bluuebunny/crossref_metadata_2025 huggingface dataset:
Sox2 maintains epithelial cell proliferation in the successional dental lamina
Authors: Kim Eun‐Jung , Jung Seo‐Yoon , Wu Zhaoming , Zhang Sushan , Jung Han‐Sung
Published: November 2019

Objectives

The successional dental lamina is the distinctive structure on the lingual side of the vertebrate tooth germ. The aim of this study was to investigate the relationship among Sox2, Claudin10 and laminin5 and the role of Sox2 in successional dental lamina proliferation during vertebrate tooth development.

Materials and Methods

To understand the successional dental lamina, two types of successional tooth formation, that in geckos (with multiple rounds of tooth generation) and that in mice (with only one round of tooth generation), were analysed.

Results

Unique coexpression patterns of Sox2 and Claudin10 expression were compared in the successional dental lamina from the cap stage to the late bell stage in the mouse tooth germ and in juvenile gecko teeth to support continuous tooth replacement. Furthermore, Laminin5 expression was shown in the cap stage and decreased after the bell stage. Upon comparing the epithelial cell cycles and cell proliferation in successional dental lamina regions between mouse and gecko molars using BrdU and IdU staining and pulse‐chase methods, distinctive patterns of continuous expression were revealed. Moreover, Sox2 overexpression with a lentiviral system resulted in hyperplastic dental epithelium in mouse molars.

Conclusions

Our findings indicate that the regulation of Sox2 in dental lamina proliferation is fundamental to the successional dental lamina in both species.
Electroencephalography reveals a selective disruption of cognitive control processes in craving cigarette smokers
Authors: Donohue Sarah E. , Harris Joseph A. , Loewe Kristian , Hopf Jens‐Max , Heinze Hans‐Jochen , Woldorff Marty G. , Schoenfeld Mircea A.
Published: November 2019

Addiction to nicotine is extremely challenging to overcome, and the intense craving for the next cigarette often leads to relapse in smokers who wish to quit. To dampen the urges of craving and inhibit unwanted behaviour, smokers must harness cognitive control, which is itself impaired in addiction. It is likely that craving may interact with cognitive control, and the present study sought to test the specificity of such interactions. To this end, data from 24 smokers were gathered using EEG and behavioural measures in a craving session (following a three‐hour nicotine abstention period) and a non‐craving session (having just smoked). In both sessions, participants performed a task probing various facets of cognitive control (response inhibition, task switching and conflict processing). Results showed that craving smokers were less flexible with the implementation of cognitive control, with demands of task switching and incongruency yielding greater deficits under conditions of craving. Importantly, inhibitory control was not affected by craving, suggesting that the interactions of craving and cognitive control are selective. Together, these results provide evidence that smokers already exhibit specific control‐related deficits after brief nicotine deprivation. This disruption of cognitive control while craving may help to explain why abstinence is so difficult to maintain.
Investigator‐initiated clinical study of a functional peptide, SR‐0379, for limb ulcers of patients with Werner syndrome as a pilot study
Authors: Nakagami Hironori , Sugimoto Ken , Ishikawa Takahiro , Koshizaka Masaya , Fujimoto Taku , Kiyohara Eiji , Hayashi Misa , Nakagawa Yukinobu , Ando Hiroshi , Terabe Yuta , Takami Yoichi , Yamamoto Koichi , Takeya Yasushi , Takemoto Minoru , Ebihara Tamotsu , Nakamura Ayumi , Nishikawa Mitsunori , Yao Xiang Jing , Hanaoka Hideki , Yokote Koutaro , Rakugi Hiromi
Published: November 2019

Aim

An investigator‐initiated clinical study was carried out to evaluate the therapeutic potency of SR‐0379 for the treatment of leg ulcers in patients with Werner syndrome.

Methods

A multicenter, open‐label study was carried out from September 2017 to February 2018. The inclusion criteria for leg ulcers were: (i) leg ulcers in patients with Werner syndrome, diabetes or critical limb ischemia/venous stasis; and (ii) a wound size of >1 cm and <6 cm in diameter. Four individuals with Werner syndrome and diabetic ulcers, respectively, were enrolled. SR‐0379 (0.1%) was sprayed on skin ulcers once per day for 4 weeks. Efficacy was evaluated by determining the rate of wound size reduction as a primary end‐point at 4 weeks after the first treatment compared with the pretreatment wound size. As secondary end‐points, the DESIGN‐R score index, the 50% wound size reduction ratio, time to wound closure and quantification of wound bacteria were also evaluated. The safety of SR‐0379 was evaluated during the study period.

Results

The reduction rate of ulcer size treated with 0.1% SR‐0379 was 22.90% (mean) in the Werner syndrome ulcers group (n = 4) and 35.70% (mean) in the diabetic ulcers group (n = 4), respectively. The DESIGN‐R score decreased by 4.0 points in the Werner syndrome ulcers group and 4.3 points in the diabetic ulcers group. Two mild adverse events were reported in two patients, and causal relationships were denied in any events.

