bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection and Identification of Six Monilinia spp. Causing Brown Rot Using TaqMan Real-Time PCR from Pure Cultures and Infected Apple Fruit
Authors: Wang Jing-ru , Guo Li-yun , Xiao Chang-lin , Zhu Xiao-qiong
Published: February 2018

Brown rot is a severe disease affecting stone and pome fruit. This disease was recently confirmed to be caused by the following six closely related species: Monilinia fructicola, M. laxa, M. fructigena, Monilia polystroma, M. mumecola, and M. yunnanensis. Because of differences in geographic distributions, some of these species are important quarantine pathogens in certain countries. In this study, we developed TaqMan real-time polymerase chain reaction (PCR) assays to detect and identify the six species. Primer pairs and probes were designed for Monilinia fructicola, M. fructigena, M. laxa, and Monilia polystroma based on sequence differences in the laccase-2 genes. Additionally, based on sequence differences in the elongation factor genes, primer pairs and probes were designed for Monilia mumecola and M. yunnanensis. The real-time PCR assays were able to specifically identify the target pathogens, with detection limits of 10 to 100 fg of DNA, which is equivalent to one to seven conidia. The assays were also able to detect the target pathogens in a mixed DNA sample comprising all six Monilinia spp. and related species. The real-time PCR assays accurately detected target fungi from infected apple fruit. Furthermore, the identification results were consistent with those of traditional morphological methods.
Molecular Methods to Detect and Quantify Botryosphaeriaceae Inocula Associated With Grapevine Dieback in Australia
Authors: Billones-Baaijens Regina , Úrbez-Torres José Ramón , Liu Meifang , Ayres Matthew , Sosnowski Mark , Savocchia Sandra
Published: February 2018

Botryosphaeria dieback, caused by species of Botryosphaeriaceae, is an important grapevine trunk disease in Australia. Inocula produced by the pathogens are primarily dispersed by rain splash and wind and infect pruning wounds leading to cankers, dieback, and eventually death of vines. The objective of this study was to develop molecular tools to detect and quantify Botryosphaeriaceae inocula from the environment. These tools are essential for investigating spore dispersal patterns of Botryosphaeriaceae pathogens in Australian vineyards. DNA extraction protocols were evaluated and one modified protocol was found suitable for extracting Botryosphaeriaceae DNA from artificially and naturally inoculated Burkard volumetric spore sampler tapes. Multispecies primers and a hydrolysis probe for quantitative PCR (qPCR) were further developed to detect and quantify Botryosphaeriaceae inocula from environmental samples. Specificity tests showed that the multispecies primers were able to amplify the DNA of 10 Botryosphaeriaceae species (58 isolates) found in Australia while none of the 27 nontarget fungal species (90 isolates) tested were amplified. The qPCR assay was suitable for amplifying purified DNA, synthetic DNA fragments (gBlocks), and mixed DNA from spore trap tapes. The qPCR method developed in this study was shown to be rapid and sensitive in detecting Botryosphaeriaceae inocula from the environment using spore traps.
Changes inCryphonectria parasiticaPopulations Affect Natural Biological Control of Chestnut Blight
Authors: Ježić Marin , Mlinarec Jelena , Vuković Rosemary , Katanić Zorana , Krstin Ljiljana , Nuskern Lucija , Poljak Igor , Idžojtić Marilena , Tkalec Mirta , Ćurković-Perica Mirna
Published: February 2018

Invasive species, especially plant pathogens, have a potential to completely eradicate native plant species and remodel landscapes. Tripartite interactions among sweet chestnut (Castanea sativa), chestnut blight-causing invasive fungus Cryphonectria parasitica, and hyperparasitic virus Cryphonectria hypovirus 1 (CHV1) were studied in two populations. The number of different vegetative compatibility (vc) types of C. parasitica more than doubled over the 10 years, while the hypovirulence incidence dropped in one population and slightly increased in the other one. Over the course of our 3-year monitoring experiment, the prevalence of hypovirulent isolates obtained from monitored cankers increased slowly (i.e., more hypovirulent isolates were being obtained from the same cankers over time). Within studied cankers, considerable changes in vc type and CHV1 presence were observed, indicating a highly dynamic system in which virulent and hypovirulent mycelia, sometimes of discordant vc types, often appeared together. The increase in hypovirulence prevalence did not have any observable curative effect on the cankers and, occasionally, reactivation of healed cankers by new, virulent C. parasitica isolates was observed. Both short- and long-term observations and revalidation of the infected plant populations are necessary to accurately estimate disease progress and formulate an adequate disease management strategy.
T-Lymphoblastic Leukemia/Lymphoma With Annular Skin Rash and Epidermotropism
Authors: Mansoori Parisa , Taheri Arash , O'Neill Stacey S. , Sangueza Omar P.
Published: February 2018

Leukemia cutis is uncommon in patients with acute lymphoblastic leukemia. It typically presents with dermal papules or subcutaneous nodules, with no epidermal or upper papillary dermal involvement on histopathology. We present an unusual clinical presentation of leukemia cutis, with annular plaques and epidermotropism.
Out of the Closet, Into the Clinic: Opportunities for Expanding Men Who Have Sex With Men–Competent Services in China
Authors: Watson Julia , Tang Weiming , Pan Stephen , Wu Dan , Zhao Peipei , Cao Bolin , Liu Chuncheng , Bien Cedric , Huang Wenting , Luo Zhenzhou , Tucker Joseph D.
Published: February 2018

Background

Despite the high human immunodeficiency virus (HIV) burden among men who have sex with men (MSM), there is little research on health services provided to MSM in China and other low- and middle-income countries. Discrimination and inadequate services may discourage MSM from seeking health care services. This study examined essential services provided to MSM and health care discrimination among MSM in China.

