Phenotypic plasticity is the capacity for an individual genotype to produce different phenotypes in response to environmental variation. Most traits are plastic, but the degree to which plasticity is ...adaptive or non-adaptive depends on whether environmentally induced phenotypes are closer or further away from the local optimum. Existing theories make conflicting predictions about whether plasticity constrains or facilitates adaptive evolution. Debate persists because few empirical studies have tested the relationship between initial plasticity and subsequent adaptive evolution in natural populations. Here we show that the direction of plasticity in gene expression is generally opposite to the direction of adaptive evolution. We experimentally transplanted Trinidadian guppies (Poecilia reticulata) adapted to living with cichlid predators to cichlid-free streams, and tested for evolutionary divergence in brain gene expression patterns after three to four generations. We find 135 transcripts that evolved parallel changes in expression within the replicated introduction populations. These changes are in the same direction exhibited in a native cichlid-free population, suggesting rapid adaptive evolution. We find 89% of these transcripts exhibited non-adaptive plastic changes in expression when the source population was reared in the absence of predators, as they are in the opposite direction to the evolved changes. By contrast, the remaining transcripts exhibiting adaptive plasticity show reduced population divergence. Furthermore, the most plastic transcripts in the source population evolved reduced plasticity in the introduction populations, suggesting strong selection against non-adaptive plasticity. These results support models predicting that adaptive plasticity constrains evolution, whereas non-adaptive plasticity potentiates evolution by increasing the strength of directional selection. The role of non-adaptive plasticity in evolution has received relatively little attention; however, our results suggest that it may be an important mechanism that predicts evolutionary responses to new environments.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Inhibitory control or the ability to refrain from incorrect responses is a critical executive function known to diminish during aging. Imaging studies have elucidated cerebral changes that may ...underlie the age-related deficits. However, it remains unclear whether the structural and functional changes occur in the same brain regions and whether reduced gray matter volumes (GMV) mediate decreased activation during inhibition. Here, in a sample of 149 participants, we addressed the issues using structural and functional magnetic resonance imaging. Individual's response inhibition was evaluated by the stop signal reaction time (SSRT) in a stop signal task. The results showed that age was associated with prolonged SSRT across participants. Many cortical and subcortical regions demonstrated age-related reduction in GMV and activation to response inhibition. Additionally, age-related diminution in inhibitory control, as indexed by the SSRT, was associated with both shared and distinct morphometric and functional changes. Voxel-based morphometry demonstrated age-related reduction in GMV in the right dorsolateral prefrontal cortex and caudate head as well as bilateral insula, in association with prolonged SSRT. In a contrast of stop success versus go success trials, age was associated with lower activation in the medial and inferior frontal cortex and inferior parietal cortex. Further, reduction in GMV mediated age-related differences in activations only of the medial prefrontal cortex, providing limited evidence for structure function association. Thus, the decline in inhibitory control, as evidenced in the stop signal task, manifest with both shared and distinct structural and functional processes during aging.
How underlying mechanisms bias evolution toward predictable outcomes remains an area of active debate. In this study, we leveraged phenotypic plasticity and parallel adaptation across independent ...lineages of Trinidadian guppies (Poecilia reticulata) to assess the predictability of gene expression evolution during parallel adaptation. Trinidadian guppies have repeatedly and independently adapted to high‐ and low‐predation environments in the wild. We combined this natural experiment with a laboratory breeding design to attribute transcriptional variation to the genetic influences of population of origin and developmental plasticity in response to rearing with or without predators. We observed substantial gene expression plasticity, as well as the evolution of expression plasticity itself, across populations. Genes exhibiting expression plasticity within populations were more likely to also differ in expression between populations, with the direction of population differences more likely to be opposite those of plasticity. While we found more overlap than expected by chance in genes differentially expressed between high‐ and low‐predation populations from distinct evolutionary lineages, the majority of differentially expressed genes were not shared between lineages. Our data suggest alternative transcriptional configurations associated with shared phenotypes, highlighting a role for transcriptional flexibility in the parallel phenotypic evolution of a species known for rapid adaptation.
During the COVID-19 pandemic, community-based research studies experienced prolonged shutdowns unless able to pivot to remote study procedures.
