108 research outputs found
Lower Limb Muscle Activation in Young Adults Walking in Water and on Land
Previous research has shown that exercise interventions requiring increased activation of the tibialis anterior (TA), the primary ankle dorsiflexor, can improve walking performance in individuals with foot drop. Correspondingly, heightened drag forces experienced during walking performed in water may augment TA activation during the swing phase of gait, potentially leading to improved walking gait on land. Therefore, this study aimed to compare surface electromyographic (sEMG) activation in the TA and medial gastrocnemius (GM) during gait performed in water versus on land. Thirty-eight healthy, recreationally active young adults, comprising 18 females and 20 males, participated in the study. Each participant completed 2 min walking trials under five conditions: land 2.5 mph, land 3.5 mph, water 2.5 mph, water 3.5 mph, and water 3.5 mph with added jet resistance. Stride kinematics were collected using 2-dimensional underwater motion capture. TA and GM, muscle activation magnitudes, were quantified using sEMG root-mean-square (RMS) amplitudes for both the swing and stance phases of walking. Additionally, TA and GM co-activation (Co-A) indices were estimated. Two-way within-subjects repeated measures analyses of variance were used to evaluate the main effects of and interactions between the environment and walking speed. Additionally, paired sample t-tests were conducted as a secondary analysis to investigate differences between walking in water at 3.5 mph with and without added jet resistance. Main effects and interactions were observed across various stride kinematics and sEMG measures. Notably, TA sEMG RMS during the swing phase of walking gait performed at 2.5 mph was 15% greater in water than on land (p \u3c 0.001). This effect increased when walking gait was performed at 3.5 mph (94%; p \u3c 0.001) and when jet resistance was added to the 3.5 mph condition (52%; p \u3c 0.001). Furthermore, TA Co-A was increased during the stance phase of gait in water compared to on land (p \u3c 0.001), while GM Co-A was reduced during the swing phase (p \u3c 0.001). The findings of this study offer compelling evidence supporting the efficacy of aquatic treadmill walking as a potential treatment for individuals suffering from foot drop. However, further research is needed to evaluate whether a causal relationship exists between heightened TA activation observed during aquatic treadmill walking and improvements in voluntary dorsiflexion during gait
Embryo movement is more frequent in avian brood parasites than birds with parental reproductive strategies.
Funder: Tanzanian Commission for Science and TechnologyFunder: Tanzania Wildlife Research InstituteFunder: NERCFunder: National Science FoundationFunder: Ministry of EducationFunder: German Academic Exchange ServiceFunder: University of Cape TownFunder: Max-Planck-GesellschaftMovement of the embryo is essential for musculoskeletal development in vertebrates, yet little is known about whether, and why, species vary. Avian brood parasites exhibit feats of strength in early life as adaptations to exploit the hosts that rear them. We hypothesized that an increase in embryonic movement could allow brood parasites to develop the required musculature for these demands. We measured embryo movement across incubation for multiple brood-parasitic and non-parasitic bird species. Using a phylogenetically controlled analysis, we found that brood parasites exhibited significantly increased muscular movement during incubation compared to non-parasites. This suggests that increased embryo movement may facilitate the development of the stronger musculoskeletal system required for the demanding tasks undertaken by young brood parasites
Mapping Polyclonal HIV-1 Antibody Responses via Next-Generation Neutralization Fingerprinting
Computational neutralization fingerprinting, NFP, is an efficient and accurate method for predicting the epitope specificities of polyclonal antibody responses to HIV-1 infection. Here, we present next-generation NFP algorithms that substantially improve prediction accuracy for individual donors and enable serologic analysis for entire cohorts. Specifically, we developed algorithms for: (a) selection of optimized virus neutralization panels for NFP analysis, (b) estimation of NFP prediction confidence for each serum sample, and (c) identification of sera with potentially novel epitope specificities. At the individual donor level, the next-generation NFP algorithms particularly improved the ability to detect multiple epitope specificities in a sample, as confirmed both for computationally simulated polyclonal sera and for samples from HIV-infected donors. Specifically, the next-generation NFP algorithms detected multiple specificities in twice as many samples of simulated sera. Further, unlike the first-generation NFP, the new algorithms were able to detect both of the previously confirmed antibody specificities, VRC01-like and PG9-like, in donor CHAVI 0219. At the cohort level, analysis of ~150 broadly neutralizing HIV-infected donor samples suggested a potential connection between clade of infection and types of elicited epitope specificities. Most notably, while 10E8-like antibodies were observed in infections from different clades, an enrichment of such antibodies was predicted for clade B samples. Ultimately, such largescale analyses of antibody responses to HIV-1 infection can help guide the design of epitope-specific vaccines that are tailored to take into account the prevalence of infecting clades within a specific geographic region. Overall, the next-generation NFP technology will be an important tool for the analysis of broadly neutralizing polyclonal antibody responses against HIV-1
Structural survey of HIV-1-neutralizing antibodies targeting Env trimer delineates epitope categories and suggests vaccine templates
HIV-1 broadly neutralizing antibodies are desired for their therapeutic potential and as templates for vaccine design. Such antibodies target the HIV-1-envelope (Env) trimer, which is shielded from immune recognition by extraordinary glycosylation and sequence variability. Recognition by broadly neutralizing antibodies thus provides insight into how antibody can bypass these immune-evasion mechanisms. Remarkably, antibodies neutralizing >25% of HIV-1 strains have now been identified that recognize all major exposed surfaces of the prefusion-closed Env trimer. Here we analyzed all 206 broadly neutralizing antibody-HIV-1 Env complexes in the PDB with resolution suitable to define their interaction chemistries. These segregated into 20 antibody classes based on ontogeny and recognition, and into 6 epitope categories (V1V2, glycan-V3, CD4-binding site, silent face center, fusion peptide, and subunit interface) based on recognized Env residues. We measured antibody neutralization on a 208-isolate panel and analyzed features of paratope and B cell ontogeny. The number of protruding loops, CDR H3 length, and level of somatic hypermutation for broadly HIV-1 neutralizing antibodies were significantly higher than for a comparison set of non-HIV-1 antibodies. For epitope, the number of independent sequence segments was higher (P < 0.0001), as well as the glycan component surface area (P = 0.0005). Based on B cell ontogeny, paratope, and breadth, the CD4-binding site antibody IOMA appeared to be a promising candidate for lineage-based vaccine design. In terms of epitope-based vaccine design, antibody VRC34.01 had few epitope segments, low epitope-glycan content, and high epitope-conformational variability, which may explain why VRC34.01-based design is yielding promising vaccine results
Preferential infection and depletion of Mycobacterium tuberculosis–specific CD4 T cells after HIV-1 infection
HIV-1 preferentially infects M. tuberculosis-specific CD4+ T cells due to their increased production of IL-2
Structure of an N276-dependent HIV-1 neutralizing antibody targeting a rare V5 glycan hole adjacent to the CD4 binding site.
