bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of p16 and p21 in the frontal association cortex of ALS/MND brains suggests neuronal cell cycle dysregulation and astrocyte senescence in early stages of the disease
Authors: Vazquez‐Villaseñor I. , Garwood C. J. , Heath P. R. , Simpson J. E. , Ince P. G. , Wharton S. B. 
Published: May 2019

AimsCellular senescence plays a role in organismal ageing and has been linked to persistent DNA damage in age‐related diseases. Brain senescence has been described in astrocytes and microglia, but it is less well understood in neurones. Evidence suggests that neurones activate a senescence‐like mechanism that could contribute to neurodegeneration. We aimed to determine whether a persistent DNA damage response (DDR) and senescence activation are features of motor neurone disease (amyotrophic lateral sclerosis, ALS/MND).MethodsWe examined expression of senescence (p16 and p21) and DNA damage markers (8‐OHdG and γH2AX) in motor cortex (MCx), frontal association cortex (FACx) and occipital cortex (OCx) in post‐mortem tissue donated by patients with ALS/MND and controls.ResultsNuclear expression of p16 and p21 was detected in glial cells; double immunofluorescence for p16/p21 and glial fibrillary acidic protein (GFAP) suggested that some of these cells were GFAP+ astrocytes. p21 nuclear expression was also found in neurones. Higher levels of p16+ (glia, P = 0.028) and p21+ (glia, P = 0.003; neurones, P = 0.008) cells were found in the FACx of ALS/MND donors but not in the MCx or OCx. Expression of p16 and p21 did not correlate with 8‐OHdG or γH2AX.ConclusionsExpression of p16 and p21 in glia, mainly in astrocytes, suggests senescence induction in these cells; however, neuronal p21 expression might reflect a more general mechanism of age‐related cell cycle dysregulation. The significantly higher proportion of cells expressing either p16 or p21 in the FACx of ALS/MND donors could indicate senescence activation and cell cycle dysregulation in early stages of the disease.
Phylogenomic analysis reveals multiple evolutionary origins of selfing from outcrossing in a lineage of heterostylous plants
Authors: Zhong Li , Barrett Spencer C. H. , Wang Xin‐Jia , Wu Zhi‐Kun , Sun Hua‐Ying , Li De‐Zhu , Wang Hong , Zhou Wei 
Published: May 2019

Summary

Evolutionary transitions from outcrossing to selfing often occur in heterostylous plants. Selfing homostyles originate within distylous populations and frequently evolve to become reproductively isolated species. We investigated this process in 10 species of Primula section Obconicolisteri using phylogenomic approaches and inferred how often homostyly originated from distyly and its consequences for population genetic diversity and floral trait evolution.

We estimated phylogenetic relationships and reconstructed character evolution using the whole plastome comprised of 76 protein‐coding genes. To investigate mating patterns and genetic diversity we screened 15 microsatellite loci in 40 populations. We compared floral traits among distylous and homostylous populations to determine how phenotypically differentiated homostyles were from their distylous ancestors.

Section Obconicolisteri was monophyletic and we estimated multiple independent transitions from distyly to homostyly. High selfing rates characterised homostylous populations and this was associated with reduced genetic diversity. Flower size and pollen production were reduced in homostylous populations, but pollen size was significantly larger in some homostyles than in distylous morphs.

Repeated transitions to selfing in section Obconicolisteri are likely to have been fostered by the complex montane environments that species occupy. Unsatisfactory pollinator service is likely to have promoted reproductive assurance in homostyles leading to subsequent population divergence through isolation.
Surgical management of a large radicular cyst using modified guided tissue regeneration techniques: a case report with 4 years follow‐up
Authors: Camargo J.M.P. , Braga T. , Camargo R. , Love R.M. , Reher P. 
Published: May 2019

AbstractThis case report discusses the management of a large radicular cyst using current periapical surgery techniques associated with the use of modified guided tissue regeneration (GTR) techniques. The cyst involved several anterior teeth and measured 40 mm in its widest dimension, involving both cortical plates, and extending into the floor of the nose. The surgical endodontics techniques used here included the use of enhanced magnification, minimal root resection, ultrasonic root‐end preparation and retrograde obturation with a bioceramic root repair material. The large bone defect was reconstructed with the use of a mixture of autogenous bone harvested from the mandibular ramus, Bio‐oss® and platelet‐rich fibrin (PRF), covered with a thin PRF membrane acting as a modified GTR. The combination of these techniques ensured successful clinical, radiographic and tomographic outcomes after 4 years of follow‐up.
Can noninvasive testing identify benign patterns of suggested pre‐excitation on electrocardiogram?
Authors: Robinson Jeffrey A. , Anderson Jeffrey B. , Knilans Timothy K. , Spar David S. , Czosek Richard J. 
Published: May 2019

