bluuebunny/crossref_metadata_2025 huggingface dataset:
Parameters of Fibrinolysis in Peritoneal Fluid and Plasma in Different Stages of the Menstrual Cycle
Authors: Dörr P J , Brommer E J P , Dooijewaard G , Vemer H M
Published: July 2018

The purpose of this study was to investigate differences in fibrinolytic activity in peritoneal fluid and plasma of women in the first and second part of the menstrual cycle. Given the classic concept of decreased fibrinolytic activity as a cause of adhesion formation, and if such differences are found, the stage of women’s menstrual cycle should be taken into consideration when scheduling a laparotomy.

We measured fibrinolytic parameters in peritoneal fluid and plasma in eight women in the pre-ovulatory period and in eleven women in the post-ovulatory period of the menstrual cycle.

There were no differences in t-PA-Ag, t-PA-Act, u-PA-Ag and scu-PA concentrations in peritoneal fluid between the pre- and post-ovulatory group. Nevertheless, PAI-1-Ag in peritoneal fluid was three-fold higher in the post-ovulatory phase (p <0.02). In peritoneal fluid the concentrations of both TDP and FbDP were three-fold higher at the same phase (p ≥0.05).

Plasma u-PA-Ag and scu-PA concentrations were significantly lower (30%, p <0.05) in the post-ovulatory phase and also lower than plasma u-PA-Ag and scu-PA (measured with the same assay) in a group of 50 healthy individuals. No differences in t-PA and PAI concentration were found.

In conclusion, the intraperitoneal fibrinolytic capacity might be impaired in the second part of the menstrual cycle, regarding the elevated levels of PAI-1-Ag, leading to an increased risk for postovulatory adhesion formation. The low plasma u-PA-Ag and scu- PA levels post-ovulatory may have clinical relevance.
Lithium Inhibits Adenylate Cyclase of Human Platelets
Authors: Imandt Leon , Tijhuis Dorien , Wessels Hans , Haanen Clemens
Published: July 2018

The ADP-induced aggregation of human platelets is markedly increased after preincubation with lithiumchloride, whereas lithium has the opposite effect on rabbit platelets. Since this phenomenon might be related to cAMP metabolism, the influence of lithium on total cAMP content and adenylate cyclase activity was investigated. Lithium does not significantly change the total cAMP content of human platelets neither during incubation nor during ADP-induced aggregation. Basal adenylate cyclase activity, however, was slightly inhibited by lithium in human platelets. The inhibition of adenylate cyclase by ADP appeared to be enhanced by lithium. Prostacyclin induced stimulation of adenylate cyclase is counteracted by this ion.

In rabbit platelets the prostacyclin stimulated adenylate cyclase activity is not affected by lithium.

These data suggest that a correlation exists between the influence of lithium on the aggregation of human and rabbit platelets and the sensitivity of their adenylate cyclase for this ion.
A Factor VIII Neutralizing Monoclonal Antibody and a Human Inhibitor Alloantibody Recognizing Epitopes in the C2 Domain Inhibit Factor VIII Binding to von Willebrand Factor and to Phosphatidylserine
Authors: Shima Midori , Scandella Dorothea , Yoshioka Akira , Nakai Hiroaki , Tanaka Ichiro , Kamisue Seiki , Terada Shigeki , Fukui Hiromu
Published: July 2018

A neutralizing monoclonal antibody, NMC-VIII/5, recognizing the 72 kDa thrombin-proteolytic fragment of factor VIII light chain was obtained. Binding of the antibody to immobilized factor VIII (FVIII) was completely blocked by a light chain-specific human alloantibody, TK, which inhibits FVIII activity. Immunoblotting analysis with a panel of recombinant protein fragments of the C2 domain deleted from the amino-terminal or the carboxy-terminal ends demonstrated binding of NMC-VIII/5 to an epitope located between amino acid residues 2170 and 2327. On the other hand, the epitope of the inhibitor alloantibody, TK, was localized to 64 amino acid residues from 2248 to 2312 using the same recombinant fragments. NMC-VIII/5 and TK inhibited FVIII binding to immobilized von Willebrand factor (vWF). The IC50 of NMC-VIII/5 for the inhibition of binding to vWF was 0.23 μg/ml for IgG and 0.2 μg/ml for F(ab)'2. This concentration was 100-fold lower than that of a monoclonal antibody NMC-VIII/10 which recognizes the amino acid residues 1675 to 1684 within the amino-terminal portion of the light chain. The IC50 of TK was 11 μg/ml by IgG and 6.3 μg/ml by F(ab)'2. Furthermore, NMC-VIII/5 and TK also inhibited FVIII binding to immobilized phosphatidylserine. The IC50 for inhibition of phospholipid binding of NMC-VIII/5 and TK (anti-FVIII inhibitor titer of 300 Bethesda units/mg of IgG) was 10 μg/ml.
Potentiating Effect of Clopidogrel and SR 46349, a Novel 5-HT2 Antagonist, on Streptokinase-Induced Thrombolysis in the Rabbit
Authors: Herbert J M , Bernat A , Sainte-Marie M , Dol F , Rinaldi M
Published: July 2018

Current thrombolytic strategies have a number of important shortcomings including resistance to recanalization and development of acute reocclusion. The purpose of this study was to investigate whether the lysis of venous thrombi by streptokinase could be enhanced by SR 46349, a novel 5-HT2 receptor antagonist, or clopidogrel, an analogue of ticlopidine. The activity of these compounds was evaluated by following the lysis of radiolabelled fibrin under a continuous infusion of streptokinase (4,000 IU kg−1 h−1 over 4 h). Streptokinase alone induced 42% thrombolysis when compared to saline. The i. v. co-administration of SR 46349 or clopidogrel (10 mg/kg) enhanced significantly streptokinase-induced thrombolysis. Thrombolysis measured by [125I]-fibrinogen lysis increased to 65 and 59% respectively. This efficacy was achieved without additional prolongation of the template bleeding time observed with streptokinase alone.

