Detection of an intermediate during the unfolding process of the dimeric ketosteroid isomerase

AbstractFailure to detect the intermediate in spite of its existence often leads to the conclusion that two-state transition in the unfolding process of the protein can be justified. In contrast to the previous equilibrium unfolding experiment fitted to a two-state model by circular dichroism and fluorescence spectroscopies, an equilibrium unfolding intermediate of a dimeric ketosteroid isomerase (KSI) could be detected by small angle X-ray scattering (SAXS) and analytical ultracentrifugation. The sizes of KSI were determined to be 18.7Å in 0M urea, 17.3Å in 5.2M urea, and 25.1Å in 7M urea by SAXS. The size of KSI in 5.2M urea was significantly decreased compared with those in 0M and 7M urea, suggesting the existence of a compact intermediate. Sedimentation velocity as obtained by ultracentrifugation confirmed that KSI in 5.2M urea is distinctly different from native and fully-unfolded forms. The sizes measured by pulse field gradient nuclear magnetic resonance (NMR) spectroscopy were consistent with those obtained by SAXS. Discrepancy of equilibrium unfolding studies between size measurement methods and optical spectroscopies might be due to the failure in detecting the intermediate by optical spectroscopic methods. Further characterization of the intermediate using 1H NMR spectroscopy and Kratky plot supported the existence of a partially-folded form of KSI which is distinct from those of native and fully-unfolded KSIs. Taken together, our results suggest that the formation of a compact intermediate should precede the association of monomers prior to the dimerization process during the folding of KSI

Nasopharyngeal carriage of Streptococcus pneumoniae in children under 5 years of age before introduction of pneumococcal vaccine (PCV10) in urban and rural districts in Pakistan

Background: Benefits of pneumococcal conjugate vaccine programs have been linked to the vaccine’s ability to disrupt nasopharyngeal carriage and transmission. The 10-valent pneumococcal vaccine (PCV10) was included in the Expanded Program on Immunization (EPI) in Sindh, Pakistan in February 2013. This study was carried out immediately before PCV10 introduction to establish baseline pneumococcal carriage and prevalent serotypes in young children and to determine if carriage differed in urban and rural communities.Methods: Nasopharyngeal specimens were collected from a random sample of children 3-11 and 12-59 months of age in an urban community (Karachi) and children 3-11 months of age in a rural community (Matiari). Samples were processed in a research laboratory in Karachi. Samples were transported in STGG media, enriched in Todd Hewitt broth, rabbit serum and yeast extract, cultured on 5% sheep blood agar, and serotyped using the CDC standardized sequential multiplex PCR assay. Serotypes were categorized into PCV10-type and non-vaccine types.Results: We enrolled 670 children. Pneumococci were detected in 73.6% and 79.5 % of children in the infant group in Karachi and Matiari, respectively, and 78.2% of children 12 to 59 months of age in Karachi. In infants, 38. 9% and 33.5% of those carrying pneumococci in Karachi and Matiari, respectively, had PCV10 types. In the older age group in Karachi, the proportion was 30.7%, not significantly different from infants. The most common serotypes were 6A, 23F, 19A, 6B and 19F.Conclusion: We found that about 3 of 4 children carried pneumococci, and this figure did not vary with age group or urban or rural residence. Planned annual surveys in the same communities will inform change in carriage of PCV10 serotype pneumococci after the introduction and uptake of PCV10 in these communitie

The roles of immune cells in bone healing; what we know, do not know and future perspectives