AbstractBackgroundThe presence of anterograde conduction through an accessory pathway (AP) has been linked to sudden cardiac death. Unfortunately, pre‐excitation associated with classic pathways can be difficult to differentiate from benign APs such as nodofascicular fibers.ObjectiveIdentifying characteristics on electrocardiogram (ECG) and exercise that differentiate classic and benign AP connections in suggested pre‐excitation patterns.MethodsRetrospective review of patients presenting between 1995 and 2017 with ventricular pre‐excitation on ECG, determined to have either typical left‐lateral AP during electrophysiology study (EPS), or benign, or no AP determined by either transesophageal electrophysiology study (TEP), or EPS.ResultsA total of 96 patients were included, 14.2 years (4‐24), 45% female, 90% Caucasian. Of these, 60 (63%) had a classic APs identified on EPS and 58 (97%) underwent successful ablation. Conversely, 36 (37%) had benign pathways identified. ECG findings differed between the groups: PR‐interval 102 versus 120 ms (P < .0001), QRS‐duration 110 versus 102 ms (P < .0001), QRS‐axis 74 versus 59 degrees (P = .0005), and QRS onset to peak R/S in limb leads 64 versus 42 ms (P < .0001), and precordial leads 66 versus 46 ms (P < .0001). Change in QRS duration during exercise differed between the groups: 25 versus 2 ms (P < .0001) and ECG characteristics identified the presence of an AP with 97% sensitivity and 94% negative predictive value.ConclusionClassic and benign APs exhibit different ECG characteristics, though clinical overlap does not allow for absolute differentiation. These data may help with risk stratification decision making though does not obviate the need for additional invasive testing.
Genetic dissection of drought and heat‐responsive agronomic traits in wheat
Authors: Li Long , Mao Xinguo , Wang Jingyi , Chang Xiaoping , Reynolds Matthew , Jing Ruilian 
Published: May 2019

AbstractHigh yield and wide adaptation are principal targets of wheat breeding but are hindered by limited knowledge on genetic basis of agronomic traits and abiotic stress tolerances. In this study, 277 wheat accessions were phenotyped across 30 environments with non‐stress, drought‐stressed, heat‐stressed, and drought‐heat‐stressed treatments and were subjected to genome‐wide association study using 395 681 single nucleotide polymorphisms. We detected 295 associated loci including consistent loci for agronomic traits across different treatments and eurytopic loci for multiple abiotic stress tolerances. A total of 22 loci overlapped with quantitative trait loci identified by biparental quantitative trait loci mapping. Six loci were simultaneously associated with agronomic traits and abiotic stress tolerance, four of which fell within selective sweep regions. Selection in Chinese wheat has increased the frequency of superior marker alleles controlling yield‐related traits in the four loci during past decades, which conversely diminished favourable genetic variation controlling abiotic stress tolerance in the same loci; two promising candidate paralogous genes colocalized with such loci, thereby providing potential targets for studying the molecular mechanism of stress tolerance–productivity trade‐off. These results uncovering promising alleles controlling agronomic traits and/or multiple abiotic stress tolerances, providing insights into heritable covariation between yield and abiotic stress tolerance, will accelerate future efforts for wheat improvement.
The TYRP1‐mediated protection of human tyrosinase activity does not involve stable interactions of tyrosinase domains
Authors: Dolinska Monika B. , Wingfield Paul T. , Young Kenneth L. , Sergeev Yuri V. 
Published: May 2019

AbstractTyrosinases are melanocyte‐specific enzymes involved in melanin biosynthesis. Mutations in their genes cause oculocutaneous albinism associated with reduced or altered pigmentation of skin, hair, and eyes. Here, the recombinant human intra‐melanosomal domains of tyrosinase, TYRtr (19–469), and tyrosinase‐related protein 1, TYRP1tr (25–472), were studied in vitro to define their functional relationship. Proteins were expressed or coexpressed in whole Trichoplusia ni larvae and purified. Their associations were studied using gel filtration and sedimentation equilibrium methods. Protection of TYRtr was studied by measuring the kinetics of tyrosinase diphenol oxidase activity in the presence (1:1 and 1:20 molar ratios) or the absence of TYRP1tr for 10 hr under conditions mimicking melanosomal and ER pH values. Our data indicate that TYRtr incubation with excess TYRP1tr protects TYR, increasing its stability over time. However, this mechanism does not appear to involve the formation of stable hetero‐oligomeric complexes to maintain the protective function.
Trends and factors in antipsychotic use of outpatients with anxiety disorders in Taiwan, 2005–2013: A population‐based study
Authors: Huang Chih‐Wan , Chiu Yu‐Wen , Chen Pei‐Jung , Yu Nan‐Wen , Tsai Hui‐Ju , Chang Chia‐Ming 
Published: May 2019