Thus, the concomitant use of a 5-HT2 receptor antagonist or an anti-ADP agent during streptokinase therapy may facilitate clot lysis.
Platelet Factor XIII Becomes Active without the Release of Activation Peptide during Platelet Activation
Authors: Muszbek László , Polgár János , Boda Zoltán
Published: July 2018

The potentially active A subunit of factor XIII of blood coagulation has also been detected in platelets and monocytes/macrophages though the exact function of this cellular protransglutaminase has not yet been elucidated. In physiological conditions the first step in the activation of plasma factor XIII is the removal of an activation peptide from the N-terminal end of subunit A by thrombin. The A subunit then, in the presence of Ca2+, dissociates from the inhibitory B subunit and assumes an active conformation. Cellular factor XIII, which lacks B subunit, can be proteolytically activated in vitro by thrombin and the intracellular Ca2+ sensitive protease, calpain, in the same way as plasma factor XIII subunit A, and calpain has been suggested as the intracellular protease involved in the activation of cellular factor XIII in platelets. In the present experiments it was shown by SDS PAGE that during long-term stimulation of platelets with thrombin nondisulfide-crosslinked high M
r protein polymers not penetrating the concentrating gel were formed. The lack of these polymers in thrombin-stimulated factor XIII deficient platelets clearly indicated that their formation in normal platelets was due to factor XIII that became active during platelet activation. However, no release of the activation peptide could be detected by Western blotting during this process. Similarly, no proteolytic cleavage of factor XIII was detectable when platelets were stimulated by Ca2+ ionophore through this stimulus activated calpain as it was clearly demonstrated by the breakdown of major intracellular calpain substrates. The results indicate: 1) during thrombin induced platelet activation factor XIII becomes active and crosslinks platelet protein, 2) platelet factor XIII is not an intracellular substrate of calpain, 3) cellular factor XIII could be activated without the proteolytic removal of activation peptide. It is presumed that the nonproteolytic pathway for the activation of cellular factor XIII, we reported most recently, might have physiological implications under such conditions.
The Pharmacokinetics of LMW Dermatan Sulphate: Long-Term Persistence of Intact Material
Authors: Dawes Joan
Published: July 2018

An iodinated derivative of the low molecular weight dermatan sulphate Desmin 370 was administered to rats by intravenous, subcutaneous and intramuscular routes in conjunction with unlabelled Desmin 370. Following intravenous injection radiolabel was cleared from the plasma according to a tri-exponential function with elimination half-lives of 45 min and 13 h; there was a high concentration in tissues, particularly the kidney, compared with plasma. The apparent bioavailability following s. c. injection was 52-65%, but 84-100% after i. m. administration. Undegraded as well as desulphated molecules were identified in plasma, and intact 125I-Desmin 370 comprised > 85% of the radiolabel in urine 48 h post-injection. Thus intact Desmin 370 persists for a long period after a single injection. The pharmacological significance of these findings, however, remainsto be determined.
Single Step Purification of Platelet Factor XIII Using an Immobilized Factor XIII A-Subunit Monoclonal Antibody
Authors: Lukacova Daniela , Reed Guy L
Published: July 2018

To facilitate the analysis of the catalytic subunit of factor XIII we have developed a method for the immunoaffinity purification of this protein from platelets. This method employs a monoclonal antibody that binds to the a-subunit of factor XIII. The anti-factor XIII antibody was immobilized on agarose and then incubated with platelet lysate. Subsequently factor XIII was isolated from the platelet lysate in a single step with a 41% yield as measured by enzyme assay. The purified platelet factor XIII appeared nearly homogeneous when analyzed by polyacrylamide electrophoresis and by immunoblotting with another factor XIII monoclonal antibody.
Dialysis and Renal Transplant in a Hemophiliac
Authors: Gomperts Edward D , Malekzadeh Mohammed H , Fine Richard N
Published: July 2018

Hemodialysis was initiated in a mild-moderate hemophiliac at 15 years of age. Hematuria had been a frequent and persisting feature from the age of five years without documented cause. Anemia and proteinuria was first detected at 13 years. A cadaver donor renal transplant was carried out after three months of hemodialysis. Massive intravesical bleeding complicated the immediate post-transplantation period. The allograft rejected after three months and the patient was maintained for eight years on home hemodialysis. A second cadaver donor allograft was
carried out at 23 years of age. Again, massive intravesical hemorrhage was a problem post-transplant. The allograft is currently functioning 27 months post-transplant. Factor VIIIc activities have fluctuated between 5% and 40% in the absence of factor infusions.
Neutralization of Human Extrinsic (Tissue-Type) Plasminogen Activator in Human Plasma: No Evidence for a Specific Inhibitor
Authors: Korninger C , Collen D
Published: July 2018

