Old nuclei spring new leaks.

The nuclear pore complex (NPC) regulates the bidirectional movement of cell components across the nuclear envelope. In this issue, D'Angelo et al. (2009) demonstrate that the NPC loses essential protein subunits as cells age, resulting in increased nuclear permeability and potentially contributing to organismal aging.

Comparative analysis of metazoan chromatin organization.

Genome function is dynamically regulated in part by chromatin, which consists of the histones, non-histone proteins and RNA molecules that package DNA. Studies in Caenorhabditis elegans and Drosophila melanogaster have contributed substantially to our understanding of molecular mechanisms of genome function in humans, and have revealed conservation of chromatin components and mechanisms. Nevertheless, the three organisms have markedly different genome sizes, chromosome architecture and gene organization. On human and fly chromosomes, for example, pericentric heterochromatin flanks single centromeres, whereas worm chromosomes have dispersed heterochromatin-like regions enriched in the distal chromosomal 'arms', and centromeres distributed along their lengths. To systematically investigate chromatin organization and associated gene regulation across species, we generated and analysed a large collection of genome-wide chromatin data sets from cell lines and developmental stages in worm, fly and human. Here we present over 800 new data sets from our ENCODE and modENCODE consortia, bringing the total to over 1,400. Comparison of combinatorial patterns of histone modifications, nuclear lamina-associated domains, organization of large-scale topological domains, chromatin environment at promoters and enhancers, nucleosome positioning, and DNA replication patterns reveals many conserved features of chromatin organization among the three organisms. We also find notable differences in the composition and locations of repressive chromatin. These data sets and analyses provide a rich resource for comparative and species-specific investigations of chromatin composition, organization and function.

Inflammatory pseudotumour.

A 29 year old female patient with submandibular swelling, anaemia, fever was diagnosed to have inflammatory pseudotumour of neck. We are reporting this case as it can affect diverse locations in body with varied clinical manifestations mimicking malignancy and posing a diagnostic challenge.

Psychiatric Manifestations of COVID-19: A Literature Review.

BACKGROUND: COVID-19 (coronavirus disease of 2019) occurs due to the highly contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It uses angiotensin-converting enzyme- 2 (ACE-2) as its primary receptor to enter the host cell. Recent reports suggest that this pathogen also has a large impact on the CNS alongside other organs. Various inflammatory mediators, such as cytokines, chemokines, and numerous metabolites, are poorly regulated during infection as well as in several psychiatric diseases, which leads to conditions of hypoxia and cytokine storm. The persistence of COVID-19 infection may also result in aggravation of the already present neuro-psychiatric symptoms in patients. METHODS: We systematically searched various sources of journals and assessed the varied neurological routes of propagation and pathogenesis of SARS-CoV-2 neurotoxicity, like ACE2-mediated neuroinvasion induced hypoxia and the cytokine storm syndrome. Several case studies were also referred to obtain a better idea of the current mental health scenario as a consequence of infection and inflammation due to SARS-CoV-2. CONCLUSION: Several risk factors for the causation of mental health issues during as well as after the infection include female gender, presence of necrosis, and pain in avascular regions. Most psychiatric disorders are directly associated with the socioeconomic and psychosocial changes that have occurred as a consequence of the pandemic. These psychiatric manifestations have only started to unravel, which calls for the development of faster means of diagnosis and integrated pharmacological and epidemiological studies to curb the growing rate of neuronal complications as well as mortality.

Impact of nanocarrier aggregation on EPR-mediated tumor targeting.

The aim of this study was to investigate the influence of excipients on retaining the particle size of methotrexate (MTX) loaded chitosan nanocarriers (CsNP) during lyophilization, which relates to the ability to enlarge the particle size and target specific areas. The nanocarriers were prepared using the ionic gelation technique with tripolyphosphate as a crosslinker. Three lyophilized formulations were used: nanosuspension without Lyoprotectant (NF), with mannitol (NFM), and with sucrose (NFS). The lyophilized powder intended for injection (PI) was examined to assess changes in particle size, product integrity, and comparative biodistribution studies to evaluate targeting ability. After lyophilization, NFS was excluded from in-vivo studies due to the product melt-back phenomenon. The particle size of the NF lyophile significantly increased from 176 nm to 261 nm. In contrast, NFM restricted the nanocarrier size to 194 nm and exhibited excellent cake properties. FTIR, XRD, and SEM analysis revealed the transformation of mannitol into a stable ß, δ polymorphic form. Biodistribution studies showed that the nanocarriers significantly increased MTX accumulation in tumor tissue (NF = 2.04 ± 0.27; NFM = 2.73 ± 0.19) compared to the marketed PI (1.45 ± 0.25 µg), but this effect was highly dependent on the particle size. Incorporating mannitol yielded positive results in restricting particle size and favoring successful tumor targeting. This study demonstrates the potential of chitosan nanocarriers as promising candidates for targeted tumor drug delivery and cancer treatment.

