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Cryo-electron microscopy (cryoEM) has become a well established technique with the potential to produce structures of large and dynamic supramolecular complexes that are not amenable to traditional approaches for studying structure and dynamics. The size and low resolution of such molecular systems often make structural modelling and molecular dynamics simulations challenging and computationally expensive. This, together with the growing wealth of structural data arising from cryoEM and other structural biology methods, has driven a trend in the computational biophysics community towards the development of new pipelines for analysing global dynamics using coarse-grained models and methods. At the centre of this trend has been a return to elastic network models, normal mode analysis (NMA) and ensemble analyses such as principal component analysis, and the growth of hybrid simulation methodologies that make use of them. Here, this field is reviewed with a focus on ProDy, the Python application programming interface for protein dynamics, which has been developed over the last decade. Two key developments in this area are highlighted: (i) ensemble NMA towards extracting and comparing the signature dynamics of homologous structures, aided by the recent SignDy pipeline, and (ii) pseudoatom fitting for more efficient global dynamics analyses of large and low-resolution supramolecular assemblies from cryoEM, revisited in the CryoDy pipeline. It is believed that such a renewal and extension of old models and methods in new pipelines will be critical for driving the field forward into the next cryoEM revolution.

Objectives. To test whether fruit drink countermarketing messages alone or combined with water promotion messages reduce Latinx parents’ purchases of fruit drinks for children aged 0 to 5 years. Methods. We performed a 3-arm randomized controlled online trial enrolling 1628 Latinx parents in the United States during October and November 2019. We assessed the effect of culturally tailored fruit drink countermarketing messages (fruit drink‒only group), countermarketing and water promotion messages combined (combination group), or car-seat safety messages (control) delivered via Facebook groups for 6 weeks on parental beverage choices from a simulated online store. Results. The proportion of parents choosing fruit drinks decreased by 13.7 percentage points in the fruit drink‒only group (95% confidence interval [CI] = −20.0, −7.4; P Conclusions. Fruit drink countermarketing messages, alone or combined with water promotion messages, significantly decreased parental selection of fruit drinks and increased water selection for their children. Public Health Implications. Countermarketing social media messages may be an effective and low-cost intervention for reducing parents’ fruit drink purchases for their children. (Am J Public Health. 2021;111(11):1997–2007. https://doi.org/10.2105/AJPH.2021.306488 )

A new tool based on 3D Zernike polynomials is presented that allows the study of the continuous heterogeneity of biological macromolecules, revealing the structural relationships present among different states by the approximation of deformation fields., Structural biology has evolved greatly due to the advances introduced in fields like electron microscopy. This image-capturing technique, combined with improved algorithms and current data processing software, allows the recovery of different conformational states of a macromolecule, opening new possibilities for the study of its flexibility and dynamic events. However, the ensemble analysis of these different conformations, and in particular their placement into a common variable space in which the differences and similarities can be easily recognized, is not an easy matter. To simplify the analysis of continuous heterogeneity data, this work proposes a new automatic algorithm that relies on a mathematical basis defined over the sphere to estimate the deformation fields describing conformational transitions among different structures. Thanks to the approximation of these deformation fields, it is possible to describe the forces acting on the molecules due to the presence of different motions. It is also possible to represent and compare several structures in a low-dimensional mapping, which summarizes the structural characteristics of different states. All these analyses are integrated into a common framework, providing the user with the ability to combine them seamlessly. In addition, this new approach is a significant step forward compared with principal component analysis and normal mode analysis of cryo-electron microscopy maps, avoiding the need to select components or modes and producing localized analysis.

People with low incomes have a disproportionate prevalence of diabetes and its complications and experience many barriers to self-management, which community health workers (CHWs) may help address. We sought to examine the effects of an in-home CHW-led intervention for adults with diabetes and incomes

Many proteins select from a small repertoire of 3-dimensional folds retained over evolutional timescales and recruited for different functions, with changes in local structure and sequence to enable specificity. Recent studies have revealed the evolutionary constraints on protein dynamics to achieve function. The significance of protein dynamics in simultaneously satisfying conformational flexibility/malleability and stability/precision requirements becomes clear upon dissecting the spectrum of equilibrium motions accessible to fold families. Accessibility to highly conserved global modes of motions shared by family members, to low-to-intermediate-frequency modes that distinguish subfamilies and confer specificity, and to conserved high-frequency modes ensuring chemical precision and core stability underlies functional specialization while exploiting highly versatile folds. These design principles are illustrated for the family of PDZ domains.

