bluuebunny/crossref_metadata_2025 huggingface dataset:
Male origin microchimerism and ovarian cancer
Authors: Hallum Sara , Jakobsen Marianne Antonius , Gerds Thomas Alexander , Pinborg Anja , Tjønneland Anne , Kamper-Jørgensen Mads
Published: January 2020

Background

Reduced risk of ovarian cancer is commonly ascribed to reduced exposure to endogenous hormones during pregnancy, using oral contraceptives or not using hormone replacement therapy. However, exposure to hormones alone account for less than half of all cases. Many women carry small amounts of male cells—known as male origin microchimerism—in their circulation and remarkable impacts of these cells on women’s health are being published. Here, we pursue the possibility that male origin microchimerism has a role in reducing ovarian cancer risk.

Methods

We conducted a prospective case-cohort study using blood samples and questionnaire data from 700 women participating in the Danish Diet, Cancer, and Health cohort. Blood samples were analysed for Y chromosome presence as a marker of male microchimerism. We evaluated the association between male microchimerism and ovarian cancer, using weighted Cox regression models reporting hazard ratios (HRs) and corresponding 95% confidence intervals (CIs).

Results

Male microchimerism was detected in 46% of cases and 65.9% of controls. Women testing positive for male microchimerism had a reduced hazard rate of ovarian cancer compared with women testing negative (HR = 0.44, 95% CI: 0.29-0.68). We found no evidence of interaction with measures of hormonal exposures (P = 0.50).

Conclusions

For the first time we report that women who test positive for male microchimerism in their circulation have reduced rates of ovarian cancer compared with women who test negative. Although the underlying mechanisms are presently unknown, we believe male microchimerism is potent in preventing ovarian cancer.
Traps and Attractants for Monitoring Navel Orangeworm (Lepidoptera: Pyralidae) in the Presence of Mating Disruption
Authors: Burks Charles S , Higbee Bradley S , Beck John J
Published: January 2020

The use of aerosol mating disruption for management of the navel orangeworm Amyelois transitella (Walker) in California tree nuts has increased markedly. This treatment suppresses pheromone monitoring traps in neighboring orchards as well as in the orchard under treatment. The current study, therefore, addresses the interrelated topics of which attractant is most effective, how the number of adults captured is affected by trap design, and what sex is captured. Under most circumstances, wing traps baited with phenyl propionate (PPO) captured more adults than those baited with a 5-compound kairomone blend. Adding a pheromone lure along with the dispenser for the experimental attractant increased the number of adults captured with PPO both in and near-mating disruption. In contrast, addition of a pheromone lure along with the kairomone blend only increased the number of adults captured in orchards near but not under mating disruption. Delta traps, which are preferred by the industry, captured fewer adults than wing traps. Improvements in the number of adults captured with PPO in delta traps from addition of a pheromone lure and from design modifications were additive. Both sexes were captured by all attractants and trap designs tested, and the sex ratio was highly variable. Open traps like the wing trap captured a slightly higher proportion of males than closed traps. These findings are discussed in the context of management of the navel orangeworm.
Harnessing symbiotic plant–fungus interactions to unleash hidden forces from extreme plant ecosystems
Authors: Pérez-Alonso Marta-Marina , Guerrero-Galán Carmen , Scholz Sandra S , Kiba Takatoshi , Sakakibara Hitoshi , Ludwig-Müller Jutta , Krapp Anne , Oelmüller Ralf , Vicente-Carbajosa Jesús , Pollmann Stephan
Published: January 2020

Global climate change is arguably one of the biggest threats of modern times and has already led to a wide range of impacts on the environment, economy, and society. Owing to past emissions and climate system inertia, global climate change is predicted to continue for decades even if anthropogenic greenhouse gas emissions were to stop immediately. In many regions, such as central Europe and the Mediterranean region, the temperature is likely to rise by 2–5 °C and annual precipitation is predicted to decrease. Expected heat and drought periods followed by floods, and unpredictable growing seasons, are predicted to have detrimental effects on agricultural production systems, causing immense economic losses and food supply problems. To mitigate the risks of climate change, agricultural innovations counteracting these effects need to be embraced and accelerated. To achieve maximum improvement, the required agricultural innovations should not focus only on crops but rather pursue a holistic approach including the entire ecosystem. Over millions of years, plants have evolved in close association with other organisms, particularly soil microbes that have shaped their evolution and contemporary ecology. Many studies have already highlighted beneficial interactions among plants and the communities of microorganisms with which they coexist. Questions arising from these discoveries are whether it will be possible to decipher a common molecular pattern and the underlying biochemical framework of interspecies communication, and whether such knowledge can be used to improve agricultural performance under environmental stress conditions. In this review, we summarize the current knowledge of plant interactions with fungal endosymbionts found in extreme ecosystems. Special attention will be paid to the interaction of plants with the symbiotic root-colonizing endophytic fungus Serendipita indica, which has been developed as a model system for beneficial plant–fungus interactions.
The transition clinic in chronic kidney disease care
Authors: Evans Marie , Lopau Kai
Published: January 2020