Exploring the contribution of pro-inflammatory cytokines to impaired wound healing in diabetes.

Background: Impaired wound healing is the most common and significant complication of Diabetes. While most other complications of Diabetes have better treatment options, diabetic wounds remain a burden as they can cause pain and suffering in patients. Wound closure and repair are orchestrated by a sequence of events aided by the release of pro-inflammatory cytokines, which are dysregulated in cases of Diabetes, making the wound environment unfavorable for healing and delaying the wound healing processes. This concise review provides an overview of the dysregulation of pro-inflammatory cytokines and offers insights into better therapeutic outcomes. Purpose of review: Although many therapeutic approaches have been lined up nowadays to treat Diabetes, there are no proper treatment modalities proposed yet in treating diabetic wounds due to the lack of understanding about the role of inflammatory mediators, especially Pro-inflammatory mediators- Cytokines, in the process of Wound healing which we mainly focus on this review. Recent findings: Although complications of Diabetes mellitus are most reported after years of diagnosis, the most severe critical complication is impaired Wound Healing among Diabetes patients. Even though Trauma, Peripheral Artery Disease, and Peripheral Neuropathy are the leading triggering factors for the development of ulcerations, the most significant issue contributing to the development of complicated cutaneous wounds is wound healing impairment. It may even end up with amputation. Newer therapeutic approaches such as incorporating the additives in the present dressing materials, which include antimicrobial molecules and immunomodulatory cytokines is of better therapeutic value. Summary: The adoption of these technologies and the establishment of novel therapeutic interventions is difficult since there is a gap in terms of a complete understanding of the pathophysiological mechanisms at the cellular and molecular level and the lack of data in terms of the assessment of safety and bioavailability differences in the individuals' patients. The target-specific pro-inflammatory cytokines-based therapies, either by upregulation or downregulation of them, will be helpful in the wound healing process and thereby enhances the Quality of life in patients, which is the goal of drug therapy.

Anti-obesity effects of olivetol in adult zebrafish model induced by short-term high-fat diet.

Obesity is a complex disease caused by various factors, and synthetic drugs used to treat it can have side effects. Natural compounds, such as olivetol, could be a promising alternative. Olivetol is a substance found in certain lichen species and has anti-inflammatory and anti-cancer properties. In this study, researchers conducted in-silico molecular docking studies and found that olivetol had significant binding affinity with receptors involved in obesity. They also investigated the effects of olivetol on a diet-induced obese zebrafish model and found that high doses of olivetol reduced excessive fat accumulation and triglyceride and lipid accumulation. The low dose of olivetol showed a significant reduction in liver enzymes' levels. However, the high dose of olivetol resulted in a significant increase in HMG-CoA levels. These results suggest that olivetol may be a promising anti-obesity agent for the treatment of hyperlipidemia-related disorders, but further research is necessary to understand its full effects on the body.

Duration of seroprotection of the live attenuated SA-14-14-2 Japanese encephalitis vaccine in children in India.

