow cytometric analysis of immune cells in the brains of α-syn tg mice revealed that CD1d-tet+ T cells were also increased in the brains of α-syn tg mice suggestive of natural killer T cells. In post-mortem DLB brains, we similarly detected increased numbers of infiltrating CD3+/CD4+ T cells in close proximity with blood vessels. CONCLUSION: These results suggest that infiltrating adaptive immune cells play an important role in neuroinflammation and neurodegeneration in synucleinopathies and that modulating peripheral T cells may be a viable therapeutic strategy for PD/DLB.

Repeated evolution of terrestrial lineages in a continental lizard radiation.

The "early-burst" model of adaptive radiation predicts an early increase in phenotypic disparity concurrent with lineage diversification. Although most studies report a lack of this coupled pattern, the underlying processes are not identified. The continental radiation of Hemidactylus geckos from Peninsular India includes morphologically diverse species that occupy various microhabitats. This radiation began diversifying ~36 Mya with an early increase in lineage diversification. Here, we test the "early-burst" hypothesis by investigating the presence of ecomorphs and examining the pattern of morphological diversification in a phylogenetic framework. Two ecomorphs-terrestrial and scansorial species-that vary significantly in body size and toepad size were identified. Unlike the prediction of the "early-burst" model, we find that disparity in toepad morphology accumulated more recently ~14 Mya and fit the Ornstein-Ulhenbeck model. Ancestral state reconstruction of the two ecomorphs demonstrates that terrestrial lineages evolved independently at least five times from scansorial ancestors, with the earliest diversification in terrestrial lineages 19-12 Mya. Our study demonstrates a delayed increase in morphological disparity as a result of the evolution of terrestrial ecomorphs. The diversification of terrestrial lineages is concurrent with the establishment of open habitat and grasslands in Peninsular India, suggesting that the appearance of this novel resource led to the adaptive diversification.

MiR-101a loaded extracellular nanovesicles as bioactive carriers for cardiac repair.

Myocardial infarction (MI) remains a major cause of mortality worldwide. Despite significant advances in MI treatment, many who survive the acute event are at high risk of chronic cardiac morbidity. Here we developed a cell-free therapeutic that capitalizes on the antifibrotic effects of micro(mi)RNA-101a and exploits the multi-faceted regenerative activity of mesenchymal stem cell (MSC) extracellular nanovesicles (eNVs). While the majority of MSC eNVs require local delivery via intramyocardial injection to exert therapeutic efficacy, we have developed MSC eNVs that can be administered in a minimally invasive manner, all while remaining therapeutically active. When loaded with miR-101a, MSC eNVs substantially decreased infarct size (9.2 ±â€¯1.7% vs. 20.0 ±â€¯6.5%) and increased ejection fraction (53.6 ±â€¯7.6% vs. 40.3 ±â€¯6.0%) and fractional shortening (23.6 ±â€¯4.3% vs. 16.6 ±â€¯3.0%) compared to control. These findings are significant as they represent an advance in the development of minimally invasive cardio-therapies.

Rapid steroid hormone actions via membrane receptors.

Steroid hormones regulate a wide variety of physiological and developmental functions. Traditional steroid hormone signaling acts through nuclear and cytosolic receptors, altering gene transcription and subsequently regulating cellular activity. This is particularly important in hormonally-responsive cancers, where therapies that target classical steroid hormone receptors have become clinical staples in the treatment and management of disease. Much progress has been made in the last decade in detecting novel receptors and elucidating their mechanisms, particularly their rapid signaling effects and subsequent impact on tumorigenesis. Many of these receptors are membrane-bound and lack DNA-binding sites, functionally separating them from their classical cytosolic receptor counterparts. Membrane-bound receptors have been implicated in a number of pathways that disrupt the cell cycle and impact tumorigenesis. Among these are pathways that involve phospholipase D, phospholipase C, and phosphoinositide-3 kinase. The crosstalk between these pathways has been shown to affect apoptosis and proliferation in cardiac cells, osteoblasts, and chondrocytes as well as cancer cells. This review focuses on rapid signaling by 17ß-estradiol and 1α,25-dihydroxy vitamin D3 to examine the integrated actions of classical and rapid steroid signaling pathways both in contrast to each other and in concert with other rapid signaling pathways. This new approach lends insight into rapid signaling by steroid hormones and its potential for use in targeted drug therapies that maximize the benefits of traditional steroid hormone-directed therapies while mitigating their less desirable effects.