Conclusion

Treatment with SR‐0379 was safe, well‐tolerated, and effective for leg ulcers of both Werner syndrome and diabetes patients. Geriatr Gerontol Int 2019; 19: 1118–1123.
Reappraisal of the GL‐O Reference Material for K‐Ar Dating: New Insight from Microanalysis, Single‐Grain and Milligram Ar Measurements
Authors: Boulesteix Thomas , Solé Jesús , Pi Teresa , Cathelineau Michel
Published: November 2019

The homogeneity and Ar‐dating suitability of the GL‐O reference material were re‐evaluated to determine whether this material is sufficiently homogeneous to be suitable for the calibration of modern high sensitivity instruments. Based on new micro‐analyses and noble gas determinations, our contribution reveals several kinds of inhomogeneity at the grain scale: disparity in the glauconitisation among and within the pellets, variable occurrence of a phosphatic component within pellets (1% m/m on average), and rare occurrences of calcite and detrital grains. Measurements on test portions of ≤ 1 mg reflect such heterogeneity with variability in 40Ar* content that exceeds analytical uncertainty, including a few highly anomalous values. The lesser evolved glauconite population yielded 40Ar* contents ~ 15% lower than the value of 24.8 nl g−1 recommended by Odin et al. (1982, Numerical dating in stratigraphy. Wiley (Chichester, UK), 123–148). But the measured concentrations of 40Ar* converge towards the aforementioned value as test portion mass increased to > 3 mg. A few rare 3 mg experiments still yielded 40Ar* contents lower than the recommended value (down to 24.0 nl g−1), and we recommend using more conservative minimum masses of 5–10 mg. A further purification step for GL‐O or the intercalibration of its powder version could be considered to diminish the size of the test portions and the intensity of the measured signals.
In God's name: Calling, gender and career success in religious ministry
Authors: Sturges Jane
Published: November 2019

This article uses a gender lens to examine how people with a calling conceptualize what career success means to them, that is, what work‐related outcomes they seek to accomplish in their career. Qualitative data were gathered from ministers of religion working for the Church of England, an organization where gender discrimination is deeply embedded. The findings show that people with the same calling may conceptualize their own career success in quite different ways. Many of the male and female ministers who took part in the study conceived their own career success in a way that reflected the gendered context of the Church of England. This suggests that gender is important for understanding how a calling is pursued in the workplace.
Investigation of the crystallization behavior of laser‐irradiated EXTREME pattern by Raman spectroscopy
Authors: Driggers Megan , Rivero‐Baleine Clara
Published: November 2019

This paper investigates the crystallization behavior of a Ge2Sb2Se4Te1 (GSST) chalcogenide phase change material film using Raman spectroscopy. The properties of as‐deposited, thermally treated, and laser‐written GSST films are investigated. A single mask exposure laser excitation process was developed using a spatial light modulator with an 800 nm femto‐second laser to generate a direct laser‐written EXTREME pattern. The correlation between the laser‐imprinted EXTREME pattern and the phase change transition from amorphous to crystalline state of the GSST film was characterized using Raman spectroscopy.
Residential mobility in early childhood and obesity at kindergarten age among children from the United States
Authors: Krupsky Kathryn L. , Andridge Rebecca R. , Anderson Sarah E.
Published: November 2019

Background

Children who frequently move have poorer behavioural, emotional, and overall health. For similar reasons, the experience of changing home may contextualize children's risk for obesity. Few studies have assessed the relationship between residential mobility and obesity; even fewer explore this relationship with assessment of obesity before school age.

Methods

We analysed data from the Early Childhood Longitudinal Study—Birth Cohort. Obesity at kindergarten age was determined from measured height and weight. Early childhood residential mobility was categorized as not moving or having moved once, twice, or three or more times. Analyses are weighted to be representative of children from the United States and variance estimates account for the complex survey design.

Results

The prevalence of obesity at kindergarten age was 17.5%, and most children (71%) moved in early childhood. Compared with children who did not move, the adjusted odd ratios for obesity at kindergarten age were 0.72 (95% CI, 0.57‐0.92), 0.70 (95% CI, 0.55‐0.89), and 0.64 (95% CI, 0.50‐0.84) for children who experienced 1, 2, or 3+ moves.

Conclusions

Our study suggests that obesity and mobility in early life are associated, but not in the way we might expect. Residential mobility may fit into a broader picture of instability and, on its own, may not elevate a child's risk for obesity.
Non‐parametric association analysis of additive and dominance effects of casein complex SNPs on milk content and quality in Murciano‐Granadina goats
Authors: Pizarro Inostroza María Gabriela , Landi Vincenzo , Navas González Francisco Javier , León Jurado José Manuel , Martínez Martínez María del Amparo , Fernández Álvarez Javier , Delgado Bermejo Juan Vicente
Published: November 2019

