Laparoscopic Management of Transcervical Fallopian Tube Prolapse

Laparoscopic total salpingectomy appears to provide effective treatment with minimal invasiveness for transcervical fallopian tube prolapse

The Pore-Forming Protein Cry5B Elicits the Pathogenicity of Bacillus sp. against Caenorhabditis elegans

The soil bacterium Bacillus thuringiensis is a pathogen of insects and nematodes and is very closely related to, if not the same species as, Bacillus cereus and Bacillus anthracis. The defining characteristic of B. thuringiensis that sets it apart from B. cereus and B. anthracis is the production of crystal (Cry) proteins, which are pore-forming toxins or pore-forming proteins (PFPs). Although it is known that PFPs are important virulence factors since their elimination results in reduced virulence of many pathogenic bacteria, the functions by which PFPs promote virulence are incompletely understood. Here we study the effect of Cry proteins in B. thuringiensis pathogenesis of the nematode Caenorhabditis elegans. We find that whereas B. thuringiensis on its own is not able to infect C. elegans, the addition of the PFP Cry protein, Cry5B, results in a robust lethal infection that consumes the nematode host in 1–2 days, leading to a “Bob” or bag-of-bacteria phenotype. Unlike other infections of C. elegans characterized to date, the infection by B. thuringiensis shows dose-dependency based on bacterial inoculum size and based on PFP concentration. Although the infection process takes 1–2 days, the PFP-instigated infection process is irreversibly established within 15 minutes of initial exposure. Remarkably, treatment of C. elegans with Cry5B PFP is able to instigate many other Bacillus species, including B. anthracis and even “non-pathogenic” Bacillus subtilis, to become lethal and infectious agents to C. elegans. Co-culturing of Cry5B-expressing B. thuringiensis with B. anthracis can result in lethal infection of C. elegans by B. anthracis. Our data demonstrate that one potential property of PFPs is to sensitize the host to bacterial infection and further that C. elegans and probably other roundworms can be common hosts for B. cereus-group bacteria, findings with important ecological and research implications

Multi-ancestry sleep-by-SNP interaction analysis in 126,926 individuals reveals lipid loci stratified by sleep duration.

Both short and long sleep are associated with an adverse lipid profile, likely through different biological pathways. To elucidate the biology of sleep-associated adverse lipid profile, we conduct multi-ancestry genome-wide sleep-SNP interaction analyses on three lipid traits (HDL-c, LDL-c and triglycerides). In the total study sample (discovery + replication) of 126,926 individuals from 5 different ancestry groups, when considering either long or short total sleep time interactions in joint analyses, we identify 49 previously unreported lipid loci, and 10 additional previously unreported lipid loci in a restricted sample of European-ancestry cohorts. In addition, we identify new gene-sleep interactions for known lipid loci such as LPL and PCSK9. The previously unreported lipid loci have a modest explained variance in lipid levels: most notable, gene-short-sleep interactions explain 4.25% of the variance in triglyceride level. Collectively, these findings contribute to our understanding of the biological mechanisms involved in sleep-associated adverse lipid profiles

Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity.

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels

Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity

The present work was largely supported by a grant from the US National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (R01HL118305). The full list of acknowledgments appears in the Supplementary Notes 3 and 4.Peer reviewedPublisher PD

Comparative metabolomic profiling reveals that dysregulated glycolysis stemming from lack of salvage NAD⁺ biosynthesis impairs reproductive development in Caenorhabditis elegans

Temporal developmental progression is highly coordinated in Caenorhabditis elegans. However, loss of nicotinamidase PNC-1 activity slows reproductive development, uncoupling it from its typical progression relative to the soma. Using LC/MS we demonstrate that pnc-1 mutants do not salvage the nicotinamide released by NAD(+) consumers to resynthesize NAD(+), resulting in a reduction in global NAD(+) bioavailability. We manipulate NAD(+) levels to demonstrate that a minor deficit in NAD(+) availability is incompatible with a normal pace of gonad development. The NAD(+) deficit compromises NAD(+) consumer activity, but we surprisingly found no functional link between consumer activity and reproductive development. As a result we turned to a comparative metabolomics approach to identify the cause of the developmental phenotype. We reveal widespread metabolic perturbations, and using complementary pharmacological and genetic approaches, we demonstrate that a glycolytic block accounts for the slow pace of reproductive development. Interestingly, mitochondria are protected from both the deficiency in NAD(+) biosynthesis and the effects of reduced glycolytic output. We suggest that compensatory metabolic processes that maintain mitochondrial activity in the absence of efficient glycolysis are incompatible with the requirements for reproductive development, which requires high levels of cell division. In addition to demonstrating metabolic requirements for reproductive development, this work also has implications for understanding the mechanisms behind therapeutic interventions that target NAD(+) salvage biosynthesis for the purposes of inhibiting tumor growth

Infection of <i>C. elegans</i> by <i>B. anthracis-gfp</i> in presence of <i>B. thuringiensis</i> expressing Cry5B spores (non-<i>gfp</i>) and <i>B. anthracis-gfp</i> spores.

<p>(A) Transmitted-light view of the worm cuticle filled with vegetative and sporulated Bacillus. (B) View of the same worm using the fluorescence light: rod-shaped bacteria expressing GFP are visible, indicating that <i>B. anthracis</i> is capable of infecting <i>C. elegans</i> in presence of Cry5B expressing-<i>B. thuringiensis</i>. In this animal and all similar animals examined, the vast majority of bacteria inside the nematode cuticle were GFP positive. Scale bar is 50 µm.</p

Infectivity of <i>B. anthracis</i> in the presence of Cry-plus B. <i>thuringiensis.</i>

<p>Infectivity of <i>B. anthracis</i> in the presence of Cry-plus B. <i>thuringiensis.</i></p

Temporal aspects of the infection process.

<p>(A) Infections are established upon a short exposure to pathogen. Upper: schematic of experiment. Worms are added to the well on the left containing <i>B. thuringiensis</i> and Cry5B. Following either 5 min, 15 min, 30 min, 1 h, 2 h, 4 h, or 8 h, the worms were then moved through a series of five wells lacking Cry5B protein and containing non-infectious <i>B. megaterium</i> instead of <i>B. thuringiensis</i>. Infection outcomes in the final well were scored 48 h later. Lower: results of the experiment depicted in upper schematic. Data shown represent a total of three independent experiments with ∼30 animals per time point per experiment. Error bars indicate SEM. Only the infection rate for a 5-minute pulse is significantly different from the other data points (ANOVA, <i>p</i><0.05, Tukey's post test). (B) Cry5B acts early in the infection process as temporal addition of Cry5B protein after, and separate from, pathogen exposure results in a significant drop in infections. Upper: schematic of experiment in which worms are exposed to pathogen first and then to Cry5B. Lower: results in which two sets of experiments were set up simultaneously—a normal 15 minute pulse chase with both Cry5B PFP and pathogen added together (light gray bars; see (A) for set up) and pulse chase in which Cry5B was not added until the end (dark gray bars). Error bars represent SEM. ∼30 worms/condition/trial; 3–4 independent trials per condition. (C) The infection process appears to begin with colonization of the anterior intestine. The anterior intestine of a nematode 3 hr after exposure to <i>B. thuringiensis</i> (407-gfp) under pathogenic conditions. The left panel is a DIC image; the right panel deconvolved fluorescent (FITC) of the same animal. Images taken at 600×. Anterior is down.</p