Vremenske i prostorne varijacije salaniteta podzemnih voda u ravnici Mazandaran, Iran, tijekom dugogodišnjeg razdoblja od 26 godina

Groundwater resources are one of the main sources of water supply for agricultural sector in Iran. Therefore, this study aimed to investigate the situation of groundwater salinity in Mazandaran for use in agriculture. In this study, statistical analysis of collected data, proper semivariogram model selection, cross validation of predictions and preparing probabilistic and zoning maps using geostatistical tools in the ArcGIS software, were performed. To investigate the spatial variations and preparing zoning maps of water salinity, ordinary kriging (OK) was used and the zoning maps were prepared. Spatial structure of electrical conductivity (EC) assessment showed a moderate spatial dependence in most years. Zoning and probabilistic maps of EC showed that the salinity of groundwater will be added and the most probable salinity is related the lowland areas in the eastern part of the plain. The use of this groundwater for irrigation in the long term can decrease the rice yield and faced rice production with a serious risk. The results of the Mann-Kendall and the Sen tests indicated a decreasing trend in the area of groundwater with EC higher than one dS/m in Mazandaran plain that this expressing an improvement in the quality of groundwater in the plain.Resursi podzemnih voda jedan su od glavnih izvora vodoopskrbe poljoprivrednog sektora u Iranu. Stoga je ova studija usmjerena na istraživanje stanja saliniteta podzemnih voda u Mazandaranu koje se koriste u poljoprivredi. U ovoj studiji provedena je: statistička analiza prikupljenih podataka, odabir pravilnog modela semivariograma, unakrsno potvrđivanje predviđanja i pripremanje probabilističkih i zoniranje karata koristeći geostatističke alate u ArcGIS softveru. Da bi se istražile prostorne varijacije i pripremile karte slanosti vode korišteno je obično krigiranje (OK) i pripremljene su karte zoniranja. Prostorna struktura procjene električne provodljivosti (EC) pokazala je umjerenu prostornu ovisnost u većini godina. Zoniranje i probabilističke karte električne vodljivosti pokazale su da će se dodati slanost podzemnih voda, a najvjerojatnija slanost povezana je s nizinskim područjima u istočnom dijelu ravnice. Korištenje takvih podzemnih voda za navodnjavanje dugoročno može smanjiti prinos riže i proizvodnju s rižom s ozbiljnim rizikom. Rezultati ispitivanja pomoću Mann-Kendall-ovog i Senovog testa ukazali su na trend pada podzemnih voda s električnom vodljivošću 1 dS/m, što upućuje na poboljšanje kvalitete podzemnih voda u ravnici Mazandaran

Use of modified heulandite by cationic surfactant as new adsorbent for removing anions from recirculation aquaculture system

Water treatment in recirculation aquaculture systems (RAS) is one of the main methods in water quality management. In organic Ion exchange materials are used only for ammonia adsorption in rearing systems. Zeolites have negative charge in their surfaces and this property capable them to remove cations and metal ions. At this study by using a cationic surfactant (Tetradecyltrimethylamonium bromide) clinoptilolite surface for removing nitrogenous compound is changed. Studied zeolite was analysed by XRD and XRF. Results indicated that Heulandit was the main element in the sample. Experiment was done at three replicates under environmental conditions (temperature (10, 15 and 20) and pH (6, 6.5, 7, 7.5 and 8)). Results indicated that environmental factors influenced absorption capacity. Results showed that increased in temperature have significant effect on nitrate and nitrite removal by SMZ (P<0/05).Temperature cause Increasing in anion mobility and finally anion adsorption. pH have significant effect on nitrate adsorption (P<0/05) while any regular trend didn’t observe about nitrite. Increasing pH cause increase in ionization degree and adsorption. Results indicated that other factor such as anion concentration, existing other anions and counter ions impressed adsorption

Bi-allelic GAD1 variants cause a neonatal onset syndromic developmental and epileptic encephalopathy.

