Summary
This is the first systematic review of reviews to assess the effect of obesity and weight loss on health‐related quality of life (HRQoL). We identified 12 meta‐analyses/systematic reviews ...published between January 2001 and July 2016. They addressed the following themes: (i) the relationship between weight/body mass index and HRQoL (baseline/pre‐intervention; n = 2). (ii) HRQoL after weight loss (varied interventions and/or study design; n = 2). (iii) HRQoL after weight loss (randomized controlled trials only; n = 2). (iv) HRQoL after bariatric surgery (n = 6). We found that in all populations, obesity was associated with significantly lower generic and obesity‐specific HRQoL. The relationship between weight loss and improved HRQoL was consistently demonstrated after bariatric surgery, perhaps due to a greater than average weight loss compared with other treatments. Improved HRQoL was evident after non‐surgical weight loss, but was not consistently demonstrated, even in randomized controlled trials. This inconsistency may be attributed to variation in quality of reporting, assessment measures, study populations and weight‐loss interventions. We recommend longer‐term studies, using both generic and obesity‐specific measures, which go beyond HRQoL in isolation to exploring mediators of HRQoL changes and interactions with other variables, such as comorbidities, fitness level and body image.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The complement system is an essential element of the innate immune response that becomes activated upon recognition of molecular patterns associated with microorganisms, abnormal host cells, and ...modified molecules in the extracellular environment. The resulting proteolytic cascade tags the complement activator for elimination and elicits a pro‐inflammatory response leading to recruitment and activation of immune cells from both the innate and adaptive branches of the immune system. Through these activities, complement functions in the first line of defense against pathogens but also contributes significantly to the maintenance of homeostasis and prevention of autoimmunity. Activation of complement and the subsequent biological responses occur primarily in the extracellular environment. However, recent studies have demonstrated autocrine signaling by complement activation in intracellular vesicles, while the presence of a cytoplasmic receptor serves to detect complement‐opsonized intracellular pathogens. Furthermore, breakthroughs in both functional and structural studies now make it possible to describe many of the intricate molecular mechanisms underlying complement activation and the subsequent downstream events, as well as its cross talk with, for example, signaling pathways, the coagulation system, and adaptive immunity. We present an integrated and updated view of complement based on structural and functional data and describe the new roles attributed to complement. Finally, we discuss how the structural and mechanistic understanding of the complement system rationalizes the genetic defects conferring uncontrolled activation or other undesirable effects of complement.
The complement system is an essential element of the innate immune response to pathogens. This review provides a comprehensive overview of the complement system with particular emphasis on understanding the role of complement proteins in health and disease.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Brown adipose tissue (BAT) has attracted scientific interest as an antidiabetic tissue owing to its ability to dissipate energy as heat. Despite a plethora of data concerning the role of BAT in ...glucose metabolism in rodents, the role of BAT (if any) in glucose metabolism in humans remains unclear. To investigate whether BAT activation alters whole-body glucose homeostasis and insulin sensitivity in humans, we studied seven BAT-positive (BAT(+)) men and five BAT-negative (BAT(-)) men under thermoneutral conditions and after prolonged (5-8 h) cold exposure (CE). The two groups were similar in age, BMI, and adiposity. CE significantly increased resting energy expenditure, whole-body glucose disposal, plasma glucose oxidation, and insulin sensitivity in the BAT(+) group only. These results demonstrate a physiologically significant role of BAT in whole-body energy expenditure, glucose homeostasis, and insulin sensitivity in humans, and support the notion that BAT may function as an antidiabetic tissue in humans.
