Seeding activity of human superoxide dismutase 1 aggregates in familial and sporadic amyotrophic lateral sclerosis postmortem neural tissues by real-time quaking-induced conversion.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease with average lifespan of 2-5 years after diagnosis. The identification of novel prognostic and pharmacodynamic biomarkers are needed to facilitate therapeutic development. Metalloprotein human superoxide dismutase 1 (SOD1) is known to accumulate and form aggregates in patient neural tissue with familial ALS linked to mutations in their SOD1 gene. Aggregates of SOD1 have also been detected in other forms of ALS, including the sporadic form and the most common familial form linked to abnormal hexanucleotide repeat expansions in the Chromosome 9 open reading frame 72 (C9ORF72) gene. Here, we report the development of a real-time quaking-induced conversion (RT-QuIC) seed amplification assay using a recombinant human SOD1 substrate to measure SOD1 seeding activity in postmortem spinal cord and motor cortex tissue from persons with different ALS etiologies. Our SOD1 RT-QuIC assay detected SOD1 seeds in motor cortex and spinal cord dilutions down to 10-5. Importantly, we detected SOD1 seeding activity in specimens from both sporadic and familial ALS cases, with the latter having mutations in either their SOD1 or C9ORF72 genes. Analyses of RT-QuIC parameters indicated similar lag phases in spinal cords of sporadic and familial ALS patients, but higher ThT fluorescence maxima by SOD1 familial ALS specimens and sporadic ALS thoracic cord specimens. For a subset of sporadic ALS patients, motor cortex and spinal cords were examined, with seeding activity in both anatomical regions. Our results suggest SOD1 seeds are in ALS patient neural tissues not linked to SOD1 mutation, suggesting that SOD1 seeding activity may be a promising biomarker, particularly in sporadic ALS cases for whom genetic testing is uninformative.

Identifying Paucisymptomatic or Asymptomatic and Unrecognized Ebola Virus Disease Among Close Contacts Based on Exposure Risk Assessments and Screening Algorithms.

BACKGROUND: There is limited evidence to evaluate screening algorithms with rapid antigen testing and exposure assessments as identification strategies for paucisymptomatic or asymptomatic Ebola virus (EBOV) infection and unrecognized EBOV disease (EVD). METHODS: We used serostatus and self-reported postexposure symptoms from a cohort study to classify contact-participants as having no infection, paucisymptomatic or asymptomatic infection, or unrecognized EVD. Exposure risk was categorized as low, intermediate, or high. We created hypothetical scenarios to evaluate the World Health Organization (WHO) case definition with or without rapid diagnostic testing (RDT) or exposure assessments. RESULTS: This analysis included 990 EVD survivors and 1909 contacts, of whom 115 (6%) had paucisymptomatic or asymptomatic EBOV infection, 107 (6%) had unrecognized EVD, and 1687 (88%) were uninfected. High-risk exposures were drivers of unrecognized EVD (adjusted odds ratio, 3.5 [95% confidence interval, 2.4-4.9]). To identify contacts with unrecognized EVD who test negative by the WHO case definition, the sensitivity was 96% with RDT (95% confidence interval, 91%-99%), 87% with high-risk exposure (82%-92%), and 97% with intermediate- to high-risk exposures (93%-99%). The proportion of false-positives was 2% with RDT and 53%-93% with intermediate- and/or high-risk exposures. CONCLUSION: We demonstrated the utility and trade-offs of sequential screening algorithms with RDT or exposure risk assessments as identification strategies for contacts with unrecognized EVD.

Risk Factors for Ebola Virus Persistence in Semen of Survivors in Liberia.

