bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex-specific autosomal genetic effects across 26 human complex traits
Authors: Lin Wan-Yu , Chan Chang-Chuan , Liu Yu-Li , Yang Albert C , Tsai Shih-Jen , Kuo Po-Hsiu
Published: March 2020

Previous studies have shown that men and women have different genetic architectures across many traits. However, except waist-to-hip ratio (WHR) and waist circumference (WC), it remains unknown whether the genetic effects of a certain trait are weaker or stronger on men/women. With ~18 000 Taiwan Biobank subjects, we comprehensively investigate sexual heterogeneity in autosomal genetic effects, for traits regarding cardiovascular health, diabetes, kidney, liver, anthropometric profiles, blood, etc. ‘Gene-by-sex interactions’ (G $\times$ S) were detected in 18 out of 26 traits, each with an interaction P-value (${{P}}_{{INT}}$) less than $0.05/104={0.00048}$, where 104 is the number of tests conducted in this study. The most significant evidence of G $\times$ S was found in WHR (${{P}}_{{INT}}$ = 3.2 $\times{{10}}^{-{55}}$) and WC (${{P}}_{{INT}}$ = 2.3$\times{{10}}^{-{41}}$). As a novel G$\times$S investigation for other traits, we here find that the autosomal genetic effects are weaker on women than on men, for low-density lipoprotein cholesterol (LDL-C), uric acid (UA) and diabetes-related traits such as fasting glucose and glycated hemoglobin. For LDL-C and UA, the evidence of G$\times$S is especially notable in subjects aged less than 50 years, where estrogen can play a role in attenuating the autosomal genetic effects of these two traits. Men and women have systematically distinct environmental contexts caused by hormonal milieu and their specific society roles, which may trigger diverse gene expressions despite the same DNA materials. As many environmental exposures are difficult to collect and quantify, sex can serve as a good surrogate for these factors.
Multi-scale vector quantization with reconstruction trees
Authors: Cecini Enrico , De Vito Ernesto , Rosasco Lorenzo
Published: March 2020

We propose and study a multi-scale approach to vector quantization (VQ). We develop an algorithm, dubbed reconstruction trees, inspired by decision trees. Here the objective is parsimonious reconstruction of unsupervised data, rather than classification. Contrasted to more standard VQ methods, such as $k$-means, the proposed approach leverages a family of given partitions, to quickly explore the data in a coarse-to-fine multi-scale fashion. Our main technical contribution is an analysis of the expected distortion achieved by the proposed algorithm, when the data are assumed to be sampled from a fixed unknown distribution. In this context, we derive both asymptotic and finite sample results under suitable regularity assumptions on the distribution. As a special case, we consider the setting where the data generating distribution is supported on a compact Riemannian submanifold. Tools from differential geometry and concentration of measure are useful in our analysis.
Asymptotic Properties of the Solutions to the Vlasov–Maxwell System in the Exterior of a Light Cone
Authors: Bigorgne Léo
Published: March 2020

This paper is concerned with the asymptotic behavior of small data solutions to the three-dimensional Vlasov–Maxwell system in the exterior of a light cone. The plasma does not have to be neutral, and no compact support assumptions are required on the data. In particular, the initial decay in the velocity variable of the particle density is optimal and we only require an $L^2$ bound on the electromagnetic field with no additional weight. We use vector field methods to derive improved decay estimates in null directions for the electromagnetic field, the particle density, and their derivatives. In contrast with [ 2], where we studied the behavior of the solutions in the whole spacetime, the initial data have less decay and we do not need to modify the commutation vector fields of the relativistic transport operator. To control the solutions under these assumptions, we crucially use the strong decay satisfied by the particle density in the exterior of the light cone, null properties of the Vlasov equation, and certain hierarchies in the energy norms.
A Rigid Hyperfinite Type II1 Factor
Authors: Farah Ilijas , Hirshberg Ilan
Published: March 2020

We show that it is relatively consistent with Zermelo-Fraenkel set theory with the axiom of choice that there exists a hyperfinite type $\textrm{II}_1$-factor of density character $\aleph _1$ that is not isomorphic to its opposite, does not have any outer automorphisms, and has trivial fundamental group.
The House We Live In: Religio-Racial Theories and the Study of Religion
Authors: Weisenfeld Judith
Published: March 2020

This article reviews the origins and goals of the religio-racial framework that grounds the approach to early twentieth-century Black new religious movements in New World A-Coming. It discusses how the articles in the roundtable offer case studies that extend the framework of “religio-racial identity” to model approaches for locating the analysis of connections between race and religion as central to the work of religious studies.
Centering Black Catholic Religio-Racial Identity, Revealing White Catholicism
Authors: Cressler Matthew J
Published: March 2020

In New World A-Coming: Black Religion and Racial Identity during the Great Migration, Judith Weisenfeld presents numerous instances when members of religio-racial movements contested the racial classificatory system provided by the federal government and confronted state administrators with their own alternative religio-racial identities. For Weisenfeld, these sorts of exchanges highlight, first and foremost, Black agency in religio-race making. But, as she indicates, they also make visible the contours of religio-racial whiteness as state administrators struggled to defend the status quo. In this article, I focus on how Black contestation and confrontation with racial hierarchy can reveal the racial whiteness operating beneath the surface of normative “religion.” This article draws on sources ranging from a police surveillance report to angry letters from white Catholics in order to argue that Black Catholics interrupted the presumed normativity of white Catholic religious life and, in so doing, revealed white Catholicism as a racial formation.
Azithromycin susceptibility testing for Salmonella enterica isolates: discordances in results using MIC gradient strips
Authors: Goldblatt Jennifer , Ward Andrew , Yusuf Mohammed , Day Martin , Godbole Gauri , Morris-Jones Stephen
Published: March 2020

Background

Azithromycin resistance is emerging in typhoidal Salmonella. Confirmation of azithromycin MIC is the most frequent antibiotic susceptibility request made to the Gastrointestinal Bacteria Reference Unit (GBRU) laboratory in England by local diagnostic laboratories.

