bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel lead structures and activation mechanisms for CO‐releasing molecules (CORMs)
Authors: Schatzschneider U 
Published: March 2014

Carbon monoxide (CO) is an endogenous small signalling molecule in the human body, produced by the action of haem oxygenase on haem. Since it is very difficult to apply safely as a gas, solid storage and delivery forms for CO are now explored. Most of these CO‐releasing molecules (CORMs) are based on the inactivation of the CO by coordinating it to a transition metal centre in a prodrug approach. After a brief look at the potential cellular target structures of CO, an overview of the design principles and activation mechanisms for CO release from a metal coordination sphere is given. Endogenous and exogenous triggers discussed include ligand exchange reactions with medium, enzymatically‐induced CO release and photoactivated liberation of CO. Furthermore, the attachment of CORMs to hard and soft nanomaterials to confer additional target specificity to such systems is critically assessed. A survey of analytical methods for the study of the stoichiometry and kinetics of CO release, as well as the tracking of CO in living systems by using fluorescent probes, concludes this review. CORMs are very valuable tools for studying CO bioactivity and might lead to new drug candidates; however, in the design of future generations of CORMs, particular attention has to be paid to their drug‐likeness and the tuning of the peripheral ‘drug sphere’ for specific biomedical applications. Further progress in this field will thus critically depend on a close interaction between synthetic chemists and researchers exploring the physiological effects and therapeutic applications of CO.Linked ArticlesThis article is part of a themed section on Pharmacology of the Gasotransmitters. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-6
Shift in Trophic Level of Mediterranean Mariculture Species
Authors: TSIKLIRAS ATHANASSIOS C. , STERGIOU KONSTANTINOS I. , ADAMOPOULOS NIKOLAOS , PAULY DANIEL , MENTE ELENI 
Published: March 2014

AbstractThe mean trophic level of the farmed fish species in the Mediterranean has been increasing. We examined the farming‐up hypothesis (i.e., the increase in the production of high‐trophic‐level species) in the Mediterranean by determining the trophic level of the aquafeeds (i.e., what the fish are fed) of 5 species of farmed marine fishes: common dentex (Dentex dentex), common pandora (Pagellus erythrinus), European seabass (Dicentrarchus labrax), gilthead seabream (Sparus aurata), and red porgy (Pagrus sp.). The mean trophic level of aquafeed used in mariculture from 1950 to 2011 was higher (3.93) than the prey farmed fish consume in the wild (3.72) and increased at a faster rate (0.48/decade) compared with that based on their diets in the wild (0.43/decade). Future expected replacement of the fishmeal and oil in aquafeeds by plant materials may reverse the farming‐up trend, although there are a number of concerns regarding operational, nutritional, environmental, and economic issues. The farming‐up reversal can be achieved in an ecologically friendly manner by facilitating the mariculture of low‐trophic‐level fishes and by promoting high efficiency in the use of living marine resources in aquafeeds.Cambios en el Nivel Trófico de las Especies de Maricultura Mediterránea
Using genomics to characterize evolutionary potential for conservation of wild populations
Authors: Harrisson Katherine A. , Pavlova Alexandra , Telonis‐Scott Marina , Sunnucks Paul 
Published: March 2014

AbstractGenomics promises exciting advances towards the important conservation goal of maximizing evolutionary potential, notwithstanding associated challenges. Here, we explore some of the complexity of adaptation genetics and discuss the strengths and limitations of genomics as a tool for characterizing evolutionary potential in the context of conservation management. Many traits are polygenic and can be strongly influenced by minor differences in regulatory networks and by epigenetic variation not visible in DNA sequence. Much of this critical complexity is difficult to detect using methods commonly used to identify adaptive variation, and this needs appropriate consideration when planning genomic screens, and when basing management decisions on genomic data. When the genomic basis of adaptation and future threats are well understood, it may be appropriate to focus management on particular adaptive traits. For more typical conservations scenarios, we argue that screening genome‐wide variation should be a sensible approach that may provide a generalized measure of evolutionary potential that accounts for the contributions of small‐effect loci and cryptic variation and is robust to uncertainty about future change and required adaptive response(s). The best conservation outcomes should be achieved when genomic estimates of evolutionary potential are used within an adaptive management framework.
‘They Died of a Broken Heart’: Connecting Women's Experiences of Trauma and Criminalisation to Survival and Death Post‐imprisonment
Authors: Carlton Bree , Segrave Marie 
Published: March 2014

