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Background: Biallelic variants in POLR1C are associated with POLR3-related leukodystrophy (POLR3-HLD), or 4H leukodystrophy (Hypomyelination, Hypodontia, Hypogonadotropic Hypogonadism), and Treacher Collins syndrome (TCS). The clinical spectrum of POLR3-HLD caused by variants in this gene has not been described. Methods: A cross-sectional observational study involving 25 centers worldwide was conducted between 2016 and 2018. The clinical, radiologic and molecular features of 23 unreported and previously reported cases of POLR3-HLD caused by POLR1C variants were reviewed. Results: Most participants presented between birth and age 6 years with motor difficulties. Neurological deterioration was seen during childhood, suggesting a more severe phenotype than previously described. The dental, ocular and endocrine features often seen in POLR3-HLD were not invariably present. Five patients (22%) had a combination of hypomyelinating leukodystrophy and abnormal craniofacial development, including one individual with clear TCS features. Several cases did not exhibit all the typical radiologic characteristics of POLR3-HLD. A total of 29 different pathogenic variants in POLR1C were identified, including 13 new disease-causing variants. Conclusions: Based on the largest cohort of patients to date, these results suggest novel characteristics of POLR1C-related disorder, with a spectrum of clinical involvement characterized by hypomyelinating leukodystrophy with or without abnormal craniofacial development reminiscent of TCS.
Agriculture in the Central Himalayan Region depends on the availability of suitable germplasm as well as natural conditions. Due to extreme weather conditions, food and nutrition security is a major issue for communities inhabiting these remote and inaccessible areas. Millets are common crops grown in these areas. Foxtail millet (Setaria italica (L.) P. Beauv) is an important crop and forms a considerable part of the diet in this region. The aim of the present study was to explore, collect, conserve and evaluate the untapped genetic diversity of foxtail millet at the molecular level and discover variability in their nutritional traits. A total of 30 accessions having unique traits of agronomic importance were collected and molecular profiling was performed. A total of 63 alleles were generated with an average of 2.52 alleles per locus and average expected heterozygosity of 0.37 ± 0.231. Significant genetic variability was revealed through the genetic differentiation (Fst) and gene flow (Nm) values. Structure-based analysis divided whole germplasm into three sub-groups. Rich variability was found in nutritional traits such as dietary fibre in husked grains, carbohydrate, protein, lysine and thiamine content. The collected germplasm may be useful for developing nutritionally rich and agronomically beneficial varieties of foxtail millet and also designing strategies for utilization of unexploited genetic diversity for food and nutrition security in this and other similar agro-ecological regions.
Influenza A(H1N1) viruses of the 2009 pandemic (A(H1N1)pdm09) continue to cause outbreaks in the post-pandemic period. During January to May 2015, an upsurge of influenza was recorded that resulted in high fatality in central India. Genetic lineage, mutations in the hemagglutinin (HA) gene and infection by quasi-species are reported to affect disease severity. The objective of this study is to present the molecular and epidemiological trends during the 2015 influenza outbreak in central India. All the referred samples were subjected to qRT–PCR for diagnosis. HA gene sequencing (23 survivors and 24 non-survivors) and cloning were performed and analyzed using Molecular Evolutionary Genomic Analyzer (MEGA 5·05). Of the 3625 tested samples, 1607 (44·3%) were positive for influenza A(H1N1)pdm09, of which 228 (14·2%) individuals succumbed to death. A significant trend was observed in positivity (P = 0·003) and mortality (P < 0·0001) with increasing age. The circulating A(H1N1)pdm09 virus was characterized as belonging to clade-6B. Clinically significant mutations were detected. Patients infected with the quasi-species of the virus had a greater risk of death (P = 0·009). This study proposes a robust molecular and clinical surveillance program for the detection and characterization of the virus, along with prompt treatment protocols to prevent outbreaks.
Clozapine is an atypical antipsychotic agent used primarily in the management of treatment-resistant schizophrenia. Previous studies have demonstrated clozapine’s superior efficacy over other antipsychotic medications in treating this population of patients. The aim of this study was to assess if the number of hospital admissions and days spent in hospital reduced with the initiation of clozapine, compared with when the same sample of patients were prescribed other antipsychotics prior to clozapine initiation.
A mirror-image study design was adopted. In this case the intervention under study was the initiation of clozapine. Information was collected retrospectively from the charts of patients attending the University Hospital Galway clozapine clinic. The number of admissions and number of hospital days were collected for each patient over the 3 years before and after clozapine initiation. Wilcoxon’s signed-rank test was used to test for statistical significance.
