bluuebunny/crossref_metadata_2025 huggingface dataset:
Environment‐sensitive mass changes influence breeding frequency in a capital breeding marine top predator
Authors: Smout Sophie , King Ruth , Pomeroy Patrick
Published: November 2019

The trade‐off between survival and reproduction in resource‐limited iteroparous animals can result in some individuals missing some breeding opportunities. In practice, even with the best observation regimes, deciding whether ‘missed’ years represent real pauses in breeding or failures to detect breeding can be difficult, posing problems for the estimation of individual reproductive output and overall population fecundity.

We corrected fecundity estimates by determining whether breeding had occurred in skipped years, using long‐term capture–recapture observation datasets with parallel longitudinal mass measurements, based on informative underlying relationships between individuals’ mass, breeding status and environmental drivers in a capital breeding phocid, the grey seal.

Bayesian modelling considered interacting processes jointly: temporal changes in a phenotypic covariate (mass); relationship of mass to breeding probability; effects of maternal breeding state and mark type on resighting. Full reproductive histories were imputed, with the status of unobserved animals estimated as breeding or non‐breeding, accounting for local environmental variation. Overall fecundity was then derived for Scottish breeding colonies with contrasting pup production trends.

Maternal mass affected breeding likelihood. Mothers with low body mass at the end of breeding were less likely to bear a pup the following year. Successive breeding episodes incurred a cost in reduced body mass which was more pronounced for North Rona, Outer Hebrides (NR) mothers. Skipping breeding increased subsequent pupping probability substantially for low mass females. Poor environmental conditions were associated with declines in breeding probability at both colonies. Seal mass gain between breeding seasons was (a) negatively associated with lagged North Atlantic Oscillation for seals at NR and (b) positively associated with an index of seal prey (Ammodytes spp) abundance at Isle of May, Firth of Forth (IM). Overall fecundity was marginally greater at IM (increasing/stable pup production) than at NR (decreasing). No effects of mass were detected on maternal survival.

Skipping breeding in female grey seals appears to be an individual mass‐dependent constraint moderated by previous reproductive output and local environmental conditions. Different demographic trends at breeding colonies were consistent with the fecundities estimated using this method, which is general and adaptable to other situations.
Tracking the resource pulse: Movement responses of fish to dynamic floodplain habitat in a tropical river
Authors: Crook David A. , Buckle Duncan J. , Morrongiello John R. , Allsop Quentin A. , Baldwin Wayne , Saunders Thor M. , Douglas Michael M.
Published: November 2019

Natural river floodplains are among the Earth's most biologically diverse and productive ecosystems but face a range of critical threats due to human disturbance. Understanding the ecological processes that support biodiversity and productivity in floodplain rivers is essential for their future protection and rehabilitation.

Fish assemblage structure on tropical river floodplains is widely considered to be driven by dispersal limitation during the wet season and by environmental filtering and interspecific interactions during the dry season. However, the individual‐level movement behaviours (e.g. site attachment, nomadism, homing) that regulate dispersal of fish on floodplains are poorly understood.

We combined radiotelemetry and remote sensing to examine the movement behaviour of two large‐bodied fishes (barramundi Lates calcarifer, forktail catfish Neoarius leptaspis) over the flood cycle in a tropical river‐floodplain system in northern Australia to: (a) quantify movement responses in relation to dynamic habitat resources at a landscape scale; and (b) determine the extent of spatial ‘reshuffling’ of individual fish following the wet season.

Both species altered their behaviour rapidly in response to changes in the availability and distribution of aquatic habitat, with most individuals undertaking extensive movements (up to ~27 km from the tagging location) on the inundated floodplain during the wet season. Although there was considerable individual variation in movement patterns, overall barramundi distributions closely tracked the extent of floodplain primary productivity, whereas catfish distributions were most closely associated with the extent of flooded area. Most individuals of both species exhibited homing back to previously occupied dry season refugia during the wet‐to‐dry transition, even though other potential refugia were available in closer proximity to wet season activity areas.

We postulate that homing behaviour modulates temporal variation in fish assemblage composition and abundance and limits the transfer of aquatic‐derived energy and nutrients into terrestrial food webs by reducing fish mortality on drying floodplains. Our study demonstrates the importance of quantifying individual‐level behaviour across the three stages of dispersal (emigration, inter‐patch movement, immigration) for our understanding of how animal movement influences energetic subsidies and other large‐scale ecosystem processes.
Future of South Korea–Japan Relations: Decoupling or Liberal Discourse
Authors: Phillips Joe , Lee Wondong , Yi Joseph
Published: November 2019

South Korea–Japan relations are at their lowest point in decades, as colonial era disputes flare once again. Most pundits argue that the South Korean public is strongly united against Japan. We argue that South Korean elites are sharply divided over how to manage the crisis; this division is starting to impact how South Koreans understand colonial era narratives; and, long‐term, bilateral relations depend on how these growing divisions play out. Despite state censorship, a rising counter‐narrative in South Korea challenges the dominant, Manichaean, anti‐Japanese one. For the first time, Korea and Japan have a realistic chance of reconciling based on liberal public discourse and a nuanced, empirically based understanding of history.
Sclerotinia Sclerotiorum (White Mold): Cytotoxic, Mutagenic, and Antimalarial Effects In Vivo and In Vitro
Authors: Pressete Carolina Girotto , Giannini Laila Santos Vieira , de Paula Daniela Aparecida Chagas , do Carmo Mariana Araújo Vieira , Assis Diego Magno , Santos Mário Ferreira Conceição , Machado José da Cruz , Marques Marcos José , Soares Marisi Gomes , Azevedo Luciana
Published: November 2019