The eukaryotic chaperonin TRiC/CCT plays a major role in assisting the folding of many proteins through an ATP-driven allosteric cycle. Recent structures elucidated by cryo-electron microscopy provide a broad view of the conformations visited at various stages of the chaperonin cycle, including a sequential activation of its subunits in response to nucleotide binding. But we lack a thorough mechanistic understanding of the structure-based dynamics and communication properties that underlie the TRiC/CCT machinery. In this study, we present a computational methodology based on elastic network models adapted to cryo-EM density maps to gain a deeper understanding of the structure-encoded allosteric dynamics of this hexadecameric machine. We have analysed several structures of the chaperonin resolved in different states toward mapping its conformational landscape. Our study indicates that the overall architecture intrinsically favours cooperative movements that comply with the structural variabilities observed in experiments. Furthermore, the individual subunits CCT1-CCT8 exhibit state-dependent sequential events at different states of the allosteric cycle. For example, in the ATP-bound state, subunits CCT5 and CCT4 selectively initiate the lid closure motions favoured by the overall architecture; whereas in the apo form of the heteromer, the subunit CCT7 exhibits the highest predisposition to structural change. The changes then propagate through parallel fluxes of allosteric signals to neighbours on both rings. The predicted state-dependent mechanisms of sequential activation provide new insights into TRiC/CCT intra- and inter-ring signal transduction events., Support is gratefully acknowledged from NIH grants P41 GM103712 and P30DA035778 (IB) and MINECO BIO2016-76400-R (JMC and COSS).

With the explosion of normal mode analyses (NMAs) based on elastic network models (ENMs) in the last decade, and the proven precision of MD simulations for visualizing interactions at atomic scale, many hybrid methods have been proposed in recent years. These aim at exploiting the best of both worlds: the atomic precision of MD that often fall short of exploring time and length scales of biological interest, and the capability of ENM-NMA to predict the cooperative and often functional rearrangements of large structures and assemblies, albeit at low resolution. We present an overview of recent progress in the field with examples of successful applications highlighting the utility of such hybrid methods and pointing to emerging future directions guided by advances in experimental characterization of biomolecular systems structure and dynamics.

Summary Objective To examine whether the promotion of water intake could reduce sugar‐sweetened beverage (SSB) consumption or purchases independent of interventions that target SSBs. Methods Seven databases were systematically searched. Included studies used water promotion as the primary intervention; used a controlled trial, single group pre‐post, or prospective cohort study design; included a measure of SSB consumption or purchase; enrolled human participants of any age who lived in high‐income or middle‐income countries; contained original data; and appeared in a peer‐reviewed English‐language article published from 1 January 2000 to January 4, 2019. The search yielded 7068 publications, from which 108 were chosen for full‐text review. Seventeen were included in this review. Results Nine of the 17 studies were randomized controlled trials, six were nonrandomized controlled trials, and 2 were single‐group pre‐post studies. Participants were primarily children and adolescents. Interventions included water provision, education or promotion activities. Ten of 17 studies were at low or some/moderate risk of bias. Seven studies showed a statistically significant decrease in SSB consumption of which only 2 were at low or some/moderate risk of bias. Conclusions This review found limited evidence that interventions aimed solely at increasing water consumption reduce SSB intake. Further research is needed to investigate whether interventions that combine water promotion and SSB reduction strategies could be synergistic for reducing SSB intake.

Increased fruit and vegetable (FV) intake is associated with decreased risk of nutrition-related chronic diseases. Sociodemographic disparities in FV intake indicate the need for strategies that promote equitable access to FVs. The United States Department of Agriculture’s Gus Schumacher Nutrition Incentive Program (GusNIP) supports state and local programs that offer nutrition incentives (NIs) that subsidize purchase of FVs for people participating in the Supplemental Nutrition Assistance Program (SNAP). While a growing body of research indicates NIs are effective, the pathways through which GusNIP achieves its results have not been adequately described. We used an equity-focused, participatory process to develop a retrospective Theory of Change (TOC) to address this gap. We reviewed key program documents; conducted a targeted NI literature review; and engaged GusNIP partners, practitioners, and participants through interviews, workshops, and focus groups in TOC development. The resulting TOC describes how GusNIP achieves its long-term outcomes of increased participant FV purchases and intake and food security and community economic benefits. GusNIP provides NIs and promotes their use, helps local food retailers develop the capacity to sell FVs and accept NIs in accessible and welcoming venues, and supports local farmers to supply FVs to food retailers. The TOC is a framework for understanding how GusNIP works and a tool for improving and expanding the program.

