3D finite element modeling of pelvic organ prolapse

Objectives: The purpose of this study is to develop a validated 3D finite element model of the pelvic floor system which can offer insights into the mechanics of anterior vaginal wall prolapse and have the ability to assess biomedical device treatment methods. The finite element results should accurately mimic the clinical findings of prolapse due to intra-abdominal pressure (IAP) and soft tissues impairment conditions. Methods: A 3D model of pelvic system was created in Creo Parametric 2.0 based on MRI Images, which included uterus, cervix, vagina, cardinal ligaments, uterosacral ligaments, and a simplified levator plate and rectum. The geometrical model was imported into ANSYS Workbench 14.5. Mechanical properties of soft tissues were based on experimental data of tensile test results from current literature. Studies were conducted for IAP loadings on the vaginal wall and uterus, increasing from lowest to extreme values. Results: Anterior vaginal wall collapse occurred at an IAP value corresponding to maximal valsalva and showed similar collapsed shape as clinical findings. Prolapse conditions exhibited high sensitivity to vaginal wall stiffness, whereas healthy tissues was found to support the vagina against prolapse. Ligament impairment was found to have only a secondary effect on prolapse.     

Genomic potential for arsenic efflux and methylation varies among global Prochlorococcus populations

The globally significant picocyanobacterium Prochlorococcus is the main primary producer in oligotrophic subtropical gyres. When phosphate concentrations are very low in the marine environment, the mol:mol availability of phosphate relative to the chemically similar arsenate molecule is reduced, potentially resulting in increased cellular arsenic exposure. To mediate accidental arsenate uptake, some Prochlorococcus isolates contain genes encoding a full or partial efflux detoxification pathway, consisting of an arsenate reductase (arsC), an arsenite-specific efflux pump (acr3) and an arsenic-related repressive regulator (arsR). This efflux pathway was the only previously known arsenic detox pathway in Prochlorococcus. We have identified an additional putative arsenic mediation strategy in Prochlorococcus driven by the enzyme arsenite S-adenosylmethionine methyltransferase (ArsM) which can convert inorganic arsenic into more innocuous organic forms and appears to be a more widespread mode of detoxification. We used a phylogenetically informed approach to identify Prochlorococcus linked arsenic genes from both pathways in the Global Ocean Sampling survey. The putative arsenic methylation pathway is nearly ubiquitously present in global Prochlorococcus populations. In contrast, the complete efflux pathway is only maintained in populations which experience extremely low PO₄:AsO₄, such as regions in the tropical and subtropical Atlantic. Thus, environmental exposure to arsenic appears to select for maintenance of the efflux detoxification pathway in Prochlorococcus. The differential distribution of these two pathways has implications for global arsenic cycling, as their associated end products, arsenite or organoarsenicals, have differing biochemical activities and residence times.     

The ultrastructure and cytochemistry of microbodies in dinoflagellates

Summary Microbodies, similar in morphology to those of higher plants and animals, have been observed in thirteen genera of dinoflagellates. As in other unicellular algae, they did not show any staining after incubation in DAB/H₂O₂ medium although the mitochondrial cristae and chloroplast lamellae did give a positive reaction. The microbodies of Scrippsiella sweeneyae were found to be associated with a membranous reticulate structure, which may be involved in their formation.     

Application of high throughput pretreatment and co‐hydrolysis system to thermochemical pretreatment. Part 1: Dilute acid

Because conventional approaches for evaluating sugar release from the coupled operations of pretreatment and enzymatic hydrolysis are extremely time and material intensive, high throughput (HT) pretreatment and enzymatic hydrolysis systems have become vital for screening large numbers of lignocellulosic biomass samples to identify feedstocks and/or processing conditions that significantly improve performance and lower costs. Because dilute acid pretreatment offers many important advantages in rendering biomass highly susceptible to subsequent enzymatic hydrolysis, a high throughput pretreatment and co‐hydrolysis (HTPH) approach was extended to employ dilute acid as a tool to screen for enhanced performance. First, a single‐step neutralization and buffering method was developed to allow effective enzymatic hydrolysis of the whole pretreated slurry. Switchgrass and poplar were then pretreated with 0.5% and 1% acid loadings at a 5% solids concentration, the resulting slurry conditioned with the buffering approach, and the entire mixture enzymatically hydrolyzed. The resulting sugar yields demonstrated that single‐step neutralizing and buffering was capable of adjusting the pH as needed for enzymatic saccharification, as well as overcoming enzyme inhibition by compounds released in pretreatment. In addition, the effects of pretreatment conditions and biomass types on susceptibility of pretreated substrates to enzymatic conversion were clearly discernible, demonstrating the method to be a useful extension of HTPH systems. Biotechnol. Bioeng. 2013; 110: 754–762. © 2012 Wiley Periodicals, Inc.     

Species succession and the development of a lacustrine fish community in an ephemeral lake