BACKGROUND: Long-term persistence of Ebola virus (EBOV) in immunologically privileged sites has been implicated in recent outbreaks of Ebola virus disease (EVD) in Guinea and the Democratic Republic of Congo. This study was designed to understand how the acute course of EVD, convalescence, and host immune and genetic factors may play a role in prolonged viral persistence in semen. METHODS: A cohort of 131 male EVD survivors in Liberia were enrolled in a case-case study. "Early clearers" were defined as those with 2 consecutive negative EBOV semen test results by real-time reverse-transcription polymerase chain reaction (rRT-PCR) ≥2 weeks apart within 1 year after discharge from the Ebola treatment unit or acute EVD. "Late clearers" had detectable EBOV RNA by rRT-PCR >1 year after discharge from the Ebola treatment unit or acute EVD. Retrospective histories of their EVD clinical course were collected by questionnaire, followed by complete physical examinations and blood work. RESULTS: Compared with early clearers, late clearers were older (median, 42.5 years; P < .001) and experienced fewer severe clinical symptoms (median 2, P = .006). Late clearers had more lens opacifications (odds ratio, 3.9 [95% confidence interval, 1.1-13.3]; P = .03), after accounting for age, higher total serum immunoglobulin G3 (IgG3) titers (P = .005), and increased expression of the HLA-C*03:04 allele (0.14 [.02-.70]; P = .007). CONCLUSIONS: Older age, decreased illness severity, elevated total serum IgG3 and HLA-C*03:04 allele expression may be risk factors for the persistence of EBOV in the semen of EVD survivors. EBOV persistence in semen may also be associated with its persistence in other immunologically protected sites, such as the eye.

Factors affecting the fate of nanoencapsulates post administration.

Nanoencapsulation has found numerous applications in the food and nutraceutical industries. Micro and nanoencapsulated forms of bioactives have proven benefits in terms of stability, release, and performance in the body. However, the encapsulated ingredient is often subjected to a wide range of processing conditions and this is followed by storage, consumption, and transit along the gastrointestinal tract. A strong understanding of the fate of nanoencapsulates in the biological system is mandatory as it provides valuable insights for ingredient selection, formulation, and application. In addition to their efficacy, there is also the need to assess the safety of ingested nanoencapsulates. Given the rising research and commercial focus of this subject, this review provides a strong focus on their interaction factors and mechanisms, highlighting their prospective biological fate. This review also covers various approaches to studying the fate of nanoencapsulates in the body. Also, with emphasis on the overall scope, the need for a new advanced integrated common methodology to evaluate the fate of nanoencapsulates post-administration is discussed.

Predictors of Completion of Clinically Necessary Radiologist-Recommended Follow-Up Imaging: Assessment Using an Automated Closed-Loop Communication and Tracking Tool.

BACKGROUND. Patients with adverse social determinants of health may be at increased risk of not completing clinically necessary follow-up imaging. OBJECTIVE. The purpose of this study was to use an automated closed-loop communication and tracking tool to identify patient-, referrer-, and imaging-related factors associated with lack of completion of radiologist-recommended follow-up imaging. METHODS. This retrospective study was performed at a single academic health system. A tool for automated communication and tracking of radiologist-recommended follow-up imaging was embedded in the PACS and electronic health record. The tool prompted referrers to record whether they deemed recommendations to be clinically necessary and assessed whether clinically necessary follow-up imaging was pursued. If imaging was not performed within 1 month after the intended completion date, the tool prompted a safety net team to conduct further patient and referrer follow-up. The study included patients for whom a follow-up imaging recommendation deemed clinically necessary by the referrer was entered with the tool from October 21, 2019, through June 30, 2021. The electronic health record was reviewed for documentation of eventual completion of the recommended imaging at the study institution or an outside institution. Multivariable logistic regression analysis was performed to identify factors associated with completion of follow-up imaging. RESULTS. Of 5856 recommendations entered during the study period, the referrer agreed with 4881 recommendations in 4599 patients (2929 women, 1670 men; mean age, 61.3 ± 15.6 years), who formed the study sample. Follow-up was completed for 74.8% (3651/4881) of recommendations. Independent predictors of lower likelihood of completing follow-up imaging included living in a socioeconomically disadvantaged neighborhood according to the area deprivation index (odds ratio [OR], 0.67 [95% CI, 0.54-0.84]), inpatient (OR, 0.25 [95% CI, 0.20-0.32]) or emergency department (OR, 0.09 [95% CI, 0.05-0.15]) care setting, and referrer surgical specialty (OR, 0.70 [95% CI, 0.58-0.84]). Patient age, race and ethnicity, primary language, and insurance status were not independent predictors of completing follow-up (p > .05). CONCLUSION. Socioeconomically disadvantaged patients are at increased risk of not completing recommended follow-up imaging that referrers deem clinically necessary. CLINICAL IMPACT. Initiatives for ensuring completion of follow-up imaging should be aimed at the identified patient groups to reduce disparities in missed and delayed diagnoses.

Effect of different drying methods on the functional properties of probiotics encapsulated using prebiotic substances.

