Two-Year Results of a Five-Year Personalized Integrative Obesity Coaching Program (IBO) Based upon a Systems Health Perspective and an Evolutionary Longitudinal Study Approach.

This study presents the outcomes of a 5-year personalized integrative coaching program for adults with obesity (body mass index BMI ≥ 30 kg/m2), based upon a systems health perspective, during the first 2 years. This longitudinal study, which had an evolutionary design, included all adults who enrolled in the program. Health-related quality of life (HRQoL) was measured with the Short Form-36 (SF-36), and physical outcomes included weight, waist circumference, aerobic capacity, lipid profile, and HbA1c. Subsequently, participants completed questionnaires (e.g., the Symptom Checlist-90 (SCL-90) and the Checklist Individual Strength (CIS)). Seventy-nine adults with a mean BMI of 39.5 kg/m2 (SD 5.3) were included. Forty-four participants completed 2 years in the program. Compared to baseline, there were significant improvements in the SF-36 subscales 'physical functioning' (MD 9.9 points, 95% CI: 2.1-17.5, p = 0.013) and 'general health perceptions' (MD 9.3 points, 95% CI 2.9-15.7, p = 0.006). Furthermore, significant improvements in physical outcomes and psychosocial questionnaires (e.g., weight loss (MD 3.5 kg, 95% CI: 1.2-5.7, p = 0.003), waist circumference (MD 5.1 cm, 95% CI: 2.4-7.8, p < 0.001), and CIS fatigue (MD 6.8, 95% CI: 3.1-10.5, p = 0.001) were observed. This study highlights the importance of a systems health perspective supporting the development of a personalized integrative coaching program for adults with obesity in a 'real-world' setting.

Systematic Exploration of SARS-CoV-2 Adaptation to Vero E6, Vero E6/TMPRSS2, and Calu-3 Cells.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread globally, and scientists around the world are currently studying the virus intensively in order to fight against the on-going pandemic of the virus. To do so, SARS-CoV-2 is typically grown in the lab to generate viral stocks for various kinds of experimental investigations. However, accumulating evidence suggests that such viruses often undergo cell culture adaptation. Here, we systematically explored cell culture adaptation of two SARS-CoV-2 variants, namely the B.1.36.16 variant and the AY.30 variant, a sub lineage of the B.1.617.2 (Delta) variant, propagated in three different cell lines, including Vero E6, Vero E6/TMPRSS2, and Calu-3 cells. Our analyses detected numerous potential cell culture adaptation changes scattering across the entire virus genome, many of which could be found in naturally circulating isolates. Notable ones included mutations around the spike glycoprotein's multibasic cleavage site, and the Omicron-defining H655Y mutation on the spike glycoprotein, as well as mutations in the nucleocapsid protein's linker region, all of which were found to be Vero E6-specific. Our analyses also identified deletion mutations on the non-structural protein 1 and membrane glycoprotein as potential Calu-3-specific adaptation changes. S848C mutation on the non-structural protein 3, located to the protein's papain-like protease domain, was also identified as a potential adaptation change, found in viruses propagated in all three cell lines. Our results highlight SARS-CoV-2 high adaptability, emphasize the need to deep-sequence cultured viral samples when used in intricate and sensitive biological experiments, and illustrate the power of experimental evolutionary study in shedding lights on the virus evolutionary landscape.

Compositional features and pattern of codon usage for mitochondrial CO genes among reptiles.

The phenomenon of non-random occurrence of synonymous nucleotide triplets (codons) in the coding sequences of genes is the codon usage bias (CUB). In this study, we used bioinformatic tool kit to analyze the compositional pattern and CUB of mitogenes namely COI, COII and COIII across different orders of reptiles. Estimation of overall base composition in the protein-coding sequences of COI, COII and COIII genes of the reptilian orders revealed an uneven usage of nucleotides. The overall count of A nucleotide was found to be the highest while the overall count of G nucleotide was the least. The CO genes across the three reptilian orders were prominently AT biased. Comparison of the GC proportion at each codon position displayed that GC1 percentage ranked the highest in all the three CO genes of the reptilian orders. SCUO values indicated weaker CUB, while considerable variation of SCUO values existed in the three CO genes across the studied reptiles. Relative synonymous codon usage (RSCU) values indicated that mostly the A ending codons were preferred. Based on the parameters namely neutrality plot, mutational responsive index and translational selection, we could conclude that natural selection was the major evolutionary force in COI, COII and COIII genes in the studied reptilian orders. However, correspondence analysis, parity plot and correlation studies indicated the existence of mutation pressure as well on the CO genes.