Goat milk casein proteins (αS1, αS2, β and κ) are encoded by four loci (CSN1S1, CSN1S2, CSN2 and CSN3, respectively) clustered within 250 kb in chromosome 6. In this study, 159 Murciano‐Granadina goats were genotyped for 48 SNPs within the entire casein region. Phenotypes on milk yield and components were obtained from 2,594 dairy registries. Additive and dominance effects on milk composition and quality were studied using non‐parametric tests and principal component analysis to prevent SNPs multicollinearity. Two deletions in exon 4 (CSN1S1 and CSN3), one in exon 7 (CSN2) and one in exon 15 (CSN1S2) have been found at frequencies ranging from 0.12 to 0.50. Bonferroni‐corrected significant SNP additive and dominance effects were found for milk yield, fat, protein, dry matter and lactose, and somatic cells. Exons 15 and 7 were significantly associated with milk yield and components except for lactose and somatic cells, while exon 4 was significantly associated with milk yield and components except for protein and dry matter. SNPs' associations with somatic cells were less frequent and weaker than those with milk yield and components. As caseins increase, somatic cells decrease, reducing milk enzymatic activity and consumption suitability. Hence, including molecular information in breeding schemes may promote production efficiency, as selecting against undesirable alleles could prevent the compromises derived from their dominance effects.
Important factors in left atrial posterior wall isolation using 28‐mm cryoballoon ablation for persistent atrial fibrillation—Block line or isolation area?
Authors: Nanbu Tadafumi , Yotsukura Akihiko , Suzuki George , Ishidoya Yuki , Sano Fumihiko , Yoshida Izumi , Sakurai Masayuki
Published: November 2019

Introduction

Left atrial (LA) roof ablation using the cryoballoon technique, combined with pulmonary vein isolation (PVI), has been reported to be beneficial for ablation therapy in patients with persistent atrial fibrillation (AF). Left posterior wall ablation also results in improved patient outcomes. However, the contribution of these techniques to the success of cryoballoon ablation (CBA) treatment of AF is not known. The present study examined the influence of the roofline block and isolation area on outcomes after CBA.

Methods and Results

We enrolled 78 patients with persistent AF. LA roof ablation was performed using a 28‐mm cryoballoon with a single freezing of 3 minutes at each region (median number of freezes: 4) after PVI. After CBA, bipolar voltage amplitude mapping was performed during sinus rhythm using the NavX mapping system. Patients were divided into two subgroups according to the voltage and activation map: the roof‐conduction (n = 46) and roofline‐block groups (n = 32). Atrial tachyarrhythmia recurred in 20 patients of the conduction group and 4 patients of the roofline‐block group. The rate of 12‐month freedom from tachyarrhythmia after a single ablation procedure was 78% (95% confidence interval [CI], 60%‐89%) in the roofline‐block group and 45% (95% CI, 30%‐60%) in the conduction group (P = .048). Cox proportional hazard analysis revealed that the isolated area was not a significant predictor of recurrence (hazard ratio, 0.94; 95% CI, 0.86‐1.02; P = .15).

Conclusion

Creating a complete roofline block is the major factor predicting the maintenance of sinus rhythm in patients with persistent AF.
Circular RNA circFOXO3 promotes prostate cancer progression through sponging miR‐29a‐3p
Authors: Kong Zhe , Wan Xuechao , Lu Yali , Zhang Yingyi , Huang Yan , Xu Yi , Liu Yajuan , Zhao Peiqing , Xiang Xinxin , Li Liang , Li Yao
Published: November 2019

Circular RNA FOXO3 (CircFOXO3, also termed as Hsa_circ_0006404) is derived from exon 2 of forkhead box O3 (FOXO3) gene, and abnormal expression is shown in different diseases. However, whether circFOXO3 plays important roles in tumorigenesis and progression of prostate cancer (PCa) remains unclear. In this study, we found that circFOXO3 was up‐regulated in both PCa tissues and serum samples. Moreover, circFOXO3 was positively correlated with the Gleason score in PCa samples. CircFOXO3 was observed to be up‐regulated in Gleason score > 6 PCa samples compared with Gleason score = 6 PCa samples. Knock‐down circFOXO3 could remarkably inhibit PCa cell cycle, proliferation and promote cell apoptosis in vitro. Furthermore, we demonstrated circFOXO3 could act as miR‐29a‐3p sponge to up‐regulate SLC25A15 expression by bioinformatics analysis, dual‐luciferase reporter assays and biotinylated RNA pull‐down assays. SLC25A15 could reverse the tumour suppressing roles of knock‐down circFOXO3 in PCa. Of note, we found that miR‐29a‐3p was down‐regulated; however, SLC25A15 was overexpressed in PCa samples compared with normal tissues. In conclusion, circFOXO3 acts as a miR‐29a‐3p sponge to exhibit oncogenic activity that affects the cell cycle and cell apoptosis in PCa through transcriptional up‐regulation of SLC25A15. Our analysis suggests circFOXO3 could act as promising prostate cancer biomarkers.
The efficacy and safety of pulse vs. continuous therapy for dermatophyte toenail onychomycosis
Authors: Gupta A.K. , Stec N. , Bamimore M.A. , Foley K.A. , Shear N.H. , Piguet V.
Published: November 2019

Background

Onychomycosis is a chronic, fungal infection of the nails. Complete cure remains challenging, but oral antifungal medications have been successful in managing the fungus for a significant proportion of patients. Treatment with these drugs can be continuous or intermittent, albeit the evidence on their relative efficacies remains unclear.

Objective

To determine the relative effectiveness and safety of pulse versus continuous administration, of three common oral therapies for dermatophyte onychomycosis, by conducting multiple‐treatment meta‐analysis.

Methods

This systematic review and network meta‐analysis compared the efficacy (as per mycological cure) and adverse event rates of three oral antifungal medications in the treatment of dermatophyte toenail onychomycosis, namely terbinafine, itraconazole and fluconazole. A total of 30 studies were included in the systematic review, while 22 were included in the network meta‐analysis.

