Genetic Algorithm and Multi-objective Function Optimization with the Jumping Gene(Transposon) Adaptation-A Primer

I am going to deliver a lecture on "Genetic Algorithm and Multi-objective Optimization with the Jumping Gene (Transposon ) Adaptation - A Primer".Optimization techn-iques have long been applied to problems of industrial importance.Several excellent texts1 -5 describe the vari-ous methods with examples. These usually involve a single objective function and constraints . Most real-world engineering problems, however, require the simultaneous optimization of several objectives ( multi-objective optimization ) that cannot be compared easily with each other (are non-commensurate), and so cannot be combined into a single , meaningful scalar objective function. An example is the maximization of the product, while mini-mizing the production of an undesirable side product. A very popular and robust technique for solving optimiza-tion problems with a single objective function is genetic algorithm (GA), also referred to as simple GA (SGA). This, is a search technique developed by Holland .It mimics the process of natural selection and natural genetics. The Darwinian principle of'survival of the fittest ' is used to obtain the optimal solution. This technique is better than calculus-based methods (both direct and indirect methods)that generally obtain the local optimum, and that may miss the global optimum . This technique does not need derivatives either. A recent adaptation of GA [non domi-nated sorting genetic algorithm' with elitism ' and the jumping gene operator, NSGA II-JG4] has been developed to solve multi-objective function optimization problems. In this paper we describe GA and its adaptations in a manner quite suited to a beginner

CLINICAL PROFILE AND THE OUTCOME OF COVID-19 IN PATIENTS WITH HEMATOLOGICAL MALIGNANCY: A SINGLE CENTRE EXPERIENCE

Objective: In the present study, we are reporting the clinical profile; and outcomes of COVID-19 in patients with hematological malignancy at tertiary care hospitals. Methods: Data from laboratory-confirmed 40 COVID-19 patients diagnosed between January 1, 2021 and July 31, 2021, were analyzed retrospectively. All COVID-19 patients with hematological malignancy (n=40) were included in the study. Results: In the present study, a total of 40 patients were included. Of 40, 25 (62.5%) were males, and 15 (37.5%) were females. The median age in this study was 43 years (Range, 8–70). Of these 40 patients, acute myeloid leukemia was the most common malignancy 11 (27.5%), followed by acute lymphoblastic leukemia 9 (22.5%) than non-Hodgkin lymphoma 5 (12.5%), plasma cell dyscrasia 4 (10%), chronic myeloid leukemia 4 (10%), chronic lymphocytic leukemia 3 (7.5%), acute promyelocytic leukemia 2 (5%), chronic myelomonocytic leukemia 2 (5%). Mean hemoglobin was (8.04 g/dl), white blood cell count was (10.14×109/l), platelet count was (77.7×109/l) creatinine was (0.86 mg/dl), bilirubin was (1.24 mg/dl). The overall case-fatality rate was 8 (22.5%). Conclusion: Patients with hematological malignancy are immunocompromised, and our study reveals that there is an increased case fatality rate among these patients. Hence, physicians should be aggressive in the management of COVID‐19 patients with hematological malignancy

Thioredoxin-1 maintains mechanistic target of rapamycin (mTOR) function during oxidative stress in cardiomyocytes

Thioredoxin 1 (Trx1) is a 12-kDa oxidoreductase that catalyzes thiol-disulfide exchange reactions to reduce proteins with disulfide bonds. As such, Trx1 helps protect the heart against stresses, such as ischemia and pressure overload. Mechanistic target of rapamycin (mTOR) is a serine/threonine kinase that regulates cell growth, metabolism, and survival. We have shown previously that mTOR activity is increased in response to myocardial ischemia-reperfusion injury. However, whether Trx1 interacts with mTOR to preserve heart function remains unknown. Using a substrate-trapping mutant of Trx1 (Trx1C35S), we show here that mTOR is a direct interacting partner of Trx1 in the heart. In response to H2O2 treatment in cardiomyocytes, mTOR exhibited a high molecular weight shift in non-reducing SDS-PAGE in a 2-mercaptoethanol-sensitive manner, suggesting that mTOR is oxidized and forms disulfide bonds with itself or other proteins. The mTOR oxidation was accompanied by reduced phosphorylation of endogenous substrates, such as S6 kinase (S6K) and 4E-binding protein 1 (4E-BP1) in cardiomyocytes. Immune complex kinase assays disclosed that H2O2 treatment diminished mTOR kinase activity, indicating that mTOR is inhibited by oxidation. Of note, Trx1 overexpression attenuated both H2O2-mediated mTOR oxidation and inhibition, whereas Trx1 knockdown increased mTOR oxidation and inhibition. Moreover, Trx1 normalized H2O2-induced down-regulation of metabolic genes and stimulation of cell death, and an mTOR inhibitor abolished Trx1-mediated rescue of gene expression. H2O2-induced oxidation and inhibition of mTOR were attenuated when Cys-1483 of mTOR was mutated to phenylalanine. These results suggest that Trx1 protects cardiomyocytes against stress by reducing mTOR at Cys-1483, thereby preserving the activity of mTOR and inhibiting cell death