People with advanced chronic kidney disease and evidence of progression have a high risk of renal replacement therapy. Specialized transition clinics could offer a better option for preparing these patients for dialysis, transplantation or conservative care. This review focuses on the different aspects of such transition clinics. We discuss which patients should be referred to these units and when referral should take place. Patient involvement in the decision-making process is important and requires unbiased patient education. There are many themes, both patient-centred and within the healthcare structure, that will influence the process of shared decision-making and the modality choice. Aspects of placing an access for haemodialysis and peritoneal dialysis are reviewed. Finally, we discuss the importance of pre-emptive transplantation and a planned dialysis start, all with a focus on multidisciplinary collaboration at the transition clinic.
Subtype switching in breast cancer brain metastases: a multicenter analysis
Authors: Hulsbergen Alexander F C , Claes An , Kavouridis Vasileios K , Ansaripour Ali , Nogarede Claudine , Hughes Melissa E , Smith Timothy R , Brastianos Priscilla K , Verhoeff Joost J C , Lin Nancy U , Broekman Marike L D
Published: January 2020

Background

Breast cancer (BC) brain metastases (BM) can have discordant hormonal or human epidermal growth factor receptor 2 (HER2) expression compared with corresponding primary tumors. This study aimed to describe incidence, predictors, and survival outcomes of discordant receptors and associated subtype switching in BM.

Methods

BCBM patients seen at 4 tertiary institutions who had undergone BM resection or biopsy were included. Surgical pathology reports were retrospectively assessed to determine discordance between the primary tumor and the BCBM. In discordant cases, expression in extracranial metastases was also assessed.

Results

In BM from 219 patients, prevalence of any discordance was 36.3%; receptor-specific discordance was 16.7% for estrogen, 25.2% for progesterone, and 10.4% for HER2. Because estrogen and progesterone were considered together for hormonal status, 50 (22.8%) patients switched subtype as a result; 20 of these switches were HER2 based. Baseline subtype predicted switching, which occurred in up to 37.5% of primary HR+ patients. Moreover, 14.8% of initially HER2-negative patients gained HER2 in the BM. Most (63.6%) discordant patients with extracranial metastases also had discordance between BM and extracranial subtype. Loss of receptor expression was generally associated with worse survival, which appeared to be driven by estrogen loss (hazard ratio = 1.80, P = 0.03). Patients gaining HER2 status (n = 8) showed a nonsignificant tendency toward improved survival (hazard ratio = 0.64, P = 0.17).

Conclusions

In this multicenter study, we report incidence and predictors of subtype switching, the risk of which varies considerably by baseline subtype. Switches can have clinical implications for prognosis and treatment choice.
Four-Dimensional Magnetic Resonance Imaging Assessment of Intracranial Aneurysms: A State-of-the-Art Review
Authors: Castle-Kirszbaum Mendel , Maingard Julian , Lim Ruth P , Barras Christen D , Kok Hong Kuan , Chandra Ronil V , Chong Winston , Asadi Hamed
Published: January 2020

Treatment of unruptured intracranial aneurysms can reduce the risk of subarachnoid hemorrhage and its associated morbidity and mortality. However, current methods to predict the risk of rupture and optimize treatment strategies for intracranial aneurysms are limited. Assessment of intra-aneurysmal flow using 4-dimensional magnetic resonance imaging (4D MRI) is a novel tool that could be used to guide therapy. A systematic search of the literature was performed to provide a state-of-the-art review on 4D MRI assessment of unruptured intracranial aneurysms. A total of 18 studies were available for review. Eccentric flow on 4D MRI is associated with a greater aspect ratio and peak wall shear stress (WSS). WSS, vorticity, and peak velocity are greater in saccular than fusiform aneurysms. Unstable aneurysms are associated with greater WSS, peak wall stress, and flow jet angle and may exhibit wall enhancement. In comparison to computational fluid dynamics (CFD), 4D MRI has a lower spatial resolution and reports lower WSS and velocity magnitudes, but these parameters equalize when spatial resolution is matched. 4D MRI demonstrates the intra-aneurysmal hemodynamic changes associated with flow diversion, including significantly decreased flow velocity. Thus, 4D MRI is a novel, noninvasive imaging tool used for the evaluation of hemodynamics within intracranial aneurysms. Hemodynamic indices derived from 4D MRI appear to correlate well with the simulated (CFD) values and may be used to measure the success of endovascular therapies and risk factors for aneurysm growth and rupture.
Sideline Concussion Assessment: The Current State of the Art
Authors: Yue John K , Phelps Ryan R L , Chandra Ankush , Winkler Ethan A , Manley Geoffrey T , Berger Mitchel S
Published: January 2020

More than 200 million American adults and children participate in organized physical activity. Growing awareness has highlighted that concussion, especially when repeated, may be associated with prolonged neurological, cognitive, and/or neuropsychiatric sequelae. Objective diagnosis of concussion remains challenging. Although some concussion symptoms may be apparent even to nonmedical observers, diagnosis and removal from play for evaluation depend on validated assessment tools and trained, vigilant healthcare personnel. Over the past 2 decades, sideline concussion measures have undergone significant revision and augmentation to become more comprehensive batteries in order to detect a wide spectrum of symptomatology, eg, neurocognitive function, postconcussive symptoms, gait/balance, and saccadic eye movements. This review summarizes the current state-of-the-art concussion evaluation instruments, ranging from the Sports Concussion Assessment Tool (SCAT) and tools that may enhance concussion detection, to near-term blood-based biomarkers and emerging technology (eg, head impact sensors, vestibulo-ocular/eye-tracking, and mobile applications). Special focus is directed at feasibility, utility, generalizability, and challenges to implementation of each measure on-field and on the sidelines. This review finds that few instruments beyond the SCAT provide guidance for removal from play, and establishing thresholds for concussion detection and removal from play in qualification/validation of future instruments is of high importance. Integration of emerging sideline concussion evaluation tools should be supported by resources and education to athletes, caregivers, athletic staff, and medical professionals for standardized administration as well as triage, referral, and prevention strategies. It should be noted that concussion evaluation instruments are used to assist the clinician in sideline diagnosis, and no single test can diagnose concussion as a standalone investigation.
Associations Between Nicotine Metabolite Ratio and Gender With Transitions in Cigarette Smoking Status and E-Cigarette Use: Findings Across Waves 1 and 2 of the Population Assessment of Tobacco and Health (PATH) Study
Authors: Verplaetse Terril L , Peltier MacKenzie R , Roberts Walter , Moore Kelly E , Pittman Brian P , McKee Sherry A
Published: January 2020