Human extrinsic plasminogen activator (EPA), highly purified from a melanoma cell culture fluid is inactivated in human plasma with a half-life (t ½) of 90–105 min. Gel filtration on Ultrogel AcA 34 of mixtures of 125I-labeled EPA and human plasma, incubated at 37°C, revealed the progressive formation of two radioactive components, one with an apparent Mr of 150,000 and one eluting at the void volume. The component with an Mr of 150,000 was identified as consisting at least in part of EPA-α2-antiplasmin complex since: 1) it reacted with antibodies against α2-antiplasmin, but not with antibodies against the other known plasma protease inhibitors, and 2) formation of this component was strongly reduced in plasma specifically depleted in α2-antiplasmin or when the active site of EPA was blocked. The component eluting at the void volume was identified as consisting at least in part of EPA-α2-macroglobulin complex since: 1) it only reacted with antibodies against these two proteins and 2) was not formed in plasma depleted in α2-macroglobulin or when the active site of EPA was blocked.

In purified systems α2-antiplasmin inhibited one-chain EPA with a rate constant of 60 M-1s-1 and two-chain EPA with a rate constant of 130 M-1s-1, which corresponds to a t ½ in plasma of 180 min or 90 min, respectively. α2-Macroglobulin inhibited one-chain EPA with a rate constant of 15 M-1s-1 and two-chain EPA with a rate constant of 30 M-1s-1, which corresponds to a t ½ plasma of 4 or 2 hrs.

All these findings taken together indicate that EPA is slowly neutralized in human plasma primarily by α2-antiplasmin and to a lesser extent by α2-macroglobulin. There appears to be no specific inhibitor in human plasma, which would inactivate EPA either rapidly or to a significant extent.
Essential Athrombia
Authors: Khanduri U , Pulimood R , Sudarasanam A , Carman R H , Jadhav M , Pereira S , Pulimood B M
Published: July 2018

Four cases of essential athrombia have been diagnosed in the 14 year period from June, 1966 to June, 1980 at the Coagulation Laboratory of the Christian Medical College Hospital, Vellore. All cases fit Inceman’s description of the original case and fulfill the diagnostic criteria of prolonged bleeding time, decreased platelet aggregation, normal platelet count, normal morphology and normal clot retraction. No cases have been reported from India in the past 15 years.
Dynamics of a flexible superhydrophobic surface during a drop impact
Authors: Kim Jeong-Hyun , Rothstein Jonathan P. , Shang Jessica K.
Published: July 2018

In this study, coupled dynamic responses of flexible superhydrophobic surfaces during a drop impact were investigated with position sensing and high-speed imaging. A smooth polydimethylsiloxane surface was spray coated with commercially available superhydrophobic paint particles. The influence of initial and subsequent impacts of a water droplet on the surface dynamics was studied at various natural frequencies of the surface (50 < fs < 230 Hz) and Weber numbers (2 < We < 90). We discovered that the flexible superhydrophobic surface was deflected twice during contact of the droplet by an impact force of the droplet as well as its reaction force during recoil. The magnitude of the droplet reaction force was estimated to be comparable to the droplet impact force. As the Weber number increased, however, the influence of the droplet reaction force on the surface displacement was attenuated because of the instability of the droplet rim. The contact time of the droplet and surface dynamics were found to be dependent on the phase of the surface. The contact time was reduced as much as 7% when a completion of the droplet spreading matched to the upward motion of the surface. One of the two local minima of the surface position observed during the contact of the droplet was diminished by matching the instance of the droplet reaction force to the downward motion of the surface. This study provides new insight into the effect of the droplet reaction force on dynamics of flexible superhydrophobic surfaces.
Inducing movement controls the emission of a random laser
Authors: Cesare Chris
Published: July 2018

A new technique actuates a composite material made of liquid crystal elastomers and nanoparticles, allowing researchers to move the material into the path of a pump laser and activate the generation of coherent light.
Only recent sexual partners contribute to oropharyngeal gonorrhoea positivity: the number of sexual partners over different time periods as an indicator of gonorrhoea and chlamydia infection duration among men who have sex with men
Authors: Priest David , Read Tim R. H. , Chen Marcus Y. , Bradshaw Catriona S. , Fairley Christopher K. , Chow Eric P. F.
Published: July 2018

Background Mathematical models have demonstrated that the majority of gonococcal transmission is from oropharynx to oropharynx (i.e. kissing) among men who have sex with men (MSM). The aim of this study is to investigate the association between the number of partners within specific time periods and gonorrhoea and chlamydia positivity. Methods: This was a retrospective data analysis of MSM attending the Melbourne Sexual Health Centre between 2007 and 2016. Univariable and multivariable logistic regression analyses, with generalised estimating equations (GEE), were performed to determine if the number of partners within specified time periods was associated with site-specific gonorrhoea and chlamydia positivity. Results: There were 45933 consultations which included 15197 MSM. Oropharyngeal gonorrhoea positivity was associated with the number of partners in the past 3 months, but not the number of partners 4–12 months ago; men who had ≥6 partners in the past 3 months had significantly higher odds of acquiring oropharyngeal gonorrhoea (aOR 1.93; 95% CI 1.61–2.31), but this was not the case for men who had ≥6 partners 4–12 months ago. Anorectal gonorrhoea and chlamydia and urethral chlamydia were associated with the number of partners in both time periods after adjusting for age and condom use. Conclusions: The association of oropharyngeal gonorrhoea with the number of recent partners, but not partners from an earlier period, unlike anorectal gonorrhoea and anorectal and urethral chlamydia, could be explained by a shorter duration of oropharyngeal gonococcal infection. Annual screening for gonorrhoea may be insufficient to materially reduce oropharyngeal prevalence.
One-step fabrication of biomimetic PVDF-BaTiO3 nanofibrous
composite using DoE
Authors: Ramesh Dinesh , D’Souza Nandika Anne
Published: July 2018

