bluuebunny/crossref_metadata_2025 huggingface dataset:
Ovarian insufficiency and CTNNB1 mutations drive malignant transformation of endometrial hyperplasia with altered PTEN/PI3K activities
Authors: Terakawa Jumpei , Serna Vanida Ann , Taketo Makoto Mark , Daikoku Takiko , Suarez Adrian A. , Kurita Takeshi
Published: February 2019

Significance

Our mouse model of endometrial cancer (EC) reveals the mechanism underlying the presence of multiple driver mutations in early EC along with the menopause-associated risk in endometrial carcinogenesis. Human ECs carry multiple driver mutations even when they are low grade, whereas a single driver mutation caused EC in previous mouse studies. Our study established that multiple driver mutations are essential for clonal expansion of preneoplastic epithelial cells within the anticancer environment of the normal endometrium. The tumor-suppressing activity of normal endometrium is maintained by estradiol and progesterone, indicating that menopause itself can promote ECs. In the absence of estradiol and progesterone, a
CTNNB1
mutation drives myometrial invasion and metastasis of ECs.
Compatibility of quantitative X-ray spectroscopy with continuous distribution models of water at ambient conditions
Authors: Niskanen Johannes , Fondell Mattis , Sahle Christoph J. , Eckert Sebastian , Jay Raphael M. , Gilmore Keith , Pietzsch Annette , Dantz Marcus , Lu Xingye , McNally Daniel E. , Schmitt Thorsten , Vaz da Cruz Vinicius , Kimberg Victor , Gel’mukhanov Faris , Föhlisch Alexander
Published: February 2019

Significance

Water is the matrix of life and behaves anomalously in many of its properties. Since Wilhelm Conrad Röntgen, two distinct separate phases have been argued to coexist in ambient water, competing with the alternative view of the single-phase liquid, footing on X-ray scattering experiment and theory. We conducted a quantitative and high-resolution X-ray spectroscopic multimethod investigation and analysis (X-ray absorption, X-ray emission, and resonant inelastic X-ray scattering). We find that all known X-ray spectroscopic observables can be fully and consistently described with continuous-distribution models of near-tetrahedral liquid water at ambient conditions with 1.74

±

2.1% donated and accepted H-bonds per molecule.
Dual AAV-mediated gene therapy restores hearing in a DFNB9 mouse model
Authors: Akil Omar , Dyka Frank , Calvet Charlotte , Emptoz Alice , Lahlou Ghizlene , Nouaille Sylvie , Boutet de Monvel Jacques , Hardelin Jean-Pierre , Hauswirth William W. , Avan Paul , Petit Christine , Safieddine Saaid , Lustig Lawrence R.
Published: February 2019

Significance

In humans, inner ear development is completed in utero, with hearing onset at ∼20 weeks of gestation. However, genetic forms of congenital deafness are typically diagnosed during the neonatal period. Gene therapy approaches in animal models should therefore be tested after the period of hearing onset, to determine whether they can reverse an existing deafness phenotype. Here, we used a mouse model of DFNB9, a human deafness form accounting for 2–8% of all cases of congenital genetic deafness. We show that local gene therapy in the mutant mice not only prevents deafness when administered to immature hearing organs, but also durably restores hearing when administered at a mature stage, raising hopes for future gene therapy trials in DFNB9 patients.
Genomic evidence for shared common ancestry of East African hunting-gathering populations and insights into local adaptation
Authors: Scheinfeldt Laura B. , Soi Sameer , Lambert Charla , Ko Wen-Ya , Coulibaly Aoua , Ranciaro Alessia , Thompson Simon , Hirbo Jibril , Beggs William , Ibrahim Muntaser , Nyambo Thomas , Omar Sabah , Woldemeskel Dawit , Belay Gurja , Froment Alain , Kim Junhyong , Tishkoff Sarah A.
Published: February 2019

Anatomically modern humans arose in Africa ∼300,000 years ago, but the demographic and adaptive histories of African populations are not well-characterized. Here, we have generated a genome-wide dataset from 840 Africans, residing in western, eastern, southern, and northern Africa, belonging to 50 ethnicities, and speaking languages belonging to four language families. In addition to agriculturalists and pastoralists, our study includes 16 populations that practice, or until recently have practiced, a hunting-gathering (HG) lifestyle. We observe that genetic structure in Africa is broadly correlated not only with geography, but to a lesser extent, with linguistic affiliation and subsistence strategy. Four East African HG (EHG) populations that are geographically distant from each other show evidence of common ancestry: the Hadza and Sandawe in Tanzania, who speak languages with clicks classified as Khoisan; the Dahalo in Kenya, whose language has remnant clicks; and the Sabue in Ethiopia, who speak an unclassified language. Additionally, we observed common ancestry between central African rainforest HGs and southern African San, the latter of whom speak languages with clicks classified as Khoisan. With the exception of the EHG, central African rainforest HGs, and San, other HG groups in Africa appear genetically similar to neighboring agriculturalist or pastoralist populations. We additionally demonstrate that infectious disease, immune response, and diet have played important roles in the adaptive landscape of African history. However, while the broad biological processes involved in recent human adaptation in Africa are often consistent across populations, the specific loci affected by selective pressures more often vary across populations.
Linking plasma formation in grapes to microwave resonances of aqueous dimers
Authors: Khattak Hamza K. , Bianucci Pablo , Slepkov Aaron D.
Published: February 2019

