Are GSTM1 Null and GSTT1 Null Risk Factor of Autism Spectrum Disorder? a Preliminary Study

Background: Low plasma total glutathione (tGSH) levels, elevated levels of oxidized glutathione (GSSG) and low ratios of tGSH to GSSG in autism were reported. Glutathione S-transferases (GST) are antioxidant enzymes that play important role in cellular detoxification and the excretion of environmental pollutants including heavy metals. Glutathione S-transferase mu (GSTM1) and Glutathione S-transferase theta (GSTT1) are known to be highly polymorphic. Homozygous deletions of these genes result in lack ofenzyme activity and impaired the ability to excrete metals including mercury. Combined effects of mercury (Hg) accumulation coupled with decreased levels of antioxidants (low glutathione and antioxidant enzymes) contribute to the phenotypic presentation of autism spectrum disorder (ASD). Association of GSTM1 null genotype with autism has been reported. Therefore the preliminary study was performed to investigate the role of GSTM1 null and GSTT1 null as risk factor of ASD associated with phenotype expression.Method: Fifty one ASD patients were recruited from special need & autism school and 45 controls from Semarang & Solo. Blood veins samples were collected and genomic DNA was extracted by salting-out method in CEBIOR Semarang. Genotyping for GSTM1 and GSTT1 gene was done in UMBI Malaysia. Multiplex PCR was performed and PCR products were separated on 1.2 % agarose gel, stained with ethidium bromide and visualized on UV transiluminator. GSTM1 & GSTT1 gene product is about 625 bp and 459 bp. Absence of GSTM1 and GSTT1 gene band was interpreted as GSTM1 null & GSTT1 null.Results: The frequency of GSTM1 null and GSTT1 null in ASD higher compared with control group but the difference is not statistically significant (p=0.357, OR=0.504; 95% CI 0.117-2.168 and p=0.364, OR=0.674; 95% CI 0.287-1.580). There is also no statistically different in the distribution of GSTM1 null and GSTT1 null between mild to moderately autistic and severely autistic (p=0.983, OR=0.980; 95% CI 0.158-6.095 and p=0.439, OR=1.633; 95% CI 0.471-5.656).Conclusion: GSTM1 null and GSTT1 null are not risk factor of ASD. Further investigations are needed with a bigger sample size, analyzing multiple GST genes and GST activity determination to find out the gene susceptibility of ASD and factors that contribute to the phenotype expression of ASD

Photon Orbital Angular Momentum and Mass in a Plasma Vortex

We analyse the Anderson-Higgs mechanism of photon mass acquisition in a plasma and study the contribution to the mass from the orbital angular momentum acquired by a beam of photons when it crosses a spatially structured charge distribution. To this end we apply Proca-Maxwell equations in a static plasma with a particular spatial distribution of free charges, notably a plasma vortex, that is able to impose orbital angular momentum (OAM) onto light. In addition to the mass acquisition of the conventional Anderson-Higgs mechanism, we find that the photon acquires an additional mass from the OAM and that this mass reduces the Proca photon mass.Comment: Four pages, no figures. Error corrections, improved notation, refined derivation

Detecting orbital angular momentum in radio signals

Electromagnetic waves with an azimuthal phase shift are known to have a well defined orbital angular momentum. Different methods that allow for the detection of the angular momentum are proposed. For some, we discuss the required experimental setup and explore the range of applicability

Utilization of photon orbital angular momentum in the low-frequency radio domain

We show numerically that vector antenna arrays can generate radio beams which exhibit spin and orbital angular momentum characteristics similar to those of helical Laguerre-Gauss laser beams in paraxial optics. For low frequencies (< 1 GHz), digital techniques can be used to coherently measure the instantaneous, local field vectors and to manipulate them in software. This opens up for new types of experiments that go beyond those currently possible to perform in optics, for information-rich radio physics applications such as radio astronomy, and for novel wireless communication concepts.Comment: 4 pages, 5 figures. Changed title, identical to the paper published in PR

Safety and efficacy of human Wharton's Jelly-derived mesenchymal stem cells therapy for retinal degeneration

Purpose To investigate the safety and efficacy of subretinal injection of human Wharton’s Jelly-derived mesenchymal stem cells (hWJ-MSCs) on retinal structure and function in Royal College of Surgeons (RCS) rats. Methods RCS rats were divided into 2 groups: hWJ-MSCs treated group (n = 8) and placebo control group (n = 8). In the treatment group, hWJ-MSCs from healthy donors were injected into the subretinal space in one eye of each rat at day 21. Control group received saline injection of the same volume. Additional 3 animals were injected with nanogold-labelled stem cells for in vivo tracking of cells localisation using a micro-computed tomography (microCT). Retinal function was assessed by electroretinography (ERG) 3 days before the injection and repeated at days 15, 30 and 70 after the injection. Eyes were collected at day 70 for histology, cellular and molecular studies. Results No retinal tumor formation was detected by histology during the study period. MicroCT scans showed that hWJ-MSCs stayed localised in the eye with no systemic migration. Transmission electron microscopy showed that nanogold-labelled cells were located within the subretinal space. Histology showed preservation of the outer nuclear layer (ONL) in the treated group but not in the control group. However, there were no significant differences in the ERG responses between the groups. Confocal microscopy showed evidence of hWJ-MSCs expressing markers for photoreceptor, Müller cells and bipolar cells. Conclusions Subretinal injection of hWJ-MSCs delay the loss of the ONL in RCS rats. hWJ-MSCs appears to be safe and has potential to differentiate into retinal-like cells. The potential of this cell-based therapy for the treatment of retinal dystrophies warrants further studies