To describe the revision of two National Institutes of ...Health funded community-based palliative-focused clinical trials serving underserved populations to accommodate remote subject enrollment and examine its impact.
Transitioning to remote processes required multiple protocol and procedural changes including: altering informed consent processes; reducing the number of surveys administered; adding internet access as an inclusion criterion. To understand technological challenges, a screening tool was developed for one study to identify potentially eligible subjects’ technology abilities and accessibility.
Subjects’ limited access to the internet and internet-enabled devices and discomfort with technology led to changes in recruitment patterns. Lack of familiarity with technology increased the amount of time it took research team members and subjects to connect remotely. Patients with significant cognitive and/or sensory deficits were at higher risk of experiencing fatigue during remote study visits leading to streamlining of data collection. A researcher-developed technology screening tool found that potential subjects were not comfortable with videoconferencing through Zoom expressing a preference for phone visits. Reduced travel time made scheduling remote study visits more efficient.
Future community- and home-based palliative care trials must consider the best way to utilize remote recruitment, enrollment, and data collection processes to increase efficiency and reduce costs. Researchers should consider technology accessibility and train staff to ensure the greatest possible opportunity to recruit underserved populations who have traditionally been underrepresented in research studies.
•Decreased amygdala-dACC connectivity was associated with increased alcohol misuse.•Interrupted connectivity was found in the right amygdala and latero-basal amygdala.•Men showed more severe ...alcohol-related disruption of connectivity than women.
Alcohol misuse is associated with dysfunction of the amygdala-prefrontal cortical circuit. The amygdala and its cortical targets show decreased activity during a variety of task challenges in individuals engaged in problem drinking. On the other hand, it is less clear how amygdala resting state functional connectivity (rsFC) may be altered in association with alcohol misuse and whether such changes are restricted to prefrontal cortical structures. Further, the influences of comorbid substance use and depression and potential sex differences have not been assessed in earlier work. Here, with fMRI data from a Nathan Kline Institute/Rockland sample of 83 non-dependent alcohol drinkers (26 men), we addressed changes in whole brain rsFC of the amygdala in association with problem drinking as indexed by an alcohol involvement score. Imaging data were processed with Statistical Parametric Mapping following standard routines and all results were examined at voxel p < 0.001 uncorrected in combination with cluster p < 0.05 corrected for false discovery rate. Alcohol misuse was correlated with decreased amygdala connectivity with the dorsal anterior cingulate cortex (dACC) irrespective of depression and other substance use. Changes in amygdala-dACC connectivity manifested in the latero-basal subdivision of the amygdala. Further, men as compared to women showed a significantly stronger relationship in decreased amygdala-dACC connectivity and problem drinking, although it should be noted that men also showed a trend toward higher alcohol involvement score than women. The findings add to a growing literature documenting disrupted amygdala-prefrontal cortical functions in relation to alcohol misuse.
Metabolic-dysfunction-associated fatty liver disease (MAFLD) is a major cause of morbidity and mortality in HIV-infected individuals, even those receiving optimal antiretroviral therapy. Here, we ...utilized the SIV rhesus macaque model and advanced laparoscopic techniques for longitudinal collection of liver tissue to elucidate the timing of pathologic changes. The livers of both SIV-infected (N = 9) and SIV-naïve uninfected (N = 8) macaques were biopsied and evaluated at four time points (weeks -4, 2, 6, and 16-20 post-infection) and at necropsy (week 32). SIV DNA within the macaques' livers varied by over 4 logs at necropsy, and liver SIV DNA significantly correlated with SIV RNA in the plasma throughout the study. Acute phase liver pathology (2 weeks post-infection) was characterized by evidence for fat accumulation (microvesicular steatosis), a transient elevation in both AST and cholesterol levels within the serum, and increased hepatic expression of the PPARA gene associated with cholesterol metabolism and beta oxidation. By contrast, the chronic phase of the SIV infection (32 weeks post-infection) was associated with sinusoidal dilatation, while steatosis resolved and concentrations of AST and cholesterol remained similar to those in uninfected macaques. These findings suggest differential liver pathologies associated with the acute and chronic phases of infection and the possibility that therapeutic interventions targeting metabolic function may benefit liver health in people newly diagnosed with HIV.
