bluuebunny/crossref_metadata_2025 huggingface dataset:
Mathematical models incorporating a multi-stage cell cycle replicate normally-hidden inherent synchronisation in cell proliferation
Authors: Vittadello Sean T. , McCue Scott W. , Gunasingh Gency , Haass Nikolas K. , Simpson Matthew J.
Published: February 2019

We present a suite of experimental data showing that cell proliferation assays, prepared using standard methods thought to produce asynchronous cell populations, persistently exhibit inherent synchronisation. Our experiments use fluorescent cell cycle indicators to reveal the normally-hidden cell synchronisation by highlighting oscillatory subpopulations within the total cell population. These oscillatory subpopulations would never be observed without these cell cycle indicators. On the other hand, our experimental data show that the total cell population appears to grow exponentially, as in an asynchronous population. We reconcile these seemingly inconsistent observations by employing a multi-stage mathematical model of cell proliferation that can replicate the oscillatory subpopulations. Our study has important implications for understanding and improving experimental reproducibility. In particular, inherent synchronisation may affect the experimental reproducibility of studies aiming to investigate cell cycle-dependent mechanisms, including changes in migration and drug response.
Dengue and Zika virus 5’-UTRs harbor IRES functions
Authors: Song Yutong , Mugavero JoAnn , Stauft Charles B. , Wimmer Eckard
Published: February 2019

Members ofFlavivirus, a genus ofFlaviviridae, encompass numerous enveloped plus strand RNA viruses, of which globally dengue virus (DENV) is the leading cause of serious arthropod-borne disease. The genomes of DENV, just as those of yellow fever virus (YFV), West Nile fever virus (WNV), or Zika virus (ZIKV), control their translation by a 5’-terminal capping group. Three other genera of Flaviviridae are remarkable because their viruses use internal ribosomal entry sites (IRESs) to control translation and they are not arthropod transmitted. In 2006 E. Harris’ group published work suggesting that DENV RNA does not stringently need a cap for translation. They proposed that instead DENV translation is controlled by an interplay between 5’ and 3’ termini. Here we present evidence that the DENV or ZIKV 5’-untranslated regions (5’-UTRs) alone have IRES competence. This conclusion is based, first, on the observation that uncapped mono-cistronic mRNAs 5’ terminated with the DENV or ZIKV 5’-UTRs can efficiently direct translation of a reporter gene in BHK and C6/36 cells; second, that either 5’-UTR placed between two reporter genes can efficiently induce expression of the downstream gene in BHK but not in C6/36 cells. These experiments followed observations that uncapped DENV/ZIKV genomic transcripts, 5’ terminated with pppAN… or GpppAN…, can initiate infections of mammalian (BHK) or mosquito (C6/36) cells. IRES competence of the 5’-UTRs of DENV/ZIKV raises many open questions regarding the biology and control, as well as the evolution, of insect-borne flaviviruses.

Importance

Members of the genusFlavivirusofFlaviviridaeare important human pathogens of great concern because they cause serious diseases, sometimes death, in human populations living in tropical, subtropical (dengue, DENV; Zika, ZIKV; yellow fever virus), or moderate climates (West Nile virus). Flaviviruses are known to control their translation by a cap-dependent mechanism. We have observed, however, that the uncapped genomes of DENV or ZIKV can initiate infection of mammalian and insect cells. We provide evidence that the short 5’ untranslated region (5’-UTR) of DENV or ZIKV genomes can fulfill the function of an internal ribosomal entry site (IRES). This strategy frees these organisms from the cap-dependent mechanism of gene expression at an as yet unknown stage of proliferation. The data raise new questions about the biology and evolution of flaviviruses, possibly leading to new controls of flavivirus disease.
Chronic Ethanol Differentially Modulates Glutamate Release from Dorsal and Ventral Prefrontal Cortical Inputs onto Rat Basolateral Amygdala Principal Neurons
Authors: McGinnis Molly M. , Parrish Brian C. , Chappell Ann M. , McCool Brian A.
Published: February 2019