Results

The likelihood of mycological cure was not significantly different between continuous and pulse regimens for each of terbinafine and itraconazole. Use of continuous terbinafine for 24 weeks – but not 12 weeks – was significantly more likely to result in mycological cure than continuous itraconazole for 12 weeks or weekly fluconazole for 9–12 months. Rank probabilities demonstrated that 24‐week continuous treatment of terbinafine was the most effective. There were no significant differences in the likelihood of adverse events between any continuous and pulse regimens of terbinafine, itraconazole and fluconazole. Drug treatments were similar to placebo in terms of their likelihood of producing adverse events.

Conclusion

More knowledge about the fungal life cycle and drugs’ pharmacokinetics in nail and plasma could further explain the relative efficacy and safety of the pulse and continuous treatment regimens. Our results indicate that in the treatment of dermatophyte toenail onychomycosis, the continuous and pulse regimens for terbinafine and itraconazole have similar efficacies and rates of adverse events.
GLUT1 expression in human papillomavirus‐positive anogenital lesions
Authors: Samama B. , Benardais K. , Lipsker D. , Boehm N.
Published: November 2019

Background

GLUT1, an ubiquitous glucose transporter in the mammalian cells, is upregulated in many tumours, including human papillomavirus (HPV)‐induced head and neck or cervical cancer.

Objective

To study in anogenital lesions whether or not GLUT1 expression correlates with genomic high‐risk HPV integration, the first step in neoplastic transformation.

Methods

Forty‐three HPV‐positive biopsies positive for either low‐risk or high‐risk HPV were selected. Paraffin sections adjacent to those tested for the presence of HPV were processed for GLUT1 immunocytochemistry. GLUT1 expression was analysed by two histologists, blinded to HPV type and status and then compared with HPV typing results.

Results

Two main staining patterns were observed, either staining from the basal to the granular layer or staining of superficial layers only. The first staining pattern corresponded to lesions with high number of episomal HPV‐positive nuclei. Superficial staining was observed in lesions with low number of episomal HPV nuclei or when high‐risk HPV was integrated in the cell genome.

Conclusion

Our results show that GLUT1 overexpression correlates with the number of episomally infected cells in the lesion, but not with the type (low or high risk) of HPV.
Significance of the angiotensin I/angiotensin II/angiotensin‐(1‐7) axis in the pathogenesis of systemic sclerosis
Authors: Miziołek B. , Bergler‐Czop B. , Kucharz E. , Kotyla P. , Kopeć‐Mędrek M. , Widuchowska M. , Sieńczyk M. , Brzezińska‐Wcisło L.
Published: November 2019

Background

Systemic sclerosis (SSc) is a multisystemic disease with an extensive microvasculopathy. Previously, disturbances in plasma levels of angiotensin II (Ang II) and its antagonistic angiotensin‐(1‐7) (Ang‐(1‐7)) were found in patients with SSc. Their significance in a pathogenesis of SSc stays unclear due to discrepancies of earlier studies.

Objectives

To evaluate a significance of disturbances in production pathway of angiotensins in a development of SSc.

Methods

There were enrolled 27 patients with established SSc, 23 subjects with very early SSc and 23 healthy controls. The diagnosis of SSc was established in patients who met EULAR/ACR 2013 classification criteria. Very early SSc described patients with Raynaud's phenomenon having SSc‐specific antinuclear antibodies and SSc‐like abnormalities in nailfold videocapillaroscopy. Patients were submitted to evaluation of internal organ involvement and blood sampling to assay plasma levels of angiotensin I, angiotensin II and angiotensin‐(1‐7) with ELISA technique.

Results

Plasma level of angiotensin‐(1‐7) was significantly reduced in both SSc group (median = 47.2 pg/mL; P < 0.001) and ones with very early SSc (median = 102.7 pg/mL; P = 0.002) when compared to healthy controls (median = 176.1 pg/mL). A tendency to higher than in control group (median = 214 pg/mL) plasma level of angiotensin I was seen in SSc group (median = 392 pg/mL; P = 0.059). Differences in plasma level of angiotensin II were insignificant between all study groups. Those disturbances produced unfavourable angiotensin‐(1‐7)/angiotensin II (%) ratio in both groups of patients, which achieved statistical significance in subjects with established SSc (P < 0.001). Production pathway of angiotensins showed a dependence on a subtype of SSc, immune profile and a presence of interstitial lung disease.

