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1.
Cell ; 163(3): 698-711, 2015 Oct 22.
Article in English | MEDLINE | ID: mdl-26496609

ABSTRACT

Most human transcripts are alternatively spliced, and many disease-causing mutations affect RNA splicing. Toward better modeling the sequence determinants of alternative splicing, we measured the splicing patterns of over two million (M) synthetic mini-genes, which include degenerate subsequences totaling over 100 M bases of variation. The massive size of these training data allowed us to improve upon current models of splicing, as well as to gain new mechanistic insights. Our results show that the vast majority of hexamer sequence motifs measurably influence splice site selection when positioned within alternative exons, with multiple motifs acting additively rather than cooperatively. Intriguingly, motifs that enhance (suppress) exon inclusion in alternative 5' splicing also enhance (suppress) exon inclusion in alternative 3' or cassette exon splicing, suggesting a universal mechanism for alternative exon recognition. Finally, our empirically trained models are highly predictive of the effects of naturally occurring variants on alternative splicing in vivo.


Subject(s)
Alternative Splicing , Genome, Human , Models, Genetic , Polymorphism, Single Nucleotide , Base Sequence , Humans , Molecular Sequence Data , Nucleotide Motifs , RNA Splice Sites
2.
Mikrochim Acta ; 189(9): 362, 2022 09.
Article in English | MEDLINE | ID: mdl-36044085

ABSTRACT

There has been a rise in pesticide use as a result of the growing industrialization of agriculture. Organophosphorus pesticides have been widely applied as agricultural and domestic pest control agents for nearly five decades, and they remain as health and environmental hazards in water supplies, vegetables, fruits, and processed foods causing serious foodborne illness. Thus, the rapid and reliable detection of these harmful organophosphorus toxins with excellent sensitivity and selectivity is of utmost importance. Aptasensors are biosensors based on aptamers, which exhibit exceptional recognition capability for a variety of targets. Aptasensors offer numerous advantages over conventional approaches, including increased sensitivity, selectivity, design flexibility, and cost-effectiveness. As a result, interest in developing aptasensors continues to expand. This paper discusses the historical and modern advancements of aptasensors through the use of nanotechnology to enhance the signal, resulting in high sensitivity and detection accuracy. More importantly, this review summarizes the principles and strategies underlying different organophosphorus aptasensors, including electrochemical, electrochemiluminescent, fluorescent, and colorimetric ones.


Subject(s)
Biosensing Techniques , Pesticides , Biosensing Techniques/methods , Colorimetry , Nanotechnology , Organophosphorus Compounds , Pesticides/analysis
3.
PLoS Genet ; 10(10): e1004592, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25340400

ABSTRACT

In addition to their protein coding function, exons can also serve as transcriptional enhancers. Mutations in these exonic-enhancers (eExons) could alter both protein function and transcription. However, the functional consequence of eExon mutations is not well known. Here, using massively parallel reporter assays, we dissect the enhancer activity of three liver eExons (SORL1 exon 17, TRAF3IP2 exon 2, PPARG exon 6) at single nucleotide resolution in the mouse liver. We find that both synonymous and non-synonymous mutations have similar effects on enhancer activity and many of the deleterious mutation clusters overlap known liver-associated transcription factor binding sites. Carrying a similar massively parallel reporter assay in HeLa cells with these three eExons found differences in their mutation profiles compared to the liver, suggesting that enhancers could have distinct operating profiles in different tissues. Our results demonstrate that eExon mutations could lead to multiple phenotypes by disrupting both the protein sequence and enhancer activity and that enhancers can have distinct mutation profiles in different cell types.


Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Enhancer Elements, Genetic , Exons/genetics , Membrane Transport Proteins/genetics , PPAR gamma/genetics , Receptors, LDL/genetics , Animals , Binding Sites , Gene Expression Regulation , HeLa Cells , Humans , Liver/metabolism , Mice , Mutation, Missense , Polymorphism, Single Nucleotide , RNA Splicing/genetics , Transcription Factors/biosynthesis
4.
Trop Med Int Health ; 21(10): 1255-1262, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27495900

ABSTRACT

Enteric fever is a major cause of morbidity and mortality in tropical areas worldwide. The Indian subcontinent bears the brunt of the disease, both in terms of absolute case numbers and drug-resistant strains. Recent phylogenetic studies suggest that the multidrug-resistant clade H58 originated in India and subsequently expanded through Asia and Africa. In Africa, it caused unrecognised outbreaks in areas previously considered free of the disease. In this study, we discuss the current status of enteric fever in India, the factors preventing its control and its future directions in this rapidly developing nation.


