Climate change, extinction, and Sky Island biogeography in a montane lizard.

Around the world, many species are confined to "Sky Islands," with different populations in isolated patches of montane habitat. How does this pattern arise? One scenario is that montane species were widespread in lowlands when climates were cooler, and were isolated by local extinction caused by warming conditions. This scenario implies that many montane species may be highly susceptible to anthropogenic warming. Here, we test this scenario in a montane lizard (Sceloporus jarrovii) from the Madrean Sky Islands of southeastern Arizona. We combined data from field surveys, climate, population genomics, and physiology. Overall, our results support the hypothesis that this species' current distribution is explained by local extinction caused by past climate change. However, our results for this species differ from simple expectations in several ways: (a) their absence at lower elevations is related to warm winter temperatures, not hot summer temperatures; (b) they appear to exclude a low-elevation congener from higher elevations, not the converse; (c) they are apparently absent from many climatically suitable but low mountain ranges, seemingly "pushed off the top" by climates even warmer than those today; (d) despite the potential for dispersal among ranges during recent glacial periods (~18,000 years ago), populations in different ranges diverged ~4.5-0.5 million years ago and remained largely distinct; and (e) body temperatures are inversely related to climatic temperatures among sites. These results may have implications for many other Sky Island systems. More broadly, we suggest that Sky Island species may be relevant for predicting responses to future warming.

Demystifying the marine-terrestrial biodiversity gradient: response to Vermeij et al.

We respond to seven criticisms made by Vermeij et al. () regarding Miller & Wiens (). Their criticisms generally reflect misunderstandings, unsupported speculations, and topics that were explicitly addressed in our paper.

Evaluating methods for phylogenomic analyses, and a new phylogeny for a major frog clade (Hyloidea) based on 2214 loci.

Phylogenomic approaches offer a wealth of data, but a bewildering diversity of methodological choices. These choices can strongly affect the resulting topologies. Here, we explore two controversial approaches (binning genes into "supergenes" and inclusion of only rapidly evolving sites), using new data from hyloid frogs. Hyloid frogs encompass ∼53% of frog species, including true toads (Bufonidae), glassfrogs (Centrolenidae), poison frogs (Dendrobatidae), and treefrogs (Hylidae). Many hyloid families are well-established, but relationships among these families have remained difficult to resolve. We generated a dataset of ultraconserved elements (UCEs) for 50 ingroup species, including 18 of 19 hyloid families and up to 2214 loci spanning >800,000 aligned base pairs. We evaluated these two general approaches (binning, rapid sites only) based primarily on their ability to recover and strongly support well-established clades. Data were analyzed using concatenated likelihood and coalescent species-tree methods (NJst, ASTRAL). Binning strongly affected inferred relationships, whereas use of only rapidly evolving sites did not (indicating ∼87% of the data contributed little information). The optimal approaches for maximizing recovery and support of well-established clades were concatenated likelihood analysis and the use of a limited number of naive bins (statistical binning gave more problematic results). These two optimal approaches converged on similar relationships among hyloid families, and resolved them with generally strong support. The relationships found were very different from most previous estimates of hyloid phylogeny, and a new classification is proposed. The new phylogeny also suggests an intriguing biogeographical scenario, in which hyloids originated in southern South America before radiating throughout the world.

Extinction and time help drive the marine-terrestrial biodiversity gradient: is the ocean a deathtrap?

The marine-terrestrial richness gradient is among Earth's most dramatic biodiversity patterns, but its causes remain poorly understood. Here, we analyse detailed phylogenies of amniote clades, paleontological data and simulations to reveal the mechanisms underlying low marine richness, emphasising speciation, extinction and colonisation. We show that differences in diversification rates (speciation minus extinction) between habitats are often weak and inconsistent with observed richness patterns. Instead, the richness gradient is explained by limited time for speciation in marine habitats, since all extant marine clades are relatively young. Paleontological data show that older marine invasions have consistently ended in extinction. Simulations show that marine extinctions help drive the pattern of young, depauperate marine clades. This role for extinction is not discernible from molecular phylogenies alone, and not predicted by most previously hypothesised explanations for this gradient. Our results have important implications for the marine-terrestrial biodiversity gradient, and studies of biodiversity gradients in general.