Significance

In a popular parlor trick, plasma is created by irradiating grape hemispheres in a household microwave oven. This work ties the source of the plasma to microwave photonic hotspots at the junction of aqueous dielectric spherical dimers. We use a combination of thermal-imaging techniques and computer simulations to show that grape-sized fruit and hydrogel beads form resonant cavities that concentrate electromagnetic fields to extreme subwavelength regions. This is enabled by the large dielectric susceptibility of water at microwave frequencies. Furthermore, the absorptive properties of water are key to washing out complex internal modes and for allowing the evanescent hotspot build-up. Our approach to microwave resonances in high-dielectric materials opens a sandbox for nanocluster photonics research.
Loss of BOP1 confers resistance to BRAF kinase inhibitors in melanoma by activating MAP kinase pathway
Authors: Gupta Romi , Bugide Suresh , Wang Biao , Green Michael R. , Johnson Douglas B. , Wajapeyee Narendra
Published: February 2019

Significance

Oncogenic mutations in the
BRAF
gene are found in ∼50% of melanomas and drive melanoma growth. Thus, BRAF kinase inhibitors (BRAFi), such as vemurafenib and dabrafenib, have been developed and used for the treatment of BRAF-mutant metastatic melanoma in clinic. However, the clinical benefits of BRAFi are temporary and short-lived due to the emergence of drug resistance. Although several mechanisms of acquired BRAFi resistance have been identified, the basis for acquired resistance remains unknown in over 40% of melanomas. Identifying a new mechanism of acquired resistance to BRAFi may provide new opportunities to effectively treat BRAF-mutant melanoma. In this study, we have identified Block of Proliferation 1 as a new factor the loss of which results in resistance to BRAFi.
Microstructure and mechanical properties of as-built and heat-treated electron beam melted Ti–6Al–4V
Authors: Syed Abdul Khadar , Awd Mustafa , Walther Frank , Zhang Xiang
Published: February 2019

This paper investigates the effect of post-deposition heat treatment on porosity, microstructure, and mechanical properties of Ti–6Al–4V produced via an Electron Beam Melting process. Samples were studied in the conditions of as-built and heat treated at 920°C and 1030°C. The as-built samples were characterised by columnar β grains consists of α+β microstructure with Widmanstätten and colony morphologies were found. Heat treatment resulted in increased α lath width. The yield strength and ultimate tensile strength was greater in the as-built condition than wrought material. Porosity re-growth occurred after heat treatment but it did not affect the tensile properties. Greater ductility after heat treatment was attributed to the larger α lath width which increases effective slip length.
A novel method of producing the key intermediate ASI-2 of ranirestat using a porcine liver esterase (PLE) substitute enzyme
Authors: Yamamura Ei-Tora , Tsuzaki Kazuya , Kita Shinji
Published: February 2019

(R)-2-amino-2-ethoxycarbonylsuccinimide (ASI-2) is a key intermediate used in the pharmaceutical industry and is valuable for the industrial synthesis of ranirestat, which is a potent aldose reductase inhibitor. ASI-2 was synthesized in a process combining chemical synthesis and bioconversion. Bioconversion in this study is a key reaction, since optically active carboxylic acid derivative ((R)-1-ethyl hydrogen 3-benzyloxycarbonylamino-3-ethoxycarbonylsuccinate, Z-MME-AE) is synthesized from a prochiral ester, diethyl 2-benzyloxycarbonylamino-2-ethoxycarbonylsuccinate, Z-MDE-AE, at a theoretical yield of 100%. Upon screening for microorganisms that asymmetrically hydrolyze Z-MDE-AE, Bacillus thuringiensis NBRC13866 was found. A novel esterase EstBT that produces Z-MME-AE was purified from Bacillus thuringiensis NBRC13866 and was stably produced in Escherichia coli JM109 cells. Using EstBT rather than porcine liver esterase (PLE), ASI-2 was synthesized with a 17% higher total yield by a novel method, suggesting that the esterase EstBT is a PLE substitute enzyme and therefore, may be of interest for future industrial applications.
Degradation of Blos1 mRNA by IRE1 repositions lysosomes and protects cells from stress
Authors: Bae Donghwi , Moore Kristin A. , Mella Jessica M. , Hayashi Samantha Y. , Hollien Julie
Published: February 2019

Cells respond to stress in the ER by initiating the widely conserved unfolded protein response. Activation of the ER transmembrane nuclease IRE1 leads to the degradation of specific mRNAs, but how this pathway affects the ability of cells to recover from stress is not known. Here, we show that degradation of the mRNA encoding biogenesis of lysosome-related organelles 1 subunit 1 (Blos1) leads to the repositioning of late endosomes (LEs)/lysosomes to the microtubule-organizing center in response to stress in mouse cells. Overriding Blos1 degradation led to ER stress sensitivity and the accumulation of ubiquitinated protein aggregates, whose efficient degradation required their independent trafficking to the cell center and the LE-associated endosomal sorting complexes required for transport. We propose that Blos1 regulation by IRE1 promotes LE-mediated microautophagy of protein aggregates and protects cells from their cytotoxic effects.
Claudia Jakubzick: Work hard, play hard
Authors: Houston Stephanie
Published: February 2019

