Protein-folding landscapes in multichain systems

Computational studies of proteins have significantly improved our understanding of protein folding. These studies are normally carried out by using chains in isolation. However, in many systems of practical interest, proteins fold in the presence of other molecules. To obtain insight into folding in such situations, we compare the thermodynamics of folding for a Miyazawa-Jernigan model 64-mer in isolation to results obtained in the presence of additional chains. The melting temperature falls as the chain concentration increases. In multichain systems, free-energy landscapes for folding show an increased preference for misfolded states. Misfolding is accompanied by an increase in interprotein interactions; however, near the folding temperature, the transition from folded chains to misfolded and associated chains is entropically driven. A majority of the most probable interprotein contacts are also native contacts, suggesting that native topology plays a role in early stages of aggregation.     

Bacterial Heterogeneity Is a Requirement for Host Superinfection by the Lyme Disease Spirochete

In nature, mixed Borrelia burgdorferi infections are common and possibly can be acquired by either superinfection or coinfection. Superinfection by heterologous B. burgdorferi strains has been established experimentally, although the ability of homologous B. burgdorferi clones to superinfect a host has not been studied in detail. Information regarding any potential immune barriers to secondary infection also currently is unavailable. In the present study, the ability to superinfect various mouse models by homologous wild-type clones was examined and compared to superinfection by heterologous strains. To assess the ability of homologous B. burgdorferi clones to successfully superinfect a mouse host, primary- and secondary-infecting spirochetes were recovered via in vitro cultivation of collected blood or tissue samples. This was accomplished by generating two different antibiotic-resistant versions of the wild-type B31-A3 clone in order to distinguish superinfecting B. burgdorferi from primary-infecting spirochetes. The data demonstrate an inability of homologous B. burgdorferi to superinfect immunocompetent mice as opposed to heterologous strains. Attempts to superinfect different types of immunodeficient mice with homologous B. burgdorferi indicate that the murine innate immune system represents a major barrier to intrastrain superinfection. Consequently, the possibility of innate immunity as a driving force for B. burgdorferi heterogeneity during the enzootic cycle is discussed.     

Neural latencies across auditory cortex of macaque support a dorsal stream supramodal timing advantage in primates

Sensory systems across the brain are specialized for their input, yet some principles of neural organization are conserved across modalities. The pattern of anatomical connections from the primate auditory cortex to the temporal, parietal, and prefrontal lobes suggests a possible division into dorsal and ventral auditory processing streams, with the dorsal stream originating from more caudal areas of the auditory cortex, and the ventral stream originating from more rostral areas. These streams are hypothesized to be analogous to the well-established dorsal and ventral streams of visual processing. In the visual system, the dorsal processing stream shows substantially faster neural response latencies than does the ventral stream. However, the relative timing of putative dorsal and ventral stream processing has yet to be explored in other sensory modalities. Here, we compare distributions of neural response latencies from 10 different areas of macaque auditory cortex, confirmed by individual anatomical reconstructions, to determine whether a similar timing advantage is found for the hypothesized dorsal auditory stream. Across three varieties of auditory stimuli (clicks, noise, and pure tones), we find that latencies increase with hierarchical level, as predicted by anatomical connectivity. Critically, we also find a pronounced timing differential along the caudal-to-rostral axis within the same hierarchical level, with caudal (dorsal stream) latencies being faster than rostral (ventral stream) latencies. This observed timing differential mirrors that found for the dorsal stream of the visual system, suggestive of a common timing advantage for the dorsal stream across sensory modalities.     

A review of postoperative feeding regimens in infantile hypertrophic pyloric stenosis

Infantile hypertrophic pyloric stenosis is a condition well known to pediatric surgeons. Postoperative length of hospital stay is a financial concern and remains a potential target for reduction in hospital costs. Ultimately, these costs are directly affected by the ability to effectively advance postoperative enteral nutrition. This review will serve to: 1) identify clinically relevant postoperative feeding patterns following pyloromyotomy, 2) review the relevant literature to determine an optimal feeding pattern, and 3) identify possible preoperative predictors that may determine the success of postoperative feeding regiments.     