BACKGROUND: Acute encephalitis syndrome (AES) is a major public health concern in India, and the Japanese Encephalitis (JE) virus is the most common cause of viral encephalitis in Asia affecting children under the age of 15 years. In India, despite the introduction of the JE vaccine (SA-14-14-2) in the immunization programme, JE continues to account for 15-20% of AES cases to date. This study evaluates the immunogenicity of live attenuated SA-14-14-2 JE vaccine in terms of persistence of the humoral response after two doses. METHODS: A cross-sectional study was conducted among 266 children belonging to one of the JE endemic regions of Uttar Pradesh, India. Blood samples were taken from children (2-10 years) and grouped according to the duration (in years) after two doses of the vaccine (5 groups with a class interval of 2 years). Informed written consent was obtained from the parents/guardians. All the samples collected were tested for the presence of anti-JEV-specific IgG antibodies by enzyme-linked immunosorbent assay (ELISA) and further confirmed by micro neutralization test (MNT) and immunofluorescence assays. RESULTS: Of the 266 samples tested by ELISA for anti-JEV-specific IgG antibodies, 260 (97.74%) were negative and 6 (2.26%) were equivocal. The geometric mean immune status ratio across the five groups, 0-2 years (n = 59), 2-4 years (n = 73), 4-6 years (n = 65), 6-8 years (n = 48) and 8-10 years (n = 21) post-two doses of SA-14-14-2 JE vaccine was 1.143, 1.059, 1.138, 1.075 and 1.130, respectively, and the geometric mean titre obtained from MNT across the five groups was 10.77, 8.400, 8.453, 9.517 and 9.674, respectively. CONCLUSION: The study showed a decreasing trend of anti-JEV specific IgG antibody titres across the five groups based on the duration following two doses of SA-14-14-2 vaccine. The results emphasize the significance of booster doses of vaccine for children living in endemic areas.

A pathway containing the Ipl1/aurora protein kinase and the spindle midzone protein Ase1 regulates yeast spindle assembly.

It is critical to elucidate the pathways that mediate spindle assembly and therefore ensure accurate chromosome segregation during cell division. Our studies of a unique allele of the budding yeast Ipl1/Aurora protein kinase revealed that it is required for centrosome-mediated spindle assembly in the absence of the BimC motor protein Cin8. In addition, we found that the Ase1 spindle midzone-associated protein is required for bipolar spindle assembly. The cin8 ipl1 and cin8 ase1 double mutant cells exhibit similar defects, and Ase1 overexpression completely restores spindle assembly in cin8 ipl1 strains. Consistent with the possibility that Ipl1 regulates Ase1, an ase1 mutant lacking the Ipl1 consensus phosphorylation sites cannot assemble spindles in the absence of Cin8. In addition, Ase1 phosphorylation and localization were altered in an ipl1 mutant. We therefore propose that Ipl1/Aurora and Ase1 constitute a previously unidentified spindle assembly pathway that becomes essential in the absence of Cin8.

The role of plant-based products in the prevention of neurological complications.

BACKGROUND: Neurological complications are most likely to be fatal and cause loss of ability to function or care for self. These include Alzheimer's disease and cognitive impairment. The main aim of the review is to determine the effects of various drugs and their cognitive risk with the need to opt for herbal therapy as an adjuvant in treating neurological conditions like Alzheimer's disease with lesser-known side effects. The Methodology: Involved a detailed literature survey which was performed through an online database, such as Science Direct, Google Scholar, Scopus, Cochrane, and PubMed. The study included randomized trials and original research conducted by herbal supplements on animal models to assess expression of upregulation of signalling pathways. Various studies involved in treating dementia, neurological disorders, Alzheimer disease, cognitive dysfunction were included. RESULTS: Found that various studies involved plant-based products were showing improvement in prevention of disease and signalling pathways with lesser-known side effects. CONCLUSION: It was observed that plant-based products play a major role in the prevention of neurological complications. Herbal medicines could most suitably prevent Alzheimer's risk with less known side effects in contrast with the existing treatment patterns. However, to improve the utility of herbal medicines, more evidences from in vitro, in vivo, and clinical trials need to be addressed.

Enzyme-assisted extraction of flavorings and colorants from plant materials.