Claudia Jakubzick will be an Associate Professor at Dartmouth in the Department of Microbiology and Immunology working on immune homeostasis and how the immune system can recognize and target precancerous cells. She started her own laboratory at National Jewish Health in 2014, becoming a tenure-track Assistant Professor and an Associate Professor in 2017, and will relocate to Dartmouth mid-2019. She is also a member of the American Association of Immunologists’ Minority Affairs Committee. We contacted Claudia to find out about her career in science.
The relationship between metastatic potential and in vitro mechanical properties of osteosarcoma cells
Authors: Holenstein Claude N. , Horvath Aron , Schär Barbara , Schoenenberger Angelina D. , Bollhalder Maja , Goedecke Nils , Bartalena Guido , Otto Oliver , Herbig Maik , Guck Jochen , Müller Daniel A. , Snedeker Jess G. , Silvan Unai
Published: February 2019

Osteosarcoma is the most frequent primary tumor of bone and is characterized by its high tendency to metastasize in lungs. Although treatment in cases of early diagnosis results in a 5-yr survival rate of nearly 60%, the prognosis for patients with secondary lesions at diagnosis is poor, and their 5-yr survival rate remains below 30%. In the present work, we have used a number of analytical methods to investigate the impact of increased metastatic potential on the biophysical properties and force generation of osteosarcoma cells. With that aim, we used two paired osteosarcoma cell lines, with each one comprising a parental line with low metastatic potential and its experimentally selected, highly metastatic form. Mechanical characterization was performed by means of atomic force microscopy, tensile biaxial deformation, and real-time deformability, and cell traction was measured using two-dimensional and micropost-based traction force microscopy. Our results reveal that the low metastatic osteosarcoma cells display larger spreading sizes and generate higher forces than the experimentally selected, highly malignant variants. In turn, the outcome of cell stiffness measurements strongly depends on the method used and the state of the probed cell, indicating that only a set of phenotyping methods provides the full picture of cell mechanics.
Mps1 regulates spindle morphology through MCRS1 to promote chromosome alignment
Authors: Yang Hongdan , Zhang Fengxia , Huang Ching-Jung , Liao Jun , Han Ying , Hao Piliang , Chu Youjun , Lu Xiaoai , Li Wenshu , Yu Hongtao , Kang Jungseog
Published: February 2019

Accurate partitioning of chromosomes during mitosis is essential for genetic stability and requires the assembly of the dynamic mitotic spindle and proper kinetochore–microtubule attachment. The spindle assembly checkpoint (SAC) monitors the incompleteness and errors in kinetochore–microtubule attachment and delays anaphase. The SAC kinase Mps1 regulates the recruitment of downstream effectors to unattached kinetochores. Mps1 also actively promotes chromosome alignment during metaphase, but the underlying mechanism is not completely understood. Here, we show that Mps1 regulates chromosome alignment through MCRS1, a spindle assembly factor that controls the dynamics of the minus end of kinetochore microtubules. Mps1 binds and phosphorylates MCRS1. This mechanism enables KIF2A localization to the minus end of spindle microtubules. Thus, our study reveals a novel role of Mps1 in regulating the dynamics of the minus end of microtubules and expands the functions of Mps1 in genome maintenance.
Prognostic Value of the Estimated Glomerular Filtration Rate Decline in Hypertensive Patients Without Chronic Kidney Disease
Authors: Coll-de-Tuero Gabriel , Comas-Cufí Marc , Rodríguez-Poncelas Antonio , Barrot-de-la Puente Joan , Blanch Jordi , Figa-Vaello Josep , Barceló Maria A , Saez Marc
Published: February 2019

BACKGROUND

Our objective of this study was to determine if rate of estimated glomerular filtration rate (eGFR) decline and its intensity was associated with cardiovascular risk and death in patients with hypertension whose baseline eGFR was higher than 60 ml/minute/1.73 m2.

METHODS

This study comprised 2,516 patients with hypertension who had had at least 2 serum creatinine measurements over a 4-year period. An eGFR reduction of ≥10% per year has been deemed as high eGFR and a reduction in eGFR of less than 10% per year as a low decline. The end points were coronary artery disease, stroke, transitory ischemic accident, peripheral arterial disease, heart failure, atrial fibrillation, and death from any cause. Cox regression analyses adjusted for potentially confounding factors were conducted.

RESULTS

A total of 2,354 patients with low rate of eGFR decline and 149 with high rate of eGFR decline were analyzed. The adjusted model shows that a −10% rate of eGFR decline per year is associated with a higher risk of the primary end point (HR 1.9; 95% CI 1.1–3.5; P = 0.02) and arteriosclerotic vascular disease (HR 2.2; 95% CI 1.2–4.2; P < 0.001) in all hypertensive groups. The variables associated to high/low rate of eGFR decline in the logistic regression model were serum creatinine (OR 3.35; P < 0.001), gender, women (OR 15.3; P < 0.001), tobacco user (OR 1.9; P < 0.002), and pulse pressure (OR 0.99; P < 0.05).