The medial prefrontal cortex (mPFC) and the basolateral amygdala (BLA) have strong reciprocal connectivity. Projections from the BLA to the mPFC can bidirectionally modulate anxiety-related behaviors but it is unclear if the same is true for mPFC to BLA projections. Our laboratory is specifically interested in withdrawal-related anxiety-like behavior and the underlying synaptic plasticity. Here, we use optogenetics and chemogenetics to characterize the neurophysiological and behavioral alterations produced by chronic ethanol exposure and withdrawal on dorsal mPFC/prelimbic (dmPFC/PL) and ventral mPFC (vmPFC/IL) terminals in the BLA. We exposed adult male Sprague-Dawley rats to chronic intermittent ethanol (CIE) using vapor chambers, measured anxiety-like behavior on the elevated zero maze (EZM), and used electrophysiology to record glutamatergic and GABAergic responses in BLA principal neurons. We found that 24-hour withdrawal following a 7-day CIE exposure significantly increased the glutamate release probability from PL/dmPFC terminals, but significantly decreases the glutamate release probability from IL/vmPFC terminals. Chemogenetic inhibition of PL/dmPFC terminals in the BLA attenuated the increased withdrawal-dependent, anxiety-like behavior. These data demonstrate that chronic ethanol exposure and withdrawal strengthens the PL/dmPFC – BLA pathway but weakens the IL/vmPFC – BLA pathway. Moreover, we provide novel evidence that the PL/dmPFC – BLA pathway can modulate anxiety-like behavior. These findings suggest that mPFC-BLA circuits known to regulate the acquisition of aversive behaviors are up-regulated by chronic ethanol while those involved with the extinction of these behaviors are down-regulated.

Significance Statement

Accumulating evidence suggests that the medial prefrontal cortex and its projections to the basolateral amygdala bidirectionally modulate fear-related behaviors. Since the neuronal circuits for fear and anxiety are thought to overlap, we sought to examine the role of prelimbic and infralimbic subdivisions of the medial prefrontal cortex and their inputs to the basolateral amygdala in regulating anxiety. Specifically, we focused on alcohol withdrawal-induced anxiety-like behavior, which is a commonly reported cause of relapse in human alcoholics. In our study, we used optogenetics and chemogenetics to demonstrate, for the first time, that withdrawal from chronic ethanol exposure strengthens prelimbic synapses, but weakens infralimbic synapses in the basolateral amygdala and that inhibiting glutamate release from prelimbic terminal in the basolateral amygdala reduces anxiety-like behavior.
Cardiovascular effects of intravenous colforsin in normal and acute respiratory acidosis canine models: a dose–response study
Authors: Itami Takaharu , Hanazono Kiwamu , Oyama Norihiko , Sano Tadashi , Yamashita Kazuto
Published: February 2019

In acidosis, catecholamines are attenuated and higher doses are often required to improve cardiovascular function. Colforsin activates adenylate cyclase in cardiomyocytes without mediating the beta adrenoceptor. In this study, six beagles were administered either colforsin or dobutamine four times during eucapnia (partial pressure of arterial carbon dioxide 35-40 mm Hg; normal) and hypercapnia (ibid 90-110 mm Hg; acidosis) conditions. The latter was induced by carbon dioxide inhalation. Anesthesia was induced with propofol and maintained with isoflurane. Cardiovascular function was measured by thermodilution and a Swan-Ganz catheter. Cardiac output, heart rate, and systemic vascular resistance were determined at baseline and 60 min after 0.3 μg/kg/min (low), 0.6 μg/kg/min (middle), and 1.2 μg/kg/min (high) colforsin administration. The median pH was 7.38 [range 7.34–7.42] and 7.04 [range 7.01–7.08] at baseline in the Normal and Acidosis conditions, respectively. Endogenous adrenaline and noradrenaline levels at baseline were significantly (P< 0.05) higher in the Acidosis than in the Normal condition. Colforsin induced cardiovascular effects similar to those caused by dobutamine. Colforsin increased cardiac output in the Normal condition (baseline: 198.8 mL/kg/min [range 119.6–240.9], low: 210.8 mL/kg/min [range 171.9–362.6], middle: 313.8 mL/kg/min [range 231.2–473.2], high: 441.4 mL/kg/min [range 373.9–509.3];P< 0.001) and the Acidosis condition (baseline: 285.0 mL/kg/min [range 195.9–355.0], low: 297.4 mL/kg/min [213.3–340.6], middle: 336.3 mL/kg/min [291.3–414.5], high: 366.7 mL/kg/min [339.7–455.7] ml/kg/min;P< 0.001). Colforsin significantly increased heart rate (P< 0.05 in both conditions) and decreased systemic vascular resistance (P< 0.05 in both conditions) compared to values at baseline. Systemic vascular resistance was lower in the Acidosis than in the Normal condition (P< 0.001). Dobutamine increased pulmonary artery pressure, whereas colforsin did not. Colforsin offsets the effects of endogenous catecholamines and may not increase cardiac output during hypercapnia.
Rapid Detection of Burkholderia pseudomallei with a Lateral Flow Recombinase Polymerase Amplification Assay
Authors: Peng Yao , Xiao Zheng , Kan Biao , Li Wei , Zhang Wen , Lu Jinxing , Qin Aiping
Published: February 2019