This work aimed includes performing the sclerotia chemical profile and evaluates their biological effects on mutagenesis, oxidative stress, cancer, and malaria. A chemical profile was determined by ultraperformance liquid chromatography mass spectrometry (UHPLC–HRMS) analysis dereplicating norditerpenoid dilactone, sclerolide, and other compounds. The GI50 values to cancer cells (19.8 to 277.6 µg/mL) were higher than normal (16.05 µg/mL), meaning high cytotoxicity. Regarding the oxidative stress, the results showed that the all AcOET fraction concentrations tested on IMR90 noncancer cell increased reactive oxygen species (ROS) production in more intense way (by fivefold) than in tested cancer cells. The in vivo study showed an increase of the following biomarkers (by 296.00%): % DNA in comet tail in peripheral blood and liver cells; micronucleated erythrocytes and colon cells and lipid serum peroxidation. These results indicate the sclerotia as genotoxic and mutagenic agent and its contamination may lead to fungal toxic effects with a risk to human health.
Pesticides (Hexachlorocyclohexane, Aldrin, and Malathion) Residues in Home‐Grown Eggs: Prevalence, Distribution, and Effect of Storage and Heat Treatments
Authors: Alaboudi Akram R. , Osaili Tareq M. , Alrwashdeh Arwa
Published: November 2019

The abuse of pesticides in home gardens may lead to contamination of home‐grown eggs. This study aimed to determine the prevalence of hexachlorocyclohexane (HCH), aldrin, and malathion pesticides residues in egg white and egg yolk of home‐grown eggs in Jordan; and the effect of refrigerated storage and heat treatment (boiling and frying) on residues level. High‐performance liquid chromatography was used to detect pesticide residues in egg samples (n = 200) obtained from households that raise laying hens in Jordan. About 96% of the tested eggs showed pesticide residues. None of the tested egg samples showed residual level above maximum residue limit (MRL 0.02 mg/kg) for HCH, whereas 33% and 44% of samples were above MRL for aldrin and malathion, respectively. All studied pesticide residues were detected from both egg yolk and egg white. The concentrations of malathion and aldrin (0.075 and 0.067 mg/kg) in egg yolk were higher than those (0.049 and 0.058 mg/kg) in egg white samples. Pesticide residue levels were quite stable during refrigeration storage whereas heat treatment (boiling at 100 °C and frying at 160 °C) significantly reduced contamination levels to values below MRL. The high level of pesticide residues in home‐grown egg in Jordan may reflect the improper use of pesticides in home gardens and thus exposing the environment to unwanted pollution and the risk they may pose on human health.

Practical Application

Home‐grown eggs could be exposed to pesticides more than commercial eggs as free‐range hens interact directly with the environment and ingest soil or materials on/in the soil that might be contaminated with pesticides used in home gardens or farms. Exploring pesticides residues in home‐grown eggs and effect of refrigerated storage and heat treatment (boiling and frying) on residue levels would be useful to consumers and health authorities.
Probiotic Yogurt with Brazilian Red Propolis: Physicochemical and Bioactive Properties, Stability, and Shelf Life
Authors: Santos Marly S. , Estevinho Leticia M. , Carvalho Carlos Alfredo L. , Morais Jorge S. , Conceição Antonio Leandro S. , Paula Vanessa B. , Magalhães‐Guedes Karina , Almeida Rogeria C. C.
Published: November 2019

This study aimed to evaluate the quality parameters in probiotic yogurt produced with Brazilian red propolis to replace potassium sorbate used in conventional yogurt (CY). Microbiological stability and shelf life, physicochemical properties (pH, acidity, chemical composition, and fatty acids), and bioactive properties (phenolic compounds and antioxidant activity) were evaluated. The addition of red propolis (0.05%) to replace the potassium sorbate did not change the pH, acidity, fatty acid profile, chemical composition, or shelf life. Microbiological stability of at least 28 days was achieved, while a drastic reduction in the lactic acid bacteria content was observed in the CY during refrigeration storage. Phenolic total contents were higher than those of the control, and consequently, yogurt with red propolis showed higher antioxidant activity.

Practical Application

The study indicates that Brazilian red propolis at 0.05% concentration to replace the potassium sorbate is an efficient alternative for use in yogurt production. The knowledge acquired about these types of Brazilian propolis provides an important contribution to food research in the discovery of new functional products to the market, seeking a healthier diet. Therefore, the produced yogurt proves to be an innovative product with functional and probiotic potential to be placed on the market.
Carpesium abrotanoides (L.) Root as a Potential Source of Natural Anticancer Compounds: Targeting Glucose Metabolism and PKM2/HIF‐1α Axis of Breast Cancer Cells
Authors: Chai Xin‐Xin , Le Yi‐Fei , Wang Jun‐Cheng , Mei Chen‐Xuan , Feng Jia‐Fan , Zhao Hong , Wang Cui , Lu De‐Zhao
Published: November 2019

Carpesium abrotanoides L. (CA) is widely used as a medicinal plant in Asia. The biological activities of the extract from the roots of Carpesium abrotanoides L. (PCA) and its major components were analyzed in this study. PCA was separated and identified with mass spectrometry. Furthermore, we sought to elucidate the anticancer activity of PCA and its mechanisms. PCA exerted its anti–breast cancer activity through inhibiting the expression of glycolysis‐related genes, such as glucose transporter 1, lactate dehydrogenase A, and hexokinase 2. Moreover, PCA downregulated the expression of pyruvate kinase M2 and altered its cellular translocation. We also demonstrated PCA is an inhibitor of the PKM2/hypoxia‐inducible factor‐1α axis, indicating that PCA is potentially useful as an anti–breast cancer agent.