Developmental and epileptic encephalopathies are a heterogeneous group of early-onset epilepsy syndromes dramatically impairing neurodevelopment. Modern genomic technologies have revealed a number of monogenic origins and opened the door to therapeutic hopes. Here we describe a new syndromic developmental and epileptic encephalopathy caused by bi-allelic loss-of-function variants in GAD1, as presented by 11 patients from six independent consanguineous families. Seizure onset occurred in the first 2 months of life in all patients. All 10 patients, from whom early disease history was available, presented with seizure onset in the first month of life, mainly consisting of epileptic spasms or myoclonic seizures. Early EEG showed suppression-burst or pattern of burst attenuation or hypsarrhythmia if only recorded in the post-neonatal period. Eight patients had joint contractures and/or pes equinovarus. Seven patients presented a cleft palate and two also had an omphalocele, reproducing the phenotype of the knockout Gad1-/- mouse model. Four patients died before 4 years of age. GAD1 encodes the glutamate decarboxylase enzyme GAD67, a critical actor of the γ-aminobutyric acid (GABA) metabolism as it catalyses the decarboxylation of glutamic acid to form GABA. Our findings evoke a novel syndrome related to GAD67 deficiency, characterized by the unique association of developmental and epileptic encephalopathies, cleft palate, joint contractures and/or omphalocele

Biallelic MFSD2A variants associated with congenital microcephaly, developmental delay, and recognizable neuroimaging features

Major Facilitator Superfamily Domain containing 2a (MFSD2A) is an essential endothelial lipid transporter at the blood-brain barrier. Biallelic variants affecting function in MFSD2A cause autosomal recessive primary microcephaly 15 (MCPH15, OMIM# 616486). We sought to expand our knowledge of the phenotypic spectrum of MCPH15 and demonstrate the underlying mechanism of inactivation of the MFSD2A transporter. We carried out detailed analysis of the clinical and neuroradiological features of a series of 27 MCPH15 cases, including eight new individuals from seven unrelated families. Genetic investigation was performed through exome sequencing (ES). Structural insights on the human Mfsd2a model and in-vitro biochemical assays were used to investigate the functional impact of the identified variants. All patients had primary microcephaly and severe developmental delay. Brain MRI showed variable degrees of white matter reduction, ventricular enlargement, callosal hypodysgenesis, and pontine and vermian hypoplasia. ES led to the identification of six novel biallelic MFSD2A variants (NG_053084.1, NM_032793.5: c.556+1G>A, c.748G>T; p.(Val250Phe), c.750_753del; p.(Cys251SerfsTer3), c.977G>A; p.(Arg326His), c.1386_1435del; p.(Gln462HisfsTer17), and c.1478C>T; p.(Pro493Leu)) and two recurrent variants (NM_032793.5: c.593C>T; p.(Thr198Met) and c.476C>T; p.(Thr159Met)). All these variants and the previously reported NM_032793.5: c.490C>A; p.(Pro164Thr) resulted in either reduced MFSD2A expression and/or transport activity. Our study further delineates the phenotypic spectrum of MCPH15, refining its clinical and neuroradiological characterization and supporting that MFSD2A deficiency causes early prenatal brain developmental disruption. We also show that poor MFSD2A expression despite normal transporter activity is a relevant pathomechanism in MCPH15

PRUNE is crucial for normal brain development and mutated in microcephaly with neurodevelopmental impairment.

PRUNE is a member of the DHH (Asp-His-His) phosphoesterase protein superfamily of molecules important for cell motility, and implicated in cancer progression. Here we investigated multiple families from Oman, India, Iran and Italy with individuals affected by a new autosomal recessive neurodevelopmental and degenerative disorder in which the cardinal features include primary microcephaly and profound global developmental delay. Our genetic studies identified biallelic mutations of PRUNE1 as responsible. Our functional assays of disease-associated variant alleles revealed impaired microtubule polymerization, as well as cell migration and proliferation properties, of mutant PRUNE. Additionally, our studies also highlight a potential new role for PRUNE during microtubule polymerization, which is essential for the cytoskeletal rearrangements that occur during cellular division and proliferation. Together these studies define PRUNE as a molecule fundamental for normal human cortical development and define cellular and clinical consequences associated with PRUNE mutation

Clinico-radiological features, molecular spectrum, and identification of prognostic factors in developmental and epileptic encephalopathy due to inosine triphosphate pyrophosphatase (ITPase) deficiency

