Chemokines from a Structural Perspective Miller, Michelle C; Mayo, Kevin H
International journal of molecular sciences,
10/2017, Letnik:
18, Številka:
10
Journal Article
Recenzirano
Odprti dostop
Chemokines are a family of small, highly conserved cytokines that mediate various biological processes, including chemotaxis, hematopoiesis, and angiogenesis, and that function by interacting with ...cell surface G-Protein Coupled Receptors (GPCRs). Because of their significant involvement in various biological functions and pathologies, chemokines and their receptors have been the focus of therapeutic discovery for clinical intervention. There are several sub-families of chemokines (e.g., CXC, CC, C, and CX3C) defined by the positions of sequentially conserved cysteine residues. Even though all chemokines also have a highly conserved, three-stranded β-sheet/α-helix tertiary structural fold, their quarternary structures vary significantly with their sub-family. Moreover, their conserved tertiary structures allow for subunit swapping within and between sub-family members, thus promoting the concept of a "chemokine interactome". This review is focused on structural aspects of CXC and CC chemokines, their functional synergy and ability to form heterodimers within the chemokine interactome, and some recent developments in structure-based chemokine-targeted drug discovery.
Abstract
Study Objectives
To assess the prospective relationship between sleep and obesity in a paediatric population.
Methods
We performed a systematic search using PubMed, Embase, Web of Science, ...and Cochrane (up to September 25, 2017). Included studies were prospective, had follow-up of ≥1 year, had duration of sleep at baseline, and measures of incidence of overweight or obesity and/or changes in body mass index (BMI) z-score and BMI during follow-up. We extracted relative risks or changes in BMI z-score or BMI and 95% confidence intervals (CI) and pooled them using a random effect model.
Results
Forty-two studies were included but, as there was significant heterogeneity, results are presented by age strata. Short sleep was associated with a greater risk of developing overweight or obesity in infancy (seven studies, 14738 participants, risk ratio RR: 1.40; 95% CI 1.19 to 1.65; p < .001), early childhood (eight studies, 31104 participants, RR: 1.57; 1.40 to 1.76; p < .001), middle childhood (three studies, 3005 participants, RR: 2.23; 2.18 to 2.27; p < .001), and adolescence (three studies, 26652 participants, RR: 1.30; 1.11 to 1.53; p < .002). Sleep duration was also associated with a significant change in BMI z-score (14 studies, 18 cohorts, 31665 participants; mean difference −0.03; −0.04 to −0.01 per hour sleep; p = .001) and in BMI (16 studies, 24 cohorts, 24894 participants; mean difference −0.03 kg/m2; −0.04 to −0.01 for every hour of increase in sleep; p = .001)
Conclusions
Short sleep duration is a risk factor or marker of the development of obesity in infants, children, and adolescents.
The aims of the study were to review the rapidly emerging COVID-19 literature to determine 1) the relationship between obstructive sleep apnoea (OSA) and adverse COVID-19 outcomes and, 2) potential ...causal mechanisms 3) what effect COVID-19 has had on OSA diagnosis and 4) what effect COVID-19 has had on treatment and management of OSA during this period. PubMed was systematically searched up to 020620. Studies were included if they had examined the relationship between COVID-19 and OSA. Studies were included that were in English and had the full text available. The findings from this study suggest that many of the risk factors and co-morbidities associated for OSA which include obesity, hypertension and diabetes mellitus are associated with poor COVID-19 outcomes. There are plausible mechanisms by which OSA may independently increase one's risk of morbidity and mortality associated with COVID-19 and data from the newly published CORONADO study suggests that OSA treated patients may be at increased risk of death from COVID-19. It is clear that the pandemic has had a major effect on the treatment management and diagnosis of OSA and moving forward it may be necessary to explore new diagnosis and treatment pathways for these individuals.
