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Abstract Background The 15q11–q13 region is a genetic locus with genes subject to genomic imprinting, significantly influencing neurodevelopment. Genomic imprinting is an epigenetic phenomenon that causes differential gene expression based on the parent of origin. In most diploid organisms, gene expression typically involves an equal contribution from both maternal and paternal alleles, shaping the phenotype. Nevertheless, in mammals, including humans, mice, and marsupials, the functional equivalence of parental alleles is not universally maintained. Notably, during male and female gametogenesis, parental alleles may undergo differential marking or imprinting, thereby modifying gene expression without altering the underlying DNA sequence. Neurodevelopmental disorders, such as Prader–Willi syndrome (PWS) (resulting from the absence of paternally expressed genes in this region), Angelman syndrome (AS) (associated with the absence of the maternally expressed UBE3A gene), and 15q11–q13 duplication syndrome (resulting from the two common forms of duplications—either an extra isodicentric 15 chromosome or an interstitial 15 duplication), are the outcomes of genetic variations in this imprinting region. Methods Conducted a genomic study to identify the frequency of pathogenic variants impacting the 15q11–q13 region in an ethnically homogenous population from Bangladesh. Screened all known disorders from the DECIPHER database and identified variant enrichment within this cohort. Using the Horizon analysis platform, performed enrichment analysis, requiring at least >60% overlap between a copy number variation and a disorder breakpoint. Deep clinical phenotyping was carried out through multiple examination sessions to evaluate a range of clinical symptoms. Results This study included eight individuals with clinically suspected PWS/AS, all previously confirmed through chromosomal microarray analysis, which revealed chromosomal breakpoints within the 15q11–q13 region. Among this cohort, six cases (75%) exhibited variable lengths of deletions, whereas two cases (25%) showed duplications. These included one type 2 duplication, one larger atypical duplication, one shorter type 2 deletion, one larger type 1 deletion, and four cases with atypical deletions. Furthermore, thorough clinical assessments led to the diagnosis of four PWS patients, two AS patients, and two individuals with 15q11–q13 duplication syndrome. Conclusion Our deep phenotypic observations identified a spectrum of clinical features that overlap and are unique to PWS, AS, and Dup15q syndromes. Our findings establish genotype–phenotype correlation for patients impacted by variable structural variations within the 15q11–q13 region.

Ethnopharmacological relevance: A catastrophic outbreak of severe acute respiratory syndrome (SARS-CoV-2; Coronavirus disease-19; COVID-19) was first detected in Wuhan, Hubei Province, China, in December 2019. Many experimental and clinical studies have focused on the effectiveness of medicinal plants such as Nigella sativa (NS) in combating SARS-CoV-2. In this study, we aimed to evaluate the in vitro effect of NS seed extract on SARS-CoV-2 spike protein (S1)-angiotensin-converting enzyme 2 (S-ACE2) interaction. Materials and methods: NS seed extracts used for the assay were prepared in chloroform, ethanol, and water by Soxhlet extraction and recovered by rotary evaporation. The inhibition percentage of S1-ACE2 interaction was analyzed using ELISA-SARS-CoV-2 S1 Protein-ACE2 Binding Inhibitor Screening Kit. Chemical finger-printing of the extracts was done using RP-HPLC. Results: Significant concentration-dependent inhibition of the S1-ACE2 interaction was observed with chloroform, ethanol, and water extracts, ranging from 0.01 to 10 mg/ml. The P-values for the extracts were as follows: 0.0055, 0.0937, 0.0013, and 0.0003 for chloroform extract; 0.0876, 0.0703, 0.0183, and 0.0071 for ethanol extract; and 0.0915, 0.0312, 0.0006, and 0.0006 for water extract. The 50% inhibitory concentration (IC50) was determined to be 0.132 mg/ml, 0.288 mg/ml, and 4.06 mg/ml for chloroform, ethanol, and water extracts, respectively. Conclusion: The in vitro analysis utilizing SARS-CoV2 spike (S1) and ACE2 proteins proved that NS seed extracts have the potential to inhibit the S-ACE2 interaction, which warrants further studies that could lead to potential drug discovery for SARS-CoV2 infection.