Structural insight into molecular mechanism of poly (ethylene terephthalate) degradation

Plastics, including poly(ethylene terephthalate) (PET), possess many desirable characteristics and thus are widely used in daily life. However, non-biodegradability, once thought to be an advantage offered by plastics, is causing major environmental problem. Recently, a PET-degrading bacterium, Ideonella sakaiensis, was identified and suggested for possible use in degradation and/or recycling of PET. However, the molecular mechanism of PET degradation is not known. Here we report the crystal structure of I. sakaiensis PETase (IsPETase) at 1.5 angstrom resolution. IsPETase has a Ser-His-Asp catalytic triad at its active site and contains an optimal substrate binding site to accommodate four monohydroxyethyl terephthalate (MHET) moieties of PET. Based on structural and site-directed mutagenesis experiments, the detailed process of PET degradation into MHET, terephthalic acid, and ethylene glycol is suggested. Moreover, other PETase candidates potentially having high PET-degrading activities are suggested based on phylogenetic tree analysis of 69 PETase-like proteins

Toward New Therapeutics for Skin and Soft Tissue Infections: Propargyl-Linked Antifolates Are Potent Inhibitors of MRSA and Streptococcus pyogenes

Hospital- and community-acquired, complicated skin and soft tissue infections, often attributed to Staphylococcus aureus and Streptococcus pyogenes, present a significant health burden that is associated with increased health care costs and mortality. As these two species are difficult to discern on diagnosis and are associated with differential profiles of drug resistance, the development of an efficacious antibacterial agent that targets both organisms is a high priority. Herein we describe a structure-based drug development effort that has produced highly potent inhibitors of dihydrofolate reductase from both species. Optimized propargyl-linked antifolates containing a key pyridyl substituent display antibacterial activity against both methicillin-resistant S. aureus and S. pyogenes at MIC values below 0.1 µg/mL and minimal cytotoxicity against mammalian cells. Further evaluation against a panel of clinical isolates shows good efficacy against a range of important phenotypes such as hospital- and community-acquired strains as well as strains resistant to vancomycin

Toxic Epidermal Necrolysis after Pemetrexed and Cisplatin for Non-Small Cell Lung Cancer in a Patient with Sharp Syndrome

Background: Pemetrexed is an antifolate drug approved for maintenance and second-line therapy, and, in combination with cisplatin, for first-line treatment of advanced nonsquamous non-small cell lung cancer. The side-effect profile includes fatigue, hematological and gastrointestinal toxicity, an increase in hepatic enzymes, sensory neuropathy, and pulmonary and cutaneous toxicity in various degrees. Case Report: We present the case of a 58-year-old woman with history of Sharp's syndrome and adenocarcinoma of the lung, who developed toxic epidermal necrolysis after the first cycle of pemetrexed, including erythema, bullae, extensive skin denudation, subsequent systemic inflammation and severe deterioration in general condition. The generalized skin lesions occurred primarily in the previous radiation field and responded to immunosuppressive treatment with prednisone. Conclusion: Although skin toxicity is a well-known side effect of pemetrexed, severe skin reactions after pemetrexed administration are rare. Caution should be applied in cases in which pemetrexed is given subsequent to radiation therapy, especially in patients with pre-existing skin diseases

Some doubts on the validity of the foreground Galactic contribution subtraction from microwave anisotropies

The Galactic foreground contamination in CMBR anisotropies, especially from the dust component, is not easily separable from the cosmological or extragalactic component. In this paper, some doubts will be raised concerning the validity of the methods used to date to remove Galactic dust emission in order to show that none of them achieves its goal. First, I review the recent bibliography on the topic and discuss critically the methods of foreground subtraction: the cross-correlation with templates, analysis assuming the spectral shape of the Galactic components, the "maximum entropy method", "internal linear combination", and "wavelet-based high resolution fitting of internal templates". Second, I analyse the galactic latitude dependence from WMAP data. The frequency dependence is discussed with the data in the available literature. The result is that all methods of subtracting the Galactic contamination are inaccurate. The galactic latitude dependence analysis or the frequency dependence of the anisotropies in the range 50-250 GHz put a constraint on the maximum Galactic contribution in the power spectrum to be less than a ~10% (68% C. L.) for a ~1 degree scale, and possibly higher for larger scales. The origin of most of the signal in the CMBR anisotropies is not Galactic. In any case, the subtraction of the Galaxy is not accurate enough to allow a "precision Cosmology"; other sources of contamination (extragalactic, solar system) are also present.Comment: 24 pages, 1 figure, accepted to be published in J. Astrophys. Ast

Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation

We conducted a genome-wide association study (GWAS) on multiple sclerosis (MS) susceptibility in German cohorts with 4888 cases and 10,395 controls. In addition to associations within the major histocompatibility complex (MHC) region, 15 non-MHC loci reached genome-wide significance. Four of these loci are novel MS susceptibility loci. They map to the genes L3MBTL3, MAZ, ERG, and SHMT1. The lead variant at SHMT1 was replicated in an independent Sardinian cohort. Products of the genes L3MBTL3, MAZ, and ERG play important roles in immune cell regulation. SHMT1 encodes a serine hydroxymethyltransferase catalyzing the transfer of a carbon unit to the folate cycle. This reaction is required for regulation of methylation homeostasis, which is important for establishment and maintenance of epigenetic signatures. Our GWAS approach in a defined population with limited genetic substructure detected associations not found in larger, more heterogeneous cohorts, thus providing new clues regarding MS pathogenesis