The total sample size comprised of 62 patients, of which the majority were male (74.2%) and had a diagnosis of schizophrenia (82.3%). The mean dose of clozapine was 417 mg, and mean age of the sample was 38 years. Mean number of hospital admissions reduced from 2.8 to 0.8 (p<0.0001) following initiation of clozapine. Mean number of days spent in hospital reduced from 116.4 to 17.1 (p<0.0001).
After initiation of clozapine treatment, patients experience a substantial reduction in number of hospital admissions and number of days spent in hospital when compared with a similar period prior to clozapine initiation.
This study explored how coping with war-related traumatic events in Sierra Leone impacted mental health outcomes among 529 youth (aged 10–17 at baseline; 25% female) using longitudinal data from three time points (Time 1 in 2002, Time 2 in 2004, and Time 3 in 2008). We examined two types of coping items (approach and avoidance); used multiple regression models to test their relations with long-term mental health outcomes (internalizing behaviors, externalizing behaviors, adaptive/prosocial behaviors, and posttraumatic stress symptoms); and used mediation analyses to test whether coping explained the relation between previous war exposures (being raped, death of parent(s), or killing/injuring someone during the war) and those outcomes. We found that avoidance coping items were associated with lower internalizing and posttraumatic stress behaviors at Time 3, and provided some evidence of mediating the relation between death of parent(s) during the war and the two outcomes mentioned above. Approach coping was associated with higher Time 3 adaptive/prosocial behaviors, whereas avoidance coping was associated with lower Time 3 adaptive/prosocial behaviors. Avoidance coping may be a protective factor against mental illness, whereas approach coping may be a promotive factor for adaptive/prosocial behaviors in war-affected societies. This study has important implications for designing and implementing mental health interventions for youth in postconflict settings.
The binary X-ray source GX 1 + 4 was observed during a balloon flight in 1986, November. The source was in a relatively high intensity state. Time analysis of the data shows that the pulsation period was 111.8 ± 1.0 s indicating that one or more episodes of spin-down occurred between 1980 and 1986. Folded pulse profiles are very broad with an indication of a notch at the peak. Evidence has been found for a correlation between hard X-ray intensity and phase of the proposed 304 day orbital period. The time averaged intensity since 1980 is an order of magnitude lower than during the 1970’s. A survey of the post 1980 data shows that several reversals of the period derivative have occurred. Spin-up at the rates typical of the 1970’s has been followed by a dramatic spin-down episode with dP/dt>2.4 × 10−7 s/s.
In search of a suitable resource conservation technology under pigeonpea (Cajanus cajan L.)–wheat (Triticum aestivum L.) system in the Indo-Gangetic Plains, the effects of conservation agriculture (CA) on crop productivity and water-use efficiency (WUE) were evaluated during a 3-year study. The treatments were: conventional tillage (CT), zero tillage (ZT) with planting on permanent narrow beds (PNB), PNB with residue (PNB + R), ZT with planting on permanent broad beds (PBB) and PBB + R. The PBB + R plots had higher pigeonpea grain yield than the CT plots in all 3 years. However, wheat grain yields under all plots were similar in all years except for PBB + R plots in the second year, which had higher wheat yield than CT plots. The contrast analysis showed that pigeonpea grain yield of CA plots was significantly higher than CT plots in the first year. However, both pigeonpea and wheat grain yields during the last 2 years under CA and CT plots were similar. The PBB + R plots had higher system WUE than the CT plots in the second and third years. Plots under CA had significantly higher WUE and significantly lower water use than CT plots in these years. The PBB + R plots had higher WUE than PNB + R and PNB plots. Also, the PBB plots had higher WUE than PNB in the second and third years, despite similar water use. The interactions of bed width and residue management for all parameters in the second and third years were not significant. Those positive impacts under PBB + R plots over CT plots were perceived to be due to no tillage and significantly higher amount of estimated residue retention. Thus, both PBB and PBB + R technologies would be very useful under a pigeonpea–wheat cropping system in this region.
Aspiration pneumonia is an important cause of death in head and neck cancer patients. This study therefore aimed to evaluate the risk factors associated with aspiration pneumonia in head and neck cancer patients.
Hospital death records from 12 years (2000–2012) were reviewed to obtain the number of deaths. Treatment details and cause of death were analysed. Statistical analysis was performed to identify the risk factors for aspiration pneumonia.
