A Neuro-Muscular Elasto-Dynamic Model of the Human Arm Part 2: Musculotendon Dynamics and Related Stress Effects

In this paper we develop an elasto-dynamic model of the human arm that includes effects of neuro-muscular control uponelastic deformation in the limb.The elasto-dynamic model of the arm is based on hybrid parameter multiple body systemvariational projection principles presented in the companion paper.Though the technique is suitable for detailed bone and jointmodeling,we present simulations for simplified geometry of the bones,discretized as Rayleigh beams with elongation,whileallowing for large deflections.Motion of the upper extremity is simulated by incorporating muscle forces derived from aHill-type model of musculotendon dynamics.The effects of muscle force are modeled in two ways.In one approach,aneffective joint torque is calculated by multiplying the muscle force by a joint moment ann.A second approach models themuscle as acting along a straight line between the origin and insertion sites of the tendon.Simple arm motion is simulated byutilizing neural feedback and feedforward control.Simulations illustrate the combined effects of neural control strategies,models of muscle force inclusion,and elastic assumptions on joint trajectories and stress and strain development in the bone andtendon.     

Comparative Genotyping of Campylobacter jejuni Strains from Patients with Guillain-Barré Syndrome in Bangladesh

Background

Campylobacter jejuni is a common cause of acute gastroenteritis and is associated with post-infectious neuropathies such as the Guillain-Barré syndrome (GBS) and the Miller Fisher syndrome (MFS). We here present comparative genotyping of 49 C. jejuni strains from Bangladesh that were recovered from patients with enteritis or GBS. All strains were serotyped and analyzed by lipo-oligosaccharide (LOS) genotyping, amplified fragment length polymorphism (AFLP) analysis, multilocus sequence typing (MLST), and pulsed-field gel electrophoresis (PFGE).

Methodology/Principal Findings

C. jejuni HS:23 was a predominant serotype among GBS patients (50%), and no specific serotype was significantly associated with GBS compared to enteritis. PCR screening showed that 38/49 (78%) of strains could be assigned to LOS classes A, B, C, or E. The class A locus (4/7 vs 3/39; p<0.01) was significantly associated in the GBS-related strains as compared to enteritis strains. All GBS/oculomotor related strains contained the class B locus; which was also detected in 46% of control strains. Overlapping clonal groups were defined by MLST, AFLP and PFGE for strains from patients with gastroenteritis and GBS. MLST defined 22 sequence types (STs) and 7 clonal complexes including 7 STs not previously identified (ST-3742, ST-3741, ST-3743, ST-3748, ST-3968, ST-3969 and ST-3970). C. jejuni HS:23 strains from patients with GBS or enteritis were clonal and all strains belonged to ST-403 complex. Concordance between LOS class B and ST-403 complex was revealed. AFLP defined 25 different types at 90% similarity. The predominant AFLP type AF-20 coincided with the C. jejuni HS:23 and ST-403 complex.

Conclusion/Significance

LOS genotyping, MLST, AFLP and PFGE helped to identify the HS:23 strains from GBS or enteritis patients as clonal. Overall, genotypes exclusive for enteritis or for GBS-related strains were not obtained although LOS class A was significantly associated with GBS strains. Particularly, the presence of a clonal and putative neuropathogenic C. jejuni HS:23 serotype may contribute to the high prevalence of C. jejuni related GBS in Bangladesh.     

Multi‐locus sequence types of Campylobacter carried by flies and slugs acquired from local ruminant faeces

Aims: To assess whether flies and slugs acquire strains of Campylobacter jejuni and Campylobacter coli present in local ruminant faeces. Methods and Results: Campylobacter was cultured from flies, slugs and ruminant faeces that were collected from a single farm in Scotland over a 19‐week period. The isolates were typed using multi‐locus sequence typing (MLST) and compared with isolates from cattle and sheep faeces. Campylobacter jejuni and Camp. coli were isolated from 5·8% (n = 155, average of 75 flies per pool) and 13·3% (n = 15, average of 8·5 slugs per pool) of pooled fly and slug samples, respectively. The most common sequence type (ST) in flies was Camp. coli ST‐962 (approx. 40%) regardless of the prevalence in local cattle (2·3%) or sheep (25·0%) faeces. Two positive slug pools generated the same ST that has not been reported elsewhere. Conclusions: Despite their low carriage rate, flies are able to acquire Campylobacter STs that are locally present, although the subset carried may be biased when compared to local source. Slugs were shown to carry a previously unreported Campylobacter ST. Significance and Impact of the Study: This study has demonstrated that flies carry viable Campylobacter and may contribute to the transfer of STs within and between groups of animals on farms. Further, they may therefore present a risk to human health via their contact with ready‐to‐eat foods or surfaces.     