CONCLUSIONS

A rate of eGFR decline equal to or higher than −10% per year is a marker of cardiovascular risk for patients with arterial hypertension without chronic kidney disease at baseline. It may be useful to consider intensifying the global risk approach for these patients.
Human Immunodeficiency Virus Epidemic Control in the United States: An Assessment of Proposed UNAIDS Metrics, 2010–2015
Authors: Bosh Karin A , Brooks John T , Hall H Irene
Published: February 2019

Epidemic control is necessary to eliminate human immunodeficiency virus infections. We assessed epidemic control in the United States by applying 4 proposed UNAIDS metrics to national surveillance data collected between 2010 and 2015. Although epidemic control in the United States is possible, progress by UNAIDS metrics has been mixed.
Effects of renal denervation on kidney function and long-term outcomes: 3-year follow-up from the Global SYMPLICITY Registry
Authors: Mahfoud Felix , Böhm Michael , Schmieder Roland , Narkiewicz Krzysztof , Ewen Sebastian , Ruilope Luis , Schlaich Markus , Williams Bryan , Fahy Martin , Mancia Giuseppe
Published: February 2019

Aims

Several studies and registries have demonstrated sustained reductions in blood pressure (BP) after renal denervation (RDN). The long-term safety and efficacy after RDN in real-world patients with uncontrolled hypertension, however, remains unknown. The objective of this study was to assess the long-term safety and efficacy of RDN, including its effects on renal function.

Methods and results

The Global SYMPLICITY Registry is a prospective, open-label registry conducted at 196 active sites worldwide in hypertensive patients receiving RDN treatment. Among 2237 patients enrolled and treated with the SYMPLICITY Flex catheter, 1742 were eligible for follow-up at 3 years. Baseline office and 24-h ambulatory systolic BP (SBP) were 166 ± 25 and 154 ± 18 mmHg, respectively. SBP reduction after RDN was sustained over 3 years, including decreases in both office (−16.5 ± 28.6 mmHg, P < 0.001) and 24-h ambulatory SBP (−8.0 ± 20.0 mmHg; P < 0.001). Twenty-one percent of patients had a baseline estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Between baseline and 3 years, renal function declined by 7.1 mL/min/1.73 m2 in patients without chronic kidney disease (CKD; eGFR ≥60 mL/min/1.73 m2; baseline eGFR 87 ± 17 mL/min/1.73 m2) and by 3.7 mL/min/1.73 m2 in patients with CKD (eGFR <60 mL/min/1.73 m2; baseline eGFR 47 ± 11 mL/min/1.73 m2). No long-term safety concerns were observed following the RDN procedure.

Conclusion

Long-term data from the Global SYMPLICITY Registry representing the largest available cohort of hypertensive patients receiving RDN in a real-world clinical setting demonstrate both the safety and efficacy of the procedure with significant and sustained office and ambulatory BP reductions out to 3 years.
Febuxostat for Cerebral and CaRdiorenovascular Events PrEvEntion StuDy
Authors: Kojima Sunao , Matsui Kunihiko , Hiramitsu Shinya , Hisatome Ichiro , Waki Masako , Uchiyama Kazuaki , Yokota Naoto , Tokutake Eiichi , Wakasa Yutaka , Jinnouchi Hideaki , Kakuda Hirokazu , Hayashi Takahiro , Kawai Naoki , Mori Hisao , Sugawara Masahiro , Ohya Yusuke , Kimura Kazuo , Saito Yoshihiko , Ogawa Hisao
Published: February 2019

Aims

To compare the occurrence of cerebral, cardiovascular, and renal events in patients with hyperuricaemia treated with febuxostat and those treated with conventional therapy with lifestyle modification.

Methods and results

This multicentre, prospective, randomized open-label, blinded endpoint study was done in 141 hospitals in Japan. A total of 1070 patients were included in the intention-to-treat population. Elderly patients with hyperuricaemia (serum uric acid >7.0 to ≤9.0 mg/dL) at risk for cerebral, cardiovascular, or renal disease, defined by the presence of hypertension, Type 2 diabetes, renal disease, or history of cerebral or cardiovascular disease, were randomized to febuxostat and non-febuxostat groups and were observed for 36 months. Cerebral, cardiovascular, and renal events and all deaths were defined as the primary composite event. The serum uric acid level at endpoint (withdrawal or completion of the study) in the febuxostat (n = 537) and non-febuxostat groups (n = 533) was 4.50 ± 1.52 and 6.76 ± 1.45 mg/dL, respectively (P < 0.001). The primary composite event rate was significantly lower in the febuxostat group than in non-febuxostat treatment [hazard ratio (HR) 0.750, 95% confidence interval (CI) 0.592–0.950; P = 0.017] and the most frequent event was renal impairment (febuxostat group: 16.2%, non-febuxostat group: 20.5%; HR 0.745, 95% CI 0.562–0.987; P = 0.041).

Conclusion

Febuxostat lowers uric acid and delays the progression of renal dysfunction.

Registration

ClinicalTrials.gov (NCT01984749).
Effects of home visits for pregnant and postpartum women on premature birth, low birth weight and rapid repeat birth: a meta-analysis and systematic review of randomized controlled trials
Authors: Liu Na , Li Ping , Wang Jie , Chen Dandan , Sun Weijia , Zhang Wei
Published: February 2019

Background

Home visits seem promising for improving the health of women and infants during pregnancy and postpartum. This review aimed to quantitatively analyse the effects of home visits delivered during pregnancy and postpartum on premature birth (PTB), low birth weight (LBW) and rapid repeat birth (RRB).

Methods

Literature was retrieved from PubMed, EMBASE, Web of Science and the Cochrane Library from January 1960 to October 2018 and the references lists of related studies and reviews were also screened. Eligible papers were randomized controlled trials (RCTs) that focussed on home visits conducted with women during pregnancy or postpartum and reported at least one of the following results: PTB, LBW and RRB. Fixed- or random-effects models were used to analyse the pooled results.