Subject(s)
Typhoid Fever/epidemiology , Typhoid Fever/prevention & control , Anti-Bacterial Agents/therapeutic use , Drug Resistance, Bacterial , Humans , India/epidemiology , Risk Factors
5.
J Environ Sci Health B ; 50(2): 90-8, 2015.
Article in English | MEDLINE | ID: mdl-25587778

ABSTRACT

The rate of degradation of kresoxim methyl and its effect on soil extra-cellular (acid phosphatase, alkaline phosphatase and ß-glucosidase) and intra-cellular (dehydrogenase) enzymes were explored in four different soils of India. In all the tested soils, the degradation rate was faster at the beginning, which slowed down with time indicating a non-linear pattern of degradation. Rate of degradation in black soil was fastest followed by saline, brown and red soils, respectively and followed 1st or 1st + 1st order kinetics with half-life ranging between 1-6 days for natural soil and 1-19 days for sterile soils. The rate of degradation in natural against sterilized soils suggests that microbial degradation might be the major pathway of residue dissipation. Although small changes in enzyme activities were observed, kresoxim methyl did not have any significant deleterious effect on the enzymatic activity of the various test soils in long run. Simple correlation studies between degradation percentage and individual enzyme activities did not establish any significant relationships. The pattern and change of enzyme activity was primarily due to the effect of the incubation period rather than the effect of kresoxim methyl itself.


Subject(s)
Acid Phosphatase/metabolism , Alkaline Phosphatase/metabolism , Fungicides, Industrial/pharmacokinetics , Oxidoreductases/metabolism , Phenylacetates/pharmacokinetics , Soil Pollutants/pharmacokinetics , beta-Glucosidase/metabolism , Environmental Pollution/analysis , Enzyme Activation , Half-Life , India , Methacrylates/pharmacokinetics , Strobilurins
6.
Environ Monit Assess ; 187(7): 436, 2015 Jul.
Article in English | MEDLINE | ID: mdl-26082423

ABSTRACT

The sorption and leaching behavior of kresoxim-methyl was explored in four different soils, viz., clay, sandy loam, loamy sand, and sandy loam (saline), representing vegetables and fruits growing regions of India. Adsorption of kresoxim-methyl in all the soils reached equilibrium within 48 h. The rate constants for adsorption and desorption at two different temperatures were obtained from the Lindstrom model, which simultaneously evaluated adsorption and desorption kinetics. The data for rate constants, activation energies, enthalpy of activation, entropy of activation, and free energy indicated physical adsorption of kresoxim-methyl on soil. The relative adsorptivity of the test soils could be attributed to different organic matter and clay contents of the soils. A good fit to the linear and Freundlich isotherms was observed for both adsorption as well as desorption. The groundwater ubiquity score (GUS) for different soils varied between 0 and 2.26. The GUS and leaching study indicated moderately low leaching potential of kresoxim-methyl. The adsorption on four soil types largely depended on the soil physicochemical properties such as organic carbon content, cation-exchange capacity, and texture of the soil.


Subject(s)
Phenylacetates/chemistry , Soil Pollutants/chemistry , Water Pollution, Chemical , Adsorption , Aluminum Silicates , Clay , Entropy , India , Kinetics , Methacrylates/analysis , Methacrylates/chemistry , Phenylacetates/analysis , Risk Assessment , Soil/chemistry , Strobilurins , Thermodynamics
7.
Nat Methods ; 7(2): 119-22, 2010 Feb.
Article in English | MEDLINE | ID: mdl-20081835

ABSTRACT

We demonstrate subassembly, an in vitro library construction method that extends the utility of short-read sequencing platforms to applications requiring long, accurate reads. A long DNA fragment library is converted to a population of nested sublibraries, and a tag sequence directs grouping of short reads derived from the same long fragment, enabling localized assembly of long fragment sequences. Subassembly may facilitate accurate de novo genome assembly and metagenome sequencing.