Melioidosis is a severe infectious disease caused by gram-negative, facultative intracellular pathogen Burkholderia pseudomallei (B. pseudomallei). Although cases are increasing reported from other parts of the world, it is an illness of tropical and subtropical climates primarily found in southeast Asia and northern Australia. Because of a 40% mortality rate, this life-threatening disease poses a public health risk in endemic area. Early detection of B. pseudomallei infection benefits greatly to implement effective treatment timely, which is vital for prognosis of a melioidosis patient. In this study, a novel isothermal recombinase polymerase amplification combined with lateral flow dipstick (LF-RPA) assay was established for rapid detection of B.pseudomallei. A set of probe and primers targeting orf2 gene of B. pseudomallei were generated and parameters for the LF-RPA assay were optimized. Result can be easy visualized in 30 minutes with the limit of detection (LoD) as low as 20 femtogram (ca. 25.6 copies) of B. pseudomallei genomic DNA. The assay is highly specific as no cross amplification was observed with 35 non-B. pseudomallei pathogens. Isolates (N=19) from patients of Hainan province of China were retrospectively confirmed by the newly developed method. LoD for B. pseudomallei spiked soil and blood samples were 2.1×103 CFU/g and 4.2×103 CFU/ml respectively. Sensitivity of the LF-RPA assay was comparable to TaqMan Real-Time PCR, however, the LF-RPA assay exhibited a better tolerant to inhibitors in blood than the later. Our results showed that the LF-RPA assay is an alternative to existing PCR-based methods for detection of B. pseudomallei with a potentiality of early accurate diagnosis of melioidosis at point of care or in-field use.
A Systematic Assessment Of Current Genome-Scale Metabolic Reconstruction Tools
Authors: Mendoza S. N. , Olivier B. G , Molenaar D , Teusink B
Published: February 2019

Several genome-scale metabolic reconstruction software platforms have been developed and are being continuously updated. These tools have been widely applied to reconstruct metabolic models for hundreds of microorganisms ranging from important human pathogens to species of industrial relevance. However, these platforms, as yet, have not been systematically evaluated with respect to software quality, best potential uses and intrinsic capacity to generate high-quality, genome-scale metabolic models. It is therefore unclear for potential users which tool best fits the purpose of their research. In this work, we performed a systematic assessment of the current genome-scale reconstruction software platforms. To meet our goal, we first defined a list of features for assessing software quality related to genome-scale reconstruction, which we expect to be useful for the potential users of these tools. Subsequently, we used the feature list to evaluate the performance of each tool. In order to assess the similarity of the draft reconstructions to high-quality models, we compared each tool’s output networks with that of the high-quality, manually curated, models of Lactobacillus plantarum and Bordetella pertussis, representatives of gram-positive and gram-negative bacteria, respectively. We showed that none of the tools outperforms the others in all the defined features and that model builders should carefully choose a tool (or combinations of tools) depending on the intended use of the metabolic model.

Author Summary

Metabolic networks that comprise biochemical reactions at genome-scale have become very useful to study and predict the phenotype of important microorganisms. Several software platforms exist to build these metabolic networks. Based on different approaches and utilizing a variety of databases it is, unfortunately, unclear what are the best scenarios to use each of these tools. Hence, to understand the potential uses of these tools, we created a list of relevant features for metabolic reconstruction and we evaluated the tools in all these categories. Here, we show that none of the tools is better than the other in all the evaluated categories; instead, each tool is more suitable for particular purposes. Therefore, users should carefully select the tool(s) that best fit the purpose of their research. This is the first time these tools are systematically evaluated and this overview can be used as a guide for selecting the correct tool(s) for each case.
N′-[5-Acetyl-3-(4-bromophenyl)-2,3-dihydro-1,3,4-thiadiazol-2-ylidene]-5-(1H-indol-3-yl)-1-phenyl-1H-pyrazole-3-carbohydrazide dimethylformamide monosolvate
Authors: El-Hiti Gamal A. , Abdel-Wahab Bakr F. , Yousif Emad , Alotaibi Mohammad Hayal , Hegazy Amany S. , Kariuki Benson M.
Published: February 2019