Conclusions

Production of angiotensin‐(1‐7) was significantly reduced in both SSc patients and those ones with very early SSc, although a significant imbalance between angiotensin II and angiotensin‐(1‐7) occurred only in subjects with established disease.
Quantifying individual variation in reaction norms: Mind the residual
Authors: Ramakers Jip J. C. , Visser Marcel E. , Gienapp Phillip
Published: November 2019

Phenotypic plasticity is a central topic in ecology and evolution. Individuals may differ in the degree of plasticity (individual‐by‐environment interaction (I × E)), which has implications for the capacity of populations to respond to selection. Random regression models (RRMs) are a popular tool to study I × E in behavioural or life‐history traits, yet evidence for I × E is mixed, differing between species, populations, and even between studies on the same population. One important source of discrepancies between studies is the treatment of heterogeneity in residual variance (heteroscedasticity). To date, there seems to be no collective awareness among ecologists of its influence on the estimation of I × E or a consensus on how to best model it. We performed RRMs with differing residual variance structures on simulated data with varying degrees of heteroscedasticity and plasticity, sample size and environmental variability to test how RRMs would perform under each scenario. The residual structure in the RRMs affected the precision of estimates of simulated I × E as well as statistical power, with substantial lack of precision and high false‐positive rates when sample size, environmental variability and plasticity were small. We show that model comparison using information criteria can be used to choose among residual structures and reinforce this point by analysis of real data of two study populations of great tits (Parus major). We provide guidelines that can be used by biologists studying I × E that, ultimately, should lead to a reduction in bias in the literature concerning the statistical evidence and the reported magnitude of variation in plasticity.
Automated Test Assembly with Mixed‐Integer Programming: The Effects of Modeling Approaches and Solvers
Authors: Luo Xiao
Published: November 2019

Automated test assembly (ATA) is a modern approach to test assembly that applies advanced optimization algorithms on computers to build test forms automatically. ATA greatly improves the efficiency and accuracy of the test assembly. This study investigated the effects of the modeling methods and solvers in the mixed‐integer programming (MIP) approach to ATA in the context of assembling parallel linear test forms and multistage testing (MST) panels. The results of two simulation studies indicated that the newly proposed maximin modeling method significantly improved the parallelism of the test information functions (TIFs) among assembled test forms while maintaining relatively high overall TIFs, and the newly proposed binary minimax method considerably reduced the overall discrepancies from the targets. A comparison of four freely available noncommercial MIP solvers from the utilitarian, as opposed to the benchmarking, perspective was also included in this study.
Use of fluid structure interaction technique for flash flood impact assessment of structural components
Authors: Kankanamge Sunindu L. , Mendis Priyan , Ngo Tuan
Published: November 2019

Prediction of the initial impact force is a major task associated with flood damage assessment of structures subjected to flash flooding especially due to dam break and levee breach. Investigation of failure modes such as overturning and sliding due to soil scouring or erosion is not relevant if the structure first fails by the massive initial dynamic impact. Therefore, a careful assessment of the initial flood impact is critical for the design of structures and during the flood damage assessment process. In most of the past flood damage studies, total flood load acting on the structures was estimated by maximum velocities and water depths obtained from the two‐dimensional hydrodynamic models or the field data. The outcome of these results has shown potential uncertainty in current methods. We present a new approach to calculate the load on structural components impacted by a dam break wave, by modelling the three‐dimensional free surface fluid–structure interaction (FSI) using the incompressible computational fluid dynamics (ICFD) techniques. Two experimental datasets available in the literature are used to validate the results. Finally, we conclude that FSI/IFCD method can be used to accurately determine the initial impact force on structural components subjected to flash floods for flood damage assessment.
Evolutionary basis for the human diet: consequences for human health
Authors: Andrews P. , Johnson R.J.
Published: November 2019

The relationship of evolution with diet and environment can provide insights into modern disease. Fossil evidence shows apes, and early human ancestors were fruit eaters living in environments with strongly seasonal climates. Rapid cooling at the end of the Middle Miocene (15–12 Ma: millions of years ago) increased seasonality in Africa and Europe, and ape survival may be linked with a mutation in uric acid metabolism. Climate stabilized in the later Miocene and Pliocene (12–5 Ma), and fossil apes and early hominins were both adapted for life on ground and in trees. Around 2.5 Ma, early species ofHomointroduced more animal products into their diet, and this coincided with developing bipedalism, stone tool technology and increase in brain size. Early species ofHomosuch asHomo habilisstill lived in woodland habitats, and the major habitat shift in human evolution occurred at 1.8 Ma with the origin ofHomo erectus.Homo erectushad increased body size, greater hunting skills, a diet rich in meat, control of fire and understanding about cooking food, and moved from woodland to savannah. Group size may also have increased at the same time, facilitating the transmission of knowledge from one generation to the next. The earliest fossils ofHomo sapiensappeared about 300 kyr, but they had separated from Neanderthals by 480 kyr or earlier. Their diet shifted towards grain‐based foods about 100 kyr ago, and settled agriculture developed about 10 kyr ago. This pattern remains for many populations to this day and provides important insights into current burden of lifestyle diseases.
NUDT1: A potential independent predictor for the prognosis of patients with oral squamous cell carcinoma
Authors: Shen Yuchen , Zhang Lei , Piao Songlin , Li Lili , Li Jianhao , Xia Yanyun , Li Jichen , Saiyin Wuliji
Published: November 2019

Objective

The current study was aimed to investigate the association of nudix hydrolase 1 (NUDT1) levels with the prognosis of oral squamous cell carcinoma (OSCC) patients.

Material and Methods

Western immunoblotting and qRT‐PCR were used to detect the protein and mRNA levels of NUDT1 in 31 cases of OSCC and normal tissues. The paraffin‐embedded 62 cases of OSCC and 18 normal tissues were collected, and the pathological alterations were assessed by immunohistochemistry. The prognosis of all patients was followed up. Kaplan‐Meier method was used to analyze the survival rate, and Cox regression was used for multivariate analysis.