The records revealed that aspiration pneumonia was the cause of death in 51 out of 85 patients. Primary tumour site (oropharynx and hypopharynx, odds ratio 3.3; 95 per cent confidence interval 1.17–9.4, p = 0.02) and advanced tumour stage (odds ratio 4.2, 95 per cent confidence interval 1.16–15.61, p = 0.02) had significant negative impacts on aspiration pneumonia related mortality.
Advanced pharyngeal cancer patients are at an increased risk of aspiration pneumonia related death. Investigations for the early detection of this condition are recommended in these high-risk patients.
A cardiac source is often implicated in strokes where the deficit includes aphasia. However, less is known about the etiology of isolated aphasia during transient ischemic attack (TIA). Our objective was to determine whether patients with isolated aphasia are likely to have a cardioembolic etiology for their TIA.
We prospectively studied a cohort of TIA patients in eight tertiary-care emergency departments. Patients with isolated aphasia were identified by the treating physician at the time of emergency department presentation. Patients with dysarthria (i.e., a phonation disturbance) were not included. Potential cardiac sources for embolism were defined as atrial fibrillation on history, electrocardiogram, Holter monitor, atrial fibrillation on echocardiography, or thrombus on echocardiography.
Of the 2,360 TIA patients identified, 1,155 had neurological deficits at the time of the emergency physician assessment and were included in this analysis, and 41 had isolated aphasia as their only neurological deficit. Patients with isolated aphasia were older (73.9±10.0 v. 67.2±14.5 years; p=0.003), more likely to have a history of heart failure (9.8% v. 2.6%; p=0.027), and were twice as likely to have any cardiac source of embolism (22.0% v. 10.6%; p=0.037).
Isolated aphasia is associated with a high rate of cardioembolic sources of embolism after TIA. Emergency patients with isolated aphasia diagnosed with a TIA warrant a rapid and thorough assessment for a cardioembolic source.
Abnormalities in the anterior inter-hemispheric connectivity have previously been implicated in major depressive disorder. Disruptions in fractional anisotropy in the callosum and fornix have been reported in schizophrenia and major depressive disorder. Oligodendrocyte density and overall size of the callosum and fornix show no alteration in either illness, suggesting that gross morphology is unchanged but more subtle organizational disruption may exist within these brain regions in mood and affective disorders.
Using high-resolution oil-immersion microscopy we examined the cross-sectional area of the nerve fibre and the axonal myelin sheath, and using standard high-resolution light microscopy we measured the density of myelinated axons. These measurements were made in the genu of the corpus callosum and the medial body of the fornix at its most dorsal point. Measures were taken in the sagittal plane in the callosal genu and in the coronal plane at the most dorsal part of the fornix body.
Cases of major depressive disorder had significantly greater mean myelin cross-sectional area (p = 0.017) and myelin thickness (p = 0.004) per axon in the genu than in control or schizophrenia groups. There was no significant change in the density of myelinated axons, and no changes observed in the fornix.
The results suggest a clear increase of myelin in the axons of the callosal genu in MDD, although this type of neuropathological study is unable to clarify whether this is caused by changes during life or has a developmental origin.
Plant genetic resources are raw materials and their use in breeding is one of the most sustainable ways to conserve biodiversity. The ICRISAT has over 120,000 accessions of its five mandate crops and six small millets. The management and utilization of such large diversity are greatest challenges to germplasm curators and crop breeders. New sources of variations have been discovered using core and minicore collections developed at the ICRISAT. About 1.4 million seed samples have been distributed; some accessions with specific attributes have been requested more frequently. The advances in genomics have led researchers to dissect population structure and diversity and mine allelic variations associated with agronomically beneficial traits. Genome-wide association mapping in sorghum has revealed significant marker–trait associations for many agronomically beneficial traits. Wild relatives harbour genes for resistance to diseases and insect pests. Resistance to pod borer in chickpea and pigeonpea and resistance to rust and late leaf spot in groundnut have been successfully introgressed into a cultivated genetic background. Synthetics in groundnut are available to broaden the cultigen's gene pool. ICRISAT has notified the release of 266 varieties/cultivars, germplasm, and elite genetic stocks with unique traits, with some having a significant impact on breeding programs. Seventy-five germplasm lines have been directly released for cultivation in 39 countries.
The main point of this chapter is to highlight the significance and relevance of caste–class nexus as an approach to the study of social stratification in India. Such an approach exposes misconceptions such as that caste and class are antithetical formations, being at opposite poles, caste is a socio-cultural entity and class is an economic phenomenon.