Introduction

Nicotine metabolite ratio (NMR), the ratio of trans 3′-hydroxycotinine to cotinine, is a biomarker of nicotine metabolism. Discrepant findings among clinical trials and population-based studies warrant replication on whether higher NMR, or faster nicotine metabolism, is associated with quitting cigarette smoking. Associations of NMR and e-cigarette use are largely unknown, as well as the relationship between NMR and gender on quitting cigarette smoking or e-cigarette use.

Methods

The Population Assessment of Tobacco and Health (PATH) Study is a nationally representative, longitudinal cohort study assessing tobacco use in the US population. In the current study, the PATH (waves 1 and 2; adult interviews) was used to evaluate longitudinal predictions in relationships among NMR and gender and their association with transitions (quit vs. current stable) in cigarette smoking status and e-cigarette use status across waves 1 and 2 of the PATH study.

Results

NMR and gender were not significantly associated with quit behavior for combustible cigarettes. Regarding e-cigarettes, a significant two-way interaction demonstrated that women with higher NMR were less likely to quit e-cigarette use compared to women with lower NMR (odds ratio [OR] = 0.10, 95% confidence interval [CI] = 0.02–0.57; p = .01).

Conclusions

Findings identify that women with faster nicotine metabolism were 10 times less likely to quit e-cigarettes compared to women with slower nicotine metabolism across waves 1 and 2 of the PATH study. Results suggest that NMR may be used as a biomarker for transitions in e-cigarette quit behavior for women.

Implications

Findings identify that women with faster nicotine metabolism were 10 times less likely to quit e-cigarettes compared to women with slower nicotine metabolism. Results suggest that NMR may be used as a biomarker for transitions in e-cigarette quit behavior for women. Establishing parameters for NMR collection and for the use of NMR as a biomarker for cigarette smoking behavior and e-cigarette use is an important next step, and may have implications for early intervention and treatment for cessation.
Long-Term Outcomes of Endoscopic Third Ventricle Colloid Cyst Resection: Case Series With a Proposed Grading System
Authors: Isaacs Albert M , Bezchlibnyk Yarema B , Dronyk Jarred , Urbaneja Geberth , Yong Heather , Hamilton Mark G
Published: January 2020

BACKGROUND

Endoscopic resection of colloid cysts has gained recent widespread practice. However, reported complication and recurrence rates are variable, possibly, in part, because of a lack of consistency with reporting of the extent of cyst capsule removal.

OBJECTIVE

To present the long-term outcomes of endoscopic resection of third ventricle colloid cysts without complete capsule removal and propose a grading system to allow consistent description of surgical outcomes.

METHODS

A retrospective review of 74 patients who underwent endoscopic resection of symptomatic third ventricle colloid cysts between 1995 and 2018 was performed. Kaplan-Meier analyses were used to assess recurrence-free survival rates.

RESULTS

Median patient age and cyst diameter were 48.0 (13.0-80.0) yr and 12.0 (5.0-27.0) mm, respectively. Complete emptying of cyst contents with capsule coagulation was achieved in 73 (98.6%) patients. All patients improved or remained stable postoperatively, with a median follow-up duration of 10.3 (0.3-23.7) yr. Radiographic recurrence occurred in 6 (8.1%) patients after their initial surgery, 5 (6.8%) of whom underwent redo endoscopic resection. No major complications or mortality was encountered at primary or recurrence surgery.

CONCLUSION

Endoscopic resection of third ventricle colloid cysts without emphasizing complete capsule removal is a viable option for successfully treating colloid cysts of the third ventricle. Long-term follow-up demonstrates that it is associated with low risks of complications, morbidity, mortality, and recurrence. The proposed extent of the resection grading scheme will permit comparison between the different surgical approaches and facilitate the establishment of treatment guidelines for colloid cysts.
The Reliability of a Grading System for Digital Subtraction Imaging Quality During Cervical Transforaminal Epidural Steroid Injection
Authors: Binler Danielle , House L McLean , Mattie Ryan , Saltychev Mikhail , Nagao Masato , Pekmeczi Murat , Metz Lionel , O’Neil Conor , Shah Vinil , McCormick Zachary L
Published: January 2020

Objective

Digital subtraction imaging (DSI) decreases the risk of intravascular injection during cervical transforaminal epidural steroid injection (CTFESI); however, sequence acquisition and interpretation are operator-dependent skills. This study tests the reliability of a grading system to determine adequate DSI during CTFESI.

Setting

Academic tertiary medical center.

