Summary Bacterial secretion systems often employ molecular chaperones to recognize and facilitate export of their substrates. Recent work demonstrated that a secreted component of the type VI secretion system (T6SS), hemolysin co-regulated protein (Hcp), binds directly to effectors, enhancing their stability in the bacterial cytoplasm. Herein, we describe a quantitative cellular proteomics screen for T6S substrates that exploits this chaperone-like quality of Hcp. Application of this approach to the Hcp secretion island I-encoded T6SS (H1-T6SS) of Pseudomonas aeruginosa led to the identification of a novel effector protein, termed Tse4 (type VI secretion exported 4), subsequently shown to act as a potent intra-specific H1-T6SS-delivered antibacterial toxin. Interestingly, our screen failed to identify two predicted H1-T6SS effectors, Tse5 and Tse6, which differ from Hcp-stabilized substrates by the presence of toxin-associated PAAR-repeat motifs and genetic linkage to members of the valine-glycine repeat protein G (vgrG) genes. Genetic studies further distinguished these two groups of effectors: Hcp-stabilized effectors were found to display redundancy in interbacterial competition with respect to the requirement for the two H1-T6SS-exported VgrG proteins, whereas Tse5 and Tse6 delivery strictly required a cognate VgrG. Together, we propose that interaction with either VgrG or Hcp defines distinct pathways for T6S effector export.

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Institutionalized seniors, even those who are physically frail, incontinent and/or have mild dementia, can respond positively to a challenging exercise program. The FFLTC program demonstrated clear benefits over typical, seated ROM exercises. Moreover, with minimal training, the program can be safely delivered at low cost by institutional staff and volunteers.

Aerobic exercise may acutely prime the brain to be more responsive to rehabilitation, thus facilitating neurologic recovery from conditions like stroke. This aerobic priming effect could occur through multiple mechanisms, including upregulation of circulating brain-derived neurotrophic factor (BDNF), increased corticospinal excitability, and decreased intracortical inhibition. However, optimal exercise parameters for targeting these mechanisms are poorly understood. This study tested the effects of exercise intensity on acute BDNF and neurophysiological responses. Sixteen ambulatory persons >6 mo poststroke performed three different 20-min exercise protocols in random order, approximately 1 wk apart, including the following: 1) treadmill high-intensity interval training (HIT-treadmill); 2) seated-stepper HIT (HIT-stepper); and 3) treadmill moderate-intensity continuous exercise (MCT-treadmill). Serum BDNF and transcranial magnetic stimulation measures of paretic lower limb excitability and inhibition were assessed at multiple time points during each session. Compared with MCT-treadmill, HIT-treadmill elicited significantly greater acute increases in circulating BDNF and corticospinal excitability. HIT-stepper initially showed BDNF responses similar to HIT-treadmill but was no longer significantly different from MCT-treadmill after decreasing the intensity in reaction to two hypotensive events. Additional regression analyses showed that an intensity sufficient to accumulate blood lactate appeared to be important for eliciting BDNF responses, that the interval training approach may have facilitated the corticospinal excitability increases, and that the circulating BDNF response was (negatively) related to intracortical inhibition. These findings further elucidate neurologic mechanisms of aerobic exercise and inform selection of optimal exercise-dosing parameters for enhancing acute neurologic effects. NEW & NOTEWORTHY Acute exercise-related increases in circulating BDNF and corticospinal excitability are thought to prime the brain for learning. Our data suggest that these responses can be obtained among persons with stroke using short-interval treadmill high-intensity interval training, that a vigorous aerobic intensity sufficient to generate lactate accumulation is needed to increase BDNF, that interval training facilitates increases in paretic quadriceps corticospinal excitability, and that greater BDNF response is associated with lesser intracortical inhibition response.

The study provides "normative" cardiorespiratory function data of a random sample of independently living men and women aged 55-86 yr.

The relationships between isometric and isokinetic-concentric knee extensor and knee flexor strength, and quadriceps and hamstring cross-sectional area (CSA) were determined in young (n = 13, M = 24.5y) and elderly (n = 12, M = 70.7y) men. Quadriceps and hamstring CSA was determined by computed tomography. Knee extensor and flexor strength at 0 degree/s and 120 degree/s was determined on a Kin-Com isokinetic dynamometer. Compared to the young men, elderly men had significantly smaller quadriceps muscles and were weaker (22-32%) in knee flexion and knee extension at both angular velocities. Strength:CSA ratios were similar at 0 degree/s, but elderly men had decreased ratios for both extensors and flexors at 120 degree/s. Correlations of knee extensor and flexor strength with muscle CSA were significant at both velocities in elderly men, but not at either velocity for the knee flexors in young men. The decrease in isometric strength in elderly men can be accounted for by their decrease in muscle CSA, but their decrease in isokinetic-concentric strength was greater than their loss of CSA. Further study is required to determine the reason for this nonproportional loss of isokinetic-concentric strength.

Computed tomography (CT) was used to quantify components of the thigh in young (n = 13) and elderly (n = 11) men. Cross-sectional areas (CSA) of the total limb, total muscle plus bone, quadriceps compartment, hamstring compartment and bone were measured at each of five scan sites along the length of the thigh. Non-muscle tissue (NMT) areas within the muscle compartments were measured using changes in density based on Hounsfield units. Skin plus subcutaneous fat areas and quadriceps and hamstring lean muscle areas were calculated by subtraction. Geometric formulae were used to calculate related volumes for each thigh component. Volumes were also predicted from regression equations employing thigh length and component CSA from single mid-limb CT scans. The results showed that while total thigh CSA was not different in elderly men, they had significantly smaller total muscle plus bone (13.0%), and quadriceps (26.4%), and hamstring (17.9%) muscle areas. The elderly men also had significantly greater CSA for skin plus subcutaneous fat (37.6%), and for NMT in the quadriceps (59.4%) and hamstring (127.3%) muscle compartments. These results suggest that comparisons of relative leg muscle strength between young and elderly men may be misleading due to the decrease in actual muscle tissue associated with ageing. Appropriate quantification of muscle size and CSA must be carried out before such comparisons can be meaningful.