Colonialism, policies of the contemporary Indian state, western frames of reference and ideological moorings have undermined the caste–class nexus and its dynamics. Neither the ‘caste alone’ and nor the ‘class alone’ approach would bring out the complex social inequality. The caste–class nexus approach does not imply a correspondence between caste hierarchy and class ranking. It refers to the dynamics of caste–class contexts and situations at a given point of time and also over a period of time. For example, it has been argued that caste system was never absolutely rigid and stagnant. There are innumerable evidences of protests and movements against rigidity and hegemony of the upper castes by the middle and lower castes. There were also institutional mechanisms for redressal of grievances and for settlement of disputes.
Both individuals and families have been units of status-evaluation within and between castes. ‘Caste model’ ignores this historical fact which is evident in the analyses of ancient, medieval and modern Indian society. Today, castes are acting more as interest groups rather than as socio-cultural entities. Emergence of a new class structure comprising industrialists, big businessmen, entrepreneurs, professionals, government functionaries, workers, etc., cuts across caste hierarchy.
Ranajit Guha, the founder of the subaltern studies in South Asia, is considered as the practitioner of a critical Marxist historiography, who sought an active political engagement with the postcolonial present, inspired by Antonio Gramsci and Mao Zedong (Chatterjee, 2009). Guha, as founder and guiding spirit of subaltern studies, has provided a critic of both the colonialist and the nationalist historiographies of modern South Asia. He critically examined in the first volume of Subaltern Studies (1982) itself the two elitisms — the colonialist and the nationalist (Chatterjee, 2009). David Arnold, Shahid Amin and Gyanendra Pandey joined Guha in England on debates on the two elitisms and the new path of historiography. In 1980, in India, Gautam Bhadra, Dipesh Chakrabarty and Partha Chatterjee joined him in the ongoing initial discourse on subalternity.
Partha Chatterjee (2009) states that the early volumes of Subaltern Studies (1982–89) were mostly concerned with the studies of peasant agitations during the nationalist movement. Guha's emphasis in these volumes was on the autonomy of peasant consciousness. The nationalist politics of the peasantry was not the same as that of the elite. Guha published his essay on this theme under the title – Dominance without Hegemony: History and Power in Colonial India (1997).
HERMES is a new high-resolution multi-object spectrograph on the Anglo Australian Telescope. The primary science driver for HERMES is the GALAH survey, GALactic Archaeology with HERMES. We are planning a spectroscopic survey of about a million stars, aimed at using chemical tagging techniques to reconstruct the star-forming aggregates that built up the disk, the bulge and halo of the Galaxy. This project will benefit greatly from the stellar distances and transverse motions from the Gaia mission.
Phosphoryl transfer plays key roles in signaling, energy transduction, protein synthesis, and maintaining the integrity of the genetic material. On the surface, it would appear to be a simple nucleophile displacement reaction. However, this simplicity is deceptive, as, even in aqueous solution, the low-lying d-orbitals on the phosphorus atom allow for eight distinct mechanistic possibilities, before even introducing the complexities of the enzyme catalyzed reactions. To further complicate matters, while powerful, traditional experimental techniques such as the use of linear free-energy relationships (LFER) or measuring isotope effects cannot make unique distinctions between different potential mechanisms. A quarter of a century has passed since Westheimer wrote his seminal review, ‘Why Nature Chose Phosphate’ (Science 235 (1987), 1173), and a lot has changed in the field since then. The present review revisits this biologically crucial issue, exploring both relevant enzymatic systems as well as the corresponding chemistry in aqueous solution, and demonstrating that the only way key questions in this field are likely to be resolved is through careful theoretical studies (which of course should be able to reproduce all relevant experimental data). Finally, we demonstrate that the reason that nature really chose phosphate is due to interplay between two counteracting effects: on the one hand, phosphates are negatively charged and the resulting charge-charge repulsion with the attacking nucleophile contributes to the very high barrier for hydrolysis, making phosphate esters among the most inert compounds known. However, biology is not only about reducing the barrier to unfavorable chemical reactions. That is, the same charge-charge repulsion that makes phosphate ester hydrolysis so unfavorable also makes it possible to regulate, by exploiting the electrostatics. This means that phosphate ester hydrolysis can not only be turned on, but also be turned off, by fine tuning the electrostatic environment and the present review demonstrates numerous examples where this is the case. Without this capacity for regulation, it would be impossible to have for instance a signaling or metabolic cascade, where the action of each participant is determined by the fine-tuned activity of the previous piece in the production line. This makes phosphate esters the ideal compounds to facilitate life as we know it.
