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1.
Plant Physiol Biochem ; 213: 108836, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38941724

ABSTRACT

The root system architecture is an important complex trait in rice. With changing climatic conditions and soil nutrient deficiencies, there is an immediate need to breed nutrient-use-efficient rice varieties with robust root system architectural (RSA) traits. To map the genomic regions associated with crucial component traits of RSA viz. root length and root volume, a biparental F2 mapping population was developed using TI-128, an Ethyl Methane Sulphonate (EMS) mutant of a mega variety BPT-5204 having high root length (RL) and root volume (RV) with wild type BPT-5204. Extreme bulks having high RL and RV and low RL and RV were the whole genome re-sequenced along with parents. Genetic mapping using the MutMap QTL-Seq approach elucidated two genomic intervals on Chr.12 (3.14-3.74 Mb, 18.11-20.85 Mb), and on Chr.2 (23.18-23.68 Mb) as potential regions associated with both RL and RV. The Kompetitive Allele Specific PCR (KASP) assays for SNPs with delta SNP index near 1 were associated with higher RL and RV in the panel of sixty-two genotypes varying in root length and volume. The KASP_SNPs viz. Chr12_S4 (C→T; Chr12:3243938), located in the 3' UTR region of LOC_Os12g06670 encoding a protein kinase domain-containing protein and Chr2_S6 (C→T; Chr2:23181622) present upstream in the regulator of chromosomal condensation protein LOC_Os2g38350. Validation of these genes using qRT-PCR and in-silico studies using various online tools and databases revealed higher expression in TI-128 as compared to BPT- 5204 at the seedling and panicle initiation stages implying the functional role in enhancing RL and RV.


Subject(s)
Chromosome Mapping , Oryza , Plant Roots , Quantitative Trait Loci , Oryza/genetics , Oryza/growth & development , Oryza/metabolism , Plant Roots/genetics , Plant Roots/growth & development , Plant Roots/metabolism , Quantitative Trait Loci/genetics , Polymorphism, Single Nucleotide/genetics , Chromosomes, Plant/genetics , Genotype
2.
Appl Opt ; 63(4): 874-887, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38437383

ABSTRACT

A single Raman cell configuration useful for DIAL ozone lidar is designed and optimized. The conversion efficiency and flexibility of using a single Raman cell filled with a mixture of high pressure Raman active gases hydrogen (H 2) and methane (C H 4) have been examined and reported. The stimulated Raman scattering (SRS) conversion efficiency of Raman active gases with different total cell pressures and the volume mixing ratio excited with a focused, frequency quadrupled Nd:YAG laser with a maximum pulse energy of 25 mJ and a pulse duration of 10 ns at 100 Hz repetition rate are examined in detail. The gas combination of H 2:C H 4 emits a coaxial beam of two wavelengths, 288.4 nm (C H 4) and 299.1 nm (H 2), with a maximum total conversion efficiency of about 45%. The optimum volume mixing ratio for generating the required wavelength pair with almost equal energies is found to be 2:1 (H 2:C H 4) at a total cell pressure of 18 bar. The contribution of cascade Raman scattering (CRS) and four-wave mixing (FWM) to the higher order Stokes lines is examined. The laser attenuation due to soot formation under various mixing ratios in the cell is also presented.

3.
Front Plant Sci ; 14: 1247014, 2023.
Article in English | MEDLINE | ID: mdl-37731986

ABSTRACT

Biotic stress is one of the major threats to stable rice production. Climate change affects the shifting of pest outbreaks in time and space. Genetic improvement of biotic stress resistance in rice is a cost-effective and environment-friendly way to control diseases and pests compared to other methods such as chemical spraying. Fast deployment of the available and suitable genes/alleles in local elite varieties through marker-assisted selection (MAS) is crucial for stable high-yield rice production. In this review, we focused on consolidating all the available cloned genes/alleles conferring resistance against rice pathogens (virus, bacteria, and fungus) and insect pests, the corresponding donor materials, and the DNA markers linked to the identified genes. To date, 48 genes (independent loci) have been cloned for only major biotic stresses: seven genes for brown planthopper (BPH), 23 for blast, 13 for bacterial blight, and five for viruses. Physical locations of the 48 genes were graphically mapped on the 12 rice chromosomes so that breeders can easily find the locations of the target genes and distances among all the biotic stress resistance genes and any other target trait genes. For efficient use of the cloned genes, we collected all the publically available DNA markers (~500 markers) linked to the identified genes. In case of no available cloned genes yet for the other biotic stresses, we provided brief information such as donor germplasm, quantitative trait loci (QTLs), and the related papers. All the information described in this review can contribute to the fast genetic improvement of biotic stress resistance in rice for stable high-yield rice production.

