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Globally, siltation of water reservoirs is a major risk and cost to the provision of fresh water. Therefore, managing reservoir sedimentation is a significant task for water management agencies. In Kenya, the Ruiru water reservoir, one of four water reservoirs supplying Nairobi with drinking water has experienced a significant loss of volume since construction in 1949. However, there have been no studies characterizing the long-term catchment dynamics such as erosion, sedimentation and accumulation in the reservoir. A detailed understanding of the sediment dynamics such as identification of sediment source area; processes driving soil erosion in the catchment and accumulation in the reservoir, and identification of flood layers are necessary for the reservoir and landscape management. The accumulated sediment has not been characterized; therefore, long-term land-use and climate change impacts on the catchment on the reservoir are not documented. The study aims to identify the historical land use and climate events in the catchment impacting the reservoir through a multiproxy sediment characterization of the sediment accumulating in the Ruiru reservoir. An undisturbed 1-m sediment core retrieved in 2017 from Ruiru Reservoir was dated using 210 Pb and 137 Cs and particle size distribution and chemical element profiles analyzed. The accumulated sediment is a predominantly fine-grained red silt, with a particle size end-member analysis identifying four possible sources or processes of sediment accumulation. The multi-proxy analysis reveals six periods of significant accumulation, 1949, 1963/64, 1974/75, 1982/83, 1997/98 and 2013/14. The peaks coincide with high rainfall events and two are attributed to significant land-use changes in the catchment. The study identifies the catchment dynamics with a significant sediment input into the reservoir. This highlights the importance of reservoirs as environmental archives documenting 20th century land -use and climate events while providing a long-term perspective for management of critical water infrastructure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: ATP2B2 encodes the variant-constrained plasma-membrane calcium-transporting ATPase-2, expressed in sensory ear cells and specialized neurons. ATP2B2/Atp2b2 variants were previously linked to isolated hearing loss in patients and neurodevelopmental deficits with ataxia in mice. We aimed to establish the association between ATP2B2 and human neurological disorders., Methods: Multinational case recruitment, scrutiny of trio-based genomics data, in silico analyses, and functional variant characterization were performed., Results: We assembled 7 individuals harboring rare, predicted deleterious heterozygous ATP2B2 variants. The alleles comprised 5 missense substitutions that affected evolutionarily conserved sites and 2 frameshift variants in the penultimate exon. For 6 variants, a de novo status was confirmed. Unlike described patients with hearing loss, the individuals displayed a spectrum of neurological abnormalities, ranging from ataxia with dystonic features to complex neurodevelopmental manifestations with intellectual disability, autism, and seizures. Two cases with recurrent amino-acid variation showed distinctive overlap with cerebellar atrophy-associated ataxia and epilepsy. In cell-based studies, all variants caused significant alterations in cytosolic calcium handling with both loss- and gain-of-function effects., Conclusion: Presentations in our series recapitulate key phenotypic aspects of Atp2b2-mouse models and underline the importance of precise calcium regulation for neurodevelopment and cerebellar function. Our study documents a role for ATP2B2 variants in causing heterogeneous neurodevelopmental and movement-disorder syndromes., Competing Interests: Conflict of Interest The authors declare no conflicts of interest., (Copyright © 2023 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.)