Dielectric polyvinylidene fluoride (PVDF) and Barium titanate
(BaTiO3)-PVDF nano-fibrous composites were made using the
electrospinning process based on a design of experiments approach. An
ultrasonication process was optimized using 2
k

factorial DoE approach to disperse BaTiO3 particles in PVDF solution
in DMF. Scanning electron microscopy was used to characterize the microstructure
of the fabricated mesh. The FT-IR and Raman analysis were carried out to
investigate the crystal structure of the prepared mesh. Surface morphology
contribution to the adhesive property of the composite was explained through
contact angle measurements. The capacitance of the prepared
PVDF-BaTiO3 nanofibrous mesh was a more than 40% increase
over the pure PVDF nanofibers. The results obtained indicates that
electrospinning offers a potential way to produce nanofibers with desired
crystalline nature which was not observed in molded samples. In addition,
BaTiO3 can be used to increase the capacitance, desired surface
characteristics of the PVDF nanofibers which can find potential application as
flexible piezoelectric sensor mimicking biological skin for use in structural
health monitoring applications.
Constructing disease onset signatures using multi-dimensional network-structured biomarkers
Authors: Li Xiang , Zeng Donglin , Marder Karen , Wang Yuanjia
Published: July 2018

Potential disease-modifying therapies for neurodegenerative disorders need to be introduced prior to the symptomatic stage in order to be effective. However, current diagnosis of neurological disorders mostly rely on measurements of clinical symptoms and thus only identify symptomatic subjects in their late disease course. Thus, it is of interest to select and integrate biomarkers that may reflect early disease-related pathological changes for earlier diagnosis and recruiting pre-sypmtomatic subjects in a prevention clinical trial. Two sources of biological information are relevant to the construction of biomarker signatures for time to disease onset that is subject to right censoring. First, biomarkers’ effects on disease onset may vary with a subject’s baseline disease stage indicated by a particular marker. Second, biomarkers may be connected through networks, and their effects on disease may be informed by this network structure. To leverage these information, we propose a varying-coefficient hazards model to induce double smoothness over the dimension of the disease stage and over the space of network-structured biomarkers. The distinctive feature of the model is a non-parametric effect that captures non-linear change according to the disease stage and similarity among the effects of linked biomarkers. For estimation and feature selection, we use kernel smoothing of a regularized local partial likelihood and derive an efficient algorithm. Numeric simulations demonstrate significant improvements over existing methods in performance and computational efficiency. Finally, the methods are applied to our motivating study, a recently completed study of Huntington’s disease (HD), where structural brain imaging measures are used to inform age-at-onset of HD and assist clinical trial design. The analysis offers new insights on the structural network signatures for premanifest HD subjects.
Strong-lensing measurement of the total-mass-density profile out to three effective radii for z ∼ 0.5 early-type galaxies
Authors: Li Rui , Shu Yiping , Wang Jiancheng
Published: July 2018

We measure the total-mass-density profiles out to three effective radii for a sample of 63$z$ ∼ 0.5, massive early-type galaxies (ETGs) acting as strong gravitational lenses through a joint analysis of lensing and stellar dynamics. The compilation is selected from three galaxy-scale strong-lens samples, namely the Baryon Oscillation Spectroscopic Survey (BOSS) Emission-Line Lens Survey (BELLS), the BELLS for GALaxy-Lyα EmitteR sYstems Survey (BELLS GALLERY), and the Strong Lensing Legacy Survey (SL2S). Utilizing the wide source-redshift coverage (0.8–3.5) provided by these three samples, we build a statistically significant ensemble of massive ETGs for which robust mass measurements can be achieved within a broad range of Einstein radii up to three effective radii. Characterizing the three-dimensional total-mass-density distribution by a power-law profile as ρ ∝ r−γ, we find that the average logarithmic density slope for the entire sample is $\langle \gamma \rangle =2.000_{-0.032}^{+0.033}$ (68 per cent CL) with an intrinsic scatter of $\delta =0.180_{-0.028}^{+0.032}$. Further parametrizing 〈γ〉 as a function of redshift $z$ and the ratio of Einstein radius to effective radius Rein/Reff, we find that the average density distributions of these massive ETGs become steeper at later cosmic times and at larger radii, with magnitudes $\mathrm{d} \langle \gamma \rangle / \mathrm{d}z=-0.309_{-0.160}^{+0.166}$ and $\mathrm{d} \langle \gamma \rangle / \mathrm{d} \log _{10} ({R_{\rm ein}}/{R_{\rm eff}})=0.194_{-0.083}^{+0.092}$.
Rhizosphere Fungal Community Dynamics Associated with Rehmannia glutinosa Replant Disease in a Consecutive Monoculture Regime
Authors: Wu Linkun , Chen Jun , Khan Muhammad Umar , Wang Juanying , Wu Hongmiao , Xiao Zhigang , Zhang Zhongyi , Lin Wenxiong
Published: July 2018