Results

Fourteen RCTs were included. Pooled estimates showed a beneficial effect on LBW (odds ratio (OR) = 0.83; P = 0.03; low-quality evidence) and RRB in the professional-visit subgroup (OR = 0.62; P = 0.003; moderate-quality evidence). However, there was insufficient evidence to support the favourable effects of home visits on PTB (OR = 0.96; P = 0.59, moderate-quality evidence) and RRB in the non-professional-visit subgroup (OR = 0.86; P = 0.53, moderate-quality evidence). The overall methodological quality was moderate. Egger’s test suggested no publication bias for PTB and LBW.

Conclusion

This meta-analysis is the first to suggest that home visits can prevent and decrease LBW and RRB; however, it remains unclear whether home visits benefit PTB. Therefore, home visits can be an alternative and complementary part of primary health care for women, especially those with risk factors.
Moderation of the Association Between Chronic Medical Conditions and Functional Limitations Over Time by Physical Activity: Effects of Age
Authors: Rector Jerrald L , Marceau Kristine , Friedman Elliot M
Published: February 2019

Background

Age-related accumulation of chronic medical conditions increases disability in older adults. Physical activity potently combats chronic conditions and disability. However, it is unclear whether activity maintenance alleviates the effects of chronic conditions on disability and if this buffering effect differs with age. This study examined whether long-term physical activity can forestall functional limitations in the face of accumulating chronic conditions among middle-aged and older adults.

Methods

Participants (n = 2,119; 54.7% female) were from the Survey of Midlife Development in the United States. Self-reported physical activity, number of chronic conditions, and functional limitations were obtained across 18–20 years. Functional limitations were regressed against the change in chronic conditions, physical activity, and their interaction over time in a multilevel model of change. Baseline age was added as an additional moderator.

Results

Faster accumulation of chronic conditions [B(SE) = 2.08(0.32), p < .001] and steeper declines in activity [B(SE) = −2.29(0.41), p < .001] were associated with greater increases in functional limitations over time. Among those with faster-than-average increases in conditions, those who maintained activity had a slower progression of functional limitations, compared to those whose activity declined more rapidly [B(SE) = −11.18(3.96), p = .005]. Baseline age moderated the buffering effect of activity maintenance; older adults were protected against functional limitations only when conditions accumulated slowly [B(SE) = 0.23(0.08), p = .005].

Conclusion

This study provides evidence for an age-dependent buffering effect of activity maintenance on the longitudinal relationship between chronic conditions and functional limitations. Intervention strategies using physical activity to forestall disability should target midlife adults and consider the rate of condition accumulation.
Numerical approximation of curve evolutions in Riemannian manifolds
Authors: Barrett John W , Garcke Harald , Nürnberg Robert
Published: February 2019

We introduce variational approximations for curve evolutions in two-dimensional Riemannian manifolds that are conformally flat, i.e. conformally equivalent to the Euclidean plane. Examples include the hyperbolic plane, the hyperbolic disc and the elliptic plane, as well as any conformal parameterization of a two-dimensional manifold in ${{\mathbb{R}}}^d$, $d\geqslant 3$. In these spaces we introduce stable numerical schemes for curvature flow and curve diffusion, and we also formulate schemes for elastic flow. Variants of the schemes can also be applied to geometric evolution equations for axisymmetric hypersurfaces in ${{\mathbb{R}}}^d$. Some of the schemes have very good properties with respect to the distribution of mesh points, which is demonstrated with the help of several numerical computations.
Distinct molecular assembly of homologous peroxiredoxins from Pyrococcus horikoshii and Thermococcus kodakaraensis
Authors: Himiyama Tomoki , Oshima Maki , Uegaki Koichi , Nakamura Tsutomu
Published: February 2019

Peroxiredoxins from Pyrococcus horikoshii (PhPrx) and Thermococcus kodakaraensis (TkPrx) are highly homologous proteins sharing 196 of the 216 residues. We previously reported a pentagonal ring-type decameric structure of PhPrx. Here, we present the crystal structure of TkPrx. Despite their homology, unlike PhPrx, the quaternary structure of TkPrx was found to be a dodecamer comprised of six homodimers arranged in a hexagonal ring-type assembly. The possibility of the redox-dependent conversion of the molecular assembly, which had been observed in PhPrx, was excluded for TkPrx based on the crystal structure of a mutant in which all of the cysteine residues were substituted with serine. The monomer structures of the dodecameric TkPrx and decameric PhPrx coincided well, but there was a slight difference in the relative orientation of the two domains. Molecular assembly of PhPrx and TkPrx in solution evaluated by gel-filtration chromatography was consistent with the crystallographic results. For both PhPrx and TkPrx, the gel-filtration elution volume slightly increased with a decrease in the protein concentration, suggesting the existence of an equilibrium state between the decameric/dodecameric ring and lower-order assembly. This structural assembly difference between highly homologous Prxs suggests a significant influence of quaternary structure on function, worthy of further exploration.
Knowledge From Vice: Deeply Social Epistemology
Authors: Levy Neil , Alfano Mark
Published: February 2019