Here, we present a gillnet survey of Lake Liambezi a 370 km² shallow ephemeral floodplain lake situated in north-eastern Namibia, which is fed irregularly by the upper Zambezi and Kwando Rivers during years of high flooding. The lake dried up in 1985 and, with the exception of sporadic minor annual inundation events, remained dry until 2007. We describe the temporal succession of fish species over an 8 year period from initial inundation 2007 to maturation in 2014. The succession of the fish community did not follow the typical pattern of opportunistic strategists during colonisation, to periodic strategists that are eventually succeeded by equilibrium strategists. Instead, the evolution of the fish community was characterised by three distinct phases. The first phase involved the inundation and colonisation of the lake in 2007, followed by its decline until the floods that filled the lake in 2009. During this phase the lake was colonised by fishes from the adjacent upper Zambezi and Chobe River floodplains. Fish communities predominantly comprised floodplain specialists including the barbs Enteromius paludinosus and Enteromius poechii, the mormyrid Marcusenius altisambesi and catfishes Schilbe intermedius and Clarias gariepinus. The filling of the lake in the March 2009 floods marked the beginning of the second, successional phase. The barbs declined in abundance and the alestid Rhabdalestes maunensis underwent explosive population growth between 2009 and 2010, but populations crashed equally rapidly and were replaced by Brycinus lateralis which, together with S. intermedius went on to dominate the fish community 2011–2014. Larger, slower growing tilapiine cichlids increased steadily in abundance and became the dominant components in a 2700 t y^–1 artisanal fishery that developed on the lake. The fish community in the ephemeral Lake Liambezi is clearly influenced by numerous factors including connectivity, lake level fluctuations, competition and the effects of fishing, which may disrupt typical succession processes in floodplain ecosystems.     

Ocean acidification disrupts induced defences in the intertidal gastropod Littorina littorea

Carbon dioxide-induced ocean acidification is predicted to have major implications for marine life, but the research focus to date has been on direct effects. We demonstrate that acidified seawater can have indirect biological effects by disrupting the capability of organisms to express induced defences, hence, increasing their vulnerability to predation. The intertidal gastropod Littorina littorea produced thicker shells in the presence of predation (crab) cues but this response was disrupted at low seawater pH. This response was accompanied by a marked depression in metabolic rate (hypometabolism) under the joint stress of high predation risk and reduced pH. However, snails in this treatment apparently compensated for a lack of morphological defence, by increasing their avoidance behaviour, which, in turn, could affect their interactions with other organisms. Together, these findings suggest that biological effects from ocean acidification may be complex and extend beyond simple direct effects.     

Selection of an HLA-C*03:04-Restricted HIV-1 p24 Gag Sequence Variant Is Associated with Viral Escape from KIR2DL3+ Natural Killer Cells: Data from an Observational Cohort in South Africa

Background

Viruses can evade immune surveillance, but the underlying mechanisms are insufficiently understood. Here, we sought to understand the mechanisms by which natural killer (NK) cells recognize HIV-1-infected cells and how this virus can evade NK-cell-mediated immune pressure.

Methods and Findings

Two sequence mutations in p24 Gag associated with the presence of specific KIR/HLA combined genotypes were identified in HIV-1 clade C viruses from a large cohort of infected, untreated individuals in South Africa (n = 392), suggesting viral escape from KIR+ NK cells through sequence variations within HLA class I—presented epitopes. One sequence polymorphism at position 303 of p24 Gag (T_Gag303V), selected for in infected individuals with both KIR2DL3 and HLA-C*03:04, enabled significantly better binding of the inhibitory KIR2DL3 receptor to HLA-C*03:04-expressing cells presenting this variant epitope compared to the wild-type epitope (wild-type mean 18.01 ± 10.45 standard deviation [SD] and variant mean 44.67 ± 14.42 SD, p = 0.002). Furthermore, activation of primary KIR2DL3+ NK cells from healthy donors in response to HLA-C*03:04+ target cells presenting the variant epitope was significantly reduced in comparison to cells presenting the wild-type sequence (wild-type mean 0.78 ± 0.07 standard error of the mean [SEM] and variant mean 0.63 ± 0.07 SEM, p = 0.012). Structural modeling and surface plasmon resonance of KIR/peptide/HLA interactions in the context of the different viral sequence variants studied supported these results. Future studies will be needed to assess processing and antigen presentation of the investigated HIV-1 epitope in natural infection, and the consequences for viral control.

Conclusions

These data provide novel insights into how viruses can evade NK cell immunity through the selection of mutations in HLA-presented epitopes that enhance binding to inhibitory NK cell receptors. Better understanding of the mechanisms by which HIV-1 evades NK-cell-mediated immune pressure and the functional validation of a structural modeling approach will facilitate the development of novel targeted immune interventions to harness the antiviral activities of NK cells.     

Maternal lineages in native Canadian equine populations and their relationship to the Nordic and Mountain and Moorland pony breeds

A 378-bp section of the mitochondrial displacement loop was used to estimate genetic diversity in the native Canadian equine populations. The inclusion of 10 Mountain and Moorland, 3 Nordic pony breeds, 2 feral populations, and 5 horse breeds were also investigated as they may have influenced the development (or rejuvenation) of the native Canadian populations. A total of 281 samples were sequenced, which produced 75 haplotypes derived from 54 informative sites. On further investigation, 36 of these 75 haplotypes were found to be previously unreported. Overall, total diversity was lowest in the feral Sable Island population with a haplotype diversity (0.27 ± 0.12), nucleotide diversity (0.0007 ± 0.0004), and pairwise difference of 0.286 ± 0.317. This is not surprising due to the geographic isolation of this population. Haplotype diversity was highest (1.00 ± 0.13) in the New Forest population, pairwise difference was highest (8.061 ± 4.028) in the Icelandic breed, whereas nucleotide diversity was highest in the Exmoor breed (0.0209 ± 0.0025). Within the Canadian populations, haplotype diversity was highest in the Newfoundland pony (0.96 ± 0.08), whereas pairwise difference and nucleotide diversity was highest in the Canadian horse (7.090 ± 3.581 and 0.0188 ± 0.0042, respectively). Three different estimates of genetic distances were used to examine the phylogenetic relationships amongst these populations. All 3 estimates produced similar topologies. In general, the native Canadian populations were highly represented in the D clade, with particular emphasis in the D1 and D2 clades. This is an important factor when considering the phylogenetic conservation of these Canadian equine populations.