Objectives

(i) Determine concordance between local diagnostic and reference laboratory estimations of azithromycin MIC by gradient strip in Salmonella enterica serovars Typhi and Paratyphi. (ii) Consider causes of variation.

Methods

Isolates from patients with enteric fever attending a central London hospital between May 2011 and April 2019 were tested for azithromycin susceptibility using gradient strips, according to EUCAST methodology. Matched local diagnostic and reference laboratory estimations of azithromycin and ciprofloxacin (as a comparator) MICs were included; concordance in estimations was examined.

Results

Local diagnostic laboratory readings overestimated azithromycin MIC values compared with the reference laboratory, resulting in poor concordance in susceptibility/resistance attribution (concordant susceptibility interpretation in 8/19, κ = 0). In contrast, ciprofloxacin MIC estimation demonstrated superior concordance (concordant susceptibility interpretation in 16/17, κ = 0.85). None of the isolates was resistant to azithromycin at the reference laboratory and no known genes associated with azithromycin resistance were detected in any isolate using WGS.

Conclusions

Overestimation of azithromycin resistance is likely to be due to difficulty in interpreting the point of intersection of the ‘trailing edge’ with the gradient strip, used to determine MIC. We advise local diagnostic laboratories to review their experience and consider adopting a ‘second reader’ system to mitigate this.
Detection of Intravascular Hemolysis in Newborn Infants Using Urinary Carbonic Anhydrase I Immunoreactivity
Authors: Hulikova Alzbeta , Kramer Holger , Khan Hammad , Swietach Pawel
Published: March 2020

Background

Mild hemolysis occurs physiologically in neonates, but more severe forms can lead to life-threatening anemia. Newborns in developing regions are particularly at-risk due to the higher incidence of triggers (protozoan infections, sepsis, certain genetic traits). In advanced healthcare facilities, hemolysis is monitored indirectly using resource-intensive methods that probe downstream ramifications. These approaches could potentially delay critical decisions in early-life care, and are not suitable for point-of-care testing. Rapid and cost-effective testing could be based on detecting red blood cell (RBC)-specific proteins, such as carbonic anhydrase I (CAI), in accessible fluids (e.g., urine).

Methods

Urine was collected from 26 full-term male neonates and analyzed for CAI using immunoassays (ELISA, western blot) and proteomics (mass spectrometry). The cohort included a range of hemolytic states, including admissions with infection, ABO incompatibility, and receiving phototherapy. Data were paired with hemoglobin, serum bilirubin (SBR), and C-reactive protein (CRP) measurements.

Results

Urine from a control cohort (CRP < 20 mg/L, SBR < 125µmol/L) had no detectable CAI, in line with results from healthy adults. CAI excretion was elevated in neonates with raised SBR (>125 µmol/L), including those qualifying for phototherapy. Newborns with low SBR (<125 µmol/L) but elevated CRP (>20 mg/L) produced urine with strong CAI immunoreactivity. Proteomics showed that CAI was the most abundant RBC-specific protein in CAI-immunopositive samples, and did not associate with other RBC-derived peptides, indicating an intravascular hemolytic source followed by CAI-selective excretion.

Conclusions

CAI is a direct biomarker of intravascular hemolysis that can be measured routinely in urine using non-invasive methods under minimal-laboratory conditions.
Apparent total tract digestibility, fecal characteristics, and blood parameters of healthy adult dogs fed high-fat diets
Authors: Kilburn Logan R , Allenspach Karin , Jergens Albert E , Bourgois-Mochel Agnes , Mochel Jonathan P , Serao Mariana C Rossoni
Published: March 2020

Pet foods may be formulated with decreased starch to meet consumer demands for less processed diets. Fats and oils may be added to low-starch diets to meet energy requirements, but little is known about its effects on canine health. The study objective was to evaluate the effects of feeding healthy adult dogs low carbohydrate, high-fat diets on apparent total tract digestibility, fecal characteristics, and overall health status. Eight adult Beagles were enrolled in a replicated 4 × 4 Latin Square design feeding trial. Dogs were randomly assigned to one of four dietary fat level treatments (T) within each period: 32% (T1), 37% (T2), 42% (T3), and 47% (T4) fat on a dry matter basis. Fat levels were adjusted with the inclusion of canola oil added to a commercial diet. Each dog was fed to exceed its energy requirement based on NRC (2006). Blood samples were analyzed for complete blood counts, chemistry profiles, and canine pancreatic lipase immunoreactivity levels. Apparent total tract digestibility improved (P < 0.05) as the fat level increased for dry matter, organic matter, fat, and gross energy. Fecal output decreased as levels of fat increased in the diet (P = 0.002). There was no effect of fat level on stool quality or short-chain fatty acid and ammonia concentrations in fecal samples (P ≥ 0.20). Blood urea nitrogen levels decreased with increased fat level (P = 0.035). No significant differences were seen in canine pancreatic lipase immunoreactivity (P = 0.110). All blood parameters remained within normal reference intervals. In summary, increased dietary fat improved apparent total tract digestibility, did not alter fecal characteristics, and maintained the health status of all dogs.
PCR-based approach for site-specific conjugation of long double-stranded DNA to a single-domain VHH antibody
Authors: Akazawa-Ogawa Yoko , Komatsu Yasuo , Nakajima Yoshihiro , Kojima Naoshi , Hagihara Yoshihisa
Published: March 2020