In the past two decades, epistemologists have significantly expanded the focus of their field. To the traditional question that has dominated the debate — under what conditions does belief amount to knowledge? — they have added questions about testimony, epistemic virtues and vices, epistemic trust, and more. This broadening of the range of epistemic concern has coincided with an expansion in conceptions of epistemic agency beyond the individualism characteristic of most earlier epistemology. We believe that these developments have not gone far enough. While the weak anti-individualism we see in contemporary epistemology may be adequate for the kinds of cases it tends to focus on, a great deal of human knowledge production and transmission does not conform to these models. Furthermore, the dispositions and norms that are knowledge-conducive in the familiar cases may not be knowledge-conducive generally. In fact, dispositions that, at an individual level, count as epistemic vices may be epistemic virtues in common social contexts. We argue that this overlooked feature of human social life means that epistemology must become more deeply and pervasively social.
Vaccine-driven selection and the changing molecular epidemiology of Bordetella pertussis
Authors: Lan Ruiting , Octavia Sophie
Published: February 2019

Pertussis remains one of the least controlled vaccine-preventable diseases despite high vaccine coverage in many countries. There are ongoing debates about the causes of its resurgence. Major changes have occurred in the Bordetella pertussis population since the introduction of vaccination. Currently circulating strains in Australia and many other developed countries are grouped in single nucleotide polymorphism (SNP) cluster I (also known as ptxP3 strains). The emergence and expansion of SNP cluster I has been associated with two major genetic changes in B. pertussis: a change in its pertussis toxin promoter (to ptxP3) which leads to increased pertussis toxin production and the change of the acellular vaccine pertactin gene allele to prn2. More recently, strains that lack pertactin have emerged independently in different lineages. The resurgence of pertussis in highly vaccinated populations can be, at least in part, explained by genetic changes that increase the fitness of circulating B. pertussis strains.
Curbing Their Antagonism: Topics Associated with a Reduction in Personal Attacks at Prime Minister’s Questions
Authors: Waddle Maurice , Bull Peter
Published: February 2019

This study of leaders’ exchanges in Prime Minister’s Questions considers the potential for foreign policy debate to be associated with uncharacteristic personal respect between political opponents. Using an existing dataset coded for a specific form of verbal aggression—personal attacks—questions to the Prime Minister spanning a 37-year period were further analysed for policy topic. Compared to questions and responses focused on domestic policies, foreign policy exchanges were significantly lower in personal attacks. Discussion includes the possibility of this being a British example of the old US adage politics stops at the water’s edge. Credible theoretical explanations include intergroup theories, and one linked to another US political science phenomenon (the rally ‘round the flag effect), specifically, patriotism.
Plant AP180 N-Terminal Homolog Proteins Are Involved in Clathrin-Dependent Endocytosis during Pollen Tube Growth in Arabidopsis thaliana
Authors: Kaneda Minako , van Oostende-Triplet Chlo� , Chebli Youssef , Testerink Christa , Bednarek Sebastian Y , Geitmann Anja
Published: February 2019

Polarized cell growth in plants is maintained under the strict control and exquisitely choreographed balance of exocytic and endocytic membrane trafficking. The pollen tube has become a model system for rapid polar growth in which delivery of cell wall material and membrane recycling are controlled by membrane trafficking. Endocytosis plays an important role that is poorly understood. The plant AP180 N-Terminal Homolog (ANTH) proteins are putative homologs of Epsin 1 that recruits clathrin to phosphatidylinositol 4, 5-bisphosphate (PIP2) containing membranes to facilitate vesicle budding during endocytosis. Two Arabidopsis ANTH encoded by the genes AtAP180 and AtECA2 are highly expressed in pollen tubes. Pollen tubes from T-DNA inserted knockout mutant lines display significant morphological defects and unique pectin deposition. Fluorescent tagging reveals organization into dynamic foci located at the lateral flanks of the pollen tube. This precisely defined subapical domain coincides which clathrin-mediated endocytosis (CME) and PIP2 localization. Using a liposome-protein binding test, we showed that AtECA2 protein and ANTH domain recombinant proteins have strong affinity to PIP2 and phosphatidic acid containing liposomes in vitro. Taken together these data suggest that Arabidopsis ANTH proteins may play an important role in CME, proper cell wall assembly and morphogenesis.
Modeling Epidemics in Seed Systems and Landscapes To Guide Management Strategies: The Case of Sweet Potato in Northern Uganda
Authors: Andersen K. F. , Buddenhagen C. E. , Rachkara P. , Gibson R. , Kalule S. , Phillips D. , Garrett K. A.
Published: February 2019

Seed systems are critical for deployment of improved varieties but also can serve as major conduits for the spread of seedborne pathogens. As in many other epidemic systems, epidemic risk in seed systems often depends on the structure of networks of trade, social interactions, and landscape connectivity. In a case study, we evaluated the structure of an informal sweet potato seed system in the Gulu region of northern Uganda for its vulnerability to the spread of emerging epidemics and its utility for disseminating improved varieties. Seed transaction data were collected by surveying vine sellers weekly during the 2014 growing season. We combined data from these observed seed transactions with estimated dispersal risk based on village-to-village proximity to create a multilayer network or “supranetwork.” Both the inverse power law function and negative exponential function, common models for dispersal kernels, were evaluated in a sensitivity analysis/uncertainty quantification across a range of parameters chosen to represent spread based on proximity in the landscape. In a set of simulation experiments, we modeled the introduction of a novel pathogen and evaluated the influence of spread parameters on the selection of villages for surveillance and management. We found that the starting position in the network was critical for epidemic progress and final epidemic outcomes, largely driven by node out-degree. The efficacy of node centrality measures was evaluated for utility in identifying villages in the network to manage and limit disease spread. Node degree often performed as well as other, more complicated centrality measures for the networks where village-to-village spread was modeled by the inverse power law, whereas betweenness centrality was often more effective for negative exponential dispersal. This analysis framework can be applied to provide recommendations for a wide variety of seed systems.

