Antidepressant medications reduce subcortical-cortical resting-state functional connectivity in healthy volunteers

Studies have revealed abnormalities in resting-state functional connectivity in those with major depressive disorder specifically in areas such as the dorsal anterior cingulate, thalamus, amygdala, the pallidostriatum and subgenual cingulate. However, the effect of antidepressant medications on human brain function is less clear and the effect of these drugs on resting-state functional connectivity is unknown. Forty volunteers matched for age and gender with no previous psychiatric history received either citalopram (SSRI; selective serotonergic reuptake inhibitor), reboxetine (SNRI; selective noradrenergic reuptake inhibitor) or placebo for 7 days in a double-blind design. Using resting-state functional magnetic resonance imaging and seed based connectivity analysis we selected the right nucleus accumbens, the right amygdala, the subgenual cingulate and the dorsal medial prefrontal cortex as seed regions. Mood and subjective experience were also measured before and after drug administration using self-report scales. Despite no differences in mood across the three groups, we found reduced connectivity between the amygdala and the ventral medial prefrontal cortex in the citalopram group and the amygdala and the orbitofrontal cortex for the reboxetine group. We also found reduced striatal-orbitofrontal cortex connectivity in the reboxetine group. These data suggest that antidepressant medications can decrease resting-state functional connectivity independent of mood change and in areas known to mediate reward and emotional processing in the brain. We conclude that hypothesis-driven seed based analysis of resting-state fMRI supports the proposition that antidepressant medications might work by normalising the elevated resting-state functional connectivity seen in depressed patients.

Disorder-specific functional abnormalities during temporal discounting in youth with Attention Deficit Hyperactivity Disorder (ADHD), Autism and comorbid ADHD and Autism

Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) are often comorbid and share cognitive abnormalities in temporal foresight. A key question is whether shared cognitive phenotypes are based on common or different underlying pathophysiologies and whether comorbid patients have additive neurofunctional deficits, resemble one of the disorders or have a different pathophysiology. We compared age- and IQ-matched boys with non-comorbid ADHD (18), non-comorbid ASD (15), comorbid ADHD and ASD (13) and healthy controls (18) using functional magnetic resonance imaging (fMRI) during a temporal discounting task. Only the ASD and the comorbid groups discounted delayed rewards more steeply. The fMRI data showed both shared and disorder-specific abnormalities in the three groups relative to controls in their brain-behaviour associations. The comorbid group showed both unique and more severe brain-discounting associations than controls and the non-comorbid patient groups in temporal discounting areas of ventromedial and lateral prefrontal cortex, ventral striatum and anterior cingulate, suggesting that comorbidity is neither an endophenocopy of the two pure disorders nor an additive pathology.

Functional identity and diversity of animals predict ecosystem functioning better than species-based indices

Drastic biodiversity declines have raised concerns about the deterioration of ecosystem functions and have motivated much recent research on the relationship between species diversity and ecosystem functioning. A functional trait framework has been proposed to improve the mechanistic understanding of this relationship, but this has rarely been tested for organisms other than plants. We analysed eight datasets, including five animal groups, to examine how well a trait-based approach, compared with a more traditional taxonomic approach, predicts seven ecosystem functions below- and above-ground. Trait-based indices consistently provided greater explanatory power than species richness or abundance. The frequency distributions of single or multiple traits in the community were the best predictors of ecosystem functioning. This implies that the ecosystem functions we investigated were underpinned by the combination of trait identities (i.e. single-trait indices) and trait complementarity (i.e. multi-trait indices) in the communities. Our study provides new insights into the general mechanisms that link biodiversity to ecosystem functioning in natural animal communities and suggests that the observed responses were due to the identity and dominance patterns of the trait composition rather than the number or abundance of species per se.

