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The 'polio eradication initiative' launched by the World Health Assembly in 1988, although successfully implemented in several countries, could not achieve the goal of global eradication by the year 2000. It has components on strengthening routine immunization system, observance of National Immunization Days (NIDs) and strengthening of surveillance for Acute Flaccid Paralysis (AFP). Recently, this strategy was challenged in Kerala, India. Kerala has excellent health indicators compared with other Indian states. In 1999, Intensified Pulse Polio Immunization (IPPI) was introduced with four NIDs throughout India. More than 2000 doctors working under the Kerala Government challenged the strategy, demanding its redesign. Zero prevalence of polio for 2 years, near-complete coverage of children by the routine system, probable business interests of vaccine manufactures and suppliers, dubious interests of officials, and weakening of the routine system by concentrating more on NIDs were all cited as reasons for discontinuing current strategy. The authorities, citing the success stories of polio eradication by the global initiative in several countries, discard the allegations as baseless. They alleged that the medical officers who were on strike demanding higher pay and better conditions were using the 'polio issue' to win their strike. The incidence of two polio cases in Malappuram in northern Kerala during September 2000 has further complicated the issue. As the controversy continues it is felt that the 'eradication initiative' will have to be revisited. [ABSTRACT FROM AUTHOR]

The elemental composition of the lunar surface provides insights into mechanisms of the formation and evolution of the Moon 1,2 . The chemical composition of lunar regolith have so far been precisely measured using the samples collected by the Apollo, Luna and Chang'e 5 missions, which are from equatorial to mid-latitude regions 3,4 ; lunar meteorites, whose location of origin on the Moon is unknown 5,6 ; and the in situ measurement from the Chang'e 3 and Chang'e 4 missions 7-9 , which are from the mid-latitude regions of the Moon. Here we report the first in situ measurements of the elemental abundances in the lunar southern high-latitude regions by the Alpha Particle X-ray Spectrometer (APXS) experiment 10 aboard the Pragyan rover of India's Chandrayaan-3 mission. The 23 measurements in the vicinity of the Chandrayaan-3 landing site show that the local lunar terrain in this region is fairly uniform and primarily composed of ferroan anorthosite (FAN), a product of the lunar magma ocean (LMO) crystallization. However, observation of relatively higher magnesium abundance with respect to calcium in APXS measurements suggests the mixing of further mafic material. The compositional uniformity over a few tens of metres around the Chandrayaan-3 landing site provides an excellent ground truth for remote-sensing observations., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Stabilization of microtubule plus end-directed kinesin CENP-E at the metaphase kinetochores is important for chromosome alignment, but its mechanism remains unclear. Here, we show that CKAP5, a conserved microtubule plus tip protein, regulates CENP-E at kinetochores in human cells. Depletion of CKAP5 impairs CENP-E localization at kinetochores at the metaphase plate and results in increased kinetochore-microtubule stability and attachment errors. Erroneous attachments are also supported by computational modeling. Analysis of CKAP5 knockout cancer cells of multiple tissue origins shows that CKAP5 is preferentially essential in aneuploid, chromosomally unstable cells, and the sensitivity to CKAP5 depletion is correlated to that of CENP-E depletion. CKAP5 depletion leads to reduction in CENP-E-BubR1 interaction and the interaction is rescued by TOG4-TOG5 domain of CKAP5. The same domain can rescue CKAP5 depletion-induced CENP-E removal from the kinetochores. Interestingly, CKAP5 depletion facilitates recruitment of PP1 to the kinetochores and furthermore, a PP1 target site-specific CENP-E phospho-mimicking mutant gets stabilized at kinetochores in the CKAP5-depleted cells. Together, the results support a model in which CKAP5 controls mitotic chromosome attachment errors by stabilizing CENP-E at kinetochores and by regulating stability of the kinetochore-attached microtubules., (© 2024. The Author(s).)