Subject(s)
Chromosome Mapping/methods , Sequence Analysis, DNA/methods , Base Sequence , Expressed Sequence Tags , Molecular Sequence Data
8.
Brain ; 135(Pt 10): 3062-73, 2012 Oct.
Article in English | MEDLINE | ID: mdl-23043143

ABSTRACT

Neuroimaging data demonstrate that carpal tunnel syndrome, a peripheral neuropathy, is accompanied by maladaptive central neuroplasticity. To further investigate this phenomenon, we collected magnetoencephalography data from 12 patients with carpal tunnel syndrome and 12 healthy control subjects undergoing somatosensory stimulation of the median nerve-innervated Digits 2 and 3, as well as Digit 5, which is innervated by the ulnar nerve. Nerve conduction velocity and psychophysical data were acquired to determine whether standard clinical measures correlated with brain response. In subjects with carpal tunnel syndrome, but not healthy controls, sensory nerve conduction velocity for Digits 2 and 3 was slower than Digit 5. However, somatosensory M20 latencies for Digits 2 and 3 were significantly longer than those of Digit 5. The extent of the M20 delay for median nerve-innervated Digit 2 was positively correlated with decreasing nerve conduction velocity and increasing pain severity. Thus, slower peripheral nerve conduction in carpal tunnel syndrome corresponds to greater delays in the first somatosensory cortical response. Furthermore, spectral analysis demonstrated weaker post-stimulus beta event-related desynchronization and earlier and shorter event-related synchronization in subjects with carpal tunnel syndrome. The extent of the decreased event-related desynchronization for median nerve-innervated digits was positively correlated with paraesthesia severity. We propose that ongoing paraesthesias in median nerve-innervated digits render their corresponding sensorimotor cortical areas 'busy', thus reducing their capacity to process external stimulation. Finally, subjects with carpal tunnel syndrome demonstrated a smaller cortical source separation for Digits 2 and 3 compared with healthy controls. This supports our hypothesis that ongoing paraesthesias promote blurring of median nerve-innervated digit representations through Hebbian plasticity mechanisms. In summary, this study reveals significant correlation between the clinical severity of carpal tunnel syndrome and the latency of the early M20, as well as the strength of long latency beta oscillations. These temporal magnetoencephalography measures are novel markers of neuroplasticity in carpal tunnel syndrome and could be used to study central changes that may occur following clinical intervention.


Subject(s)
Brain Mapping/methods , Carpal Tunnel Syndrome/physiopathology , Magnetoencephalography/methods , Neuronal Plasticity/physiology , Somatosensory Cortex/physiopathology , Adult , Carpal Tunnel Syndrome/diagnosis , Female , Fingers/innervation , Fingers/physiopathology , Humans , Magnetoencephalography/instrumentation , Male , Middle Aged , Neural Conduction/physiology , Somatosensory Cortex/physiology
9.
J Postgrad Med ; 59(4): 258-62, 2013.
Article in English | MEDLINE | ID: mdl-24346381

ABSTRACT

CONTEXT: Antiretroviral therapy (ART) is associated with a myriad of metabolic complications which are potential cardiovascular risk factors. Early detection of these risk factors could help in alleviating morbidity and mortality in human immunodeficiency virus (HIV) infected patients on ART. AIMS: To study the prevalence of cardiovascular risk factors in patients on a combination of nucleoside reverse transcriptase inhibitors (NRTIs) and non-NRTIs (NNRTIs) - the standard combination first line ART regimen used in tertiary referral center. SETTINGS AND DESIGN: The prevalence of cardiovascular risk factors in HIV infected subjects with stage 1t disease on standard first line ART for at least 1 year, HIV infected subjects with stage 1 disease and not on ART and HIV negative subjects was assessed. The study was a cross-sectional study design. MATERIALS AND METHODS: Basic demographic data was collected and patients were examined for anthropometric data and blood was collected for analysis of blood glucose, serum lipids, and fasting insulin levels. STATISTICAL ANALYSIS: Chi-square test was used to calculate significance. Statistical Package for Social Sciences (SPSS) software version 16.0 was used for data analysis. RESULTS: The prevalence of hypercholesterolemia and hypertriglyceridemia was higher in the patients on ART when compared to patients not on ART (P<0.001). There was no difference in the prevalence of abnormal glycemic status, obesity, abdominal obesity, insulin resistance, and hyperinsulinemia between patients on ART and those not on ART. CONCLUSIONS: First line ART is associated with increased prevalence of dyslipidemia. Early detection and treatment of dyslipidemia should help in reducing the cardiovascular morbidity in patients on ART.