4.
Arch Dis Child ; 2022 Jul 20.
Article in English | MEDLINE | ID: mdl-35858775

ABSTRACT

OBJECTIVE: To understand community seroprevalence of SARS-CoV-2 in children and adolescents. This is vital to understanding the susceptibility of this cohort to COVID-19 and to inform public health policy for disease control such as immunisation. DESIGN: We conducted a community-based cross-sectional seroprevalence study in participants aged 0-18 years old recruiting from seven regions in England between October 2019 and June 2021 and collecting extensive demographic and symptom data. Serum samples were tested for antibodies against SARS-CoV-2 spike and nucleocapsid proteins using Roche assays processed at UK Health Security Agency laboratories. Prevalence estimates were calculated for six time periods and were standardised by age group, ethnicity and National Health Service region. RESULTS: Post-first wave (June-August 2020), the (anti-spike IgG) adjusted seroprevalence was 5.2%, varying from 0.9% (participants 10-14 years old) to 9.5% (participants 5-9 years old). By April-June 2021, this had increased to 19.9%, varying from 13.9% (participants 0-4 years old) to 32.7% (participants 15-18 years old). Minority ethnic groups had higher risk of SARS-CoV-2 seropositivity than white participants (OR 1.4, 95% CI 1.0 to 2.0), after adjusting for sex, age, region, time period, deprivation and urban/rural geography. In children <10 years, there were no symptoms or symptom clusters that reliably predicted seropositivity. Overall, 48% of seropositive participants with complete questionnaire data recalled no symptoms between February 2020 and their study visit. CONCLUSIONS: Approximately one-third of participants aged 15-18 years old had evidence of antibodies against SARS-CoV-2 prior to the introduction of widespread vaccination. These data demonstrate that ethnic background is independently associated with risk of SARS-CoV-2 infection in children. TRIAL REGISTRATION NUMBER: NCT04061382.

5.
Mymensingh Med J ; 31(3): 704-710, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35780354

ABSTRACT

This cross sectional, descriptive study was conducted at Paediatrics department of BSMMU from July 2016 to June 2018 to find out histopathological pattern of Coeliac disease according to Modified Marsh criteria and to correlate it with tissue transglutaminase IgA level. A total of 62 children (age <18 years) attending the Paediatrics department of BSMMU with clinical suspicion of celiac disease were enrolled for the study. Mean age of studied children was 7.87±4.67 years. Ratio of the male and female was 2.27:1. Maximum (66.1%) children came from middle income class family. Out of 62 children, 35.5% (22) were positive for IgA anti-tTG of who female were 11.3% and male 24.2%. Mean duration of symptoms was 44.07±21.77 months in serology positive patients and 34.49±30.52 months in serology negative patients. The age group, 10-14 year showed the highest (50.0%) prevalence of positive anti-tTG. In the tTG positive group mean Hb was 9.6±1.14gm/dl and which is lower than that in tTG negative group (11.7±1.47gm/dl). Among 22 sero-positive patients, histological changes compatible with CD were found in 19 (86.3%) cases and normal in 3 cases. Histological changes were of 3a category of Marsh was found in 12(63.2%) cases, 3b in 4(21.1%) cases and 3c in 3(15.8%) cases. Strong correlation was observed between the serological level of tTGA and histological types of CD by Modified Marsh criteria. In conclusion, screening for celiac disease may be included in diagnostic tests to investigate clinically suspected children and serum tTGA level can be used to predict histopathological severity of coeliac disease.