Background: Healthcare-based interventions to address sugary beverage intake could achieve broad reach, but intensive in-person interventions are unsustainable in clinical settings. Technology-based interventions may provide an alternative, scalable approach. Methods: Within an academic health system in the United States that already performs electronic health record-based sugary drink screening, we conducted a pilot randomized trial of a technology-driven family beverage choice intervention. The goal of the intervention was to reduce sugar-sweetened beverage (SSB) and fruit juice (FJ) consumption in 60 parent–child dyads, in which children were 1–8 years old. The pediatrician-initiated intervention consisted of a water promotion toolkit, a video, a mobile phone application, and 14 interactive voice-response phone calls to parents over 6 months. The study was conducted between June 2021 and May 2022. The aim of the pilot study was to assess the potential feasibility and efficacy of the newly developed intervention. Results: Intervention fidelity was excellent, and acceptability was high for all intervention components. Children in both the intervention and the control groups substantially decreased their consumption of SSB and FJ over follow-up (mean combined baseline 2.5 servings/day vs. 1.4/day at 6 months) and increased water consumption, but constrained linear mixed-effects models showed no differences between groups on these measures. Compared to parents in the control group, intervention parents had larger decreases in SSB intake at 3 months (−0.80 (95% CI: −1.54, −0.06, p = 0.03) servings daily), but these differences were not sustained at 6 months. Conclusion: These findings suggest that, though practical to implement in a clinical care setting and acceptable to a diverse participant group, our multicomponent intervention may not be universally necessary to achieve meaningful behavior changes around family beverage choice. A lower-intensity intervention, such as EHR-based clinical screening alone, might be a less resource-intense way for health systems to achieve similar behavioral outcomes. Future studies might therefore explore whether, instead of applying a full intervention to all families whose children overconsume SSB or FJ, a stepped approach, starting with clinical screening and brief counseling, could be a better use of health system resources.

Highlights • 7 U.S. cities have a sugar-sweetened-beverage tax, raising $134 million annually. • Early childhood programs received the largest investment of tax revenues ($58M). • Community improvements (e.g., rec centers & libraries) were second largest ($21M). • Increasing healthy food and beverage access (e.g., produce subsidies) received $17M. • 85% of revenues supported projects and programs in impacted communities., We sought to describe how revenues from sugar-sweetened beverage (SSB) excise taxes in 7 U.S. cities are being allocated, who is benefiting from these investments, and whether allocations are consistent with the original intent of tax legislation. We collected information from public documents and key informants about allocations in the most recent fiscal year available (ranging from 2018 to 2021). Across the 7 U.S. cities with taxes, the average annual revenue from SSB taxes totaled $133.9 M. In the fiscal year studied, cities allocated a total of $133.2 M in SSB tax revenues. Human and community capital investments totaled $89.6 M (67% of all allocations) funding early childhood development, community infrastructure improvements, and youth and workforce development. Health-related investments totaled $36.9 M (28% of total allocations), funding access to healthy foods and beverages; support for physical activity opportunities; promotion of overall physical, mental or social health and wellbeing; health and nutrition education; chronic-disease prevention and management; and reducing SSB consumption. In the 3 cities that specified how tax revenues would be spent, allocations were consistent with promised uses of revenues. In addition, 85% of aggregated revenues ($112.9 M) were targeted to support work and programs in impacted communities (communities that experience health inequities, discrimination and exclusion). SSB tax revenues are supporting initiatives to improve community health, develop human and community capital, and advance equity. These investments may yield additional health benefits beyond those resulting from lower SSB consumption. Consistent tracking and public reporting on revenue allocations would increase transparency and accountability.

Recent years have seen progress in druggability simulations, that is, molecular dynamics simulations of target proteins in solutions containing drug‐like probe molecules to characterize their drug‐binding abilities, if any. An important consecutive step is to analyze the trajectories to construct pharmacophore models (PMs) to use for virtual screening of libraries of small molecules. While considerable success has been observed in this type of computer‐aided drug discovery, a systematic tool encompassing multiple steps from druggability simulations to pharmacophore modeling, to identifying hits by virtual screening of libraries of compounds, has been lacking. We address this need here by developing a new tool, Pharmmaker, building on the DruGUI module of our ProDy application programming interface. Pharmmaker is composed of a suite of steps: (Step 1) identification of high affinity residues for each probe molecule type; (Step 2) selecting high affinity residues and hot spots in the vicinity of sites identified by DruGUI; (Step 3) ranking of the interactions between high affinity residues and specific probes; (Step 4) obtaining probe binding poses and corresponding protein conformations by collecting top‐ranked snapshots; and (Step 5) using those snapshots for constructing PMs. The PMs are then used as filters for identifying hits in structure‐based virtual screening. Pharmmaker, accessible online at http://prody.csb.pitt.edu/pharmmaker/, can be used in conjunction with other tools available in ProDy.