Functional and Structural Connectivity Between the Perigenual Anterior Cingulate and Amygdala in Bipolar Disorder

Objective: Abnormalities in the morphology and function of two gray matter structures central to emotional processing, the perigenual anterior cingulate cortex (pACC) and amygdala, have consistently been reported in bipolar disorder (BD). Evidence implicates abnormalities in their connectivity in BD. This study investigates the potential disruptions in pACC-amygdala functional connectivity and associated abnormalities in white matter that provides structural connections between the two brain regions in BD. Methods: Thirty-three individuals with BD and 31 healthy comparison subjects (HC) participated in a scanning session during which functional magnetic resonance imaging (fMRI) during processing of face stimuli and diffusion tensor imaging (DTI) were performed. The strength of pACC-amygdala functional connections was compared between BD and HC groups, and associations between these functional connectivity measures from the fMRI scans and regional fractional anisotropy (FA) from the DTI scans were assessed. Results: Functional connectivity was decreased between the pACC and amygdala in the BD group compared with HC group, during the processing of fearful and happy faces (p < .005). Moreover, a significant positive association between pACC-amygdala functional coupling and FA in ventrofrontal white matter, including the region of the uncinate fasciculus, was identified (p < .005). Conclusion: This study provides evidence for abnormalities in pACC-amygdala functional connectivity during emotional processing in BD. The significant association between pACC-amygdala functional connectivity and the structural integrity of white matter that contains pACC-amygdala connections suggest that disruptions in white matter connectivity may contribute to disturbances in the coordinated responses of the pACC and amygdala during emotional processing in BD.

Trypanosoma cruzi MSH2: Functional analyses on different parasite strains provide evidences for a role on the oxidative stress response

Components of the DNA mismatch repair (MMR) pathway are major players in processes known to generate genetic diversity, such as mutagenesis and DNA recombination. Trypanosoma cruzi, the protozoan parasite that causes Chagas disease has a highly heterogeneous population, composed of a pool of strains with distinct characteristics. Studies with a number of molecular markers identified up to six groups in the T. cruzi population, which showed distinct levels of genetic variability. To investigate the molecular basis for such differences, we analyzed the T. cruzi MSH2 gene, which encodes a key component of MMR, and showed the existence of distinct isoforms of this protein. Here we compared cell survival rates after exposure to genotoxic agents and levels of oxidative stress-induced DNA in different parasite strains. Analyses of msh2 mutants in both T. cruzi and T. brucei were also used to investigate the role of Tcmsh2 in the response to various DNA damaging agents. The results suggest that the distinct MSH2 isoforms have differences in their activity. More importantly, they also indicate that, in addition to its role in MMR, TcMSH2 acts in the parasite response to oxidative stress through a novel mitochondrial function that may be conserved in T. brucei. (C) 2010 Elsevier B.V. All rights reserved.

Perceptions of Sustainability and Functional Aspects on Liquid Carton Board Packaging Materials versus Competing Materials for Juice Applications in Sweden

This research explores the downstream perceptions of liquid carton board versus competing materials in packaging applications for juice. The methodology used is focus groups. The context is sustainability and functional performance, and related potential implications for the beverage industry value chain. The purpose is to get a deeper insight and understanding of functionality in relation to juice beverage packaging. The results confirm that there is no optimal packaging for every juice product, but a multitude, depending on the distribution channel, retail outlet, customer preferences, and context of consumption. There are some general packaging preferences, but the main deciding criteria for purchase seem to be the product characteristics in terms of quality, taste, brand, price and shelf life. For marketing reasons, packaging has to be adopted to the product and its positioning, liquid carton board packaging seem to have some functional advantages in distribution and is considered as sustainable and functional among many consumers. Major drawbacks seem to be shape limitations, lack of transparency, and lack of a “premium look”. To improve packaging performance and avoid sub-optimization, actors in the beverage industry value chain need to be integrated in development processes.