A Holistic Evolutionary and 3D Pharmacophore Modelling Study Provides Insights into the Metabolism, Function, and Substrate Selectivity of the Human Monocarboxylate Transporter 4 (hMCT4).

Monocarboxylate transporters (MCTs) are of great research interest for their role in cancer cell metabolism and their potential ability to transport pharmacologically relevant compounds across the membrane. Each member of the MCT family could potentially provide novel therapeutic approaches to various diseases. The major differences among MCTs are related to each of their specific metabolic roles, their relative substrate and inhibitor affinities, the regulation of their expression, their intracellular localization, and their tissue distribution. MCT4 is the main mediator for the efflux of L-lactate produced in the cell. Thus, MCT4 maintains the glycolytic phenotype of the cancer cell by supplying the molecular resources for tumor cell proliferation and promotes the acidification of the extracellular microenvironment from the co-transport of protons. A promising therapeutic strategy in anti-cancer drug design is the selective inhibition of MCT4 for the glycolytic suppression of solid tumors. A small number of studies indicate molecules for dual inhibition of MCT1 and MCT4; however, no selective inhibitor with high-affinity for MCT4 has been identified. In this study, we attempt to approach the structural characteristics of MCT4 through an in silico pipeline for molecular modelling and pharmacophore elucidation towards the identification of specific inhibitors as a novel anti-cancer strategy.

Evolutionary study of COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as an emerging coronavirus: Phylogenetic analysis and literature review.

Since emerging coronaviruses have always become a human health concern globally especially severe acute respiratory syndrome coronavirus 2 (SARS-CoV) and Middle East respiratory syndrome coronavirus and a novel coronavirus was introduced in Wuhan, China, in December 2019 (called SARS-CoV-2), many researchers focused on its epidemics, virological and clinical features. SARS-CoV-2 is classified as Betacoronaviruses genus and Sarbecovirus subgenus (lineage B). The virus shows a great similarity with SARS-CoV and bat SARS-like coronaviruses. In this study, we evaluate SARS-CoV-2 virus phylogeny and evolution by using current virus and related sequences.

Photosynthetic and transcriptomic responses of two C4 grass species with different NaCl tolerance.

This report reveals the effects of salt on the photosynthetic electron transport and transcriptome of the glycophyte Setaria viridis (S. viridis) and its salt-tolerant close relative halophyte Spartina alterniflora (S. alterniflora). S. viridis was unable to survive exposed to sodium chloride (NaCl) levels higher than 100 mM, in contrast, S. alterniflora could tolerate NaCl up to 550 mM, with negligible effect on gas exchange related parameters and conductance of electrons transport chain (gETC). Under salt, the prompt fluorescence (OJIP-curves) exhibits an increase in the O- and J-steps in S. viridis and much less for S. alterniflora. Flowing NaCl stress, a dramatic decline in the photosystem II (PSII) primary photochemistry was observed for S. viridis, as reflected by the drastic drop in Fv/Fm, Fv/Fo and ΦPSII; however, no substantial change was recorded for these parameters in S. alterniflora. Interestingly, we found an increase in the primary PSII photochemistry (ΦPSII) for S. alterniflora with increasing either NaCl concentration or NaCl treatment duration. The NPQ magnitude was strongly enhanced for S. viridis even at a low NaCl (50 mM); however, it remains unchangeable or slightly increased for S. alterniflora at NaCl levels above 400 mM. After NaCl treatment, we found an increase in both the proportion of oxidized P700 and the amount of active P700 in S. viridis and almost no change for S. alterniflora. Under salt, the net photosynthetic rate (A) and stomatal conductance (gs) measurements demonstrate that A decreases earlier in S. viridis, even after one week exposure to only 50 mM NaCl; in contrast, in S. alterniflora, the effect of NaCl on A and gs was minor even after exposure for two weeks to high NaCl levels. For S. viridis exposed to 50 mM NaCl for 12 d, carbon dioxide (CO2) at a concentration of 2000 µL L-1 could not fully restore A to the control (Ctrl) level. Conversely, in S. alterniflora, high CO2 can fully restore A for all NaCl treatments except at 550 mM. RNA-seq data shows a major impact of NaCl on metabolic pathways in S. viridis and we found a number of transcription factors potentially related to NaCl responses. For S. alterniflora, no major changes in the transcriptomic levels were recorded under NaCl stress. To confirm our data analysis of RNA-seq, we performed quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis for randomly selected four genes for each species (8 genes in total) and we found that our results (up- and/or down-regulated genes) are fully consistent and match well our RNA-seq data. Overall, this study showed drastically different photosynthetic and transcriptomic responses of a salt-tolerant C4 grass species and one salt-sensitive C4 grass species to NaCl stress, which suggests that S. alterniflora could be used as a promising model species to study salt tolerance in C4 or monocot species.