The main molecule of the title dimethylformamide monosolvate, C28H20BrN7O2S·C3H7NO, comprises bromophenyl (A), thiadiazolyl (B), pyrazolyl (C), phenyl (D) and indolyl (E) ring systems with twist angles between the planes through neigbouring rings A/B, B/C, C/D and C/E of 33.7 (1), 14.8 (1), 60.7 (2) and 20.9 (1)°, respectively. In the crystal, the molecules are related by c-glide symmetry to form columns parallel to [001] which are linked by intermolecular N—H...O, C—H...O and C—H...Br contacts.
Consumers’ decisions in social commerce: the role of guanxi elements
Authors: Yang Xue
Published: February 2019

Purpose

Recently, the popularity and growth of social media have boosted the development of social commerce (s-commerce). The purpose of this paper is to investigate consumers’ decisions in s-commerce, for which this study conducted empirical research on WeChat, a very popular social media in China, to validate how guanxi elements (e.g. ganqing, renqing and xinren) affect consumers’ decisions in s-commerce.

Design/methodology/approach

To examine the research model, an online survey instrument was developed to gather data. The hypotheses were tested using partial least squares modeling.

Findings

The results confirm that guanxi elements are positively related to eWOM sharing intention and social shopping intention. Moreover, these effects are mediated by a sense of belonging.

Originality/value

This study enhances the existing literature by introducing the concept of guanxi elements to the context of s-commerce, and linking the concept of guanxi elements and consumers’ decisions. Moreover, this study improves the theoretical and empirical understanding of guanxi elements by investigating its impact on eWOM sharing intention and social shopping intention. Third, the results confirm that guanxi elements not only influence a sense of belonging but also conjointly impacts eWOM sharing intention and social shopping intention in s-commerce.
De‐legitimising complementary medicine: framings of the Friends of Science in Medicine‐CAM debate in Australian media reports
Authors: Lewis Monique
Published: February 2019

Complementary and alternative medicine (CAM) has developed into a complex and formidable commercial, sociocultural and political force in Australia, and given its influence, it is a relevant subject for scholars, health practitioners, health communicators, journalists, policy‐makers, and consumers of healthcare products and services. This research will consider a relative newcomer to the claims‐making space about CAM in the Australian health media‐scape; the Friends of Science in Medicine (FSM), an activist group of medical practitioners, researchers, and scientists, founded in late 2011. Using content analysis supported by NVivo, I searched for articles specifically referring to FSM and measured the patterns and frequencies of media frames, intonation and sources that are featured in Australian mainstream news reports between December 2011 and April 2017. The negative headlining and intonation of reports predominated, along with framing CAM as part of a lucrative, undisciplined and unethical industry as well as an illegitimate healthcare approach, more broadly. The findings offer insight into how journalists respond, replicate or reconstruct the framings that are provided by an influential and elite group of medical practitioners and scientists, and readdresses issues surrounding the need for more critical health reporting in Australia.
Sensory and Consumer Evaluation of Smoked Pulled Pork Prepared Using Different Smokers and Different Types of Wood
Authors: Swaney‐Stueve Marianne , Talavera Martin , Jepsen Tegan , Severns Bryan , Wise Robert , Deubler Grace
Published: February 2019

Smoked and barbecued meats have continued to gain popularity in recent years, however, no consensus exists on the best methods for preparation. Several smoker types and many varieties of wood are used for smoking meat in the restaurant industry and by amateur “pit‐masters.” In this research, pork was smoked with an outdoor offset smoker and an indoor electric smoker using four wood types: hickory, apple, oak, and mesquite. Descriptive and consumer acceptance tests were conducted to evaluate the different treatments and determine drivers of liking. Pork smoked with the offset smoker using hickory wood had the highest overall acceptance. Appearance characteristics, such as intensity of red color, were the top drivers of liking for the smoked pork product.

Practical Application

This research demonstrates the drivers of liking for smoked pork products commonly found in American barbecue, specifically Kansas City‐style barbecue. The results have application in both retail and restaurant environments and can be used to produce an optimized smoked pork product.
Twenty‐first‐century chemical odyssey: fuels versus commodities and cell factories versus chemical plants
Authors: Ramos Juan L. , Duque Estrella
Published: February 2019

The harmful effects of pollution from the massive and widespread use of fossil fuels have led various organizations and governments to search for alternative energy sources. To address this, a new energy bioprocess is being developed that utilizes non‐edible lignocellulose – the only sustainable source of organic carbon in nature. In this mini‐review, we consider the potential use of synthetic biology to develop new‐to‐nature pathways for the biosynthesis of chemicals that are currently synthesized using classical industrial approaches. The number of industrial processes based on starch or lignocellulose is still very modest. Advances in the area require the development of more efficient approaches to deconstruct plant materials, better exploitation of the catalytic potential of prokaryotes and lower eukaryotes and the identification of new and useful genes for product synthesis. Further research and progress is urgently needed in order for government and industry to achieve the major milestone of transitioning 30% of the total industry to renewable sources by 2050.
CRISPR interference‐mediated gene regulation in Pseudomonas putida KT2440
Authors: Kim Seong Keun , Yoon Paul K. , Kim Soo‐Jung , Woo Seung‐Gyun , Rha Eugene , Lee Hyewon , Yeom Soo‐Jin , Kim Haseong , Lee Dae‐Hee , Lee Seung‐Goo
Published: February 2019