Probiotics and prebiotics together work synergistically as synbiotics and confer various health benefits. Many studies on synbiotic foods only focus on the survival of probiotics but fail to evaluate their functional properties. The impact on functional properties should be explored to better understand its therapeutic efficacy. In this work, probiotics (Lactiplantibacillus plantarum NCIM 2083) were encapsulated with prebiotics (fructooligosaccharide + whey protein + maltodextrin) using spray-drying (SD), freeze-drying (FD), spray-freeze-drying (SFD), and refractance window-drying (RWD) techniques. Aggregation, intestinal adhesion, antagonistic activity, and bile salt hydrolase (BSH) activity of probiotics were studied before and after the encapsulation process. The SFD probiotics showed better aggregation ability (79% at 24-h incubation), on par with free cells (FC) (81% at 24-h incubation). The co-aggregation ability of encapsulated probiotics has drastic variations with each pathogenic strain. The adhesion ability of probiotics in chicken intestinal mucus was assessed by the crystal violet method, indicating no significant variations between FC and SFD probiotics. Also, encapsulated probiotics exhibit antagonistic activity (zone of inhibition in mm) against gut pathogens E. coli (11.33 to 17.34), S. faecalis (8.83 to 15.32), L. monocytogenes (13.67 to 18), S. boydii (12.17 to 15.5), and S. typhi (2.17 to 6.86). Overall, these studies confirm the significance and impact of various drying techniques on the functionality of encapsulated probiotics in synbiotic powders. KEY POINTS: • Understanding the relevance of processing effects on the functionality of probiotics. • Spray-freeze-dried probiotics showed superior functional properties. • The encapsulation process had no significant impact on bile salt hydrolase activity.

The impact of same-day antiretroviral therapy initiation on retention in care and clinical outcomes at four eThekwini clinics, KwaZulu-Natal, South Africa.

BACKGROUND: Same-day initiation (SDI) of antiretroviral therapy (ART) increases ART uptake, however retention in care after ART initiation remains a challenge. Public health behaviours, such as retention in HIV care and adherence to antiretroviral therapy (ART) pose major challenges to reducing new Human Immunodeficiency Virus (HIV) transmission and improving health outcomes among HIV patients. METHODS: We evaluated 6-month retention in care, and clinical outcomes of an ART cohort comprising of SDI and delayed ART initiators. We conducted a 6 months' observational prospective cohort study of 403 patients who had been initiated on ART. A structured questionnaire was used to abstract data from patient record review which comprised the medical charts, laboratory databases, and Three Interlinked Electronic Registers.Net (TIER.Net). Treatment adherence was ascertained by patient visit constancy for the clinic scheduled visit dates. Retention in care was determined by status at 6 months after ART initiation. RESULTS: Among the 403 participants enrolled in the study and followed up, 286 (70.97%) and 267 (66.25%) complied with scheduled clinics visits at 3 months and 6 months, respectively. One hundred and thirteen (28.04%) had been loss to follow-up. 17/403 (4.22%) had died and had been out of care after 6 months. 6 (1.49%) had been transferred to other health facilities and 113 (28.04%) had been loss to follow-up. Among those that had been lost to follow-up, 30 (33.63%) deferred SDI while 75 (66.37%) initiated ART under SDI. One hundred and eighty-nine (70.79%) participants who had remained in care were SDI patients while 78 (29.21%) were SDI deferred patients. In the bivariate analysis; gender (OR: 1.672; 95% CI: 1.002-2.791), number of sexual partners (OR: 2.092; 95% CI: 1.07-4.061), age (OR: 0.941; 95% CI: 0.734-2.791), ART start date (OR: 0.078; 95% CI: 0.042-0.141), partner HIV status (OR: 0.621; 95% CI: 0.387-0.995) and the number of hospitalizations after HIV diagnosis (OR: 0.173; 95% CI: 0.092-0.326). were significantly associated with viral load detection. Furthermore, SDI patients who defaulted treatment were 2.4 (95% CI: 1.165-4.928) times more likely to have increased viral load than those who had been returned in care. CONCLUSION: Viral suppression under SDI proved higher but with poor retention in care. However, the results also emphasise a vital need, to not only streamline processes to increase immediate ART uptake further, but also to ensure retention in care.

Patients' views on health promotion and disease prevention services provided by healthcare workers in a South African tertiary hospital.