NeoCoV Is Closer to MERS-CoV than SARS-CoV.

Recently, Coronavirus has been given considerable attention from the biomedical community based on the emergence and isolation of a deadly coronavirus infecting human. To understand the behavior of the newly emerging MERS-CoV requires knowledge at different levels (epidemiologic, antigenic, and pathogenic), and this knowledge can be generated from the most related viruses. In this study, we aimed to compare between 3 species of Coronavirus, namely Middle East Respiratory Syndrome (MERS-CoV), Severe Acute Respiratory Syndrome (SARS-CoV), and NeoCoV regarding whole genomes and 6 similar proteins (E, M, N, S, ORF1a, and ORF1ab) using different bioinformatics tools to provide a better understanding of the relationship between the 3 viruses at the nucleotide and amino acids levels. All sequences have been retrieved from National Center for Biotechnology Information (NCBI). Regards to target genomes' phylogenetic analysis showed that MERS and SARS-CoVs were closer to each other compared with NeoCoV, and the last has the longest relative time. We found that all phylogenetic methods in addition to all parameters (physical and chemical properties of amino acids such as the number of amino acid, molecular weight, atomic composition, theoretical pI, and structural formula) indicated that NeoCoV proteins were the most related to MERS-CoV one. All phylogenetic trees (by both maximum-likelihood and neighbor-joining methods) indicated that NeoCoV proteins have less evolutionary changes except for ORF1a by just maximum-likelihood method. Our results indicated high similarity between viral structural proteins which are responsible for viral infectivity; therefore, we expect that NeoCoV sooner may appear in human-related infection.

Epidemiological and molecular analysis of avian influenza A(H7N9) virus in Shanghai, China, 2013-2017.

BACKGROUND: Human infections with a novel avian influenza A virus (H7N9) were reported in Shanghai municipality, China, at the beginning of 2013. High-pathogenic avian influenza (HPAI) H7N9 virus emerged in late February 2017 along with existing low-pathogenic avian influenza (LPAI) H7N9 virus, and this has the potential to develop into a pandemic that could be harmful to humans. METHODS: To elucidate the epidemiological characteristics of H7N9-infected cases from 2013 to 2017 in Shanghai, data on the 59 laboratory-confirmed human cases and 26 bird and environmental contamination cases were collected from the WHO website and Food and Agriculture Organization Emergency Prevention System for Animal Health (FAO EMPRES-AH). Full-length sequences of H7N9 viruses that emerged in Shanghai were collected from the Global Initiative on Sharing Avian Influenza Data to analyze the evolutionary and genetic features. RESULTS: We found that genetically different strains emerged in every epidemic in Shanghai, and most of the circulating H7N9 strains had affinity to human-type receptors, with the characteristics of high-virulence and low-pathogenic influenza viruses. Furthermore, our findings suggest that the Shanghai chicken strains are closely related to the HPAI H7N9 virus A/Guangdong/17SF003/2016, indicating that this viral strain is of avian origin and generated from the LPAI H7N9 viruses in Shanghai. The gradual decrease in H7N9 human infection in Shanghai was probably due to the control measures taken by the Shanghai government and the enhanced public awareness leading to a reduced risk of H7N9 virus infection. However, LPAI H7N9 viruses from poultry and environmental samples were continually detected in Shanghai across the epidemics, increasing the risk of new emerging H7N9 outbreaks. CONCLUSION: It is important to consistently obtain sufficient surveillance data and implement prevention measures against H7N9 viruses in Shanghai municipality.