Subject(s)
Celiac Disease , Adolescent , Autoantibodies , Biopsy , Celiac Disease/diagnosis , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Immunoglobulin A , Male , Protein Glutamine gamma Glutamyltransferase 2 , Transglutaminases
6.
Indian J Ophthalmol ; 70(5): 1713-1717, 2022 05.
Article in English | MEDLINE | ID: mdl-35502058

ABSTRACT

Purpose: To study clinical and pathological features of parasitic lesions in the ocular adnexa in a tertiary care ophthalmic center in south India. Methods: 43 cases of ocular parasitosis were analysed clinically and correlated with the pathological findings (gross morphology and histopathology) over a period of five years (2015-2020). Results: Among the 43 cases, the age group ranged from 9 months to 78 years (mean age of 41.6 years). Female patients were more common than male patients, with a percentage of 63% (27) and 37% (16) respectively. Cystic lesion in the lid or orbit was seen in 23 cases (53.4%); solid mass lesions were seen in 17 cases (39.5%); subconjunctival worms in three cases; and subretinal parasite in one. Gross examination and histopathologic study showed Dirofilaria in 23 cases (53.5%), followed by Cysticercus in six cases (14%) and Microfilariae in four cases (9.3%). Exact species identification was not possible in ten cases (23.25%). Correlation between the type of lesion and type of inflammatory cells with the specific parasite was done. Conclusion: Our study showed that important clinicopathological correlations can be made from the parasitic lesions in the eye and adnexa, which can aid in definitive diagnosis and prompt identification of the parasite for patient management.


Subject(s)
Parasites , Animals , Eye , Face , Female , Humans , India/epidemiology , Male , Tertiary Healthcare
7.
J Basic Microbiol ; 62(2): 185-196, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34913505

ABSTRACT

Bacterial blight (BB) of rice is a devastating disease caused by Xanthomonas oryzae pv. oryzae (Xoo). The evolution of new pathogenic races of bacterial blight pathogen is always a potential threat for rice production. The deployment of pathotype-specific resistant genes in the host plants is a feasible strategy to develop BB-resistant varieties. Therefore, continuous disease monitoring, identification of Xoo pathotypes, and their distribution are crucial to managing BB. In this study, 71 Xoo isolates were collected from the Godavari delta in Andhra Pradesh (India) and their virulence profiles on rice BB differentials were characterized. Data revealed that different International Rice Bacterial Blight (IRBB) lines with single BB resistance genes were susceptible to 73.2%-97.2% of the isolates, except IRBB13 (possessing BB resistance gene, xa13) which showed a moderately susceptible or susceptible reaction to 47.9% of the isolates. Three gene combination rice differentials like IRBB56 (Xa4 + xa5 + xa13), IRBB57 (Xa4 + xa5 + Xa21), IRBB58 (Xa4 + xa13 + Xa21), and IRBB59 (xa5 + xa13 + Xa21) showed very broad-spectrum resistance to majority of the Xoo isolates from the region. None of the tested Xoo isolates were virulent on IRBB58 (Xa4 + xa13 + Xa21), IRBB60 (Xa4 + xa5 + xa13 + Xa21), and IRBB66 (Xa4 + xa5 + Xa7 + xa13 + Xa21). Based on the virulence reaction, 71 Xoo isolates were grouped into 10 major pathotypes. Highly virulent pathotypes viz., IXoPt # 14, 17, 19, and 22 can break the resistance of major BB-resistant genes and were commonly distributed throughout the surveyed regions. Genotypic data of 71 Xoo isolates using J3 primer divided them into three major clusters. Cluster I consisted of 24 Xoo isolates that belonged to pathotype IXoPt-19. Cluster II consisted of 41 Xoo isolates belonging to seven different pathotypes, and Cluster III was composed of six isolates from three different pathotypes. The findings of this study will be helpful to develop rice varieties with pathotype-specific broad-spectrum resistance against BB.