Site-specific conjugation of double-stranded DNA using antibodies enables the development of unique applications for antibody–drug conjugates utilizing recent advances in nucleic acid medicines. Here, we describe a novel method to conjugate a camelid-derived single-domain VHH (variable domain of a heavy chain antibody) antibody with arbitrarily sized double-stranded DNA by PCR. Cysteine in anti-human epidermal growth factor receptor (EGFR) VHH was replaced by alanine, and an unpaired cysteine was introduced at the carboxyl terminus. These modifications enabled site-specific labelling with a maleimide-modified DNA oligo via thioether bond formation; the ensuing product—single-stranded DNA conjugated at the carboxyl terminus of VHH—retained its affinity for EGFR. To investigate whether this VHH–single-stranded DNA conjugate might be used as a forward primer, we subjected it to PCR, producing 100–500 bp DNA. We confirmed the amplification of the VHH–double-stranded DNA conjugate by examining its mobility on acrylamide gel; retention of the binding affinity of the conjugate for EGFR was identified by immuno-PCR.
Embedding quasi-static time series within a genetic algorithm for stochastic optimization: the case of reactive power compensation on distribution systems
Authors: Lujano-Rojas Juan M , Zubi Ghassan , Dufo-López Rodolfo , Bernal-Agustín José L , Atencio-Guerra José L , Catalão João P S
Published: March 2020

This paper presents a methodology for the optimal placement and sizing of reactive power compensation devices in a distribution system (DS) with distributed generation. Quasi-static time series is embedded in an optimization method based on a genetic algorithm to adequately represent the uncertainty introduced by solar photovoltaic generation and electricity demand and its effect on DS operation. From the analysis of a typical DS, the reactive power compensation rating power results in an increment of 24.9% when compared to the classical genetic algorithm model. However, the incorporation of quasi-static time series analysis entails an increase of 26.8% on the computational time required.
Probing Behavior of Diaphorina citri (Hemiptera: Liviidae) on Valencia Orange Influenced by Sex, Color, and Size
Authors: Ebert Timothy A , Rogers Michael E
Published: March 2020

Candidatus Liberibacter asiaticus Jagoueix, Bové, and Garnier (Rhizobiales: Rhizobiaceae) is transmitted by the psyllid Diaphorina citri Kuwayama and putatively causes Huanglongbing disease in citrus. Huanglongbing has reduced yields by 68% relative to pre-disease yields in Florida. Disease management is partly through vector control. Understanding vector biology is essential in this endeavor. Our goal was to document differences in probing behavior linked to sex. Based on both a literature review and our results, we conclude that there is either no effect of sex or that identifying such an effect requires a sample size at least four times larger than standard methodologies. Including both color and sex in statistical models did not improve model performance. Both sex and color are correlated with body size, and body size has not been considered in previous studies on sex in D. citri in terms of probing behavior. An effect of body size was found wherein larger psyllids took longer to reach ingestion behaviors and larger individuals spent more time-ingesting phloem, but these relationships explained little of the variability in these data. We suggest that the effects of sex can be ignored when running EPG experiments on healthy psyllids.
Functional evaluation following deltoid muscle resection in patients with soft tissue sarcoma
Authors: Hamada Shunsuke , Nishida Yoshihiro , Takanari Keisuke , Ota Takehiro , Urakawa Hiroshi , Ikuta Kunihiro , Sakai Tomohisa , Tsukushi Satoshi , Kamei Yuzuru , Ishiguro Naoki
Published: March 2020

Background

The present study aimed to determine functional outcomes in patients undergoing deltoid muscle resection for soft tissue sarcoma.

Methods

Between 2002 and 2014, 18 patients with soft tissue sarcoma of the shoulder who underwent wide resection including the deltoid muscle, and were followed up for more than 12 months, were retrospectively included in the study. In all, 11 patients were male and 7 were female. The median age was 59 years, median follow-up duration was 37 months. The extent of resection of deltoid muscle, with or without rotator cuff damage, reconstruction methods, adjuvant therapy, oncological outcomes, and the International Society of Limb Salvage (ISOLS) score as functional outcomes were analyzed.

Results

Six patients underwent total resection, and twelve underwent partial resections of deltoid muscle. The rotator cuff was resected in four patients. Soft tissue reconstruction was performed in 17 patients using a pedicled latissimus dorsi muscle flap. Two local recurrences and three distant metastases occurred during follow-up. Median overall survival was 72 months. The mean ISOLS score was 25.0 points (±4.6points). Univariate analysis revealed that there was no significant difference in ISOLS score regarding the extent of deltoid muscle resection. Multivariate analysis identified only combined resection of the rotator cuff as a significant prognostic factor for poor functional outcomes (P < 0.001).