The multifunctional features of noble metal nanoparticles (MNPs) were exploited in various biomedical applications, which eventually demanded the development of a sustainable green synthesis approach. In the present study, Quercetin (Q) was employed as a promising green reductant for the generation of noble metal nanoparticles such as silver (Q-AgNPs), gold (Q-AuNPs), and bimetallic (Q-Ag-AuNPs) towards biomedical perspective. Initially, the NPs were successfully synthesized in a size-controlled manner via optimizing temperature, pH, metal ion concentration, and stoichiometric ratio of the reaction mix. The redox reaction and conversion of metal ions (Ag+ and Au3+) into their respective metal nano-forms were confirmed through their surface plasmonic resonance (SPR) in UV-visible spectroscopy. In addition, different instrumentation like FT-IR, XRD, HR-TEM, and XPS analyses were performed to confirm the size, shape, and chemical composition of fabricated NPs. The bactericidal effect of fabricated NPs was tested against Gram-positive and Gram-negative pathogens. Moreover, the cytotoxic potential was screened against breast (MCF-7) and colorectal (HCT-116) carcinoma cell lines. This work revealed that the flavonoid-functionalized noble metal NPs were associated with good antibacterial and anticancer potential against selected cancer cell lines.

Introduction: Copy number variations (CNVs) play a critical role in the pathogenesis of neurodevelopmental disorders (NDD) among children. In this study, we aim to identify clinically relevant CNVs, genes and their phenotypic characteristics in an ethnically underrepresented homogenous population of Bangladesh.Methods: We have conducted chromosomal microarray analysis (CMA) for 212 NDD patients with male to female ratio of 2.2:1.0 to identify rare CNVs. To identify candidate genes within the rare CNVs, gene constraint metrics [i.e., “Critical-Exon Genes (CEGs)”] were applied to the population data. Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) was followed in a subset of 95 NDD patients to assess the severity of autism and all statistical tests were performed using the R package.Results: Of all the samples assayed, 12.26% (26/212) and 57.08% (121/212) patients carried pathogenic and variant of uncertain significance (VOUS) CNVs, respectively. While 2.83% (6/212) patients’ pathogenic CNVs were found to be located in the subtelomeric regions. Further burden test identified females are significant carriers of pathogenic CNVs compared to males (OR = 4.2; p = 0.0007). We have observed an increased number of Loss of heterozygosity (LOH) within cases with 23.85% (26/109) consanguineous parents. Our analyses on imprinting genes show, 36 LOH variants disrupting 69 unique imprinted genes and classified these variants as VOUS. ADOS-2 subset shows severe social communication deficit (p = 0.014) and overall ASD symptoms severity (p = 0.026) among the patients carrying duplication CNV compared to the CNV negative group. Candidate gene analysis identified 153 unique CEGs in pathogenic CNVs and 31 in VOUS. Of the unique genes, 18 genes were found to be in smaller (

We previously detected a potentially novel reassortant of Crimean-Congo hemorrhagic fever virus in camels at the largest livestock market in the United Arab Emirates. A broader survey of large mammals at the site indicated zoonotic transmission is associated with dromedaries and camel ticks. Seroprevalence in cattle, sheep, and goats is minimal.

The main mode of transmission of Middle East respiratory syndrome-related coronavirus (MERS-CoV) between dromedaries is likely via the respiratory route. However, there must be other modes to explain how the infection is brought to MERS-CoV-negative closed herds, such as transmission by ticks. Here, we present a study performed at three different locations in the United Arab Emirates (UAE) involving 215 dromedary camels (Camelus dromedarius) and the ticks attached to them. We tested the camels and ticks via RT-(q)PCR for the presence of MERS-CoV nucleic acids, as well as flaviviruses that may be present in the region (e.g., Alkhumra hemorrhagic fever virus). Camel sera were additionally analyzed for evidence of previous exposure to MERS-CoV. In total, 8 out of 242 tick pools were positive for MERS-CoV RNA (3.3%; Ct 34.6–38.3), 7 of which contained Hyalomma dromedarii ticks, and one contained a Hyalomma sp. tick (species not identified). All of the virus-positive ticks’ host camels were also positive for MERS-CoV RNA in their nasal swab samples. Short sequences established in the N gene region from two positive tick pools were identical to viral sequences from their hosts’ nasal swabs. In total, 59.3% of dromedaries at the livestock market had MERS-CoV RNA in their nasal swabs (Ct 17.7–39.5). While dromedaries at all locations were negative for MERS-CoV RNA in their serum samples, antibodies were detected in 95.2% and 98.7% of them (tested by ELISA and indirect immunofluorescence test, respectively). Given the probably transient and/or low level of MERS-CoV viremia in dromedaries and the rather high Ct values observed in the ticks, it seems unlikely that Hyalomma dromedarii is a competent vector for MERS-CoV; however, its role in mechanical or fomite transmission between camels should be investigated.