Subject(s)
Oryza , Xanthomonas , Genotype , Plant Diseases , Xanthomonas/genetics
8.
Oxf Open Neurosci ; 1: kvac007, 2022.
Article in English | MEDLINE | ID: mdl-38596701

ABSTRACT

The initiation of nascent projections, or neurites, from the neuronal cell body is the first stage in the formation of axons and dendrites, and thus a critical step in the establishment of neuronal architecture and nervous system development. Neurite formation relies on the polarized remodelling of microtubules, which dynamically direct and reinforce cell shape, and provide tracks for cargo transport and force generation. Within neurons, microtubule behaviour and structure are tightly controlled by an array of regulatory factors. Although microtubule regulation in the later stages of axon development is relatively well understood, how microtubules are regulated during neurite initiation is rarely examined. Here, we discuss how factors that direct microtubule growth, remodelling, stability and positioning influence neurite formation. In addition, we consider microtubule organization by the centrosome and modulation by the actin and intermediate filament networks to provide an up-to-date picture of this vital stage in neuronal development.

9.
Open Access Emerg Med ; 13: 155-159, 2021.
Article in English | MEDLINE | ID: mdl-33880070

ABSTRACT

PURPOSE: To evaluate functional outcomes of severe traumatic brain injuries after insertion of intracranial pressure (ICP) monitor at King Saud Medical City (KSMC) and their correlation to each other. PATIENTS AND METHODS: A retrospective observational study for all adult patients (age >18 years) who were diagnosed with severe head injury and underwent ICP insertion at KSMC. Patients diagnosed between 2017 and 2019 were included. Data for measured outcomes, Glasgow outcome scale (GOS), Karnofsky Performance Score (KPS) and length of stay (LOS) and prognostic factors, data like: age, gender and primary Glasgow coma score (GCS) was obtained from patients' files and direct communication with patients or their caregivers. We also compared patients who underwent ICP monitoring alone with those who underwent ICP with decompressive craniectomy (DC). Follow-up period ranged from 6-24 months. RESULTS: Seventy-four patients were included in this cohort study. Outcome measurements for patients with decompression and ICP were lower than those with ICP alone. KPS and GOS showed strong correlation (p<0.01) in whole cohort and in both subgroups (ICP alone and ICP with DC). KPS showed significant correlation with length of stay (p=0.026). CONCLUSION: ICP monitoring is valid tool in management of severely head injured patients. Patients who underwent DC had a worse outcome. KPS can be used as alternative tool to measure functional outcome in severe traumatic brain injury.

10.
Sci Rep ; 11(1): 308, 2021 Jan 11.
Article in English | MEDLINE | ID: mdl-33431935

ABSTRACT

Changing patterns in aerosol concentrations over the Asian region is well documented with a concurrent increase over India and a marked reduction over China. However, aerosol vertical distribution in the changing climate is not fully understood. By combining long-term satellite observations from MODIS and CALIOP, here we show rapid changes in the aerosol vertical distribution over the South and East Asia covering India and China. A statistically significant decreasing (increasing) trend in the boundary layer (free troposphere) aerosol concentrations is noticed over India. ERA-Interim reanalysis model suggests that this increase in free tropospheric aerosol concentrations are due to the lifting of boundary layer pollutants through an increase in convection (and vertical velocity) in a changing climate. In contrast, a consistent decreasing trend is observed over China irrespective of the altitude. Interestingly, a decreasing trend in Aerosol Optical Depth is observed over the northwest India and we relate this to an observed increase in precipitation leading to increase in the vegetation. It is also found that long-term oscillations like QBO, ENSO and solar cycle significantly affect the aerosol concentrations. Thus, it is prudent to conclude that background meteorology and dynamics play an important role in changing patterns of aerosol vertical distribution.