Conclusions

The extent of resection of the deltoid muscle might not affect the functional outcomes determined by ISOLS score. If the rotator cuff is resected concurrently, satisfactory functional outcomes might not be obtained.
Lockean Copyright versus Lockean Property
Authors: Chatterjee Mala
Published: March 2020

Locke’s labor theory, the most familiar of property theories, has faced centuries of philosophical criticism. Nonetheless, recent legal scholars have applied it to intellectual property while overlooking these philosophical critiques. Philosophers, on the other hand, are largely absent in IP theorizing, thus not asking whether Locke’s resilient intuition is salvageable in copyright’s domain. This Article argues that Lockean copyright is actually far more plausible than Lockean property, for it avoids the most devastating objections the latter faces. It then defends a surprising doctrinal implication of this theoretical conclusion: a workable Lockean copyright favors rights far more limited than present law.
Aggressive FUS-Mutant Motor Neuron Disease Without Profound Spinal Cord Pathology
Authors: Wongworawat Yan Chen , Liu Yin Allison , Raghavan Ravi , White Charles L , Dietz Robin , Zuppan Craig , Rosenfeld Jeffrey
Published: March 2020

A 29-year-old man presented with rapidly progressive severe neck weakness, asymmetrical bilateral upper extremity weakness, bulbar dysfunction, profound muscle wasting, and weight loss. Within 1 year, his speech became unintelligible, he became gastrostomy- and tracheostomy/ventilator-dependent, and wheelchair bound. Electrophysiology suggested motor neuron disease. Whole exome sequencing revealed a heterozygous pathogenic variant in the fused in sarcoma gene (FUS), c.1574C>T,p. R525L, consistent with autosomal dominant amyotrophic lateral sclerosis. Autopsy revealed extensive denervation atrophy of skeletal musculature. Surprisingly, there was only minimal patchy depletion of motor neurons within the cervico-thoracic spinal cord anterior horn cells, and the tracts were largely preserved. TDP-43 inclusions were absent. Abnormal expression of FUS mutation product (cytoplasmic inclusions) was demonstrated by immunohistochemistry within anterior horn motor neurons. The most prominent finding was a disparity between profound neck weakness and relatively low-grade anterior horn cell loss or tract degeneration in the cervico-thoracic cord.
The Promise and Perils of Voice
Authors: Moy Patricia
Published: March 2020

This article, based on the author's presidential address at the International Communication Association's 69th annual conference, speaks to the dual-edged nature of voice. It positions voice and the public as two closely related concepts, and reviews how varying definitions of the public throughout the years have played a critical role in determining which voices get heard. The article then discusses the normative foregrounding of voice in deliberative democracy and how, facilitated by technology, voices also bring with them noise and clamor. Finally, this article highlights concerns that arise from an overabundance of voices, and calls for mindful, disciplinary exercising of voice.
Comparison of Diagnostic Yield of Tuberculosis Loop-Mediated Isothermal Amplification Assay With Cartridge-Based Nucleic Acid Amplification Test, Acid-Fast Bacilli Microscopy, and Mycobacteria Growth Indicator Tube Culture in Children With Pulmonary Tuberculosis
Authors: Dayal Rajeshwar , Yadav Alok , Agarwal Dipti , Kumar Manoj , Kamal Raj , Singh Dharmendra , Bhatnagar Shailendra
Published: March 2020

Background

Cartridge-based nucleic acid amplification test (CB-NAAT) has been recommended for diagnosis of tuberculosis (TB) in children, but its wide use is limited by high cost and the need for well-equipped laboratories. This study was conducted in children with pulmonary TB to compare the diagnostic yield of TB-LAMP (loop-mediated isothermal amplification test) with CB-NAAT and other conventional methods.

Methods

Patients ≤ 14 years of age diagnosed with probable pulmonary TB were included in the study. Induced sputum/gastric aspirate was obtained and subjected to acid-fast bacilli (AFB) microscopy, mycobacteria growth indicator tube (MGIT) culture, CB-NAAT, and TB-LAMP. The TB-LAMP assay was performed using 2 different primers, IS6110 and mpb64, for detection of Mycobacterium tuberculosis (MTB). TB-LAMP assays were compared to other assays using appropriate statistical tests.

Results

One hundred fourteen subjects were recruited in the study. AFB microscopy, MGIT culture, CB-NAAT, TB-LAMP IS6110, and TB-LAMP mpb64 showed positivity of 32 (28.1%), 59 (51.7%), 66 (57.9%), 75 (65.8%), and 81 (71%), respectively. TB-LAMP IS6110 showed significantly higher MTB detection in comparison to AFB microscopy and MGIT culture (P = .0001 and P = .03, respectively), and showed no significant difference in MTB detection in comparison with CB-NAAT (P = .219). TB-LAMP mpb64 showed significantly higher MTB detection as compared to AFB microscopy, MGIT culture, and CB-NAAT (P = .0001, P = .003, and P = .037, respectively). TB-LAMP mpb64 and IS6110 showed sensitivity of 94.9% (95% confidence interval [CI], 85.9%–98.9%) and 89.8% (95% CI, 79.7%–96.2%), respectively, in reference to MGIT culture. The degree of agreement between TB-LAMP (mpb64 and IS6110) with CB-NAAT showed κ values of 0.718 and 0.834, respectively.

