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Various lineages of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have contributed to prolongation of the Coronavirus Disease 2019 (COVID-19) pandemic. Several non-synonymous mutations in SARS-CoV-2 proteins have generated multiple SARS-CoV-2 variants. In our previous report, we have shown that an evenly uneven distribution of unique protein variants of SARS-CoV-2 is geo-location or demography-specific. However, the correlation between the demographic transmutability of the SARS-CoV-2 infection and mutations in various proteins remains unknown due to hidden symmetry/asymmetry in the occurrence of mutations. This study tracked how these mutations are emerging in SARS-CoV-2 proteins in six model countries and globally. In a geo-location, considering the mutations having a frequency of detection of at least 500 in each SARS-CoV-2 protein, we studied the country-wise percentage of invariant residues. Our data revealed that since October 2020, highly frequent mutations in SARS-CoV-2 have been observed mostly in the Open Reading Frame (ORF) 7b and ORF8, worldwide. No such highly frequent mutations in any of the SARS-CoV-2 proteins were found in the UK, India, and Brazil, which does not correlate with the degree of transmissibility of the virus in India and Brazil. However, we have found a signature that SARS-CoV-2 proteins were evolving at a higher rate, and considering global data, mutations are detected in the majority of the available amino acid locations. Fractal analysis of each protein's normalized factor time series showed a periodically aperiodic emergence of dominant variants for SARS-CoV-2 protein mutations across different countries. It was noticed that certain high-frequency variants have emerged in the last couple of months, and thus the emerging SARS-CoV-2 strains are expected to contain prevalent mutations in the ORF3a, membrane, and ORF8 proteins. In contrast to other beta-coronaviruses, SARS-CoV-2 variants have rapidly emerged based on demographically dependent mutations. Characterization of the periodically aperiodic nature of the demographic spread of SARS-CoV-2 variants in various countries can contribute to the identification of the origin of SARS-CoV-2.
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COVID-19 , SARS-CoV-2 , Humanos , Mutación , IncertidumbreRESUMEN
A global emergency due to the COVID-19 pandemic demands various studies related to genes and genomes of the SARS-CoV2. Among other important proteins, the role of accessory proteins are of immense importance in replication, regulation of infections of the coronavirus in the hosts. The largest accessory protein in the SARS-CoV2 genome is ORF3a which modulates the host response to the virus infection and consequently it plays an important role in pathogenesis. In this study, an attempt is made to decipher the conservation of nucleotides, dimers, codons and amino acids in the ORF3a genes across thirty-two genomes of Indian patients. ORF3a gene possesses single and double point mutations in Indian SARS-CoV2 genomes suggesting the change of SARS-CoV2's virulence property in Indian patients. We find that the parental origin of the ORF3a gene over the genomes of SARS-CoV2 and Pangolin-CoV is same from the phylogenetic analysis based on conservation of nucleotides and so on. This study highlights the accumulation of mutation on ORF3a in Indian SARS-CoV2 genomes which may provide the designing therapeutic approach against SARS-CoV2.
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Betacoronavirus/genética , Secuencia Conservada , Infecciones por Coronavirus/virología , Mutación , Neumonía Viral/virología , Proteínas Reguladoras y Accesorias Virales/genética , Animales , Secuencia de Bases , Evolución Biológica , COVID-19 , Quirópteros/virología , Infecciones por Coronavirus/veterinaria , Euterios/virología , Genoma Viral , Genómica , Humanos , India , Pandemias , Filogenia , SARS-CoV-2 , Proteínas Reguladoras y Accesorias Virales/química , Proteínas Estructurales Virales/química , Proteínas Estructurales Virales/genética , Proteínas ViroporinasRESUMEN
Honey bees can communicate navigational information which makes them unique amongst all prominent insect navigators. Returning foragers recruit nest mates to a food source by communicating flight distance and direction using a small scale walking pattern: the waggle dance. It is still unclear how bees transpose flight information to generate corresponding dance information. In single feeder shift experiments, we monitored for the first time how individual bees update dance duration after a shift of feeder distance. Interestingly, the majority of bees (86%) needed two or more foraging trips to update dance duration. This finding demonstrates that transposing flight navigation information to dance information is not a reflexive behavior. Furthermore, many bees showed intermediate dance durations during the update process, indicating that honey bees highly likely use two memories: (i) a recently acquired navigation experience and (ii) a previously stored flight experience. Double-shift experiments, in which the feeder was moved forward and backward, created an experimental condition in which honey bee foragers did not update dance duration; suggesting the involvement of more complex memory processes. Our behavioral paradigm allows the dissociation of foraging and dance activity and opens the possibility of studying the molecular and neural processes underlying the waggle dance behavior.