Phosphoribosyl diphosphate (PRPP) is an important intermediate in cellular metabolism. PRPP is synthesized by PRPP synthase, as follows: ribose 5-phosphate + ATP → PRPP + AMP. PRPP is ubiquitously ...found in living organisms and is used in substitution reactions with the formation of glycosidic bonds. PRPP is utilized in the biosynthesis of purine and pyrimidine nucleotides, the amino acids histidine and tryptophan, the cofactors NAD and tetrahydromethanopterin, arabinosyl monophosphodecaprenol, and certain aminoglycoside antibiotics. The participation of PRPP in each of these metabolic pathways is reviewed. Central to the metabolism of PRPP is PRPP synthase, which has been studied from all kingdoms of life by classical mechanistic procedures. The results of these analyses are unified with recent progress in molecular enzymology and the elucidation of the three-dimensional structures of PRPP synthases from eubacteria, archaea, and humans. The structures and mechanisms of catalysis of the five diphosphoryltransferases are compared, as are those of selected enzymes of diphosphoryl transfer, phosphoryl transfer, and nucleotidyl transfer reactions. PRPP is used as a substrate by a large number phosphoribosyltransferases. The protein structures and reaction mechanisms of these phosphoribosyltransferases vary and demonstrate the versatility of PRPP as an intermediate in cellular physiology. PRPP synthases appear to have originated from a phosphoribosyltransferase during evolution, as demonstrated by phylogenetic analysis. PRPP, furthermore, is an effector molecule of purine and pyrimidine nucleotide biosynthesis, either by binding to PurR or PyrR regulatory proteins or as an allosteric activator of carbamoylphosphate synthetase. Genetic analyses have disclosed a number of mutants altered in the PRPP synthase-specifying genes in humans as well as bacterial species.
Cognitive Control Signals for Neural Prosthetics Musallam, S.; Corneil, B. D.; Greger, B. ...
Science (American Association for the Advancement of Science),
07/2004, Volume:
305, Issue:
5681
Journal Article
Peer reviewed
Open access
Recent development of neural prosthetics for assisting paralyzed patients has focused on decoding intended hand trajectories from motor cortical neurons and using this signal to control external ...devices. In this study, higher level signals related to the goals of movements were decoded from three monkeys and used to position cursors on a computer screen without the animals emitting any behavior. Their performance in this task improved over a period of weeks. Expected value signals related to fluid preference, the expected magnitude, or probability of reward were decoded simultaneously with the intended goal. For neural prosthetic applications, the goal signals can be used to operate computers, robots, and vehicles, whereas the expected value signals can be used to continuously monitor a paralyzed patient's preferences and motivation.
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The ability of root cells to distinguish mutualistic microbes from pathogens is crucial for plants that allow symbiotic microorganisms to infect and colonize their internal root tissues. Here we show ...that Lotus japonicus and Medicago truncatula possess very similar LysM pattern-recognition receptors, LjLYS6/MtLYK9 and MtLYR4, enabling root cells to separate the perception of chitin oligomeric microbe-associated molecular patterns from the perception of lipochitin oligosaccharide by the LjNFR1/MtLYK3 and LjNFR5/MtNFP receptors triggering symbiosis. Inactivation of chitin-receptor genes in Ljlys6, Mtlyk9, and Mtlyr4 mutants eliminates early reactive oxygen species responses and induction of defense-response genes in roots. Ljlys6, Mtlyk9, and Mtlyr4 mutants were also more susceptible to fungal and bacterial pathogens, while infection and colonization by rhizobia and arbuscular mycorrhizal fungi was maintained. Biochemical binding studies with purified LjLYS6 ectodomains further showed that at least six GlcNAc moieties (CO6) are required for optimal binding efficiency. The 2.3-Å crystal structure of the LjLYS6 ectodomain reveals three LysM βααβ motifs similar to other LysM proteins and a conserved chitin-binding site. These results show that distinct receptor sets in legume roots respond to chitin and lipochitin oligosaccharides found in the heterogeneous mixture of chitinaceous compounds originating from soil microbes. This establishes a foundation for genetic and biochemical dissection of the perception and the downstream responses separating defense from symbiosis in the roots of the 80–90% of land plants able to develop rhizobial and/or mycorrhizal endosymbiosis.