Results

Both the protein and gene levels of NUDT1 were statistically increased (P = .0007 and P < .0001) in the OSCC tissue and had a significant association with the histopathologic grades of OSCC (P < .0001 and P = .0223). Immunohistochemistry detection of NUDT1 in 62 human OSCC tissues and 18 normal control tissues showed that NUDT1 expression was significantly increased in OSCC tissue and showed a strong association with histopathologic grades (P < .0001) and tumor stage (P = .005). Patients with high NUDT1 expression exhibited poorer overall survival rate (OS) and tumor‐specific survival rate (TSS) than those with low NUDT1 expression (P < .0001 and P = .0008), and NUDT1 was independent prognostic factors for OS and TSS (P < .0001 and P < .001).

Conclusion

The expression level of NUDT1 might be used to predict the prognosis of OSCC patients.
Adaptation of aerobic training essentially involved autophagy, mitochondrial marker and muscle fibre genetic modulation in rat cardiac muscles
Authors: Gunadi Julia Windi , Tarawan Vita Murniati , Setiawan Iwan , Goenawan Hanna , Ratnawati Hana , Limyati Yenni , Adhika Oeij Anindita , Santoso Andreas Wardono , Lesmana Ronny , Supratman Unang
Published: November 2019

Information about the role of moderate acute treadmill training in modulating autophagy and mitochondrial markers that might be correlated with alteration of muscle fibre gene expression in rat cardiac muscles is very limited. In this present study, the researchers divided twenty male Wistar rats into four groups: sedentary control, 3, 6 and 15 days and subjected them to treadmill training with moderate intensity (20 m/min), 30 min each day. RNA was extracted from cardiac muscles and stored in temperature of −80°C. Specific primers were utilized for semi‐quantitative PCR. Treadmill training decreased autophagy‐related gene expression (LC3, p62) and upper stream signalling of autophagy (PIK3CA, Akt and mTOR) in 3 and 6 d, but stimulated gene expression of mitochondrial markers (PGC1α, Cox1, Cox2 and Cox4) in 15 days. αMHC gene expression increased while βMHC gene expression decreased in 15 days. In line with this, autophagy‐related genes increased in 3 and 6 days and returned to baseline in 15 days. The increment in mitochondrial gene expression might be correlated with shifting gene expression of αMHC and βMHC in 15 days. Taken together, acute adaptation in cardiac muscles is stimulated by genetic modulation of autophagy, mitochondrial marker and muscle fibre that may explain physiological cardiac adaptation after training. This study can be used as a reference for optimizing performance in period of cardiac muscle adaptation stimulated by treadmill training.
Influence of historical landscape on aquatic plant diversity
Authors: Jamoneau Aurélien , Bouraï Liess , Devreux Lise , Percaille Louise , Queau Audrey , Bertrin Vincent
Published: November 2019

Questions

The historical composition of landscapes is recognized as an important factor for explaining plant diversity, because species assemblages are not only patterned by current ecological conditions, but also represent legacies of the past. Contrary to terrestrial ecosystems, the influence of history has rarely been considered for aquatic communities. Here, we examined the effect of past land use on aquatic plant communities of freshwater shallow lakes. We first aimed to identify the relevant scale for studying landscape effects on macrophyte communities and then to test the relative influence of environmental variables and past and recent land use on aquatic plant assemblages.

Location

Atlantic coastline, southwestern France.

Methods

We surveyed shoreline macrophyte communities of 17 lakes and used species accumulation curves to estimate taxonomic richness. We used water chemistry and lakes’ morphological features as environmental variables and reconstructed land‐use occupancies of lakes’ watershed with aerial pictures of 1945, 1965, 1985 (past) and 2002 (recent). We examined landscape change with principal component analysis and taxonomic composition with non‐metrical multidimensional scaling. We then evaluated the relative influence of morphological, chemical, past and recent land‐use factors on taxonomic richness and composition with variation partitioning methods.

Results

We found that the studied landscapes exhibit a trend toward an increase of urban and arable fields areas at the expense of semi‐natural ones. Water chemical composition and past land use of the whole watershed (particularly urban and semi‐urban areas) were strongly inter‐correlated, and explained the major part of the variation of taxonomic richness and composition.

Conclusions

These results underline the importance of historical factors in explaining aquatic plant diversity and suggest delayed responses of communities to anthropogenic pressures. Integrating historical factors in future analyses of aquatic ecosystems would thus greatly contribute to understanding ecological processes, and is crucial for the conservation and management of macrophyte communities.
Ready for change: Seed traits contribute to the high adaptability of mudflat species to their unpredictable habitat
Authors: Phartyal Shyam S. , Rosbakh Sergey , Ritz Christian , Poschlod Peter
Published: November 2019

Question

A better understanding of species distribution and establishment requires in‐depth information on their seed ecology. We hypothesised that seed traits of mudflat species may indicate a strong environmental adaptation in their highly specialised habitat. Furthermore, we asked the question, do seeds of mudflat species have a specific trait value to contribute high adaptability to small‐scale variation in their unpredictable habitat?

Location

Central Europe.