Subject(s)
Anti-Retroviral Agents/adverse effects , HIV Infections/drug therapy , Hypercholesterolemia/epidemiology , Hypertriglyceridemia/epidemiology , Adult , Cardiovascular Diseases/epidemiology , Cross-Sectional Studies , Drug Therapy, Combination , Female , Humans , Hypercholesterolemia/chemically induced , Hypertriglyceridemia/chemically induced , India/epidemiology , Lamivudine/adverse effects , Male , Middle Aged , Nevirapine/adverse effects , Prevalence , Risk Factors , Stavudine/adverse effects , Zidovudine/adverse effects
10.
Natl Med J India ; 26(4): 214-5, 2013.
Article in English | MEDLINE | ID: mdl-24758444

ABSTRACT

BACKGROUND: Disseminated histoplasmosis is a chronic granulomatous disease caused by the dimorphic fungus, Histoplasma capsulatum. Clinical presentation can vary from the acute pulmonary to the chronic disseminated form. In India, disseminated histoplasmosis often presents with pyrexia of unknown origin with a presentation similar to 'disseminated tuberculosis' involving the adrenal glands and bone marrow. Due to rarity of the disease, data are lacking regarding its clinical presentation and outcome among immunocompromised and immunocompetent patients. METHODS: During January 2000 to December 2010, we identified 37 patients of disseminated histoplasmosis and attempted to characterize the differences between immuno- compromised and immunocompetent patients. Demographic characteristics, clinical presentation, risk factors, laboratory findings, diagnostic yield, treatment received and prognosis were noted and compared between the two groups. RESULTS: Eleven of 37 patients with disseminated histo- plasmosis were immunocompromised and 26 were immuno- competent. Comparison of their clinical features showed a higher frequency of skin lesions in the immunocompromised compared to the immunocompetent group (54.5% v. 11.5%). Pancytopenia and anaemia were more common among the immunocompromised (81.8%) compared to the immunocompetent (46.2%) group. In the immuno- compromised patients, the diagnosis was made most often by bone marrow aspirate and culture (72.7%) compared to the immunocompromised group where the diagnosis was most often obtained by adrenal gland biopsy and fungal cultures (57.7%). The cure rate was significantly higher in the immunocompetent group (73% v. 45%). CONCLUSION: The clinical presentation and outcome of patients with disseminated histoplasmosis differs among immunocompromised and immunocompetent patients.


Subject(s)
Adrenal Glands/pathology , Bone Marrow/pathology , Histoplasmosis/complications , Histoplasmosis/diagnosis , Immunocompetence , Immunocompromised Host , Adult , Anemia/immunology , Anemia/microbiology , Antifungal Agents/therapeutic use , Biopsy , Female , Histoplasmosis/drug therapy , Humans , Male , Middle Aged , Pancytopenia/immunology , Pancytopenia/microbiology , Skin Diseases/immunology , Skin Diseases/microbiology , Treatment Outcome
11.
Natl Med J India ; 25(3): 148-50, 2012.
Article in English | MEDLINE | ID: mdl-22963292

ABSTRACT

Mucocutaneous leishmaniasis has rarely been reported from India. The usual causative organisms of this infection are Leishmania braziliensis and L. tropica. Another species, L. donovani, which usually causes visceral leishmaniasis, has recently been reported to cause mucocutaneous disease in a few patients from Sri Lanka. We report two patients who had undiagnosed chronic skin lesions for several years. Skin biopsies revealed Leishmania and the species was characterized as L. donovani in both patients. There was considerable improvement in the skin lesions following treatment with liposomal amphotericin B.