Effect of six weeks of dura disc and mini-trampoline balance training on postural sway in athletes with functional ankle instability

Lateral ankle sprain (LAS) is one of the most common injuries incurred during sporting activities, and effective rehabilitation programs for this condition are challenging to develop. The purpose of this research was to compare the effect of 6 weeks of balance training on either a mini-trampoline or a dura disc on postural sway and to determine if the mini-trampoline or the dura disc is more effective in improving postural sway. Twenty subjects (11 men, 9 women) with a mean age of 25.4 ± 4.2 years were randomly allocated into a control group, a dura disc training (DT) group, or a mini-trampoline (MT) group. Subjects completed 6 weeks of balance training. Postural sway was measured by subjects performing a single limb stance on a force plate. The disbursement of the center of pressure was obtained from the force plate in the medial-lateral and the anterior-posterior sway path and was subsequently used for pretest and posttest analysis. After the 6-week training intervention, there was a significant (p < 0.05) difference in postural sway between pre- and posttesting for both the MT (pretest = 56.8 ± 20.5 mm, posttest = 33.3 ± 8.5 mm) and DT (pretest = 41.3 ± 2.6 mm, posttest = 27.2 ± 4.8 mm) groups. There was no significant (p > 0.05) difference detected for improvements between the MT and DT groups. These results indicate that not only is the mini-trampoline an effective tool for improving balance after LAS, but it is equally as effective as the dura disc.

Liver cell transplantation leads to repopulation and functional correction in a mouse model of Wilson's disease

Background and Aim: The toxic milk (tx) mouse is a non-fatal animal model for the metabolic liver disorder, Wilson's disease. The tx mouse has a mutated gene for a copper-transporting protein, causing early copper accumulation in the liver and late accumulation in other tissues. The present study investigated the efficacy of liver cell transplantation (LCT) to correct the tx mouse phenotype.

Methods: Congenic hepatocytes were isolated and intrasplenically transplanted into 3–4-month-old tx mice, which were then placed on various copper-loaded diets to examine its influence on repopulation by transplanted cells. The control animals were age-matched untransplanted tx mice. Liver repopulation was determined by comparisons of restriction fragment length polymorphism ratios (DNA and mRNA), and copper levels were measured by atomic absorption spectroscopy.

Results: Repopulation in recipient tx mice was detected in 11 of 25 animals (44%) at 4 months after LCT. Dietary copper loading (whether given before or after LCT, or both) provided no growth advantage for donor cells, with similar repopulation incidences in all copper treatment groups. Overall, liver copper levels were significantly lower in repopulated animals (538 ± 68 µg/g, n = 11) compared to non-repopulated animals (866 ± 62 µg/g, n = 14) and untreated controls (910 ± 103 µg/g, n = 6; P < 0.05). This effect was also seen in the kidney and spleen. Brain copper levels remained unchanged.

Conclusion: Transplanted liver cells can proliferate and correct a non-fatal metabolic liver disease, with some restoration of hepatic copper homeostasis after 4 months leading to reduced copper levels in the liver and extrahepatic tissues, but not in the brain.

Discovery of structural and functional features in RNA pseudoknots

An RNA pseudoknot consists of nonnested double-stranded stems connected by single-stranded loops. There is increasing recognition that RNA pseudoknots are one of the most prevalent RNA structures and fulfill a diverse set of biological roles within cells, and there is an expanding rate of studies into RNA pseudoknotted structures as well as increasing allocation of function. These not only produce valuable structural data but also facilitate an understanding of structural and functional characteristics in RNA molecules. PseudoBase is a database providing structural, functional, and sequence data related to RNA pseudoknots. To capture the features of RNA pseudoknots, we present a novel framework using quantitative association rule mining to analyze the pseudoknot data. The derived rules are classified into specified association groups regarding structure, function, and category of RNA pseudoknots. The discovered association rules assist biologists in filtering out significant knowledge of structure-function and structure-category relationships. A brief biological interpretation to the relationships is presented, and their potential correlations with each other are highlighted.

The effect of resistance training on functional capacity and quality of life in individuals with high and low number of metabolic risk factors

OBJECTIVE—There are limited data on the effects of resistance training on the capacity to perform activities of daily living (ADLs) and quality of life (QoL) for individuals with a high number of metabolic risk factors (HiMF). In this study, we examined the effect of resistance training on the capacity to perform ADLs and QoL in individuals with HiMF and compared any benefits with individuals with a low number of metabolic risk factors (LoMF).