Consecutive monoculture of Rehmannia glutinosa in the same field leads to a severe decline in both quality and yield of tuberous roots, the most useful part in traditional Chinese medicine. Fungi are an important and diverse group of microorganisms in the soil ecosystem and play crucial roles in soil health. In this study, high-throughput pyrosequencing of internal transcribed spacer 2 ribosomal DNA amplicons was applied to gain insight into how consecutive monoculture practice influence and stimulate R. glutinosa rhizosphere and bulk soil fungal communities. The results from nonmetric multidimensional scaling ordination and clustering analysis revealed distinctive differences between rhizosphere and bulk soil fungal communities. However, longer-term monocultured bulk soils were more similar to the rhizosphere soils in comparison with the shorter-term monocultured bulk soils. Moreover, consecutive monoculture caused a gradual shift in the composition and structure of the soil fungal community. The cultivation of this plant led to the appearance of some exclusive operational taxonomic units in rhizosphere or bulk soils that were assigned to the genera Fusarium, Rhizoctonia, and so on. Furthermore, the sum of the relative abundance of species of Fusarium, Cylindrocarpon, and Gibberella (belonging to the family Nectriaceae); Rhizoctonia, Thanatephorus, and Ceratobasidium (belonging to the family Ceratobasidiaceae); and Lectera and Plectosporium (belonging to the family Plectosphaerellaceae) was significantly higher in consecutively monocultured (CM) than in newly planted (NP) soil in both rhizosphere and bulk soils. In particular, Fusarium abundance was significantly higher in CM than in NP in the rhizosphere, and higher in rhizosphere soils than in bulk soils for each treatment. A pathogenicity test showed that both Fusarium strains isolated were pathogenic to R. glutinosa seedlings. In addition, the culture filtrate and mycotoxins produced by Fusarium oxysporum significantly repressed the growth of the antagonistic bacterium, Pseudomonas aeruginosa. In conclusion, consecutive monoculture of R. glutinosa restructured the fungal communities in both rhizosphere and bulk soils but bulk effects developed more slowly over time in comparison with rhizosphere effects. Furthermore, microbial interactions might lead to a reduction in the abundance of beneficial microbes.
Can Neuropathic Pain Predict Response to Arthroplasty in Knee Osteoarthritis? A Prospective Observational Cohort Study
Authors: Soni Anushka , Leyland Kirsten M , Kiran Amit , Arden Nigel K , Cooper Cyrus , Wanigasekera Vishvarani , Tracey Irene , Javaid M Kassim , Price Andrew J
Published: July 2018

A significant proportion of patients with knee osteoarthritis (OA) continue to have severe ongoing pain following knee replacement surgery. Central sensitization and features suggestive of neuropathic pain before surgery may result in a poor outcome post-operatively. In this prospective observational study of patients undergoing primary knee arthroplasty (n=120), the modified PainDETECT score was used to divide patients, with primary knee OA, into nociceptive (<13), unclear (13–18) and neuropathic -like pain (>18) groups pre-operatively. Response to surgery was compared between groups using the Oxford Knee Score (OKS) and the presence of moderate to severe long-term pain 12 months after arthroplasty. The analyses were replicated in a larger independent cohort study (n=404). 120 patients were recruited to the main study cohort: 63 (52%) nociceptive pain; 32 (27%) unclear pain; 25 (21%) neuropathic-like pain. Patients with neuropathic-like pain had significantly worse OKS pre and post-operatively, compared to the nociceptive pain group, independent of age, sex and BMI. At 12-months post-operatively the mean OKS was 4 points lower in the neuropathic-like group compared with the nociceptive group in the study cohort (non-significant); with a difference of 5 points in the replication cohort (p<0.001). Moderate to severe long-term pain after arthroplasty at 12-months was present in 50% of the neuropathic-like pain group versus 24% in the nociceptive pain group, in the replication cohort (p<0.001). Neuropathic pain is common and targeted therapy pre, peri and post-operatively may improve treatment response.
Illuminating women’s hidden contribution to the foundation of theoretical population genetics
Authors: Dung Samantha Kristin , López Andrea , Barragan Ezequiel Lopez , Reyes Rochelle-Jan , Thu Ricky , Castellanos Edgar , Catalan Francisca , Sanchez Emilia Huerta , Rohlfs Rori V.
Published: July 2018