Methods

A nationwide cross-sectional online survey was conducted among MSM who saw a physician in the last 24 months in China. The survey included items on sociodemographic information, HIV testing, experiences from the last physician encounter, and history of perceived health care discrimination. We defined MSM-competent physicians as physicians who asked their patient about having sex with other men, asked about anal sex, and either asked about or recommended HIV testing at the most recent visit.

Results

Among the 503 participants, 35.0% (176/503) saw an MSM-competent physician. In multivariate analyses, respondents who saw an MSM-competent physician were more likely to be younger (adjusted odds ratio [AOR], 0.87; 95% confidence interval [CI], 0.81–0.94), have a primary care physician (AOR, 3.24; 95% CI, 1.85–5.67), and be living with HIV (AOR, 2.01; 95% CI, 1.13–3.56). 61.2% (308/503) of MSM had ever experienced health care discrimination.

Conclusions

Our data suggest that there is variability in the extent to which physicians are meeting the needs of MSM in China. There is an urgent need to evaluate and expand MSM-competent services in China.
Fat Grafting for Facial Rejuvenation and Contouring
Authors: Pu Lee L. Q.
Published: February 2018

The clinical outcome after fat grafting for facial rejuvenation and contouring can be less optimal because lack of standardized techniques is performed by the surgeon for the procedure. In this review, the author has tried to provide a rationalized approach to fat grafting for facial rejuvenation and contouring. The preferred donor sites include low abdomen and inner thigh especially in younger patients. Fat grafts should be harvested with low negative pressure via syringe liposuction technique to ensure the integrity as well as the optimal level of cellular function. Fat grafts should be processed with proper centrifugation that can reliably produce purified fat and concentrated growth factors and adipose-derived stem cells, all of which are beneficial to improve graft survival. Fat grafts should be placed after certain principles with gentle injection of small amount during the withdraw phase of each pass in multiple tissue planes and levels with multiple passes to ensure maximal contact of graft with vascularized tissue in the recipient site. The approach described in this review is supported by the most recent scientific studies and thus can likely provide a more predictable long-lasting result if performed properly.
The focused abdominal sonography for trauma examination can reliably identify patients with significant intra-abdominal hemorrhage in life-threatening pelvic fractures
Authors: Christian Nicole Townsend , Burlew Clay Cothren , Moore Ernest E. , Geddes Andrea E. , Wagenaar Amy E. , Fox Charles J. , Pieracci Fredric M.
Published: February 2018

BACKGROUND

The focused abdominal sonography for trauma (FAST) examination has been reported to be unreliable in pelvic fracture patients. Additionally, given the advent of new therapeutic interventions, such as resuscitative endovascular balloon occlusion of the aorta (REBOA), rapid identification of intra-abdominal hemorrhage compared with Zone III hemorrhage may guide different therapeutic strategies. Wehypothesizedthat FAST is reliable for detecting clinically significant intra-abdominal hemorrhage in the face of complex pelvic fractures.

METHODS

Our pelvic fracture database of all hemodynamically unstable patients requiring intervention from January 1, 2005, to July 1, 2015, was reviewed. The FAST examination was compared with operative and computed tomography (CT) scan findings. Confirmatory evaluation for FAST(−) patients was considered positive if therapeutic intervention was required.

RESULTS

During the study period, 81 patients in refractory shock with FAST imaging in our emergency department (ED) underwent pelvic packing. Mean age was 45 ± 2 years and Injury Severity Score was 50 ± 1.5. The FAST examination was negative in 53 patients; 52 patients did not require operative intervention for abdominal bleeding while one patient required splenectomy. The FAST examination was positive in 28 patients; 26 had findings confirmed by CT or laparotomy while two patients did not have intra-abdominal hemorrhage on further evaluation. The sensitivity and specificity for FAST in this population was 96% and 96%, respectively, positive predictive value was 93%, and negative predictive value was 98%. The false-negative and -positive rates for FAST were 2% and 7%.

CONCLUSION

Focused abdominal sonography for trauma examination reliably identifies clinically significant hemoperitoneum in life-threatening, pelvic fracture related hemorrhage. The incidence of a false-negative FAST in this unstable pelvic fracture population was 2%. FAST results may be used when determining the role of REBOA in these multisystem trauma patients and requires further study. REBOA placement should be considered in hemodynamically unstable pelvic fracture patients who are FAST(−), while laparotomy should be used in FAST(+) patients.