Practical Application

In this study, the extract from roots of Carpesium abrotanoides Linn. (PCA) was shown to have a noticeable anticancer effect against breast cancer in vitro, and PCA exerts the anticancer activity by regulating glucose metabolism and PKM2 expression. These findings indicate that PCA is a promising agent with practical applications in the development of functional food containing Carpesium abrotanoides L. root extracts.
Physicochemical Properties and Consumer Acceptance of High‐Pressure Processed, Sous Vide‐Cooked Lobster Tails
Authors: Humaid Sami , Nayyar Dhriti , Bolton Jason , Skonberg Denise I.
Published: November 2019

Sous vide (SV) and high‐pressure processing (HPP) are promising techniques in the development of high‐quality seafood products. The objectives of this study were to evaluate the impacts of HPP on the physicochemical quality and consumer acceptance of subsequently SV‐cooked lobster tails. Raw shucked lobster tails were processed at 150 or 350 MPa for 5 or 10 min. Subsequently, half were SV cooked to a core temperature of 65 °C/10 min. Texture profile analysis, shear force, color, salt soluble protein content, water‐holding capacity (WHC), moisture content, and weight loss were analyzed. Pressurization at 150 MPa/10 min decreased (P < 0.05) the hardness of raw lobsters compared to non‐HPP‐treated controls. However, 350 MPa for 5 or 10 min increased (P < 0.05) the shear force in raw and SV‐cooked samples. HPP increased (P < 0.05) the L* values but did not affect moisture content, WHC, or weight loss of raw or SV‐cooked lobsters. Lobsters were subjected to consumer acceptability testing using a 9‐point hedonic scale. Although panelists rated the flavor, texture, and overall liking of the 350 MPa/10 min samples higher than the control and 150 MPa/10 min samples, there were no significant differences among treatment means, indicating that physicochemical changes induced by HPP did not affect consumer acceptance. In addition, approximately 84% of panelists reported that the 350 MPa product met their expectations compared to approximately 75% for the control and 150 MPa treatments. These results suggest that HPP has the potential to be applied in combination with SV cooking to produce consumer‐acceptable, value‐added lobster products.

Practical Application

Lobsters are an expensive menu item in restaurants. However, they are susceptible to being overcooked using conventional methods, producing a tough and rubbery texture. Sous vide cooking is reported to provide evenly cooked lobsters with a succulent and juicy texture. In this study, lobsters were sous vide cooked to reach a core temperature of 65 °C, and then maintained at that temperature for 10 min. The application of moderate processing pressures to vacuum‐packaged raw lobsters prior to SV cooking altered some physicochemical attributes but has the potential to increase the availability of high‐quality, minimally processed seafood with good consumer acceptability.
Association between antiphospholipid antibodies and factor Bb in lupus nephritis patients with glomerular microthrombosis
Authors: Zhou Yan , Chen Peirong , Li Yongji
Published: November 2019

Background and purpose

The mechanism of glomerular microthrombosis (GMT) in patients with lupus nephritis (LN) is largely unknown. The aim of this study is to investigate the association between antiphospholipid antibodies (aPLs) and factor Bb in LN patients with GMT.

Methods

Patients with biopsy‐proven LN hospitalized from July 2015 to July 2018 in our hospital were selected for this study. Levels of lupus anticoagulant (LAC), anticardiolipin antibodies (aCLs), anti‐β2‐glycoprotein I (anti‐β2‐GPI) antibodies and factor Bb were measured, and other clinical and pathological data were also obtained during the same period before renal biopsy.

Results

A total of 25 LN patients with GMT and 76 LN patients without GMT were included in this study. In LN patients with GMT, the presence of anti‐β2GPI and LAC were both significantly higher than in those without GMT (P < .001 and P = .039, respectively). The level of factor Bb was also higher in LN patients with GMT than in those without GMT (P = .021). In the correlation analysis, Bb level was positively correlated with serum creatinine (r = 0.28, P = .014), activity index (r = 0.24, P = .021) GMT (r = 0.65, P < .001) and IgG‐anti‐β2GPI (r = 0.771, P < .001).

Conclusions

Our work suggests that aPLs, especially IgG‐anti‐β2GPI, may play a role in the progress of GMT, and this process might involve alternative complement activation.
Polylinear incursions and autochthonous adaptations: Neolithisation and sustainable sedentarisation of the Arabian Peninsula
Authors: Gebel Hans Georg K.
Published: November 2019