AbstractIn this article we document women's experiences of post‐release survival and death in Victoria, Australia. In particular, we map the interrelated impacts of trauma, criminalisation, institutionalisation and imprisonment. We build upon the existing post‐release mortality research, which has focused on quantifying and describing death, and provide a critical account of survival through the lens of women's experiences. Critically, we challenge the assumption that there is a distinction between survival and death, as many participants reported near‐death experiences occurring in a range of contexts. Ultimately we highlight the need to attend to these contexts in order to advance depth of understanding regarding the structural nature of post‐release disadvantage and survival.
Clinical outcomes of toe amputation in patients with type 2 diabetes in Tianjin, China
Authors: Chu Yue‐Jie , Li Xi‐Wen , Wang Peng‐Hua , Xu Jun , Sun Hao‐Jie , Ding Min , Jiao Jiao , Ji Xiao‐Yan , Feng Shu‐hong 
Published: March 2014

AbstractThe aim of this study is to determine the predictors for reulceration, reamputation and mortality in patients with diabetes following toe amputation, and the impact of activities of daily living on clinical outcomes.This prospective cohort study included 245 patients who had undergone toe amputation (202 healing and 43 non‐healing) and was followed for a 5‐year period. Data regarding new foot ulceration, reamputation and mortality were recorded, and the patients' activities of daily living were evaluated.The rate of wound healing was 82·4%. The rate of follow‐up in the healed group was 91·6%. In years 1, 3 and 5, the cumulative incidence of patients who developed a new foot ulcer was 27·3%, 57·2% and 76·4%, respectively, leading to reamputation in 12·5%, 22·3% and 47·1%, respectively. The cumulative mortality was 5·8%, 15·1% and 32·7% at 1, 3 and 5 years, respectively. Multivariate analysis showed that GHbA1c > 9% (75 mmol/mol) was identified as an independent predictor of impaired wound healing, reulceration and reamputation. An age of >70 years was identified as an independent predictor of reamputation, mortality and impairment of activities of daily living.Despite a satisfactory initial healing rate after the first toe amputation, with the extension course after the toe amputation, the long‐term outcomes are not optimistic. In developing countries like China, taking measures to prevent reulceration and reamputation is very important for patients with diabetic foot minor amputations, especially following toe amputation.
Overexpression of microRNA‐99a attenuates heart remodelling and improves cardiac performance after myocardial infarction
Authors: Li Qiaoling , Xie Jun , Li Ruotian , Shi Jian , Sun Jiayin , Gu Rong , Ding Liang , Wang Lian , Xu Biao 
Published: March 2014

AbstractMicroRNAs are involved in the regulation of various cellular processes, including cell apoptosis and autophagy. Expression of microRNA‐99a (miR‐99a) is reduced in apoptotic neonatal mice ventricular myocytes (NMVMs) subjected to hypoxia. We hypothesize that miR‐99a might restore cardiac function after myocardial infarction (MI) by up‐regulation of myocyte autophagy and apoptosis. We observed down‐regulated miR‐99a expression in NMVMs exposed to hypoxia using TaqMan quantitative reverse transcriptase‐polymerase chain reaction analysis (RT‐PCR). We also observed that miR‐99a overexpression decreased hypoxia‐mediated apoptosis in cultured NMVMs. To investigate whether overexpression of miR‐99a in vivo could improve cardiac function in ischaemic heart, adult C57/BL6 mice undergoing MI were randomized into two groups and were intra‐myocardially injected with lenti‐99a‐green fluorescent protein (GFP) or lenti‐GFP (control). Four weeks after MI, lenti‐99a‐GFP group showed significant improvement in both left ventricular (LV) function and survival ratio, as compared to the lenti‐GFP group. Histological analysis, western blotting analysis and electron microscopy revealed decreased cellular apoptosis and increased autophagy in cardiomyocytes of lenti‐99a‐GFP group. Furthermore, western blotting analysis showed inhibited mammalian target of rapamycin (mTOR) expression in the border zones of hearts in miR‐99a‐treated group. Our results demonstrate that miR‐99a overexpression improves both cardiac function and survival ratio in a murine model of MI by preventing cell apoptosis and increasing autophagy via an mTOR/P70/S6K signalling pathway. These findings suggest that miR‐99a plays a cardioprotective role in post‐infarction LV remodelling and increased expression of miR‐99a may have a therapeutic potential in ischaemic heart disease.
Combined treatment of rituximab, idarubicin, dexamethasone, cytarabine, methotrexate with radiotherapy for primary central nervous system lymphoma
Authors: Zhao Defeng , Qian Liren , Shen Jianliang , Liu Xiaopeng , Mei Ke , Cen Jian , Wang Yaming , Li Congyong , Ma Yuanyuan 
Published: March 2014

