Clinical, biochemical, cellular and molecular characterization of mitochondrial DNA depletion syndrome due to novel mutations in the MPV17 gene

Mitochondrial DNA (mtDNA) depletion syndromes (MDS) are severe autosomal recessive disorders associated with decreased mtDNA copy number in clinically affected tissues. The hepatocerebral form (mtDNA depletion in liver and brain) has been associated with mutations in the POLG, PEO1 (Twinkle), DGUOK and MPV17 genes, the latter encoding a mitochondrial inner membrane protein of unknown function. The aims of this study were to clarify further the clinical, biochemical, cellular and molecular genetic features associated with MDS due to MPV17 gene mutations. We identified 12 pathogenic mutations in the MPV17 gene, of which 11 are novel, in 17 patients from 12 families. All patients manifested liver disease. Poor feeding, hypoglycaemia, raised serum lactate, hypotonia and faltering growth were common presenting features. mtDNA depletion in liver was demonstrated in all seven cases where liver tissue was available. Mosaic mtDNA depletion was found in primary fibroblasts by PicoGreen staining. These results confirm that MPV17 mutations are an important cause of hepatocerebral mtDNA depletion syndrome, and provide the first demonstration of mosaic mtDNA depletion in human MPV17 mutant fibroblast cultures. We found that a severe clinical phenotype was associated with profound tissue-specific mtDNA depletion in liver, and, in some cases, mosaic mtDNA depletion in fibroblasts

Expanding the genetic heterogeneity of intellectual disability

Intellectual disability (ID) is a common morbid condition with a wide range of etiologies. The list of monogenic forms of ID has increased rapidly in recent years thanks to the implementation of genomic sequencing techniques. In this study, we describe the phenotypic and genetic findings of 68 families (105 patients) all with novel ID-related variants. In addition to established ID genes, including ones for which we describe unusual mutational mechanism, some of these variants represent the first confirmatory disease-gene links following previous reports (TRAK1, GTF3C3, SPTBN4 and NKX6-2), some of which were based on single families. Furthermore, we describe novel variants in 14 genes that we propose as novel candidates (ANKHD1, ASTN2, ATP13A1, FMO4, MADD, MFSD11, NCKAP1, NFASC, PCDHGA10, PPP1R21, SLC12A2, SLK, STK32C and ZFAT). We highlight MADD and PCDHGA10 as particularly compelling candidates in which we identified biallelic likely deleterious variants in two independent ID families each. We also highlight NCKAP1 as another compelling candidate in a large family with autosomal dominant mild intellectual disability that fully segregates with a heterozygous truncating variant. The candidacy of NCKAP1 is further supported by its biological function, and our demonstration of relevant expression in human brain. Our study expands the locus and allelic heterogeneity of ID and demonstrates the power of positional mapping to reveal unusual mutational mechanisms

Parkinsonism‐dystonia‐2: Case‐series study from Saudi Arabia

Abstract Parkinsonism‐dystonia‐2 PKDYS2 is an autosomal‐recessive disorder, caused by pathogenic biallelic variants in SLC18A2 which encodes the vesicular monoamine transporter (VMAT2) protein. PKDYS2 is a treatable neurotransmitter disease, and the rate of diagnosis of this disorder has increased significantly with the advance of genomic technologies. Our report highlights a novel pathologic variant in one case and a novel finding on MRI Brain, consisting of a normal symmetrical signal intensity in the dorsal brainstem and pons, and it substantiates the significance of genetic testing in the evaluation of children with developmental delays, which influences clinical decisions to enhance patient outcomes

Experimental investigation of porous carbon for cooling and desalination applications