This contribution’s broad and in parts essayistic approach to Arabia’s Neolithic is less a discussion of findings than an explicit advocacy for future holistic research strategies. Based on the contribution’s meta‐theoretical inputs, it suggests two sets of theses to be tested by the hitherto gained fragmentary information and future research on Arabia’s Neolithic. It aims to encourage an “emancipation” of Arabia’s early to mid‐Holocene research from conceptions developed outside its regions, and to identify the Neolithic elements and developments of the Arabian lands by distinguishing incursions from primarily autochthonous and/or autonomous adaptations in their own right. It is suggested that productive lifeways are considered to be the only crucial parameter to testify a Neolithic status. In our view this is the case, provokingly enough, for the productive foraging management of natural resources which attests surplus and pre‐planning strategies and contacts with established Neolithic socio‐economies. Polylinear incursions and autochthonous adaptations are discussed as the two poles between which early to mid‐Holocene developments in Arabia took place. A set of basic and a set of trajectory hypotheses on Arabia’s neolithisation and finally sustainable sedentarisation (reliance on oases economies) is presented, offered as a possible framework for future multi‐/ transdisciplinary research.
A quantitative approach to the study of Neolithic projectile points from south‐eastern Arabia
Authors: Maiorano Maria Pia , Crassard Rémy , Charpentier Vincent , Bortolini Eugenio
Published: November 2019

Lithic projectile points always had an important diagnostic value for documenting the development and expansion of Arabian Neolithic material culture (c. eighth–fourth millennium BC) and subsistence strategies due to the remarkable abundance of surface assemblages. Given the limitations of traditional arrowhead typology for analysing the increasing variability emerging from archaeological research in the region, we propose here a new systematic description of Neolithic projectile points, based on the consistent observation of technological and morphological change over time and space in a number of diagnostic parameters. A quantitative exploration of variation is carried out on both published and unpublished data through a number of pattern‐recognition techniques and exploratory analyses such as principal component and cluster analysis. By presenting the first application of this approach to Arabian Neolithic projectile points, the research offers a valid tool for investigating temporal and cultural trends through different phases of the Neolithic in the region of interest.
Dendrochronology and archival texts: Dating the Ottoman fortress of Seddülbahir on the Gallipoli Peninsula, Turkey*
Authors: Akkemik Ü. , Köse N. , Çatalbaş M. , Thys‐Şenocak L.
Published: November 2019

This paper provides the results of the dendrochronological analyses of seven wood samples from the Ottoman fortress of Seddülbahir on the Gallipoli Peninsula or Turkey. It concludes that the trees were cut in the late spring of 1656. The data collected allows the first building phase of the fortress to be securely dated. By bringing together the dendrochronological results with various archival records about the fortress, a more precise building chronology for the fortress can be reconstructed. The probable initial period of construction was between 1656 and 1661.
The ecology of chronic wasting disease in wildlife
Authors: Escobar Luis E. , Pritzkow Sandra , Winter Steven N. , Grear Daniel A. , Kirchgessner Megan S. , Dominguez‐Villegas Ernesto , Machado Gustavo , Townsend Peterson A. , Soto Claudio
Published: November 2019

Prions are misfolded infectious proteins responsible for a group of fatal neurodegenerative diseases termed transmissible spongiform encephalopathy or prion diseases. Chronic Wasting Disease (CWD) is the prion disease with the highest spillover potential, affecting at least seven Cervidae (deer) species. The zoonotic potential of CWD is inconclusive and cannot be ruled out. A risk of infection for other domestic and wildlife species is also plausible. Here, we review the current status of the knowledge with respect to CWD ecology in wildlife. Our current understanding of the geographic distribution of CWD lacks spatial and temporal detail, does not consider the biogeography of infectious diseases, and is largely biased by sampling based on hunters' cooperation and funding available for each region. Limitations of the methods used for data collection suggest that the extent and prevalence of CWD in wildlife is underestimated. If the zoonotic potential of CWD is confirmed in the short term, as suggested by recent results obtained in experimental animal models, there will be limited accurate epidemiological data to inform public health. Research gaps in CWD prion ecology include the need to identify specific biological characteristics of potential CWD reservoir species that better explain susceptibility to spillover, landscape and climate configurations that are suitable for CWD transmission, and the magnitude of sampling bias in our current understanding of CWD distribution and risk. Addressing these research gaps will help anticipate novel areas and species where CWD spillover is expected, which will inform control strategies. From an ecological perspective, control strategies could include assessing restoration of natural predators of CWD reservoirs, ultrasensitive CWD detection in biotic and abiotic reservoirs, and deer density and landscape modification to reduce CWD spread and prevalence.
Brain perivascular macrophages: Recent advances and implications in health and diseases
Authors: Yang Tuo , Guo Ruiming , Zhang Feng
Published: November 2019

Brain perivascular macrophages (PVMs) belong to a distinct population of brain‐resident myeloid cells located within the perivascular space surrounding arterioles and venules. Their characterization depends on the combination of anatomical localization, phagocytic capacity, and molecular markers. Under physiological status, they provide structural and functional support for maintaining brain homeostasis, including facilitation of blood‐brain barrier integrity and lymphatic drainage, and exertion of immune functions such as phagocytosis and antigen presentation. Increasing evidence also implicates their specific roles in diseased brain, ranging from cerebrovascular diseases, Aβ pathologies, infections, and autoimmunity. Collectively, PVMs are key components of the brain‐resident immune system, actively participate in a broad‐spectrum of processes in normal and diseased status. Details of the processes are largely underexplored. Targeting PVMs would lead to new insights and be a promising strategy for a broad array of human diseases.
A systematic study of dyeing polybutylene succinate fibres
Authors: Li Dawei , Zhang Bingjie , Wang Shugen , Zhou Chang E. , Sun Chang , Zha Quanliang
Published: November 2019

