PTPA variants and impaired PP2A activity in early-onset parkinsonism with intellectual disability

The protein phosphatase 2A complex (PP2A), the major Ser/Thr phosphatase in the brain, is involved in a number of signalling pathways and functions, including the regulation of crucial proteins for neurodegeneration, such as alpha-synuclein, tau and LRRK2. Here, we report the identification of variants in the PTPA/PPP2R4 gene, encoding a major PP2A activator, in two families with early-onset parkinsonism and intellectual disability. We carried out clinical studies and genetic analyses, including genome-wide linkage analysis, whole-exome sequencing, and Sanger sequencing of candidate variants. We next performed functional studies on the disease-associated variants in cultured cells and knock-down of ptpa in Drosophila melanogaster. We first identified a homozygous PTPA variant, c.893T&gt;G (p.Met298Arg), in patients from a South African family with early-onset parkinsonism and intellectual disability. Screening of a large series of additional families yielded a second homozygous variant, c.512C&gt;A (p.Ala171Asp), in a Libyan family with a similar phenotype. Both variants co-segregate with disease in the respective families. The affected subjects display juvenile-onset parkinsonism and intellectual disability. The motor symptoms were responsive to treatment with levodopa and deep brain stimulation of the subthalamic nucleus. In overexpression studies, both the PTPA p.Ala171Asp and p.Met298Arg variants were associated with decreased PTPA RNA stability and decreased PTPA protein levels; the p.Ala171Asp variant additionally displayed decreased PTPA protein stability. Crucially, expression of both variants was associated with decreased PP2A complex levels and impaired PP2A phosphatase activation. PTPA orthologue knock-down in Drosophila neurons induced a significant impairment of locomotion in the climbing test. This defect was age-dependent and fully reversed by L-DOPA treatment. We conclude that bi-allelic missense PTPA variants associated with impaired activation of the PP2A phosphatase cause autosomal recessive early-onset parkinsonism with intellectual disability. Our findings might also provide new insights for understanding the role of the PP2A complex in the pathogenesis of more common forms of neurodegeneration.</p

Response of winter barley varieties to different agrotechnical factors

The article is study of the repoonse of different winter barley varieties to different fertilization levels and plant protection levels to be able to determine the yield, the physiological and the agronomical point of references in the cultivation the varieties. This research and experiments was conducted at the University of Debrecen, Látókép Experimental Station of Plant Production on 5 different winter barley varieties which were selected for the research there include: SU Ellen, KH Tas, KG Puszta, KG Apavar and lastly Jallon which are all varieties found in Hungary.BSc/BAAgricultural Engineerin

The grapevine VvWRKY2 gene enhances salt and osmotic stress tolerance in transgenic Nicotiana tabacum

Our study aims to assess the implication of WRKY transcription factor in the molecular mechanisms of grapevine adaptation to salt and water stresses. In this respect, a full-length VvWRKY2 cDNA, isolated from a Vitis vinifera grape berry cDNA library, was constitutively over-expressed in Nicotiana tabacum seedlings. Our results showed that transgenic tobacco plants exhibited higher seed germination rates and better growth, under both salt and osmotic stress treatments, when compared to wild type plants. Furthermore, our analyses demonstrated that, under stress conditions, transgenic plants accumulated more osmolytes, such as soluble sugars and free proline, while no changes were observed regarding electrolyte leakage, H2O2, and malondialdehyde contents. The improvement of osmotic adjustment may be an important mechanism underlying the role of VvWRKY2 in promoting tolerance and adaptation to abiotic stresses. Principal component analysis of our results highlighted a clear partition of plant response to stress. On the other hand, we observed a significant adaptation behaviour response for transgenic lines under stress. Taken together, all our findings suggest that over-expression of VvWRKY2 gene has a compelling role in abiotic stress tolerance and, therefore, would provide a useful strategy to promote abiotic stress tolerance in grape via molecular-assisted breeding and/or new biotechnology tools

Using KASP technique to screen LRRK2 G2019S mutation in a large Tunisian cohort

Abstract Background In North African populations, G2019S mutation in LRRK2 gene, encoding for the leucine-rich repeat kinase 2, is the most prevalent mutation linked to familial and sporadic Parkinson’s disease (PD). Early detection of G2019S by fast genetic testing is very important to guide PD’s diagnosis and support patients and their family caregivers for better management of their life according to disease’s evolution. Methods In our study, a genetic PD’s diagnosis tool was developed for large scale genotyping using Kompetitive Allele Specific PCR (KASP) technology. We investigated G2019S’s frequency in 250 Tunisian PD patients and 218 controls. Results We found that 33.6% of patients and 1.3% of controls were carriers. Demographic characteristics of patients with G2019S had no differences compared with non-carrier patients. Thereby, we could emphasize the implication of G2019S in PD without any distinctive demographic factors in the studied cohort. Sixty patients out of 250 were genotyped using Taqman assay and Sanger sequencing. The genotyping results were found to be concordant with KASP assay. Conclusions The G2019S mutation frequency in our cohort was similar to that reported in previous studies. Comparing to Taqman assay and Sanger sequencing, KASP was shown to be a reliable, time and cost effective genotyping assay for routine G2019S screening in genetic testing laboratories