Abstract Adsorption cooling and desalination (ACD) system presents a solution for water, energy, and environmental dilemma. This study expresses an enhancement of adsorption system performance in terms of cooling and desalination effects by improving an activated carbon Maxsorb III (Max) as an adsorbent. Max has been initially treated with HCl. Then, it has been activated by impregnating it in salt hydrates ((NH4)2CO3). Characterization methods, including XRD, N2 and water adsorption isotherm, and water adsorption kinetics have been conducted for raw Max, treated Max, and activated Max with (NH4)2CO3. The experimental values have been fitted with the Dubinin & Astakhov equilibrium model for isotherm and the model of linear driving force for kinetics. These fitted parameters have been utilized in a previously validated model to estimate adsorption cooling-desalination system performance with and without heat recovery. Max/(NH4)2CO3 achieves a water uptake of 0.53 kgH2O.kg-1. Max/(NH4)2CO3 produces 13.2 m3.ton-1 of freshwater per day with a specific cooling power of 373 W.kg-1 and 0.63 COP. Also, the freshwater reaches 22.5 m3.ton-1 of Max/(NH4)2CO3 per day with condenser-evaporator heat recovery. These results indicate the potential of utilizing the Max material in dual cooling and desalination applications to achieve double what silica gel can offer

Hybrid Solar-Driven Desalination/Cooling Systems: Current Situation and Future Trend

Global warming and climate change, accompanied and assisted by rapid economic and population growth, are causing a sharp rise in cooling demands and stressing the already-limited supply of freshwater for many countries worldwide, especially those developing under hot-climate conditions. Thus, it is imperative to find solutions to meet cooling and freshwater needs without negatively affecting the environment and exacerbating the global warming problem. Solar-driven hybrid desalination/cooling technologies are a promising solution that can help in reducing greenhouse gas emissions and increasing overall efficiency and energy savings. The present study summarizes research efforts in meeting cooling and freshwater demands using the available solar resources. Various solar desalination technologies, such as multi-effect distillation (MED), single and multi-stage flash (MSF), reverse osmosis (RO), adsorption, absorption desalination, and membrane distillation (MD), and their integration with different cooling technologies, are reported. The study reported system performance indicators, such as water production rate, cooling capacity, Coefficient of Performance, and freshwater cost

Breast cancer knowledge and practice of breast self‐examination among Palestinian female, West Bank: A cross‐sectional study

Abstract Background Worldwide, breast cancer (BC) is the most frequently discovered tumor in women. Breast self‐examination (BSE) is a helpful screening method that gives women more control over their bodies by educating them about the structures of their breasts and assisting in the early detection of any developing breast abnormalities. The purpose of this research was to assess Palestinian girls' degree of BSE awareness and practice. Method A self‐administered questionnaire was used to gauge participants' knowledge about BC and associated topics. Through an online survey, all girls above the age of 20 are encouraged to take part in the study. Female university students at academic levels I, II, III, and IV in Palestine were also invited to participate in the study by way of an online survey. Results The study included 467 female participants, with 69% of the individuals being single. The majority of females (68.7%) scored poorly on knowledge of BC disease (possible risk, methods of detection, methods of diagnosis, methods of treatment, signs and symptoms, information about mammography, and other knowledge questions), whereas only 31.7% scored well. Conclusion BC, which is thought to be the most common malignant development among them and the second leading cause of cancer mortality, is one of the issues that women in the West Bank face. Screening methods are crucial for the early detection of BC and for lowering disease‐related morbidity and mortality. It has been advised that starting at age 20, every woman should take the BSE

Oil Prices and the Renewable Energy Sector

Energy security, climate change, and growing energy demand issues are moving up on the global political agenda, and contribute to the rapid growth of the renewable energy sector. In this paper we investigate the effects of oil price shocks, and also of uncertainty about oil prices, on the stock returns of clean energy and technology companies. In doing so, we use monthly data that span the period from May 1983 to December 2016, and a bivariate structural VAR model that is modified to accommodate GARCH-in-mean errors, and it is used to generate impulse response functions. Moreover, we examine the asymmetry of stock responses to oil price shocks and compare them accounting for oil price uncertainty, while effects of oil price shocks of different magnitude are also investigated. Our evidence indicates that oil price uncertainty has no statistically significant effect on stock returns, and that the relationship between oil prices and stock returns is symmetric. Our results are robust to alternative model specifications and stock prices of clean energy companies