Functional Incompatibility between the Generic NF-κB Motif and a Subtype-Specific Sp1III Element Drives the Formation of the HIV-1 Subtype C Viral Promoter.

UNLABELLED: Of the various genetic subtypes of human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) and simian immunodeficiency virus (SIV), only in subtype C of HIV-1 is a genetically variant NF-κB binding site found at the core of the viral promoter in association with a subtype-specific Sp1III motif. How the subtype-associated variations in the core transcription factor binding sites (TFBS) influence gene expression from the viral promoter has not been examined previously. Using panels of infectious viral molecular clones, we demonstrate that subtype-specific NF-κB and Sp1III motifs have evolved for optimal gene expression, and neither of the motifs can be replaced by a corresponding TFBS variant. The variant NF-κB motif binds NF-κB with an affinity 2-fold higher than that of the generic NF-κB site. Importantly, in the context of an infectious virus, the subtype-specific Sp1III motif demonstrates a profound loss of function in association with the generic NF-κB motif. An additional substitution of the Sp1III motif fully restores viral replication, suggesting that the subtype C-specific Sp1III has evolved to function with the variant, but not generic, NF-κB motif. A change of only two base pairs in the central NF-κB motif completely suppresses viral transcription from the provirus and converts the promoter into heterochromatin refractory to tumor necrosis factor alpha (TNF-α) induction. The present work represents the first demonstration of functional incompatibility between an otherwise functional NF-κB motif and a unique Sp1 site in the context of an HIV-1 promoter. Our work provides important leads as to the evolution of the HIV-1 subtype C viral promoter with relevance for gene expression regulation and viral latency. IMPORTANCE: Subtype-specific genetic variations provide a powerful tool to examine how these variations offer a replication advantage to specific viral subtypes, if any. Only in subtype C of HIV-1 are two genetically distinct transcription factor binding sites positioned at the most critical location of the viral promoter. Since a single promoter regulates viral gene expression, the promoter variations can play a critical role in determining the replication fitness of the viral strains. Our work for the first time provides a scientific explanation for the presence of a unique NF-κB binding motif in subtype C, a major HIV-1 genetic family responsible for half of the global HIV-1 infections. The results offer compelling evidence that the subtype C viral promoter not only is stronger but also is endowed with a qualitative gain-of-function advantage. The genetically variant NF-κB and the Sp1III motifs may be respond differently to specific cell signal pathways, and these mechanisms must be examined.

Genetic diversity and proviral DNA load in different neural compartments of HIV-1 subtype C infection.

In India, the low prevalence of HIV-associated dementia (HAD) in the Human immunodeficiency virus type 1 (HIV-1) subtype C infection is quite paradoxical given the high-rate of macrophage infiltration into the brain. Whether the direct viral burden in individual brain compartments could be associated with the variability of the neurologic manifestations is controversial. To understand this paradox, we examined the proviral DNA load in nine different brain regions and three different peripheral tissues derived from ten human subjects at autopsy. Using a highly sensitive TaqMan probe-based real-time PCR, we determined the proviral load in multiple samples processed in parallel from each site. Unlike previously published reports, the present analysis identified uniform proviral distribution among the brain compartments examined without preferential accumulation of the DNA in any one of them. The overall viral DNA burden in the brain tissues was very low, approximately 1 viral integration per 1000 cells or less. In a subset of the tissue samples tested, the HIV DNA mostly existed in a free unintegrated form. The V3-V5 envelope sequences, demonstrated a brain-specific compartmentalization in four of the ten subjects and a phylogenetic overlap between the neural and non-neural compartments in three other subjects. The envelope sequences phylogenetically belonged to subtype C and the majority of them were R5 tropic. To the best of our knowledge, the present study represents the first analysis of the proviral burden in subtype C postmortem human brain tissues. Future studies should determine the presence of the viral antigens, the viral transcripts, and the proviral DNA, in parallel, in different brain compartments to shed more light on the significance of the viral burden on neurologic consequences of HIV infection.

Spray drying of fruit and vegetable juices--a review.