Plentiful evidence shows an historic and continuing gender gap in participation and success in scientific research. However, less attention has been directed at clarifying obscured contributions of women to science. The lack of visible women role models (particularly in computational fields) contributes to a reduced sense of belonging and retention among women. We seek to counteract this cycle by illuminating the contribution of women programmers to the foundation of our own fields—population and evolutionary genetics. We consider past ‘acknowledged programmers’ (APs), who developed, ran, and sometimes analyzed the results of early computer programs. Due to authorship norms at the time, these programmers were credited in the acknowledgments sections of manuscripts, rather than being recognized as authors. For example, one acknowledgement reads “I thanks Mrs. M. Wu for help with the numerical work, and in particular for computing table I.”. We identified APs inTheoretical Population Biologyarticles published between 1970 and 1990. While only 7% of authors were women, 43% of APs were women. This significant difference (p = 4.0×10−10) demonstrates a substantial proportion of women’s contribution to foundational computational population genetics has been unrecognized. The proportion of women APs, as well as number of APs decreased over time. These observations correspond to the masculinization of computer programming, and the shifting of programming responsibilities to individuals credited as authors (likely graduate students). Finally, we note recurrent APs who contributed to several highly-cited manuscripts. We conclude that, while previously overlooked, historically, women have made substantial contributions to computational biology.
Why mediation analysis trumps Mendelian randomization in population epigenomics studies of the Dutch Famine
Authors: Tobi Elmar W. , van Zwet Erik W. , Lumey L.H. , Heijmans Bastiaan T.
Published: July 2018

Our recent analysis of genome-wide DNA methylation data in men and women exposed to the Dutch Famine met passionate criticism by several researchers active on Twitter. It also prompted a more reasoned letter by Richmond and colleagues. At the core of the debate is the proper interpretation of findings from a mediation analysis. We used this method to identify specific DNA methylation changes that statistically provide a link between prenatal exposure to famine and adult metabolic traits. Our critics first argue that our results do not suggest mediation but reverse-causation, where famine-induced metabolic traits drive changes in DNA methylation. We rebut this scenario in a simulation study showing that our test of mediation was unlikely to become statistically significant in the case of reverse-causation. Some critics then argue that Mendelian randomization provides the sole path to correct inference. This belief misses a crucial point: DNA methylation, especially when measured in peripheral blood, is not likely to be a causal mediator from a biological point of view. It could however be a proxy of epigenetic regulation changes in specific tissues, for example at the level of transcription factor binding. If so, a Mendelian randomization approach using genetic variants affecting local DNA methylation in blood will be disconnected from the underlying biological mechanism and is bound to yield false-negative results. Our new simulation studies strengthen the original reasoning that the relationship between prenatal famine and metabolic traits is statistically mediated by specific DNA methylation changes while the specific molecular mechanism awaits elucidation.
Evaluation of strategies for the assembly of diverse bacterial genomes using MinION long-read sequencing
Authors: Goldstein Sarah , Beka Lidia , Graf Joerg , Klassen Jonathan L.
Published: July 2018

Background

Short-read sequencing technologies have made microbial genome sequencing cheap and accessible. However, closing genomes is often costly and assembling short reads from genomes that are repetitive and/or have extreme %GC content remains challenging. Long-read, single-molecule sequencing technologies such as the Oxford Nanopore MinION have the potential to overcome these difficulties, although the best approach for harnessing their potential remains poorly evaluated.

Results

We sequenced nine bacterial genomes spanning a wide range of GC contents using Illumina MiSeq and Oxford Nanopore MinION sequencing technologies to determine the advantages of each approach, both individually and combined. Assemblies using only MiSeq reads were highly accurate but lacked contiguity, a deficiency that was partially overcome by adding MinION reads to these assemblies. Even more contiguous genome assemblies were generated by using MinION reads for initial assembly, but these were more error-prone and required further polishing. This was especially pronounced when Illumina libraries were biased, as was the case for our strains with both high and low GC content. Increased genome contiguity dramatically improved the annotation of insertion sequences and secondary metabolite biosynthetic gene clusters, likely because long-reads can disambiguate these highly repetitive but biologically important genomic regions.

Conclusions

Genome assembly using short-reads is challenged by repetitive sequences and extreme GC contents. Our results indicate that these difficulties can be largely overcome by using single-molecule, long-read sequencing technologies such as the Oxford Nanopore MinION. Using MinION reads for assembly followed by polishing with Illumina reads generated the most contiguous genomes and enabled the accurate annotation of important but difficult to sequence genomic features such as insertion sequences and secondary metabolite biosynthetic gene clusters. The combination of Oxford Nanopore and Illumina sequencing is cost effective and dramatically advances studies of microbial evolution and genome-driven drug discovery.
Searching for structure in collective systems
Authors: Twomey Colin R. , Hartnett Andrew T. , Grobis Matthew M. , Romanczuk Pawel
Published: July 2018

Collective systems such as fish schools, bird flocks, and neural networks are comprised of many mutually-influencing individuals, often without long-term leaders, well-defined hierarchies, or persistent relationships. The remarkably organized group-level behaviors readily observable in these systems contrast with the ad hoc, often difficult to observe, and complex interactions among their constituents. While these complex individual-level dynamics are ultimately the drivers of group-level coordination, they do not necessarily offer the most parsimonious description of a group’s macroscopic properties. Rather, the factors underlying group organization may be better described at some intermediate, mesoscopic scale. We introduce a novel method from information-theoretic first principles to find a compressed description of a system based on the actions and mutual dependencies of its constituents, thus revealing the natural structure of the collective. We emphasize that this method is computationally tractable and requires neither pairwise nor Gaussian assumptions about individual interactions.
An EDS1 EP-domain surface mediating timely transcriptional reprogramming of immunity genes
Authors: Bhandari Deepak D. , Lapin Dmitry , Kracher Barbara , von Born Patrick , Bautor Jaqueline , Niefind Karsten , Parker Jane E.
Published: July 2018