CAPRISA, 2016.Abstract available in pdf
Structural survey of HIV-1-neutralizing antibodies targeting Env trimer delineates epitope categories and suggests vaccine templates
HIV-1 broadly neutralizing antibodies are desired for their therapeutic potential and as templates for vaccine design. Such antibodies target the HIV-1-envelope (Env) trimer, which is shielded from immune recognition by extraordinary glycosylation and sequence variability. Recognition by broadly neutralizing antibodies thus provides insight into how antibody can bypass these immune-evasion mechanisms. Remarkably, antibodies neutralizing >25% of HIV-1 strains have now been identified that recognize all major exposed surfaces of the prefusion-closed Env trimer. Here we analyzed all 206 broadly neutralizing antibody-HIV-1 Env complexes in the PDB with resolution suitable to define their interaction chemistries. These segregated into 20 antibody classes based on ontogeny and recognition, and into 6 epitope categories (V1V2, glycan-V3, CD4-binding site, silent face center, fusion peptide, and subunit interface) based on recognized Env residues. We measured antibody neutralization on a 208-isolate panel and analyzed features of paratope and B cell ontogeny. The number of protruding loops, CDR H3 length, and level of somatic hypermutation for broadly HIV-1 neutralizing antibodies were significantly higher than for a comparison set of non-HIV-1 antibodies. For epitope, the number of independent sequence segments was higher (P < 0.0001), as well as the glycan component surface area (P = 0.0005). Based on B cell ontogeny, paratope, and breadth, the CD4-binding site antibody IOMA appeared to be a promising candidate for lineage-based vaccine design. In terms of epitope-based vaccine design, antibody VRC34.01 had few epitope segments, low epitope-glycan content, and high epitope-conformational variability, which may explain why VRC34.01-based design is yielding promising vaccine results
Staged induction of HIV-1 glycan–dependent broadly neutralizing antibodies
A preventive HIV-1 vaccine should induce HIV-1–specific broadly neutralizing antibodies (bnAbs). However, bnAbs generally require high levels of somatic hypermutation (SHM) to acquire breadth, and current vaccine strategies have not been successful in inducing bnAbs. Because bnAbs directed against a glycosylated site adjacent to the third variable loop (V3) of the HIV-1 envelope protein require limited SHM, the V3-glycan epitope is an attractive vaccine target. By studying the cooperation among multiple V3-glycan B cell lineages and their coevolution with autologous virus throughout 5 years of infection, we identify key events in the ontogeny of a V3-glycan bnAb. Two autologous neutralizing antibody lineages selected for virus escape mutations and consequently allowed initiation and affinity maturation of a V3-glycan bnAb lineage. The nucleotide substitution required to initiate the bnAb lineage occurred at a low-probability site for activation-induced cytidine deaminase activity. Cooperation of B cell lineages and an improbable mutation critical for bnAb activity defined the necessary events leading to breadth in this V3-glycan bnAb lineage. These findings may, in part, explain why initiation of V3-glycan bnAbs is rare, and suggest an immunization strategy for inducing similar V3-glycan bnAbs
Delineating antibody recognition in polyclonal sera from patterns of HIV-1 isolate neutralization.
Serum characterization and antibody isolation are transforming our understanding of the humoral immune response to viral infection. Here, we show that epitope specificities of HIV-1–neutralizing antibodies in serum can be elucidated from the serum pattern of neutralization against a diverse panel of HIV-1 isolates. We determined “neutralization fingerprints” for 30 neutralizing antibodies on a panel of 34 diverse HIV-1 strains and showed that similarity in neutralization fingerprint correlated with similarity in epitope. We used these fingerprints to delineate specificities of
polyclonal sera from 24 HIV-1–infected donors and a chimeric siman-human immunodeficiency virus–infected macaque. Delineated specificities matched published specificities and were further confirmed by antibody isolation for two sera. Patterns of virus-isolate neutralization can thus afford a detailed epitope-specific understanding of neutralizing-antibody responses to viral infection
- …