Methods

Seeds of 30 typical mudflat species were used to measure 15 traits that govern seed dispersal (buoyancy and production), persistence (seed desiccation, mass and persistence in soil), and germination and establishment (germination response to different light, temperature and oxygen conditions). Cluster analysis and phylogenetic principal components analysis (pPCA) were conducted to define potential mudflat species functional groups as per their ecological optima.

Results

Seed production and seed mass displayed extremely high variation while seed buoyancy, desiccation and persistence in soil showed almost no variation. All study species produced buoyant, desiccation‐tolerant and long‐term persistent seeds. Germination and establishment traits also displayed similarity in their responses to different germination treatments as the majority (73%) of species has a moderate seed germination niche width. They germinated well under light/aerobic conditions irrespective to temperature fluctuations. The cluster analysis and pPCA separated species into three potential plant functional groups as ‘true’, ‘flood‐resistant’ and ‘facultative’, mudflat species.

Conclusion

Moderate variation in the seed traits of mudflat plants suggests they employ different ecological strategies that seem highly predictive to the peculiarity of their specific micro‐habitats, which are largely controlled by the hydroperiod gradient. It implies that seed trait information, which further needs to be tested for their adaptability, can advance our understanding of how community composition at the micro‐habitat level depends on trait values of participating species.
Decomposing demographic contributions to the effective population size with moose as a case study
Authors: Lee Aline Magdalena , Myhre Ane Marlene , Markussen Stine Svalheim , Engen Steinar , Solberg Erling Johan , Haanes Hallvard , Røed Knut , Herfindal Ivar , Heim Morten , Sæther Bernt‐Erik
Published: November 2019

Levels of random genetic drift are influenced by demographic factors, such as mating system, sex ratio and age structure. The effective population size (Ne) is a useful measure for quantifying genetic drift. Evaluating relative contributions of different demographic factors to Ne is therefore important to identify what makes a population vulnerable to loss of genetic variation. Until recently, models for estimating Ne have required many simplifying assumptions, making them unsuitable for this task. Here, using data from a small, harvested moose population, we demonstrate the use of a stochastic demographic framework allowing for fluctuations in both population size and age distribution to estimate and decompose the total demographic variance and hence the ratio of effective to total population size (Ne/N) into components originating from sex, age, survival and reproduction. We not only show which components contribute most to Ne/N currently, but also which components have the greatest potential for changing Ne/N. In this relatively long‐lived polygynous system we show that Ne/N is most sensitive to the demographic variance of older males, and that both reproductive autocorrelations (i.e., a tendency for the same individuals to be successful several years in a row) and covariance between survival and reproduction contribute to decreasing Ne/N (increasing genetic drift). These conditions are common in nature and can be caused by common hunting strategies. Thus, the framework presented here has great potential to increase our understanding of the demographic processes that contribute to genetic drift and viability of populations, and to inform management decisions.
‘Man up’: Medical students’ perceptions of gender and learning in clinical practice: A qualitative study
Authors: Samuriwo Ray , Patel Yasumati , Webb Katie , Bullock Alison
Published: November 2019

Context

Gender‐related inequality and disparity hinders efforts to develop a medical workforce that facilitates universal access to safe, just and equitable health care. Little is known about how medical students perceive the impact of their gender on their learning in clinical practice. Our aim in this study was to address this gap, establishing students’ perceptions of the impact of their gender on learning in the clinical context as part of the wider medical education community of practice.

Methods

We undertook a qualitative study that simultaneously gathered data through narrative individual interviews and online case reports from male and female students (n = 31) from different academic cohorts with prior experience of clinical practice in a Russell Group University medical school in the UK. Interviews were transcribed and analysed thematically alongside case report data.

Results and discussion

The participants revealed that there was a culture in clinical practice where their gender influenced how they were taught and supported by senior medical and surgical colleagues. Gender was also said to determine the clinical learning opportunities afforded to students, especially with regards to the care of patients of a different gender. The mentorship and support for learning provided to students in clinical practice was also said to be influenced by the medical student's gender.

Conclusion

Our findings suggest that students undergo a gendered clinical apprenticeship within what are in effect gendered communities of practice with some distinct features. These findings underscore the imperative for further work to establish how medical students of all genders can be supported to fulfil their potential in clinical practice.
Positional cloning and characterization of the papaya diminutive mutant reveal a truncating mutation in the CpMMS19 gene
Authors: Wang Ying , Singh Ratnesh , Tong Eric , Tang Min , Zheng Liwei , Fang Hongkun , Li Ruoyu , Guo Lin , Song Jinjin , Srinivasan Rajeswari , Sharma Anupma , Lin Lianyu , Trujillo Jorge A. , Manshardt Richard , Chen Li‐Yu , Ming Ray , Yu Qingyi
Published: November 2019

The papaya diminutive mutant exhibits miniature stature, retarded growth and reduced fertility. This undesirable mutation appeared in the variety ‘Sunset’, the progenitor of the transgenic line ‘SunUp’, and was accidentally carried forward into breeding populations.

The diminutive mutation was mapped to chromosome 2 and fine mapped to scaffold 25. Sequencing of a bacterial artificial chromosome in the fine mapped region led to the identification of the target gene responsible for the diminutive mutant, a gene orthologous to MMS19 with a 36.8 kb deletion co‐segregating with the diminutive mutant.