Recent studies have drawn attention to the evolution of protein dynamics, in addition to sequence and structure, based on the premise structure-encodes-dynamics-encodes-function. Of interest is to understand how functional differentiation is accomplished while maintaining the fold, or how intrinsic dynamics plays out in the evolution of structural variations and functional specificity. We performed a systematic computational analysis of 26,899 proteins belonging to 116 CATH superfamilies. Characterizing cooperative mechanisms and convergent/divergent features that underlie the shared/differentiated dynamics of family members required a methodology that lends itself to efficient analyses of large ensembles of proteins. We therefore introduced, SignDy, an integrated pipeline for evaluating the signature dynamics of families based on elastic network models. Our analysis confirmed that family members share conserved, highly cooperative (global) modes of motion. Importantly, our analysis discloses a subset of motions that sharply distinguishes subfamilies, which lie in a low-to-intermediate frequency regime of the mode spectrum. This regime has maximal impact on functional differentiation of families into subfamilies, while being evolutionarily conserved among subfamily members. Notably, the high-frequency end of the spectrum also reveals evolutionary conserved features across and within subfamilies; but in sharp contrast to global motions, high-frequency modes are minimally collective. Modulation of robust/conserved global dynamics by low-to-intermediate frequency fluctuations thus emerges as a versatile mechanism ensuring the adaptability of selected folds and the specificity of their subfamilies. SignDy further allows for dynamics-based categorization as a new layer of information relevant to distinctive mechanisms of action of subfamilies, beyond sequence or structural classifications.

Introduction Calorie labeling is now required on all large U.S. chain restaurant menus, but its influence on consumer behavior is mixed. This study examines whether different parent-targeted messages encourage parents to order lower-calorie meals for their children in a hypothetical online setting. Methods An online RCT was conducted with sociodemographically diverse primary caregivers of children aged 6–12 years (data collected and analyzed in 2017–2019). Participants (N=2,373) were randomized to see 1 of 4 messages: (1) nonfood control, (2) kids’ meals are the right size for children, (3) doctors recommend a 600 kcal per meal limit for kids, or (4) 600 kcal per meal is a generally recommended limit for kids. Participants ordered hypothetical meals for their children and themselves and rated meal and message perceptions. Results There were no significant differences between conditions in calories ordered for children at either restaurant, although all 3 food message conditions ordered fewer calories for their children than the control (full service: 27–68 fewer kcal, fast food: 18–64 fewer kcal). The general 600 kcal/meal limit message consistently performed best across outcomes, encouraging parents to order the fewest calories for their children at both restaurants (5%–7% fewer) and significantly increasing their understanding of calorie recommendations for kids’ meals. It also significantly reduced fast-food calories parents ordered for themselves compared with the control (−106 kcal, p=0.042). Conclusions Although no statistically significant differences were detected, messages with specific calorie recommendations for kids led parents to order lower-calorie restaurant meals for their children, suggesting that additional real-world studies with larger sample sizes are warranted.

MotivationThe SARS-CoV-2 variants emerging from South Africa (501.V2) and the UK (B.1.1.7) necessitate rapid assessment of the effects of the corresponding amino acid substitutions in the spike (S) receptor-binding domain (RBD) of the variants on the interactions with the human ACE2 receptor and monoclonal antibodies (mAbs) reported earlier to neutralize the spike.ResultsMolecular modeling and simulations reveal that N501Y, shared by both variants, increases ACE2 binding affinity, and may impact the collective dynamics of the ACE2-RBD complex, occupying a central hinge site that modulates the overall dynamics of the complex. In contrast, the substitutions K417N and E484K in the South African variant 501.V2 would reduce the ACE2-binding affinity by abolishing two interfacial salt bridges that facilitate RBD binding to ACE2, K417(S)-D30(ACE2) and E484 (S)-K31(ACE2). These two mutations may thus be more than compensating the attractive effect induced by N501Y, overall resulting in an ACE2-binding affinity comparable to that of the wildtype RBD. Further analysis of the impact of these mutations on the interactions with mAbs targeting the spike indicate that the substitutions K417N and E484K may also abolish the salt bridges between the spike and selected mAbs, such as REGN10933, BD23, H11_H4, and C105, thus reducing the binding affinity and effectiveness of these mAbs.Contactbahar@pitt.eduSupplementary informationSupplementary data are available atBioinformaticsonline.