Methods

A grading scheme for adequate DSI quality during CTFESI was created by the study authors based on patient positioning, mask image, and volume of contrast injected. The inter-rater and intrarater reliability values of this grading scheme were tested using 50 DSI images evaluated by three raters during two distinct sessions separated by four weeks. Based on a power analysis, a sample of 50 scans was sufficient to detect significant correlations. Inter-rater reliability was determined by percent agreement between graders for dichotomized categories of “quality of DSI is adequate for safe C-TFESI” vs “quality of DSI is inadequate for safe C-TFESI.” The percentage of agreement was reported, along with Gwet’s agreement coefficient (AC). The intrarater (pre/post) correlation was assessed using Yule’s Q statistics.

Results

Correlation coefficients were interpreted as follows: 0.00–0.19 “very weak,” 0.20–0.39 “weak,” 0.40–0.59 “moderate,” 0.60–0.79 “strong,” and 0.80–1.00 “very strong.” Inter-rater reliability analyses demonstrated that the patient position category had “very strong” agreement, contrast volume had “strong” agreement, and mask image had “moderate” agreement. The overall inter-rater reliability was “moderate.” All of the raters demonstrated “very strong” intrarater reliability.

Conclusions

The proposed grading system for adequate-quality DSI during CTFESI showed overall “moderate” and “very strong” inter- and intrarater reliability, respectively. This scheme provides an objective measure of DSI quality for CTFESI. Refinement is needed to improve the reliability of this scheme.
Predictors of presenteeism, absenteeism and job loss in patients commencing methotrexate or biologic therapy for rheumatoid arthritis
Authors: Gwinnutt James M , Leggett Sarah , Lunt Mark , Barton Anne , Hyrich Kimme L , Walker-Bone Karen , Verstappen Suzanne M M ,   RAMS and BRAGGSS co-investigators
Published: January 2020

Objectives

Work is an important health outcome. This study aimed to identify predictors of work loss, absenteeism and presenteeism over 1 year in RA patients commencing treatment with MTX or biologics.

Methods

Patients aged 18–65 years in full/part-time employment from two UK prospective cohorts were included: MTX-starters = Rheumatoid Arthritis Medication Study; and biologic-starters = Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate. Presenteeism and absenteeism were assessed using the RA-specific Work Productivity Survey at baseline, and 6 and 12 months. Potential predictors including baseline age, gender, clinical measures (e.g. disability, pain, fatigue), psychological distress, occupation and EULAR response from baseline to 6 months were investigated.

Results

A total of 51/463 MTX-starters and 30/260 biologic-starters left work over 12 months. Higher baseline psychological distress in MTX-starters [odds ratio (OR) 1.1 (95% CI: 1.0, 1.1)] and higher disability in biologic-starters [OR 3.5 (95% CI: 1.4, 8.6)] predicted work loss. Some 16.1% of patients reported sick-leave, which was predicted by disability [OR (95% CI): MTX-starters: 1.5 (0.9, 2.3); biologic-starters: 2.4 (1.1, 5.2)]. Median presenteeism scores were very low (minimal interference) in both cohorts. Higher fatigue for MTX starters [incidence rate ratio 1.2 (95% CI: 1.0, 1.4)] and higher disability in biologic-starters (incidence rate ratio 1.4 (95% CI: 1.1, 1.7)] predicted presenteeism. Good EULAR response was associated with lower absenteeism and presenteeism in both cohorts.

Conclusion

Patients with RA still face significant limitations regarding their ability to work. Disability and EULAR response were the main predictors of work outcomes, emphasizing the need to control the disease and the importance of function in enabling work participation.
Serum CA72-4 is specifically elevated in gout patients and predicts flares
Authors: Bai Xueshan , Sun Mingshu , He Yuwei , Liu Ruhua , Cui Lingling , Wang Can , Wan Fang , Wang Ming , Li Xinde , Li Hailong , Wu Xinjiang , Li Changgui
Published: January 2020

Objectives

Serum CA72-4 levels are elevated in some gout patients but this has not been comprehensively described. The present study profiled serum CA72-4 expression in gout patients and verified the hypothesis that CA72-4 is a predictor of future flares in a prospective gout cohort.

Methods

To profile CA72-4 expression, a cross-sectional study was conducted in subjects with gouty arthritis, asymptomatic hyperuricaemia, four major arthritis types (OA, RA, SpA, septic arthritis) and healthy controls. A prospective gout cohort study was initiated to test the value of CA72-4 for predicting gout flares. During a 6-month follow-up, gout flares, CA72-4 levels and other gout-related clinical variables were observed at 1, 3 and 6 months.

Results

CA72-4 was highly expressed in patients with gouty arthritis [median (interquartile range) 4.55 (1.56, 32.64) U/ml] compared with hyperuricaemia patients [1.47 (0.87, 3.29) U/ml], healthy subjects [1.59 (0.99, 3.39) U/ml] and other arthritis patients [septic arthritis, 1.38 (0.99, 2.66) U/ml; RA, 1.58 (0.95, 3.37) U/ml; SpA, 1.56 (0.98, 2.85) U/ml; OA, 1.54 (0.94, 3.34) U/ml; P < 0.001, respectively]. Gout patients with frequent flares (twice or more in the last year) had higher CA72-4 levels than patients with fewer flares (fewer than twice in the last year). High CA72-4 level (>6.9 U/ml) was the strongest predictor of gout flares (hazard ratio = 3.889). Prophylactic colchicine was effective, especially for patients with high CA72-4 levels (P = 0.014).