Plant intracellular NLR receptors recognize pathogen interference to trigger immunity. NLR signalling mechanisms have not been resolved. Enhanced disease susceptibility 1 (EDS1) heterodimers are recruited by Toll-interleukin1-receptor domain NLRs (TNLs) to transcriptionally mobilize resistance pathways. Using an Arabidopsis EDS1 heterodimer crystal structure we interrogate the conserved but functionally uncharacterized EDS1 α-helical EP-domain. We identify EP-domain positively charged residues lining a cavity that are essential for TNL immunity signalling, beyond heterodimer formation. Mutating arginine (R493) to alanine creates a weak EDS1 allele which disables TNL immunity against bacteria producing a virulence factor, coronatine (COR). Arabidopsis plants expressing EDS1R493A are slow to mobilize defence gene expression changes, independently of COR. The transcriptional delay has severe consequences for pathogen resistance and for countering bacterial COR. We uncover a set of host immunity genes whose repression by COR is blocked by wild-type EDS1 but not by EDS1R493A in the TNL response. These data uncover an EDS1 signalling surface lining the heterodimer EP-domain cavity which confers timely transcriptional reprogramming of host defence pathways and blocks bacterial virulence in NLR receptor immunity.
Sensing Plant Physiology and Environmental Stress by Automatically Tracking Fj and Fi Features in PSII Chlorophyll Fluorescence Induction
Authors: Xia Qian , Tan Jinglu , Cheng Shengyang , Jiang Yongnian , Guo Ya
Published: July 2018

Following a step excitation, chlorophyll fluorescence (ChlF) from photosystem II of a dark-adapted plant leaf exhibits the well-known OJIP pattern. The OJIP induction has been widely applied in plant science, agriculture engineering, and environmental engineering. While the J and I phases are related to transitions of photochemical reaction redox states, characteristic fluorescence intensities for the two phases (Fj and Fi) are often treated as fixed time points in routine measurement and thus do not account for variations in plant and experimental conditions, which (1) neglects the time differences, potentially useful information for characterizing plant status and environmental factors, and (2) leads to errors in measured Fj and Fi values. In this work, a method for consistent measurement of Fj and Fi was developed through polynomial fitting and curvature analysis. The method measures the curvatures in the OJIP curve and automatically tracks the characteristic transition points under variable sample and experimental conditions. Experiments were carried out to demonstrate the concept and classification capabilities of the developed method. This research established a new framework to analyze ChlF and enhanced the applications of ChlF.
A toolbox for nodule development studies in chickpea: a hairy-root transformation protocol and an efficient laboratory strain of Mesorhizobium sp
Authors: Mandal Drishti , Sinharoy Senjuti
Published: July 2018

Mesorhizobium sp. produces root nodules in chickpea. Chickpea and model legume Medicago truncatula are members of inverted repeat lacking clade (IRLC). The rhizobia after internalization inside plant cell called ‘bacteroid’. Nodule Specific Cysteine-rich (NCR) peptides in IRLC legumes guide bacteroids to a ‘terminally differentiated swollen (TDS)’ form. Bacteroids in chickpea are less TDS than those in Medicago. Nodule development in chickpea indicates recent evolutionary diversification and merits further study. A hairy root transformation protocol and an efficient laboratory strain are prerequisites for performing any genetic study on nodulation. We have standardized a protocol for composite plant generation in chickpea with a transformation frequency above 50%, as shown by fluorescent markers. This protocol also works well in different ecotypes of chickpea. Localization of subcellular markers in these transformed roots is similar to Medicago. When checked inside transformed nodules, peroxisomes were concentrated along the periphery of the nodules, while ER and golgi bodies surrounded the symbiosomes. Different Mesorhizobium strains were evaluated for their ability to initiate nodule development, and efficiency of nitrogen fixation. Inoculation with different strains resulted in different shapes of TDS bacteroids with variable nitrogen fixation. Our study provides a toolbox to study nodule development in the crop legume chickpea.
Notch signalling patterns retinal composition by regulatingatoh7during post-embryonic growth
Authors: Saturnino Alicia Pérez , Lust Katharina , Wittbrodt Joachim
Published: July 2018

Patterning of a continuously growing naive field in the context of a life-long growing organ, the teleost eye is of highest functional relevance. Intrinsic and extrinsic signals were proposed to regulate lineage specification in progenitors that exit the stem cell niche in the ciliary marginal zone (CMZ). The proper cell type composition arising from those progenitors is prerequisite for retinal function. Our findings in the teleost medaka (Oryzias latipes) uncover that the Notch–Atoh7 axis continuously patterns the CMZ. The complement of cell-types originating from the two juxtaposed progenitors marked by Notch or Atoh7 activity contains all constituents of a retinal column. Modulation of Notch signalling specifically in Atoh7-expressing cells demonstrates the crucial role of this axis in generating the correct cell type proportions. After transiently blocking Notch signalling, retinal patterning and differentiation is reinitiatedde novo. Taken together we show that Notch activity in the CMZ continuously structures the growing retina by juxtaposing Notch and Atoh7 progenitors giving rise to distinct, complementary lineages, revealing a coupling ofde novopatterning and cell-type specification in the respective lineages.
China feels the heat: negative impacts of high temperatures on China's rice sector
Authors: Chen Xiaoguang , Chen Shuai
Published: July 2018