LEVEL OF EVIDENCE

Therapeutic, level IV.
Vestigial singing behaviour persists after the evolutionary loss of song in crickets
Authors: Schneider Will T. , Rutz Christian , Hedwig Berthold , Bailey Nathan W.
Published: February 2018

The evolutionary loss of sexual traits is widely predicted. Because sexual signals can arise from the coupling of specialized motor activity with morphological structures, disruption to a single component could lead to overall loss of function. Opportunities to observe this process and characterize any remaining signal components are rare, but could provide insight into the mechanisms, indirect costs and evolutionary consequences of signal loss. We investigated the recent evolutionary loss of a long-range acoustic sexual signal in the Hawaiian field cricket
Teleogryllus oceanicus
. Flatwing males carry mutations that remove sound-producing wing structures, eliminating all acoustic signalling and affording protection against an acoustically-orientating parasitoid fly. We show that flatwing males produce wing movement patterns indistinguishable from those that generate sonorous calling song in normal-wing males. Evolutionary song loss caused by the disappearance of structural components of the sound-producing apparatus has left behind the energetically costly motor behaviour underlying normal singing. These results provide a rare example of a vestigial behaviour and raise the possibility that such traits could be co-opted for novel functions.
Genomes to space stations: the need for the integrative study of migration for avian conservation
Authors: Fudickar Adam M. , Ketterson Ellen D.
Published: February 2018

Ongoing changes to global weather patterns and human modifications of the environment have altered the breeding and non-breeding ranges of migratory species, the timing of their migrations, and even whether they continue to migrate at all. Animal movements are arguably one of the most difficult behaviours to study, particularly in smaller birds that migrate tens to thousands of kilometres seasonally, often moving hundreds of kilometres each day. The recent miniaturization of tracking and logging devices has led to a radical transformation in our understanding of avian migratory behaviour and migratory connectivity. While advances in technology have altered the way researchers study migratory behaviour in the field, advances in techniques related to the study of physiological and genetic mechanisms underlying migratory behaviour have rarely been integrated into field studies of tracking. To predict the capacity of migrants to adjust to a changing planet, it is essential that we combine avian migration data with physiological and genetic measurements taken at key time points prior to, during and after migration.
Effects of eco-friendly carbohydrate-based superabsorbent polymers on seed germination and seedling growth of maize
Authors: Tao Jinghe , Zhang Wenxu , Liang Li , Lei Ziqiang
Published: February 2018

Desertification is the degradation of land in arid and semi-arid areas. Nowadays, lack of water and desertification are extreme problems for plant survival and growth in the arid and semi-arid areas of the world. It becomes increasingly important as to how to let the plant absorb moisture more effectively for keeping growth strong. We synthesized superabsorbent polymers (SAPs) with carbohydrate and characterized them by Fourier transform infrared spectra analyses, scanning electron microscopy and thermogravimetric/differential thermal analyses. Then, a completely randomized experiment was conducted to assess the effect of carbohydrate-based SAPs on seed germination and seedling growth of maize in an artificial climate chest. The results showed that adding an appropriate amount of SAPs could improve root length, shoot length, total biomass, germination potential and germination rate. It indicates that this SAP is not toxic to plants and can promote seed germination, and at the same time provides a possibility of replacing other substrates.
The narrow gap between norms and cooperative behaviour in a reindeer herding community
Authors: Thomas Matthew Gwynfryn , Bårdsen Bård-Jørgen , Næss Marius Warg
Published: February 2018

Cooperation evolves on social networks and is shaped, in part, by norms: beliefs and expectations about the behaviour of others or of oneself. Networks of cooperative social partners and associated norms are vital for pastoralists, such as Saami reindeer herders in northern Norway. However, little is known quantitatively about how norms structure pastoralists' social networks or shape cooperation. Saami herders reported their social networks and participated in field experiments, allowing us to gauge the overlap between reported and emergent cooperation. We show that individuals' perceptions of reciprocal cooperation within their social networks exceeded actual reciprocity, although both occurred frequently and were concentrated within herding groups. Herders with more extensive cooperation networks received more rewards in an economic game. Although herders overestimated reciprocal helping, cooperation in this community was still extensive, suggesting that perceived norms potentially allow network structures promoting cooperation to emerge and be maintained.
Amadori-glycated phosphatidylethanolamine enhances the physical stability and selective targeting ability of liposomes
Authors: Miyazawa Taiki , Kamiyoshihara Reina , Shimizu Naoki , Harigae Takahiro , Otoki Yurika , Ito Junya , Kato Shunji , Miyazawa Teruo , Nakagawa Kiyotaka
Published: February 2018

Liposomes consisting of 100% phosphatidylcholine exhibit poor membrane fusion, cellular uptake and selective targeting capacities. To overcome these limitations, we used Amadori-glycated phosphatidylethanolamine, which is universally present in animals and commonly consumed in foods. We found that liposomes containing Amadori-glycated phosphatidylethanolamine exhibited significantly reduced negative membrane potential and demonstrated high cellular uptake.
Multiscale analysis of enantioselectivity in enzyme-catalysed ‘lethal synthesis’ using projector-based embedding
Authors: Zhang Xinglong , Bennie Simon J. , van der Kamp Marc W. , Glowacki David R. , Manby Frederick R. , Mulholland Adrian J.
Published: February 2018

The action of fluoroacetate as a broad-spectrum mammalian pesticide depends on the ‘lethal synthesis’ of fluorocitrate by citrate synthase, through a subtle enantioselective enolization of fluoroacetyl-coenzyme A. In this work, we demonstrate how a projection-based embedding method can be applied to calculate coupled cluster (CCSD(T)) reaction profiles from quantum mechanics/molecular mechanics optimized pathways for this enzyme reaction. Comparison of pro-
R
and pro-
S
proton abstraction in citrate synthase at the CCSD(T)-in-DFT//MM level yields the correct enantioselectivity. We thus demonstrate the potential of projection-based embedding for determining stereoselectivity in enzymatic systems. We further show that the method is simple to apply, eliminates variability due to the choice of density functional theory functional and allows the efficient calculation of CCSD(T) quality enzyme reaction barriers.
Group social rank is associated with performance on a spatial learning task
Authors: Langley Ellis J. G. , van Horik Jayden O. , Whiteside Mark A. , Madden Joah R.
Published: February 2018