BACKGROUND: Patients' views and experiences in healthcare institutions provide a means of assessing the quality of services patients receive from healthcare workers (HCWs). However, the views of patients on the health promotion (HP) and disease prevention (DP) services offered by HCWs and the delivery mode have not been adequately studied. AIM: This study assessed the views of patients on HP and DP services provided by various categories of HCWs. SETTING: The study was conducted at a tertiary hospital in the Nelson Mandela Bay Municipality, South Africa. METHOD: An exploratory cross-sectional study was conducted among 500 patients. The questionnaire elicited responses from patients regarding the HP and DP services received from the different cadres of HCWs at three different admission phases: pre-admission phase (PAP), admission phase (ADP), and post-admission phase (POP). Descriptive, bivariate, and multivariate analysis was conducted. RESULTS: In the PAP, most patients (83.33%, n = 5; 87.85%, n = 217; and 76.14%, n = 150) seen by the rehabilitation health workers, medical doctors, and nurses respectively were empowered to manage their health. Patients attended to by nurses were 0.45 (95% CI 0.27-0.74) times less likely than those attended to by medical doctors to receive information that that will help them address the physical and environmental needs. In the ADP, patients attended to by nurses were less likely, compared to those attended to by medical doctors to be empowered to have good control over their health. In the POP, patients attended to by nurses are more likely to have their health behaviours change for better compared to those not seen by any HCW. CONCLUSION: Patients attending tertiary hospital received greater HP and DP services during the PAP and ADP of patient care. Greatest influence for behavioural change of patients on HP and DP were achieved from the medical doctors, nurses and rehabilitation service staff. Improving structural factors may prove beneficial in enhancing patients' experience from all HCW groups and phases of patient care.

Community engagement processes in low- and middle-income countries health research settings: a systematic review of the literature.

BACKGROUND: Community Engagement is an important ethical imperative in research. Although substantial research emphasizes its real value and strategic importance, much of the available literature focuses primarily on the success of community participation, with little emphasis given to specific community engagement processes, mechanisms and strategies in relation to intended outcomes in research environments. The systematic literature review's objective was to explore the nature of community engagement processes, strategies and approaches in health research settings in low- and middle-income countries. METHODS: The systematic literature review design was informed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched for peer-reviewed, English-language literature published between January 2011 and December 2021 through three databases on the internet (PubMed, Web of Science and Google Scholar). The terms "community engagement," "community involvement," "participation," "research settings," and "low- and middle-income countries" were merged in the search. RESULTS: The majority of publications [8/10] were led by authors from low- and middle-income countries, with many of them, [9/10] failing to continuously include important aspects of study quality. Even though consultation and information sessions were less participatory, articles were most likely to describe community engagement in these types of events. The articles covered a wide range of health issues, but the majority were concerned with infectious diseases such as malaria, human immunodeficiency virus, and tuberculosis, followed by studies on the environment and broader health factors. Articles were largely under-theorized. CONCLUSIONS: Despite the lack of theoretical underpinnings for various community engagement processes, strategies and approaches, community engagement in research settings was variable. Future studies should go deeper into community engagement theory, acknowledge the power dynamics underpin community engagement, and be more practical about the extent to which communities may participate.

Residual Structure in the Denatured State of the Fast-Folding UBA(1) Domain from the Human DNA Excision Repair Protein HHR23A.

The structure of the first ubiquitin-associated domain from HHR23A, UBA(1), was determined by X-ray crystallography at a 1.60 Å resolution, and its stability, folding kinetics, and residual structure under denaturing conditions have been investigated. The concentration dependence of thermal denaturation and size-exclusion chromatography indicate that UBA(1) is monomeric. Guanidine hydrochloride (GdnHCl) denaturation experiments reveal that the unfolding free energy, ΔGu°'(H2O), of UBA(1) is 2.4 kcal mol-1. Stopped-flow folding kinetics indicates sub-millisecond folding with only proline isomerization phases detectable at 25 °C. The full folding kinetics are observable at 4 °C, yielding a folding rate constant, kf, in the absence of a denaturant of 13,000 s-1 and a Tanford ß-value of 0.80, consistent with a compact transition state. Evaluation of the secondary structure via circular dichroism shows that the residual helical structure in the denatured state is replaced by polyproline II structure as the GdnHCl concentration increases. Analysis of NMR secondary chemical shifts for backbone 15NH, 13CO, and 13Cα atoms between 4 and 7 M GdnHCl shows three islands of residual helical secondary structure that align in sequence with the three native-state helices. Extrapolation of the NMR data to 0 M GdnHCl demonstrates that helical structure would populate to 17-33% in the denatured state under folding conditions. Comparison with NMR data for a peptide corresponding to helix 1 indicates that this helix is stabilized by transient tertiary interactions in the denatured state of UBA(1). The high helical content in the denatured state, which is enhanced by transient tertiary interactions, suggests a diffusion-collision folding mechanism.