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Comunicación Animal , Abejas/fisiología , Navegación Espacial , Animales , Conducta Apetitiva , Memoria EspacialRESUMEN
Rare diseases, defined by their low prevalence, present significant challenges, including delayed detection, expensive treatments, and limited research. This study delves into the genetic basis of two noteworthy rare diseases in Saudi Arabia: Phenylketonuria (PKU) and Spinal Muscular Atrophy (SMA). PKU, resulting from mutations in the phenylalanine hydroxylase (PAH) gene, exhibits geographical variability and impacts intellectual abilities. SMA, characterized by motor neuron loss, is linked to mutations in the survival of motor neuron 1 (SMN1) gene. Recognizing the importance of unveiling signature genomics in rare diseases, we conducted a quantitative study on PAH and SMN1 proteins of multiple organisms by employing various quantitative techniques to assess genetic variations. The derived signature-genomics contributes to a deeper understanding of these critical genes, paving the way for enhanced diagnostics for disorders associated with PAH and SMN1.
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Genómica , Atrofia Muscular Espinal , Fenilalanina Hidroxilasa , Fenilcetonurias , Enfermedades Raras , Proteína 1 para la Supervivencia de la Neurona Motora , Atrofia Muscular Espinal/genética , Fenilcetonurias/genética , Humanos , Fenilalanina Hidroxilasa/genética , Proteína 1 para la Supervivencia de la Neurona Motora/genética , Genómica/métodos , Enfermedades Raras/genética , Mutación , Arabia Saudita/epidemiologíaRESUMEN
Moonlighting proteins, known for their ability to perform multiple, often unrelated functions within a single polypeptide chain, challenge the traditional "one gene, one protein, one function" paradigm. As organisms evolved, their genomes remained relatively stable in size, but the introduction of post-translational modifications and sub-strategies like protein promiscuity and intrinsic disorder enabled multifunctionality. Enzymes, in particular, exemplify this phenomenon, engaging in unrelated processes alongside their primary catalytic roles. This study employs a systematic, quantitative informatics approach to shed light on human moonlighting protein sequences. Phylogenetic analyses of human moonlighting proteins are presented, elucidating the distal-proximal relationships among these proteins based on sequence-derived quantitative features. The findings unveil the captivating world of human moonlighting proteins, urging further investigations in the emerging field of moonlighting proteomics, with the potential for significant contributions to our understanding of multifunctional proteins and their roles in diverse cellular processes and diseases.
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Procesamiento Proteico-Postraduccional , Proteínas , Humanos , Filogenia , Proteínas/química , GenomaRESUMEN
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the rapidly evolving RNA virus behind the COVID-19 pandemic, has spawned numerous variants since its 2019 emergence. The multifunctional Nonstructural protein 14 (NSP14) enzyme, possessing exonuclease and messenger RNA (mRNA) capping capabilities, serves as a key player. Notably, single and co-occurring mutations within NSP14 significantly influence replication fidelity and drive variant diversification. This study comprehensively examines 120 co-mutations, 68 unique mutations, and 160 conserved residues across NSP14 homologs, shedding light on their implications for phylogenetic patterns, pathogenicity, and residue interactions. Quantitative physicochemical analysis categorizes 3953 NSP14 variants into three clusters, revealing genetic diversity. This research underscoresthe dynamic nature of SARS-CoV-2 evolution, primarily governed by NSP14 mutations. Understanding these genetic dynamics provides valuable insights for therapeutic and vaccine development.
