•Guidelines for studies examining the effects of stress on cognition are provided.•Following these guidelines will maximize the interpretability of obtained results.•Understanding these guidelines ...will help readers to interpret prior studies of stress and cognition.
Fueling the rapid growth in our understanding of how stress influences cognition, the number of studies examining the effects of stress on various cognitive processes has grown substantially over the last two decades. Despite this growth, few published guidelines exist for designing these studies, and divergent paradigm designs can diminish typical effects of stress or even reverse them. The goal of this review, therefore, is to survey necessary considerations (e.g., validating a stress induction), important considerations (e.g., specifying the timing of the stressor and cognitive task), and best practices (e.g., using Bayesian analyses) when designing a study that aims at least in part to examine the effects of acute stress on some cognitive process or function. These guidelines will also serve to help readers of these studies interpret what may otherwise be very confusing, anomalous results. Designing and interpreting studies with these considerations and practices in mind will help to move the field of stress and cognition forward by clarifying how, exactly, stress influences performance on a given cognitive task in a population of interest.
•We conducted a meta-analysis of associations between obesity/overweight and various executive functions.•Obese participants showed broad impairments on executive function.•Overweight participants ...showed significant deficits on inhibition and working memory performances.•Measures of executive function moderated effects of obesity on working memory and decision-making.
Prior research has suggested that obesity/overweight may be associated with deficits in executive function. If true, this has important clinical implications. In this review, we synthesize the current literature by conducting a meta-analysis of studies comparing executive functions in overweight/obese individuals to normal weight controls. We identified 72 studies—with 4904 overweight/obese participants—that met our inclusion criteria. Effect sizes were analyzed using the robust variance estimation random effects meta-regression technique. It was found that obese participants showed broad impairments on executive function, including on tasks primarily utilizing inhibition, cognitive flexibility, working memory, decision-making, verbal fluency, and planning; overweight participants only showed significant deficits in inhibition and working memory. The only moderator of effects of obesity to emerge significant was the task used to assess the respective executive function, which moderated effects of obesity on working memory and decision-making. There were not enough studies of overweight individuals to make strong claims about moderating effects in those studies. In sum, current evidence supports the existence of broad executive function deficits in obese individuals, and inhibition and working memory deficits in overweight individuals.
Macrophage activation syndrome (MAS) is an acute episode of overwhelming inflammation characterized by activation and expansion of T lymphocytes and hemophagocytic macrophages. In rheumatology, it ...occurs most frequently in patients with systemic juvenile idiopathic arthritis (SJIA) and systemic lupus erythematosus. The main clinical manifestations include cytopenias, liver dysfunction, coagulopathy resembling disseminated intravascular coagulation, and extreme hyperferritinemia. Clinically and pathologically, MAS bears strong similarity to hemophagocytic lymphohistiocytosis (HLH), and some authors prefer the term secondary HLH to describe it. Central to its pathogenesis is a cytokine storm, with markedly increased levels of numerous proinflammatory cytokines including IL-1, IL-6, IL-18, TNFα, and IFNγ. Although there is evidence that IFNγ may play a central role in the pathogenesis of MAS, the role of other cytokines is still not clear. There are several reports of SJIA-associated MAS dramatically benefiting from anakinra, a recombinant IL-1 receptor antagonist, but the utility of other biologics in MAS is not clear. The mainstay of treatment remains corticosteroids; other medications, including cyclosporine, are used in patients who fail to respond.
A growing body of research has indicated that acute stress can critically impact memory. However, there are a number of inconsistencies in the literature, and important questions remain regarding the ...conditions under which stress effects emerge as well as basic questions about how stress impacts different phases of memory. In this meta-analysis, we examined 113 independent studies in humans with 6,216 participants that explored effects of stress on encoding, postencoding, retrieval, or postreactivation phases of episodic memory. The results indicated that when stress occurred prior to or during encoding it impaired memory, unless both the delay between the stressor and encoding was very short and the study materials were directly related to the stressor, in which case stress improved encoding. In contrast, postencoding stress improved memory unless the stressor occurred in a different physical context than the study materials. When stress occurred just prior to or during retrieval, memory was impaired, and these effects were larger for emotionally valenced materials than neutral materials. Although stress consistently increased cortisol, the magnitude of the cortisol response was not related to the effects of stress on memory. Nonetheless, the effects of stress on memory were generally reduced in magnitude for women taking hormonal contraceptives. These analyses indicate that stress disrupts some episodic memory processes while enhancing others, and that the effects of stress are modulated by a number of critical factors. These results provide important constraints on current theories of stress and memory, and point to new questions for future research.