Increased postoperative day one discharges after implementation of a hysterectomy enhanced recovery pathway: a retrospective cohort study.

PURPOSE: In 2011, the hysterectomy enhanced recovery (HER) pathway, a multi-disciplinary, evidence-based care plan designed to improve recovery after open gynecologic surgery for non-malignant lesions, was introduced at The Ottawa Hospital (TOH). This before-and-after study examined the impact of the HER pathway on postoperative day (POD) 1 hospital discharge. METHODS: Ethical approval was obtained. This retrospective cohort study included patients who had undergone open abdominal gynecologic surgery for non-malignant lesions at TOH Civic Campus between July 2010 and September 2012 (the year before and year after HER implementation). Patients were analyzed in either a pre-HER or post-HER group depending on their surgery date. Patients with chronic pain and emergent surgery were excluded. Data were obtained via medical chart review. Our primary outcome was the percentage of POD 1 discharges before and after HER implementation. Secondary outcomes included return to hospital within 30 days of discharge, median length of stay (LOS), clinician compliance with HER, and an exploratory analysis with multivariable modelling to evaluate which aspects of the HER independently predicted POD 1 discharge. Variables used included American Society of Anesthesiologists physical status (≥ II), prior abdominal surgery, body mass index, use of transversus abdominis plane blocks, and anesthetic type. RESULTS: Among the 223 patients, significantly more POD 1 discharges occurred for post-HER compared to pre-HER patients (34% vs 7%, respectively; adjusted odds ratio [OR] = 7.33; 95% confidence interval [CI] = 3.05 to 17.62). Rates of return to hospital at 30 days were similar between the groups (10% post-HER and 13% pre-HER; adjusted OR = 0.74; 95% CI = 0.32 to 1.74). The median length of stay was two days in the post-HER group and three days in the pre-HER group (P < 0.0001). Only inhalational general anesthesia was independently associated with decreased odds of POD 1 discharge (adjusted OR = 0.16, 95% CI = 0.04 to 0.65). CONCLUSION: For patients undergoing abdominal hysterectomy, implementation of a HER pathway is associated with a higher POD 1 discharge rate, with no increase in the early return to hospital rate.

A prevalent C3 mutation in aHUS patients causes a direct C3 convertase gain of function.

Atypical hemolytic uremic syndrome (aHUS) is a rare renal thrombotic microangiopathy commonly associated with rare genetic variants in complement system genes, unique to each patient/family. Here, we report 14 sporadic aHUS patients carrying the same mutation, R139W, in the complement C3 gene. The clinical presentation was with a rapid progression to end-stage renal disease (6 of 14) and an unusually high frequency of cardiac (8 of 14) and/or neurologic (5 of 14) events. Although resting glomerular endothelial cells (GEnCs) remained unaffected by R139W-C3 sera, the incubation of those sera with GEnC preactivated with pro-inflammatory stimuli led to increased C3 deposition, C5a release, and procoagulant tissue-factor expression. This functional consequence of R139W-C3 resulted from the formation of a hyperactive C3 convertase. Mutant C3 showed an increased affinity for factor B and a reduced binding to membrane cofactor protein (MCP; CD46), but a normal regulation by factor H (FH). In addition, the frequency of at-risk FH and MCP haplotypes was significantly higher in the R139W-aHUS patients, compared with normal donors or to healthy carriers. These genetic background differences could explain the R139W-aHUS incomplete penetrance. These results demonstrate that this C3 mutation, especially when associated with an at-risk FH and/or MCP haplotypes, becomes pathogenic following an inflammatory endothelium-damaging event.

Three new species of triplefin blennies of the genus Enneanectes (Teleostei, Tripterygiidae) from the tropical eastern Pacific with a key to Pacific species of Enneanectes.