Background: Definition of the individual genotypes that cause a Mendelian phenotype is of great importance both to clinical diagnostics and disease characterization. Heterozygous de novo gain-of-function missense variants in RARB are associated with syndromic microphthalmia 12 (MCOPS12), a developmental disorder characterized by eye malformations and variable involvement of other organs. A subset of patients were described with poorly delineated movement disorders. Additionally, RARB bi-allelic loss-of-function variants, inherited from asymptomatic heterozygous carrier parents, have been found in a recessive family with four MCOPS12-affected members., Patient/methods: We used trio whole-exome sequencing to explore the molecular basis of disease in an individual with congenital eye abnormality and movement disorder. All patients with reported RARB variants were reviewed., Results: We report on identification of a heterozygous de novo RARB nonsense variant in a girl with microphthalmia and progressive generalized dystonia. Public database entries indicate that the de novo variant is recurrently present in clinically affected subjects but a literature report has not yet been available., Conclusions: We provide the first detailed evidence for a role of dominant RARB truncating alterations in congenital eye-brain disease, expanding the spectrum of MCOPS12-associated mutations. Considered together with the published family with bi-allelic variants, the data suggest manifestation and non-manifestation of disease in relation to almost identical RARB loss-of-function variations, an apparent paradox that is seen in a growing number of human genetic conditions associated with both recessive and dominant inheritance patterns., Competing Interests: Declaration of competing interest The authors declare that no conflict of interest exists., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Purpose: We sought to delineate the genotypic and phenotypic spectrum of female and male individuals with X-linked, MSL3-related disorder (Basilicata-Akhtar syndrome)., Methods: Twenty-five individuals (15 males, 10 females) with causative variants in MSL3 were ascertained through exome or genome sequencing at ten different sequencing centers., Results: We identified multiple variant types in MSL3 (ten nonsense, six frameshift, four splice site, three missense, one in-frame-deletion, one multi-exon deletion), most proven to be de novo, and clustering in the terminal eight exons suggesting that truncating variants in the first five exons might be compensated by an alternative MSL3 transcript. Three-dimensional modeling of missense and splice variants indicated that these have a deleterious effect. The main clinical findings comprised developmental delay and intellectual disability ranging from mild to severe. Autism spectrum disorder, muscle tone abnormalities, and macrocephaly were common as well as hearing impairment and gastrointestinal problems. Hypoplasia of the cerebellar vermis emerged as a consistent magnetic resonance image (MRI) finding. Females and males were equally affected. Using facial analysis technology, a recognizable facial gestalt was determined., Conclusion: Our aggregated data illustrate the genotypic and phenotypic spectrum of X-linked, MSL3-related disorder (Basilicata-Akhtar syndrome). Our cohort improves the understanding of disease related morbidity and allows us to propose detailed surveillance guidelines for affected individuals.

Purpose: This study characterizes the clinical and genetic features of nine unrelated patients with de novo variants in the NR4A2 gene., Methods: Variants were identified and de novo origins were confirmed through trio exome sequencing in all but one patient. Targeted RNA sequencing was performed for one variant to confirm its splicing effect. Independent discoveries were shared through GeneMatcher., Results: Missense and loss-of-function variants in NR4A2 were identified in patients from eight unrelated families. One patient carried a larger deletion including adjacent genes. The cases presented with developmental delay, hypotonia (six cases), and epilepsy (six cases). De novo status was confirmed for eight patients. One variant was demonstrated to affect splicing and result in expression of abnormal transcripts likely subject to nonsense-mediated decay., Conclusion: Our study underscores the importance of NR4A2 as a disease gene for neurodevelopmental disorders and epilepsy. The identified variants are likely causative of the seizures and additional developmental phenotypes in these patients.