DONSON: Slding in 2 the limelight Stewart, Grant S.
DNA repair,
February 2024, 2024-Feb, 2024-02-00, 20240201, Letnik:
134
Journal Article
Recenzirano
Odprti dostop
For over a decade, it has been known that yeast Sld2, Dpb11, GINS and Polε form the pre-loading complex (pre-LC), which is recruited to a CDC45-bound MCM2–7 complex by the Sld3/Sld7 heterodimer in a ...phospho-dependent manner. Whilst functional orthologs of Dbp11 (TOPBP1), Sld3 (TICRR) and Sld7 (MTBP) have been identified in metazoans, controversy has surrounded the identity of the Sld2 ortholog. It was originally proposed that the RECQ helicase, RECQL4, which is mutated in Rothmund-Thomson syndrome, represented the closest vertebrate ortholog of Sld2 due to a small region of sequence homology at its N-Terminus. However, there is no clear evidence that RECQL4 is required for CMG loading. Recently, new findings suggest that the functional ortholog of Sld2 is actually DONSON, a replication fork stability factor mutated in a range of neurodevelopmental disorders characterised by microcephaly, short stature and limb abnormalities. These studies show that DONSON forms a complex with TOPBP1, GINS and Polε analogous to the pre-LC in yeast, which is required to position the GINS complex on the MCM complex and initiate DNA replication. Taken together with previously published functions for DONSON, these observations indicate that DONSON plays two roles in regulating DNA replication, one in promoting replication initiation and one in stabilising the fork during elongation. Combined, these findings may help to uncover why DONSON mutations are associated with such a wide range of clinical deficits.
•DONSON is the functional ortholog of yeast Sld2.•DONSON forms a complex with TOPBP1, GINS and Polε to form the pre-loading complex.•DONSON functions to initiate DNA replication by loading the GINS complex onto the MCM helicase.
Recent estimates suggest that more than 50% of all deaths worldwide are currently attributable to inflammation-related diseases. Psychosocial interventions may represent a potentially useful strategy ...for addressing this global public health problem, but which types of interventions reliably improve immune system function, under what conditions, and for whom are unknown.
To address this issue, we conducted a systematic review and meta-analysis of randomized clinical trials (RCTs) in which we estimated associations between 8 different psychosocial interventions and 7 markers of immune system function, and examined 9 potential moderating factors.
PubMed, Scopus, PsycInfo, and ClinicalTrials.gov databases were systematically searched from February 1, 2017, to December 31, 2018, for all relevant RCTs published through December 31, 2018.
Eligible RCTs included a psychosocial intervention, immune outcome, and preintervention and postintervention immunologic assessments. Studies were independently examined by 2 investigators. Of 4621 studies identified, 62 were eligible and 56 included.
Data were extracted and analyzed from January 1, 2019, to July 29, 2019. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline was followed. Data were extracted by 2 investigators who were blind to study hypotheses and analyses, and were then analyzed using robust variance estimation. Analysis included 8 psychosocial interventions (behavior therapy, cognitive therapy, cognitive behavior therapy CBT, CBT plus additive treatment or mode of delivery that augmented the CBT, bereavement or supportive therapy, multiple or combined interventions, other psychotherapy, and psychoeducation), 7 immune outcomes (proinflammatory cytokine or marker levels, anti-inflammatory cytokine levels, antibody levels, immune cell counts, natural killer cell activity, viral load, and other immune outcomes), and 9 moderating factors (intervention type, intervention format, intervention length, immune marker type, basal vs stimulated markers, immune marker measurement timing, disease state or reason for treatment, age, and sex).
The primary a priori outcomes were pretest-posttest-control (ppc) group effect sizes (ppc g) for the 7 immunologic outcomes investigated.