Dominant individuals differ from subordinates in their performances on cognitive tasks across a suite of taxa. Previous studies often only consider dyadic relationships, rather than the more ecologically relevant social hierarchies or networks, hence failing to account for how dyadic relationships may be adjusted within larger social groups. We used a novel statistical method: randomized Elo-ratings, to infer the social hierarchy of 18 male pheasants,
Phasianus colchicus
, while in a captive, mixed-sex group with a linear hierarchy. We assayed individual learning performance of these males on a binary spatial discrimination task to investigate whether inter-individual variation in performance is associated with group social rank. Task performance improved with increasing trial number and was positively related to social rank, with higher ranking males showing greater levels of success. Motivation to participate in the task was not related to social rank or task performance, thus indicating that these rank-related differences are not a consequence of differences in motivation to complete the task. Our results provide important information about how variation in cognitive performance relates to an individual's social rank within a group. Whether the social environment causes differences in learning performance or instead, inherent differences in learning ability predetermine rank remains to be tested.
Hovering hummingbird wing aerodynamics during the annual cycle. II. Implications of wing feather moult
Authors: Achache Yonathan , Sapir Nir , Elimelech Yossef
Published: February 2018

Birds usually moult their feathers in a particular sequence which may incur aerodynamic, physiological and behavioural implications. Among birds, hummingbirds are unique species in their sustained hovering flight. Because hummingbirds frequently hover-feed, they must maintain sufficiently high flight capacities even when moulting their flight feathers. A hummingbird wing consists of 10 primary flight feathers whose absence during moult may strongly affect wing performance. Using dynamic similarity rules, we compared time-accurate aerodynamic loads and flow field measurements over several wing geometries that follow the natural feather moult sequence ofCalypte anna, a common hummingbird species in western North America. Our results suggest a drop of more than 20% in lift production during the early stages of the moult sequence in which mid-wing flight feathers are moulted. We also found that the wing's ability to generate lift strongly depended on the morphological integrity of the outer primaries and leading-edge. These findings may explain the evolution of wing morphology and moult attributes. Specifically, the high overlap between adjacent wing feathers, especially at the wing tip, and the slow sequential replacement of the wing feathers result in a relatively small reduction in wing surface area during moult with limited aerodynamic implications. We present power and efficiency analyses for hover flight during moult under several plausible scenarios, suggesting that body mass reduction could be a compensatory mechanism that preserves the energetic costs of hover flight.
Shear flow dynamics in the Beris-Edwards model of nematic liquid crystals
Authors: Murza Adrian C. , Teruel Antonio E. , Zarnescu Arghir D.
Published: February 2018

We consider the Beris-Edwards model describing nematic liquid crystal dynamics and restrict it to a shear flow and spatially homogeneous situation. We analyse the dynamics focusing on the effect of the flow. We show that in the co-rotational case one has gradient dynamics, up to a periodic eigenframe rotation, while in the non-co-rotational case we identify the short- and long-time regimes of the dynamics. We express these in terms of the physical variables and compare with the predictions of other models of liquid crystal dynamics.
Considerations for the design of vaccine efficacy trials during public health emergencies
Authors: Dean Natalie E. , Gsell Pierre-Stéphane , Brookmeyer Ron , De Gruttola Victor , Donnelly Christl A. , Halloran M. Elizabeth , Jasseh Momodou , Nason Martha , Riveros Ximena , Watson Conall , Henao-Restrepo Ana Maria , Longini Ira M.
Published: February 2018

Public Health Emergencies (PHEs) provide a complex and challenging environment for vaccine evaluation. Under the R&D Blueprint Plan of Action, the World Health Organization (WHO) has convened a group of experts to agree on standard procedures to rapidly evaluate experimental vaccines during PHEs while maintaining the highest scientific and ethical standards. The Blueprint priority diseases, selected for their likelihood to cause PHEs and the lack of adequate medical countermeasures, were used to frame our methodological discussions. Here, we outline major vaccine study designs to be used in PHEs and summarize high-level recommendations for their use in this setting. We recognize that the epidemiology and transmission dynamics of the Blueprint priority diseases may be highly uncertain and that the unique characteristics of the vaccines and outbreak settings may affect our study design. To address these challenges, our group underscores the need for novel, flexible, and responsive trial designs. We conclude that assignment to study groups using randomization is a key principle underlying rigorous study design and should be utilized except in exceptional circumstances. Advance planning for vaccine trial designs is critical for rapid and effective response to a PHE and to advance knowledge to address and mitigate future PHEs.