Conclusions

TB-LAMP assay can be a useful alternative test in diagnosis of pulmonary TB in children.
The Dilemma of Ghana-Based Liberian Refugees and the Challenges of Repatriation and Integration
Authors: Antwi-Boateng Osman , Braimah Mohammed Kamarideen
Published: March 2020

In the aftermath of the Liberian civil war and the signing of the final peace agreement among the warring factions, the international community and host countries of Liberian refugees in the West African sub-region disproportionately pursued the policy of refugee repatriation to Liberia at the expense of other options such as integration and resettlement as a solution for the refugee problem. Using the Liberian refugees in the Buduburam refugee camp in Ghana as a qualitative case study, this research argues that the policy of repatriation has largely failed. The research arrives at this conclusion via the use of focus-group interviews of a cross-section of remaining Liberian refugees in the Buduburam camp. The research discovered that while the refugees are discontent with their current circumstances in Ghana, they are hesitant to return home due to unfavourable homeland conditions. The combination of both unfavourable host and homeland conditions constitutes ‘intervening obstacles’ that mitigate against repatriation and thus put the Ghana-based Liberian refugees in a dilemma. The research recommends the option of integration as a viable option that should be legislated and institutionalized to attract the necessary buy-in from the remaining refugees.
The use of decompressive segmental sublaminoplasty to treat myelopathy caused by lumbar stenosis in tethered cord syndrome
Authors: Breton Jeffrey M , Yang Michael J , Riesenburger Ron I
Published: March 2020

A 79-year-old woman presented with acute-onset right leg pain in the setting of 3 months of progressive gait deterioration and bilateral leg weakness. On exam she had right lower extremity hyperreflexia and weakness. Lumbar spine magnetic resonance imaging demonstrated L3–L5 central canal stenosis with L4–L5 spondylolisthesis and a previously undiagnosed tethered cord. She underwent minimally invasive left segmental sublaminoplasty at L3–L4 and L4–L5 for spinal cord decompression with onlay arthrodesis resulting in resolution of her radicular pain and improved strength. This is a unique case of lumbar spinal stenosis presenting with myelopathy in the context of a previously asymptomatic and undiagnosed tethered cord.
A case of acute generalized exanthematous pustulosis caused by exposure to Atovaquone/proguanil
Authors: Arsuaga Marta , de Miguel Rosa , Trigo Elena , Barreiro Pablo , de la Calle Fernando , Tarin Eloy José , Loli-Ausejo D , Diaz Marta
Published: March 2020

We present a returning traveler with acute generalized exanthematous pustulosis after atovaquone/proguanil prophylaxis. Diagnosis was confirmed with biopsy and allergy testing, symptoms resolved after steroid treatment. Atovaquone/proguanil prophylaxis is generally well tolerated, however, some patients may present severe adverse events that require prompt medical evaluation and treatment.
Model-assisted analysis of the peach pedicel–fruit system suggests regulation of sugar uptake and a water-saving strategy
Authors: Constantinescu Dario , Vercambre Gilles , Génard Michel
Published: March 2020

We develop a model based on the biophysical representation of water and sugar flows between the pedicel, fruit xylem and phloem, and the fruit apoplast and symplast in order to identify diurnal patterns of transport in the pedicel–fruit system of peach. The model predicts that during the night water is mainly imported to the fruit through the xylem, and that fruit phloem–xylem transfer of water allows sugar concentrations in the phloem to be higher in the fruit than in the pedicel. This results in relatively high sugar transport to the fruit apoplast, leading to relatively high sugar uptake by the fruit symplast despite low sugar concentrations in the pedicel. At midday, the model predicts a xylem backflow of water driven by a lower pressure potential in the xylem than in the fruit apoplast. In addition, fruit xylem-to-phloem transfer of water decreases the fruit phloem sugar concentration, resulting in moderate sugar uptake by the fruit symplast, despite the high sugar concentration in the pedicel. Globally, the predicted fruit xylem–phloem water transfers buffer the sugar concentrations in the fruit phloem and apoplast, leading to a diurnally regulated uptake of sugar. A possible fruit xylem-to-apoplast recirculation of water through the fruit phloem reduces water lost by xylem backflow at midday.
Unravelling the effect of two herbicide resistance mutations on acetolactate synthase kinetics and growth traits
Authors: Zhao Ning , Yan Yanyan , Du Long , Zhang Xiaolin , Liu Weitang , Wang Jinxin
Published: March 2020

Gene mutations conferring herbicide resistance are hypothesized to have negative pleiotropic effects on plant growth and fitness, which may in turn determine the evolutionary dynamics of herbicide resistance alleles. We used the widespread, annual, diploid grass weed Alopecurus aequalis as a model species to investigate the effect of two resistance mutations—the rare Pro-197-Tyr mutation and the most common mutation, Trp-574-Leu—on acetolactate synthase (ALS) functionality and plant growth. We characterized the enzyme kinetics of ALS from two purified A. aequalis populations, each homozygous for the resistance mutation 197-Tyr or 574-Leu, and assessed the pleiotropic effects of these mutations on plant growth. Both mutations reduced sensitivity of ALS to ALS-inhibiting herbicides without significant changes in extractable ALS activity. The 197-Tyr mutation slightly decreased the substrate affinity (corresponding to an increased Km for pyruvate) and maximum reaction velocity (Vmax) of ALS, whereas the 574-Leu mutation significantly increased these kinetics. Significant decrease or increase in plant growth associated, respectively, with the 197-Tyr and 574-Leu resistance mutations was highly correlated with their impact on ALS kinetics, suggesting more likely persistence of the 574-Leu mutation than the 197-Tyr mutation if herbicide application is discontinued.
Large X-Linked Palindromes Undergo Arm-to-Arm Gene Conversion across Mus Lineages
Authors: Swanepoel Callie M , Gerlinger Emma R , Mueller Jacob L
Published: March 2020

