The Slit molecules are chemorepulsive ligands that regulate axon guidance at the midline of both vertebrates and invertebrates. In mammals, there are three Slit genes, but only Slit2 has been studied ...in any detail with regard to mammalian brain commissure formation. Here, we sought to understand the relative contributions that Slit proteins make to the formation of the largest brain commissure, the corpus callosum. Slit ligands bind Robo receptors, and previous studies have shown that Robo1−/− mice have defects in corpus callosum development. However, whether the Slit genes signal exclusively through Robo1 during callosal formation is unclear. To investigate this, we compared the development of the corpus callosum in both Slit2−/− and Robo1−/− mice using diffusion magnetic resonance imaging. This analysis demonstrated similarities in the phenotypes of these mice, but crucially also highlighted subtle differences, particularly with regard to the guidance of post-crossing axons. Analysis of single mutations in Slit family members revealed corpus callosum defects (but not complete agenesis) in 100% of Slit2−/− mice and 30% of Slit3−/− mice, whereas 100% of Slit1−/−; Slit2−/− mice displayed complete agenesis of the corpus callosum. These results revealed a role for Slit1 in corpus callosum development, and demonstrated that Slit2 was necessary but not sufficient for midline crossing in vivo. However, co-culture experiments utilising Robo1−/− tissue versus Slit2 expressing cell blocks demonstrated that Slit2 was sufficient for the guidance activity mediated by Robo1 in pre-crossing neocortical axons. This suggested that Slit1 and Slit3 might also be involved in regulating other mechanisms that allow the corpus callosum to form, such as the establishment of midline glial populations. Investigation of this revealed defects in the development and dorso-ventral positioning of the indusium griseum glia in multiple Slit mutants. These findings indicate that Slits regulate callosal development via both classical chemorepulsive mechanisms, and via a novel role in mediating the correct positioning of midline glial populations. Finally, our data also indicate that some of the roles of Slit proteins at the midline may be independent of Robo signalling, suggestive of additional receptors regulating Slit signalling during development.
► Corpus callosum defects are observed in Slit single and compound mutants. ► Slits mediate callosal development by regulating axonal guidance and midline glial development. ► Slit2 is the predominant family member involved. ► Slit2−/− and Robo1−/− mice display phenotypic differences in post midline-crossing axons.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Provision of a molecularly confirmed diagnosis in a timely manner for children and adults with rare genetic diseases shortens their “diagnostic odyssey,” improves disease management, and fosters ...genetic counseling with respect to recurrence risks while assuring reproductive choices. In a general clinical genetics setting, the current diagnostic rate is approximately 50%, but for those who do not receive a molecular diagnosis after the initial genetics evaluation, that rate is much lower. Diagnostic success for these more challenging affected individuals depends to a large extent on progress in the discovery of genes associated with, and mechanisms underlying, rare diseases. Thus, continued research is required for moving toward a more complete catalog of disease-related genes and variants. The International Rare Diseases Research Consortium (IRDiRC) was established in 2011 to bring together researchers and organizations invested in rare disease research to develop a means of achieving molecular diagnosis for all rare diseases. Here, we review the current and future bottlenecks to gene discovery and suggest strategies for enabling progress in this regard. Each successful discovery will define potential diagnostic, preventive, and therapeutic opportunities for the corresponding rare disease, enabling precision medicine for this patient population.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The “pipette” or “growth cone turning” assay is widely used for studying how axons respond to diffusible guidance cues in their environment. However, little quantitative analysis has been presented ...of the gradient shapes produced by this assay, or how they depend on parameters of the assay. Here we used confocal microscopy of fluorescent gradients to characterize these shapes in 3 dimensions. We found that the shape, and more specifically the concentration at the position usually occupied by the growth cone in this assay, varied in sometimes unexpected ways with the molecular weight of the diffusible factor, charge, pulse duration and pulse frequency. These results suggest that direct observation of the gradient of the particular guidance factor under consideration may be necessary to quantitatively determine the signal to which the growth cone is responding.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
We investigated the effects of autologous bone marrow stem cell transplantation in a rat model of Huntington's Disease. Thirteen days after bilateral quinolinic lesions (QA), bone marrow was ...implanted into the damaged striatum. The ability of the transplants to reverse QA-induced cognitive deficits in the radial-arm water maze (RAWM) was examined. The transplants significantly reduced working memory deficits. Most of the transplanted cells appeared quite primitive. Because only a few cells expressed neural phenotypes, we suggest that the release of growth factors by the transplants allowed surviving cells within the caudate to function more efficiently and to facilitate other compensatory responses.