RESEARCH DESIGN AND METHODS—Fifty-five untrained individuals, aged 50.8 ± 6.5 years, were randomized to four groups: HiMF training (HiMFT), HiMF control, LoMF training (LoMFT), and LoMF control. At baseline and after 10 weeks of resistance training, participants underwent anthropometric measurements and assessments of aerobic power (Vo2peak), muscle strength, capacity to perform ADLs, and a self-perceived QoL questionnaire. A repeated-measures ANOVA was used to examine the effect of training over time among groups.

RESULTS—Training increased lean body mass in both HiMFT (P = 0.03) and LoMFT (P = 0.03) groups. Total fat content and Vo2peak improved in the LoMFT group only. Muscle strength improved in both training groups (P < 0.01). Time to complete ADLs was reduced by 8.8% in the LoMFT group (P < 0.01) and 9.7% in the HiMF group (P < 0.01). Only the HiMFT group reported improvement in QoL.

CONCLUSIONS— Resistance training improved muscle strength and the capacity to perform ADLs in individuals with HiMF and LoMF. Resistance training improved QoL for the HiMF group, and this result was independent of changes in body fat content or aerobic power. Longer training regimens may be needed to improve QoL in individuals with LoMF.

Identifying co-regulating microrna groups

Background: Current miRNA target prediction tools have the common problem that their false positive rate is high. This renders identification of co-regulating groups of miRNAs and target genes unreliable. In this study, we describe a procedure to identify highly probable co-regulating miRNAs and the corresponding co-regulated gene groups. Our procedure involves a sequence of statistical tests: (1) identify genes that are highly probable miRNA targets; (2) determine for each such gene, the minimum number of miRNAs that co-regulate it with high probability; (3) find, for each such gene, the combination of the determined minimum size of miRNAs that co-regulate it with the lowest p-value; and (4) discover for each such combination of miRNAs, the group of genes that are co-regulated by these miRNAs with the lowest p-value computed based on GO term annotations of the genes.
Results: Our method identifies 4, 3 and 2-term miRNA groups that co-regulate gene groups of size at least 3 in human. Our result suggests some interesting hypothesis on the functional role of several miRNAs through a "guilt by association" reasoning. For example, miR-130, miR-19 and miR-101 are known neurodegenerative diseases associated miRNAs. Our 3-term miRNA table shows that miR-130/19/101 form a co-regulating group of rank 22 (p-value =1.16 × 10^-2). Since miR-144 is co-regulating with miR-130, miR-19 and miR-101 of rank 4 (p-value = 1.16 × 10^-2) in our 4-term miRNA table, this suggests hsa-miR-144 may be neurodegenerative diseases related miRNA. Conclusions: This work identifies highly probable co-regulating miRNAs, which are refined from the prediction by computational tools using (1) signal-to-noise ratio to get high accurate regulating miRNAs for every gene, and (2) Gene Ontology to obtain functional related co-regulating miRNA groups. Our result has partly been supported by biological experiments. Based on prediction by TargetScanS, we found highly probable target gene groups in the Supplementary Information. This result might help biologists to find small set of miRNAs for genes of interest rather than huge amount of miRNA set.

Effects of resistance exercise and fortified milk on skeletal muscle mass, muscle size, and functional performance in middle-aged and older men: an 18-mo randomized controlled trial

Limited data have suggested that the consumption of fluid milk after resistance training (RT) may promote skeletal muscle hypertrophy. The aim of this study was to assess whether a milk-based nutritional supplement could enhance the effects of RT on muscle mass, size, strength, and function in middle-aged and older men. This was an 18-mo factorial design (randomized control trial) in which 180 healthy men aged 50–79 yr were allocated to the following groups: 1) exercise + fortified milk, 2) exercise, 3) fortified milk, or 4) control. Exercise consisted of progressive RT with weight-bearing impact exercise. Men assigned to the fortified milk consumed 400 ml/day of low-fat milk, providing an additional 836 kJ, 1000 mg calcium, 800 IU vitamin D3, and 13.2 g protein per day. Total body lean mass (LM) and fat mass (FM) (dual-energy X-ray absorptiometry), midfemur muscle cross-sectional area (CSA) (quantitative computed tomography), muscle strength, and physical function were assessed. After 18 mo, there was no significant exercise by fortified milk interaction for total body LM, muscle CSA, or any functional measure. However, main effect analyses revealed that exercise significantly improved muscle strength (∼20–52%, P < 0.001), LM (0.6 kg, P < 0.05), FM (−1.1 kg, P < 0.001), muscle CSA (1.8%, P < 0.001), and gait speed (11%, P < 0.05) relative to no exercise. There were no effects of the fortified milk on muscle size, strength, or function. In conclusion, the daily consumption of low-fat fortified milk does not enhance the effects of RT on skeletal muscle size, strength, or function in healthy middle-aged and older men with adequate energy and nutrient intakes.