Background: The emergence of SARS-CoV-2 variants, especially the Delta variant that became the dominant variant in the US and UK within weeks, necessitates a rational assessment of their impact on the recognition and potential neutralization of the virus by the host cells. Method: We carried out an extensive comparative analysis of the interactions of the variants with cognate molecules (ACE2, furin, or heparin), neutralizing nanobodies (Nbs) and monoclonal antibodies (mAbs) using in silico models and simulations, in addition to Nb-binding assays conducted for the Delta variant. Findings: The results shed light on the molecular origin of experimental observations and help make predictions on the impact of variants that have not been experimentally established to date. Notably, the increased ACE2-binding affinity of variants containing the N501Y or E484K mutations can be traced to the time-dependent disruption and/or formation of interfacial salt bridges, not necessarily apparent from structural models but detected by extensive molecular dynamics simulations. The analysis also explains why the South African variant has an increased tendency to evade mAbs such as REGN10933 (casirivimab), LY-CoV016 (etesevimab), LY-CoV555 (bamlanivimab), BD23, and C105 or the nanobody H11-H4, while being insensitive to others including REGN10987 (imdevimab). Simulations also show the distinctive response of the Delta variant to different antibodies, including the minimal effect on the neutralizing activity of the nanobody Nb20, which is confirmed by our experiments. This contrasts the reduction in the potency of the Eli Lilly mAb LY-CoV555.Interpretations. Of interest are critical substitutions T478K, L452R and P681R in the Delta variant that may explain its increased transmissibility. The former two tend to enhance the associations with ACE2 and heparin. The third, P681R, located at a putative superantigenic site, plays a critical role in enhancing the efficiency of proteolytic cleavage and thus accelerating viral entry, because the polybasic wildtype motif P 681 RRAR serving as recognition site for the polyacidic binding epitope of furin-like proteolytic enzymes is rendered even more basic and attractive upon this substitution. The distinctive behavior of the variants vis-a-vis different types of Abs highlights the significance of carrying out full-atomic structure- and dynamics-dependent studies for assessing the specific response of different Abs to newly emerging variants. Funding: National Institutes of Health (NIGMS and NAIAD awards) and a MolSSI COVID-19 Seed Software Fellowship. Declaration of Interest: Ethical Approval

Evidence showing the effectiveness of policies to reduce the consumption of sugar-sweetened beverages (SSBs) is growing. SSBs are one of the largest sources of added sugar in the diet and are linked to multiple adverse health conditions. This review presents a framework illustrating the various types of policies that have been used to reduce SSB exposure and consumption; policies are organized into four categories (financial, information, defaults, and availability) and take into consideration crosscutting policy considerations (feasibility, impact, and equity). Next, for each category, we describe a specific example and provide evidence of impact. Finally, we discuss crosscutting policy considerations, the challenge of choosing among the various policy options, and important areas for future research. Notably, no single policy will reduce SSB consumption to healthy levels, so an integrated policy approach that adapts to changing market and consumption trends; evolving social, political, and public health needs; and emerging science is critical.

International audience; Peptide ligands of class B G protein-coupled receptors (GPCRs) act via a two-step binding process, but the essential mechanisms that link their extracellular binding to intracellular receptor–arrestin interactions are not fully understood. Using NMR, crosslinking coupled to mass spectrometry, signaling experiments, and computational approaches on the parathyroid hormone (PTH) type 1 receptor (PTHR), we show that initial binding of the PTH C-terminal part constrains the conformation of the flexible PTH N-terminal signaling epitope before a second binding event occurs. A “hot spot” PTH residue, His9, that inserts into the PTHR transmembrane domain at this second step allosterically engages receptor–arrestin coupling. A conformational change in PTHR intracellular loop 3 permits favorable interactions with β-arrestin’s finger loop. These results unveil structural determinants for PTHR–arrestin complex formation and reveal that the two-step binding mechanism proceeds via cooperative fluctuations between ligand and receptor, which extend to other class B GPCRs.

We describe improbable data patterns in the work of Barbalho et al.