Full text
Available for:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
India is an agricultural country and about seventy percent of our population depends on agriculture. One-third of our national income comes from agriculture. So the disease detection of plants plays ...an important role in the agricultural field. Majority of the plant diseases are caused by the attack of bacteria, fungi, virus etc. If proper care is not taken in this area, it may lead to serious effects on plants and adversely affects the productivity and quality. To detect, the plant diseases we need a fast automatic way. The main approach adopted in practice for detection and identification of plant diseases is naked eye observation through experts. The decision making capability of an expert also depends on his/her physical condition, such as fatigue and eye sight, work pressure, climate etc. So this method is time consuming and less efficient. Here, a project is proposed with an idea of detecting plant diseases using image processing. Image processing toolbox of Matlab is used for measuring affected area of disease and to determine the difference in the color of the disease affected area. This concept can be extended to detect the symptoms of any type of plant diseases that is affected on different horticulture crops. The algorithm can be used to classify the leaves and the classified outcomes are separated using Arduino based conveyor belt system. This reduces an important task of monitoring of farms crops at very early stage itself to detect the symptom of diseases appear on plant leaves.
The unique four-level photocycle characteristics of excited-state intramolecular proton transfer (ESIPT) materials enable population inversion and large spectral separation between absorption and ...emission through their respective enol and keto forms. This leads to minimal or no self-absorption losses, a favorable feature in acting as an optical gain medium. While conventional ESIPT materials with an enol–keto tautomerism process are widely known, zwitterionic ESIPT materials, particularly those with high photoluminescence, are scarce. Facilitated by the synthesis and characterization of a new family of 2-hydroxyphenyl benzothiazole (HBT) with fluorene substituents, HBT-Fl1 and HBT-Fl2, we herein report the first efficient zwitterionic ESIPT lasing material (HBT-Fl2). The zwitterionic ESIPT HBT-Fl2 not only shows a remarkably low solid-state amplified spontaneous emission (ASE) threshold of 5.3 μJ/cm2 with an ASE peak at 609 nm but also exhibits high ASE photostability. Coupled with its substantially large Stokes shift (≈236 nm ≈10,390 cm–1) and an extremely small overlap of excited-state absorption with ASE emission, comprehensive density functional theory (DFT) and time-dependent DFT studies reveal the zwitterionic characteristics of HBT-Fl2. In opposition to conventional ESIPT with π-delocalized tautomerism as observed in analogue HBT-Fl1 and parent HBT, HBT-Fl2 instead shows charge redistribution in the proton transfer through the fluorene conjugation. This structural motif provides a design tactic in the innovation of new zwitterionic ESIPT materials for efficient light amplification in red and longer-wavelength emission.