Association between changes in habitual physical activity and changes in bone density, muscle strength, and functional performance in elderly men and women

OBJECTIVES: To investigate the long-term effects of habitual physical activity on changes in musculoskeletal health, functional performance, and fracture risk in elderly men and women.

DESIGN: Ten-year prospective population-based study.

SETTING: Malmö-Sjöbo Prospective Study, Sweden.

PARTICIPANTS: Participants were 152 men and 206 women aged 50, 60, 70, and 80 who were followed for 10 years.

MEASUREMENTS: Distal radius bone mineral density (BMD) (single photon absorptiometry), upper limb muscle (grip) strength, balance, gait velocity, occupational and leisure-time activity, and fractures (interview-administered questionnaire) were reassessed after 10 years. Annual changes for all measures were compared between participants with varying habitual physical activity histories at baseline and follow-up: inactive–inactive (n=202), active–inactive (n=47), inactive–active (n=49), and active–active (n=60). Data for men and women were pooled, because there were no sex-by-activity group interactions. To detect possible differences in fracture incidence between the varying habitual activity groups, participants were classified into two activity groups based on their activity classification at baseline and follow-up: inactive:less active versus active:more active.

RESULTS: The annual rate of bone loss was 0.6% per year less in individuals classified as active at both time points than in those classified as inactive at both time points (P<.01). Similar results were observed for balance, but there was no effect of varying habitual activity on changes in muscle strength or gait velocity. There were also no differences in fracture incidence between individuals categorized as active:more active and those categorized as inactive:less active during the follow-up (adjusted hazard ratio=0.90, 95% confidence interval (CI)=0.42–1.90).

CONCLUSION: This study showed that elderly men and women who maintained a habitually active lifestyle over 10 years had lower bone loss and retained better balance than those who remained habitually inactive.

Care needs and functional status of older acute care patients

A growing number of older adults are admitted to hospitals, and information is needed on how age-related functional decline affects nursing care needs of this population. This study compared the functional status at admission and total nursing care needs of three age groups of older inpatients. A 12-month retrospective audit was performed on the records of 225 patients in a private metropolitan hospital. The three groups of patients were matched on diagnosis. Findings revealed that older patients were significantly more dependent, had greater total nursing care needs, and were less likely to be discharged to home, indicating that in addition to medical diagnoses, age-related differences of older patients’ functional status at admission and inpatient nursing care needs should be factored into staff workloads and funding of nursing care. The finding that significantly fewer of the older patients returned home must be considered when reviewing health care policy and services.

Psychosocial antecedents of communication, trust, and relationship effectiveness in new product development projects : a functional manager perspective

The basic differences between marketing managers and their technically trained counterpart managers [e.g., research and development (R&D), engineering, and manufacturing managers] in terms of work experience, training, and differing decision-making styles have often been suggested as a source of conflict, which acts as a barrier to effective working relationships and integration during new product development (NPD) work. In this paper, we empirically explore this issue by developing and testing a model of psychosocial differences (thought worlds and psychological distance) between the two groups of managers and their effect on communication, trust, and relationship effectiveness during NPD projects. We find that while thought world differences do still matter, it was from a marketing perspective that they had a stronger effect. These findings have implications for top management trying to manage the functional manager interface during NPD projects. We propose a semi-formalized approach to relationship building that may speed up the acquisition of social data that is often necessary to elevate working relationships to trusting ones and improve the efficiency of NPD work. Our model is tested using data from two samples, 184 technically trained managers and 145 marketing managers from Australian companies involved in NPD work.