Faithful chromosome segregation requires correct attachment of kinetochores with the spindle microtubules. Erroneously-attached kinetochores recruit proteins to activate Spindle assembly checkpoint (SAC), which senses the errors and signals cells to delay anaphase progression for error correction. Temporal control of the levels of SAC activating-proteins is critical for checkpoint activation and silencing, but its mechanism is not fully understood. Here, we show that E3 ubiquitin ligase, SCF-FBXW7 targets BubR1 for ubiquitin-mediated degradation and thereby controls SAC in human cells. Depletion of FBXW7 results in prolonged metaphase arrest with increased stabilization of BubR1 at kinetochores. Similar kinetochore stabilization is also observed for BubR1-interacting protein, CENP-E. FBXW7 induced ubiquitination of both BubR1 and the BubR1-interacting kinetochore-targeting domain of CENP-E, but CENP-E domain degradation is dependent on BubR1. Interestingly, Cdk1 inhibition disrupts FBXW7-mediated BubR1 targeting and further, phospho-resistant mutation of Cdk1-targeted phosphorylation site, Thr 620 impairs BubR1-FBXW7 interaction and FBXW7-mediated BubR1 ubiquitination, supporting its role as a phosphodegron for FBXW7. The results demonstrate SCF-FBXW7 as a key regulator of spindle assembly checkpoint that controls stability of BubR1 and its associated CENP-E at kinetochores. They also support that upstream Cdk1 specific BubR1 phosphorylation signals the ligase to activate the process., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The kinetochore establishes the linkage between chromosomes and the spindle microtubule plus ends during mitosis. In vertebrates, the spindle-kinetochore-associated (Ska1,2,3) complex stabilizes kinetochore attachment with the microtubule plus ends, but how Ska is recruited to and stabilized at the kinetochore-microtubule interface is not understood. Here, our results show that interaction of Ska1 with the general microtubule plus end-associated protein EB1 through a conserved motif regulates Ska recruitment to kinetochores in human cells. Ska1 forms a stable complex with EB1 via interaction with the motif in its N-terminal disordered loop region. Disruption of this interaction either by deleting or mutating the motif disrupts Ska complex recruitment to kinetochores and induces chromosome alignment defects, but it does not affect Ska complex assembly. Atomic-force microscopy imaging revealed that Ska1 is anchored to the C-terminal region of the EB1 dimer through its loop and thereby promotes formation of extended structures. Furthermore, our NMR data showed that the Ska1 motif binds to the residues in EB1 that are the binding sites of other plus end targeting proteins that are recruited to microtubules by EB1 through a similar conserved motif. Collectively, our results demonstrate that EB1-mediated Ska1 recruitment onto the microtubule serves as a general mechanism for the formation of vertebrate kinetochore-microtubule attachments and metaphase chromosome alignment., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Development and survival of all eukaryotic organisms depend on equal partitioning of their chromosomes between the two newly formed daughter cells during mitosis. The mitotic spindle performs the task of physically segregating the chromosomes through multiple stages of mitosis. During this process, kinetochore-microtubule attachment requires to be selectively stabilized to hold the chromosomes, but at the same time, it has to be flexible enough to allow kinetochore microtubule dynamicity and chromosome movements. Research during the last decade or so has identified a number of proteins associated with the spindle microtubule plus ends that regulate these processes and orchestrate forces to spatially organize and separate the chromosomes. In this review, we describe the molecular details of those regulators and their mechanisms of action at the kinetochore-microtubule interface. © 2018 IUBMB Life, 70(2):101-111, 2018., (© 2018 International Union of Biochemistry and Molecular Biology.)