The hydrogen isotopic composition of leaf wax-derived n-alkanes (δ 2 H n-alkanes ) is a widely applied proxy for (paleo)climatic changes. It has been suggested that the coupling with the oxygen isotopic composition of hemicellulose-derived sugars (δ 18 O sugar ) - an approach dubbed 'paleohygrometer' - might allow more robust and quantitative (paleo)hydrological reconstructions. However, the paleohygrometer remains to be evaluated and tested regionally. In this study, topsoil samples from South Africa, covering extensive environmental gradients, are analysed. δ 2 H n-alkanes correlates significantly with the isotopic composition of precipitation (δ 2 H p ), whereas no significant correlation exists between δ 18 O sugar and δ 18 O p . The apparent fractionation (ε app ) is the difference between δ 2 H n-alkanes and δ 2 H p (ε app 2H ) and δ 18 O sugar and δ 18 O p (ε app 18O ), respectively, and integrates i) isotopic enrichment due to soil water evaporation, ii) leaf (and xylem) water transpiration and iii) biosynthetic fractionation. We find no correlation of ε app 18O nor for ε app 2H with temperature, and no correlation of ε app 2H with potential evapotranspiration and an aridity index. By contrast, ε app 18O correlates significantly with both potential evapotranspiration and the aridity index. This highlights the strong effect of evapotranspirative enrichment on δ 18 O sugar . In study areas without plant predominance using Crassulacean Acid Metabolism (CAM), coupling δ 18 O sugar and δ 2 H n-alkanes enables to reconstruct δ 2 H p and δ 18 O p with an offset of Δδ 2 H = 6 ± 27‰ and Δδ 18 O = 0.8 ± 3.7‰, respectively, as well as relative humidity (RH) with an offset of ΔRH = 6 ± 17%. The paleohygrometer does, however, not work well for our study areas where CAM plants prevail (reconstructed δ 18 O p , δ 2 H p and RH are off by 3.1‰, 27.2‰ and 31.7%). This probably reflects plant-specific (phenological) adaptations and/or post-photosynthetic exchange reactions related to CAM metabolism. Overall, our findings corroborate that δ 2 H n-alkanes and δ 18 O sugar are valuable proxies, and the paleohygrometer is a promising approach for paleoclimate reconstructions in southern Africa., Competing Interests: Declaration of competing interest PS, TH, MB, JS, BG, MZ and RZ declare that they have no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: The purpose of this study was to expand the genetic architecture of neurodevelopmental disorders, and to characterize the clinical features of a novel cohort of affected individuals with variants in ZNF142, a C 2 H 2 domain-containing transcription factor., Methods: Four independent research centers used exome sequencing to elucidate the genetic basis of neurodevelopmental phenotypes in four unrelated families. Following bioinformatic filtering, query of control data sets, and secondary variant confirmation, we aggregated findings using an online data sharing platform. We performed in-depth clinical phenotyping in all affected individuals., Results: We identified seven affected females in four pedigrees with likely pathogenic variants in ZNF142 that segregate with recessive disease. Affected cases in three families harbor either nonsense or frameshifting likely pathogenic variants predicted to undergo nonsense mediated decay. One additional trio bears ultrarare missense variants in conserved regions of ZNF142 that are predicted to be damaging to protein function. We performed clinical comparisons across our cohort and noted consistent presence of intellectual disability and speech impairment, with variable manifestation of seizures, tremor, and dystonia., Conclusion: Our aggregate data support a role for ZNF142 in nervous system development and add to the emergent list of zinc finger proteins that contribute to neurocognitive disorders.

The elucidation of the metabolic requirements of human embryos in vivo or in vitro remains, despite being intensively investigated, a work in progress. The adoption of extended embryo culture to the blastocyst stage during the last decade has entailed new challenges. With the increased attention to culture media formulations, more evidence on the sensitivity of embryos to their early environmental conditions is accumulating which might affect phenotype and developmental potential. A retrospective study was conducted that comprised 286 IVF cycles to evaluate the effect of two different culture media on blastocyst development and pregnancy outcome. Embryos were either cultured in a one step or a sequential medium. Higher fertilization rates and augmented blastocyst rates as well as higher implantation rates were observed when embryos were cultured in one step medium (P<0.05). Interestingly, the transfer of two embryos where one embryo was cultured in either medium resulted in a significantly higher rate of twin pregnancies. Although multiple pregnancies should be avoided in assisted reproduction treatment to reduce risks for offspring and mother, this higher frequency of twin pregnancies resulting from the transfer of embryos derived from different culture media suggests that each embryo makes individual demands on its early environment., (Copyright © 2010 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

The use of high levels of cryoprotectants (CPs) in solutions applied to vitrify oocytes or embryos is an argument to still prefer slow freezing procedure. Is it a justified argument? Out of three studies using mice zygotes we may assume that (i) the intracellular concentration of CPs is far lower than the one in the vitrification solutions, (ii) the intracellular concentration of CPs in the vitrified zygote is in contrary to the common beliefs even lower than the one observed after a slow freezing procedure, (iii) survival after slow freezing reflects the presence of an intracellular vitrified state in these cells., (Copyright © 2010. Published by Elsevier SAS.)

Increased gliosis has been previously described in schizophrenic brain. In this study, the degree of gliosis in schizophrenic and control brains was assessed quantitatively using an antibody to glial fibrillary acidic protein, immunocytochemical techniques, and a computed image analysis system. Twenty separate brain areas were assessed, and no significant differences were found between the schizophrenic and control groups. It seems unlikely that a specific pattern of pathologically significant gliosis is present in schizophrenic brains. These negative findings are of note because of previously reported structural differences in the temporal lobe in the schizophrenic group in this series.