We analysed a county‐level data set of single‐season rice yield and daily weather outcomes in China to examine the effects of temperature on China's rice sector. We found that rice yield exhibited highly nonlinear responses to temperature changes: rice yield increased with temperature up to 28°C and decreased sharply with higher temperatures. Holding current growing seasons and regions constant, average rice yield in China is projected to decrease by 10–19 per cent by 2050 and 11–33 per cent by 2070 due to future warming under the global climate models HadGEM2‐ES and NorESM1‐M. These results imply that future warming poses a major challenge for Chinese rice farmers and that the effectiveness of adaptations will depend on how well they reduce the negative temperature impacts on rice yield because of very hot days.
Prolonged balloon tamponade in the initial management of inferior vena cava injury following complicated filter retrieval, without the need for surgery
Authors: Lee Jonathan TL , Goh Gerard S , Joseph Tim , Koukounaras Jim , Phan Tuan , Clements Warren
Published: July 2018

Advanced techniques have been described to remove embedded inferior vena cava (IVC) filters including the loop snare and modified loop snare (Hangman) techniques. Retrieval of embedded filters have been associated with higher rates of complications including IVC injury and stenosis. We report two challenging embedded retrievals complicated by IVC injury and haemorrhage. Haemostasis was successfully achieved with prolonged balloon tamponade, suggesting that injury to the IVC during filter retrieval may not need urgent surgery. However, both patients received short‐term complications related to caval thrombosis and patients in this cohort should be closely observed after retrieval. These cases support rigorous attention to filter indication and follow‐up.
A 22‐Year Follow‐Up (Range 16 to 23) of Original Subjects with Baseline Alcohol Use Disorders from the Collaborative Study on Genetics of Alcoholism
Authors: Schuckit Marc A. , Smith Tom L. , Danko George , Kramer John , Bucholz Kathleen K. , McCutcheon Vivia , Chan Grace , Kuperman Samuel , Hesselbrock Victor , Dick Danielle M. , Hesselbrock Michie , Porjesz Bernice , Edenberg Howard J. , Nureberger John I. , Gregg Marcy , Schoen Lara , Kawamura Mari , Mendoza Lee Anne
Published: July 2018

Background

Recent reports indicate higher‐than‐expected problematic drinking in older populations. However, few data describe how to predict which older individuals are most likely to demonstrate alcohol‐related problems, including those with earlier alcohol use disorders (AUDs). These analyses evaluate predictors of alcohol outcomes in individuals with earlier AUDs in the Collaborative Study on Genetics of Alcoholism (COGA).

Methods

Original COGA participants with baseline AUDs at about age 40 were interviewed 13 to 26 years later and placed into clinically derived outcome categories. Chi‐square and analysis of variance evaluated baseline differences across 4 outcome groups, with significant items entered into binary logistic regression backwards elimination analyses predicting outcomes.

Results

Low‐Risk Drinkers (N = 100) at follow‐up were predicted by baseline higher levels of response to alcohol (high LRs), lower histories of alcohol treatment, experience with fewer types of illicit drugs, and were more likely to have been widowed. At follow‐up, Problem Drinkers (N = 192) differed from High‐Risk Drinkers (N = 93) who denied multiple alcohol problems by exhibiting baseline lower LRs, higher Sensation Seeking, and a higher proportion who were widowed. Abstinent (N = 278) outcomes were predicted by a history of higher baseline AUD treatments, higher alcohol problems, lower usual drinks, as well as older age and European American heritage. Thirty‐four subjects (4.9%) could not be classified and were not included in these analyses.

Conclusions

These results generated from AUD individuals from both treatment and nontreatment settings reinforce low probabilities of recent Low‐Risk Drinking in individuals with AUDs, but also suggest many individuals with AUDs demonstrate good outcomes 2 decades later.
The Stratification of Attendance at Cultural Activities in Canada
Authors: Vanzella‐Yang Adam
Published: July 2018

Scholars have debated the relative applicability of homology and omnivorousness, two theories of cultural stratification, for explaining links between socioeconomic position and cultural repertoires. However, the discussion has mostly focused on musical tastes rather than attendance at cultural activities. Using data from the 2010 Canadian General Social Survey on Time Use, I examine how measures of socioeconomic position predict attendance at 12 different kinds of cultural activities. I apply three analytical techniques to this data set: (1) binary logistic regressions to investigate the socioeconomic bases of attendance at each cultural activity; (2) ordered logistic regression to assess the nature of the relationship between socioeconomic position and omnivorous attendance; and (3) latent class analysis to identify clusters of attendance and the socioeconomic bases thereof. Controlling for demographic factors, I find that education and income are positively associated with attendance at each activity and with omnivorous cultural engagement. The latent class model reveals four distinct groups: highbrow omnivores, selective omnivores, univores, and inactive people. Education and income predict membership in the omnivorous groups, with stronger effects for highbrow omnivores. I confirm that omnivorousness is associated with cultural and economic elites, but also reveal different gradations of omnivorousness, thus suggesting that the two theoretical frameworks are to a degree entangled with one another.