AbstractThe overall response rates and long‐term survival of primary central nervous system lymphoma (PCNSL) are still significantly inferior to the results achieved in similar subtypes of extranodal non‐Hodgkin's lymphoma. It is clearly necessary to investigate new therapeutic methods on PCNSL. We encountered three patients histologically documented PCNSL as diffuse large B‐cell lymphoma (DLBCL). They were treated with R‐IDARAM which comprised rituximab, idarubicin, dexamethasone, cytarabine and methotrexate. Patient 1 received stereotactic brachytherapy (SBT) prior to chemotherapy performed with iodine‐125 seeds (cumulative therapeutic dose 50 Gy). After six cycles of R‐IDARAM at 3‐weekly intervals, radiotherapy was applied at a dosage of 2000–4000 cGy in conventional schedule (180 or 200 cGy/day) to whole brain or spinal cord in all patients. Complete remission (CR) was achieved after first two cycles of R‐IDARAM in all patients. All three patients remained in CR at the time of this report with a median duration of follow‐up of 23 months (ranging from 13 to 41 months). Three patients have been alive for 41, 13, 16 months respectively until now. The patient with the longest survival time was the one given SBT prior to chemotherapy. This study suggests that R‐IDARAM combining with radiotherapy maybe a high effective regimen in PCNSL patients especially those with primary central nervous system DLBCL. A comprehensive treatment combining internal radiotherapy by SBT, modified R‐IDARAM and followed reduced external radiotherapy may be a new treatment concept for PCNSL with higher efficiency and lower toxicity.
Enucleation: a possible mechanism of cancer cell death
Authors: Paunescu Virgil , Bojin Florina M. , Gavriliuc Oana I. , Taculescu Elena A. , Ianos Robert , Ordodi Valentin L. , Iman Vlad F. , Tatu Calin A. 
Published: March 2014

AbstractThere are few major morphologies of cell death that have been described so far: apoptosis (type I), cell death associated with autophagy (type II), necrosis (type III) and anchorage‐dependent mechanisms—anoikis. Here, we show for the first time a possibly novel mechanism inducing tumour cell death under in vitro conditions—enucleation. We pursued the influence of colloidal suspensions of Fe3O4 nanoparticles on tumour cell lines (SK‐BR‐3 and MCF‐7 breast cancer cell lines) grown according to standard cell culture protocols. Magnetite nanoparticles were prepared by combustion synthesis and double layer coated with oleic acid. Scanning and transmission electron microscopy revealed that tumour cells developed a network of intracytoplasmic stress fibres, which induce extrusion of nuclei, and enucleated cells die. Normal adult mesenchymal stem cells, used as control, did not exhibit the same behaviour. Intact nuclei were found in culture supernatant of tumour cells, and were visualized by immunofluorescence. Enucleation as a potential mechanism of tumour cell death might open new horizons in cancer biology research and development of therapeutic agents capable of exploiting this behaviour.
Effect of peroral endoscopic myotomy in achalasia patients with failure of prior pneumatic dilation: A prospective case–control study
Authors: Ling Tingsheng , Guo Huimin , Zou Xiaoping 
Published: March 2014