The Risk of Incarceration During Nonoperative Management of Incisional Hernias: A Population-based Analysis of 30,998 Patients.

OBJECTIVE: The aim of the study was to quantify the risk of incarceration of incisional hernias. BACKGROUND: Operative repair is the definitive treatment for incisional ventral hernias but is often deferred if the perceived risk of elective operation is elevated secondary to comorbid conditions. The risk of incarceration during nonoperative management (NOM) factors into shared decision making by patient and surgeon; however, the incidence of acute incarceration remains largely unknown. METHODS: A retrospective analysis of adult patients with an International Classification of Diseases, Ninth Revision or Tenth Revision diagnosis of incisional hernia was conducted from 2010 to 2017 in 15 hospitals of a single healthcare system. The primary outcome was incarceration necessitating emergent operation. The secondary outcome was 30-, 90-, and 365-day mortality. Univariate and multivariate analyses were used to determine independent predictors of incarceration. RESULTS: Among 30,998 patients with an incisional hernia (mean age 58.1 ±â€Š15.9 years; 52.7% female), 23,022 (78.1%) underwent NOM of whom 540 (2.3%) experienced incarceration, yielding a 1- and 5-year cumulative incidence of 1.24% and 2.59%, respectively. Independent variables associated with incarceration included: age older than 40 years, female sex, current smoker, body mass index 30 or greater, and a hernia-related inpatient admission. All-cause mortality rates at 30, 90, and 365 days were significantly higher in the incarceration group at 7.2%, 10%, and 14% versus 1.1%, 2.3%, and 5.3% in patients undergoing successful NOM, respectively. CONCLUSIONS: Incarceration is an uncommon complication of NOM but is associated with a significant risk of death. Tailored decision making for elective repair and considering the aforementioned risk factors for incarceration provides an initial step toward mitigating the excess morbidity and mortality of an incarceration event.

Impact of processing techniques on the glycemic index of rice.

Rice is an important starchy staple food and generally, rice varieties are known to have a higher glycemic index (GI). Over the years, the significance of GI on human health is being better understood and is known to be associated with several lifestyle disorders. Apart from the intrinsic characteristics of rice, different food processing techniques are known to have implications on the GI of rice. This work details the effect of domestic and industrial-level processing techniques on the GI of rice by providing an understanding of the resulting physicochemical changes. An attempt has been made to relate the process-dependent digestion behavior, which in turn reflects on the GI. The role of food constituents is elaborated and the various in vitro and in vivo approaches that have been used to determine the GI of foods are summarized. Considering the broader perspective, the effect of cooking methods and additives is explained. Given the significance of the cereal grain, this work concludes with the challenges and key thrust areas for future research.

Mucilages: sources, extraction methods, and characteristics for their use as encapsulation agents.

The increasing interest in the use of natural ingredients has driven keen research and commercial interest in the use of mucilages for a range of applications. Typically, mucilages are polysaccharide hydrocolloids with distinct physicochemical and structural diversity, possessing characteristic functional and health benefits. Apart from their role as binding, thickening, stabilizing, and humidifying agents, they are valued for their antimicrobial, antihypertensive, antioxidant, antiasthmatic, hypoglycemic, and hypolipidemic activities. The focus of this review is to present the range of mucilages that have been explored as encapsulating agents. Encapsulation of food ingredients, nutraceutical, and pharmaceutical ingredients is an attractive technique to enhance the stability of targeted compounds, apart from providing benefits on delivery characteristics. The most widely adopted conventional and emerging extraction and purification methods are explained and supplemented with information on the key criteria involved in characterizing the physicochemical and functional properties of mucilages. The unique traits and benefits of using mucilages as encapsulation agents are detailed with the different methods used by researchers to encapsulate different food and bioactive compounds.

Factors Influencing Rapid Antiretroviral Therapy Initiation at Four eThekwini Clinics, KwaZulu-Natal, South Africa.

