615 results match your criteria: "Qatar Biomedical Research Institute[Affiliation]"

Retracing our steps: A review on autism research in children, its limitation and impending pharmacological interventions.

Pharmacol Ther

January 2024

Neurological Disorders Research Center, Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Qatar Foundation, Doha, Qatar. Electronic address:

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by three core impairments: impaired communication, impaired reciprocal social interaction, and restricted, repetitive, and stereotypical behavior patterns. Spectrum refers to the heterogeneity of presentation, severity of symptoms, and medical comorbidities associated with ASD. Among the most common underlying medical conditions are attention-deficit/hyperactivity disorder (ADHD), anxiety, depression, epilepsy, digestive disorders, metabolic disorders, and immune disorders.

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Thyroid hormone (T3) plays a vital role in brain development and its dysregulation can impact behavior, nervous system function, and cognitive development. Large case-cohort studies have associated abnormal maternal T3 during early pregnancy to epilepsy, autism, and attention deficit hyperactivity disorder (ADHD) in children. Recent experimental findings have also shown T3's influence on the fate of neural precursor cells and raise the question of its convergence with embryonic neural progenitors.

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Ubiquitination of histone H2B on chromatin is key to gene regulation. E3 ligase Bre1 and E2 Rad6 in Saccharomyces cerevisiae associate together to catalyze mono-ubiquitination at histone H2B Prior studies identified the role of a highly dynamic C-terminal acidic tail of Rad6 indispensable for H2B mono-ubiquitination. However, the mechanistic basis for the Rad6-acidic tail role remained elusive.

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Article Synopsis
  • - Autism spectrum disorder (ASD) is a neurodevelopmental condition with varying symptoms, primarily affecting social/communication skills and causing repetitive behaviors, with no approved diagnostic biomarker currently available.
  • - This study analyzed serum samples from 93 ASD cases and 28 healthy controls to identify autoantibodies associated with ASD using advanced protein-array technology, resulting in the discovery of 29 differential autoantibodies.
  • - The findings suggest that these autoantibodies are linked to essential brain functions, such as axonal guidance and metabolic pathways, and their expression varies with the age of individuals diagnosed with ASD.
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Genetic Deletion of DNAJB3 Using CRISPR-Cas9, Produced Discordant Phenotypes.

Genes (Basel)

September 2023

Department of Nutritional Sciences & Obesity Research Institute, Texas Tech University, Lubbock, TX 79409, USA.

Article Synopsis
  • This study investigates the role of the DNAJB3 gene in obesity-induced insulin resistance and type 2 diabetes, showing that its impaired expression correlates with increased metabolic stress.
  • Using CRISPR-Cas9, three DNAJB3 knockout mouse lines were created to explore how the absence of DNAJB3 affects body weight, fat mass, and insulin sensitivity when fed a high-fat diet.
  • Results indicated that knockout mice (specifically KO 47) gained more weight, had slower glucose clearance, and showed higher inflammatory markers compared to wild-type mice, highlighting DNAJB3's potential protective role against obesity-related health issues.
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The field of Alzheimer's disease (AD) has witnessed recent breakthroughs in the development of disease-modifying biologics and diagnostic markers. While immunotherapeutic interventions have provided much-awaited solutions, nucleic acid-based tools represent other avenues of intervention; however, these approaches are costly and invasive, and they have serious side effects. Previously, we have shown in AD animal models that tolfenamic acid (TA) can lower the expression of AD-related genes and their products and subsequently reduce pathological burden and improve cognition.

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Lissencephaly (LIS) is a malformation of cortical development due to deficient neuronal migration and abnormal formation of cerebral convolutions or gyri. Thirty-one LIS-associated genes have been previously described. Recently, biallelic pathogenic variants in CRADD and PIDD1, have associated with LIS impacting the previously established role of the PIDDosome in activating caspase-2.

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Transforming growth factor β (TGFβ) pathway is a master regulator of cell proliferation, differentiation, and death. Deregulation of TGFβ signalling is well established in several human diseases including autoimmune disorders and cancer. Thus, understanding molecular pathways governing TGFβ signalling may help better understand the underlying causes of some of those conditions.

