Browsing by Subject "Disorder"

Now showing 1 - 6 of 6
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    A Study on the Nature of SARS-CoV-2 Using the Shell Disorder Models: Reproducibility, Evolution, Spread, and Attenuation
    (MDPI, 2022-09-23) Goh, Gerard Kian-Meng; Dunker, A. Keith; Foster, James A.; Uversky, Vladimir N.; Biochemistry and Molecular Biology, School of Medicine
    The basic tenets of the shell disorder model (SDM) as applied to COVID-19 are that the harder outer shell of the virus shell (lower PID-percentage of intrinsic disorder-of the membrane protein M, PIDM) and higher flexibility of the inner shell (higher PID of the nucleocapsid protein N, PIDN) are correlated with the contagiousness and virulence, respectively. M protects the virion from the anti-microbial enzymes in the saliva and mucus. N disorder is associated with the rapid replication of the virus. SDM predictions are supported by two experimental observations. The first observation demonstrated lesser and greater presence of the Omicron particles in the lungs and bronchial tissues, respectively, as there is a greater level of mucus in the bronchi. The other observation revealed that there are lower viral loads in 2017-pangolin-CoV, which is predicted to have similarly low PIDN as Omicron. The abnormally hard M, which is very rarely seen in coronaviruses, arose from the fecal-oral behaviors of pangolins via exposure to buried feces. Pangolins provide an environment for coronavirus (CoV) attenuation, which is seen in Omicron. Phylogenetic study using M shows that COVID-19-related bat-CoVs from Laos and Omicron are clustered in close proximity to pangolin-CoVs, which suggests the recurrence of interspecies transmissions. Hard M may have implications for long COVID-19, with immune systems having difficulty degrading viral proteins/particles.
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    Catalytic Contribution of Threonine 244 in Human ALDH2
    (Elsevier, 2013) González-Segura, Lilian; Ho, K.-K.; Perez-Miller, Samantha; Weiner, Henry; Hurley, Thomas D.; Biochemistry and Molecular Biology, School of Medicine
    Amongst the numerous conserved residues in the aldehyde dehydrogenase superfamily, the precise role of Thr-244 remains enigmatic. Crystal structures show that this residue lies at the interface between the coenzyme-binding and substrate-binding sites with the side chain methyl substituent oriented toward the B-face of the nicotinamide ring of the NAD(P)(+) coenzyme, when in position for hydride transfer. Site-directed mutagenesis in ALDH1A1 and GAPN has suggested a role for Thr-244 in stabilizing the nicotinamide ring for efficient hydride transfer. Additionally, these studies also revealed a negative effect on cofactor binding which is not fully explained by the interaction with the nicotinamide ring. However, it is suggestive that Thr-244 immediately precedes helix αG, which forms one-half of the primary binding interface for the coenzyme. Hence, in order to more fully investigate the role of this highly conserved residue, we generated valine, alanine, glycine and serine substitutions for Thr-244 in human ALDH2. All four substituted enzymes exhibited reduced catalytic efficiency toward substrate and coenzyme. We also determined the crystal structure of the T244A enzyme in the absence and presence of coenzyme. In the apo-enzyme, the alpha G helix, which is key to NAD binding, exhibits increased temperature factors accompanied by a small displacement toward the active site cysteine. This structural perturbation was reversed in the coenzyme-bound complex. Our studies confirm a role for the Thr-244 beta methyl in the accurate positioning of the nicotinamide ring for efficient catalysis. We also identify a new role for Thr-244 in the stabilization of the N-terminal end of helix αG. This suggests that Thr-244, although less critical than Glu-487, is also an important contributor toward coenzyme binding.