Subject(s)
Leishmania donovani/isolation & purification , Leishmaniasis, Cutaneous/pathology , Leishmaniasis, Cutaneous/parasitology , Leishmaniasis, Mucocutaneous/pathology , Leishmaniasis, Mucocutaneous/parasitology , Adult , Amphotericin B/therapeutic use , Antiprotozoal Agents/therapeutic use , Bhutan/ethnology , Humans , India , Leishmaniasis, Cutaneous/drug therapy , Leishmaniasis, Mucocutaneous/drug therapy , Male , Middle Aged
12.
Int J Tuberc Lung Dis ; 26(5): 441-445, 2022 05 01.
Article in English | MEDLINE | ID: mdl-35505481

ABSTRACT

INTRODUCTION: Xpert Ultra (Ultra) was developed to improve the detection of TB; however, data on Ultra´s diagnostic accuracy in extrapulmonary TB (EPTB) are limited.METHODS: In this prospective diagnostic accuracy study, 242 EPTB samples were subjected to Ultra and Xpert MTB/Rif (Xpert) testing, and these were compared with both culture and a composite gold standard.RESULTS: Compared to culture, Ultra sensitivity and specificity using bone, cerebrospinal fluid (CSF), lymph node and tissue samples, and overall were respectively 100% and 77.3%, 75% and 100%, 87.5% and 87.5%, 100% and 87%, and 89.7% and 87.4%; in comparison to the composite gold standard, Ultra´s sensitivity and specificity were respectively 66.7% and 100%, 17.6% and 100%, 46.9% and 95.7%, 38.5% and 94.1%, and 46.2% and 96.9%. Using latent class analysis, sensitivity and specificity were respectively 94.5% and 96.3% for Ultra, 65.5% and 99.8% for Xpert, and 58.6% and 99.2% for culture. There were 22/242 (9%) trace calls on Ultra.CONCLUSION: We found improved sensitivity for Ultra compared to Xpert, although Ultra specificity was lower, with a large number of trace results (9%).


Subject(s)
Mycobacterium tuberculosis , Tuberculosis , Humans , Lymph Nodes , Mycobacterium tuberculosis/genetics , Prospective Studies , Sensitivity and Specificity , Tuberculosis/diagnosis
13.
BMC Neurosci ; 12: 73, 2011 Jul 27.
Article in English | MEDLINE | ID: mdl-21794103

ABSTRACT

BACKGROUND: FMRI studies focus on sub-cortical effects of acupuncture stimuli. The purpose of this study was to assess changes in primary somatosensory (S1) activity over the course of different types of acupuncture stimulation. We used whole head magnetoencephalography (MEG) to map S1 brain response during 15 minutes of electroacupuncture (EA) and acupressure (AP). We further assessed how brain response changed during the course of stimulation. RESULTS: Evoked brain response to EA differed from AP in its temporal dynamics by showing clear contralateral M20/M30 peaks while the latter demonstrated temporal dispersion. Both EA and AP demonstrated significantly decreased response amplitudes following five minutes of stimulation. However, the latency of these decreases were earlier in EA (~30 ms post-stimulus) than AP (> 100 ms). Time-frequency responses demonstrated early onset, event related synchronization (ERS), within the gamma band at ~70-130 ms and the theta band at ~50-200 ms post-stimulus. A prolonged event related desynchronization (ERD) of alpha and beta power occurred at ~100-300 ms post-stimulus. There was decreased beta ERD at ~100-300 ms over the course of EA, but not AP. CONCLUSION: Both EA and AP demonstrated conditioning of SI response. In conjunction with their subcortical effects on endogenous pain regulation, these therapies show potential for affecting S1 processing and possibly altering maladaptive neuroplasticity. Thus, further investigation in neuropathic populations is needed.


Subject(s)
Acupressure , Electroacupuncture , Magnetoencephalography/methods , Somatosensory Cortex/physiology , Adult , Brain Mapping , Female , Humans , Magnetic Resonance Imaging , Male , Neuronal Plasticity/physiology , Somatosensory Cortex/cytology , Young Adult
14.
Neuroimage ; 47(3): 1055-65, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19500677

