Biallelic Variants in Seven Different Genes Associated with Clinically Suspected Bardet-Biedl Syndrome.

Bardet-Biedl syndrome (BBS) is a rare clinically and genetically heterogeneous autosomal recessive multi-systemic disorder with 22 known genes. The primary clinical and diagnostic features include six different hallmarks, such as rod-cone dystrophy, learning difficulties, renal abnormalities, male hypogonadism, post-axial polydactyly, and obesity. Here, we report nine consanguineous families and a non-consanguineous family with several affected individuals presenting typical clinical features of BBS. In the present study, 10 BBS Pakistani families were subjected to whole exome sequencing (WES), which revealed novel/recurrent gene variants, including a homozygous nonsense mutation (c.94C>T; p.Gln32Ter) in the IFT27 (NM_006860.5) gene in family A, a homozygous nonsense mutation (c.160A>T; p.Lys54Ter) in the BBIP1 (NM_001195306.1) gene in family B, a homozygous nonsense variant (c.720C>A; p.Cys240Ter) in the WDPCP (NM_015910.7) in family C, a homozygous nonsense variant (c.505A>T; p.Lys169Ter) in the LZTFL1 (NM_020347.4) in family D, pathogenic homozygous 1 bp deletion (c.775delA; p.Thr259Leufs*21) in the MKKS/BBS5 (NM_170784.3) gene in family E, a pathogenic homozygous missense variant (c.1339G>A; p.Ala447Thr) in BBS1 (NM_024649.4) in families F and G, a pathogenic homozygous donor splice site variant (c.951+1G>A; p?) in BBS1 (NM_024649.4) in family H, a pathogenic bi-allelic nonsense variant in MKKS (NM_170784.3) (c.119C>G; p.Ser40*) in family I, and homozygous pathogenic frameshift variants (c.196delA; p.Arg66Glufs*12) in BBS5 (NM_152384.3) in family J. Our findings extend the mutation and phenotypic spectrum of four different types of ciliopathies causing BBS and also support the importance of these genes in the development of multi-systemic human genetic disorders.

Independent Associated SNPs at SORCS3 and Its Protein Interactors for Multiple Brain-Related Disorders and Traits.

Sortilin-related vacuolar protein sorting 10 (VPS10) domain containing receptor 3 (SORCS3) is a neuron-specific transmembrane protein involved in the trafficking of proteins between intracellular vesicles and the plasma membrane. Genetic variation at SORCS3 is associated with multiple neuropsychiatric disorders and behavioural phenotypes. Here, we undertake a systematic search of published genome-wide association studies to identify and catalogue associations between SORCS3 and brain-related disorders and traits. We also generate a SORCS3 gene-set based on protein-protein interactions and investigate the contribution of this gene-set to the heritability of these phenotypes and its overlap with synaptic biology. Analysis of association signals at SORSC3 showed individual SNPs to be associated with multiple neuropsychiatric and neurodevelopmental brain-related disorders and traits that have an impact on the experience of feeling, emotion or mood or cognitive function, while multiple LD-independent SNPs were associated with the same phenotypes. Across these SNPs, alleles associated with the more favourable outcomes for each phenotype (e.g., decreased risk of neuropsychiatric illness) were associated with increased expression of the SORCS3 gene. The SORCS3 gene-set was enriched for heritability contributing to schizophrenia (SCZ), bipolar disorder (BPD), intelligence (IQ) and education attainment (EA). Eleven genes from the SORCS3 gene-set were associated with more than one of these phenotypes at the genome-wide level, with RBFOX1 associated with SCZ, IQ and EA. Functional annotation revealed that the SORCS3 gene-set is enriched for multiple ontologies related to the structure and function of synapses. Overall, we find many independent association signals at SORCS3 with brain-related disorders and traits, with the effect possibly mediated by reduced gene expression, resulting in a negative impact on synaptic function.

Accompanying effects of sewage sludge and pine needle biochar with selected organic additives on the soil and plant variables.

The effects of synthetic fertilizer and nutrient leaching are causing serious problems impacting soil function and its fertility. Mitigation of nutrient leaching and use of chemical fertilizer is crucial as fertile land adds up sustainability to climate changes. Biochar produced from agricultural bio-waste and municipal solid waste has been used for crop production and when applied in combination with organic nutrients may support mitigation of nutrient loss and adverse effects of chemical fertilizers. Different types of biochar and their application for soil enhancement have been observed, pine needle and sewage sludge derived low-temperature biochar along with compost, organic fertilizer in the form of manure and microalgal biomass may interact with soil chemistry and plant growth to impact nutrient loss and compensate the hazardous effect of chemical fertilizer, but it has not been investigated yet. This present study elaborates application of sewage sludge and pine needle biochar produced at 400 °C in an application rate of 5 % w/w and 10 t h-1 in combination with compost, manure and microalgal biomasses of Closteriopsis acicularis (BM1) and Tetradesmus nygaardi (BM2) on the growth of Chickpea (Cicer arietinum) and Fenugreek (Trigonella foenum-graecum) crop assessed in a pot experiment over a two crop (Chickpea - Fenugreek) cycle in Pakistan. Results depict that the pine needle biochar with additives has increased plant height by 104.1 ± 2.76 cm and fresh biomass by 49.9 ± 1.02 g, buffered the soil pH to 6.5 for optimum growth of crops and enhance carbon retention by 36 %. This study highlights the valorization of sewage sludge and pine needle into biochar and the effect of biochar augmentation, its impact on soil nutrients and plant biomass enhancement. The greener approach also mitigates and helps in the sustainable management of solid wastes.