AimAntipsychotics off‐label use is common in clinical practice but information is limited in regards to the trends of antipsychotic use in specific mental disorders in Taiwan. This study aimed to examine the trends and associated factors of antipsychotic use among outpatients with anxiety disorders in Taiwan during 2005–2013.MethodsWe assessed the annual prescriptions of antipsychotic use in nine consecutive years (2005–2013) using the National Health Insurance Research Database among adults (aged ≥18 years) with anxiety disorders in outpatient visits in Taiwan. We applied logistic regression to examine the trends and associated factors of antipsychotic use.ResultsThe proportion of antipsychotic medication use for anxiety disorder increased from 8.4% in 2005 to 9.1% in 2013. First‐generation antipsychotics (FGA) use was more than that of second‐generation antipsychotics (SGA) use in patients with anxiety disorder through the 9‐year period. Sulpiride and flupentixol were the two most common FGA in the treatment of anxiety disorder. Patients with specific anxiety disorder (post‐traumatic stress disorder, panic disorder/agoraphobia, generalized anxiety disorder, and obsessive–compulsive disorder), female sex, younger age (age < 65 years), comorbidity with major depression or minor depression, antidepressants concurrent use, and visits to psychiatrists, medical centers and primary care were significantly more likely to take prescribed antipsychotics.ConclusionAntipsychotic off‐label use significantly increased among patients with anxiety disorder in this national representative cohort. Such increased use of antipsychotics could be driven by augmentation of their prescription for major depression. As their efficacy and safety remain uncertain, further study is warranted.
Cellular characterization of actin gene concerned with contact‐dependent mechanisms in Naegleria fowleri
Authors: Sohn Hae‐Jin , Song Kyoung‐Ju , Kang Heekyoung , Ham A‐Jeong , Lee Jae‐Ho , Chwae Yong‐Joon , Kim Kyongmin , Park Sun , Kim Jong‐Hyun , Shin Ho‐Joon 
Published: May 2019

AbstractFree‐living amoeba, Naegleria fowleri, destroys target cells through contact‐dependent mechanisms, such as phagocytosis and/or trogocytosis. A previous experiment showed that the nf‐actin gene consisted of 1.2 kbp, produced a 50.1 kDa recombinant protein (Nf‐actin), and was localized on the cytoskeleton, pseudopodia and amoebastome. In this study, cellular characterization of the nf‐actin gene concerned with contact‐dependent mechanisms in N fowleri was performed. The nf‐actin gene was amplified from a gene‐cloned vector, pEXQP5‐T7/NT TOPO. The nf‐actin gene was introduced into the Ubi‐pEGFP‐C2 vector, and Ubi‐pEGFP‐C2/nf‐actin was transfected into N fowleri trophozoites. Strong GFP fluorescence was detected in N fowleri trophozoites transfected with Ubi‐pEGFP‐C2/nf‐actin. Expression of EGFP‐Nf‐actin protein was detected by Western blot analysis. The nf‐actin‐overexpressing N fowleri showed significantly increased adhesion activity against extracellular matrix components, fibronectin, collagen I and fibrinogen, compared with wild‐type N fowleri. Moreover, nf‐actin‐overexpressing N fowleri showed increased phagocytic activity and cytotoxicity in comparison with wild‐type N fowleri. In summary, the overexpressed nf‐actin gene has an important function in ability to increase cell adhesion, cytotoxicity and phagocytosis by N fowleri.
Combined microRNAome and transcriptome analysis of follicular phase and luteal phase in porcine ovaries
Authors: Zhang Xiaodong , Zhang Liang , Shang Jinnan , Tao Qiangqiang , Tian Mi , Ma Yingchun , Xu Yiliang , Ding Yueyun , Zhou Rong , Li Kui , Yin Zongjun 
Published: May 2019