11.
Sci Adv ; 6(21): eabb0601, 2020 05.
Article in English | MEDLINE | ID: mdl-32494754

ABSTRACT

Cellular differentiation leads to the formation of specialized cell types and complex morphological variations. Often, differentiating cells transition between states by switching how they respond to the signaling environment. However, the mechanisms regulating these transitions are poorly understood. Differentiating neurons delaminate from the neuroepithelium through the regulated process of apical abscission, which mediates an acute loss of polarity and primary cilium disassembly. Using high-resolution live-cell imaging in chick neural tube, we show that these cells retain an Arl13b+ particle, which elongates and initiates intraflagellar trafficking as it transits toward the cell body, indicating primary cilium remodeling. Notably, disrupting cilia during and after remodeling inhibits axon extension and leads to axon collapse, respectively. Furthermore, cilium remodeling corresponds to a switch from a canonical to noncanonical cellular response to Shh. This work transforms our understanding of how cells can rapidly reinterpret signals to produce qualitatively different responses within the same tissue context.


Subject(s)
Cilia , Signal Transduction , Neural Tube/metabolism , Neurogenesis , Neurons , Signal Transduction/physiology
12.
PLoS Biol ; 18(3): e3000470, 2020 03.
Article in English | MEDLINE | ID: mdl-32150534

ABSTRACT

In the spinal cord, the central canal forms through a poorly understood process termed dorsal collapse that involves attrition and remodelling of pseudostratified ventricular layer (VL) cells. Here, we use mouse and chick models to show that dorsal ventricular layer (dVL) cells adjacent to dorsal midline Nestin(+) radial glia (dmNes+RG) down-regulate apical polarity proteins, including Crumbs2 (CRB2) and delaminate in a stepwise manner; live imaging shows that as one cell delaminates, the next cell ratchets up, the dmNes+RG endfoot ratchets down, and the process repeats. We show that dmNes+RG secrete a factor that promotes loss of cell polarity and delamination. This activity is mimicked by a secreted variant of Crumbs2 (CRB2S) which is specifically expressed by dmNes+RG. In cultured MDCK cells, CRB2S associates with apical membranes and decreases cell cohesion. Analysis of Crb2F/F/Nestin-Cre+/- mice, and targeted reduction of Crb2/CRB2S in slice cultures reveal essential roles for transmembrane CRB2 (CRB2TM) and CRB2S on VL cells and dmNes+RG, respectively. We propose a model in which a CRB2S-CRB2TM interaction promotes the progressive attrition of the dVL without loss of overall VL integrity. This novel mechanism may operate more widely to promote orderly progenitor delamination.


Subject(s)
Membrane Proteins/metabolism , Spinal Cord/cytology , Spinal Cord/embryology , Animals , Cell Adhesion , Chick Embryo , Dogs , Gene Expression Regulation, Developmental , HEK293 Cells , Humans , Madin Darby Canine Kidney Cells , Membrane Proteins/genetics , Mice, Inbred C57BL , Mice, Knockout , Mice, Transgenic , SOXB1 Transcription Factors/genetics , SOXB1 Transcription Factors/metabolism , Tight Junctions/metabolism , Time-Lapse Imaging
13.
Environ Pollut ; 254(Pt A): 112932, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31369909

ABSTRACT

Black carbon (BC) aerosol emitted in incomplete combustion processes is known for causing warming in the climate system also poses serious health issues. Identification of the sources of BC is essential for the development of mitigation strategies to regulate their effects in changing climate. Among different observational and analytical techniques currently available, source apportionment methods based on optical measurements are relatively simple. For example, 'Aethalometer model' was developed based on Aethalometer observations. However, there are a few limitations with this model arising from assumption of wavelength and angstrom exponent pairs. We have developed an empirical method which also relies on Aethalometer observations named as 'Two alpha method' which assumes angstrom exponent from fossil fuel as 1 and estimates bio-mass fraction and angstrom exponent for bio-mass burning. This method has been applied to Aethalometer observations from five different locations (rural, semi-urban and urban) over Indian sub-continent to quantify sources of BC. Fossil fuel is found to be the major source of BC (∼70%) irrespective of the location. Collocated measurements of Carbon Monoxide (CO) over rural site correlated well with derived bio-mass fraction. Results from this study demonstrated the capabilities of empirical method and shall provide spatio-temporal variability in sources of BC if applied to more locations.