Biodegradable polybutylene succinate (PBS) fibre is a new type of textile fibre, but its application in the textile industry is limited by the lack of related dyeing methods. In this study, the solubility parameters of PBS fibres are calculated, and solvent dyes with similar solubility parameters are proposed to dye PBS fibres to show that the dyeing scheme creatively resolves the difficulty in dyeing PBS fibres. The technical parameters of suitable dyes, and the dyeing conditions with ethanol as the dyeing medium, consisted of a dyeing temperature of 90°C, a dyeing time of 30 minutes and a liquor ratio of 30:1. The dyeing results show that the levelling property is good, the dyebath exhaustion is high, and the washing fastness, the rubbing fastness and the perspiration fastness index of the dyed fibres are satisfactory.
Circadian BMAL1 regulates mandibular condyle development by hedgehog pathway
Authors: Yu Shaoling , Tang Qingming , Xie Mengru , Zhou Xin , Long Yanlin , Xie Yanling , Guo Fengyuan , Chen Lili
Published: November 2019

Objective

Chondrogenesis and endochondral ossification in mandibular condyle play crucial roles in maxillofacial morphogenesis and function. Circadian regulator brain and muscle arnt‐like 1 (BMAL1) is proven to be essential for embryonic and postnatal development. The goal of this study was to define the functions of BMAL1 in the embryonic and postnatal growth of mandibular condylar cartilages (MCC).

Materials and Methods

Micro‐CT, TUNEL staining and EdU assay were performed using BMAL1‐deficient mice model, and in vitro experiments were performed using rat chondrocytes isolated from MCC. RNA sequencing in mandibular condyle tissues from Bmal1‐/‐ mice and the age‐matched wild‐type mice was used for transcriptional profiling at different postnatal stages.

Results

The expression levels of BMAL1 decrease gradually in MCC. BMAL1 is proved to regulate sequential chondrocyte differentiation, and its deficiency can result in the impairment of endochondral ossification of MCC. RNA sequencing reveals hedgehog signalling pathway is the potential target of BMAL1. BMAL1 regulates hedgehog signalling and affects its downstream cascades through directly binding to the promoters of Ptch1 and Ihh, modulating targets of hedgehog signalling which is indispensable for endochondral ossification. Importantly, the short stature phenotypes caused by BMAL1 deficiency can be rescued by hedgehog signalling activator.

Conclusions

Collectively, these results indicate that BMAL1 plays critical roles on chondrogenesis and endochondral ossification of MCC, giving a new insight on potential therapeutic strategies for facial dysmorphism.
Clinical epigenetics: a primer for the practitioner
Authors: Aygun Deniz , Bjornsson Hans T
Published: November 2019

Disruption of epigenetic modifications and the factors that maintain these modifications is rapidly emerging as a cause of developmental disorders. Here we summarize some of the major principles of epigenetics including how epigenetic modifications are: (1) normally reset in the germ line, (2) form an additional layer of interindividual variation, (3) are environmentally sensitive, and (4) change over time in humans. We also briefly discuss the disruption of growth and intellect associated with the Mendelian disorders of the epigenetic machinery and the classical imprinting disorders (such as Beckwith–Wiedemann syndrome, Silver–Russell syndrome, Prader–Willi syndrome, and Angelman syndrome), as well as suggesting some diagnostic considerations for the clinicians taking care of these patients. Finally, we discuss novel therapeutic strategies targeting epigenetic modifications, which may offer a safe alternative to up and coming genome editing strategies for the treatment of genetic diseases. This review provides a starting point for clinicians interested in epigenetics and the role epigenetic disruption plays in human disease.

What this paper adds

Clinicians are introduced to four main principles of epigenetics.

Clinical features of imprinting disorders and Mendelian disorders of epigenetic machinery are presented.
A 12‐week, randomized, double‐blind, placebo‐controlled, four‐arm dose‐finding phase 2 study evaluating bexagliflozin as monotherapy for adults with type 2 diabetes
Authors: Halvorsen Yuan‐Di , Walford Geoffrey , Thurber Tara , Russell Heidy , Massaro Monica , Freeman Mason W.
Published: November 2019

Aim

To compare the safety and efficacy of bexagliflozin administered as monotherapy at three dosage strengths over a 12‐week period to patients with type 2 diabetes who were either naïve to pharmacotherapy or were previously prescribed one oral hypoglycaemic agent and underwent a 6‐week period of medication abstinence.

Methods

Adults with type 2 diabetes (n = 292) having an HbA1c of between 7.0% and 8.5% were randomized to receive one of three dosage strengths of bexagliflozin (5, 10 or 20 mg) or placebo. The primary endpoint was the change from baseline to week 12 in the %HbA1c. Secondary endpoints included the changes from baseline in fasting plasma glucose (FPG), systolic blood pressure and diastolic blood pressure, body mass and fraction of patients achieving an HbA1c of <7%.

Results

The mixed model repeated measure estimates of the placebo‐adjusted change in %HbA1c from baseline to week 12 for the 5, 10 and 20 mg groups were −0.55% (95% CI: −0.76%, −0.34%, P < 0.0001), −0.68% (95% CI: −0.89%, −0.47%, P < 0.0001) and −0.80% (95% CI: −1.01%, −0.59%, P < 0.0001), respectively. Significant and dose‐dependent placebo‐adjusted mean reductions from baseline to week 12 in FPG and body mass were observed. The fraction of subjects achieving an HbA1c of <7% was significantly greater in the 20 mg bexagliflozin group. The incidence of adverse events was similar for participants in all active arms (42.3%) compared with the rate measured in those receiving placebo (40.3%).