What does memory mean for learning in an age of smartphones and search engines?Human minds are made of memories, and today those memories have competition. Biological memory capacities are being ...supplanted, or at least supplemented, by digital ones, as we rely on recording—phone cameras, digital video, speech-to-text—to capture information we'll need in the future and then rely on those stored recordings to know what happened in the past. Search engines have taken over not only traditional reference materials but also the knowledge base that used to be encoded in our own brains. Google remembers, so we don't have to. And when we don't have to, we no longer can. Or can we?Remembering and Forgetting in the Age of Technology offers concise, nontechnical explanations of major principles of memory and attention—concepts that all teachers should know and that can inform how technology is used in their classes. Teachers will come away with a new appreciation of the importance of memory for learning, useful ideas for handling and discussing technology with their students, and an understanding of how memory is changing in our technology-saturated world.
Increasing evidence suggests an association between both short and long duration of habitual sleep with adverse health outcomes.
To assess whether the population longitudinal evidence supports the ...presence of a relationship between duration of sleep and all-cause mortality, to investigate both short and long sleep duration and to obtain an estimate of the risk.
We performed a systematic search of publications using MEDLINE (1966-2009), EMBASE (from 1980), the Cochrane Library, and manual searches without language restrictions. We included studies if they were prospective, had follow-up >3 years, had duration of sleep at baseline, and all-cause mortality prospectively. We extracted relative risks (RR) and 95% confidence intervals (CI) and pooled them using a random effect model. We carried out sensitivity analyses and assessed heterogeneity and publication bias.
Overall, the 16 studies analyzed provided 27 independent cohort samples. They included 1,382,999 male and female participants (followup range 4 to 25 years), and 112,566 deaths. Sleep duration was assessed by questionnaire and outcome through death certification. In the pooled analysis, short duration of sleep was associated with a greater risk of death (RR: 1.12; 95% CI 1.06 to 1.18; P < 0.01) with no evidence of publication bias (P = 0.74) but heterogeneity between studies (P = 0.02). Long duration of sleep was also associated with a greater risk of death (1.30; 1.22 to 1.38; P < 0.0001) with no evidence of publication bias (P = 0.18) but significant heterogeneity between studies (P < 0.0001).
Both short and long duration of sleep are significant predictors of death in prospective population studies.
Aims
To assess the relationship between duration of sleep and morbidity and mortality from coronary heart disease (CHD), stroke, and total cardiovascular disease (CVD).
Methods and results
We ...performed a systematic search of publications using MEDLINE (1966-2009), EMBASE (from 1980), the Cochrane Library, and manual searches without language restrictions. Studies were included if they were prospective, follow-up >3 years, had duration of sleep at baseline, and incident cases of CHD, stroke, or CVD. Relative risks (RR) and 95% confidence interval (CI) were pooled using a random-effect model. Overall, 15 studies (24 cohort samples) included 474 684 male and female participants (follow-up 6.9-25 years), and 16 067 events (4169 for CHD, 3478 for stroke, and 8420 for total CVD). Sleep duration was assessed by questionnaire and incident cases through certification and event registers. Short duration of sleep was associated with a greater risk of developing or dying of CHD (RR 1.48, 95% CI 1.22-1.80, P < 0.0001), stroke (1.15, 1.00-1.31, P = 0.047), but not total CVD (1.03, 0.93-1.15, P = 0.52) with no evidence of publication bias (P = 0.95, P = 0.30, and P = 0.46, respectively). Long duration of sleep was also associated with a greater risk of CHD (1.38, 1.15-1.66, P = 0.0005), stroke (1.65, 1.45-1.87, P < 0.0001), and total CVD (1.41, 1.19-1.68, P < 0.0001) with no evidence of publication bias (P = 0.92, P = 0.96, and P = 0.79, respectively).
Conclusion
Both short and long duration of sleep are predictors, or markers, of cardiovascular outcomes.