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Glutaminase (GLS), which deaminates glutamine to form glutamate, is a mitochondrial tetrameric protein complex. Although inorganic phosphate (Pi) is known to promote GLS filamentation and activation, the molecular basis of this mechanism is unknown. Here we aimed to determine the molecular mechanism of Pi-induced mouse GLS filamentation and its impact on mitochondrial physiology.

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Therapeutic targeting of the TPX2/TTK network in colorectal cancer.

Cell Commun Signal

September 2023

Translational Cancer and Immunity Center (TCIC), Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), PO Box 34110, 00000, Doha, Qatar.

Background: While the increased screening, changes in lifestyle, and recent advances in treatment regimen have decreased colorectal cancer (CRC) mortality, metastatic disease and recurrence remains a major clinical challenge. In the era of precision medicine, the identification of actionable novel therapeutic targets could ultimately offer an alternative treatment strategy for CRC.

Methods: RNA-Seq was conducted using the illumina platform, while bioinformatics analyses were conducted using CLC genomics workbench and iDEP.

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: Harnessing Its Potential for Industrial, Medical, and Agricultural Applications-A Comprehensive Review.

Microorganisms

August 2023

Faculty of Medical and Health Sciences, Liwa College, Abu Dhabi P.O. Box 41009, United Arab Emirates.

, a Gram-positive bacterium, has emerged as a versatile microorganism with significant applications in various fields, including industry, medicine, and agriculture. This comprehensive review aims to provide an in-depth understanding of the characteristics, genetic tools, and metabolic capabilities of , while highlighting its potential as a chassis cell for synthetic biology, metabolic engineering, and protein expression. We discuss the bacterium's role in the production of chemicals, enzymes, and other industrial bioproducts, as well as its applications in medicine, such as combating infectious diseases and promoting gut health.

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Background: A key question for any psychopathological diagnosis is whether the condition is continuous or discontinuous with typical variation. The primary objective of this study was to use a multi-method approach to examine the broad latent categorical versus dimensional structure of autism spectrum disorder (ASD).

Method: Data were aggregated across seven independent samples of participants with ASD, other neurodevelopmental disorders (NDD), and non-ASD/NDD controls (aggregate s = 512-16,755; ages 1.

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Purpose: Genetic and environmental risk factors associated with Autism Spectrum Disorders (ASD) continue to be a focus of research worldwide. Consanguinity, the cultural practice of marrying within a family, is common in cultures and societies of the Middle East, North Africa and parts of Asia. Consanguinity has been investigated as a risk factor for ASD in a limited number of studies, with mixed results.

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Cancer Incidence and Mortality Estimates in Arab Countries in 2018: A GLOBOCAN Data Analysis.

Cancer Epidemiol Biomarkers Prev

December 2023

Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University, Qatar Foundation, Doha, Qatar.

Background: Arab countries are projecting increase in cancer incidence and mortality; however, there are limited studies that compare the epidemiology of cancer in Arab countries compared with other parts of the world.

Methods: We used the 2018 Global Cancer Observatory data to compare the age-standardized incidence and mortality estimates in Arab-speaking countries to the rest of the world.

Results: Rates for incidence and mortality for all cancers in Arab countries were lower than the world's rates but the incidence rates of non-Hodgkin and Hodgkin lymphoma, bladder, breast, and liver cancers were higher.

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Long non-coding RNA AC099850.4 correlates with advanced disease state and predicts worse prognosis in triple-negative breast cancer.

Front Med (Lausanne)

August 2023

Translational Cancer and Immunity Center (TCIC), Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha, Qatar.

Our understanding of the function of long non-coding RNAs (lncRNAs) in health and disease states has evolved over the past decades due to the many advances in genome research. In the current study, we characterized the lncRNA transcriptome enriched in triple-negative breast cancer (TNBC, = 42) and estrogen receptor (ER+, = 42) breast cancer compared to normal breast tissue ( = 56). Given the aggressive nature of TNBC, our data revealed selective enrichment of 57 lncRNAs in TNBC.

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Genome-wide differential expression profiling of long non-coding RNAs in FOXA2 knockout iPSC-derived pancreatic cells.

Cell Commun Signal

September 2023

Diabetes Research Center (DRC), Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), PO Box 34110, Doha, Qatar.