From times immemorial, colorants, and flavorings have been used in foods. Color and flavor are the major attributes to the quality of a food product, affecting the appearance and acceptance of the product. As a consequence of the increased demand of natural flavoring and colorant from industries, there is a renewed interest in the research on the composition and recovery of natural food flavors and colors. Over the years, numerous procedures have been proposed for the isolation of aromatic compounds and colors from plant materials. Generally, the methods of extraction followed for aroma and pigment from plant materials are solvent extraction, hydro-distillation, steam distillation, and super critical carbon dioxide extraction. The application of enzymes in the extraction of oil from oil seeds like sunflower, corn, coconut, olives, avocado etc. are reported in literature. There is a great potential for this enzyme-based extraction technology with the selection of appropriate enzymes with optimized operating conditions. Various enzyme combinations are used to loosen the structural integrity of botanical material thereby enhancing the extraction of the desired flavor and color components. Recently enzymes have been used for the extraction of flavor and color from plant materials, as a pre-treatment of the raw material before subjecting the plant material to hydro distillation/solvent extraction. A deep knowledge of enzymes, their mode of action, conditions for optimum activity, and selection of the right type of enzymes are essential to use them effectively for extraction. Although the enzyme hydrolases such as lipases, proteases (chymotrypsin, subtilisin, thermolysin, and papain), esterases use water as a substrate for the reaction, they are also able to accept other nucleophiles such as alcohols, amines, thio-esters, and oximes. Advantages of enzyme-assisted extraction of flavor and color in some of the plant materials in comparison with conventional methods are dealt with in this reveiw.

Teleost Model as an Alternative in Parkinson's Disease.

In the experimental models of Parkinson's disease (PD), a well-known neurotoxin 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine or MPTP, pesticides like benomyl, paraquat,etc. are successfully used to induce a Parkinson's disease in human and nonhuman primates, which can be reversed by the drugs such as L-DOPA. A review on the alternative methods and alternative models in Parkinson's disease is documented here to understand their advantages and importance. Earlier researchers proved MPTP is effective in the goldfish, which reliably mirrors the neurochemical and behavioral changes caused by MPTP in the higher vertebrates. Gold fish brain has the "nucleus pars medialis," similar to the substanitia nigra of the human brain can be destructed by chemicals like MPTP, 6-hydroxydopamine and has selective protection by L-Dopa (Levodopa) and MAO-B (Monoamine oxidase B) inhibitors. In addition, zebrafish along with mice was successfully employed in the study of pesticides leading to neurodegeneration in PD. As the current animal models often couldn't replicate the true pathophysiology of idiopathic PD, alternative models have gained importance in the research. Upon having a glance at different models utilized in Parkinson's disease studies, one can get an idea on preferring alternative models, especially the zebra fish model in the study of neurodegenerative disorders.

Diurnal intraocular pressure fluctuation and associated risk factors in eyes with angle closure.

OBJECTIVE: To investigate diurnal intraocular pressure (IOP) fluctuation in eyes with angle closure in comparison with normal subjects and to look for associated risk factors for IOP fluctuation. DESIGN: Prospective, cross-sectional study. PARTICIPANTS: Ninety-eight eyes of 98 Asian subjects with angle closure (consisting of 32 primary angle-closure suspects [PACS], 34 subjects with primary angle closure [PAC], and 32 subjects with primary angle-closure glaucoma [PACG]) and 21 eyes of 21 normal control subjects. METHODS: All angle-closure subjects were enrolled after laser peripheral iridotomy but before commencement of any medical or surgical treatment. Ophthalmic examination, including dynamic gonioscopy and automated perimetry, were performed, and diurnal IOP measurements were obtained using noncontact air-puff tonometry at hourly intervals between 8:00 am and 5:00 pm. Mean diurnal IOP, peak diurnal IOP, trough IOP, and IOP fluctuation (peak IOP-trough IOP) were compared between groups. Multiple linear regression analysis was performed to study the association of IOP fluctuation with clinical variables such as age, extent of peripheral anterior synechiae (PAS), central corneal thickness, vertical cup-to-disc ratio, and pattern standard deviation (PSD) on automated perimetry. MAIN OUTCOME MEASURES: Mean diurnal IOP, peak IOP, and IOP fluctuation. RESULTS: Most subjects were Chinese (89.1%) and female (61.3%). Intraocular pressure fluctuation was significantly higher in PACG (5.4+/-2.4 mmHg) and PAC (4.5+/-2.3 mmHg) subjects compared with PACS subjects (3.7+/-1.2 mmHg) and normal controls (3.8+/-1.1 mmHg; P = 0.005), with highest IOP found in the early morning. The combined PACG and PAC group had more than twice the risk (odds ratio, 2.38; 95% confidence interval, 1.1-5.1; P = 0.025) of having IOP fluctuation of more than 3 mmHg compared with the combined PACS and normal group. Extent of PAS (Pearson's correlation coefficient, r = 0.37; P = 0.0001) and visual field PSD (r = 0.34; P = 0.0002) were found to be associated with greater IOP fluctuation. CONCLUSIONS: The PACG and PAC eyes showed diurnal IOP fluctuation of 4 to 5 mmHg, and this fluctuation was higher than in PACS subjects and normal controls. The degree of PAS and visual field loss were associated with IOP fluctuation in PAC and PACG eyes.