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COVID-19 , Exorribonucleasas , SARS-CoV-2 , Proteínas no Estructurales Virales , Humanos , COVID-19/genética , Exorribonucleasas/química , Exorribonucleasas/genética , Exorribonucleasas/metabolismo , Mutación/genética , Pandemias , Filogenia , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , Replicación Viral/genética , Proteínas no Estructurales Virales/metabolismoRESUMEN
Taste is one of the essential senses in providing the organism a faithful representation of the external world. Taste perception is responsible for basic food and drink appraisal and bestows the organism with valuable discriminatory power. Umami and sweet are "good" tastes that promote consumption of nutritive food, whereas bitter and sour are "bad" tastes that alert the organism to toxins and low pH, promoting rejection of foods containing harmful substances. Not every animal has the same sense of taste as humans. Variation in the taste receptor genes contributes to inter and intra organism differences of taste (sweet/bitter) sensation and preferences. Therefore a deeper understanding was needed to comprehend taste perception by various vertebrates and accordingly elucidate a possible proximity among them. In this study, a total 20 Type-1 (sweet) and 189 Type-2 (bitter) taste receptor complete-amino acid sequences were taken from the 20 vertebrate organisms (18 mammalian, 1 Aves, and 1 amphibian). Among 10 primates, 8 including humans were very close based on genomics of taste receptors and rodent organisms viz. the rat and mouse were away from them. This investigation throws light on the similitude and dissimilitude of perception of sweet and bitter taste among 20 different organisms, steered by quantitative analysis of their genomic data. Furthermore, it enlightened that ligand binding affinity of sweet/bitter taste molecules in the taste receptors of any proximal pair of organisms would be similar.
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Papilas Gustativas , Gusto , Humanos , Ratones , Ratas , Animales , Gusto/genética , Biología Computacional , Papilas Gustativas/metabolismo , Percepción del Gusto , Primates , MamíferosRESUMEN
The devastating impact of the ongoing coronavirus disease 2019 (COVID-19) on public health, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has made targeting the COVID-19 pandemic a top priority in medical research and pharmaceutical development. Surveillance of SARS-CoV-2 mutations is essential for the comprehension of SARS-CoV-2 variant diversity and their impact on virulence and pathogenicity. The SARS-CoV-2 open reading frame 10 (ORF10) protein interacts with multiple human proteins CUL2, ELOB, ELOC, MAP7D1, PPT1, RBX1, THTPA, TIMM8B, and ZYG11B expressed in lung tissue. Mutations and co-occurring mutations in the emerging SARS-CoV-2 ORF10 variants are expected to impact the severity of the virus and its associated consequences. In this article, we highlight 128 single mutations and 35 co-occurring mutations in the unique SARS-CoV-2 ORF10 variants. The possible predicted effects of these mutations and co-occurring mutations on the secondary structure of ORF10 variants and host protein interactomes are presented. The findings highlight the possible effects of mutations and co-occurring mutations on the emerging 140 ORF10 unique variants from secondary structure and intrinsic protein disorder perspectives.
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COVID-19/virología , Interacciones Microbiota-Huesped/inmunología , Sistemas de Lectura Abierta , SARS-CoV-2/genética , Proteínas Virales , Humanos , Mutación , Proteínas Virales/genética , Proteínas Virales/inmunologíaRESUMEN
UNLABELLED: This is a comparative study between 60 asphyxiated newborns (cases) and 60 normal neonates (controls) in respect of their plasma glucose and uric acid levels and also their clinical and neurological status. The mean plasma glucose level was significantly lower (35.1 +/- 11.4 mg/dl vs. 56.9 +/- 5.5 mg/dl; P < 0.001) and the mean serum uric acid level was higher (8.0 +/- 1.2 mg/dl vs. 4.5 +/- 0.83 mg/dl; P < 0.001) in the asphyxiated group when compared to the controls. Within the perinatal asphyxia group, the plasma glucose level and Apgar scores showed a significant positive linear correlation (r = 0.740, P < 0.001), whereas a significant negative linear correlation was observed between the glucose level and different stages of hypoxic ischemic encephalopathy (HIE) (r = -0.875, P < 0.001). Although a strong positive linear correlation was found between uric acid and HIE stages (r = 0.734, P < or = 0.001), the linear correlation between uric acid and Apgar scores (r = -0.885, P < 0.001) and uric acid and the plasma glucose level (r = -0.725, P < 0.001) were found to be significantly negative among the cases. CONCLUSION: The severity of encephalopathy and cellular damage varies with the severity of hypoglycemia.