Three new species of the triplefin blenny genus Enneanectes found in the Pacific Ocean off southern Mexico are described. Two, Enneanectes glendae and Enneanectes macrops, are mainland species, while the third, Enneanectes exsul, is endemic to the Islas Revillagigedo. A key to the five species of Enneanectes known from the tropical eastern Pacific is provided.

Autoantibody stabilization of the classical pathway C3 convertase leading to C3 deficiency and Neisserial sepsis: C4 nephritic factor revisited.

C3 deficiency is a rare disorder that leads to recurrent pyogenic infections. Here we describe a previously healthy 18 y/o Caucasian male with severe meningococcal disease. Total hemolytic activity was zero secondary to an undetectable C3. The C3 gene was normal by sequencing. Mixing the patient's serum with normal human serum led to C3 consumption. An IgG autoantibody in the patient's serum was identified that stabilized the classical pathway C3 and C5 convertases, thus preventing decay of these enzyme complexes. This autoantibody is an example of a C4 nephritic factor, with an additional feature of stabilizing the C5 convertase. Previous patients with C4 nephritic factor had membranoproliferative glomerulonephritis. Two years after presentation, this patient's C3 remains undetectable with no evidence of renal disease. We revisit the role of autoantibodies to classical pathway convertases in disease, review the literature on C4-NeF and comment on its detection in the clinical laboratory.

Why do Canadian women fail to achieve optimal pre-conceptional folic acid supplementation? An observational study.

OBJECTIVES: To determine the factors that put Canadian women at risk for not supplementing with folic acid (FA) in the three months before conception, as recommended for the prevention of infant neural tube defects. METHODS: This study used data from the Canadian Maternity Experiences Survey. We used Poisson regression analysis with a robust variance to determine which factors were associated with women not supplementing with FA in the three months prior to pregnancy as compared with women who did supplement. RESULTS: Of the 6421 women surveyed, 57.7% were supplementing with FA pre-conceptionally. The risk factors associated with a lack of FA supplementation pre-conceptionally were maternal age <19 (prevalence ratio [PR] = 0.50; 95% CI 0.36 to 0.69) or 20 to 24 (PR = 0.75; 95% CI 0.67 to 0.84); education below high school level (PR = 0.73; 95% CI 0.61 to 0.87), at high school level (PR = 0.77; 95% CI 0.71 to 0.83), or at post-secondary level other than university (PR = 0.93; 95% CI 0.88 to 0.97); being at or below the low-income cut-off (PR = 0.74; 95% CI 0.67 to 0.81); smoking before pregnancy (PR = 0.79; 95% CI 0.73 to 0.86); being non-fluent in the language of the health care provider (PR = 0.66; 95% CI 0.49 to 0.88); being obese (BMI ≥ 30) (PR = 0.91; 95% CI 0.85 to 0.98); being unemployed (PR = 0.94; 95% CI 0.89 to 1.00); and being born outside of Canada (PR = 0.79; 95% CI 0.74 to 0.84). CONCLUSION: Young maternal age, low education, low income, smoking, language barriers, obesity, unemployment, and being born outside Canada are risk factors for suboptimal or lack of FA supplementation pre-conceptionally.

Speciation across the Tree of Life.