ABSTRACT

Acupuncture-induced sensations have historically been associated with clinical efficacy. These sensations are atypical, arising from sub-dermal receptors, and their neural encoding is not well known. In this fMRI study, subjects were stimulated at acupoint PC-6, while rating sensation with a custom-built, MR-compatible potentiometer. Separate runs included real (ACUP) and sham (SHAM) acupuncture, the latter characterized by non-insertive, cutaneous stimulation. FMRI data analysis was guided by the on-line rating timeseries, thereby localizing brain correlates of acupuncture sensation. Sensation ratings correlated with stimulation more (p<0.001) for SHAM (r=0.63) than for ACUP (r=0.32). ACUP induced stronger and more varied sensations with significant persistence into no-stimulation blocks, leading to more run-time spent rating low and moderate sensations compared to SHAM. ACUP sensation correlated with activation in regions associated with sensorimotor (SII, insula) and cognitive (dorsomedial prefrontal cortex (dmPFC)) processing, and deactivation in default-mode network (DMN) regions (posterior cingulate, precuneus). Compared to SHAM, ACUP yielded greater activity in both anterior and posterior dmPFC and dlPFC. In contrast, SHAM produced greater activation in sensorimotor (SI, SII, insula) and greater deactivation in DMN regions. Thus, brain encoding of ACUP sensation (more persistent and varied, leading to increased cognitive load) demonstrated greater activity in both cognitive/evaluative (posterior dmPFC) and emotional/interoceptive (anterior dmPFC) cortical regions. Increased cognitive load and dmPFC activity may be a salient component of acupuncture analgesia--sensations focus attention and accentuate bodily awareness, contributing to enhanced top-down modulation of any nociceptive afference and central pain networks. Hence, acupuncture may function as a somatosensory-guided mind-body therapy.


Subject(s)
Acupuncture Therapy , Brain Mapping , Brain/physiology , Sensation/physiology , Acupuncture Therapy/psychology , Adult , Female , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Male , Pain/physiopathology , Skin/innervation , Young Adult
15.
Int J STD AIDS ; 20(8): 522-6, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19625581

ABSTRACT

Antiretroviral treatment (ART) use in India requires information on baseline drug resistance mutations and polymorphisms in the protease (Pr) and reverse transcriptase (RT) genes of HIV-1 strains from treatment-naïve individuals. We report resistance predictor mutations and polymorphisms in the Pr and the RT sequence of non-clade B HIV-1 strains from ART naïve individuals. The genotypic resistance assay was done on 93 treatment-naïve individuals. The sequences were analysed by Stanford HIV drug resistance data for genotypic drug resistance analysis and REGA HIV-1 subtyping tool. Phylogenetic tree was generated with MEGA 4 for quality control. Ninety-two strains belonged to clade C and one to clade A (A1). Amino acid substitutions were seen at positions associated with drug resistance in Pr gene--10, 24, 74 (each 3%) and position 82 (11%). Substitutions were seen at positions 41 (1%), 100 (1%), 101 (6%), 103 (2%), 179 (6%) and 181 (1%) of the RT sequence known to confer drug resistance in clade B. Polymorphisms in HIV-1 pol gene among treatment-naïve individuals were similar when compared with previous data. One strain each had Y181C substitution, T74S and E35G substitutions in the Pr and one had A98G, K101R and L210FL substitutions in RT.


Subject(s)
Acquired Immunodeficiency Syndrome/drug therapy , Drug Resistance, Viral/genetics , HIV Protease/genetics , HIV Reverse Transcriptase/genetics , HIV-1/drug effects , Mutation , Adolescent , Adult , Amino Acid Substitution , Base Sequence , Child , Female , Genotype , HIV-1/genetics , Humans , Male , Middle Aged , Molecular Sequence Data
16.
Genome Biol Evol ; 11(12): 3353-3371, 2019 12 01.
Article in English | MEDLINE | ID: mdl-31702783

ABSTRACT

The genus Rhododendron (Ericaceae), which includes horticulturally important plants such as azaleas, is a highly diverse and widely distributed genus of >1,000 species. Here, we report the chromosome-scale de novo assembly and genome annotation of Rhododendron williamsianum as a basis for continued study of this large genus. We created multiple short fragment genomic libraries, which were assembled using ALLPATHS-LG. This was followed by contiguity preserving transposase sequencing (CPT-seq) and fragScaff scaffolding of a large fragment library, which improved the assembly by decreasing the number of scaffolds and increasing scaffold length. Chromosome-scale scaffolding was performed by proximity-guided assembly (LACHESIS) using chromatin conformation capture (Hi-C) data. Chromosome-scale scaffolding was further refined and linkage groups defined by restriction-site associated DNA (RAD) sequencing of the parents and progeny of a genetic cross. The resulting linkage map confirmed the LACHESIS clustering and ordering of scaffolds onto chromosomes and rectified large-scale inversions. Assessments of the R. williamsianum genome assembly and gene annotation estimate them to be 89% and 79% complete, respectively. Predicted coding sequences from genome annotation were used in syntenic analyses and for generating age distributions of synonymous substitutions/site between paralgous gene pairs, which identified whole-genome duplications (WGDs) in R. williamsianum. We then analyzed other publicly available Ericaceae genomes for shared WGDs. Based on our spatial and temporal analyses of paralogous gene pairs, we find evidence for two shared, ancient WGDs in Rhododendron and Vaccinium (cranberry/blueberry) members that predate the Ericaceae family and, in one case, the Ericales order.