Timely uptake of Antiretroviral therapy considerably improves the health of people living with the Human Immunodeficiency virus. We conducted a cross-sectional study of newly HIV diagnosed individuals in four clinics in eThekwini municipality, KwaZulu-Natal. Data was collected between June 2020 and December 2020. Participants completed an interviewer-administered questionnaire after HIV testing, on the day of HIV diagnosis. We evaluated factors influencing uptake of same-day ART initiation in eThekwini clinics, KwaZulu Natal, South Africa. Demographic information, health status, sexual behaviour, knowledge of universal test and treat (UTT), ART initiation uptake, and disclosure data was collected. Among the 403 participants, same-day initiation (SDI) was 69.2% (n = 279). We observed the number of sexual partners (aOR 0.35; 95% CI 0.15-0.81), HIV status of the partner (aOR 5.03; 95% CI 2.74-9.26) and knowledge of UTT (aOR 1.97; 95% CI 1.34-2.90) were identified as major factors influencing uptake of same-day ART initiation. More strategies are needed to achieve the SDI uptake within the framework of UTT.

Determining the glycaemic responses of foods: conventional and emerging approaches.

A low-glycaemic diet is crucial for those with diabetes and cardiovascular diseases. Information on the glycaemic index (GI) of different ingredients can help in designing novel food products for such target groups. This is because of the intricate dependency of material source, composition, food structure and processing conditions, among other factors, on the glycaemic responses. Different approaches have been used to predict the GI of foods, and certain discrepancies exist because of factors such as inter-individual variation among human subjects. Besides other aspects, it is important to understand the mechanism of food digestion because an approach to predict GI must essentially mimic the complex processes in the human gastrointestinal tract. The focus of this work is to review the advances in various approaches for predicting the glycaemic responses to foods. This has been carried out by detailing conventional approaches, their merits and limitations, and the need to focus on emerging approaches. Given that no single approach can be generalised to all applications, the review emphasises the scope of deriving insights for improvements in methodologies. Reviewing the conventional and emerging approaches for the determination of GI in foods, this detailed work is intended to serve as a state-of-the-art resource for nutritionists who work on developing low-GI foods.

Medium chain triglycerides (MCT): State-of-the-art on chemistry, synthesis, health benefits and applications in food industry.

Medium chain triglycerides (MCT) are esters of fatty acids with 6 to 12 carbon atom chains. Naturally, they occur in various sources; their composition and bioactivity are source and extraction process-linked. The molecular size of MCT oil permits unique metabolic pathways and energy production rates, making MCT oil a high-value functional food. This review details the common sources of MCT oil, presenting critical information on the various approaches for MCT oil extraction or synthesis. Apart from conventional techniques, non-thermal processing methods that show promising prospects are analyzed. The biological effects of MCT oil are summarized, and the range of need-driven modification approaches are elaborated. A section is devoted to highlighting the recent trends in the application of MCT oil for food, nutraceuticals, and allied applications. While much is debated about the role of MCT oil in human health and wellness, there is limited information on daily requirements, impact on specific population groups, and effects of long-term consumption. Nonetheless, several studies have been conducted and continue to identify the most effective methods for MCT oil extraction, processing, handling, and storage. A knowledge gap exists and future research must focus on technology packages for scalability and sustainability.

Denatured State Conformational Biases in Three-Helix Bundles Containing Divergent Sequences Localize near Turns and Helix Capping Residues.

Rhodopseudomonas palustris cytochrome c', a four-helix bundle, and the second ubiquitin-associated domain, UBA(2), a three-helix bundle from the human homologue of yeast Rad23, HHR23A, deviate from random coil behavior under denaturing conditions in a fold-specific manner. The random coil deviations in each of these folds occur near interhelical turns and loops in their tertiary structures. Here, we examine an additional three-helix bundle with an identical fold to UBA(2), but a highly divergent sequence, the first ubiquitin-associated domain, UBA(1), of HHR23A. We use histidine-heme loop formation methods, employing eight single histidine variants, to probe for denatured state conformational bias of a UBA(1) domain fused to the N-terminus of iso-1-cytochrome c (iso-1-Cytc). Guanidine hydrochloride (GuHCl) denaturation shows that the iso-1-Cytc domain unfolds first, followed by the UBA(1) domain. Denatured state (4 and 6 M GuHCl) histidine-heme loop formation studies show that as the size of the histidine-heme loop increases, loop stability decreases, as expected for the Jacobson-Stockmayer relationship. However, loops formed with His35, His31, and His15, of UBA(1), are 0.6-1.1 kcal/mol more stable than expected from the Jacobson-Stockmayer relationship, confirming the importance of deviations of the denatured state from random coil behavior near interhelical turns of helical domains for facilitating folding to the correct topology. For UBA(1) and UBA(2), hydrophobic clusters on either side of the turns partially explain deviations from random coil behavior; however, helix capping also appears to be important.