Ferroptosis is a death program executed via selective oxidation of arachidonic acid–phosphatidylethanolamines (AA-PE) by 15-lipoxygenases. In mammalian cells and tissues, ferroptosis has been pathogenically associated with brain, kidney, and liver injury/diseases. We discovered that a prokaryotic bacterium, Pseudomonas aeruginosa, that does not contain AA-PE can express lipoxygenase (pLoxA), oxidize host AA-PE to 15-hydroperoxy-AA-PE (15-HOO-AA-PE), and trigger ferroptosis in human bronchial epithelial cells. Induction of ferroptosis by clinical P. aeruginosa isolates from patients with persistent lower respiratory tract infections was dependent on the level and enzymatic activity of pLoxA. Redox phospholipidomics revealed elevated levels of oxidized AA-PE in airway tissues from patients with cystic fibrosis (CF) but not with emphysema or CF without P. aeruginosa. We believe that the evolutionarily conserved mechanism of pLoxA-driven ferroptosis may represent a potential therapeutic target against P. aeruginosa–associated diseases such as CF and persistent lower respiratory tract infections.

We recently discovered a superantigen-like motif sequentially and structurally similar to a staphylococcal enterotoxin B (SEB) segment, near the S1/S2 cleavage site of the SARS-CoV-2 spike protein, which might explain the multisystem inflammatory syndrome (MIS-C) observed in children and the cytokine storm in severe COVID-19 patients. We show here that an anti-SEB monoclonal antibody (mAb), 6D3, can bind this viral motif at its polybasic (PRRA) insert to inhibit infection in live virus assays. The overlap between the superantigenic site of the spike and its proteolytic cleavage site suggests that the mAb prevents viral entry by interfering with the proteolytic activity of cell proteases (furin and TMPRSS2). The high affinity of 6D3 for this site originates from a polyacidic segment at its heavy chain CDR2. The study points to the potential utility of 6D3 for possibly treating COVID-19, MIS-C, or common colds caused by human coronaviruses that also possess a furin-like cleavage site., Graphical abstract, Cheng et al. demonstrate that an anti-SEB antibody can bind the SARS-CoV-2 polybasic (PRRA) insert to inhibit infection in live virus assays. The overlap between the superantigenic site of the spike and its proteolytic cleavage site suggests that the mAb prevents viral entry by interfering with the proteolytic activity of cell proteases.

The association between drinking 100% fruit juice and long-term weight gain is controversial and has been investigated in few studies. We examined whether 100% fruit juice consumption was associated with weight change in a large prospective cohort of postmenopausal women. We analyzed data from 49,106 postmenopausal women in the United States enrolled in the Women's Health Initiative between 1993 and 1998. Food frequency questionnaires at baseline and year 3 assessed food and beverage intake. Body weight was measured at in-person clinic visits. We used linear mixed effects modeling to determine the association between change in 100% fruit juice consumption and 3-year weight change over the same time period. Covariates of interest included age, demographic factors, smoking, body mass index, hormone replacement therapy, lifestyle factors, change in whole fruit intake, and change in sugar-sweetened beverage intake. The mean weight change was 3.2 lbs. over 3 years. In multivariable adjusted analyses, each 1 serving/day increase in 100% fruit juice intake was associated with a 3-year weight gain of 0.39 lbs. (95% confidence interval: 0.10, 0.69). In conclusion, an increase in 100% fruit juice consumption was associated with a small amount of long-term weight gain in postmenopausal women.

Allosteric behavior is central to the function of many proteins, enabling molecular machinery, metabolism, signaling and regulation. Recent years have shown that the intrinsic dynamics of allosteric proteins defined by their 3-dimensional architecture or by the topology of inter-residue contacts favors cooperative motions that bear close similarity to structural changes they undergo during their allosteric actions. These conformational motions are usually driven by energetically favorable or soft modes at the low frequency end of the mode spectrum, and they are evolutionarily conserved among orthologs. These observations brought into light evolutionary adaptation mechanisms that help maintain, optimize or regulate allosteric behavior as the evolution from bacterial to higher organisms introduces sequential heterogeneities and structural complexities.

Background Taxes on sugary beverages are an emerging strategy to improve health by reducing consumption and raising revenues to support community wellbeing. However, taxes may have unintended consequences, and perceptions of these consequences may affect attitudes towards this policy. Methods In June 2017, the Seattle City Council passed an ordinance imposing a tax on sugary beverages, effective January 1, 2018. Between October and December 2017, we recruited 851 adults in Seattle to complete a survey (telephone or online) about support for the tax and their perceptions of tax-related health and economic impacts. We first analyzed data for the full sample. We then tested for differences in participants’ responses by household income level (