Summary: We describe the protocol for identifying COVID-19 severity specific cell types and their regulatory marker genes using single-cell transcriptomics data. We construct COVID-19 comorbid disease-associated gene list using multiple databases and literature resources. Next, we identify specific cell type where comorbid genes are upregulated. We further characterize the identified cell type using gene enrichment analysis. We detect upregulation of marker gene restricted to severe COVID-19 cell type and validate our findings using in silico, in vivo, and in vitro cellular models.For complete details on the use and execution of this protocol, please refer to Nassir et al. (2021b).

Hepatitis C virus (HCV) is enveloped RNA virus, encoding for a polyprotein that is processed by cellular proteases. The virus is responsible for liver cirrhosis, allograft rejection, and human hepatocellular carcinoma. Based on studies including compositional analysis, odds ratio analysis, parity analysis, skew analysis, relative synonymous codon usage, codon bias, and protein properties, it was evident that codon usage bias in HCV is dependent upon the nucleotide composition. Codon context analysis revealed CTC-CTG as a preferred codon pair. While CGA and CGT codons were rare, none of the codons were rare in HCV-like viruses envisaged in the present study. Many of the preferred codon pairs were valine amino acid-initiated, which possibly infers viral infectivity; hence the role of selection forces appears to act on the HCV genome, which was further validated by neutrality analysis where selection accounted for 87.28%, while mutation accounted for 12.72% force shaping codon usage. Furthermore, codon usage was correlated with the length of the genome. HCV viruses prefer valine-initiated codon pairs, while HCV-like viruses prefer alanine-initiated codon pairs. The HCV host range is very narrow and is confined to only humans and chimpanzees. Based on indices including codon usage correlation analysis, similarity index, and relative codon deoptimization index, it is evident in the study that the chimpanzee is the primary host of the virus. The present study helped elucidate the preferred host for HCV. The information presented in the study paved the way for generating an attenuated vaccine candidate through viral recoding, with finely tuned nucleotide composition and a perfect balance of preferred and rare codons.

The SARS-CoV-2 delta variant (B.1.617.2) appeared for the first time in December 2020 and later spread worldwide. Currently available vaccines are not so efficacious in curbing the viral pathogenesis of the delta strain of COVID; therefore, the development of a safe and effective vaccine is required. In the present study, we envisaged molecular patterns in the structural genes’ spike, nucleoprotein, membrane, and envelope of the SARS-CoV-2 delta variant. The study was based on determining compositional features, dinucleotide odds ratio, synonymous codon usage, positive and negative codon contexts, rare codons, and insight into relatedness between the human host isoacceptor tRNA and preferred codons from the structural genes. We found specific patterns, including a significant abundance of T nucleotide over all other three nucleotides. The underrepresentation of GpA, GpG, CpC, and CpG dinucleotides and the overrepresentation of TpT, ApA, CpT, and TpG were observed. A preference towards ACT- (Thr), AAT- (Asn), TTT- (Phe), and TTG- (Leu) initiated codons and aversion towards CGG (Arg), CCG (Pro), and CAC (His) was present in the structural genes of the delta strain. The interaction between the host tRNA pool and preferred codons of the envisaged structural genes revealed that the virus preferred the codons for those suboptimal numbers of isoacceptor tRNA were present. We see this as a strategy adapted by the virus to keep the translation rate low to facilitate the correct folding of viral proteins. The information generated in the study helps design the attenuated vaccine candidate against the SARS-CoV-2 delta variant using a synthetic biology approach. Three strategies were tested: changing TpT to TpA, introducing rare codons, and disrupting favored codons. It found that disrupting favored codons is a better approach to reducing virus fitness and attenuating SARS-CoV-2 delta strain using structural genes.