Quando os estudantes falam sobre os problemas de aprendizagem: um estudo psicogenético / When students talk about learning problems: a psychogenetic study / Cuando los estudiantes hablan de los problemas de aprendizaje: un estudio psicogenético

Considerando a teoria piagetiana e os estudos sobre a construção do conhecimento social, investigaram-se as ideias de estudantes sobre a aprendizagem e a não aprendizagem. Participaram 40 escolares de 6 a 16 anos, com queixas de dificuldades de aprendizagem, matriculados em escolas públicas no interior do Estado de São Paulo e submetidos a dois instrumentos: um desenho em que retratavam uma pessoa que aprende e outra que não aprende; e uma história envolvendo uma situação de não aprendizagem. Os dados obtidos apontam crenças bastante específicas construídas pela maioria dos participantes, correspondentes ao nível mais elementar de compreensão da realidade social. Suas interpretações desconsideram processos mais complexos para o fenômeno investigado e se centram em questões aparentes. Os resultados corroboram os estudos evolutivos realizados no contexto nacional, apontando ideias rudimentares, mesmo em sujeitos mais velhos. Sugere-se a necessidade de estudos que expliquem as causas desse atraso entre estudantes brasileiros.

Considering Piaget’s theory and studies on the social construction of know­ledge, we investigated the ideas of students about learning and not learning. The study included 40 children between 6 and 16 years old with complaints of learning difficulties, enrolled in public schools in the state of São Paulo and subjected to two instruments: a drawing depicting a person who learns and does not learn another; a story involving a situation of not learning. The data indicate quite specific beliefs constructed by most participants, corresponding to the most basic level of understanding of social reality. His interpretations disregard more complex processes for the investigated phenomenon and focus on apparent issues. The results corroborate the evolutionary studies in the national context, pointing rudimentary ideas, even in older subjects. We suggest the need for studies to explain the causes of this delay between brazilian students.

Teniendo en cuenta la teoría de Piaget y los estudios sobre la construcción del conocimiento social, hemos investigado las ideas de los estudiantes acerca del aprendizaje y no aprendizaje. El estudio incluyó a 40 niños entre 6 y 16 años con quejas de dificultades de aprendizaje, inscritos en escuelas públicas en el estado de São Paulo y sometidos a dos instrumentos: un dibujo que representa a una persona que aprende y outra que no se aprende; una historia que implica una situación de no aprendizaje. Los datos indican que hay creencias bastante específicas construidas por la mayoría de los participantes, correspondientes al nivel más básico de comprensión de la realidad social. Sus interpretaciones hacen caso omiso de procesos más complejos para el fenómeno investigado y consideran solamente problemas aparentes. Los resultados corroboran los estudios evolutivos en el contexto nacional, apuntando ideas rudimentarias, incluso en estudiantes mayores. Sugerimos la necesidad de estudios sobre las causas de este retraso entre los estudiantes brasileños.

3D molecular modeling and evolutionary study of the Trypanosoma brucei DNA Topoisomerase IB, as a new emerging pharmacological target.

In the present study, an outline is proposed that may lead to specific drug design targeting of the Trypanosoma brucei DNA Topoisomerase IB. In this direction, an unequivocally specific platform was designed for the development of selective modulators. The designed platform is focused on the unique structural and catalytic features of the enzyme. Extensive phylogenetic analysis based on all available published genomes indicated a broad distribution of DNA topoisomerases across eukaryotic species and revealed structurally important amino acids which could be assigned as potentially strong contributors to the regulation of the mechanism of the T. brucei DNA Topoisomerase IB. Based on the above, we propose a comprehensive in silico 3D model for the structure of the T. brucei DNA Topoisomerase IB. Our approach provides an efficient intergraded platform with both evolutionary and structural insights for the rational design of pharmacophore models as well as novel modulators as the anti-T. brucei DNA Topoisomerase IB agents with therapeutic potential.