Growth transitions and critical behavior in the non-equilibrium aggregation of short, patchy nanorods.

We have carried out Monte Carlo simulations to study the non-equilibrium aggregation of short patchy nanorods in two dimensions. Below a critical value of patch size ([Formula: see text]), the aggregates have finite sizes with small radii of gyration, [Formula: see text]. At [Formula: see text], the average radius of gyration shows a power law increase with time such that [Formula: see text], where [Formula: see text]. Above, [Formula: see text], the aggregates are fractal in nature and their fractal dimension depends on the value of patch size. These morphological differences are due to the fact that below the critical value of patch size ([Formula: see text]), the growth of the clusters is suppressed and the system reaches an 'absorbed state.' Above [Formula: see text], the system reaches an 'active state,' in which the cluster size keeps growing with a fixed rate at long times. Thus, the system encounters a non-equilibrium phase transition. Close to the transition, the growth rate scales as [Formula: see text], where [Formula: see text]. The long-time growth rate varies as [Formula: see text] where [Formula: see text]. These scaling exponents indicate that the transition belongs to the directed percolation universality class. The patchy nanorods also display a threshold patch size ([Formula: see text]), beyond which the long-time growth rate remains constant. We present geometric arguments for the existence of [Formula: see text]. The fractal dimension of the aggregates increases from 1.75, at [Formula: see text], to 1.81, at [Formula: see text]. It remains constant beyond [Formula: see text].

Consulting the Community on Strategies to Strengthen Social Capital for Community Disease Control.

Excluding communities in planning and implementing research maximizes internal risks that are otherwise visible and avoidable when there is adequate community consultation. Communities might not meaningfully use research results if majority of the researched people have minimal or no participation in information generation and dissemination. However, effective participation of researched communities in research is key to transferring knowledge to action. Using a qualitative approach, the study identified barriers to, and relevant strategies for improving health research uptake, particularly for schistosomiasis (commonly known as bilharzia) in the Ingwavuma area, uMkhanyakude District of KwaZulu-Natal. Data was collected through modified ethnography using participant observation, focus group discussions, unstructured in-depth interviews, and ethnographic conversational interviews. Results reveal that research uptake is inhibited by reduced opportunities for habitual interaction between residents, a paucity of innovative and inclusive health education activities and unsafe recreational facilities. The community's strategies on strengthening social capital for disease control include using existing social systems and power hierarchies to mobilise and organise and using the performing arts to facilitate habitual interaction and knowledge sharing. The study recommends a community consultation flow which facilitates openness about the benefits and the community's role in research, a pre-condition for community wide efforts in local disease prevention and control.

Neptune and Uranus: ice or rock giants?

Existing observations of Uranus and Neptune's fundamental physical properties can be fitted with a wide range of interior models. A key parameter in these models is the bulk rock:ice ratio and models broadly fall into ice-dominated (ice giant) and rock-dominated (rock giant) categories. Here we consider how observations of Neptune's atmospheric temperature and composition (H2, He, D/H, CO, CH4, H2O and CS) can provide further constraints. The tropospheric CO profile in particular is highly diagnostic of interior ice content, but is also controversial, with deep values ranging from zero to 0.5 parts per million. Most existing CO profiles imply extreme O/H enrichments of >250 times solar composition, thus favouring an ice giant. However, such high O/H enrichment is not consistent with D/H observations for a fully mixed and equilibrated Neptune. CO and D/H measurements can be reconciled if there is incomplete interior mixing (ice giant) or if tropospheric CO has a solely external source and only exists in the upper troposphere (rock giant). An interior with more rock than ice is also more compatible with likely outer solar system ice sources. We primarily consider Neptune, but similar arguments apply to Uranus, which has comparable C/H and D/H enrichment, but no observed tropospheric CO. While both ice- and rock-dominated models are viable, we suggest a rock giant provides a more consistent match to available atmospheric observations. This article is part of a discussion meeting issue 'Future exploration of ice giant systems'.