BackgroundCancer is the third leading cause of death in the United Arab Emirates (UAE), after cardiovascular diseases and accidents. In the UAE, colorectal cancer (CRC) is the first and fourth most common cancer in males and females, respectively. Several treatment modalities have been employed for cancer treatment, such as surgery, radiotherapy, chemotherapy, hormone replacement therapy, and immunotherapy. These treatment modalities often elicit adverse effects on normal cells, causing toxic side effects. To circumvent these toxicities, there has been an increased impetus towards the identification of alternate treatment strategies. Animal venoms are rich sources of pharmacologically active polypeptides and proteins. ObjectiveIn this proof-of-concept study, we will apply a high-throughput venomics strategy to identify and characterize anticancer bioactive peptides (BAPs) from 20 different animal venoms, specifically targeting CRC. We chose to focus on CRC because it is one of the foremost health issues in the UAE. MethodsIn the initial study, we will screen 2500 different peptides derived from 20 different animal venoms for anticancer activity specifically directed against 3 CRC cell lines and two control cell lines employing the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay for cytotoxicity. Of the 20 venoms, 3 that exhibit specific and potent anticancer activity directed against the 3 CRC cell lines will be selected; and from these 3 venoms, the specific peptides with anti-CRC activity will be isolated and characterized. ResultsThis study is at the protocol development stage only, and as such, no results are available. However, we have initiated the groundwork required to disseminate the proposed study, which includes culturing of colorectal cancer cell lines and preparation of venom screens. ConclusionsIn summary, the proposed study will generate therapeutic leads to manage and treat one of the leading health issues in the UAE, namely, CRC. International Registered Report Identifier (IRRID)PRR1-10.2196/31128

Summary: Understanding host cell heterogeneity is critical for unraveling disease mechanism. Utilizing large-scale single-cell transcriptomics, we analyzed multiple tissue specimens from patients with life-threatening COVID-19 pneumonia, compared with healthy controls. We identified a subtype of monocyte-derived alveolar macrophages (MoAMs) where genes associated with severe COVID-19 comorbidities are significantly upregulated in bronchoalveolar lavage fluid of critical cases. FCGR3B consistently demarcated MoAM subset in different samples from severe COVID-19 cohorts and in CCL3L1-upregulated cells from nasopharyngeal swabs. In silico findings were validated by upregulation of FCGR3B in nasopharyngeal swabs of severe ICU COVID-19 cases, particularly in older patients and those with comorbidities. Additional lines of evidence from transcriptomic data and in vivo of severe COVID-19 cases suggest that FCGR3B may identify a specific subtype of MoAM in patients with severe COVID-19 that may present a novel biomarker for screening and prognosis, as well as a potential therapeutic target.

We conducted a cross-sectional survey of Crimean-Congo hemorrhagic fever virus (CCHFV) in dromedary camels and attached ticks at 3 locations in the United Arab Emirates. Results revealed a high prevalence of CCHFV-reactive antibodies in camels and viral RNA in ticks and camel serum, suggesting the virus is endemic in this country.

Abstract Background In the last 50 years, the United Arab Emirates (UAE) has experienced rapid population growth and urbanization. Urbanization is known to influence biodiversity, and there appears to be a link between the emergence of arboviruses and urban growth. Very little is known about the UAE mosquito species richness and dominant vectors. We performed a mosquito survey comparing peri-urban sites in Dubai and Al Ain to a protected, natural site in Fujairah emirate. We measured mosquito biodiversity and species composition, and screened mosquito pools for common arboviruses to measure arbovirus activity in the region. Results We report ten species of mosquitoes from the UAE, with highest species diversity in the natural site, a protected wadi near the eastern coast. The predominant mosquito was Culex perexiguus, and was associated with peri-urban habitats. The site with lowest mosquito species diversity but relatively high species richness was the peri-urban site of Al Ain Zoo, where we identified Bagaza virus and Barkedji virus, two flaviviruses, in pools of Cx. perexiguus. Conclusions Decreased mosquito biodiversity was associated with increased levels of urbanization. The predominance of two species at peri-urban sites was related to the availability of their larval habitats. Arboviruses were associated with the presence of a single predominant mosquito species, Cx. perexiguus.