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    Cerebral malaria is associated with long-term mental health disorders: a cross sectional survey of a long-term cohort
    (Springer (Biomed Central Ltd.), 2016) Idro, Richard; Kakooza-Mwesige, Angelina; Asea, Benjamin; Ssebyala, Keron; Bangirana, Paul; Opoka, Robert O.; Lubowa, Samson K.; Semrud-Clikeman, Margaret; John, Chandy C.; Nalugya, Joyce; Department of Pediatrics, IU School of Medicine
    BACKGROUND: Cerebral malaria (CM) and severe malarial anaemia (SMA) are associated with neuro-developmental impairment in African children, but long-term mental health disorders in these children are not well defined. METHODS: A cohort of children previously exposed to CM (n = 173) or SMA (n = 99) had neurologic assessments performed and screening for behaviour difficulties using the Strengths and Difficulties Questionnaire (SDQ) a median of 21 months after the disease episode. These findings were compared to concurrently recruited community children (CC, n = 108). Participants with SDQ total difficulties score ≥ 17 had a mental health interview with the child and adolescent version of the Mini-International Neuropsychiatric Interview (MINI-KID) and a sample had brain magnetic resonance imaging (MRI). RESULTS: Fifty-five children had SDQ score ≥ 17. On the MINI-KID, these children were classified as having no difficulties (n = 18), behaviour difficulties only (n = 13) or a mental health disorder (n = 24). Behaviour difficulties were seen in similar frequencies in CM (3.5%), SMA (4.0%) and CC (2.8%). In contrast, mental health disorders were most frequent in CM (10.4%), followed by SMA (4.0%) and CC (1.8%). Externalizing disorders (conduct, oppositional defiance and attention deficit hyperactivity) were the most common mental health disorders. The median total coma duration was 72 (IQR 36.0-115.0) h in patients with mental health disorders compared to 48 (IQR 28.5-78.7) h in those without, p = 0.039. Independent risk factors for mental health disorder included neurologic deficit at discharge (OR 4.09 (95% CI 1.60, 10.5) and seizure recurrences during hospitalization, (OR 2.80, 95% CI 1.13, 6.97). Brain MRI findings consistent with small vessel ischaemic neural injury was seen in over half of these children. CONCLUSIONS: Cerebral malaria may predispose children to mental health disorders, possibly as a consequence of ischaemic neural injury. There is urgent need for programmes of follow-up, diagnosis and interventions for these children.
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    Recovering from Substance Use Disorders: A Case for Peer Recovery Coaches
    (The Center for Health Policy, 2019-01-01) Jacinto, Corey; Greene, Marion S.
    Peer recovery coaches (PRCs) are resources that are being increasingly utilized in the treatment of substance use disorders (SUDs). The role of a PRC is to act as mentor, guide, and role model to those with an SUD by providing a range of support services. The overall body of evidence suggests that PRCs can be effective; however, barriers to the widespread utilization of the peer-recovery approach still exist.
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    Substance Abuse in Indiana: An Urban-Rural Perspective
    (The Center for Health Policy, 2017-06-01) Kooreman, Harold E.; Greene, Marion S.
    The use of alcohol and drugs is a significant public health problem in the United States. Indiana, like many other states in the nation, is lacking in substance abuse treatment services and rural areas are particularly underserved. Rural residents may encounter additional barriers to receiving substance abuse treatment, including stigma, fear that they may know their treatment providers, a lack of access to specialized services, inferior quality of care, and having to pay more for treatment.
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    Veiled symmetry of disordered Parity-Time lattices: protected PT-threshold and the fate of localization
    (Nature Publishing Group, 2018-01-08) Harter, Andrew K.; Assogba Onanga, Franck; Joglekar, Yogesh N.; Physics, School of Science
    Open, non-equilibrium systems with balanced gain and loss, known as parity-time ([Formula: see text])-symmetric systems, exhibit properties that are absent in closed, isolated systems. A key property is the [Formula: see text]-symmetry breaking transition, which occurs when the gain-loss strength, a measure of the openness of the system, exceeds the intrinsic energy-scale of the system. We analyze the fate of this transition in disordered lattices with non-Hermitian gain and loss potentials ±iγ at reflection-symmetric sites. Contrary to the popular belief, we show that the [Formula: see text]-symmetric phase is protected in the presence of a periodic disorder which leads to a positive [Formula: see text]-symmetry breaking threshold. We uncover a veiled symmetry of such disordered systems that is instrumental for the said protection, and show that this symmetry leads to new localization behavior across the [Formula: see text]-symmetry breaking transition. We elucidate the interplay between such localization and the [Formula: see text]-symmetry breaking phenomena in disordered [Formula: see text]-symmetric lattices, with Hermitian disorder or gain-loss disorder, and support our conclusions with a beampropagation- method analysis. Our theoretical predictions provide avenues for experimental realizations of -symmetric systems with engineered disorder.