Subject(s)
Chromosomes, Plant/genetics , Ericaceae/genetics , Genome, Plant/genetics , Rhododendron/genetics , Synteny , Base Sequence , Chromatin/genetics , Chromosome Mapping , Genetic Linkage , Genomic Library , Molecular Sequence Annotation , Transposases/genetics
17.
Neuron ; 38(3): 487-97, 2003 May 08.
Article in English | MEDLINE | ID: mdl-12741994

ABSTRACT

The ability of written and spoken words to access the same semantic meaning provides a test case for the multimodal convergence of information from sensory to associative areas. Using anatomically constrained magnetoencephalography (aMEG), the present study investigated the stages of word comprehension in real time in the auditory and visual modalities, as subjects participated in a semantic judgment task. Activity spread from the primary sensory areas along the respective ventral processing streams and converged in anterior temporal and inferior prefrontal regions, primarily on the left at around 400 ms. Comparison of response patterns during repetition priming between the two modalities suggest that they are initiated by modality-specific memory systems, but that they are eventually elaborated mainly in supramodal areas.


Subject(s)
Cerebral Cortex/physiology , Neural Pathways/physiology , Reading , Speech Perception/physiology , Adult , Brain Mapping , Cerebral Cortex/anatomy & histology , Evoked Potentials, Auditory/physiology , Evoked Potentials, Visual/physiology , Functional Laterality/physiology , Humans , Magnetoencephalography , Male , Neural Pathways/anatomy & histology , Neuropsychological Tests , Pattern Recognition, Visual/physiology , Psychomotor Performance/physiology , Reaction Time/physiology , Verbal Behavior/physiology
18.
Cochrane Database Syst Rev ; (1): CD005437, 2008 Jan 23.
Article in English | MEDLINE | ID: mdl-18254080

ABSTRACT

BACKGROUND: Meningococcal disease begins suddenly and death can follow within hours. Pre-admission antibiotic therapy aims to prevent delay in starting therapy that occurs if bacterial confirmation is sought before instituting therapy. OBJECTIVES: To study the effectiveness and safety of pre-admission antibiotics versus no pre-admission antibiotics or placebo and of different pre-admission antibiotic regimens in decreasing mortality and morbidity in people suspected of meningococcal disease. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2007, Issue 1), MEDLINE (1966 to February 2007) and EMBASE (1980 to February 2007). SELECTION CRITERIA: We selected randomised controlled trials (RCTs) or quasi-RCTs, of all people with suspected meningococcal infection. We compared antibiotic treatment versus placebo or no intervention, or different antibiotic treatments administered before admission to hospital or confirmation of the diagnosis. DATA COLLECTION AND ANALYSIS: Two author authors independently assessed quality and extracted data from included trials. We calculated the relative risk (RR) and 95% confidence interval (CI) for dichotomous data. As only one trial fulfilled inclusion criteria, data synthesis was not performed. MAIN RESULTS: No RCTs were found that compared pre-admission antibiotics versus no pre-admission antibiotics or placebo. One open-label RCT evaluated a single dose of intramuscular ceftriaxone versus a single dose of intramuscular long acting (oily) chloramphenicol. Interventions did not differ significantly in mortality (RR 1.2, 95% CI 0.5 to 2.6; N = 510; 349 confirmed meningococcal meningitis; 26 deaths), nor in proportions of survivors who developed neurological sequelae (RR 1.2, 95% CI 0.6 to 2.2; N = 488; 36 with neurological sequelae), or that were classified as clinical failures (RR 0.8, 95% CI 0.4 to 1.8; N = 488, 25 clinical failures). No adverse effects of treatment were seen. No data were available for our secondary outcomes. AUTHORS' CONCLUSIONS: We found no reliable evidence to support or refute the use of pre-admission antibiotics for suspected cases of meningococcal disease. Evidence from one RCT-during an epidemic of meningococcal meningitis, indicated that single intramuscular injections of ceftriaxone and long-acting chloramphenicol were equally effective and safe in preventing mortality and morbidity. The choice between these antibiotics would be based on affordability, availability, and patterns of antibiotic resistance.Further RCTs comparing different pre-admission antibiotics, including penicillin, including participants with severe illness are ethically justifiable and are needed to provide reliable evidence to clinicians in differing clinical settings.