Analysis of Fuel Alternative Products Obtained by the Pyrolysis of Diverse Types of Plastic Materials Isolated from a Dumpsite Origin in Pakistan

The current energy crisis and waste management problems have compelled people to find alternatives to conventional non-renewable fuels and utilize waste to recover energy. Pyrolysis of plastics, which make up a considerable portion of municipal and industrial waste, has emerged as a feasible resolution to both satisfy our energy needs and mitigate the issue of plastic waste. This study was therefore conducted to find a solution for plastic waste management problems, as well as to find an alternative to mitigate the current energy crisis. Pyrolysis of five of the most commonly used plastics, polyethylene terephthalate (PET), high- and low-density polyethylene (HDPE, LDPE), polypropylene (PP), and polystyrene (PS), was executed in a pyrolytic reactor designed utilizing a cylindrical shaped stainless steel container with pressure and temperature gauges and a condenser to cool down the hydrocarbons produced. The liquid products collected were highly flammable and their chemical properties revealed them as fuel alternatives. Among them, the highest yield of fuel conversion (82%) was observed for HDPE followed by PP, PS, LDPE, PS, and PET (61.8%, 58.0%, 50.0%, and 11.0%, respectively). The calorific values of the products, 46.2, 46.2, 45.9, 42.8 and 42.4 MJ/kg for LPDE, PP, HPDE, PS, and PET, respectively, were comparable to those of diesel and gasoline. Spectroscopic and chromatographic analysis proved the presence of alkanes and alkenes with carbon number ranges of C9–C15, C9–C24, C10–C21, C10–C28, and C9–C17 for PP, PET, HDPE, LDPE, and PS, respectively. If implemented, the study will prove to be beneficial and contribute to mitigating the major energy and environmental issues of developing countries, as well as enhance entrepreneurship opportunities by replicating the process at small-scale and industrial levels

Thymic plasmacytoma presenting as polyneuropathy and revealing multiple myeloma: a case report

Abstract Background Multiple myeloma (MM) is the most frequent malignant plasma cell disorder with proliferation of neoplastic plasma cells in the bone marrow or other tissue, most commonly in the upper aerodigestive tract. The invasion of the thymus is exceptional. Neurological complications are usual, but represent exceptionally the revealing symptom. Case presentation We report a case of polyneuropathy revealing a thymic plasmacytoma as a mediastinal invasion of MM in a 48-year-old woman. She was admitted after developing progressive ascending distal paresthesias and weakness in lower limbs. Examination showed symmetrical distal sensorimotor impairment with axillary and inguinal adenopathies. Electroneuromyography revealed a sensorimotor length-dependent neuropathy. Serum protein electrophoresis showed monoclonal protein peak in β-γ globulin region. Immunoelectrophoresis showed IgA lambda monoclonal gammapathy. Myelogram and bone marrow biopsy revealed plasmocytosis of 5%. Chest computed tomography showed a histologically confirmed thymic plasmacytoma associated with a lytic lesion of the 5th rib leading to the diagnosis of MM. Conclusions The association between a thymic plasmacytoma and peripheral neuropathy is rare and a workup for MM is necessary to guide therapeutic management

Epidemiology and disease burden of tuberculosis in south of Tunisia over a 22-year period: Current trends and future projections.

BackgroundTuberculosis (TB) is a public health problem worldwide. Characterizing its trends over time is a useful tool for decision-makers to assess the efficiency of TB control programs. We aimed to give an update on the current chronological trends of TB in Southern Tunisia from 1995 to 2016 and to estimate future trajectories of TB epidemic by 2030.MethodsWe retrospectively collected data of all notified TB new cases by the Center of Tuberculosis Control between 1995 and 2016 in South of Tunisia. Joinpoint Regression Analysis was performed to analyze chronological trends and annual percentage changes (APC) were estimated.ResultsIn the past 22 years, a total of 2771 cases of TB were notified in Southern Tunisia. The annual incidence rate of TB was 13.91/100,000 population/year. There was a rise in all forms of TB incidence (APC = 1.63) and in extrapulmonary tuberculosis (EPTB) (APC = 2.04). The incidence of TB increased in children and adult females between 1995 and 2016 (APC = 4.48 and 2.37, respectively). The annual number of TB declined in urban districts between 2004 and 2016 (APC = -2.85). Lymph node TB cases increased (APC = 4.58), while annual number of urogenital TB decreased between 1995 and 2016 (APC = -3.38). Projected incidence rates would increase to 18.13 and 11.8/100,000 population in 2030 for global TB and EPTB, respectively.ConclusionsOur study highlighted a rise in all forms of TB and among high-risk groups, notably children, females and lymph node TB patients in the last two decades and up to the next one