Subject(s)
Aerosols/analysis , Air Pollutants/analysis , Environmental Monitoring/methods , Soot/analysis , Carbon Monoxide/analysis , Climate , Fossil Fuels/analysis , India
14.
Microbiome ; 6(1): 115, 2018 06 23.
Article in English | MEDLINE | ID: mdl-29935540

ABSTRACT

BACKGROUND: The caecal microbiota plays a key role in chicken health and performance, influencing digestion and absorption of nutrients, and contributing to defence against colonisation by invading pathogens. Measures of productivity and resistance to pathogen colonisation are directly influenced by chicken genotype, but host driven variation in microbiome structure is also likely to exert a considerable indirect influence. METHODS: Here, we define the caecal microbiome of indigenous Indian Aseel and Kadaknath chicken breeds and compare them with the global commercial broiler Cobb400 and Ross 308 lines using 16S rDNA V3-V4 hypervariable amplicon sequencing. RESULTS: Each caecal microbiome was dominated by the genera Bacteroides, unclassified bacteria, unclassified Clostridiales, Clostridium, Alistipes, Faecalibacterium, Eubacterium and Blautia. Geographic location (a measure recognised to include variation in environmental and climatic factors, but also likely to feature varied management practices) and chicken line/breed were both found to exert significant impacts (p < 0.05) on caecal microbiome composition. Linear discriminant analysis effect size (LEfSe) revealed 42 breed-specific biomarkers in the chicken lines reared under controlled conditions at two different locations. CONCLUSION: Chicken breed-specific variation in bacterial occurrence, correlation between genera and clustering of operational taxonomic units indicate scope for quantitative genetic analysis and the possibility of selective breeding of chickens for defined enteric microbiota.


Subject(s)
Bacteria/classification , Bacteria/genetics , Cecum/microbiology , Chickens/microbiology , Gastrointestinal Microbiome/genetics , Animals , Bacteria/isolation & purification , Base Sequence , Biodiversity , Geography , India , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA
15.
PLoS One ; 13(5): e0198260, 2018.
Article in English | MEDLINE | ID: mdl-29813124

ABSTRACT

Bacterial blight (BB) in rice caused by Xanthomonas oryzae pv. oryzae (Xoo) is a major global production constraint, particularly in irrigated and rain-fed lowland areas. Improved Samba Mahsuri (ISM) is an elite, high-yielding, fine-grain type, BB-resistant rice variety possessing three BB-resistant genes (Xa21, xa13 and xa5) and is highly popular in the southern parts of India. As the BB pathogen is highly dynamic and the evolution of pathogen virulence against the deployed resistance genes is common, we added a novel BB-resistant gene, Xa38, into ISM through marker-assisted backcross breeding (MABB) to increase the spectrum and durability of BB resistance. The breeding line PR 114 (Xa38) was used as the donor for Xa38, whereas ISM was used as the recurrent parent. Foreground selection was conducted using PCR-based gene-specific markers for the target genes, whereas background selection was conducted using a set of polymorphic SSR markers between the parents and backcrossing that continued until the third generation. Eighteen homozygous BC3F2 plants possessing all four BB-resistant genes in the homozygous state and with a recurrent parent genome (RPG) recovery of more than 92% were identified and advanced to the BC3F6 generation. These 18 backcross-derived lines (BDLs) exhibited very high level of resistance against multiple Xoo strains and displayed agro-morphological traits, grain qualities and yield levels similar to or better than those of the recurrent parent ISM.


Subject(s)
Disease Resistance/genetics , Genes, Bacterial/genetics , Hybridization, Genetic , Oryza/genetics , Oryza/microbiology , Plant Diseases/microbiology , Xanthomonas/physiology , Oryza/growth & development , Oryza/physiology , Xanthomonas/genetics
16.
Indian J Ophthalmol ; 65(11): 1228-1232, 2017 Nov.
Article in English | MEDLINE | ID: mdl-29133662