Across 56 RCTs and 4060 participants, psychosocial interventions were associated with enhanced immune system function (ppc g = 0.30, 95% CI, 0.21-0.40; t50.9 = 6.22; P < .001). Overall, being randomly assigned to a psychosocial intervention condition vs a control condition was associated with a 14.7% (95% CI, 5.7%-23.8%) improvement in beneficial immune system function and an 18.0% (95% CI, 7.2%-28.8%) decrease in harmful immune system function over time. These associations persisted for at least 6 months following treatment and were robust across age, sex, and intervention duration. These associations were most reliable for CBT (ppc g = 0.33, 95% CI, 0.19-0.47; t27.2 = 4.82; P < .001) and multiple or combined interventions (ppc g = 0.52, 95% CI, 0.17-0.88; t5.7 = 3.63; P = .01), and for studies that assessed proinflammatory cytokines or markers (ppc g = 0.33, 95% CI, 0.19-0.48; t25.6 = 4.70; P < .001).
These findings suggest that psychosocial interventions are reliably associated with enhanced immune system function and may therefore represent a viable strategy for improving immune-related health.
Acute stress impaired working memory, cognitive flexibility, and interference control.Acute stress enhanced response inhibition.Acute stress effects on executive functions were moderated by a ...number of variables.Acute stress effects differed markedly from cortisol effects on executive functions.
Core executive functions such as working memory, inhibition, and cognitive flexibility are integral to daily life. A growing body of research has suggested that acute stress may impair core executive functions. However, there are a number of inconsistencies in the literature, leading to uncertainty about how or even if acute stress influences core executive functions. We addressed this by conducting a meta-analysis of acute stress effects on working memory, inhibition, and cognitive flexibility. We found that stress impaired working memory and cognitive flexibility, whereas it had nuanced effects on inhibition. Many of these effects were moderated by other variables, such as sex. In addition, we compared effects of acute stress on core executive functions to effects of cortisol administration and found some striking differences. Our findings indicate that stress works through mechanisms aside from or in addition to cortisol to produce a state characterized by more reactive processing of salient stimuli but greater control over actions. We conclude by highlighting some important future directions for stress and executive function research.
A recently developed human norovirus cell culture system revealed that the presence of bile enhanced or was an essential requirement for the growth of certain genotypes. Before this discovery, ...histo-blood group antigens (HBGAs) were the only well-studied cofactor known for human noroviruses, and there was evidence that several genotypes poorly bound HBGAs. Therefore, the purpose of this study was to investigate how human norovirus capsids interact with bile acids. We found that bile acids had low-micromolar affinities for GII.1, GII.10, and GII.19 capsids but did not bind GI.1, GII.3, GII.4, or GII.17. We showed that bile acid bound at a partially conserved pocket on the norovirus capsid-protruding (P) domain using X-ray crystallography. Amino acid sequence alignment and structural analysis delivered an explanation of selective bile acid binding. Intriguingly, we discovered that binding of the bile acid was the critical step to stabilize several P domain loops that optimally placed an essential amino acid side chain (Asp375) to bind HBGAs in an otherwise HBGA nonbinder (GII.1). Furthermore, bile acid enhanced HBGA binding for a known HBGA binder (GII.10). Altogether, these new data suggest that bile acid functions as a loop-stabilizing regulator and enhancer of HBGA binding for certain norovirus genotypes.
Given that human norovirus virions likely interact with bile acid during a natural infection, our evidence that an HBGA nonbinder (GII.1) can be converted to an HBGA binder after bile acid binding is of major significance. Our data provide direct evidence that, like HBGAs, bile acid interaction on the capsid is an important cofactor for certain genotypes. However, more unanswered questions seem to arise from these new discoveries. For example, is there an association between the bile acid requirement and the prevalence of certain genotypes? That is, the GII.1 and GII.10 (bile acid binders) genotypes rarely caused outbreaks, whereas the GII.4 and GII.17 genotypes (bile acid nonbinders) were responsible for large epidemics. Therefore, it seems plausible that certain genotypes require bile acids, whereas others have modified their bile acid requirements on the capsid.
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