[Formula: see text] Copyright © 2019 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Quantification ofBotrytis cinereain Grapevine Bunch Trash by Real-Time PCR
Authors: Si Ammour Melissa , Fedele Giorgia , Morcia Caterina , Terzi Valeria , Rossi Vittorio
Published: February 2019

Quantification of colonization of grape bunch trash by Botrytis cinerea is crucial for Botrytis bunch rot (BBR) control. A previously developed quantitative polymerase chain reaction (qPCR) method was adapted to quantify B. cinerea DNA in grape bunch trash, and a colonization coefficient (CC) was calculated as the ratio between the DNA concentrations of B. cinerea and of Vitis vinifera. CC values increased linearly with the number of conidia of B. cinerea or the quantity of mycelium of B. cinerea added to the bunch trash increased. CC values also increased linearly in bunch trash samples containing increasing percentages of B. cinerea-colonized bunch trash; in the latter samples, CC values were correlated with subsequent assessments of B. cinerea colonization of trash (as determined by plating on agar) and sporulation on the trash (as determined by spore counts after incubation in humid chambers). The qPCR assay was also validated using trash collected from bunches treated or not treated with fungicides in three vineyards in two seasons. CC values reflected the reduction in sporulation and in latent infections of mature berries caused by fungicide application. The qPCR assay enables rapid, specific, sensitive, and reliable quantification of the degree of colonization of bunch trash by B. cinerea, which makes it a useful tool for studies of the epidemiology and management of BBR.
External mechanical work in the galloping racehorse
Authors: Self Davies Z. T. , Spence A. J. , Wilson A. M.
Published: February 2019

Horse locomotion is remarkably economical. Here, we measure external mechanical work of the galloping horse and relate it to published measurements of metabolic cost. Seven Thoroughbred horses were galloped (ridden) over force plates, under a racing surface. Twenty-six full strides of force data were recorded and used to calculate the external mechanical work of galloping. The mean sum of decrements of mechanical energy was −876 J (±280 J) per stride and increments were 2163 J (±538 J) per stride as horses were accelerating. Combination with published values for internal work and metabolic costs for galloping yields an apparent muscular efficiency of 37–46% for galloping, which would be reduced by energy storage in leg tendons. Knowledge about external work of galloping provides further insight into the mechanics of galloping from both an evolutionary and performance standpoint.
Autotomy in plants: organ sacrifice in
Oxalis
leaves
Authors: Shtein Ilana , Koyfman Alex , Eshel Amram , Bar-On Benny
Published: February 2019

Autotomy is a self-defence strategy of sacrificing a body part for survival. This phenomenon is widespread in the animal kingdom (e.g. gecko's tail) but was never reported in plants. In this study, we characterize the autotomy mechanism in the leaves of an invasive plant of South African origin,
Oxalis pes-caprae.
When the leaves and flowers of this plant are pulled, they break easily at their base, leaving the rest of the plant intact. Microscopic observations of the leaves reveal an area of small cells and a marked notch at this designated breaking point. Mechanical analysis showed that the strength statistics of the petioles follow Weibull's function. A comparison of the function parameters confirmed that strength of the tissue at that point is significantly smaller than at other points along the petiole, while the toughness of the tissue at the notch and at mid-petiole are approximately the same. We conclude that leaf fracture in
Oxalis
is facilitated by an amplification of the far-field stress in the vicinity of local, but abrupt, geometrical modification in the form of a notch. This presents an autotomy-like defence mechanism which involves the sacrifice of vital organs in order to prevent the uprooting of the whole plant.
Joseph Banks and Charles Blagden: cultures of advancement in the scientific worlds of late eighteenth-century London and Paris
Authors: Wills Hannah
Published: February 2019

This paper explores the relationship between Joseph Banks, president of the Royal Society, and Charles Blagden, secretary to Banks and the Society between 1784 and 1797. Blagden is often referred to as one of Banks's key assistants, as a trusted adviser, collaborator and source of information. Yet, despite his significance, the nature of Blagden's association with Banks has not been explored in detail. This paper traces the development of their sometimes tumultuous relationship, exposing it as one in which Blagden, an aspiring gentleman, sought Banks's patronage to further his career and social ambitions. Key to Blagden's strategy was his role as a source of information for Banks from Paris. Yet, while Blagden pursued patronage with Banks in London, on visits to Paris he encountered a situation where merit, in terms of published scientific outputs, determined one's membership of the scientific community. Exploration of these conflicting cultures of advancement—patronage versus advancement through merit—here informs a re-assessment of scientific exchange at a key moment in Blagden's career, the 1783 ‘water controversy’. The limitations of Banks's patronage for ambitious clients are also explored, in the context of a rupture in the relationship between Blagden and Banks at the end of the 1780s.
Speed-mediated properties of schooling
Authors: Kent Maud I. A. , Lukeman Ryan , Lizier Joseph T. , Ward Ashley J. W.
Published: February 2019