Developmental and epileptic encephalopathy 35 (DEE 35) is a severe neurological condition caused by biallelic variants in ITPA, encoding inosine triphosphate pyrophosphatase, an essential enzyme in purine metabolism. We delineate the genotypic and phenotypic spectrum of DEE 35, analyzing possible predictors for adverse clinical outcomes. We investigated a cohort of 28 new patients and reviewed previously described cases, providing a comprehensive characterization of 40 subjects. Exome sequencing was performed to identify underlying ITPA pathogenic variants. Brain MRI (magnetic resonance imaging) scans were systematically analyzed to delineate the neuroradiological spectrum. Survival curves according to the Kaplan–Meier method and log-rank test were used to investigate outcome predictors in different subgroups of patients. We identified 18 distinct ITPA pathogenic variants, including 14 novel variants, and two deletions. All subjects showed profound developmental delay, microcephaly, and refractory epilepsy followed by neurodevelopmental regression. Brain MRI revision revealed a recurrent pattern of delayed myelination and restricted diffusion of early myelinating structures. Congenital microcephaly and cardiac involvement were statistically significant novel clinical predictors of adverse outcomes. We refined the molecular, clinical, and neuroradiological characterization of ITPase deficiency, and identified new clinical predictors which may have a potentially important impact on diagnosis, counseling, and follow-up of affected individuals

Comparative proteomic analysis of spermatozoa isolated by swim-up or density gradient centrifugation

Abstract BACKGROUND: Reports about the morphologic and functional characteristics of spermatozoa prepared by density gradient centrifugation (DC) or swim-up (SU) have produced discordant results. We have performed a proteomic comparison of cells prepared by DC and SU providing a molecular insight into the differences between these two methods of sperm cell isolation. METHODS: Protein maps were obtained by 2-dimensional (2-D) separations consisting of isoelectrofocusing (IEF) from pI 3 to 11 followed by SDS-polyacrylamide gel electrophoresis. 2-D gels were stained with Sypro Ruby. Map images of DC and SU spermatozoa were compared using dedicated software. Intensities of a given spot were considered different between DC and SU when their group mean differed by >1.5-fold (p<0.05, Anova). RESULTS: No differences were observed for 853 spots, indicating a 98.7% similarity between DC and SU. Five spots were DC>SU and 1 was SU>DC. Proteins present in 3 of the differential spots could be identified. One DC>SU spot contained lactate dehydrogenase C and gamma-glutamylhydrolase, a second DC>SU spot contained fumarate hydratase and glyceraldehyde-3-phosphate dehydrogenase-2, and a SU>DC spot contained pyruvate kinase M1/M2. CONCLUSIONS: The differences in protein levels found on comparison of DC with SU spermatozoa indicate possible dissimilarities in their glycolytic metabolism and DNA methylation and suggest that DC cells may have a better capacitation potential

Biallelic variants in KARS1 are associated with neurodevelopmental disorders and hearing loss recapitulated by the knockout zebrafish

Purpose: Pathogenic variants in Lysyl-tRNA synthetase 1 (KARS1) have increasingly been recognized as a cause of early-onset complex neurological phenotypes. To advance the timely diagnosis of KARS1-related disorders, we sought to delineate its phenotype and generate a disease model to understand its function in vivo. Methods: Through international collaboration, we identified 22 affected individuals from 16 unrelated families harboring biallelic likely pathogenic or pathogenic in KARS1 variants. Sequencing approaches ranged from disease-specific panels to genome sequencing. We generated loss-of-function alleles in zebrafish. Results: We identify ten new and four known biallelic missense variants in KARS1 presenting with a moderate-to-severe developmental delay, progressive neurological and neurosensory abnormalities, and variable white matter involvement. We describe novel KARS1-associated signs such as autism, hyperactive behavior, pontine hypoplasia, and cerebellar atrophy with prevalent vermian involvement. Loss of kars1 leads to upregulation of p53, tissue-specific apoptosis, and downregulation of neurodevelopmental related genes, recapitulating key tissue-specific disease phenotypes of patients. Inhibition of p53 rescued several defects of kars1−/− knockouts. Conclusion: Our work delineates the clinical spectrum associated with KARS1 defects and provides a novel animal model for KARS1-related human diseases revealing p53 signaling components as potential therapeutic targets