Glc7/protein phosphatase 1 regulatory subunits can oppose the Ipl1/aurora protein kinase by redistributing Glc7.

Faithful chromosome segregation depends on the opposing activities of the budding yeast Glc7/PP1 protein phosphatase and Ipl1/Aurora protein kinase. We explored the relationship between Glc7 and Ipl1 and found that the phosphorylation of the Ipl1 substrate, Dam1, was altered by decreased Glc7 activity, whereas Ipl1 levels, localization, and kinase activity were not. These data strongly suggest that Glc7 ensures accurate chromosome segregation by dephosphorylating Ipl1 targets rather than regulating the Ipl1 kinase. To identify potential Glc7 and Ipl1 substrates, we isolated ipl1-321 dosage suppressors. Seven genes (SDS22, BUD14, GIP3, GIP4, SOL1, SOL2, and PEX31) encode newly identified ipl1 dosage suppressors, and all 10 suppressors encode proteins that physically interact with Glc7. The overexpression of the Gip3 and Gip4 suppressors altered Glc7 localization, indicating they are previously unidentified Glc7 regulatory subunits. In addition, the overexpression of Gip3 and Gip4 from the galactose promoter restored Dam1 phosphorylation in ipl1-321 mutant cells and caused wild-type cells to arrest in metaphase with unsegregated chromosomes, suggesting that Gip3 and Gip4 overexpression impairs Glc7's mitotic functions. We therefore propose that the overexpression of Glc7 regulatory subunits can titrate Glc7 away from relevant Ipl1 targets and thereby suppress ipl1-321 cells by restoring the balance of phosphatase/kinase activity.

Sinonasal neurogenic tumours.

Among the surgically excised or biopsied sinonasal tumours in a span of ten years, the neurogenic tumours formed 6.7% of all sinonasal tumours. They were eight in number, three schwannomas, two neurofibromas and three malignant schwannomas with occurrence in a wide age range and no gender predilection. Nasal obstruction and epistaxis were common modes of presentation with a unilateral location. The diagnosis of benign neurogenic tumours do not pose difficulty. However, malignant schwannoma should be considered when one encounters a cellular spindle cell lesion in sinonasal region.

Robustness in crossover regulation during meiosis.

Meiotic recombination produces physical linkages between homologous chromosomes that enable their segregation to opposite poles during meiosis I. In the absence of recombination, chromosomes mis-segregate, resulting in aneuploidy associated with severe birth defects. A recent study provides exciting insights into how recombination is fine-tuned to enforce a robust meiotic program.

Wound healing activity of Glycosmis arborea leaf extract in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Glycosmis arborea Roxb, syn. Glycosmis pentaphylla Retz, (Rutacea) is a shrub found all over India, have been used for the healing of wounds of livestock in Indian folk medicine. AIM OF THE STUDY: The present study provides a scientific evaluation for the wound healing potential of ethanolic extract of Glycosmis arborea leaves. METHODS AND MATERIALS: Excision and incision wounds were inflicted upon four groups containing six rats each. Group-1 was assigned as control (ointment base), Group-2 and Group-3 were treated with 5 and 10% EtOH extract ointment. Group-4 was treated with standard Nitrofurazone (0.2%) ointment. The parameters observed were percentage of wound contraction, epithelization period, tensile strength, hydroxyproline content. Ethanolic extract of Glycosmis arborea leaves was given orally at a dose of 200, 400mg/kg/day in dead space wound model. RESULTS: Topical application of Glycosmis arborea ointment (10%) in excision wound model significantly (P<0.05) increased the percentage of wound contraction (96.91%) compared with control (60.27%) and decreased the epithelization time. The tensile strength significantly (P<0.05) increased in Group-3 at 560.33 ± 6.48g when compared to control at 319.17±6.16 g. Rats treated with Glycosmis arborea extract (400mg/kg) showed significant (P<0.05) increase in hydroxyproline content at 54.94 ± 0.96 mg/g when compared with control at 30.77±1.13 mg/g. CONCLUSION: The ethanolic extract of Glycosmis arborea facilitated wound healing significantly, corroborating the folk medicinal use of this plant.