Much of what we know about speciation comes from detailed studies of well-known model systems. Although there have been several important syntheses on speciation, few (if any) have explicitly compared speciation among major groups across the Tree of Life. Here, we synthesize and compare what is known about key aspects of speciation across taxa, including bacteria, protists, fungi, plants, and major animal groups. We focus on three main questions. Is allopatric speciation predominant across groups? How common is ecological divergence of sister species (a requirement for ecological speciation), and on what niche axes do species diverge in each group? What are the reproductive isolating barriers in each group? Our review suggests the following patterns. (i) Based on our survey and projected species numbers, the most frequent speciation process across the Tree of Life may be co-speciation between endosymbiotic bacteria and their insect hosts. (ii) Allopatric speciation appears to be present in all major groups, and may be the most common mode in both animals and plants, based on non-overlapping ranges of sister species. (iii) Full sympatry of sister species is also widespread, and may be more common in fungi than allopatry. (iv) Full sympatry of sister species is more common in some marine animals than in terrestrial and freshwater ones. (v) Ecological divergence of sister species is widespread in all groups, including ~70% of surveyed species pairs of plants and insects. (vi) Major axes of ecological divergence involve species interactions (e.g. host-switching) and habitat divergence. (vii) Prezygotic isolation appears to be generally more widespread and important than postzygotic isolation. (viii) Rates of diversification (and presumably speciation) are strikingly different across groups, with the fastest rates in plants, and successively slower rates in animals, fungi, and protists, with the slowest rates in prokaryotes. Overall, our study represents an initial step towards understanding general patterns in speciation across all organisms.

Abyssal deposit feeders are secondary consumers of detritus and rely on nutrition derived from microbial communities in their guts.

Trophic ecology of detrital-based food webs is still poorly understood. Abyssal plains depend entirely on detritus and are among the most understudied ecosystems, with deposit feeders dominating megafaunal communities. We used compound-specific stable isotope ratios of amino acids (CSIA-AA) to estimate the trophic position of three abundant species of deposit feeders collected from the abyssal plain of the Northeast Pacific (Station M; ~ 4000 m depth), and compared it to the trophic position of their gut contents and the surrounding sediments. Our results suggest that detritus forms the base of the food web and gut contents of deposit feeders have a trophic position consistent with primary consumers and are largely composed of a living biomass of heterotrophic prokaryotes. Subsequently, deposit feeders are a trophic level above their gut contents making them secondary consumers of detritus on the abyssal plain. Based on δ13C values of essential amino acids, we found that gut contents of deposit feeders are distinct from the surrounding surface detritus and form a unique food source, which was assimilated by the deposit feeders primarily in periods of low food supply. Overall, our results show that the guts of deposit feeders constitute hotspots of organic matter on the abyssal plain that occupy one trophic level above detritus, increasing the food-chain length in this detritus-based ecosystem.

Mutations in complement C3 predispose to development of atypical hemolytic uremic syndrome.

Atypical hemolytic uremic syndrome (aHUS) is a disease of complement dysregulation. In approximately 50% of patients, mutations have been described in the genes encoding the complement regulators factor H, MCP, and factor I or the activator factor B. We report here mutations in the central component of the complement cascade, C3, in association with aHUS. We describe 9 novel C3 mutations in 14 aHUS patients with a persistently low serum C3 level. We have demonstrated that 5 of these mutations are gain-of-function and 2 are inactivating. This establishes C3 as a susceptibility factor for aHUS.

The risk of adverse pregnancy outcomes is increased in preeclamptic women who smoke compared with nonpreeclamptic women who do not smoke.

OBJECTIVE: Maternal smoking and preeclampsia independently increase the risk of adverse pregnancy outcomes; however, smoking decreases the risk of preeclampsia. We sought to estimate the risk of adverse pregnancy outcomes among preeclamptic women who smoke and hypothesized that this risk would be increased, compared with nonpreeclamptic women who smoke or preeclamptic women who do not smoke. STUDY DESIGN: With the use of the Niday Perinatal Database and multiple logistic regressions, we estimated the risk of adverse pregnancy outcomes in nonpreeclamptic women who smoke, preeclamptic women who do not smoke, and preeclamptic women who smoke in relation to nonpreeclamptic women who do not smoke. RESULTS: The incidence of adverse pregnancy outcomes was more than twice as high among preeclamptic women who smoke as among nonpreeclamptic women who do not smoke. The following data were observed: small-for-gestational-age infant (odds ratio [OR], 3.40; 95% CI, 2.27-4.89), preterm birth (OR, 5.77; 95% CI, 4.50-7.35), very preterm birth (OR, 5.44; 95% CI, 3.51-8.11), abruption (OR, 6.16; 95% CI, 3.05-11.01), Apgar <4 at 5 minutes (OR, 3.11; 95% CI, 1.48-5.72), and stillbirth (OR, 3.39; 95% CI, 1.33-6.99). CONCLUSION: Smoking decreases the risk of preeclampsia, but smokers with preeclampsia have an increased risk for adverse pregnancy outcomes.