Long-term tillage and fertilizer experiments were conducted in rice in kharif followed by lentil in dry subhumid Inceptisols at Varanasi and Faizabad; horse gram at Phulbani and linseed at Ranchi in moist subhumid Alfisols in rabi during 2001 to 2010. The study was conducted to assess the effect of conventional tillage (CT), low tillage + interculture (LT1) and low tillage + herbicide (LT2) together with 100% N (organic) (F1), 50% N (organic) + 50% N (inorganic) (F2) and 100% N (inorganic) (F3) on productivity, profitability, rainwater and energy use efficiencies. The results at Varanasi revealed that CT was superior with mean yield of 2389 kg ha−1, while F1 was superior with 2378 kg ha−1 in rice. At Faizabad, CT was superior with mean rice yield of 1851 kg ha−1 and lentil yield of 977 kg ha−1, while F1 was superior with 1704 and 993 kg ha−1 of rice and lentil, respectively. At Phulbani, F2 was superior with rice yield of 1170 kg ha−1. At Ranchi, F2 with rice yield of 986 kg ha−1 and F3 with linseed yield of 224 kg ha−1 were superior. The regression model of crop seasonal rainfall and yield deviations indicated an increasing trend in rice yield over mean (positive deviation) with increase in rainfall at all locations; while a decreasing trend (negative deviation) was found for lentil at Faizabad, horse gram at Phulbani and linseed at Ranchi. Based on economic analysis, CTF1 at Varanasi and Faizabad, CTF2 at Phulbani and LT2F2 at Ranchi were superior.
This experiment was conducted to study the long-term effect of soil management treatments on crop yields, sustainability yield indices (SYI) and soil fertility in rainfed semi-arid tropical Alfisol at Hayathnagar Research Farm, Hyderabad, India, during the period 1995 to 2009. The experiment was conducted in a split–split plot design with conventional tillage (CT) and minimum tillage (MT) as main factors, surface application of sorghum stover @ 2 t ha−1 (SS), fresh Gliricidia loppings @ 2 t ha−1 (GL) and ‘no’ residue (NR) as sub-factors and levels of N viz. 0 (N0), 30 (N30), 60 (N60) and 90 (N90) kg N ha−1 as sub–sub factors in a castor–sorghum two-year rotation. On an average, CT maintained 30.4 and 57.0% higher grain yields of sorghum and castor, respectively, over MT. Between two residues, GL performed well in both the crops. The highest yields of sorghum (1425 kg ha−1) and castor (876 kg ha−1) were recorded at 90 kg N ha−1. CT maintained higher SYI of 0.44 compared to MT (0.38) and higher agronomic efficiency (AE) of 13.5 and 6.76 kg grain kg−1 N for sorghum and castor crop, respectively. Use of crop residue as mulch had an advantage in increasing the yield of both the crops with increase in rainfall under CT even without N application (control), probably by making the soil more receptive to water infiltration, better moisture storage and by reducing the evaporative losses. Using response functions, the optimum fertilizer N requirement was also computed for a given set of tillage and residue combinations. The revised optimum fertilizer N doses for sorghum and castor varied from 45 to 56 kg ha−1 and 46 to 74 kg ha−1, respectively, under different tillage and residue combinations and could be recommended depending upon the soil management practices.
Nonvolatile unipolar resistive switching has been observed in Sm doped BFO thin films in Pt/Sm: BFO/SRO stack geometry. The initial forming voltage was found to be ∼ 11 V. After the forming process repeatable switching of the resistance of Sm:BFO film was obtained between low and high resistance states with nearly constant resistance ratio ∼ 105 and non overlapping switching voltages in the range of 0.7-1 V and 4-6 V respectively. The temperature dependent measurements of the resistance of the device indicated metallic and semiconducting conduction behavior in low and high resistance states respectively. The current conduction mechanism of the Pt/Sm:BFO/SRO device in low resistance states was found to be dominated by the Ohmic behavior while in case of high resistance state and at high voltages it deviated significantly from normal Ohmic behavior and was found to correspond the Pool-Frankel (PF) emission. The Pt/Sm:BFO/SRO structure also showed efficient photo-response in high and low resistance states with increase in photocurrent which was significantly higher in low resistance state when illuminated with white light.