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Puntaje de Apgar , Asfixia Neonatal/fisiopatología , Glucosa/metabolismo , Hipoxia-Isquemia Encefálica/fisiopatología , Ácido Úrico/sangre , Asfixia Neonatal/sangre , Asfixia Neonatal/complicaciones , Femenino , Hospitales , Humanos , Hipoxia-Isquemia Encefálica/sangre , Hipoxia-Isquemia Encefálica/etiología , Recién Nacido , Modelos Lineales , Masculino , Estudios Prospectivos , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
A randomized case control hospital based study was conducted over 12 months time on 31 asphyxiated and 31 normal newborn to see whether urinary uric acid can be used as a marker of perinatal asphyxia and can be correlated with the clinical diagnosis by Apgar score. Uric acid and creatinine were estimated in spot urine within 24 hours after birth in both cases and controls. A ratio between concentrations of uric acid to creatinine was estimated and compared between cases and controls. It was found that the ratios were significantly higher in cases than controls (3.1± 1.3 vs 0.96± 0.54; P < 0.001) and among asphyxia patients, a significant negative linear correlation was found between the uric acid to creatinine ratio and the Apgar score (r = -0.857, P < 0.001). So urinary uric acid to creatinine ratio can be used as an additional non-invasive dispace, easy and at the same time early biochemical marker of birth asphyxia which biochemically supports the clinical diagnosis and severity grading of asphyxia by Apgar score.
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Meaningful words in English need vowels to break up the sounds that consonants make. The Nature has encoded her messages in RNA molecules using only four alphabets A, U, C and G in which the nine member double-ring bases (adenine (A) and Guanine (G)) are purines, while the six member single-ring bases (cytosine (C) and uracil (U)) are pyrimidines. Four bases A, U, C and G of RNA sequences are divided into three kinds of classifications according to their chemical properties. One of the three classifications, the purine-pyrimidine class is important. In understanding the distribution (organization) of purines and pyrimidines over some of the non-coding RNAs, all miRNAs of the three species (human, gorilla and chimpanzee) of Hominidae family and two species (mouse and rat) from of Muridae family are considered. The distribution of purines and pyrimidines over miRNA shows deviation from randomness. Based on the quantitative metrics (fractal dimension, Hurst exponent, Hamming distance, distance pattern of purine-pyrimidine, density distribution of purine-pyrimidine and Shannon entropy) five different clusters have been made for the five species. We have observed some couple of results including the closeness of different clusters among the five species.