Plant-driven changes in soil microbial communities influence seed germination through negative feedbacks.

Plant-soil feedbacks (PSFs) drive plant community diversity via interactions between plants and soil microbes. However, we know little about how frequently PSFs affect plants at the seed stage, and the compositional shifts in fungi that accompany PSFs on germination.We conducted a pairwise PSF experiment to test whether seed germination was differentially impacted by conspecific versus heterospecific soils for seven grassland species. We used metagenomics to characterize shifts in fungal community composition in soils conditioned by each plant species. To investigate whether changes in the abundance of certain fungal taxa were associated with multiple PSFs, we assigned taxonomy to soil fungi and identified putative pathogens that were significantly more abundant in soils conditioned by plant species that experienced negative or positive PSFs.We observed negative, positive, and neutral PSFs on seed germination. Although conspecific and heterospecific soils for pairs with significant PSFs contained host-specialized soil fungal communities, soils with specialized microbial communities did not always lead to PSFs. The identity of host-specialized pathogens, that is, taxa uniquely present or significantly more abundant in soils conditioned by plant species experiencing negative PSFs, overlapped among plant species, while putative pathogens within a single host plant species differed depending on the identity of the heterospecific plant partner. Finally, the magnitude of feedback on germination was not related to the degree of fungal community differentiation between species pairs involved in negative PSFs. Synthesis. Our findings reveal the potential importance of PSFs at the seed stage. Although plant species developed specialized fungal communities in rhizosphere soil, pathogens were not strictly host-specific and varied not just between plant species, but according to the identity of plant partner. These results illustrate the complexity of microbe-mediated interactions between plants at different life stages that next-generation sequencing can begin to unravel.

Unilateral Transversus Abdominis Plane Block Catheter for the Treatment of Abdominal Wall Pain in Pregnancy: A Case Report.

OBJECTIVE: The transversus abdominis plane (TAP) block anesthetizes the anterior branches of spinal nerves that innervate the abdominal wall from T6 to L1 dermatomes and provide effective postoperative analgesia after abdominal surgery. Several applications of TAP catheters are described for both acute and chronic abdominal wall pain, but there are no reported cases of TAP catheters used during pregnancy. CASE REPORT: We present the case of a 23-year-old primigravida admitted to the hospital on multiple occasions during her pregnancy for right lower quadrant abdominal "stabbing" pain, with a visual analog scale score intensity of 8/10 abdominal pain. The diagnosis was unclear despite the presence of prominent ileocolic lymph nodes visualized on magnetic resonance imaging. The abdominal pain persisted despite escalating doses of intravenous opioids (up to 30 mg of intravenous hydromorphone daily). At 34 weeks' gestation, a right-sided TAP block with 0.25% bupivacaine was inserted under ultrasound guidance, and this relieved all of her pain (visual analog scale score, 0). The patient was managed with repeated boluses of 0.5% ropivacaine via a TAP catheter, which resulted in complete resolution of her pain within 3 days and allowed for complete discontinuation of opioid medications. The patient was discharged home, with no recurrence of pain. She had an uneventful cesarean delivery at term. CONCLUSIONS: A TAP catheter inserted under ultrasound guidance can be effective for the treatment of chronic abdominal pain during pregnancy and may provide an alternative analgesic modality when intravenous opioids are not providing relief or when neuraxial analgesia techniques are not feasible or contraindicated.

Tomato products, lycopene, and prostate cancer risk.