Conclusion

CA72-4 levels were upregulated in gout patients who experienced frequent flares and CA72-4 was a useful biomarker to predict future flares.
Preserving Spring Oat Yields in New York Through Varietal Resistance to Crown Rust
Authors: Fulcher Michael R. , Benscher David , Sorrells Mark E. , Bergstrom Gary C.
Published: January 2020

Crown rust is the principal disease of spring oat in New York. Management with resistance genes is effective but contingent on understanding varietal responses to local pathogen populations. Field studies were conducted from 2015 to 2018 to assess the crown rust susceptibility of commercial cultivars and public breeding lines under natural conditions in New York. Three of the 10 commercial varieties trialed were determined to be resistant, and breeding lines from five different states also exhibited resistance. On average, yield was reduced by 34.56 kg/ha for every 1% increase in crown rust severity, whereas the impact on test weight was negligible. A race differential panel was deployed in 2018 at a central screening nursery to determine the range of pathogen virulence present. Susceptible interactions were observed on only five crown rust differentials, and virulence on all five has been recorded at high levels across the country. Crown rust may be a limiting factor to oat production in New York, but yield potential and crop value can be preserved by planting an appropriately resistant variety.
Paenibacillus ottowii sp. nov. isolated from a fermentation system processing bovine manure
Authors: Velazquez Luis F. , Rajbanshi Shashi , Guan Shaohua , Hinchee Maud , Welsh Allana
Published: January 2020

Strain MS2379T was isolated from a pasteurized solution sample from a predominantly anaerobic fermentation system processing bovine manure in Pilot Point, Texas. Phylogenetic analyses based on both 16S rRNA gene and rpoB gene sequences showed that MS2379T was most closely related to

Paenibacillus polymyxa

(DSM 36T), P. jamilae (DSM 13815T), and P. peoriae (DSM 8320T), yet DNA–DNA relatedness through DNA–DNA hybridization revealed only 22.6, 32.0 and 24.7 % relatedness to these three species respectively. Rod-shaped cells of strain MS2379T are Gram-stain variable with sub-terminal, ellipsoidal, deforming endospores. The peptidoglycan contains meso-diaminopimelic acid (mDAP) and the predominant fatty acids are anteiso-C15 : 0 (61.9 %) and anteiso-C17 : 0 (11.6 %), confirming that strain MS2379T has diagnostic features of other

Paenibacillus

species. The G+C content of MS2379T is 45.9 mol%. Fermentation of glucose yields acid and gas end-products. The polar lipids found were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, and glycolipids, but also included some unidentified lipids, aminolipids, aminoglycolipid, and phosphatidylmethylethanolamine. The growth range of MS2379T was observed from 10–45 °C with optimal growth temperature at 30 °C. Growth was observed between pH 6–10 and up to 3 % NaCl. Unlike the most closely related

Paenibacillus

species, strain MS2379T was negative in the Voges-Proskauer reaction. Nucleic acid, chemotaxonomic and biochemical features support the distinctiveness of strain MS2379T. Thus, strain MS2379T represents a novel species of the genus

Paenibacillus

for which the name Paenibacillus ottowii sp. nov. is proposed with the type strain MS2379T (=DSM 107750T=ATCC TSD-165T).
Metabolic manipulation by Pseudomonas fluorescens: a powerful stratagem against oxidative and metal stress
Authors: MacLean Alex , Bley Anondo Michel , Appanna Varun P. , Appanna Vasu D.
Published: January 2020

Metabolism is the foundation of all living organisms and is at the core of numerous if not all biological processes. The ability of an organism to modulate its metabolism is a central characteristic needed to proliferate, to be dormant and to survive any assault.Pseudomonas fluorescensis bestowed with a uniquely versatile metabolic framework that enables the microbe to adapt to a wide range of conditions including disparate nutrients and toxins. In this mini-review we elaborate on the various metabolic reconfigurations evoked by this microbial system to combat reactive oxygen/nitrogen species and metal stress. The fine-tuning of the NADH/NADPH homeostasis coupled with the production of α-keto-acids and ATP allows for the maintenance of a reductive intracellular milieu. The metabolic networks propelling the synthesis of metabolites like oxalate and aspartate are critical to keep toxic metals at bay. The biochemical processes resulting from these defensive mechanisms provide molecular clues to thwart infectious microbes and reveal elegant pathways to generate value-added products.
Strategies for cellular deconvolution in human brain RNA sequencing data
Authors: Sosina Olukayode A. , Tran Matthew N , Maynard Kristen R , Tao Ran , Taub Margaret A. , Martinowich Keri , Semick Stephen A. , Quach Bryan C. , Weinberger Daniel R. , Hyde Thomas M. , Hancock Dana B. , Kleinman Joel E. , Leek Jeffrey T , Jaffe Andrew E
Published: January 2020

Statistical deconvolution strategies have emerged over the past decade to estimate the proportion of various cell populations in homogenate tissue sources like brain using gene expression data. Here we show that several existing deconvolution algorithms which estimate the RNA composition of homogenate tissue, relates to the amount of RNA attributable to each cell type, and not the cellular composition relating to the underlying fraction of cells. Incorporating “cell size” parameters into RNA-based deconvolution algorithms can successfully recover cellular fractions in homogenate brain RNA-seq data. We lastly show that using both cell sizes and cell type-specific gene expression profiles from brain regions other than the target/user-provided bulk tissue RNA-seq dataset consistently results in biased cell fractions. We report several independently constructed cell size estimates as a community resource and extend the MuSiC framework to accommodate these cell size estimates (https://github.com/xuranw/MuSiC/).
MQ: Tool for HR-AM Based Quantitative Analysis for Direct MS Workflow
Authors: Ghanate Avinash , Parmar Dharmesh , Bhattacharya Nivedita , Inamdar Ijaz , Phadke Gayatri , Panchagnula Venkateswarlu
Published: January 2020