A novel chelating resin for preconcentration of heavy metals from various seawater samples has been developed by condensing 1-amino-2-hydroxy-7-[(4-hydroxyphenyl)diazenyl] naphthalene-4-sulfonic acid (AHDNS) with formaldehyde (1:2 mole ratio) in the presence of oxalic acid as the catalyst. The resin thus obtained was used as a solid sorbent for the separation of divalent metal ions present at trace levels in seawater. The functionalized phenol (AHDNS) was characterized by spectral studies. The polymeric resin AHDNS-formaldehyde (AHDNS-F) obtained by condensing the functionalized phenol and formaldehyde was characterized by IR and NMR spectral studies. The chelating property of the AHDNS-F resin towards divalent metal ions was studied as a function of pH and in the presence of electrolyte. The metal uptake properties of the resin were determined by using an atomic absorption spectrophotometer. This procedure was validated for recovery of divalent metal ions from seawater samples. The recoveries of cadmium, cobalt, copper, manganese, lead, and zinc were above 92% under the optimum preconcentration conditions. The LOD was <0.73 μg/L and the RSDs were <2%. Thus, the AHDNS-F resin can be widely used as a solid sorbent for the preconcentration of trace metals at ppm levels in seawater samples.

A rapid, reliable and sensitive LC-MS/MS method for the determination of melatonin in milk was developed and validated. Sample was extracted with dichloromethane and cleaned by passing through Chem Elut solid phase extraction cartridge. The solvent was evaporated to dryness, reconstituted with methanol and analysed by LC-MS/MS on Agilent zorbax Eclipse XDB C-18 rapid resolution analytical column. The analytical procedure was found to be accurate, precise and linear. The method accuracy was 92.2 % (range 90.06-94.58) and the mean precision was 1.55 % and the calibration was linear for 1 to 150 pg mL(-1) (R(2) > 0.99), the lowest limit of quantification (LLOQ) was 1 pg mL(-1). 7-D Melatonin (7-DM) was used as an internal standard. This method was proved to be a promising method for the determination of melatonin for market milk and human milk samples.

Exosomes are nanosized (30-100 nm) membrane vesicles secreted by most cell types. Exosomes have been found to contain various RNA species including miRNA, mRNA and long non-protein coding RNAs. A number of cancer cells produce elevated levels of exosomes. Because exosomes have been isolated from most body fluids they may provide a source for non-invasive cancer diagnostics. Transcriptome profiling that uses deep-sequencing technologies (RNA-Seq) offers enormous amount of data that can be used for biomarkers discovery, however, in case of exosomes this approach was applied only for the analysis of small RNAs. In this study, we utilized RNA-Seq technology to analyze RNAs present in microvesicles secreted by human breast cancer cell lines. Exosomes were isolated from the media conditioned by two human breast cancer cell lines, MDA-MB-231 and MDA-MB-436. Exosomal RNA was profiled using the Ion Torrent semiconductor chip-based technology. Exosomes were found to contain various classes of RNA with the major class represented by fragmented ribosomal RNA (rRNA), in particular 28S and 18S rRNA subunits. Analysis of exosomal RNA content revealed that it reflects RNA content of the donor cells. Although exosomes produced by the two cancer cell lines shared most of the RNA species, there was a number of non-coding transcripts unique to MDA-MB-231 and MDA-MB-436 cells. This suggests that RNA analysis might distinguish exosomes produced by low metastatic breast cancer cell line (MDA-MB-436) from that produced by highly metastatic breast cancer cell line (MDA-MB-231). The analysis of gene ontologies (GOs) associated with the most abundant transcripts present in exosomes revealed significant enrichment in genes encoding proteins involved in translation and rRNA and ncRNA processing. These GO terms indicate most expressed genes for both, cellular and exosomal RNA. For the first time, using RNA-seq, we examined the transcriptomes of exosomes secreted by human breast cancer cells. We found that most abundant exosomal RNA species are the fragments of 28S and 18S rRNA subunits. This limits the number of reads from other RNAs. To increase the number of detectable transcripts and improve the accuracy of their expression level the protocols allowing depletion of fragmented rRNA should be utilized in the future RNA-seq analyses on exosomes. Present data revealed that exosomal transcripts are representative of their cells of origin and thus could form basis for detection of tumor specific markers.