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A common perception in limnology is that shallow lakes are homogeneously mixed owing to their small water volume. However, this perception is largely gained by downscaling knowledge from large lakes ...to their smaller counterparts. Here we show that shallow vegetated lakes (less than 0.6 m), in fact, undergo recurring daytime stratification and nocturnal mixing accompanied by extreme chemical variations during summer. Dense submerged vegetation effectively attenuates light and turbulence generating separation between warm surface waters and much colder bottom waters. Photosynthesis in surface waters produces oxygen accumulation and CO2 depletion, whereas respiration in dark bottom waters causes anoxia and CO2 accumulation. High daytime pH in surface waters promotes precipitation of CaCO3 which is re-dissolved in bottom waters. Nocturnal convective mixing re-introduces oxygen into bottom waters for aerobic respiration and regenerated inorganic carbon into surface waters, which supports intense photosynthesis. Our results reconfigure the basic understanding of local environmental gradients in shallow lakes, one of the most abundant freshwater habitats globally.
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Early diagnosis is a key factor in improving the outcomes of cancer patients. A greater understanding of the pre-diagnostic patient pathways is vital yet, at present, research in this field lacks ...consistent definitions and methods. As a consequence much early diagnosis research is difficult to interpret. A consensus group was formed with the aim of producing guidance and a checklist for early cancer-diagnosis researchers. A consensus conference approach combined with nominal group techniques was used. The work was supported by a systematic review of early diagnosis literature, focussing on existing instruments used to measure time points and intervals in early cancer-diagnosis research. A series of recommendations for definitions and methodological approaches is presented. This is complemented by a checklist that early diagnosis researchers can use when designing and conducting studies in this field. The Aarhus checklist is a resource for early cancer-diagnosis research that should promote greater precision and transparency in both definitions and methods. Further work will examine whether the checklist can be readily adopted by researchers, and feedback on the guidance will be used in future updates.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
We propose a novel method for the elimination of negative Monte Carlo event weights. The method is process-agnostic, independent of any analysis, and preserves all physical observables. We ...demonstrate the overall performance and systematic improvement with increasing event sample size, based on predictions for the production of a W boson with two jets calculated at next-to-leading order perturbation theory.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
Background
Hidradenitis suppurativa (HS) is a recurrent inflammatory skin disease that, apart from rare causative loss‐of‐function mutations, has a widely unknown genetic aetiology.
...Objectives
To estimate the relative importance of genetic and environmental factors underlying susceptibility to HS.
Methods
Via the Danish Twin Registry and the Danish National Patient Registry we pulled together information on zygosity with that of HS status. Cases of HS were identified by the International Classification of Diseases (ICD)‐8 (705·91) and ICD‐10 (L73·2). Heritability was assessed by the classic biometric model and the possibility of gene–gene interaction via the multilocus modelling approach.
Results
Among 100 044 registered twins, we found 170 twins (from 163 pairs) diagnosed with HS. The seven concordant pairs were all monozygotic. Monozygotic twins had a case‐wise concordance rate of 28% 95% confidence interval (CI) 7–49, corresponding to a familial risk of 73 (95% CI 13–133) times that of the background population. The biometrical modelling suggested a heritability of 0·80 (95% CI 0·67–0·93), and the multilocus index estimate was 230 (95% CI 60–400). This is highly indicative of gene–gene interactions, with the possibility of up to six interacting loci.
Conclusions
This twin study was substantially larger and employed a more valid phenotype than previous studies. Genetics account for the majority of HS susceptibility, and HS is most likely caused by gene–gene interactions rather than monogenetic mutations or solely additive genetic factors. New approaches aimed at assessing potential interactions at a single‐nucleotide polymorphism (SNP)–SNP level should be implemented in future HS genome‐wide association studies.
What is already known about this topic?
Hidradenitis suppurativa (HS) is characterized by a high heritability, estimated to be around 80%.
Causative monogenetic mutations are rare and have only been able to explain approximately 5% of cases of HS.
A large international genome‐wide association study (GWAS) collaboration is currently viewed as the best option to discover the genetic causes for HS.
What does this study add?
This study confirms the previous HS heritability estimate.
Additionally, it shows that HS is most likely caused by gene–gene interactions rather than monogenetic mutations or solely additive genetic factors.
This discovery is important for GWAS, and the possibility of gene–gene interaction should therefore be accounted for when mapping genetic causes underlying HS.
Linked Comment: K.R. van Straalen and W. Gulliver. Br J Dermatol 2022; 186:9–10.
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