One Sentence Summary

As part of the WHO research and development Blueprint for action to prevent epidemics, we describe key considerations for the design and analysis of trials and studies to evaluate experimental vaccines during public health emergencies.
Two levels of host-specificity in a fig-associatedCaenorhabditis
Authors: Woodruff Gavin C. , Phillips Patrick C.
Published: February 2018

Background

Biotic interactions are ubiquitous and require information from ecology, evolutionary biology, and functional genetics in order to be completely understood. However, study systems that are amenable to investigations across such disparate fields are rare. Figs and fig wasps are a classic system for ecology and evolutionary biology with poor functional genetics;C. elegansis a classic system for functional genetics with poor ecology. In order to help bridge these disciplines, here we describe the natural history of a close relative ofC. elegans,C.sp. 34, that is associated with the figFicus septicaand its pollinatingCeratosolenwasps.

Results

To understand the natural context of fig-associatedCaenorhabditis, freshF. septicafigs from four Okinawan islands were sampled, dissected, and observed under microscopy.C.sp. 34 was found in all islands whereF. septicafigs were found.C.sp. 34 was routinely found in the fig interior and almost never observed on the outside surface.Caenorhabditiswas only found in pollinated figs, andC.sp. 34 was more likely to be observed in figs with more foundress pollinating wasps. Actively reproducingC.sp. 34 dominated younger figs, whereas older figs with emerging wasp progeny harboredC.sp. 34 dispersal larvae. Additionally,C. sp. 34was observed dismounting from platedCeratosolenpollinating wasps.C.sp. 34 was never found on non-pollinating, parasiticPhilotrypesiswasps. Finally,C.sp. 34 was only observed inF. septicafigs among five OkinawanFicusspecies sampled.

Conclusion

These observations suggest a natural history whereC.sp. 34 proliferates in youngF. septicafigs and disperses from old figs onCeratosolenpollinating fig wasps. The fig and wasp host specificity of thisCaenorhabditisis highly divergent from its close relatives and frames hypotheses for future investigations. This natural co-occurrence of the fig/fig wasp andCaenorhabditisstudy systems sets the stage for an integrated research program that can help to explain the evolution of interspecific interactions.
Cardiovascular Disease Risk Factor Responses to a Type 2 Diabetes Care Model Including Nutritional Ketosis at One Year: An Open Label, Non-Randomized, Controlled Study
Authors: Bhanpuri Nasir H. , Hallberg Sarah J. , Williams Paul T. , McKenzie Amy L. , Ballard Kevin D. , Campbell Wayne W. , McCarter James P. , Phinney Stephen D. , Volek Jeff S.
Published: February 2018

Background

Cardiovascular disease (CVD) is a leading cause of death among adults with type 2 diabetes mellitus (T2D). We recently reported that glycemic control in patients with T2D can be significantly improved through a continuous care intervention (CCI) including nutritional ketosis. The purpose of this study was to examine CVD risk factors in this cohort.

Methods

We investigated CVD risk factors in patients with T2D who participated in a one year open label, non-randomized, controlled study. The CCI group (n = 262) received treatment from a health coach and medical provider. A usual care (UC) group (n = 87) was independently recruited to track customary T2D progression. Circulating biomarkers of cholesterol metabolism and inflammation, blood pressure (BP), carotid intima media thickness (cIMT), multi-factorial risk scores and medication use were examined.

Results

The CCI group consisted of 262 patients (baseline mean(SD): age 54(8) y, BMI 40.4(8.8) kg/m2). Intention-to-treat analysis (% change) revealed the following at 1-year with P values < 0.0019 indicating statistical significance after adjustment for multiple comparisons: total LDL-particles (LDL-P) (−4.9%, P=0.02), small LDL-P (−20.8%, P=1.2×10−12), LDL-P size (+1.1%, P=6.0×10−10), ApoB (−1.6%, P=0.37), ApoA1 (+9.8%, P<10−16), ApoB/ApoA1 ratio (−9.5%, P=1.9×10−7), triglyceride/HDL-C ratio (−29.1%, P<10−16), large VLDL-P (−38.9%, P=4.2×10−15), and LDL-C (+9.9%, P=4.9×10−5). Additional effects were reductions in blood pressure, high sensitivity C-reactive protein, and white blood cell count (all P<1×10−7) while cIMT was unchanged. The 10-year atherosclerotic cardiovascular disease (ASCVD) risk score decreased −11.9% (P=4.9×10−5). Antihypertensive medication use was discontinued in 11.4 % of CCI participants (P=5.3×10−5). The UC group of 87 patients (baseline mean(SD): age 52(10)y, BMI 36.7(7.2) kg/m2) showed no significant changes. After adjusting for baseline differences when comparing CCI and UC groups, significant improvements for the CCI group included small LDL-P, ApoA1, triglyceride/HDL-C ratio, HDL-C, hs-CRP, and ASCVD score. The CCI group showed a greater rise in LDL-C.

Conclusions

A continuous care treatment including nutritional ketosis in patients with T2D improved most biomarkers of CVD risk after one year. The increase in LDL-cholesterol appeared limited to the large LDL subfraction. LDL particle size increased, total LDL-P and ApoB were unchanged, and inflammation and blood pressure decreased.