Subject(s)
Antibiotic Prophylaxis , Meningococcal Infections/drug therapy , Humans , Patient Admission
19.
Natl Med J India ; 21(5): 222-4, 2008.
Article in English | MEDLINE | ID: mdl-19320320

ABSTRACT

BACKGROUND: Cardiopulmonary bypass (CPB) initiates an inflammatory cascade, predisposing the patient to a number of infections. The stress of surgery and anaesthesia further expose the patient to a variety of non-infectious complications. We report a group of patients who developed granulomatous disease after open heart surgery. METHODS: We retrospectively analysed a subset of patients who developed a syndrome of fever, jaundice and hepatomegaly after open heart surgery. We recruited age- and sex-matched controls who underwent open heart surgery during the same period (July 2002-July 2004). Details of demographic profiles, diagnostic evaluation and drug treatment were noted and compared between the two groups using the SPSS software. RESULTS: Five patients were identified to have the specific syndrome of high grade intermittent fever with jaundice and hepatomegaly with investigations revealing an intrahepatic cholestasis. A detailed evaluation revealed granulomas in tissue specimens of the bone marrow and/or liver in these patients. An extensive evaluation for an alternative aetiological agent was non-contributory. CONCLUSION: We found granulomatous hepatitis in 5 patients following open heart surgery and they were given conventional antituberculous therapy to which they responded. It is possible that in these patients, tuberculosis was re-activated from a dormant focus due to a period of transient immunodeficiency caused by an extracorporeal circulation.


Subject(s)
Cardiopulmonary Bypass/adverse effects , Granuloma/etiology , Hepatitis/etiology , Adult , Case-Control Studies , Female , Fever/etiology , Hepatomegaly/etiology , Humans , Inflammation/etiology , Jaundice/etiology , Male , Retrospective Studies , Time Factors
20.
Intern Med J ; 37(4): 216-23, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17388860

ABSTRACT

INTRODUCTION: A generalized epidemic of HIV infection has been evolving in Papua New Guinea over the last decade, whereas in other Pacific Island countries and territories (PICT) HIV transmission has generally been less widespread. Programmes to detect HIV infection in pregnant women and to prevent mother to child transmission (MTCT) during either delivery or breast-feeding can decrease the incidence of infection in infants. The limited health infrastructure present in some PICT may delay the implementation of effective programmes to decrease MTCT of HIV. METHODS: We used a standardized questionnaire to survey health-care providers in 22 PICT for information on the epidemiology of HIV infection and strategies used during 2004 to prevent MTCT of HIV infection in their country. We supplemented these survey responses with data obtained from regional organizations supporting national responses to HIV. RESULTS: We obtained responses from 21 PICT. The reported prevalence of known HIV infection was >150 per 100 000 persons in Papua New Guinea, approximately 100 per 100 000 persons in French Polynesia, Guam, New Caledonia and Tuvalu and <50 per 100 000 persons in the remaining 14 PICT. Other than in Papua New Guinea, where an estimated 500 pregnant women had HIV infection diagnosed in 2004, reported HIV infection among pregnant women was rare. Ten PICT reported that an HIV antibody test was offered as a routine component of antenatal care and 11 reported that antiretroviral medications were available for the prevention of MTCT of HIV infection. CONCLUSION: The prevalence of HIV infection differs greatly between PICT with a varying risk of MTCT of HIV infection. Successful prevention of MTCT of HIV infection throughout the PICT will require improved uptake of antenatal HIV antibody testing and better access to antiretroviral medications.


Subject(s)
HIV Infections/epidemiology , HIV Infections/prevention & control , Infectious Disease Transmission, Vertical/prevention & control , Female , HIV Infections/drug therapy , Health Surveys , Humans , Infant , Infant, Newborn , Pacific Islands/epidemiology , Pregnancy , Prevalence
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