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MicroARNs/química , Purinas/análisis , Pirimidinas/análisis , Animales , Gorilla gorilla/genética , Humanos , Ratones , Pan troglodytes/genética , Ratas , Especificidad de la EspecieRESUMEN
We present a comparison of the sugar-elicited search behavior in Drosophila melanogaster and Apis mellifera. In both species, intake of sugar-water elicits a complex of searching responses. The most obvious response was an increase in turning frequency. However, we also found that flies and honey bees returned to the location of the sugar drop. They even returned to the food location when we prevented them from using visual and chemosensory cues. Analyses of the recorded trajectories indicated that flies and bees use two mechanisms, a locomotor pattern involving an increased turning frequency and path integration to increase the probability to stay close or even return to the sugar drop location. However, evidence for the use of path integration in honey bees was less clear. In general, walking trajectories of honey bees showed a higher degree of curvature and were more spacious; two characters which likely masked evidence for the use of path integration in our experiments. Visual cues, i.e., a black dot, presented underneath the sugar drop made flies and honey bees stay closer to the starting point of the search. In honey bees, vertical black columns close to the sugar drop increased the probability to visit similar cues in the vicinity. An additional one trial learning experiment suggested that the intake of sugar-water likely has the potential to initiate an associative learning process. Together, our experiments indicate that the sugar-elicited local search is more complex than previously assumed. Most importantly, this local search behavior appeared to exhibit major behavioral capabilities of large-scale navigation. Thus, we propose that sugar-elicited search behavior has the potential to become a fruitful behavioral paradigm to identify neural and molecular mechanisms involved in general mechanisms of navigation.
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The eigenstate thermalization hypothesis (ETH) provides a way to understand how an isolated quantum mechanical system can be approximated by a thermal density matrix. We find a class of operators in (1+1)-dimensional conformal field theories, consisting of quasiprimaries of the identity module, which satisfy the hypothesis only at the leading order in large central charge. In the context of subsystem ETH, this plays a role in the deviation of the reduced density matrices, corresponding to a finite energy density eigenstate from its hypothesized thermal approximation. The universal deviation in terms of the square of the trace-square distance goes as the eighth power of the subsystem fraction and is suppressed by powers of inverse central charge (c). Furthermore, the nonuniversal deviations from subsystem ETH are found to be proportional to the heavy-light-heavy structure constants which are typically exponentially suppressed in sqrt[h/c], where h is the conformal scaling dimension of the finite energy density state. We also examine the effects of the leading finite-size corrections.
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OBJECTIVE: To study electrolyte status in asphyxiated newborns of different severity in early neonatal period and compare with controls. METHODS: Sodium, potassium and total calcium levels were estimated in the serum samples of asphyxiated newborns of different severity and control group immediately after birth. RESULTS: Mean serum sodium level was significantly lower (122.1 +/- 6.0 mEq/L vs 138.8 +/- 2.7 mEq/L; P < 0.001), mean serum potassium was higher (5.05 +/- 0.63 mEq/L vs 4.19 +/- 0.40 mEq/L; P < 0.001) and mean serum calcium level was found lower (6.85 +/- 0.95 mg/dl vs 9.50 +/- 0.51 mg/dl; P < 0.001) in cases than controls. Among cases, a strong positive linear correlation was found between the serum sodium, serum calcium levels and their Apgar scores, between sodium levels and total calcium levels and significant negative linear correlation between Apgar scores and serum potassium level. CONCLUSION: Among cases, hyponatremia and hypocalcemia developed early and simultaneously and the decrease in their serum levels was directly proportional to each other and to the degree of asphyxia. Though, mean potassium level was within the normal limit, the value was higher among cases than controls and directly proportional to asphyxia.
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Asfixia Neonatal/sangre , Calcio/sangre , Potasio/sangre , Sodio/sangre , Puntaje de Apgar , Estudios de Casos y Controles , Femenino , Humanos , Recién Nacido , MasculinoRESUMEN
OBJECTIVE: Study of uric acid level in spot urine of normal preterm AGA (appropriate for gestational age) babies in day one of their life. METHODS: Spot urine samples were collected from 45 normal preterm neonates within 24 hours of their birth for estimation of uric acid. RESULTS: The mean uric acid level was 36.50 +/- 5.99 mg/dl in normal preterm neonates as compared to 18.40 +/- 0.45 mg/dl in normal term babies (documented in another study) (p < 0.001). Also a significant negative linear correlation between body weight and urinary uric acid level was found {r (correlation coefficient) = - 0.970, P (probability) < 0.001 }. CONCLUSION: Higher mean uric acid level was found in spot urine samples of preterm normal neonates than that of normal term babies on day one. Further, urinary uric acid levels were found inversely proportional to the body weight or to the gestational age (as they are AGA) of the babies.