Major Depressive Disorder: Existing Hypotheses about Pathophysiological Mechanisms and New Genetic Findings.

Major depressive disorder (MDD) is a common mental disorder generally characterized by symptoms associated with mood, pleasure and effectiveness in daily life activities. MDD is ranked as a major contributor to worldwide disability. The complex pathogenesis of MDD is not yet understood, and this is a major cause of failure to develop new therapies and MDD recurrence. Here we summarize the literature on existing hypotheses about the pathophysiological mechanisms of MDD. We describe the different approaches undertaken to understand the molecular mechanism of MDD using genetic data. Hundreds of loci have now been identified by large genome-wide association studies (GWAS). We describe these studies and how they have provided information on the biological processes, cell types, tissues and druggable targets that are enriched for MDD risk genes. We detail our understanding of the genetic correlations and causal relationships between MDD and many psychiatric and non-psychiatric disorders and traits. We highlight the challenges associated with genetic studies, including the complexity of MDD genetics in diverse populations and the need for a study of rare variants and new studies of gene-environment interactions.

Identification of novel, non-edible oil seeds via scanning electron microscopy as potential feedstock for green synthesis of biodiesel.

In the present era, environmental glitches associated with extensive emission of greenhouse gases (GHG) and energy crises caused by exhausting fossil fuel reservoirs has diverted researcher's interest toward alternative and renewable energy sources. Biodiesel is a renewable, biodegradable, and sustainable alternative to petro-diesel. Biodiesel synthesized from non-edible seed oils is preferred due its cost effectiveness and eco-friendly nature. Hence, our present study focused on investigation and identification of micromorphological characters of six novel, non-edible seed oil feedstock for biodiesel production via scanning electron microscopy (SEM). Results of light microscopy of seeds revealed distinct variation in seed size (15.8-1.8 mm in length and 9.4-1.1 in width), shape (round to Cuneiform), and color (from black to yellowish green). Non-edible seed oil content fall in range of 28-38% (wt/wt). Free fatty acid (FFA) content varied from 0.56 to 2.06 mg KOH/g. Multivariate analysis was performed to investigate correlation between three significant variables of seed oil yielding feedstock such as potential for biodiesel synthesis, oil content, and FFA content via principal component analysis. Ultra morphological investigation of seeds surfaces via SEM exhibited distinctive variation in surface sculpturing, cell arrangement, cell shape, periclinal wall shape, margins, protuberances, and anticlinal wall shape. Seed surface sculpturing varied from reticulate, semitectate, wrinkled, rugose, papillate, perforate, and striate. Periclinal wall arrangements confirmed variation from glabrous, raised, depressed, elevated, smooth, pentagonal, entire, and ripple margins. Whereas, anticlinal walls pattern demonstrated variation from angular, smooth, wavy, deep, dentate, entire, irregular, puzzled, elongated, curved, and depressed. Finally, it was concluded from obtained results that SEM could be a possible useful tool in disclosing veiled micromorphological characters of non-edible oil yielding seeds, which provides useful information to researchers for their correct, authentic identification, and classification in modern synthetic system.

Deciphering role of technical bioprocess parameters for bioethanol production using microalgae.

Microalgae biomass is considered an important feedstock for biofuels and other bioactive compounds due to its faster growth rate, high biomass production and high biomolecules accumulation over first and second-generation feedstock. This research aimed to maximize the specific growth rate of fresh water green microalgae Closteriopsis acicularis, a member of family Chlorellaceae under the effect of pH and phosphate concentration to attain enhanced biomass productivity. This study investigates the individual and cumulative effect of phosphate concentration and pH on specific growth characteristics of Closteriopsis acicularis in autotrophic mode of cultivation for bioethanol production. Central-Composite Design (CCD) strategy and Response Surface Methodology (RSM) was used for the optimization of microalga growth and ethanol production under laboratory conditions. The results showed that high specific growth rate and biomass productivity of 0.342 day-1 and 0.497 g L-1 day-1 respectively, were achieved at high concentration of phosphate (0.115 g L-1) and pH (9) at 21st day of cultivation. The elemental composition of optimized biomass has shown enhanced elemental accumulation of certain macro (C, O, P) and micronutrients (Na, Mg, Al, K, Ca and Fe) except for nitrogen and sulfur. The Fourier transform infrared spectroscopic analysis has revealed spectral peaks and high absorbance in spectral range of carbohydrates, lipids and proteins, in optimized biomass. The carbohydrates content of optimized biomass was observed as 58%, with 29.3 g L-1 of fermentable sugars after acid catalyzed saccharification. The bioethanol yield was estimated as 51 % g ethanol/g glucose with maximum of 14.9 g/L of bioethanol production. In conclusion, it can be inferred that high specific growth rate and biomass productivity can be achieved by varying levels of phosphate concentration and pH during cultivation of Closteriopsis acicularis for improved yield of microbial growth, biomass and bioethanol production.