Key events occurring during the bone healing include well-orchestrated and complex interactions between immune cells, multipotential stromal cells (MSCs), osteoblasts and osteoclasts. Through three overlapping phases of this physiological process, innate and adaptive immune cells, cytokines and chemokines have a significant role to play. The aim of the escalating immune response is to achieve an osseous healing in the shortest time and with the least complications facilitating the restoration of function. The uninterrupted progression of these biological events in conjunction with a favourable mechanical environment (stable fracture fixation) remains the hallmark of successful fracture healing. When failure occurs, either the biological environment or the mechanical one could have been disrupted. Not infrequently both may be compromised. Consequently, regenerative treatments involving the use of bone autograft, allograft or synthetic matrices supplemented with MSCs are increasingly used. A better understanding of the bone biology and osteoimmunology can help to improve these evolving cell-therapy based strategies. Herein, an up to date status of the role of immune cells during the different phases of bone healing is presented. Additionally, the known and yet to know events about immune cell interactions with MSCs and osteoblasts and osteoclasts and the therapeutic implications are being discussed

A Worldwide Test of the Predictive Validity of Ideal Partner Preference-Matching

©American Psychological Association, [2024]. This paper is not the copy of record and may not exactly replicate the authoritative document published in the APA journal. The final article is available, upon publication, at: [ARTICLE DOI]”Ideal partner preferences (i.e., ratings of the desirability of attributes like attractiveness or intelligence) are the source of numerous foundational findings in the interdisciplinary literature on human mating. Recently, research on the predictive validity of ideal partner preference-matching (i.e., do people positively evaluate partners who match versus mismatch their ideals?) has become mired in several problems. First, articles exhibit discrepant analytic and reporting practices. Second, different findings emerge across laboratories worldwide, perhaps because they sample different relationship contexts and/or populations. This registered report—partnered with the Psychological Science Accelerator—uses a highly powered design (N=10,358) across 43 countries and 22 languages to estimate preference-matching effect sizes. The most rigorous tests revealed significant preference-matching effects in the whole sample and for partnered and single participants separately. The “corrected pattern metric” that collapses across 35 traits revealed a zero-order effect of β=.19 and an effect of β=.11 when included alongside a normative preference-matching metric. Specific traits in the “level metric” (interaction) tests revealed very small (average β=.04) effects. Effect sizes were similar for partnered participants who reported ideals before entering a relationship, and there was no consistent evidence that individual differences moderated any effects. Comparisons between stated and revealed preferences shed light on gender differences and similarities: For attractiveness, men’s and (especially) women’s stated preferences underestimated revealed preferences (i.e., they thought attractiveness was less important than it actually was). For earning potential, men’s stated preferences underestimated—and women’s stated preferences overestimated—revealed preferences. Implications for the literature on human mating are discussed.Unfunde

Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017

A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4% (62.3 (55.1–70.8) million) to 6.4% (58.3 (47.6–70.7) million), but is predicted to remain above the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025. Prevalence of overweight increased from 5.2% (30 (22.8–38.5) million) in 2000 to 6.0% (55.5 (44.8–67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic

A living WHO guideline on drugs for covid-19

CITATION: Agarwal, A. et al. 2022. A living WHO guideline on drugs for covid-19. British Medical Journal, 370. doi:10.1136/bmj.m3379The original publication is available at https://jcp.bmj.com/This living guideline by Arnav Agarwal and colleagues (BMJ 2020;370:m3379, doi:10.1136/bmj.m3379) was last updated on 22 April 2022, but the infographic contained two dosing errors: the dose of ritonavir with renal failure should have read 100 mg, not 50 mg; and the suggested regimen for remdesivir should have been 3 days, not 5-10 days. The infographic has now been corrected.Publishers versio

Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017

A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4 (62.3 (55.1�70.8) million) to 6.4 (58.3 (47.6�70.7) million), but is predicted to remain above the World Health Organization�s Global Nutrition Target of <5 in over half of LMICs by 2025. Prevalence of overweight increased from 5.2 (30 (22.8�38.5) million) in 2000 to 6.0 (55.5 (44.8�67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic. © 2020, The Author(s)

Author Correction: Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017 (Nature Medicine, (2020), 26, 5, (750-759), 10.1038/s41591-020-0807-6)

An amendment to this paper has been published and can be accessed via a link at the top of the paper. © 2020, The Author(s)