There is an increased interest in using high-resolution mass spectrometry (HRMS) in the full scan mode (FS) for simultaneous qualitative and quantitative analysis with accurate mass based extracted ion chromatograms (HRMS-AM) for metabolomic profiling workflows. Herein, the capabilities and features of ‘MQ’, a common platform developed to support quantitative analysis from HRMS data are described. Module for qualitative annotation utilizes peak features that include mass accuracy, peak width, and relative abundance of isotopic distribution that offer reliable metabolic confirmation. Additionally, MQ provides multivariate clustering with Principal Component Analysis and a module for high-throughput database query based on user configurable annotated metabolite lists. MQ is capable of handling system-agnostic data formats from both direct HRMS and LC-HRMS analysis. Data processed using MQ for LC-HRMS-AM quantitation of amino acids benchmarked using a commercial tool is presented that validates the quantitative capabilities of the algorithm developed. Datasets representative of three different HRMS-AM based analysis scenarios have been showcased to demonstrate the utility of MQ.

Availability and implementation

Freely available on web at,http://www.ldims.com/services/software. MQ is implemented in Java and supported on Linux and Microsoft Windows system having Java runtime environment (JRE) pre-installed.
Genomic characterization of three novelPseudomonasphages within the subfamily ofAutographivirinaeisolated from organic waste
Authors: Jørgensen Jacob B , Djuurhus Amaru M , Carstens Alexander B. , Kot Witold , Morris Cindy E. , Hansen Lars H.
Published: January 2020

Three phages targetingPseudomonas syringaeGAW0113 have been isolated from organic waste samples: Pseudomonas phage Bertil, Misse and Strit. The phages have double-stranded DNA genomes ranging from 41342 to 41374 bp in size comprising 50 to 51 open reading frames. The three phages genomes are highly similar and genomic comparison analyses shows that they all belong to theAutographivirinaesubfamily of the familyPodoviridae.The phages are however only distantly related to other members of this family, and have limited gene synteny with type-phages of other genera withinAutographivirinae, suggesting that the newly isolated phages could represent a new genus.
A morphological trait involved in reproductive isolation between Drosophila sister species is sensitive to temperature
Authors: Peluffo Alex E. , Hamdani Mehdi , Vargas-Valderrama Alejandra , David Jean R. , Mallard François , Graner François , Courtier-Orgogozo Virginie
Published: January 2020

Male genitalia are usually extremely divergent between closely related species, but relatively constant within one species. Here we examine the effect of temperature on the shape of the ventral branches, a male genital structure involved in reproductive isolation, in the sister speciesDrosophila santomeaandD. yakuba. We designed a semi-automatic measurement pipeline that can reliably identify curvatures and landmarks based on manually digitized contours of the ventral branches. With this method, we observed that temperature does not affect ventral branches inD. yakubabut that inD. santomeaventral branches tend to morph into a D. yakuba-like shape at lower temperature. Our results suggest that speciation ofD. santomeaandD. yakubawas associated with a change in genitalia plasticity.
CryoEM structure of the Nipah virus nucleocapsid assembly
Authors: Ker De-Sheng , Jenkins Huw T. , Greive Sandra J. , Antson Alfred A.
Published: January 2020

Nipah virus is a highly pathogenic zoonotic RNA virus, causing fatal encephalitis in humans. Like other negative-strand RNA viruses including Ebola and measles, its genome is wrapped by the nucleocapsid (N) protein forming a helical assembly. Here we report the CryoEM structure of the Nipah nucleocapsid protein-RNA assembly, at near atomic resolution. The N protein wraps the RNA genome with a periodicity of six nucleotides per protomer, around the outer edge of the helical assembly, in common with other paramyxoviruses. This structure uncovers details of the nucleocapsid assembly, demonstrating the role of the N-terminal arm of the N protein in the formation of the helical assembly and revealing details of the sequence-independent coordination of RNA binding in the “3-bases-in, 3-bases-out” conformation. CryoEM analysis also reveals formation of clam-shaped assemblies of the N-protein, mediated by intersubunit interactions involving several N protein loop regions.
Exploiting evolutionary trade-offs to combat antibiotic resistance
Authors: Melnikov Sergey , Stephens David L. , Fu Xian , Kwok Hui Si , Zhang Jin-Tao , Shen Yue , Sabina Jeffery , Lee Kevin , Lee Harry , Söll Dieter
Published: January 2020

Antibiotic resistance frequently evolves through fitness trade-offs in which the genetic alterations that confer resistance to a drug can also cause growth defects in resistant cells. Here, through experimental evolution in a microfluidics-based turbidostat, we demonstrate that antibiotic-resistant cells can be efficiently inhibited by amplifying the fitness costs associated with drug-resistance evolution. Using tavaborole-resistantE. colias a model, we show that genetic mutations in leucyl-tRNA synthetase (that underlie tavaborole resistance) make resistant cells intolerant to norvaline, a chemical analog of leucine that is mistakenly used by tavaborole-resistant cells for protein synthesis. We then show that tavaborole-sensitive cells quickly outcompete tavaborole-resistant cells in the presence of norvaline due to the amplified cost of the molecular defect of tavaborole resistance. This finding illustrates a potentially generalizable approach for combating therapeutic resistance, prolonging the effectiveness of drugs and enabling the use of drugs that are no longer effective due to the rapid evolution of resistance.
Neurons from human mesenchymal stem cells display both spontaneous and stimuli responsive activity
Authors: Karakaş Nihal , Bay Sadık , Türkel Nezaket , Öncül Merve , Bilgen Hülya , Shah Khalid , Şahin Fikrettin , Öztürk Gürkan
Published: January 2020