AbstractThe aim of this study was to explore the expression difference of miRNAs and mRNAs between the follicular phase (FP) and luteal phase (LP) in porcine ovaries and provide a theoretical basis for the research on mammalian reproductive regulation. RNA‐Seq and miRNA‐Seq were used to identify differentially expressed genes (DEGs) and miRNAs (DEMs) between the FP and LP in ovaries of six sows (3‐year‐old Yorkshire pigs with similar weights and same parities). Bioinformatic analysis was used to screen potential genes and miRNAs related to porcine ovarian function. Real‐time qualitative PCR was used to validate the sequencing results. RNA‐Seq results showed that 3,078 genes were up‐regulated, and 1,444 genes were down‐regulated in the LP compared with the FP, and DEGs were significantly enriched in 242 Gene Ontology (GO) terms and 33 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. miRNA‐Seq identified 112 DEMs, of which 25 were up‐regulated and 87 were down‐regulated in the LP compared with the FP. We obtained 186 intersection genes (IGs) between the 4,522 DEGs and 2,444 target genes predicted from the 112 DEMs. After constructing a miRNA‐gene‐pathway network, we identified key miRNAs and genes including miR‐17‐3p, miR‐214, miR‐221‐5p, miR‐125b, FGF1, YWHAG, YWHAZ, FDFT1 and DHCR24, which are enriched in Hippo and PI3K‐Akt signalling pathways, and various metabolic pathways. These results indicate that these key genes and miRNAs may play important roles in the developmental transition from FP to LP in porcine ovaries and represent candidate targets for further study.
Effects of cooling rates on the quality of Prochilodus lineatus (Valenciennes, 1836) sperm
Authors: de Jesus Paula Daniella Aparecida , Murgas Luis David Solis , Castro Tássia Flávia Dias , de Lima Assis Isadora , Neto Rafael Vilhena Reis , Marcussi Silvana 
Published: May 2019

AbstractThis study aims to investigate the effect of different cooling rates on the semen cryopreservation of curimba (Prochilodus lineatus). Nineteen ejaculates were obtained from adults males and cryopreserved at 15°C/min (CR15), 30°C/min (CR30) (controlled temperature inside and outside straw, speed was stable during freezing) and direct freezing in liquid nitrogen vapour (~35.6°C/min) (CRNV). The straws were thawed and seminal parameters evaluated. DNA fragmentation through the comet assay was assessed. A fresh sperm sample was not frozen and used for analyses. Data were submitted to an analysis of variance (ANOVA), and means were compared by Scott–Knott test (p < 0.05) using the R Software. Mean motility percentage was 100%, and motility duration was 39.5 ± 5.7 s for the fresh sperm (subjective analysis); 58.9 ± 8.0% and 24.5 ± 5.7 s for CR15; 64.8 ± 4.8% and 26.5 ± 7.1 s for CR30; and 50.1 ± 16% and 25.7 ± 4.7 s for CRNV, respectively. Motility percentages were higher and equal between CR15 and CR30 compared to CRNV (p < 0.05). Some sperm motion kinetics, namely average path velocity (VAP) and straight line velocity (VAS), were higher for CR30 (p < 0.05), while curvilinear velocity (VCL) and velocity progression (PRO) were lower for CRNV (p < 0.05). Straightness (STR) and wobble (WOB) were the same among treatments (p > 0.05). Sperm morphology results indicated higher means for total morphological sperm alterations in CRNV. All cooling rates caused sperm DNA fragmentation, although CR30 provided a less harmful effect. This is the first report for cryopreserved P. lineatus sperm preserved under different controlled cooling rates. The cooling rate of 30°C/min is indicated for the cryopreservation of this fish sperm as it led to the lowest detrimental spermatozoa effects.
Peripheral GABA receptors regulate colonic afferent excitability and visceral nociception
Authors: Loeza‐Alcocer Emanuel , McPherson Thomas P. , Gold Michael S. 
Published: May 2019