Several case-control and large prospective studies focusing on dietary assessment suggest that the intake of tomatoes and tomato products may be associated with a lower risk of prostate cancer [18]. Although less certain at present, the accumulated data suggest that the benefit may be most pronounced in the protection against more advanced or aggressive prostate cancer. It is possible that lycopene is one of the compounds in raw and processed tomato products that may contribute to a lower risk of prostate cancer; however, this hypothesis remains to be further investigated. Other carotenoids and phytochemicals in tomato products may also contribute to the proposed health benefits. Food processing does not seem to reduce the benefits but may, in fact, enhance the bioavailability of beneficial components. The reported correlations or associations between the consumption of tomato products and prostate cancer risk should not be interpreted as causal until additional data are available from a variety of studies in different populations. Ideally, randomized controlled intervention studies would provide an ultimate test of the tomato/lycopene hypothesis; however, the expense, long duration of exposure, and the near universal consumption of tomato products among Americans make a dietary intervention study difficult to undertake. It is reasonable to recommend to the general population the consumption of tomato products at approximately one serving per day or five servings per week as part of an overall healthy dietary pattern that may reduce the risks of prostate cancer, other malignancies, or other chronic diseases. This recommendation is consistent with current dietary guidelines to increase fruit and vegetable consumption to lower the risk of heart disease and many types of cancer [38]. Nutritional prevention of prostate cancer is very different from the use of dietary or nutritional treatments for established prostate cancer. The use of lycopene and other extracts for the treatment of prostate cancer is a separate issue that warrants individual attention and investigation.

Tomatoes, lycopene, and prostate cancer: progress and promise.

Prostate cancer has emerged as a major public health problem in nations that have an affluent culture with an aging population. The search for etiologic risk factors and an emphasis on the development of chemopreventive agents has gained momentum over the last decade. Among the landmark epidemiologic findings during this period has been the association between the consumption of tomato products and a lower risk of prostate cancer. The traditional reductionist scientific approach has led many investigators to propose that lycopene, a carotenoid consumed largely from tomato products, may be the component responsible for lowering the risk of prostate cancer. Thus, many laboratory and clinical studies are now underway with the goal of assessing the ability of pure lycopene to serve as a chemopreventive agent for prostate and other malignancies. The focus on lycopene should continue, and an improved understanding of lycopene absorption, distribution, role in antioxidant reactions, and metabolism is critical in the quest to elucidate mechanisms whereby this compound could possibly reduce prostate cancer risk. In contrast to the pharmacologic approach with pure lycopene, many nutritional scientists direct their attention upon the diverse array of tomato products as a complex mixture of biologically active phytochemicals that together may have anti-prostate cancer benefits beyond those of any single constituent. These contrasting approaches will continue to be explored in clinical, laboratory and epidemiologic studies in the near future, providing hope that the next generation will benefit from this knowledge and experience a lower risk of prostate cancer.

Rare variants in CFI, C3 and C9 are associated with high risk of advanced age-related macular degeneration.

To define the role of rare variants in advanced age-related macular degeneration (AMD) risk, we sequenced the exons of 681 genes within all reported AMD loci and related pathways in 2,493 cases and controls. We first tested each gene for increased or decreased burden of rare variants in cases compared to controls. We found that 7.8% of AMD cases compared to 2.3% of controls are carriers of rare missense CFI variants (odds ratio (OR) = 3.6; P = 2 × 10(-8)). There was a predominance of dysfunctional variants in cases compared to controls. We then tested individual variants for association with disease. We observed significant association with rare missense alleles in genes other than CFI. Genotyping in 5,115 independent samples confirmed associations with AMD of an allele in C3 encoding p.Lys155Gln (replication P = 3.5 × 10(-5), OR = 2.8; joint P = 5.2 × 10(-9), OR = 3.8) and an allele in C9 encoding p.Pro167Ser (replication P = 2.4 × 10(-5), OR = 2.2; joint P = 6.5 × 10(-7), OR = 2.2). Finally, we show that the allele of C3 encoding Gln155 results in resistance to proteolytic inactivation by CFH and CFI. These results implicate loss of C3 protein regulation and excessive alternative complement activation in AMD pathogenesis, thus informing both the direction of effect and mechanistic underpinnings of this disorder.