Mesenchymal stem cells are one of the promising tissue specific stem cell source for neural tissue regeneration applications. Previous studies on human mesenchymal stem cell (hMSC) derived neurons have been limited and not statisfactory in terms of neuronal activity. In this study, we analysed the functionality of bone marrow hMSCs differentiated into neural protein expressing cells by a single step cytokine based induction protocol. Neurons from both primary hMSCs and hMSC cell line displayed spontaneous activity (≥75%) as demonstrated by Ca++imaging. Furthermore, when electrically stimulated, hMSC induced neurons (hMd-Neuron) matched the response of a typical neuron in the process of maturation. Our results reveal that enriched neurothrophic factors enhance differentiation capacity of bone marrow hMSCs into high yielding functional neurons with spontaneous activity and mature into electrophysiologically active state. hMd-Neurons have the potential to be used as a tool for disease modelling of neuropathologies and neural differentiation studies.
Unrelated males in colonies of facultatively social bee
Authors: Mikát Michael , Benda Daniel , Straka Jakub
Published: January 2020

Colonies of social Hymenoptera are usually groups of closely related females, in which the dominant female(s) is specialized for reproduction and subordinate females care for immature offspring. Kin selection is thought to be the main factor that supports social cohesion. We have discovered a simple society of the beeCeratina chalybeawith an average of 4.68 colony members that cannot be maintained by kin selection alone. These colonies consisted of old reproductive female, young adults and provisioned brood cells. About half of young adults are unrelated to the old female, and almost all of the young adults are male. The old female provisions new brood cells, while continuing to feed young adult offspring. As young adults do not perform demanding or risky activities, they incur little or no cost, but they do benefit from the food they obtain from the old female.
RADX Sustains POT1 Function at Telomeres to Counteract RAD51 Binding, which Triggers Telomere Fragility
Authors: Briod Anna-Sophia , Glousker Galina , Lingner Joachim
Published: January 2020

The 3’ terminal DNA extensions at chromosome ends can become engaged into multiple biochemical reactions during DNA replication, telomerase-mediated telomere extension, homology directed DNA repair, nucleolytic processing and DNA damage checkpoint activation. To keep these activities in check, telomeric 3’ overhangs can be hidden in t-loop structures or they associate with specialized proteins such as POT1. Here, we explore the telomeric microenvironment using a proximity-dependent labeling approach and identify the oligonucleotide/oligosaccharide-binding (OB)-fold containing protein RADX. RADX binds single-stranded telomeric DNA throughout the cell cycle along with POT1, suppressing accumulation of fragile telomeres, which are indicative of telomere replication defects. Telomere fragility in POT1 and RADX double-depleted cells was due to accumulation of the RAD51 recombinase at telomeres. RADX also supports DNA damage signaling at POT1-depleted telomeres counteracting RAD51 binding. Thus, RADX represents next to POT1 a second OB-fold containing single-strand telomere binding protein sustaining telomere protection.
Crystal structure and interaction studies of human DHTKD1 provide insight into a mitochondrial megacomplex in lysine catabolism
Authors: Bezerra Gustavo A. , Foster William R. , Bailey Henry J. , Hicks Kevin G. , Sauer Sven W. , Dimitrov Bianca , Okun Jürgen G. , Rutter Jared , Kölker Stefan , Yue Wyatt W.
Published: January 2020

DHTKD1 is a lesser-studied E1 enzyme belonging to the family of 2-oxoacid dehydrogenases. DHTKD1, in complex with the E2 (dihydrolipoamide succinyltransferase, DLST) and E3 (lipoamide dehydrogenase, DLD) components, is implicated in lysine and tryptophan catabolism by catalysing the oxidative decarboxylation of 2-oxoadipate (2OA) in the mitochondria. Here, we solved the crystal structure of human DHTKD1 at 1.9 Å resolution in binary complex with the thiamine diphosphate (ThDP) cofactor. Our structure explains the evolutionary divergence of DHTKD1 from the well-characterized homologue 2-oxoglutarate (2OG) dehydrogenase, in its preference for the larger 2OA substrate than 2OG. InheritedDHTKD1missense mutations cause the lysine metabolic condition 2-aminoadipic and 2-oxoadipic aciduria. Reconstruction of the missense variant proteins reveal their underlying molecular defects, which include protein destabilisation, disruption of protein-protein interactions, and alterations in the protein surface. We further generated a 5.0 Å reconstruction of the human DLST inner core by single-particle electron microscopy, revealing a 24-mer cubic architecture that serves as a scaffold for assembly of DHTKD1 and DLD. This structural study provides a starting point to develop small molecule DHTKD1 inhibitors for probing mitochondrial energy metabolism.
Effect of flagellar beating pattern on sperm rheotaxis and boundary-dependent navigation
Authors: Zaferani Meisam , Javi Farhad , Mokhtare Amir , Abbaspourrad Alireza
Published: January 2020