Conclusions

Bexagliflozin confers substantial and dose‐dependent benefits on subjects with type 2 diabetes and has an acceptable safety profile. Further evaluation of bexagliflozin for the control of type 2 diabetes in adults is warranted.
Correlations between immune and metabolic serum markers and schizophrenia/bipolar disorder polygenic risk score in first‐episode psychosis
Authors: Maj Carlo , Tosato Sarah , Zanardini Roberta , Lasalvia Antonio , Favaro Angela , Leuci Emanuela , De Girolamo Giovanni , Ruggeri Mirella , Gennarelli Massimo ,   the GET‐UP GROUP, Bocchio‐Chiavetto Luisella
Published: November 2019

Aims

There is a strong interest in identifying the biological mechanisms involved in the genetic risk for psychotic disorders. In this study, we evaluated the correlation between serum concentrations of specific molecular markers and the genetic component for schizophrenia and bipolar disorder.

Methods

We analysed the association between the polygenic risk score (PRS) and the serum levels of different inflammatory/metabolic markers in a sample of 81 first‐episode psychosis patients (FEP) with a diagnosis of schizophrenia or bipolar disorder and 33 controls.

Results

A positive correlation of schizophrenia and bipolar disorder PRS with the inflammatory marker C‐C Motif Chemokine Ligand 4 serum concentration (ρ = 0.42, P = 1.56 × 10‐04 and ρ = 0.40, P = 1.65 × 10‐03, respectively) and a negative correlation with the serum ghrelin content (ρ = − 0.35, P = 4.27 × 10‐03 and ρ = − 0.45, P = 6.05 × 10‐04, respectively) were observed.

Conclusion

These findings provide new insight into the biological underpinnings of the PRS component, thus supporting a role of the genetic liability on the inflammatory and metabolic alterations that characterize psychosis onset.
Respiratory function and cognitive profile in amyotrophic lateral sclerosis
Authors: Huynh W. , Sharplin L. E. , Caga J. , Highton‐Williamson E. , Kiernan M. C.
Published: November 2019

Background and purpose

Amyotrophic lateral sclerosis (ALS) is increasingly recognized as a multisystem disorder with 30%–50% of patients exhibiting cognitive impairment. The pathophysiological mechanisms of cognitive dysfunction are probably multifactorial although hypoventilation secondary to respiratory dysfunction may contribute to cognitive decline. The current study aimed to identify the relationship between respiratory function in ALS patients and the presence and degree of cognitive impairment.

Methods

Amyotrophic lateral sclerosis patients were prospectively recruited from a multidisciplinary ALS clinic. Baseline clinical assessments including respiratory function as assessed by spirometry were recorded with forced vital capacity (FVC) ≤ 75% considered to be reduced respiratory function. Cognitive testing was performed utilizing the Addenbrooke’s Cognitive Examination (ACE) and the Mini‐Mental State Examination (MMSE).

Results

From a cohort of 100 ALS patients, 48% were categorized as having impaired respiratory function (FVC = 58.24% ± 2.15%) whilst 52% had normal function (88.65% ± 1.27%). Compared to the group with normal respiratory function (ACE 90.68 ± 0.89, MMSE 28.22 ± 0.21), patients with respiratory dysfunction had significantly reduced cognitive function (ACE 86.83 ± 1.5, P = 0.025; MMSE 26.29 ± 0.45, P = 0.029). Furthermore, subscores demonstrated significant differences between the groups with respect to domains in memory (P = 0.003) and attention (P = 0.05) with a trend observed in fluency (P = 0.082). There was a significant correlation between patient baseline FVC and ACE scores as well as between FVC and memory and fluency subscores (P < 0.01).

Conclusion

Amyotrophic lateral sclerosis patients with respiratory compromise were more likely to develop reduced cognitive function. In addition to improving physical function, it remains plausible that non‐invasive ventilation may alter the progression of cognitive impairment in ALS patients and potentially improve overall quality of life and carer burden.
Structural and biochemical analysis of Bacillus anthracis prephenate dehydrogenase reveals an unusual mode of inhibition by tyrosine via the ACT domain
Authors: Shabalin Ivan G. , Gritsunov Artyom , Hou Jing , Sławek Joanna , Miks Charles D. , Cooper David R. , Minor Wladek , Christendat Dinesh
Published: November 2019

Tyrosine biosynthesis via the shikimate pathway is absent in humans and other animals, making it an attractive target for next‐generation antibiotics, which is increasingly important due to the looming proliferation of multidrug‐resistant pathogens. Tyrosine biosynthesis is also of commercial importance for the environmentally friendly production of numerous compounds, such as pharmaceuticals, opioids, aromatic polymers, and petrochemical aromatics. Prephenate dehydrogenase (PDH) catalyzes the penultimate step of tyrosine biosynthesis in bacteria: the oxidative decarboxylation of prephenate to 4‐hydroxyphenylpyruvate. The majority of PDHs are competitively inhibited by tyrosine and consist of a nucleotide‐binding domain and a dimerization domain. Certain PDHs, including several from pathogens on the World Health Organization priority list of antibiotic‐resistant bacteria, possess an additional ACT domain. However, biochemical and structural knowledge was lacking for these enzymes. In this study, we successfully established a recombinant protein expression system for PDH from Bacillus anthracis (BaPDH), the causative agent of anthrax, and determined the structure of a BaPDH ternary complex with NAD+ and tyrosine, a binary complex with tyrosine, and a structure of an isolated ACT domain dimer. We also conducted detailed kinetic and biophysical analyses of the enzyme. We show that BaPDH is allosterically regulated by tyrosine binding to the ACT domains, resulting in an asymmetric conformation of the BaDPH dimer that sterically prevents prephenate binding to either active site. The presented mode of allosteric inhibition is unique compared to both the competitive inhibition established for other PDHs and to the allosteric mechanisms for other ACT‐containing enzymes. This study provides new structural and mechanistic insights that advance our understanding of tyrosine biosynthesis in bacteria.