Large (>10 kb), nearly identical (>99% nucleotide identity), palindromic sequences are enriched on mammalian sex chromosomes. Primate Y-palindromes undergo high rates of arm-to-arm gene conversion, a proposed mechanism for maintaining their sequence integrity in the absence of X–Y recombination. It is unclear whether X-palindromes, which can freely recombine in females, undergo arm-to-arm gene conversion and, if so, at what rate. We generated high-quality sequence assemblies of Mus molossinus and M. spretus X-palindromic regions and compared them with orthologous M. musculus X-palindromes. Our evolutionary sequence comparisons find evidence of X-palindrome arm-to-arm gene conversion at rates comparable to autosomal allelic gene conversion rates in mice. Mus X-palindromes also carry more derived than ancestral variants between species, suggesting that their sequence is rapidly diverging. We speculate that in addition to maintaining genes’ sequence integrity via sequence homogenization, palindrome arm-to-arm gene conversion may also facilitate rapid sequence divergence.
A Uniquely Complex Mitochondrial Proteome from Euglena gracilis
Authors: Hammond Michael J , Nenarokova Anna , Butenko Anzhelika , Zoltner Martin , Dobáková Eva Lacová , Field Mark C , Lukeš Julius
Published: March 2020

Euglena gracilis is a metabolically flexible, photosynthetic, and adaptable free-living protist of considerable environmental importance and biotechnological value. By label-free liquid chromatography tandem mass spectrometry, a total of 1,786 proteins were identified from the E. gracilis purified mitochondria, representing one of the largest mitochondrial proteomes so far described. Despite this apparent complexity, protein machinery responsible for the extensive RNA editing, splicing, and processing in the sister clades diplonemids and kinetoplastids is absent. This strongly suggests that the complex mechanisms of mitochondrial gene expression in diplonemids and kinetoplastids occurred late in euglenozoan evolution, arising independently. By contrast, the alternative oxidase pathway and numerous ribosomal subunits presumed to be specific for parasitic trypanosomes are present in E. gracilis. We investigated the evolution of unexplored protein families, including import complexes, cristae formation proteins, and translation termination factors, as well as canonical and unique metabolic pathways. We additionally compare this mitoproteome with the transcriptome of Eutreptiella gymnastica, illuminating conserved features of Euglenida mitochondria as well as those exclusive to E. gracilis. This is the first mitochondrial proteome of a free-living protist from the Excavata and one of few available for protists as a whole. This study alters our views of the evolution of the mitochondrion and indicates early emergence of complexity within euglenozoan mitochondria, independent of parasitism.
Phylogenetics Identifies Two Eumetazoan TRPM Clades and an Eighth TRP Family, TRP Soromelastatin (TRPS)
Authors: Himmel Nathaniel J , Gray Thomas R , Cox Daniel N
Published: March 2020

Transient receptor potential melastatins (TRPMs) are most well known as cold and menthol sensors, but are in fact broadly critical for life, from ion homeostasis to reproduction. Yet, the evolutionary relationship between TRPM channels remains largely unresolved, particularly with respect to the placement of several highly divergent members. To characterize the evolution of TRPM and like channels, we performed a large-scale phylogenetic analysis of >1,300 TRPM-like sequences from 14 phyla (Annelida, Arthropoda, Brachiopoda, Chordata, Cnidaria, Echinodermata, Hemichordata, Mollusca, Nematoda, Nemertea, Phoronida, Priapulida, Tardigrada, and Xenacoelomorpha), including sequences from a variety of recently sequenced genomes that fill what would otherwise be substantial taxonomic gaps. These findings suggest: 1) the previously recognized TRPM family is in fact two distinct families, including canonical TRPM channels and an eighth major previously undescribed family of animal TRP channel, TRP soromelastatin; 2) two TRPM clades predate the last bilaterian–cnidarian ancestor; and 3) the vertebrate–centric trend of categorizing TRPM channels as 1–8 is inappropriate for most phyla, including other chordates.
Paving the road toward the use of β-Fe2O3 in solar water splitting: Raman identification, phase transformation and strategies for phase stabilization
Authors: Zhang Ningsi , Wang Xin , Feng Jianyong , Huang Huiting , Guo Yongsheng , Li Zhaosheng , Zou Zhigang
Published: March 2020

Although β-Fe2O3 has a high theoretical solar-to-hydrogen efficiency because of its narrow band gap, the study of β-Fe2O3 photoanodes for water splitting is elusive as a result of their metastable nature. Raman identification of β-Fe2O3 is theoretically and experimentally investigated in this study for the first time, thus clarifying the debate about its Raman spectrum in the literature. Phase transformation of β-Fe2O3 to α-Fe2O3 was found to potentially take place under laser and electron irradiation as well as annealing. Herein, phase transformation of β-Fe2O3 to α-Fe2O3 was inhibited by introduction of Zr doping, and β-Fe2O3 was found to withstand a higher annealing temperature without any phase transformation. The solar water splitting photocurrent of the Zr-doped β-Fe2O3 photoanode was increased by 500% compared to that of the pure β-Fe2O3 photoanode. Additionally, Zr-doped β-Fe2O3 exhibited very good stability during the process of solar water splitting. These results indicate that by improving its thermal stability, metastable β-Fe2O3 film is a promising photoanode for solar water splitting.
Formation rate of LB-1-like systems through dynamical interactions
Authors: Tanikawa Ataru , Kinugawa Tomoya , Kumamoto Jun , Fujii Michiko S
Published: March 2020