Trial registration

Clinicaltrials.gov:NCT02519309. Registered 10 August 2015
The Spectre of Too Many Species
Authors: Leaché Adam D. , Zhu Tianqi , Rannala Bruce , Yang Ziheng
Published: February 2018

Recent simulation studies examining the performance of Bayesian species delimitation as implemented in the BPP program have suggested that BPP may detect population splits but not species divergences and that it tends to over-split when data of many loci are analyzed. Here we confirm several of these results and provide their mathematical justifications. We point out that the distinction between population and species splits made in the protracted speciation model has no influence on the generation of gene trees and sequence data, which explains why no method can use such data to distinguish between population splits and speciation. We suggest that the the protracted speciation model is unrealistic and its mechanism for assigning species status contradicts prevailing taxonomic practice. We confirm the suggestion, based on simulation, that in the case of speciation with gene flow, Bayesian model selection as implemented in BPP tends to detect population splits when the amount of data (the number of loci) increases so over-splitting is a legitimate concern. We discuss the use of a recently proposed empirical genealogical divergence index (gdi) for species delimitation and illustrate that parameter estimates produced by a full likelihood analysis as implemented in BPP provide much more reliable inference under thegdithan the approximate method PHRAPL. We suggest that the Bayesian model-selection approach is useful for identifying sympatric cryptic species while Bayesian parameter estimation under the multispecies coalescent can be used to implement empirical criteria for determining species status among allopatric populations.
Lower performance of Toxoplasma-infected, Rh-negative subjects in the weight holding and hand-grip tests
Authors: Flegr Jaroslav , Šebánková Blanka , Příplatová Lenka , Chvátalová Veronika , Kaňková Šárka
Published: February 2018

Toxoplasma, a protozoan parasite of cats, infects many species of intermediate and paratenic hosts, including about one-third of humans worldwide. After a short phase of acute infection, the tissue cysts containing slowly dividing bradyzoites are formed in various organs and toxoplasmosis proceeds spontaneously in its latent form. In immunocompetent subjects, latent toxoplasmosis was considered asymptomatic. However, dozens of studies performed on animals and humans in the past twenty years have shown that it is accompanied by a broad spectrum of specific behavioural, physiological and even morphological changes. In human hosts, the changes often go in the opposite direction in men and women, and are mostly weaker or non-existent in Rh-positive subjects. Here, we searched for the indices of lower endurance of the infected subjects by examining the performance of nearly five hundred university students tested for toxoplasmosis and Rh phenotype in two tests, a weight holding test and a grip test. The results confirmed the existence of a negative association of latent toxoplasmosis with the performance of students, especially Rh-negative men, in these tests. Surprisingly, but in an accordance with some already published data, Toxoplasma-infected, Rh-positive subjects expressed a higher, rather than lower, performance in our endurance tests. Therefore, the results only partly support the hypothesis for the lower endurance of Toxoplasma infected subjects as the performance of Rh-positive subjects (representing majority of population) correlated positively with the Toxoplasma infection.
Plant quarantine alarm: as much as 20 new alien insect pest species includingDrosophila suzukiiappeared in the Caucasus in the last seven years
Authors: Bieńkowski Andrzej O. , Orlova-Bienkowskaja Marina J. , Karpun Natalia N
Published: February 2018

In 2011-2017 an unusually high number of invasive pests new to European Russia were detected for the first time in Sochi on the Black Sea coast of the Caucasus. We present the first reports of two pests new for the Caucasus and European Russia found in 2017:Drosophila suzukii(a pest of fruit, included to EPPO A2 list) andOtiorhynchus armadillo(a pest of agricultural and ornamental plants). Other recently established insects: a polyphagous pestHalyomorpha halys(first record in 2014); pests of palm trees included to EPPO A2 list:Paysandisia archon(2014) andRhynchophorus ferrugineus(2012); a pest of Solanaceae:Epitrix hirtipennis(2013); a pest of ornamental flowers:Luperomorpha xanthodera(2016); a pest of soybeans:Medythia nigrobilineata(2016); a pest of wine production:Harmonia axyridis(2012); a pest of strawberry:Stelidota geminata(2013); pests ofEucalyptus: Ophelimus maskelli(2011),Glycaspis bremblecomblei(2014),Leptocybe invasa(2014); a pest of Cupressaceae:Lamprodila festiva(2013); a pest ofGleditsia: Dasineura gleditchiae(2011), a pest ofBuxus: Cydalima perspectalis(2012); a pest ofAlbizia: Acizzia jamatonica(2014); a pest ofCercis: Cacopsylla pulchella(2014). Probably most of insects were introduced with imported planting material during the landscaping of the city of Sochi in preparation for the Olympic Games (held in 2014). Quarantine measures should be taken to prevent dispersal of these pests to other regions of the Caucasus and countries of the Black Sea region. Attention should be paid to a new pest for EuropeMedythia nigrobilineata.
FGF21, a liver hormone that inhibits alcohol intake in mice, increases in human circulation after acute alcohol ingestion and sustained binge drinking at Oktoberfest
Authors: Søberg Susanna , Andersen Emilie S. , Dalgaard Niels B. , Jarlhelt Ida , Hansen Nina L. , Hoffmann Nina , Vilsbøll Tina , Chenchar Anne , Jensen Michal , Grevengoed Trisha J. , Trammell Sam A.J. , Knop Filip K. , Gillum Matthew P.
Published: February 2018

Objective

Excessive alcohol consumption is a leading cause of global morbidity and mortality. However, knowledge of the biological factors that influence adlibitumalcohol intake may be incomplete. Two large studies recently linked variants in theKLBlocus with levels of alcohol intake in humans.KLBencodes ß-klotho, co-receptor for the liver-derived hormone fibroblast growth factor 21 (FGF21). In mice, FGF21 reduces alcohol intake, and humanFgf21variants are enriched among heavy drinkers. Thus, the liver may limit alcohol consumption by secreting FGF21. However, whether full-length, active plasma FGF21 (FGF21 (1-181)) levels in humans increase acutely or sub-chronically in response to alcohol ingestion is uncertain.