AbstractBackground and AimTo investigate the effectiveness of peroral endoscopic myotomy (POEM) surgery in achalasia patients with failure of prior pneumatic dilation (PD).MethodsTwenty‐one patients with a history of failed PD were prospectively recruited as the case group, and 30 patients with no history of prior treatment for achalasia were included as the control group. Outcome of POEM procedures was evaluated through esophageal manometry, timed barium esophagogram and short form 36 (SF‐36) questionnaires, which were performed before surgery, at 5 days after surgery and at the last follow‐up, respectively. Relief of patients' symptoms was considered as the primary outcome. Secondary outcomes included lower esophageal sphincter pressure, esophageal emptying, quality of life of the patient, and procedure‐related complications.ResultsThe two groups were matched in terms of age, gender, body mass index, and results of preoperative examinations. For patients with failed PD, it was observed that Eckardt score, lower esophageal sphincter pressure, and height of the barium column were significantly decreased after POEM surgery. Besides, the mean physical component summary and mental component summary of patients at the final follow were significantly higher than those before surgery. Complications that occurred during the surgery included three cases of subcutaneous emphysema (14.3%) and one case of pneumothorax (4.8%). Patients with failed PD were found to have the significantly longer operation time than the control group. There was no significant difference between the two groups in terms of surgical outcome at the final follow‐up.ConclusionsPOEM is a promising therapeutic modality for achalasia patients who have failed to respond to PD therapy. Previous dilation procedures might have no obvious influence on the efficacy of POEM surgery.
Evaluation of efficacy, pharmacokinetics and tolerability of peptidomimetic aspartic proteinase inhibitors as cream formulation in experimental vaginal candidiasis
Authors: De Bernardis Flavia , Arancia Silvia , Tringali Giuseppe , Greco Maria Cristina , Ragazzoni Enzo , Calugi Chiara , Trabocchi Andrea , Sandini Silvia , Graziani Sofia , Cauda Roberto , Cassone Antonio , Guarna Antonio , Navarra Pierluigi 
Published: March 2014

Abstract

Objectives
It has been previously shown that the treatment with the two protease inhibitors APG12 and APG19 confers protection in a rat model of mucosal candidiasis; in this study, we examined whether these peptidomimetic inhibitors are also effective as a cream formulation in reducing Candida albicans vaginal infection.

Methods
These efficacy studies were performed in a rat model of estrogen-dependent rat vaginitis by C. albicans on both azole-susceptible and azole-resistant C. albicans, and on both caspofungin-susceptible and caspofungin-resistant C. albicans strains. In vivo studies were also conducted in female albino rats and rabbits to obtain information about the safety, local tolerability and principal pharmacokinetics parameters of the two compounds.

Key findings and conclusions
Both hit compounds showed remarkable results within the 48-h range as effective inhibitors of the infection, particularly causing rapid decay of vaginal C. albicans burden. Importantly, the two compounds showed marked acceleration of fungus clearance in the rats challenged with the fluconazole-resistant as well as with the capsofungin-resistant strain of C. albicans. Both compounds showed fast elimination rates when given by the intravenous route, and poor systemic absorption after intravaginal cream administration. Test drugs were also well tolerated in 7-day local tolerability experiments in the rabbit.
Occupational and socioeconomic differences in actigraphically measured sleep
Authors: Takahashi Masaya , Tsutsumi Akizumi , Kurioka Sumiko , Inoue Akiomi , Shimazu Akihito , Kosugi Yuki , Kawakami Norito 
Published: March 2014