OBJECTIVES: To examine whether promotion of water intake in the general population in and of itself reduces sugar-sweetened beverage (SSB) consumption independent from interventions that target SSBs. METHODS: Seven electronic databases were systematically searched: PubMed, Embase, PsycInfo, CINAHL Complete, Cochrane Central Register of Controlled Trials, CAB Direct, and Web of Science. The search hedge included concepts of drinking water, sweetened beverages, and clinical or controlled or longitudinal studies. Selected studies included a primary water promotion intervention and were published between 1 January 2000 and 6 January 2019, while those with more than a minimal SSB reduction intervention were excluded. We identified 5652 publications, chose 107 for full-text review and selected 17 for this review. Two authors independently extracted data using predefined data fields and rated study quality. RESULTS: Nine of the 17 studies were randomized controlled trials, six were non-randomized controlled trials, and two were single-group pre-post studies. Participants were primarily children and adolescents. Seven studies reported a decrease in sugar-sweetened beverage consumption. Among the eight studies that successfully increased water intake, five reported beneficial effects on SSB intake while three did not. Of the five positive studies, three were at serious or high risk of bias. Studies with decrease in sugar-sweetened beverage consumption tended to include a home-based or individually focused intervention. CONCLUSIONS: This review found little evidence that interventions aimed solely at increasing water consumption reduce sugar-sweetened beverage intake. Further research is needed to investigate whether interventions that combine water promotion and SSB reduction strategies could be synergistic for reducing SSB intake. SSB reduction approaches at this time should focus directly on SSBs. FUNDING SOURCES: Healthy Eating Research Program, Robert Wood Johnson Foundation.

Objective To determine whether the presence of an informal caregiver and the patient’s level of social support are associated with better diabetes self-care among adults with poorly controlled diabetes. Methods Cross-sectional study using baseline data from 253 adults of age 30–70 with poorly controlled diabetes. Participants who reported receiving assistance with their diabetes from a friend or family member in the past month were classified as having a caregiver. We used multivariate linear and logistic regression models to evaluate the associations between having a caregiver and level of social support with five self-reported diabetes self-care behaviors: diet, foot checks, blood glucose monitoring, medications, and physical activity. Results Compared to participants with no informal caregiver, those with an informal caregiver were significantly more likely to report moderate or high medication adherence (OR = 1.93, 95% CI: 1.07–3.49, p = 0.028). When we included social support in the model, having a caregiver was no longer significantly associated with medication adherence (OR = 1.50, 95% CI: 0.80–2.82), but social support score was (OR = 1.22, 95% CI: 1.03–1.45, p = 0.023). Discussion Among low-income adults with poorly controlled diabetes, having both an informal caregiver and high social support for diabetes may have a beneficial effect on medication adherence, a key self-care target to improve diabetes control.

Background US law mandates that chain restaurants with 20 or more locations post calorie information on their menus to inform consumers and encourage healthy choices. Few qualitative studies have assessed how parents perceive and use this information when ordering for their children and what types of accompanying messages might increase use of calorie labels when ordering food. Objective We aimed to better understand parents’ perceptions and use of calorie labeling and the types of messages that might increase use. Design We conducted 10 focus groups (n = 58) and 20 shop-along interviews (n = 20). Focus group participants discussed their hypothetical orders and restaurant experiences when dining with their children, and shop-along participants verbalized their decision processes while ordering at a restaurant. Both groups gave feedback on 4 public service messages aimed to increase healthier ordering for children. All interviews were voice-recorded and transcribed. Participants/Setting Participants were primary caregivers of at least 1 child between 6 and 12 years who reported having less than a college education at the time of screening and who commonly ate at chain restaurants. Focus groups were conducted in a conference room, and shop-alongs were conducted in quick-serve and full-service chain restaurants around Philadelphia between August 2016 and May 2017. Analyses A modified grounded theory approach was used to extract themes from transcripts. Results Thematic analysis of transcripts revealed 5 key themes: (1) parents’ use of calorie labels; (2) differences across restaurant settings; (3) nonjudgmental information; (4) financial value and enjoyment of food; and (5) message preferences. These themes suggested that nonjudgmental, fact-based messages that highlight financial value, feelings of fullness, and easy meal component swaps without giving up the treatlike aspect of eating out may be particularly helpful for consumers. Conclusions These findings can inform current US Food and Drug Administration campaign efforts to support consumer use of calorie labels on menus.