We estimate formation rates of LB-1-like systems through dynamical interactions in the framework of the theory of stellar evolution before the discovery of the LB-1 system. The LB-1 system contains a ∼70 ${M_{\odot}}$ black hole (BH), a so-called pair instability (PI) gap BH, and a B-type star with solar metallicity, and has nearly zero eccentricity. The most efficient formation mechanism is as follows. In an open cluster, a naked helium star (with ∼20 ${M_{\odot}}$) collides with a heavy main sequence star (with ∼50 ${M_{\odot}}$) which has a B-type companion. The collision results in a binary consisting of the collision product and the B-type star with a high eccentricity. The binary can be circularized through the dynamical tide with radiative damping of the collision product envelope. Finally, the collision product collapses to a PI-gap BH, avoiding pulsational pair instability and pair instability supernovae because its He core is as massive as the pre-colliding naked He star. We find that the number of LB-1-like systems in the Milky Way galaxy is ∼0.01(ρoc/104 ${M_{\odot}}$ pc−3), where ρoc is the initial mass densities of open clusters. If we take into account LB-1-like systems with O-type companion stars, the number increases to ∼0.03(ρoc/104 ${M_{\odot}}$ pc−3). This mechanism can form LB-1-like systems at least ten times more efficiently than the other mechanisms: captures of B-type stars by PI-gap BHs, stellar collisions between other types of stars, and stellar mergers in hierarchical triple systems. We conclude that no dynamical mechanism can explain the presence of the LB-1 system.
Cross-Sectional Associations of Fatigue Subtypes with Pain Interference in Younger, Middle-Aged, and Older Adults with Chronic Orofacial Pain
Authors: Boggero Ian A , Rojas Ramirez Marcia V , King Christopher D
Published: March 2020

Objective

Mental, emotional, physical, and general fatigue, as well as vigor, have each been associated with pain interference—defined as pain-related disruption of social, recreational, and work-related activities—in patients with chronic orofacial pain (COFP). The objectives of the current study were to compare levels of these fatigue subtypes across younger, middle-aged, and older patients with COFP and test the associations between fatigue subtypes and pain interference in these age groups.

Design

A cross-sectional cohort design was used.

Setting

Participants self-reported fatigue subtypes (Multidimensional Fatigue Symptom Inventory–Short Form), pain interference (West Haven–Yale Multidimensional Pain Inventory), pain intensity (visual analog scale), pain duration (months), depression (Symptom Checklist 90–Revised), and sleep quality (Pittsburgh Sleep Quality Index) at their initial appointment at a tertiary orofacial pain clinic.

Subjects

Sixty younger (age 18–39), 134 middle-aged (age 40–59), and 51 older (age 60–79) COFP patients provided data for the study.

Methods

Analysis of variance was used to compare levels of fatigue subtypes between the age groups. Regression with dummy-coding was used to test if the relationship between fatigue subtypes and pain interference varied by age.

Results

Older COFP patients reported less general fatigue and more vigor than younger or middle-aged adults. Fatigue subtypes were each associated with greater pain interference, but associations became nonsignificant after controlling for depression, sleep, and pain intensity/duration. Age group–by–fatigue subtype interactions were not observed.

Conclusions

Managing fatigue may be important to reduce pain interference in COFP populations and may be accomplished in part by improving depression and sleep.
The effect of the Montgomery judgment on settled claims against the National Health Service due to failure to inform before giving consent to treatment
Authors: Wald D S , Bestwick J P , Kelly P
Published: March 2020

Background

A landmark legal judgment in March 2015 (Montgomery) changed the test for determining negligence due to failing to inform patients before consent, by moving away from asking what a reasonable doctor should disclose and asking instead what a reasonable patient would expect to know.

Aim

We sought to determine the effect Montgomery has had on settled claims due to failure to inform compared with claims for other reasons and whether legal firms are adding contributory claims of failure to inform to other principal allegations of negligence.

Methods

A Freedom of Information request to NHS Resolution provided data on the number of settled claims against the NHS (2005–19) for any cause and where failure to inform before consent was the principal or contributory cause. Time-series regression was used to compare trends before and after 31 March 2015.

Results

The trend in claims/year increased 4-fold for failure to inform (an increase of 9.8/year before 2015 vs. 39.5/year after 2015, P < 0.01), 2.7-fold when failure to inform was the principal cause (7.9/year vs. 21.2/year, P = 0.02) and 9.9-fold as a contributory cause (1.9/year vs. 18.3/year, P < 0.01). There was no material difference in claims due to other causes (334/year vs. 318/year, P = 0.84).

Conclusions

Montgomery has led to a substantial increase in settled claims of failure to inform before consent, with no coincident change in claims for other causes. The increase in contributory compared with principal causes suggests that lawyers are using the judgment to increase the chances of a successful claim against the NHS.
Economic Consequences of Housing Speculation
Authors: Gao Zhenyu , Sockin Michael , Xiong Wei
Published: March 2020

By exploiting variation in state capital gains taxation as an instrument, we analyze the economic consequences of housing speculation during the U.S. housing boom in the 2000s. We find that housing speculation, anchored, in part, on extrapolation of past housing price changes, led not only to greater price appreciation, economic expansions, and housing construction during the boom in 2004–2006 but also to more severe economic downturns during the subsequent bust in 2007–2009. Our analysis supports supply overhang and local household demand as two key channels for transmitting these adverse effects.
IMPROVED EMPIRICAL LIKELIHOOD FUNCTION BASED ON NORMALIZATION-DEPENDENT REPLICATE MEASUREMENTS
Authors: Miller Guthrie , Klumpp John , Poudel Deepesh
Published: March 2020