Background: Our recent studies have demonstrated the crucial involvement of FOXA2 in the development of human pancreas. Reduction of FOXA2 expression during the differentiation of induced pluripotent stem cells (iPSCs) into pancreatic islets has been found to reduce α-and β-cell masses. However, the extent to which such changes are linked to alterations in the expression profile of long non-coding RNAs (lncRNAs) remains unraveled.

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Metabolic stress involved in several dysregulation disorders such as type 2 diabetes mellitus (T2DM) results in down regulation of several heat shock proteins (HSPs) including DNAJB3. This down regulation of HSPs is associated with insulin resistance (IR) and interventions which induce the heat shock response (HSR) help to increase the insulin sensitivity. Metabolic stress leads to changes in signaling pathways through increased activation of both c-jun N-terminal kinase-1 (JNK1) and the inhibitor of κB inflammatory kinase (IKKβ) which in turn leads to inactivation of insulin receptor substrates 1 and 2 (IRS-1 and IRS-2).

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Article Synopsis
  • - A patient with Kallmann syndrome (KS) and intellectual disability (ID) was found to have a significant deletion in a specific region of chromosome 12, suggesting that this deletion may be responsible for their conditions rather than the patient's translocation.
  • - The research team screened 48 KS patients for mutations at the translocation breakpoints but found none, further supporting the idea that the 12p11.21-12p11.23 deletion is key to the patient's symptoms.
  • - Through an analysis of various candidate genes and their expression in relevant tissues, several potential genes linked to KS and ID were identified, including TSPAN11 for KS and others like TM7SF3 and STK38L for neurodevelopment
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An optimized protocol for the preparation of blood immune cells for transmission electron microscopy.

Micron

October 2023

Neurological Disorders Research Center, Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Qatar Foundation, Doha, Qatar. Electronic address:

Article Synopsis
  • Transmission electron microscopy (TEM) is an advanced imaging technique that reveals detailed structures within cells, but requires specific preparation methods for biological samples, particularly blood.
  • The text presents a comprehensive protocol tailored for preparing blood samples for TEM, allowing for effective visualization of the ultrastructures of blood immune cells.
  • It also outlines key cellular characteristics that help differentiate various immune cells like neutrophils, eosinophils, monocytes, and lymphocytes, aiding in the study of changes in these cells during different health conditions.
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Autism spectrum disorder (ASD) is a complex and heterogeneous neurodevelopmental disorder linked to numerous rare, inherited, and arising de novo genetic variants. ASD often co-occurs with attention-deficit hyperactivity disorder and epilepsy, which are associated with hyperexcitability of neurons. However, the physiological and molecular mechanisms underlying hyperexcitability in ASD remain poorly understood.

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Background: Neuroinflammation is one of the pathophysiologies of Parkinson's disease (PD). Lewy bodies, the pathological hallmark of PD, emerge as a consequence of α-synuclein aggregation, and neuroinflammation is induced concurrently with this aggregation. Imaging and cerebrospinal fluid (CSF) biomarkers that reflect PD pathophysiology have been developed or are under investigation.

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Coronavirus disease (COVID-19) manifests many clinical symptoms, including an exacerbated immune response and cytokine storm. Autoantibodies in COVID-19 may have severe prodromal effects that are poorly understood. The interaction between these autoantibodies and self-antigens can result in systemic inflammation and organ dysfunction.

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WDR11, a gene associated with Kallmann syndrome, is important in reproductive system development but molecular understanding of its action remains incomplete. We previously reported that Wdr11-deficient embryos exhibit defective ciliogenesis and developmental defects associated with Hedgehog (HH) signalling. Here we demonstrate that WDR11 is required for primordial germ cell (PGC) development, regulating canonical and noncanonical HH signalling in parallel.

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Excess hepatic lipid accumulation is the hallmark of non-alcoholic fatty liver disease (NAFLD), for which no medication is currently approved. However, glucagon-like peptide-1 receptor agonists (GLP-1RAs), already approved for treating type 2 diabetes, have lately emerged as possible treatments. Herein we aim to investigate how the GLP-1RA exendin-4 (Ex-4) affects the microRNA (miRNAs) expression profile using an in vitro model of steatosis.

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