Improving the regional organization of food flow requires an understanding of system constraints. System transformation is necessary if the system is to include regional, independent wholesale food ...suppliers and to distribute food in an equitable and sustainable manner. Regional suppliers play a pivotal role in overall food system resilience, an emerging issue in wake of the numerous failures in conventional food supply chains exacerbated by COVID-19-related disruptions. Yet alternative supply chains that link local producers with towns and urban centers regionally, represent a small fraction of our nation's food suppliers. They struggle to compete with larger distribution networks that can supply products in-and out-of-season by global procurement. The upper Midwest harbors numerous local and regional food supply chains consisting of farms, processors, trucking companies, wholesalers and other firms that share a commitment to sustainability and local economic development. A constellation of challenges hamper their emergence, however, even as larger scale food supply chains flounder or fail to effectively serve communities. Informed by Donella Meadows's work on leverage points for systemic change, a collaborative, transdisciplinary and systems research effort examined conventional food supply networks and identified key opportunities for shifting food supply chain relationships. System concepts such as stock and flow, leverage points, and critical thresholds helped us to frame and identify challenges and opportunities in the current system. The second and third phase of our collaborative research effort occurred over 4 years (2013–2016) and involved twenty-six people in co-generation of knowledge as a loose-knit team. The team included farmers, supply chain practitioners, students, academic staff and faculty from multiple departments and colleges. Our primary method was to host public workshops with practitioner speakers and participants to identify dominant narratives and key concepts within discourses of different participants in distribution networks. The literature review was iterative, based on challenges, ideas and specific questions discussed at workshops. Our research exposed two meta-narratives shaping the supply chain: diversity and efficiency. In addition to these high-leverage narratives, we identified and examined five key operational thresholds in the Upper Midwest regional food system that could be leveraged to improve food flow in the region. Attention to these areas makes it possible for businesses to operate within environmental limits and develop social structures that can meet scale efficiencies necessary for economic success. We iteratively shared this co-produced knowledge with decision-makers via local food policy councils, local government, and national policy circles with the goal of supplying actionable information. This phased action research project created the environment necessary for a group of food system entrepreneurs to emerge and collaborate, poised to improve system resilience in anticipation of food system disruptions. It forms the basis for on-going research on food flow, regional resilience, and supply chain policy.
Sleep and Cardio-Metabolic Disease Cappuccio, Francesco P.; Miller, Michelle A.
Current cardiology reports,
11/2017, Letnik:
19, Številka:
11
Journal Article
Recenzirano
Odprti dostop
Purpose of Review
This review summarises and discusses the epidemiological evidence suggesting a causal relationship between sleep duration and cardio-metabolic risk and outcomes in population.
...Recent Findings
Sleep duration is affected by a variety of cultural, social, psychological, behavioural, pathophysiological and environmental influences. Changes in modern society—like longer working hours, more shift-work, 24/7 availability of commodities and 24-h global connectivity—have been associated with a gradual reduction in sleep duration and sleeping patterns across westernised populations. We review the evidence of an association between sleep disturbances and the development of cardio-metabolic risk and disease and discuss the implications for causality of these associations.
Summary
Prolonged curtailment of sleep duration is a risk factor for the development of obesity, diabetes, hypertension, heart disease and stroke and may contribute, in the long-term, to premature death.
The Biden Administration is reviewing supply chains as part of its response to recent supply chain failures during COVID-19, and anticipated disruptions associated with climate change. This policy ...analysis discusses supply chain management, that is, the monitoring and continual improvement of materials flow and information flow to better manage risk. We are in an era of proprietary big data and digitized applications to make sense of it. Healthy food systems require policy to address unequal access to food systems data and information that occurs between businesses as well as between private businesses and government. Managing risk to a nation’s overall food system is an important government function that includes setting fair market rules and ensuring open information exchange in food supply chains. In this way, our government ensures equitable food and market access as new technologies and disruptions arise. This paper reviews these concepts considering current policy actions of the Biden Administration.
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