Splenectomy for diagnosis of lymphomas: A case series

Splenomegaly can be caused by various etiologies such as infections, congestion/ portal hypertension, auto-immune diseases, infiltrative diseases and malignancy. It requires extensive work-up of hematological, radiological and sometimes bone marrow studies to arrive at definitive diagnosis. However, in 3-36% of cases, cause of splenomegaly remains unknown despite extensive work up; among which lymphomas (16-44%) are an important cause. Hence splenectomy and pathological examination of the spleen might be the only option in this sub-set of patients to confirm the diagnosis. Here is a series of four cases of splenomegaly of unknown etiology presented to us over a period of 3 years who underwent laparoscopic splenectomy for diagnostic purpose. All these cases were diagnosed as Non-Hodgkin's lymphoma. Thrombocytopenia, anaemia and symptoms due to mass effect that these patients had prior to surgery were reversed. All patients were started on chemotherapy with-in 4 weeks of surgery

Association of genes with phenotype in autism spectrum disorder.

Autism spectrum disorder (ASD) is a genetic heterogeneous neurodevelopmental disorder that is characterized by impairments in social interaction and speech development and is accompanied by stereotypical behaviors such as body rocking, hand flapping, spinning objects, sniffing and restricted behaviors. The considerable significance of the genetics associated with autism has led to the identification of many risk genes for ASD used for the probing of ASD specificity and shared cognitive features over the past few decades. Identification of ASD risk genes helps to unravel various genetic variants and signaling pathways which are involved in ASD. This review highlights the role of ASD risk genes in gene transcription and translation regulation processes, as well as neuronal activity modulation, synaptic plasticity, disrupted key biological signaling pathways, and the novel candidate genes that play a significant role in the pathophysiology of ASD. The current emphasis on autism spectrum disorders has generated new opportunities in the field of neuroscience, and further advancements in the identification of different biomarkers, risk genes, and genetic pathways can help in the early diagnosis and development of new clinical and pharmacological treatments for ASD

Genetics of structural and functional brain changes in autism spectrum disorder.

Autism spectrum disorder (ASD) is a neurological and developmental disorder characterized by social impairment and restricted interactive and communicative behaviors. It may occur as an isolated disorder or in the context of other neurological, psychiatric, developmental, and genetic disorders. Due to rapid developments in genomics and imaging technologies, imaging genetics studies of ASD have evolved in the last few years. Increased risk for ASD diagnosis is found to be related to many specific single-nucleotide polymorphisms, and the study of genetic mechanisms and noninvasive imaging has opened various approaches that can help diagnose ASD at the nascent level. Identifying risk genes related to structural and functional changes in the brain of ASD patients provide a better understanding of the disease's neuropsychiatry and can help identify targets for therapeutic intervention that could be useful for the clinical management of ASD patients.This study was supported by a PI grant from Sidra Medicine (5071012001) to M.H. A.A.B. is supported by Sidra Medicine internal grant (5011041002)

Role of non-coding RNA networks in leukemia progression, metastasis and drug resistance.

Early-stage detection of leukemia is a critical determinant for successful treatment of the disease and can increase the survival rate of leukemia patients. The factors limiting the current screening approaches to leukemia include low sensitivity and specificity, high costs, and a low participation rate. An approach based on novel and innovative biomarkers with high accuracy from peripheral blood offers a comfortable and appealing alternative to patients, potentially leading to a higher participation rate.Recently, non-coding RNAs due to their involvement in vital oncogenic processes such as differentiation, proliferation, migration, angiogenesis and apoptosis have attracted much attention as potential diagnostic and prognostic biomarkers in leukemia. Emerging lines of evidence have shown that the mutational spectrum and dysregulated expression of non-coding RNA genes are closely associated with the development and progression of various cancers, including leukemia. In this review, we highlight the expression and functional roles of different types of non-coding RNAs in leukemia and discuss their potential clinical applications as diagnostic or prognostic biomarkers and therapeutic targets

Genetic and Neuroimaging Approaches to Understanding Post-Traumatic Stress Disorder.

Post-traumatic stress disorder (PTSD) is a highly disabling condition, increasingly recognized as both a disorder of mental health and social burden, but also as an anxiety disorder characterized by fear, stress, and negative alterations in mood. PTSD is associated with structural, metabolic, and molecular changes in several brain regions and the neural circuitry. Brain areas implicated in the traumatic stress response include the amygdala, hippocampus, and prefrontal cortex, which play an essential role in memory function. Abnormalities in these brain areas are hypothesized to underlie symptoms of PTSD and other stress-related psychiatric disorders. Conventional methods of studying PTSD have proven to be insufficient for diagnosis, measurement of treatment efficacy, and monitoring disease progression, and currently, there is no diagnostic biomarker available for PTSD. A deep understanding of cutting-edge neuroimaging genetic approaches is necessary for the development of novel therapeutics and biomarkers to better diagnose and treat the disorder. A current goal is to understand the gene pathways that are associated with PTSD, and how those genes act on the fear/stress circuitry to mediate risk vs. resilience for PTSD. This review article explains the rationale and practical utility of neuroimaging genetics in PTSD and how the resulting information can aid the diagnosis and clinical management of patients with PTSD.Sidra Medicine funded this research to Mohammad Haris (5071012001) and Ajaz A. Bhat (5011041002)