Viral disease outbreaks remain a significant limiting factor for aquaculture. The majority of licensed vaccines used in the industry are administered as oil-adjuvanted formulations carrying ...inactivated whole pathogens. Cell-mediated immune responses, in particular those based on virus-specific cytotoxic T-cells (CTLs) to conventional inactivated oil-based vaccines, are largely unexplored. As vaccines cannot be optimized against viral pathogens if knowledge of host cellular immune mechanisms remains unknown, in this study we examined fundamental cell-mediated immune responses after vaccination of rainbow trout with an oil-adjuvanted inactivated vaccine against salmonid alphavirus (SAV) and after infection with SAV. A unique
model system was developed to examine MHC class I restricted CTL responses in a clonal line of rainbow trout. The levels of cell-mediated cytotoxicity were compared to pathology, virus load, specific antibody response, changes in immune cell populations, and mRNA expression. Our results hint that different protective mechanisms are being triggered by infection compared to vaccination. While vaccination itself did not cause a strong cytotoxic or humoral response, subsequent challenge of vaccinated fish resulted in significantly stronger and faster specific cytotoxicity, alongside reduced viral titers and pathology. Hence, testing a vaccine on the capacity to induce cell-mediated cytotoxicity will still require a challenge test. Examination of cellular markers additionally indicates that the initial innate response induced by the vaccine could play an important role in steering adaptive mechanisms.
Pregnant and parenting women with opioid use disorder face multiple challenges to recovery. Trauma histories, poverty, stigma and discrimination, and lack of access to treatment intersect to ...marginalise this population. It is important that pregnant and parenting women with opioid use disorder receive comprehensive care to improve their health, the health of their child(ren), and prevent the intergenerational transmission of opioid and other substance use disorders. For nearly 50 years the Maternal Addiction Treatment, Education, and Research program has provided an evolving and expanding range of comprehensive services for treating opioid and other substance use disorders in this population. In this review the rationale for, and processes by which, key components of a comprehensive approach are discussed. These components include patient navigation for access to care, low-barrier medications for opioid use disorder, effective trauma-responsive therapy, prenatal and well-child healthcare, and other support services that make it possible for pregnant and parenting women to engage in treatment and improve the health of the entire family. Additionally, a method for supporting staff to build resilience and reduce fatigue and burnout is discussed. These components comprise an effective model of care for pregnant and parenting women with opioid and other substance use disorders.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Though long-term weight loss maintenance is the treatment goal for obesity, weight regain is typical and few studies have evaluated lifestyle habits associated with weight regain.
...Objective
To identify dietary and physical activity habits associated with 6- and 24-month weight regain among participants in a weight loss maintenance clinical trial.
Design
Secondary analysis of randomized clinical trial data.
Participants
Adult primary care patients with recent, intentional weight loss of at least 5%.
Main Measures
Lifestyle habits included consumption of low-fat foods, fish, desserts, sugary beverages, fruits, and vegetables and eating at restaurants from the Connor Diet Habit Survey; moderate-vigorous physical activity by self-report; steps recorded by a pedometer; and sedentary behavior by self-report. The outcome variable was weight change at 6 and 24 months. Linear regression models estimated adjusted associations between changes in weight and changes in dietary and physical activity habits.
Key Results
Overall, participants (mean (SD): 53.4 (12.2) years old; 26% male; 88% white) maintained weight loss at 6 months (
n
= 178, mean (SD): − 0.02 (5.70)% change) but began to regain weight by 24 months (
n
= 157, mean (SD): 4.22 (9.15)% increase). When considered all together, more eating at restaurants, reduced fish consumption, and less physical activity were most consistently associated with weight regain in fully adjusted models at both 6 and 24 months of follow-up. In addition, more sedentary behavior was associated with weight regain at 6 months while reduced consumption of low-fat foods, and more desserts and sugary beverages were associated with weight regain at 24 months.
Conclusions
Consuming less fish, fewer steps per day, and more frequent restaurant eating were most consistently associated with weight regain in primary care patients. Primary care providers may consider addressing specific lifestyle behaviors when counseling patients after successful weight loss.
Trial Registration
ClinicalTrials.gov
Identifier: NCT01946191
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