SummaryOccupational conditions, together with socioeconomic status, may modulate sleep. This study examined the association of occupational conditions and socioeconomic status with actigraphic measures of sleep in workers. Fifty‐five employees (40 ± 12 years) wore a wrist actigraph during sleep for seven consecutive nights. Sleep variables addressed included total sleep time, sleep efficiency, mean activity during sleep, sleep‐onset latency, and wake after sleep onset. We also measured household income, occupational class, work schedule, weekly work hours, job demand, job control, worksite social support, effort–reward imbalance, organizational justice, and workplace social capital. Multiple linear regression models were used to determine the association of occupational indicators, socioeconomic status, as well as age and gender with each sleep variable. Higher workplace social capital was associated consistently with longer total sleep time (P < 0.001), higher sleep efficiency (P < 0.05) and lower mean activity during sleep (P < 0.07). Low occupational class (P < 0.01), higher job demand (P < 0.05) and lower job control (P < 0.05) were associated with longer total sleep time. No associations were significant for sleep‐onset latency or wake after sleep onset. These preliminary results suggest that enhanced workplace social capital is closely associated with better quality and quantity of sleep.
Chronotype is associated with the timing of the circadian clock and sleep in toddlers
Authors: Simpkin Charles T. , Jenni Oskar G. , Carskadon Mary A. , Wright Kenneth P. , Akacem Lameese D. , Garlo Katherine G. , LeBourgeois Monique K. 
Published: March 2014

SummaryChronotype is a construct reflecting individual differences in diurnal preference. Although chronotype has been studied extensively in school‐age children, adolescents and adults, data on young children are scarce. This study describes chronotype and its relationship to the timing of the circadian clock and sleep in 48 healthy children aged 30–36 months (33.4 ± 2.1 months; 24 males). Parents completed the Children's Chronotype Questionnaire (CCTQ) ~2 weeks before the start of the study. The CCTQ provides three measures of chronotype: midsleep time on free days, a multi‐item morningness/eveningness score and a single item chronotype score. After 5 days of sleeping on their habitual schedule (assessed with actigraphy and sleep diaries), children participated in an in‐home salivary dim light melatonin onset assessment. Average midsleep time on free days was 1:47 ± 0:35, and the average morningness/eveningness score was 26.8 ± 4.3. Most toddlers (58.4%) were rated as ‘definitely a morning type’ or ‘rather morning than evening type’, while none (0%) were rated as ‘definitely evening type’. More morning types (midsleep time on free days and morningness/eveningness score, respectively) had earlier melatonin onset times (r = 0.45, r = 0.26), earlier habitual bedtimes (r = 0.78, r = 0.54), sleep onset times (r = 0.80, r = 0.52), sleep midpoint times (r = 0.90, r = 0.53) and wake times (r = 0.74, r = 0.34). Parent ratings using the single‐item chronotype score were associated with melatonin onset (r = 0.32) and habitual bedtimes (r = 0.27), sleep onset times (r = 0.33) and sleep midpoint times (r = 0.27). Morningness may best characterize circadian preference in early childhood. Associations between chronotype and circadian physiology and sleep timing suggest adequate validity for the CCTQ in this age group. These findings have important implications for understanding the marked variability in sleep timing during the early years of life.
The transposable element Bari‐Jheh mediates oxidative stress response in Drosophila
Authors: Guio Lain , Barrón Maite G. , González Josefa 
Published: March 2014

AbstractElucidating the fitness effects of natural genetic variants is one of the current major challenges in evolutionary biology. Understanding the interplay between genotype, phenotype and environment is necessary to make accurate predictions of important biological outcomes such as stress resistance or yield in economically important plants and animals, and disease in humans. Based on population frequency patterns and footprints of selection at the DNA level, the transposable element Bari‐Jheh, inserted in the intergenic region of Juvenile Hormone Epoxy Hydrolase (Jheh) genes, was previously identified as putatively adaptive. However, the adaptive effect of this mutation remained elusive. In this work, we integrate information on transcription factor binding sites, available ChIP‐Seq data, gene expression analyses and phenotypic assays to identify the functional and the mechanistic underpinnings of Bari‐Jheh. We show that Bari‐Jheh adds extra antioxidant response elements upstream of Jheh1 and Jheh2 genes. Accordingly, we find that Bari‐Jheh is associated with upregulation of Jheh1 and Jheh2 and with resistance to oxidative stress induced by two different compounds relevant for natural D. melanogaster populations. We further show that TEs other than Bari‐Jheh might be playing a role in the D. melanogaster response to oxidative stress. Overall our results contribute to the understanding of resistance to oxidative stress in natural populations and highlight the role of transposable elements in environmental adaptation. The replicability of fitness effects on different genetic backgrounds also suggests that epistatic interactions do not seem to dominate the genetic architecture of oxidative stress resistance.