Methods

We recruited 10 healthy, fasted male subjects to receive an oral water or alcohol bolus with concurrent blood sampling for FGF21 (1-181) measurement in plasma. In addition, we measured circulating FGF21 (1-181) levels, liver stiffness, triglyceride, and other metabolic parameters in three healthy Danish men before and after consuming an average of 22.6 beers/person/day (4.4 g/kg/day of ethanol) for three days during Oktoberfest 2017 in Munich, Germany. We further correlated fasting FGF21 (1-181) levels in 49 healthy, non-alcoholic subjects of mixed sex with self-reports of alcohol-related behaviors, emotional responses, and problems. Finally, we characterized the effect of recombinant human FGF21 injection on adlibitumalcohol intake in mice.

Results

We show that alcohol ingestion (25.3 grams or ~2.5 standard drinks) acutely increases plasma levels of FGF21 (1-181) 3.4-fold in fasting humans. We also find that binge drinking for three days at Oktoberfest is associated with a 2.1-fold increase in baseline FGF21 (1-181) levels, in contrast to minor deteriorations in metabolic and hepatic biomarkers. However, basal FGF21 (1-181) levels were not correlated with differences in alcohol-related behaviors, emotional responses, or problems in our non-alcoholic subjects. Finally, we show that once-daily injection of recombinant human FGF21 reduces adlibitumalcohol intake by 21% in mice.

Conclusions

FGF21 (1-181) is markedly increased in circulation by both acute and sub-chronic alcohol intake in humans, and reduces alcohol intake in mice. These observations are consistent with a role for FGF21 as an endocrine inhibitor of alcohol appetite in humans.
Targeted mutation detection in breast cancer using MammaSeq™
Authors: Smith Nicholas G. , Gyanchandani Rekha , Gurda Grzegorz , Lucas Peter C. , Hartmaier Ryan J. , Brufsky Adam M. , Puhalla Shannon , Bahreini Amir , Kota Karthik , Wald Abigail I. , Nikiforov Yuri E. , Nikiforova Marina N. , Oesterrich Steffi , Lee Adrian V.
Published: February 2018

Background

Breast cancer is the most common invasive cancer among women worldwide. Next-generation sequencing (NGS) has revolutionized the study of cancer across research labs around the globe, however genomic testing in clinical settings remain limited. Advances in sequencing reliability, pipeline analysis, accumulation of relevant data, and the reduction of costs are rapidly increasing the feasibility of NGS-based clinical decision making.

Methods

We report the development of MammaSeq, a breast cancer specific NGS panel, targeting 79 genes and 1369 mutations, optimized for use in primary and metastatic breast cancer. To validate the panel, 46 solid tumor and 14 plasma circulating-free cfDNA samples were sequenced to a mean depth of 2311X and 1820 X respectively. Variants were called using Ion Torrent Suite 4.0 and annotated with cravat CHASM. CNVKit was used to call copy number variants in the solid tumor cohort. The oncoKB Precision Oncology Database was used to identify clinically actionable variants. ddPCR was used to validate select cfDNA mutations.

Results

In cohorts of 46 solid tumors and 14 cfDNA samples from patients with advanced breast cancer we identified 592 and 43 protein coding mutations. Mutations per sample in the solid tumor cohort ranged from 1 to 128 (median 3) and the cfDNA cohort ranged from 0 to 26 (median 2.5). Copy number analysis in the solid tumor cohort identified 46 amplifications and 35 deletions. We identified 26 clinically actionable variants (levels 1-3) annotated by OncoKB, distributed across 20 out of 46 cases (40%), in the solid tumor cohort. Allele frequencies of ESR1 and FOXA1 mutations correlated with CA.27.29 levels in patient matched blood draws.

Conclusions

In solid tumors biopsies and cfDNA, MammaSeq detects clinicaly actionable mutations (oncoKB levels 1-3) in 22/46 (48%) solid tumors and in 4/14 (29%) of cfDNA samples. MammaSeq is a targeted panel suitable for clinically actionable mutation detection in breast cancer.
Developmental Mechanisms Linking Form and Function During Jaw Evolution
Authors: Woronowicz Katherine C. , Gline Stephanie E. , Herfat Safa T. , Fields Aaron J. , Schneider Richard A.
Published: February 2018

How does form arise during development and change during evolution? How does form relate to function, and what enables embryonic structures to presage their later use in adults? To address these questions, we leverage the distinct functional morphology of the jaw in duck, chick, and quail. In connection with their specialized mode of feeding, duck develop a secondary cartilage at the tendon insertion of their jaw adductor muscle on the mandible. An equivalent cartilage is absent in chick and quail. We hypothesize that species-specific jaw architecture and mechanical forces promote secondary cartilage in duck through the differential regulation of FGF and TGFβ signaling. First, we perform transplants between chick and duck embryos and demonstrate that the ability of neural crest mesenchyme (NCM) to direct the species-specific insertion of muscle and the formation of secondary cartilage depends upon the amount and spatial distribution of NCM-derived connective tissues. Second, we quantify motility and build finite element models of the jaw complex in duck and quail, which reveals a link between species-specific jaw architecture and the predicted mechanical force environment. Third, we investigate the extent to which mechanical load mediates FGF and TGFβ signaling in the duck jaw adductor insertion, and discover that both pathways are mechano-responsive and required for secondary cartilage formation. Additionally, we find that FGF and TGFβ signaling can also induce secondary cartilage in the absence of mechanical force or in the adductor insertion of quail embryos. Thus, our results provide novel insights on molecular, cellular, and biomechanical mechanisms that couple musculoskeletal form and function during development and evolution.
Generalizing clusters of similar species as a signature of coexistence under competition
Authors: D’Andrea Rafael , Riolo Maria , Ostling Annette
Published: February 2018