[Image: see text] Accurate modeling of structural dynamics of proteins and their differentiation across different species can help us understand generic mechanisms of function shared by family members and the molecular basis of the specificity of individual members. We focused here on the family of lipoxygenases, enzymes that catalyze lipid oxidation, the mammalian and bacterial structures of which have been elucidated. We present a systematic method of approach for characterizing the sequence, structure, dynamics, and allosteric signaling properties of these enzymes using a combination of structure-based models and methods and bioinformatics tools applied to a data set of 88 structures. The analysis elucidates the signature dynamics of the lipoxygenase family and its differentiation among members, as well as key sites that enable its adaptation to specific substrate binding and allosteric activity.

Single-particle analysis by electron microscopy is a well established technique for analyzing the three-dimensional structures of biological macromolecules. Besides its ability to produce high-resolution structures, it also provides insights into the dynamic behavior of the structures by elucidating their conformational variability. Here, the different image-processing methods currently available to study continuous conformational changes are reviewed., Spanish Ministry of Economy and Competitiveness through grants BIO2013-44647-R and BIO2016-76400-R (AEI/FEDER, UE), Comunidad Autonoma de Madrid through grant S2017/BMD-3817, Instituto de Salud Carlos III through grants PT13/0001/0009 and PT17/0009/0010, the European Union (EU) and Horizon 2020 through West-Life (EINFRA-2015-1, Proposal 675858), CORBEL (INFRADEV-1-2014-1, Proposal 654248), ELIXIR–EXCELERATE (INFRADEV-3-2015, Proposal 676559), iNEXT (INFRAIA-1-2014-2015, Proposal 653706), EOSCpilot (INFRADEV-04-2016, Proposal 739563) and the National Institutes of Health (P41GM 103712) (IB).

Introduction Changing food choice architecture in school cafeterias through behavioral economics may increase student selection and consumption of healthy foods. However, most research assesses the effects of short-term interventions. We evaluated a year-long choice architecture intervention implemented by school food service staff. Methods Food service staff from 6 secondary schools in one school district received training and support to implement behavioral economics strategies in their cafeterias to promote student selection of fruit, vegetables, and low-fat white milk. We compared student selection and consumption of these foods in the intervention schools to 5 comparison schools in the same district on the basis of visual assessment of plate waste. We applied a difference-in-differences approach to estimate intervention effect. Results Data for 902 students were assessed at baseline, and data for 1,407 were assessed at follow-up. In fully adjusted analyses for all students, there were significantly greater absolute increases in the proportions of intervention school students selecting any fruit, including (0.09) and excluding (0.16) juice, and students selected more fruit items including (0.21) and excluding (0.17) juice. The absolute increase in proportion of intervention students consuming fruit excluding juice (0.14) was significantly greater. However, in some analyses, fewer intervention students who selected fruits or vegetables ate them, or they ate fewer of them. There were no intervention effects for vegetables or low-fat white milk. Conclusion Our results indicate that behavioral economics-based choice architecture can promote student selection of healthy foods, but they raise questions about whether it increases their consumption.

To describe community health workers (CHWs) roles in a diabetes self-management intervention. Retrospective qualitative inductive analysis of open text home visit encounter form from Peer Support for Achieving Independence in Diabetes (Peer AID), a randomized controlled trial in which low-income individuals with poorly controlled diabetes received either CHW home visits or usual care. Following visits, CHWs completed encounter forms documenting the health goal of the visit, the self-management strategies discussed and participant concerns. 634 encounter reports were completed for the 145 intervention participants. CHW notes revealed three main obstacles to optimal disease control: gaps in diabetes knowledge and self-management skills; socioeconomic conditions; and the complexity of the healthcare system. CHWs helped participants overcome these obstacles through extensive, hands-on education, connecting participants to community resources, and assistance navigating the medical system. In addition, the CHWs offered uncomplicated accessibility and availability to their clients. CHWs can be a valuable asset for low-income patients with chronic health conditions who may require more support than what can provided in a typical primary care visit.

Whether or not drinking 100% fruit juice causes poor health is controversial. Although 100% fruit juice may contain as much sugar as regular soda, it provides needed nutrients to Americans' diets. We systematically reviewed the current evidence of the association of 100% fruit juice consumption and chronic health conditions in children and adults. We focused on data from systematic reviews and meta-analyses about cardiometabolic health outcomes, liver disease, and caries. Aside from increased risk of tooth decay in children and small amounts of weight gain in young children and adults, there is no conclusive evidence that consumption of 100% fruit juice has adverse health effects. Guidelines from groups like the American Academy of Pediatrics and Dietary Guidelines for Americans recommending that 100% fruit juice may be consumed in moderation are consistent with the available evidence and should be used to inform food policies.

BACKGROUND Food insecurity— lack of dependable access to adequate food—may play a role in poor diabetes control.