The genomic sequence of CpMMS19 is 62 kb, consisting of 20 exons and 19 introns. It encodes a protein of 1143 amino acids while the diminutive allele encodes a truncated protein of 287 amino acids. Expression of the full‐length CpMMS19 was able to complement the thermosensitive growth of the yeast mms19 deletion mutant while expression of the diminutive allele resulted in increased thermosensitivity. Over‐expression of the diminutive allele in Arabidopsis met18 mutant results in a high frequency of seed abortion.

The papaya diminutive phenotype is caused by an alteration in gene function rather than a loss‐of‐function mutation. SCAR (sequence characterized amplified region) markers were developed for rapid detection of the diminutive allele in breeding populations.
Regional distribution patterns of wetland monocots with different root turnover strategies are associated with local variation in soil temperature
Authors: Courchesne Dominique N. , Wilson Adrienne Z. , Ryser Peter
Published: November 2019

Herbaceous perennial wetland monocots in Northern Ontario, Canada, show dichotomous root overwintering patterns, either with full senescence in autumn or survival over the winter, comparable to deciduous and evergreen leaf habits in trees.

To test if these root strategies differ in their associations with growing season length, soil temperatures were recorded in autumn, winter and spring on 38 wetland sites with their dominant species being either of these two root overwintering strategies, altogether 19 monocot species. Traits associated with these strategies were assessed in garden experiments for a subset of these species.

Sites with species with autumn‐senescing roots were, on average, warmer than sites with species with overwintering roots. The 13 coldest sites were all sites of species with overwintering roots. Spring shoot growth in the field was delayed in species with autumn‐senescing roots, despite their higher shoot relative growth rates in the garden, possibly due to the necessity to produce roots first.

We conclude that species with autumn‐senescing roots are more constrained by temperature than species with overwintering roots, limiting their occurrence in cool climates to locally warm soils and constraining their distribution towards the north. This is comparable to constraints on distribution of deciduous and evergreen trees.
Phospholipase D‐derived phosphatidic acid promotes root hair development under phosphorus deficiency by suppressing vacuolar degradation of PIN‐FORMED2
Authors: Lin De‐Li , Yao Hong‐Yan , Jia Li‐Hua , Tan Jin‐Fang , Xu Zhi‐Hong , Zheng Wen‐Ming , Xue Hong‐Wei
Published: November 2019

Root hair development is crucial for phosphate absorption, but how phosphorus deficiency affects root hair initiation and elongation remains unclear.

We demonstrated the roles of auxin efflux carrier PIN‐FORMED2 (PIN2) and phospholipase D (PLD)‐derived phosphatidic acid (PA), a key signaling molecule, in promoting root hair development in Arabidopsis thaliana under a low phosphate (LP) condition.

Root hair elongation under LP conditions was greatly suppressed in pin2 mutant or under treatment with a PLDζ2‐specific inhibitor, revealing that PIN2 and polar auxin transport and PLDζ2‐PA are crucial in LP responses. PIN2 was accumulated and degraded in the vacuole under a normal phosphate (NP) condition, whereas its vacuolar accumulation was suppressed under the LP or NP plus PA conditions. Vacuolar accumulation of PIN2 was increased in pldζ2 mutants under LP conditions. Increased or decreased PIN2 vacuolar accumulation is not observed in sorting nexin1 (snx1) mutant, indicating that vacuolar accumulation of PIN2 is mediated by SNX1 and the relevant trafficking process. PA binds to SNX1 and promotes its accumulation at the plasma membrane, especially under LP conditions, and hence promotes root hair development by suppressing the vacuolar degradation of PIN2.

We uncovered a link between PLD‐derived PA and SNX1‐dependent vacuolar degradation of PIN2 in regulating root hair development under phosphorus deficiency.
Bariatric surgery is a cost‐saving treatment for obesity—A comprehensive meta‐analysis and updated systematic review of health economic evaluations of bariatric surgery
Authors: Xia Qing , Campbell Julie A. , Ahmad Hasnat , Si Lei , de Graaff Barbara , Palmer Andrew J.
Published: November 2019

Demand for bariatric surgery to treat severe and resistant obesity far outstrips supply. We aimed to comprehensively synthesise health economic evidence regarding bariatric surgery from 1995 to 2018 (PROSPERO registration number: CRD42018094189). Meta‐analyses were conducted to calculate the annual cost changes “before” and “after” surgery, and cumulative cost differences between surgical and nonsurgical groups. An updated narrative review also summarized the full and partial health economic evaluations of surgery from September 2015. N = 101 studies were eligible for the qualitative analyses since 1995, with n = 24 studies after September 2015. Quality of reporting has increased, and the inclusion of complications/reoperations was predominantly contained in the full economic evaluations after September 2015. Technical improvements in surgery were also reflected across the studies. Sixty‐one studies were eligible for the quantitative meta‐analyses. Compared with no/conventional treatment, surgery was cost saving over a lifetime scenario. Additionally, consideration of indirect costs through sensitivity analyses increased cost savings. Medication cost savings were dominant in the before versus after meta‐analysis. Overall, bariatric surgery is cost saving over the life course even without considering indirect costs. Health economists are hearing the call to present higher quality studies and include the costs of complications/reoperations; however, indirect costs and body contouring surgery are still not appropriately considered.