A rigorous, much simplified, and accurate analysis of the modal field characteristics such as propagation constants, mode power confinement, delay and dispersion characteristics of a single-mode graded-index elliptical core fiber is presented applying a variational method and super-Gaussian approximation of the fundamental modal field. Normalized propagation constants, a fundamental parameter to evaluate other modal characteristics, obtained through this method showed a greater accuracy over the entire range of practical interest in comparison with other reported methods. The effects of various aspect ratios on these characteristics are analyzed. In addition, the effect of Kerr nonlinearity on these characteristics is investigated using the reported method, and a comparison is made with the linear results.

The determinants of utilisation of subcentre services in a random sample of 247 subcentres from three out of 14 districts of Kerala were investigated. Physical verification of the facilities was done in a subset of 90 subcentres and household surveys of 750 households were performed in the service areas of those subcentres. About 30 per cent of the beneficiaries utilised services of the subcentres during the reference period. The relationship of selected predictor variables on utilisation of the services was found out. The district in which a subcentre was physically present was found to be the most important correlate of its utilisation.

Background: Exercise tolerance is reduced in hypertension. Hypertension affects left ventricular (LV) diastolic filling by causing abnormal relaxation and decreasing compliance., Hypothesis: This study was designed to determine whether worsening of LV diastolic dysfunction during exercise causes decreased exercise tolerance in hypertension., Methods: Left ventricular diastolic filling parameters were examined at mitral valve by Doppler echocardiography at rest and at peak exercise in hypertensive patients and were compared with those of age- and gender-matched normotensive individuals. Treadmill exercise stress test was performed according to the Bruce protocol and the exercise time was recorded., Results: Exercise time was significantly shorter in the hypertensive group than that in the normotensive group (320 +/- 29 vs. 446 +/- 38 s, p 0.03). The hypertensive group demonstrated abnormal relaxation pattern of diastolic mitral inflow at rest, which became pseudonormal at peak exercise (E/A velocity ratio, rest 0.86 +/- 0.06 vs. exercise 1.19 +/- 0.09, p < 0.001). The diastolic mitral inflow pattern remained normal at peak exercise in the normotensive group. The deceleration time and the pressure half time of early mitral inflow at peak exercise were significantly shorter in the hypertensive group than those in the normotensive group (deceleration time, 182 +/- 20 vs. 238 +/- 22 ms, p 0.02: pressure half time, 54 +/- 5 vs. 70 +/- 12 ms, p 0.01)., Conclusions: This study demonstrates that reduced exercise tolerance in hypertension is associated with worsening of diastolic dysfunction during exercise consistent with an increase in left atrial pressure.

Paragangliomas are rare neoplasms of neural crest origin arising in the chromaffin (pheochromocytoma) and chemoreceptor (chemodectoma) tissues. Only a few cases of paragangliomas have been reported in the heart. Most of the cardiac paragangliomas are located in, or adjacent to, the left atrium. The biological activity indicative of catecholamine production has rarely been shown in cardiac paragangliomas. Patients with cardiac paragangliomas may present with hypertension, or with various obstructive or compressive symptoms, depending on the location of the tumour. A left atrial paraganglioma compressing the esophagus causing dysphagia is presented. A 37-year-old female patient underwent work-up for dysphagia to solids. Transesophageal echocardiography showed the presence of a large mass in the dilated left atrium. The tumour was removed completely intact and was a benign noncatecholamine-secreting paraganglioma. The patient's dysphagia was relieved. The clinical perspectives of cardiac paraganglioma and cardiac dysphagia are discussed.

Aortic dissection is a medical emergency carrying high morbidity and mortality. Prompt diagnosis is sometimes difficult because of its varying presentations, but it is critical to the achievement of good clinical outcomes. This report describes 2 cases of painless aortic dissection that presented with aortic valve regurgitation. In both, the dissection was limited to the ascending aorta just distal to the aortic valve. These dissections were diagnosed by transthoracic and transesophageal echocardiography.