Enzymes

Prephenate dehydrogenase from Bacillus anthracis (PDH): EC database ID: 1.3.1.12.

Databases

Coordinates and structure factors have been deposited in the Protein Data Bank (PDB) with accession numbers PDB ID: 6U60 (BaPDH complex with NAD+ and tyrosine), PDB ID: 5UYY (BaPDH complex with tyrosine), and PDB ID: 5V0S (BaPDH isolated ACT domain dimer). The diffraction images are available at http://proteindiffraction.org with DOIs: https://doi.org/10.18430/M35USC, https://doi.org/10.18430/M35UYY, and https://doi.org/10.18430/M35V0S.
A new continuum damage mechanics–based two‐scale model for high‐cycle fatigue life prediction considering the two‐segment characteristic in S‐N curves
Authors: Yang Susong , Hu Weiping , Meng Qingchun , Zhao Boyu
Published: November 2019

In this study, we propose a new two‐scale fatigue model based on continuum damage mechanics. A representative volume element (RVE) consisting of microinclusions and a matrix is constructed. Further, damage‐coupled constitutive equations are derived. The degradation in the mechanical properties of the RVE is determined by the damaged inclusions and matrix using the Mori‐Tanaka scheme. A numerical calculation of the fatigue lives of notched specimens is executed. This new model predicts high‐cycle fatigue (HCF) life more effectively, considering the two‐segment characteristic of S‐N curves of smooth specimens. This study provides novel insights into the evolution mechanism of HCF damage.
Sensitivity of mangrove soil organic matter decay to warming and sea level change
Authors: Arnaud Marie , Baird Andy J. , Morris Paul J. , Dang Thuong Huyen , Nguyen Tai Tue
Published: November 2019

Mangroves are among the world's most carbon‐dense ecosystems, but they are threatened by rapid climate change and rising sea levels. The accumulation and decomposition of soil organic matter (SOM) are closely tied to mangroves' carbon sink functions and resistance to rising sea levels. However, few studies have investigated the response of mangrove SOM dynamics to likely future environmental conditions. We quantified how mangrove SOM decay is affected by predicted global warming (+4°C), sea level changes (simulated by altering of the inundation duration to 0, 2, and 6 hr/day), and their interaction. Whilst changes in inundation duration between 2 and 6 hr/day did not affect SOM decay, the treatment without inundation led to a 60% increase. A warming of 4°C caused SOM decay to increase by 21%, but longer inundation moderated this temperature‐driven increase. Our results indicate that (a) sea level rise is unlikely to decrease the SOM decay rate, suggesting that previous mangrove elevation gain, which has allowed mangroves to persist in areas of sea level rise, might result from changes in root production and/or mineral sedimentation; (b) sea level fall events, predicted to double in frequency and area, will cause periods of intensified SOM decay; (c) changing tidal regimes in mangroves due to sea level rise might attenuate increases in SOM decay caused by global warming. Our results have important implications for forecasting mangrove carbon dynamics and the persistence of mangroves and other coastal wetlands under future scenarios of climate change.
‘Being called sisters’: Masculinities and black male nurses in South Africa
Authors: Kalemba Joshua
Published: November 2019

This study contributes to an understanding of the geographies of masculinities, by demonstrating how black South African male nurses negotiate hegemonic masculinity through citing masculine gendered acts. The research draws on qualitative data gathered from interviews with 15 black male nurses aged between 26 and 50 years who have worked in the paediatric, trauma, orthopaedic, oncology and midwifery fields for a period of not less than two years. It is argued that the colonially imposed hierarchies of race, gender and occupation merge with culturally specific pre‐existing African masculinities, and that this informed how the black male nurses experienced their gender identity in the occupation. The study demonstrates how, because of their career choice, the gender identities of the male nurses were positioned as marginalized and subordinate to the modes of a hegemonic masculinity, a gender identity only available to them momentarily. In this context, it was found that the modes of gender performativity in which the nurses negotiated and subverted their subordinate and marginal status was with the complicity of patients and other healthcare workers. This upheld the more generally assumed hegemony of masculinity in the hospital workplace. The study traces these experiences to the discourses of black masculinities during South Africa's pre‐colonial, colonial and apartheid eras and in the present day. In doing so, this study contributes to an understanding of the geographies of masculinities by demonstrating the locally specific modes of masculine performativity through which black male nurses negotiate their gender in South Africa.
Prevalence of apical periodontitis and its association with previous root canal treatment, root canal filling length and type of coronal restoration – a cross‐sectional study
Authors: Meirinhos J. , Martins J. N. R. , Pereira B. , Baruwa A. , Gouveia J. , Quaresma S. A. , Monroe A. , Ginjeira A.
Published: November 2019

Aim

To analyse the prevalence of periapical lesions and their association with previous root canal treatment, root canal filling length and type of coronal restoration using in vivo cone‐beam computed tomographic (CBCT) assessment.