ABSTRACT

Ticks are tiny crawling bugs in the spider family that feed by sucking blood from animals. They are second only to mosquitoes as vectors of human disease, both infectious and toxic. Infected ticks spread over a hundred diseases, some of which are fatal if undetected. They spread the spirochete (which multiplies in the insect's gut) with a subsequent bite to the next host. We describe the only reported cases of peri ocular tick bite from India that presented to us within a span of 3 days and its management. Due suspicion and magnification of the lesions revealed the ticks which otherwise masqueraded as small skin tags/moles on gross examination. The ticks were firmly latched on to the skin and careful removal prevented incarceration of the mouth parts. Rickettsial diseases that were believed to have disappeared from India are reemerging and their presence has recently been documented in at least 11 states in the country. Among vector borne diseases, the most common, Lyme disease, also known as the great mimicker, can present with rheumatoid arthritis, fibromyalgia, depression, attention deficit hyperactivity disorder, multiple sclerosis, chronic fatigue syndrome, cardiac manifestations, encephalitis, and mental illness, to name some of the many associations. Common ocular symptoms and signs include conjunctivitis, keratitis, uveitis, and retinitis. Early detection and treatment of tick borne diseases is important to prevent multi system complications that can develop later in life.


Subject(s)
Eye Infections, Parasitic/diagnosis , Eyelid Diseases/diagnosis , Lacrimal Apparatus Diseases/diagnosis , Tick-Borne Diseases/diagnosis , Ticks , Animals , Child, Preschool , Eye Infections, Parasitic/parasitology , Eye Infections, Parasitic/surgery , Eyelid Diseases/parasitology , Eyelid Diseases/surgery , Female , Humans , Lacrimal Apparatus Diseases/parasitology , Lacrimal Apparatus Diseases/surgery , Male , Middle Aged , Ophthalmologic Surgical Procedures , Tick-Borne Diseases/parasitology , Tick-Borne Diseases/surgery
17.
Elife ; 62017 10 23.
Article in English | MEDLINE | ID: mdl-29058679

ABSTRACT

Detachment of newborn neurons from the neuroepithelium is required for correct neuronal architecture and functional circuitry. This process, also known as delamination, involves adherens-junction disassembly and acto-myosin-mediated abscission, during which the centrosome is retained while apical/ciliary membranes are shed. Cell-biological mechanisms mediating delamination are, however, poorly understood. Using live-tissue and super-resolution imaging, we uncover a centrosome-nucleated wheel-like microtubule configuration, aligned with the apical actin cable and adherens-junctions within chick and mouse neuroepithelial cells. These microtubules maintain adherens-junctions while actin maintains microtubules, adherens-junctions and apical end-foot dimensions. During neuronal delamination, acto-myosin constriction generates a tunnel-like actin-microtubule configuration through which the centrosome translocates. This movement requires inter-dependent actin and microtubule activity, and we identify drebrin as a potential coordinator of these cytoskeletal dynamics. Furthermore, centrosome compromise revealed that this organelle is required for delamination. These findings identify new cytoskeletal configurations and regulatory relationships that orchestrate neuronal delamination and may inform mechanisms underlying pathological epithelial cell detachment.


Subject(s)
Actins/metabolism , Cell Differentiation , Centrosome/metabolism , Microtubules/metabolism , Morphogenesis , Nervous System/embryology , Neurons/physiology , Animals , Biological Transport , Chick Embryo , Intravital Microscopy , Microscopy, Fluorescence
18.
J Eur Acad Dermatol Venereol ; 31(8): 1324-1332, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28556418