Coronary artery aneurysm is a rare coronary abnormality, usually diagnosed incidentally by coronary angiography. Major causes of coronary aneurysms include coronary ectasia, Kawasaki disease, and atherosclerosis. Most of the discrete coronary aneurysms are of atherosclerotic origin. The incidence of atherosclerotic coronary aneurysms is about 0.2%, and the left main coronary artery is the least frequently involved artery. Only a few cases of left main coronary artery aneurysm have been reported in the literature, and a left main coronary artery aneurysm involving the proximal segments of the left anterior descending and the left circumflex arteries has not been reported previously. The authors describe this finding in a man who presented with worsening exertional angina pectoris. Coronary angiography demonstrated an aneurysm of the distal left main coronary artery extending into the proximal segments of the left anterior descending and the left circumflex arteries. In addition, a significant flow-limiting atherosclerotic lesion was present in the proximal portion of the left anterior descending artery distal to the aneurysm.

The origination of all three major coronary arteries from three separate ostia in the right sinus of Valsalva is an exceedingly rare coronary anomaly. Few radiographic and clinical details of this anomaly are available in the literature. We describe this anomaly in a patient with acute myocardial infarction who remained asymptomatic until the 8th decade of her life. Atherosclerotic narrowing of the normally originating right coronary artery caused the acute myocardial infarction. Anomalous left anterior descending and left circumflex arteries were free of any significant obstruction.

The prevalence of coronary heart disease (CHD) and its risk factors in first-generation Asian Indian immigrants to the United States of America (US) were compared with those of the native Caucasian population. A total of 1688 Asian Indian physicians and their family members (1131 men and 557 women, age > or = 20 years) completed a questionnaire and in 580 subjects serum lipoproteins were determined. The age-adjusted prevalence of myocardial infarction and/or angina was approximately three times more in Asian Indian men compared to the Framingham Offspring Study (7.2% versus 2.5%; P < 0.0001) but was similar in women (0.3% versus 1%; p = 0.64). Asian Indians had higher prevalence of noninsulin-dependent diabetes mellitus (NIDDM; 7.6% versus 1%; p < 0.0001) but markedly lower prevalence of cigarette smoking (1.3% versus 27%; p < 0.0001) and obesity (4.2% versus 22%; p < 0.0001). Hypertension was less prevalent in Asian Indian men 14.2% versus 19.1%, p < 0.008) but similar in women (11.3% versus 11.4%). The prevalence of elevated total a low-density lipoprotein (LDL) cholesterol levels was similar in men [17% versus 23.4% (p = 0.24) and 13.7% versus 22.3% (p = 0.22), respectively] but lower in women [15% versus 26.1% (p = 0.018) and 14.3% versus 19.6% (p = 0.047) respectively]. The mean levels of high-density lipoprotein (HDL) cholesterol were less in younger (30-39 years) Asian Indian men (mean: 0.98 versus 1.18 mmol/l; p < 0.001) and middle-aged (30-59 years) women (mean: 1.24 versus 1.45 mmol/l; p < 0.001). The prevalence of hypertriglyceridaemia was similar in men (18.5% versus 11.3%), but higher in Asian Indian women (8.3% versus 4.1%, p = 0.02). To conclude, immigrant Asian Indian men to the US have high prevalence of CHD, NIDDM, low HDL cholesterol levels and hypertriglyceridaemia. All these have "insulin resistance" as a common pathogenetic mechanism and seem to be the most important risk factors.

Effect of unilateral (one leg) and bilateral (two legs) sciatectomy was studied on certain serum constituents in the male frog over a period of 3 weeks. The level of creatine kinase, acid and alkaline phosphatases, urea, glucose and proteins increased initially following sciatectomy and decreased subsequently from day 14 onwards, the per cent change being more pronounced in case of bilaterally sciatectomized frogs. The present results indicate an increase in the rate of deamination of proteins in the liver, an impairment in the transportation processes across the cell membrane and an increase in cellular lysosomal activity on sciatectomy suggesting a change either in the amount or in the rate of various enzyme reactions. It is concluded that sciatectomy induces alterations in general metabolic activities and the functional state of the animal. Altered values of various serum constituents thus permit to speculate analysis of the factor that may be contributing to the atrophic processes and the wasting of the muscle fibres known to set in the denervated muscle.