Methodology

A global sample of 20 836 teeth, with a combined total of 27 046 roots, from 1160 patients, was analysed via CBCT assessment in eight health centres. Each tooth was evaluated by one out of five examiners after having performed a defined calibration procedure on the basis of 319 teeth. Intra‐ and inter‐rater reliability tests were performed. Each tooth was classified according the tooth number, presence/absence of periapical lesions, presence/absence of previous root canal treatment, length of root canal filling (short, good or overfilling) and type of coronal restoration. The z‐test for proportions was used to analyse differences between tooth subgroups, and an odds ratio was determined in order to analyse the association between treatment status and periapical lesions. A P < 0.05 was considered significant.

Results

At a tooth level, the overall prevalence of periapical lesions in the sample was 10.4%. Maxillary teeth were associated with a significantly larger percentage of lesions (13.1%), whilst maxillary first molars had the greater proportion of lesions (21.2%). The prevalence of periapical lesions was significantly larger in root filled teeth (55.5%), short root canal fillings (72.7%) and in teeth restored with crowns (46.1%). At a root level, the mesiobuccal roots of both maxillary first molars had a tendency for a larger percentage of periapical lesions.

Conclusion

History of root canal treatment, root canal filling length and type of coronal restoration influenced the presence of periapical lesions. Molars were more commonly associated with periapical lesions on root filled teeth, particularly those with short root fillings and those with crowns.
Development of pectin–eugenol emulsion coatings for inhibition of Listeria on webbed‐rind melons: a comparative study with fig and citrus pectins
Authors: Çavdaroğlu Elif , Farris Stefano , Yemenicioğlu Ahmet
Published: November 2019

The objective of this study was to employ pectin‐based antimicrobial coatings for inhibition of Listeria on surfaces of whole webbed‐rind melons that cause frequent outbreaks of listeriosis. For this purpose, emulsion‐based coatings were developed using citrus pectin (CPEC) or pectin extracted from processing wastes of sun‐dried figs (FPEC) and eugenol (EUG). The emulsions of FPEC and CPEC with EUG (droplet size range: 1.99–11.22 µm) were highly stable for minimum 10 days at 10 °C. The FPEC‐EUG films showed higher flexibility and degree of wettability than CPEC‐EUG films. In contrast, CPEC‐EUG films had a higher gas barrier performance against oxygen at 50% relative humidity than FPEC‐EUG films. The zone inhibition tests showed that FPEC‐EUG films are more effective against Listeria innocua than CPEC‐EUG films. However, FPEC and CPEC coatings with 2% EUG caused 2.2 and 2.7 decimal inactivation of Listeria on Galia melons within 1 week, respectively. The pectin coatings with EUG could reduce the risk of listeriosis from webbed‐rind melons.
Multiple Migration and Use of Ties: Bangladeshis in Italy and Beyond
Authors: Morad Mohammad , Sacchetto Devi
Published: November 2019

This article analyses previous multiple migratory trajectories of Bangladeshi first generation migrants before their arrival in Italy and within Italy. It also uncovers the role of social networks and transnational ties in their multiple migrations. The findings show that their first international migration was mainly shaped by their family’s socio‐economic condition and transnational kinship networks. They already had someone from their family or close relatives in the preferred country with whom they were connected. Their onward relocations until arriving in Italy, in most cases, was to achieve the socio‐economic success and legal status that they had failed to attain in their first and subsequent destinations, but the transnational connections with friends or acquaintances are a key resource facilitating these remigrations. Bangladeshis who arrived in Italy from various countries mostly had networks, either with someone from their local district in Bangladesh or with their earlier fellow migrants who moved to Italy before them.
The Third Design Space: A postcolonial perspective on corporate engagement with open source software communities
Authors: Kendall Kenneth E. , Kendall Julie E. , Germonprez Matt , Mathiassen Lars
Published: November 2019

Corporations increasingly engage with open source software communities in the co‐creation of software. This collaboration between corporate professionals and open source software community members is strikingly different from the early days of software development where for‐profit firms attempted to dominate and control the industry while attempting to throttle the success of independent developers offering an alternative, open source option. While many metaphors like trading zones, common pool resources and ecosystems have helped understand the phenomenon, the metaphors do not portray what the industry was like before and after the transition. We adopt a postcolonial metaphor as an analytical lens to examine such collaboration based on qualitative data gathered over three years from executives, managers and developers within corporations that engage in open source software development. Drawing on these insights, we then theorize a “Third Design Space,” based on the concept of the third space proposed by Bhabha. This metaphor encourages the cultivation of a new design environment, creation of new design associations and circulation of shared design resources. Together these practices and behaviours make it possible to nurture innovative methods and new rituals for designing software with results and methods that represent a distinct departure from the competitive and proprietary past, even creating innovative artefacts that could not have been created without the Third Design Space.
Six Ages of Uncertainty
Authors: Stewart Ian
Published: November 2019

In his new book, Do Dice Play God?, the mathematician Ian Stewart explores our evolving awareness, understanding and quantification of the things we do and do not know
All I Want for Christmas is…Rigorous Validation of Predictive Models to Prevent Hasty Generalisations
Authors: Mateen Bilal , Sonabend Raphael
Published: November 2019

Bilal Mateen and Raphael Sonabend are searching for Santa Claus, armed only with a statistical model to predict ear size based on age. The plan sounds ridiculous, but there's a serious lesson here about the limits of predictive models