ABSTRACT

BACKGROUND: OX40 (CD134) is expressed in lesional but not healthy skin of patients with psoriasis. KHK4083 is a fully human monoclonal antibody against OX40. OBJECTIVE: The primary aim of this first-in-human phase 1 study was to determine the safety and tolerability of ascending single doses of KHK4083 in patients with mild to moderate plaque psoriasis. Secondary aims were to determine the pharmacokinetics and immunogenicity of KHK4083, and an exploratory objective was to assess clinical activity. METHODS: In phase 1a, single doses of KHK4083 0.003 and 0.001 mg/kg IV were administered open label in two cohorts (each n = 6). Phase 1b had a multicentre, randomized, double-blind, placebo-controlled, ascending single-dose design in seven cohorts. Randomization was performed 3 : 1 to KHK4083 (n = 6) or placebo (n = 2) within each cohort. Ascending doses of KHK4083 were 0.03, 0.1, 0.3, 1.0, 3.0 and 10 mg/kg IV, and 1.0 mg/kg SC. RESULTS: There were no severe or serious adverse events (AEs), or discontinuations because of AEs. The most frequent treatment-related AEs in the 55 patients who received KHK4083 were mild or moderate chills (9.1%), and infusion/injection site reactions (7.3%). No clinically meaningful or dose-related changes from baseline in laboratory values, vital signs, ECG recordings or physical examinations were observed. Some KHK4083 recipients (10/54) developed anti-KHK4083 antibodies following treatment. Mean elimination half-life (t1/2 ) increased with dose, maximum serum concentration increased in a dose-proportional manner, and area under the serum concentration-time curve increased in a more than dose-proportional manner with increasing IV dose. Absolute bioavailability following SC administration was 73%. There was some indication of improvement in Psoriasis Area Severity Index (PASI) and sPGA scores at the highest IV doses (1.0 and 10 mg/kg) and the SC dose (1.0 mg/kg). The largest PASI 50 response and improvement in sPGA score ≥2 occurred with KHK4083 1.0 mg/kg SC. CONCLUSION: KHK4083 administration as a single dose up to 10 mg/kg IV or 1.0 mg/kg SC was generally safe and well tolerated in patients with mild to moderate plaque psoriasis with no dose-limiting AEs.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Psoriasis/drug therapy , Receptors, OX40/antagonists & inhibitors , Receptors, OX40/immunology , Adult , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal/pharmacokinetics , Antibodies, Monoclonal, Humanized , Cohort Studies , Dose-Response Relationship, Drug , Female , Humans , Injection Site Reaction , Injections, Subcutaneous , Male , Middle Aged , Placebos , Severity of Illness Index , Treatment Outcome
19.
Neural Netw ; 92: 89-97, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28342724

ABSTRACT

Over the past few decades, the design of an intelligent Intrusion Detection System (IDS) remains an open challenge to the research community. Continuous efforts by the researchers have resulted in the development of several learning models based on Artificial Neural Network (ANN) to improve the performance of the IDSs. However, there exists a tradeoff with respect to the stability of ANN architecture and the detection rate for less frequent attacks. This paper presents a novel approach based on Helly property of Hypergraph and Arithmetic Residue-based Probabilistic Neural Network (HG AR-PNN) to address the classification problem in IDS. The Helly property of Hypergraph was exploited for the identification of the optimal feature subset and the arithmetic residue of the optimal feature subset was used to train the PNN. The performance of HG AR-PNN was evaluated using KDD CUP 1999 intrusion dataset. Experimental results prove the dominance of HG AR-PNN classifier over the existing classifiers with respect to the stability and improved detection rate for less frequent attacks.


Subject(s)
Biometric Identification/methods , Neural Networks, Computer , Biometric Identification/standards
20.
Adv Clin Chem ; 79: 199-244, 2017.
Article in English | MEDLINE | ID: mdl-28212712

ABSTRACT

Chronic diarrhea is a frequently encountered symptom in clinical practice. The etiologies for chronic diarrhea are diverse and broad with varying clinical implications. A useful method of categorizing chronic diarrhea to guide a diagnostic work-up is a pathophysiology-based framework. Chronic diarrhea may be categorized as malabsorptive, secretory, osmotic, and inflammatory or motility related. Frequently, overlap between categories may exist for any given diarrhea etiology and diagnostic testing must occur with an understanding of the differential diagnosis. Investigations to achieve a diagnosis for chronic diarrhea range from screening blood and stool tests to more directed testing such as diagnostic imaging, and endoscopic and histological evaluation. The pathophysiology-based framework proposed in this chapter will allow the clinician to select screening tests followed by targeted tests to minimize cost and complications to the patient, while providing a highly effective method to achieve an accurate diagnosis.


Subject(s)
Diarrhea/diagnosis , Chronic Disease , Clinical Chemistry Tests , Diarrhea/physiopathology , Humans
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