Abstract Background Intellectual disability (ID) is a complex condition that can impact multiple domains of development. The genetic contribution to ID’s etiology is significant, with more than 100 implicated genes and loci currently identified. The majority of such variants are rare and de novo genetic mutations. Methods We have applied whole‐genome microarray to identify large, rare, clinically relevant copy number variants (CNVs). We have applied well‐established algorithms for variants call. Quantitative polymerase chain reaction (qPCR) was applied to validate the variants using three technical replicates for each family member. To assess whether the copy number variation was due to balanced translocation or mosaicism, we further conducted droplet digital PCR (ddPCR) on the whole family. We have, as well, applied “critical‐exon” mapping, human developmental brain transcriptome, and a database of known associated neurodevelopmental disorder variants to identify candidate genes. Results Here we present two siblings who are both impacted by a large terminal duplication and a deletion. Whole‐genome microarray revealed an 18.82 megabase (MB) duplication at terminal locus (7q34‐q36.3) of chromosome 7 and a 3.90 MB deletion impacting the terminal locus (15q26.3) of chromosome 15. qPCR and ddPCR experiments confirmed the de novo origin of the variants and the co‐occurrence of these two de novo events among the siblings, but their absence in both parents, implicates an unbalanced translocation that could have mal‐segregated among the siblings or a possible germline mosaicism. These terminal events impact IGF1R, CNTNAP2, and DPP6, shown to be strongly associated with neurodevelopmental disorders. Detailed clinical examination of the siblings revealed the presence of both shared and distinct phenotypic features. Conclusions This study identified two large rare terminal de novo events impacting two siblings. Further phenotypic investigation highlights that even in the presence of identical large high penetrant variants, spectrum of clinical features can be different between the siblings.

Moringa is a sole genus of Moringaceae family with 13 species distributed in the tropical and sub-tropical regions. Among them, Moringa peregrina is one of the species which has wide range of traditional, nutritional, industrial, and medicinal values. The plant parts are used in folk medicine for many human health care purposes including diabetes, wound healing, disinfectant, fever, constipation, muscle pains, slimness, burns, labor pain, hypertension, malaria, stomach disorder, asthma, skin problems, and to expel a retained placenta. In addition to medicinal value, M. peregrina has cultural, spiritual, and religious connections with the native people of Arabian Peninsula. M. peregrina plant parts were tested for many pharmacological activities viz, antioxidant, anti-microbial, anti-diabetic, anti-spasmodic, hypertension, hepatotoxicity, lipid lowering activity, anti-inflammatory, anti-cancer, and memory disorders. Few active molecules belong to the class isothiocyanate, flavonoid, triterpenoid, phytosterol, polyphenol, and glycoside were also isolated, identified and reported for anti-microbial, anti-oxidant, anthelmintic, anti-mutagenic, neuroprotective, anti-cancer, anti-hypertensive, anti-diabetic, anti-infective, anti-allergic, anti-inflammatory, herbicidal, lipid lowering potential, anti-trypanosomal, and cytotoxic activities. So, the aim of the present review is to provide comprehensive information from recognized sources on the traditional uses, pharmacological efficacy and phytochemistry of the desert medicinal plant, M. peregrina. The information provided in this review will be very useful for further studies to develop novel therapeutic drugs.

BACKGROUND:In this study we investigated the in vitro and in vivo anticancer effect of carnosol, a naturally occurring polyphenol, in triple negative breast cancer. RESULTS:We found that carnosol significantly inhibited the viability and colony growth induced G2 arrest in the triple negative MDA-MB-231. Blockade of the cell cycle was associated with increased p21/WAF1 expression and downregulation of p27. Interestingly, carnosol was found to induce beclin1-independent autophagy and apoptosis in MDA-MB-231 cells. The coexistence of both events, autophagy and apoptosis, was confirmed by electron micrography. Induction of autophagy was found to be an early event, detected within 3 h post-treatment, which subsequently led to apoptosis. Carnosol treatment also caused a dose-dependent increase in the levels of phosphorylated extracellular signal-regulated kinase 1 and 2 (pERK1/2). Moreover, we show that carnosol induced DNA damage, reduced the mitochondrial potential and triggered the activation of the intrinsic and extrinsic apoptotic pathway. Furthermore, we found that carnosol induced a dose-dependent generation of reactive oxygen species (ROS) and inhibition of ROS by tiron, a ROS scavenger, blocked the induction of autophagy and apoptosis and attenuated DNA damage. To our knowledge, this is the first report to identify the induction of autophagy by carnosol. CONCLUSION:In conclusion our findings provide strong evidence that carnosol may be an alternative therapeutic candidate against the aggressive form of breast cancer and hence deserves more exploration.