Key points
While the presence of GABA receptors on primary afferents has been well described, most functional analyses have focused on the regulation of transmitter release from central terminals and/or signalling in the sensory neuron cell body.
Evidence that GABA receptors are transported to peripheral terminals and that there are several sources of GABA in the colon raise the possibility that GABA signalling in the periphery may influence colonic afferent excitability.
GABAA and GABAB are present and functional in the colon, where exogenous agonists decrease the excitability of colonic afferents and suppress visceral nociception.
Endogenous GABA release within the colon is sufficient to establish the resting excitability of colonic afferents as well as the behavioural response to noxious stimulation of the colon, primarily via GABAA receptors.
Peripheral GABA receptors may serve as a viable target for the treatment of visceral pain.
AbstractIt is well established that GABA receptors at the central terminals of primary afferent fibres regulate afferent input to the superficial dorsal horn. However, the extent to which peripheral GABA signalling may also regulate afferent input remains to be determined. The colon was used to explore this issue because of the numerous endogenous sources of GABA that have been described in this tissue. The influence of GABA signalling on colonic afferent excitability was assessed in an ex vivo mouse colorectum pelvic nerve preparation where test compounds were applied to the receptive field. The visceromotor response (VMR) evoked by noxious colorectal distension was used to assess the impact of GABA signalling on visceral nociception, where test compounds were applied directly to the colon. Application of either GABAA or GABAB receptor agonists attenuated the colonic afferent response to colon stretch. Conversely, GABAA and GABAB receptor antagonists increased the stretch response. However, while the noxious distension‐induced VMR was attenuated in the presence of GABAA and GABAB receptor agonists, the VMR was only consistently increased by GABAA receptor antagonists. These results suggest that GABA receptors are present and functional in the peripheral terminals of colonic afferents and activation of these receptors via endogenous GABA release contributes to the establishment of colonic afferent excitability and visceral nociception. These results suggest that increasing peripheral GABA receptor signalling could be used to treat visceral pain.
Impact of hospitalisation of children on parental dietary habits: a qualitative study
Authors: Church Kirstyn , Campbell David , Halliday Vanessa 
Published: May 2019

Objective
To explore how prolonged hospitalisation of a child with a neurological condition influences the dietary habits of parents, taking account of their attitudes and perceptions of this experience.

Design
Qualitative study using semi-structured interviews and inductive thematic analysis.

Subjects
Fifteen parents of children (aged 2–16 years) with a neurological condition resulting in prolonged periods of hospitalisation were recruited.

Results
Mothers (n=13) and fathers (n=2) who were interviewed experienced frequent hospital visits brought about by their child’s condition, or associated medical complications. Dietary habits of parents were affected throughout their time in hospital. Three key themes were identified relating to how hospitalisation influenced this: (1) access to food, (2) emotional and physical well-being and (3) impact on eating patterns and food choice.

Conclusions
Findings from this study suggest that parents in these circumstances need to be better supported within the hospital setting as a number of barriers exist when it comes to accessing food in hospital and making healthy food choices. Additionally, having a child in hospital has a considerable effect on a parent’s emotional well-being, which further impacts on their dietary habits. The long-term physical and mental health implications of this may influence their ability to care for the sick child.
Adherence to metformin is reduced during school holidays and weekends in children with type 1 diabetes participating in a randomised controlled trial
Authors: Leggett Catherine , Giles Lynne , Anderson Jemma Jay Angela , Doogue Matthew , Couper Jennifer , Pena Alexia Sophie 
Published: May 2019

BackgroundNon-adherence to treatment in childhood chronic illness has serious consequences for health and healthcare costs. Accurate detailed objective data on adherence are minimal in this age group.ObjectiveTo evaluate medication adherence using electronic monitoring systems in children with type 1 diabetes (T1D).DesignA cohort study of 90 T1D children (aged 13.6±2.5 years, 41 males) from two paediatric diabetes clinics, participated in a 12-month double-blind, randomised, placebo-controlled trial (1:1 allocation). This cohort provided 28 336 days of study observations; 7138 school holiday and 8875 weekend/public holiday days.MethodAdherence to intervention (metformin (n=45) or placebo (n=45)) was measured objectively by Medication Event Monitoring Systems (MEMS) including proportion of medication doses taken and daily adherence patterns and by tablet count at 3, 6 and 12 months. The trial was completed in June 2015.ResultsThere was an average (SD) of 363.3 (42) days of MEMS observations available for each study participant (94.1 (12.6) school holiday days and 117.1 (13.4) weekend/public holiday days). Adherence reduced during school holidays (adjusted OR (aOR) 0.81; 95% CI 0.72 to 0.91; p<0.001) and during weekends/public holidays (aOR 0.74; 95% CI 0.69 to 0.80; p<0.001). Adverse effects to the intervention did not affect overall adherence (aOR 0.77; 95% CI 0.3 to 2.01; p=0.6). Age, gender, body mass index, diabetes duration, insulin dose, HbA1c (Haemoglobin A1c) or socioeconomic status did not predict adherence.ConclusionMedication adherence was reduced during school holidays and on weekends in children with T1D. Clinical characteristics including socioeconomic status and the presence of adverse effects did not predict adherence.Trial registration numberACTRN12611000148976.