Patterns of trait distribution among competing species can potentially reveal the processes that allow them to coexist. It has been recently proposed that competition may drive the spontaneous emergence of niches comprising clusters of similar species, in contrast with the dominant paradigm of greater-than-chance species differences. However, current clustering theory relies largely on heuristic rather than mechanistic models. Furthermore, studies of models incorporating demographic stochasticity and immigration, two key players in community assembly, did not observe clusters. Here we demonstrate clustering under partitioning of resources, partitioning of environmental gradients, and a competition-colonization tradeoff. We show that clusters are robust to demographic stochasticity, and can persist under immigration. While immigration may sustain clusters that are otherwise transient, too much dilutes the pattern. In order to detect and quantify clusters in nature, we introduce and validate metrics which have no free parameters nor require arbitrary trait binning, and weigh species by their abundances rather than relying on a presence-absence count. By generalizing beyond the circumstances where clusters have been observed, our study contributes to establishing them as an update to classical trait patterning theory.

Author Summary

Species traits determine how they compete with each other. As such, patterns in the distributions of traits in a community of competing species may reveal the processes responsible for coexistence. One central idea in theoretical ecology is that the strength of competition relates to similarity in species needs and strategies, and therefore if competition plays out at short timescales, coexisting species should be more different than expected by chance. However, recent theory suggests that competition may lead species to temporarily self-organize into groups with similar traits. Here we show that this clustering is a generic feature of competitive dynamics, which is robust to demographic stochasticity and can be indefinitely maintained by immigration. We show that clustering arises whether species coexist by partitioning resources, environmental preferences, or through tradeoffs in life-history strategies. We introduce and validate metrics that, given species traits and abundances, determine whether they are clustered, and if so, how many clusters occur. By showing the generality of self-organized species clusters and providing a tools for their detection, our study contributes to updating classical ideas about how competition shapes communities, and motivates searches for them in nature.
Determining Allele-Specific Protein Expression (ASPE) Using a QconCAT-Based Proteomics Method: a Novel Approach to Identify Cis-acting Genetic Variants
Authors: Shi Jian , Wang Xinwen , Zhu Huaijun , Jiang Hui , Wang Danxin , Nesvizhskii Alexey , Zhu Hao-Jie
Published: February 2018

Measuring allele-specific expression (ASE) is a powerful approach for identifying cis-regulatory genetic variants. Here we developed a novel targeted proteomics method for quantification of allele-specific protein expression (ASPE) based on scheduled high resolution multiple reaction monitoring (sMRM-HR) with a heavy stable isotope-labeled quantitative concatamer (QconCAT) internal protein standard. This strategy was applied to the determination of the ASPE of UGT2B15 in human livers using the common UGT2B15 nonsynonymous variant rs1902023 (i.e. Y85D) as the marker to differentiate expressions from the two alleles. The QconCAT standard contains both the wild type tryptic peptide and the Y85D mutant peptide at a ratio of 1:1 to ensure accurate measurement of the ASPE of UGT2B15. The results from 18 UGT2B15 Y85D heterozygotes revealed that the ratios between wild type Y allele and mutant D allele varied from 0.60 to 1.46, indicating the presence of cis-regulatory variants. In addition, we observed no significant correlations between the ASPE and mRNA ASE of UGT2B15, suggesting the involvement of different cis-acting variants in regulating the transcription and translation processes of the gene. This novel ASPE approach provides a powerful tool for capturing cis-genetic variants involved in post-transcription processes, an important yet understudied area of research.
Machine learning methods to reverse engineer dynamic gene regulatory networks governing cell state transitions
Authors: Tsakanikas P. , Manatakis D. , Manolakos E. S.
Published: February 2018

Deciphering the dynamic gene regulatory mechanisms driving cells to make fate decisions remains elusive. We present a novel unsupervised machine learning methodology that can be used to analyze a dataset of heterogeneous single-cell gene expressions profiles, determine the most probable number of states (major cellular phenotypes) represented and extract the corresponding cell sub-populations. Most importantly, for any transition of interest from a source to a destination state, our methodology can zoom in, identify the cells most specific for studying the dynamics of this transition, order them along a trajectory of biological progression in posterior probabilities space, determine the "key-player" genes governing the transition dynamics, partition the trajectory into consecutive phases (transition "micro-states"), and finally reconstruct causal gene regulatory networks for each phase. Application of the end-to-end methodology provides new insights on key-player genes and their dynamic interactions during the important HSC-to-LMPP cell state transition involved in hematopoiesis. Moreover, it allows us to reconstruct a probabilistic representation of the “epigenetic landscape” of transitions and identify correctly the major ones in the hematopoiesis hierarchy of states.