The main cause of spray drying is to increase the shelf life and easy handling of juices. In the present paper, the studies carried out so far on spray drying of various fruits and vegetables are reported. The major fruit juices dried are mango, banana, orange, guava, bayberry, watermelon, pineapple, etc. However, study on vegetable juices is limited. In spray drying, the major optimized parameters are inlet air temperature, relative humidity of air, outlet air temperature, and atomizer speed that are given for a particular study. The juices in spray drying require addition of drying agents that include matlodextrin, liquid glucose, etc. The drying agents are added to increase the glass transition temperature. Different approaches for spray dryer design have also been discussed in the present work.

Mandibular primary intraosseous carcinoma arising from long-standing odontogenic keratocyst.

Primary intraosseous carcinoma (PIOC) of the jaw is a rare neoplasm arising from the lining epithelium of odontogenic cysts or de novo from odontogenic epithelial rests that has no communication with the surrounding mucosa of the upper aerodigestive tract. We present a case of PIOC ex-odontogenic keratocyst (PIOC ex-OKC) in a 35-year-old male. Histopathologic examination revealed a cystic lesion with a fibrous capsule lined by corrugated parakeratinized stratified squamous epithelium resting on a basal cell layer composed of columnar cells exhibiting palisaded hyperchromatic nuclei, features consistent with OKC. Surgical treatment consisted of bilateral crestal and crevicular incision, a reflection of the flap, breaking of all OKC locules, creation of a continuous cavity, and fitting of a decompression mold around the mandibular teeth. This case highlights the importance of knowing the features of PIOC and considering PIOC in the differential diagnosis of malignant tumors of odontogenic epithelium for timely surgical treatment.

Multimodal Imaging in Mucolipidosis Type IV: Siblings With Novel Genetic Variant.

PURPOSE: Utilization of multimodal imaging techniques to diagnose cases of mucolipidosis type IV (ML-IV) and report a new genetic variant. METHODS: This study is a case report. RESULTS: Case 1 involves a 4-year-old boy with corneal haziness and global developmental delay who showed an increased reflectivity of the corneal epithelium on anterior segment optical coherence tomography (AS-OCT). In addition, neurologic evaluation was suggestive of ML-IV. Further genetics evaluation confirmed ML-IV. Histology of the button revealed a thickened epithelial basement membrane. Case 2, the younger sibling, showed a milder corneal haze with similar changes on AS-OCT prompting us to further evaluate for ML-IV by genetics (positive MCOLN1 gene mutation). Both instances highlighted varied ML-IV presentations, but a persistent feature was hyperreflective epithelium. CONCLUSIONS: Our study emphasizes AS-OCT's role in screening ML-IV and advocates the role of genetic counseling of affected parents. We present 2 South-Asian siblings with ML-IV with a new genetic variant, emphasizing the utility of detailed ophthalmic and neurologic assessments using multimodal imaging.

Increasing the accuracy of single-molecule data analysis using tMAVEN.

Time-dependent single-molecule experiments contain rich kinetic information about the functional dynamics of biomolecules. A key step in extracting this information is the application of kinetic models, such as hidden Markov models (HMMs), which characterize the molecular mechanism governing the experimental system. Unfortunately, researchers rarely know the physico-chemical details of this molecular mechanism a priori, which raises questions about how to select the most appropriate kinetic model for a given single-molecule dataset and what consequences arise if the wrong model is chosen. To address these questions, we have developed and used time-series Modeling, Analysis, and Visualization ENvironment (tMAVEN), a comprehensive, open-source, and extensible software platform. tMAVEN can perform each step of the single-molecule analysis pipeline, from pre-processing to kinetic modeling to plotting, and has been designed to enable the analysis of a single-molecule dataset with multiple types of kinetic models. Using tMAVEN, we have systematically investigated mismatches between kinetic models and molecular mechanisms by analyzing simulated examples of prototypical single-molecule datasets exhibiting common experimental complications, such as molecular heterogeneity, with a series of different types of HMMs. Our results show that no single kinetic modeling strategy is mathematically appropriate for all experimental contexts. Indeed, HMMs only correctly capture the underlying molecular mechanism in the simplest of cases. As such, researchers must modify HMMs using physico-chemical principles to avoid the risk of missing the significant biological and biophysical insights into molecular heterogeneity that their experiments provide. By enabling the facile, side-by-side application of multiple types of kinetic models to individual single-molecule datasets, tMAVEN allows researchers to carefully tailor their modeling approach to match the complexity of the underlying biomolecular dynamics and increase the accuracy of their single-molecule data analyses.