Collectively moving animals often display a high degree of synchronization and cohesive group-level formations, such as elongated schools of fish. These global patterns emerge as the result of localized rules of interactions. However, the exact relationship between speed, polarization, neighbour positioning and group structure has produced conflicting results and is largely limited to modelling approaches. This hinders our ability to understand how information spreads between individuals, which may determine the collective functioning of groups. We tested how speed interacts with polarization and positional composition to produce the elongation observed in moving groups of fish as well as how this impacts information flow between individuals. At the local level, we found that increases in speed led to increases in alignment and shifts from lateral to linear neighbour positioning. At the global level, these increases in linear neighbour positioning resulted in elongation of the group. Furthermore, mean pairwise transfer entropy increased with speed and alignment, implying an adaptive value to forming faster, more polarized and linear groups. Ultimately, this research provides vital insight into the mechanisms underlying the elongation of moving animal groups and highlights the functional significance of cohesive and coordinated movement.
TiO
2
thin films by ultrasonic spray pyrolysis as photocatalytic material for air purification
Authors: Dundar Ibrahim , Krichevskaya Marina , Katerski Atanas , Acik Ilona Oja
Published: February 2019

In this study, we showed that the TiO
2
thin films deposited onto window glass are practicable for air purification and self-cleaning applications. TiO
2
films were deposited onto window glass by ultrasonic spray pyrolysis method. Different deposition temperatures were used in the range of 250–450°C. The structural, morphological, optical properties and surface chemical composition were investigated to understand probable factors affecting photocatalytic performance and wettability of the TiO
2
thin films. The TiO
2
thin films were smooth, compacted and adhered adequately on the substrate with a thickness in the range of 100–240 nm. X-ray diffraction patterns revealed that all the TiO
2
thin films consisted of anatase phase structure with the mean crystallite size in the range of 13–35 nm. The optical measurements showed that the deposited films were highly transparent (approx. 85%). The wettability test results showed that the TiO
2
thin films sprayed at 350°C and 450°C and annealed at 500°C for 1 h were superhydrophilic. The photocatalytic activity of the films was tested for the degradation of methyl tert-butyl ether (MTBE) in multi-section plug-flow reactor. The TiO
2
film deposited at 350°C exhibited the highest amount of conversion of MTBE, approximately 80%.
Enhancement in acoustic focusing of micro and nanoparticles by thinning a microfluidic device
Authors: Ota Nobutoshi , Yalikun Yaxiaer , Suzuki Tomoyuki , Lee Sang Wook , Hosokawa Yoichiroh , Goda Keisuke , Tanaka Yo
Published: February 2019

The manipulation of micro/nanoparticles has become increasingly important in biological and industrial fields. As a non-contact method for particle manipulation, acoustic focusing has been applied in sorting, enrichment and analysis of particles with microfluidic devices. Although the frequency and amplitude of acoustic waves and the dimensions of microchannels have been recognized as important parameters for acoustic focusing, the thickness of microfluidic devices has not been considered so far. Here, we report that thin glass microfluidic devices enhance acoustic focusing of micro/nanoparticles. It was found that the thickness of a microfluidic device strongly influences its ability to focus particles via acoustic radiation, because the energy propagation of acoustic waves is affected by the total mass of the device. Acoustic focusing of submicrometre polystyrene beads and
Escherichia coli
as well as enrichment of polystyrene beads were achieved in glass microfluidic devices as thin as 0.4 mm. Modifying the thickness of a microfluidic device can thus serve as a critical parameter for acoustic focusing when conventional parameters to achieve this effect are kept unchanged. Thus, our findings enable new approaches to the design of novel microfluidic devices.
Variations in the glucosinolates of the individual edible parts of three stem mustards (
Brassica juncea
)
Authors: Sun Bo , Tian Yu-Xiao , Chen Qing , Zhang Yong , Luo Ya , Wang Yan , Li Meng-Yao , Gong Rong-Gao , Wang Xiao-Rong , Zhang Fen , Tang Hao-Ru
Published: February 2019

The composition and content of glucosinolates were investigated in the edible parts (petioles, peel and flesh) of tuber mustard, bamboo shoots mustard and baby mustard by high-performance liquid chromatography to reveal the association between the different cooking methods and their glucosinolate profiles. Eight glucosinolates were identified from tuber mustard and baby mustard, including three aliphatic glucosinolates, four indole glucosinolates and one aromatic glucosinolate. Only six of the eight glucosinolates were detected in bamboo shoots mustard. The results show that the distribution and content of glucosinolates varied widely among the different tissues and species. The highest contents of glucosinolates in tuber mustard, bamboo shoots mustard and baby mustard were found in flesh, petioles and peel, respectively. The content of total glucosinolates ranged from 5.21 µmol g
–1
dry weight in bamboo shoots mustard flesh to 25.64 µmol g
−1
dry weight in baby mustard peel. Aliphatic glucosinolates were predominant in the three stem mustards, followed by indole and aromatic glucosinolates. Sinigrin was the predominant glucosinolate in the three stem mustards. Sinigrin content in tuber mustard was slightly higher than that in baby mustard and much higher than that in bamboo shoots mustard, suggesting that the pungent-tasting stem mustards contained more sinigrin. In addition, a principal components analysis showed that bamboo shoots mustard was distinguishable from the other two stem mustards. A variance analysis indicated that the glucosinolates were primarily influenced by a species × tissue interaction. The correlations among glucosinolates were also analysed.