Metabolic syndrome: an occupational perspective.

OBJECTIVE: To study the prevalence of Metabolic Syndrome (MS) in an Indian industrial setup and to study disparity in occurrence of MS in a working population based on occupational status. MATERIALS AND METHODS: Cross-sectional study of 651 employees who underwent periodic medical examination. The International Diabetes Federation (IDF) definition of MS and International Standard Classification of Occupations (ISCO)-88 classification of occupations were used. RESULTS: The overall crude prevalence of MS was found to be 18.5%. Nineteen percent of the non-manual workers and 18.3% of the manual workers suffered from MS. The single largest occupational category with MS was ISCO-88 group 1, which included the managers and senior officials. However, no difference was found among the manual and non-manual workers in prevalence of MS.

Primary hyperparathyroidism: a clinicopathological experience.

BACKGROUND: Parathyroid neoplasms form a small percentage of head and neck neoplasms. Primary hyperparathyroidism is caused by parathyroid adenomas, hyperplasia or, rarely, a carcinoma. MATERIALS AND METHODS: This is a retrospective study of 48 parathyroidectomies received in the Department of Pathology of a major teaching hospital over a period of 10 years. Clinical, biochemical and radiological details were retrieved from medical records. Information regarding routine gross and microscopic examination findings (including frozen section and paraffin sections) was retrieved from departmental records. RESULTS: We had 43 adenomas, three hyperplasias and two carcinomas. The most common age group was 21-30 years. The female:male ratio was 2.5:1. Most patients presented with skeletal manifestations. The pre-operative diagnosis was assisted by ultrasonography in 11 cases, computerized tomography of the neck in 10 cases and sestamibi scans in three cases. Intra-operative parathormone monitoring was performed in one case of adenoma. Frozen section was requested in 28 of 48 cases. There was a discrepancy between frozen section diagnosis and paraffin section diagnosis in two cases. CONCLUSION: Histopathologic diagnosis is an important guide to decide the type of surgical management. Although pathologic features of parathyroid carcinoma are diagnostically reliable, those of the more commonly encountered lesions of adenoma and hyperplasia may be overlapping and, therefore, indistinctive, more so if only a single gland is available for examination. Because parathyroid lesions are only occasionally encountered by the surgical pathologist, awareness of the spectrum of histologic features along with knowledge of recent trends in diagnosis and surgical management are important.

Is routine pupil dilation safe among asian patients with diabetes?

PURPOSE: To investigate the risk of acute angle closure (AAC), changes in intraocular pressure (IOP), and factors associated with these outcomes after routine pupil dilation in a cohort of Asian subjects with diabetes mellitus. METHODS: The study was a prospective observational case series of 1910 consecutive Asian subjects newly referred for assessment of diabetic retinopathy at a tertiary clinic. All subjects underwent routine pupil dilation unless there was a prior history of angle-closure glaucoma. Noncontact air-puff tonometry was used to assess IOP, which was measured by the same observer before and 1 hour after pupil dilation. Subjects were assessed for signs and symptoms of AAC before leaving the clinic, and their charts were also subsequently reviewed for revisits with AAC. RESULTS: Of the 1910 subjects who participated, none developed AAC. Sixty-nine subjects (3.6%, 95% CI: 2.8%-4.5%) showed an increase in IOP of >or=5 mm Hg in the either eye, 37 subjects (1.9%, 95% CI: 1.4%-2.6%) had a postdilation IOP >25 mm Hg in either eye, and only 10 subjects (0.52%, 95% CI: 0.25%-0.96%) had an increase in IOP >or=5 mm Hg and had a postdilation IOP >25 mm Hg in either eye. The level of predilation IOP and a known history of glaucoma were significant risk factors for a postdilation IOP >or=25 mm Hg. CONCLUSIONS: In this cohort of Asian persons with diabetes, the risk of AAC was insignificant after routine dilation of pupils for fundus examination. These data substantiate the safety of routine dilation of pupils in Asian patients with diabetes.