Based on $n$ replicate measurements that require known normalization factors and assuming an underlying normal distribution for individual measurements but with unknown standard deviation, a combined likelihood function is derived that takes the form of a Student’s $t$-distribution with $\nu = n-1$ degrees of freedom and $t=(\psi -\overline{Y})/s$, where $\psi $ is the true value of the measurement quantity calculated from the forward model, and $\overline{Y}$ and $s$ are average and standard error of the mean obtained from the $n$ measurements defined with weighting proportional to the inverse of the normalization factor squared. Assuming an underlying triangle distribution rather than a normal distribution does not produce a large change for six replicates. Examples of replicate data from an animal study and sequential occupational urine and fecal monitoring are given. The use of the empirical likelihood function in data modeling is discussed.
Neural correlates of cognitive bias modification for interpretation
Authors: Sakaki Kohei , Nozawa Takayuki , Ikeda Shigeyuki , Kawashima Ryuta
Published: March 2020

The effectiveness of cognitive bias modification for interpretation (CBM-I), a treatment method employed to reduce social anxiety (SA), has been examined. However, the neural correlates of CBM-I remain unclear, and we aimed to elucidate brain activities during intervention and activity changes associated with CBM-I effectiveness in a pre–post intervention comparison. Healthy participants divided into two groups (CBM, control) were scanned before, during and after intervention using functional magnetic resonance imaging. Ambiguous social situations followed by positive outcomes were repeatedly imagined by the CBM group during intervention, while half of the outcomes in the control group were negative. Whole-brain analysis revealed that activation of the somatomotor and somatosensory areas, occipital lobe, fusiform gyrus and thalamus during intervention was significantly greater in the CBM than in the control group. Furthermore, altered activities in the somatomotor and somatosensory areas, occipital lobe and posterior cingulate gyrus during interpreting ambiguous social situations showed a significant group × change in SA interaction. Our result suggests that when facing ambiguous social situations, positive imagery instilled by CBM-I is recalled, and interpretations are modified to contain social reward. These findings may help to suggest an alternative manner of enhancing CBM-I effectiveness from a cognitive-neuroscience perspective.
Real-World Clinical Outcomes Two Years After Transition to Psychosis in Individuals at Clinical High Risk: Electronic Health Record Cohort Study
Authors: Fusar-Poli Paolo , De Micheli Andrea , Patel Rashmi , Signorini Lorenzo , Miah Syed , Spencer Thomas , McGuire Philip
Published: March 2020

The objective of this study is to describe the 2-year real-world clinical outcomes after transition to psychosis in patients at clinical high-risk. The study used the clinical electronic health record cohort study including all patients receiving a first index primary diagnosis of nonorganic International Classification of Diseases (ICD)-10 psychotic disorder within the early psychosis pathway in the South London and Maudsley (SLaM) National Health Service (NHS) Trust from 2001 to 2017. Outcomes encompassed: cumulative probability (at 3, 6, 12, and 24 months) of receiving a first (1) treatment with antipsychotic, (2) informal admission, (3) compulsory admission, and (4) treatment with clozapine and (5) numbers of days spent in hospital (at 12 and 24 months) in patients transitioning to psychosis from clinical high-risk services (Outreach and Support in south London; OASIS) compared to other first-episode groups. Analyses included logistic and 0-inflated negative binomial regressions. In the study, 1561 patients were included; those who had initially been managed by OASIS and had subsequently transitioned to a first episode of psychosis (n = 130) were more likely to receive antipsychotic medication (at 3, 6, and 24 months; all P < .023), to be admitted informally (at all timepoints, all P < .004) and on a compulsory basis (at all timepoints, all P < .013), and to have spent more time in hospital (all timepoints, all P < .007) than first-episode patients who were already psychotic when seen by the OASIS service (n = 310), or presented to early intervention services (n = 1121). The likelihood of receiving clozapine was similar across all groups (at 12/24 months, all P < .101). Transition to psychosis from a clinical high-risk state is associated with severe real-world clinical outcomes. Prevention of transition to psychosis should remain a core target of future research. The study protocol was registered on www.researchregistry.com; researchregistry5039).
Congenital Syphilis in Honiara, Solomon Islands
Authors: Lifigao Maxson , Nasi Titus , Titiulu Carol , Lumasa Steven , Duke Trevor
Published: March 2020

Introduction

Congenital syphilis remains a significant cause of newborn mortality and long-term neurodevelopmental problems in some low- and middle-income countries. This study was done in Honiara, Solomon Islands to determine the incidence of babies born to mothers with a positive venereal disease research laboratory (VDRL) test and a positive Treponema pallidum haemagglutination assay (TPHA); to determine the VDRL status of newborns and features of congenital syphilis; and to estimate the proportion of stillbirths associated with syphilis.

Methodology

All neonates born to VDRL-positive mothers, including stillbirths were included between April and July 2019. Neonates were examined, investigated and treated.

Results

Among 1534 consecutive births, 1469 were live births and 65 (4.2%) were stillbirths. One hundred and forty-three neonates were born to VDRL-positive mothers: 130 (90.1%) were live infants and 13 (8.9%) stillbirths. Of the 130 VDRL-exposed live-born infants, 72 (55%) had reactive VDRL and a positive TPHA and 7 (9.7%) had clinical signs of congenital syphilis. Five of the infants with clinical signs of syphilis infection had a 4-fold higher VDRL titre than their mother. Four infants of VDRL-positive mothers died during admission, all of whom had clinical signs of syphilis. Ninety percent of affected infants were born to mothers who were not treated or only partially treated during pregnancy.

Conclusions

In this study, 1:210 live-born babies had clinical and serological evidence of congenital syphilis, and evidence of Treponema infection was found disproportionately in stillbirths. In a setting where Treponema infections are common, an empirical approach to prevention may be needed.