Expression of EGFR, VEGF, and NOTCH1 Suggest Differences in Tumor Angiogenesis in HPV-Positive and HPV-Negative Head and Neck Squamous Cell Carcinoma

There is current interest in anti-angiogenesis therapies for head and neck squamous cell carcinomas (HNSCC), although the utility of these therapies in human papillomavirus (HPV) positive and HPV-negative HNSCC is unclear. Therefore, we explored heterogeneity in expression of a distal factor in angiogenesis (EGFR, the epidermal growth factor receptor), a proximal factor in angiogenesis (VEGF, the vascular endothelial growth factor) and a putative factor in angiogenesis (NOTCH1) in a HNSCC case series using immunohistochemistry in N = 67 cases (27 HPV-positive, 40 HPV-negative, by in situ hybridization). Box plots and the Wilcoxon rank sum or Kruskal–Wallis tests were used to compare staining scores (intensity × percent of cells staining) by HPV status and lifestyle factors. Associations between EGFR, VEGF, and NOTCH1 were assessed using box plots and Spearman correlation (ρ) in all cases, and stratified by HPV status. HPV-negative HNSCC over-expressed EGFR [median (range): 30 (0–300)] relative to HPV-positive HNSCC [7.5 (0–200)] (P = 0.006). VEGF and NOTCH1 were unrelated to HPV status (P > 0.05). EGFR was associated with VEGF in HPV-negative (ρ = 0.40, P = 0.01) but not HPV-positive HNSCC (ρ = 0.25, P = 0.20). NOTCH1 and VEGF were associated in HPV-negative (ρ = 0.40, P = 0.01) but not HPV-positive tumors (ρ = −0.12, P = 0.57). NOTCH1 was not associated with EGFR (P > 0.05). Our results are suggestive of heterogeneity in HNSCC angiogenesis. Future studies should explore angiogenesis mechanisms in HPV-positive and HPV-negative HNSCC.

Electronic supplementary material

The online version of this article (doi:10.1007/s12105-013-0447-y) contains supplementary material, which is available to authorized users.     

Ankle Dorsiflexion displacement is associated with hip and knee kinematics in females following anterior cruciate ligament reconstruction

The purpose of this study was to examine associations between ankle dorsiflexion (ankle-DF) displacement and knee and hip kinematics and kinetics during a jump-landing task in females following anterior cruciate ligament reconstruction (ACLR). Females (n = 23) with a history of unilateral ACLR (≥ 6-months post-ACLR) underwent a three-dimensional lower extremity biomechanical evaluation. Pearson Product Moment (r) correlations assessed associations between ankle-DF displacement and knee and hip kinematic and kinetic variables. On the involved-limb, individuals with lesser ankle-DF displacement demonstrated greater knee abduction displacement during the loading phase (r = -0.645, p = 0.001). On the uninvolved-limb, individuals with greater ankle-DF displacement demonstrated greater hip flexion displacement (r = 0.599, p = 0.003) and knee flexion displacement (r = -0.545, p = 0.007). There were no other significant associations between ankle-DF displacement and ankle, knee, or hip biomechanical variables on either limb (p > 0.05). Our findings demonstrate that reduced ankle-DF motion appears to share a different relationship between the involved- and uninvolved-limbs in females post-ACLR.     

Comparative studies on effects of three chitin synthesis inhibitors on common malaria mosquito (Diptera: Culicidae)

Toxicities of three chitin synthesis inhibitors (diflubenzuron, nikkomycin Z and polyoxin D) were evaluated using second instars of the common malaria mosquito, Anopheles quadrimaculatus Say (Diptera: Culicidae). Neither nikkomycin Z nor polyoxin D at 50 microg/liter caused significant larval mortality, although they reduced the body weight of the survivors by 20.5 and 33.8%, respectively, in 48 h. In contrast, exposures of the larvae to diflubenzuron at 12.5 microg/liter for 48 h resulted in 86.7% larval mortality and reduced the body weight of the survivors by 29.1%. Exposure of the pupae (<12 h old) to diflubenzuron at 100 microg/liter for 48 h caused 18.9% pupal mortality and consequently reduced the adult emergence by 24.7% from the surviving pupae. Furthermore, exposure of third instars to diflubenzuron at 4, 20, 100, and 500 microg/liter for 24 h resulted in the reduction of larval chitin contents by 4.25, 33.2, 35.2, and 57.7%, respectively. Such an effect seemed to be associated with only cuticular chitin synthesis because the same exposures did not significantly affect chitin contents in the guts. Our results indicated that diflubenzuron was highly toxic to second instars by not only causing high larval mortality but also by affecting their growth. Diflubenzuron was also fairly toxic to pupae by not only causing pupal mortality but also affecting the adult emergence. Our results suggest that diflubenzuron might affect only chitin synthesis in the cuticle but not in the peritrophic matrix, which is probably due to diflubenzuron's direct contact to mosquito larvae in water, slow distribution in insect body, rapid degradation in the insect gut, or a combination.