Full text
Available for:
IJS, KILJ, NUK, PNG, UL, UM
Primary immune deficiencies or inborn errors of immunity (IEI) are a heterogeneous group of disorders that predispose affected individuals to infections, allergy, autoimmunity, autoinflammation and ...malignancies. IEIs are increasingly being recognized in the Indian subcontinent. Two hundred and eight patients diagnosed with an IEI during February 2017 to November 2021 at a tertiary care center in South India were included in the study. The clinical features, laboratory findings including microbiologic and genetic data, and treatment and outcome details were analyzed. The diagnosis of IEI was confirmed in a total of 208 patients (198 kindreds) based on relevant immunological tests and/or genetic tests. The male-to-female ratio was 1.8:1. Of the 208 patients, 72 (34.6%) were < 1 yr, 112 (53.8%) were 1–18 years, and 24 (11.5%) were above 18 years. The most common IEI in our cohort was SCID (17.7%) followed by CGD (12.9%) and CVID (9.1%). We also had a significant proportion of patients with DOCK8 deficiency (7.2%), LAD (6.2%) and six patients (2.8%) with autoinflammatory diseases. Autoimmunity was noted in forty-six (22%) patients. Molecular testing was performed in 152 patients by exome sequencing on the NGS platform, and a genetic variant was reported in 132 cases. Twenty-nine children underwent 34 HSCT, and 135 patients remain on supportive therapy such as immunoglobulin replacement and/or antimicrobial prophylaxis. Fifty-nine (28.3%) patients died during the study period, and infections were the predominant cause of mortality. Seven families underwent prenatal testing in the subsequent pregnancy. We describe the profile of 208 patients with IEI, and to the best of our knowledge, this represents the largest data on IEI from the Indian subcontinent reported so far.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Monitoring of synthetic phenolic antioxidants in food is very important due to their potential harmfulness to human beings. Octyl gallate (OG) is a commonly used phenolic antioxidant as a ...preservative in food stuff such as margarine, lard, sunflower oil etc. Herein, a glassy carbon electrode (GCE) chemically modified with gold nanoparticles (AuNPs) followed by self-assembled monolayer of dodecane thiol (DDT) was fabricated and employed for the determination of OG. An anodic peak corresponds to the oxidation of OG was observed at a potential of 0.22 V at DDT/AuNPs/GCE by square wave voltammetry. Based on this, a novel electrochemical sensor was developed for the determination of OG in oils and fats. Linear calibration graph was obtained within the range 1.2 to 0.2 μM. The detection limit was found to be 8.3 nM which is remarkably lower than those reported previously. The applicability of the method was demonstrated by analyzing OG in commercially available food samples such as margarine, butter and sunflower oil.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Color purity is a critical prerequisite for full color displays. Creation of deep-red phosphorescent materials with high PLQYs is particularly challenging because of the “energy gap law”. ...Simultaneously achieving high yielding solution processable Pt(II) complexes further complicates this challenge. In this report, we developed a high-yielding synthetic route to a solution processable/deep-red Pt(II) complex with a rigid tetradentate structure, in which we identified an octahedral Pt(IV) complex as a major side product formed under the standard complexation conditions. We managed to effectively transform the octahedral Pt(IV) species into a highly luminescent deep-red square-planar Pt(II) complex through a base-promoted reduction. The Pt(II) complex was found to exhibit high solution and blend film PLQYs. X-ray crystal structure and DFT calculations of the Pt(II) complex showed that perpendicular orientation of molecular dipoles enhanced the luminescence properties. In neat films, there was no luminescence enhancement due to interdigitation of the attached hexyloxy tails, preventing strong Pt···Pt interactions in the solid state. Solution-processed OLEDs based on the Pt(II) complex showed a low turn-on voltage of 3.3 V (at 1 cd/m2) with a maximum brightness of 2000 cd/m2 and a maximum EQE of ≈6% (4% at 100 cd/m2). A narrow electroluminescence with a full width at half-maximum of ≈50 nm was observed with a peak at 623 nm and deep-red emission with 1931 CIE coordinates of (0.65, 0.35). Transient electroluminescence measurements were used to investigate the EQE roll-off of the OLEDs.
Full text
Available for:
IJS, KILJ, NUK, PNG, UL, UM
A 17-year-old girl presented with chondroblastoma of the fibula and pulmonary metastases. Serum creatine kinase (CK) was elevated for a decade preoperatively and fell to near normal after tumor ...excision. An episode of aseptic meningitis 3 months later led to serologic detection of three antibody markers of paraneoplastic neurologic autoimmunity that in adult patients are characteristic of thymoma and lung carcinoma: muscle-type acetylcholine receptor (AChR) autoantibody (Ab), type 2 Purkinje cell cytoplasmic Ab (PCA-2), and collapsin response-mediator protein-5-IgG (CRMP-5-IgG). Locally recurrent chondroblastoma was excised 1 year later. Serum CK was elevated, CRMP-5-IgG was positive, PCA-2 was lower, and AChR Ab was undetectable. Three years after diagnosis she has stable pulmonary metastases, with elevated CK, higher PCA-2, positive CRMP-5-IgG, and undetectable AChR Ab. The association of metastatic chondroblastoma, elevated CK, and an evolving profile of paraneoplastic autoantibodies reveals a previously unrecognized immunobiologic dimension of chondroblastoma.
PDF