Pan-genome sequence analysis using Panseq: an online tool for the rapid analysis of core and accessory genomic regions

Background  

The pan-genome of a bacterial species consists of a core and an accessory gene pool. The accessory genome is thought to be an important source of genetic variability in bacterial populations and is gained through lateral gene transfer, allowing subpopulations of bacteria to better adapt to specific niches. Low-cost and high-throughput sequencing platforms have created an exponential increase in genome sequence data and an opportunity to study the pan-genomes of many bacterial species. In this study, we describe a new online pan-genome sequence analysis program, Panseq.     

The design of potent and selective inhibitors of thrombin utilizing a piperazinedione template: part 1.

Utilizing X-ray crystallography and molecular modeling, highly potent and selective peptidomimetic thrombin inhibitors have been designed containing a rigid piperazinedione template. The synthesis and biological activity of these compounds will be described.     

The design of potent and selective inhibitors of thrombin utilizing a piperazinedione template: part 2.

Potent and selective thrombin inhibitors have been prepared with a piperazinedione template and L-amino acids. Likewise, incorporation of D-amino acids led to potent inhibitors with a novel mode of binding. Herein, the structure activity relationships and structural aspects of these compounds will be described.     

Temporal variation and host association in the Campylobacter population in a longitudinal ruminant farm study

Campylobacter jejuni and C. coli were quantified and typed, using multilocus sequence typing (MLST), from fecal samples collected from a mixed cattle and sheep farm during summer. Cattle had a significantly higher prevalence than sheep (21.9% [74/338] and 14.0% [30/214], respectively), but both decreased over time. There were no differences in the average Campylobacter concentrations shed by cattle (600 CFU g(-1)) and sheep (820 CFU g(-1)), although sheep did show a significant temporal reduction in the number of Campylobacter organisms shed in their feces. A total of 21 different sequence types (STs) (97.7% C. jejuni, 2.3% C. coli) were isolated from cattle, and 9 different STs were isolated from sheep (40.6% C. jejuni, 59.4% C. coli). The Campylobacter population in cattle was relatively stable, and the frequencies of genotypes isolated showed little temporal variation. However, the composition of subtypes isolated from sheep did show significant temporal differences. The cattle and sheep consistently showed significant differences in their carriage of Campylobacter species, STs, and CCs despite the fact that both were exposed to the same farming environment. This work has highlighted the patterns of a Campylobacter population on a ruminant farm by identifying the existence of both temporal and between-host variations.     

The role of the <Emphasis Type="Italic">TCF4</Emphasis> gene in the phenotype of individuals with 18q segmental deletions

The goal of this study is to define the effects of TCF4 hemizygosity in the context of a larger segmental deletion of chromosome 18q. Our cohort included 37 individuals with deletions of 18q. Twenty-seven had deletions including TCF4 (TCF4 ^+/−); nine had deletions that did not include TCF4 (TCF4 ^+/+); and one individual had a microdeletion that included only the TCF4 gene. We compared phenotypic data from the participants’ medical records, survey responses, and in-person evaluations. Features unique to the TCF4 ^+/− individuals included abnormal corpus callosum, short neck, small penis, accessory and wide-spaced nipples, broad or clubbed fingers, and sacral dimple. The developmental data revealed that TCF4 ^+/+ individuals were only moderately developmentally delayed while TCF4 ^+/− individuals failed to reach developmental milestones beyond those typically acquired by 12 months of age. TCF4 hemizygosity also conferred an increased risk of early death principally due to aspiration-related complications. Hemizygosity for TCF4 confers a significant impact primarily with regard to cognitive and motor development, resulting in a very different prognosis for individuals hemizygous for TCF4 when compared to individuals hemizygous for other regions of distal 18q.     

Impairment of C(4) photosynthesis by drought is exacerbated by limiting nitrogen and ameliorated by elevated [CO(2)] in maize

Predictions of future ecosystem function and food supply from staple C(4) crops, such as maize, depend on elucidation of the mechanisms by which environmental change and growing conditions interact to determine future plant performance. To test the interactive effects of elevated [CO(2)], drought, and nitrogen (N) supply on net photosynthetic CO(2) uptake (A) in the world's most important C(4) crop, maize (Zea mays) was grown at ambient [CO(2)] (～385 ppm) and elevated [CO(2)] (550 ppm) with either high N supply (168 kg N ha(-1) fertilizer) or limiting N (no fertilizer) at a site in the US Corn Belt. A mid-season drought was not sufficiently severe to reduce yields, but caused significant physiological stress, with reductions in stomatal conductance (up to 57%), A (up to 44%), and the in vivo capacity of phosphoenolpyruvate carboxylase (up to 58%). There was no stimulation of A by elevated [CO(2)] when water availability was high, irrespective of N availability. Elevated [CO(2)] delayed and relieved both stomatal and non-stomatal limitations to A during the drought. Limiting N supply exacerbated stomatal and non-stomatal limitation to A during drought. However, the effects of limiting N and elevated [CO(2)] were additive, so amelioration of stress by elevated [CO(2)] did not differ in magnitude between high N and limiting N supply. These findings provide new understanding of the limitations to C(4) photosynthesis that will occur under future field conditions of the primary region of maize production in the world.