The study of navigational mechanisms used by mammalian sperm inside a microenvironment yields better understanding of sperm locomotion during the insemination process, which aids in the design of tools for overcoming infertility. Near- and far-field hydrodynamic interactions with nearby boundaries and rheotaxis are known to be some of the steering strategies that keep sperm on the correct path toward the egg. However, it is not known how the beating patterns of sperm may influence these navigational strategies. In this study, we investigate the effect of flagellar beating pattern on navigation of sperm cells both theoretically and experimentally using a two-step approach. We first isolate bovine sperm based on their rheotactic behavior in a zone with quiescent medium using a microfluidic system. This step ensures that the swimmers are able to navigate upstream and have motilities higher than a selected value, even though they feature various flagellar beating patterns. We then explore the flagellar beating pattern of these isolated sperm and their subsequent influence on boundary-dependent navigation. Our findings indicate that rheotaxis enables sperm to navigate upstream even in the presence of circular motion in their motility, whereas boundary-dependent navigation is more sensitive to the circular motion and selects for progressive motility. This finding may explain the clinical importance of progressive motility in semen samples for fertility, as the flow of mucus may not be sufficiently strong to orient the sperm cells throughout the process of insemination.

Significance

Finding the egg and moving toward it while traversing the complex structure of the female reproductive tract is necessary for mammalian sperm. Previous studies have shown how sperm use navigational steering mechanisms that are based on swimming upstream (i.e. rheotaxis) and along the boundaries of the female reproductive tract. We demonstrate that the performance of theses navigational mechanisms is associated with the primary characteristics of sperm motility. In fact, sperm rheotaxis is more sensitive to the motility and thus average velocity of sperm while navigation via rigid boundaries is more sensitive to the flagellar beating pattern and selects for symmetric beating. Our results can be expanded to other autonomous microswimmers and their subsequent navigation mechanisms.
Synthesis, crystal structure and spectroscopic and Hirshfeld surface analysis of 4-hydroxy-3-methoxy-5-nitrobenzaldehyde
Authors: Vusak Vitomir , Vusak Darko , Molcanov Kresimir , Ernest Mestrovic
Published: January 2020

The title compound, C8H7NO5, is planar with an r.m.s. deviation for all non-hydrogen atoms of 0.018 Å. An intramolecular O—H...O hydrogen bond involving the adjacent hydroxy and nitro groups forms an S(6) ring motif. In the crystal, molecules are linked by O—H...O hydrogen bonds, forming chains propagating along the b-axis direction. The chains are linked by C—H...O hydrogen bonds, forming layers parallel to the bc plane. The layers are linked by a further C—H...O hydrogen bond, forming slabs, which are linked by C=O...π interactions, forming a three-dimensional supramolecular structure. Hirshfeld surface analysis was used to investigate intermolecular interactions in the solid state. The molecule was also characterized spectroscopically and its thermal stability investigated by differential scanning calorimetry and by thermogravimetric analysis.
Dufour and Soret effects on Darcy-Forchheimer flow of second-grade fluid with the variable magnetic field and thermal conductivity
Authors: Khan Ambreen A. , Naeem S. , Ellahi R. , Sait Sadiq M. , Vafai K.
Published: January 2020

Purpose

This study aims to investigate the effect of two-dimensional Darcy-Forchheimer flow over second-grade fluid with linear stretching. Heat transfer through convective boundary conditions is taken into account.

Design/methodology/approach

Nonlinear coupled governing equations are tackled with a homotopy algorithm, while for numerical computation the computer software package BVPh 2.0 is used. The convergence analysis is also presented for the validation of analytical and numerical results.

Findings

Valuation for the impact of key parameters such as variable thermal conductivity, Dufour and Soret effects and variable magnetic field in an electrically conducted fluid on the velocity, concentration and temperature profiles are graphically illustrated. It is observed from the results that temperature distribution rises by Dufour number whereas concentration distribution rises by Soret number. The Forchheimer number and porosity parameter raise the skin friction coefficient. The permeable medium has a vital impact and can help in reining the rate of heat transfer.

Practical implications

The permeable medium has a vital impact and can help in reining the rate of heat transfer.

Originality/value

To the best of the authors’ knowledge, this study is reported for the first time.
Preemptive scheduling with transportation delays between machines
Authors: Badaoui Ryma Zineb , Boudhar Mourad , Dahane Mohammed
Published: January 2020

Purpose

This paper studies the preemptive scheduling problem of independent jobs on identical machines. The purpose of this paper is to minimize the makespan under the imposed constraints, namely, the ones that relate the transportation delays which are required to transport a preempted job from one machine to another. This study considers the case when the transportation delays are variable.

Design/methodology/approach

The contribution is twofold. First, this study proposes a new linear programming formulation in real and binary decision variables. Then, this study proposes and implements a solution strategy, which consists of two stages. The goal of the first stage is to obtain the best machines order using a local search strategy. For the second stage, the objective is to determine the best possible sequence of jobs. To solve the preemptive scheduling problem with transportation delays, this study proposes a heuristic and two metaheuristics (simulated annealing and variable neighborhood search), each with two modes of evaluation.

Findings

Computational experiments are presented and discussed on randomly generated instances.

Practical implications

The study has implications in various industrial environments when the preemption of jobs is allowed.

Originality/value

This study proposes a new linear programming formulation for the problem with variable transportation delays as well as a corresponding heuristic and metaheuristics.