Targeted gene regulation is indispensable for reprogramming a cellular network to modulate a microbial phenotype. Here, we adopted the type II CRISPR interference (CRISPRi) system for simple and efficient regulation of target genes in Pseudomonas putida KT2440. A single CRISPRi plasmid was generated to express a nuclease‐deficient Cas9 gene and a designed single guide RNA, under control of l‐rhamnose‐inducible PrhaBAD and the constitutive Biobrick J23119 promoter respectively. Two target genes were selected to probe the CRISPRi‐mediated gene regulation: exogenous green fluorescent protein on the multicopy plasmid and endogenous glpR on the P. putida KT2440 chromosome, encoding GlpR, a transcriptional regulator that represses expression of the glpFKRD gene cluster for glycerol utilization. The CRISPRi system successfully repressed the two target genes, as evidenced by a reduction in the fluorescence intensity and the lag phase of P. putida KT2440 cell growth on glycerol. Furthermore, CRISPRi‐mediated repression of glpR improved both the cell growth and glycerol utilization, resulting in the enhanced production of mevalonate in an engineered P. putida KT2440 harbouring heterologous genes for the mevalonate pathway. CRISPRi is expected to become a robust tool to reprogram P. putida KT2440 for the development of microbial cell factories producing industrially valuable products.
Application of a real‐time pain monitoring system in Korean fibromyalgia patients: A pilot study
Authors: Lee Jennifer , Park Sung‐Hwan , Ju Ji Hyeon , Cho Jae Hyoung
Published: February 2019

Objectives

Chronic pain is a debilitating condition which should be managed with integrated multidisciplinary approaches. To this end, accurate pain assessment should be the first step, and self‐reporting pain assessment systems using smartphones or wearable devices are being introduced. The aim of the study was to evaluate the utility and efficacy of a real‐time pain monitoring system using a wearable device, referred to as the Pain Assessment and Analysis System (PAAS), in patients with fibromyalgia, which is characterized by widespread chronic pain.

Methods

In this pilot study, adult fibromyalgia patients were randomly assigned to use or to not use PAAS. Changes in the visual analog scale (VAS) were examined by rheumatologists at baseline and after 3 months, and correlations between conventional pain VAS or PAAS VAS and clinical parameters were investigated.

Results

A total of 24 fibromyalgia patients were enrolled in the study, with 14 patients assigned to the PAAS group, and 11 patients assigned to the control group. All patients completed the 3 month study. The reduction of pain on the VAS in patients who used PAAS for 3 months was significantly greater than that in the control group. The mean pain VAS calculated by PAAS showed good correlation with clinical parameters, including scores of the fibromyalgia impact questionnaire.

Conclusions

The proposed real‐time pain monitoring system can be utilized for pain assessment in Korean fibromyalgia patients. Moreover, the system accurately reflects pain status and may help to alleviate pain.
Cold treatment enhances low‐temperature flight performance in false codling moth, Thaumatotibia leucotreta (Lepidoptera: Tortricidae)
Authors: Boersma Nevill , Boardman Leigh , Gilbert Martin , Terblanche John S.
Published: February 2019

In sterile insect technique programmes, temperatures experienced by insects during rearing and handling, along with cool temperatures after release, can negatively affect performance and activity levels. Phenotypic plasticity (trait modifications caused by prior stress exposure) can offset these effects but is poorly understood in many species and traits.

We investigated the effects of a cold treatment (2 °C for 16 h) on flight performance in adult false codling moth, Thaumatotibia leucotreta. Using diverse methods, flight performance was tested using flight assays in the laboratory and in the field under varying environmental conditions.

The flight performance of T. leucotreta in the laboratory was affected by cold treatment (relative to a 25 °C control group), test temperature and their interaction. Field recapture of released moths was significantly affected by the interaction between cold treatment and environmental conditions.

Field recapture counts depended on the ambient temperature upon release. For example, under warmer conditions (>17 °C), the recapture count of cold‐treated moths was lower than that of the untreated control group, whereas the recapture count of cold‐treated moths at cooler temperatures was significantly higher.

Our results suggest a temperature‐dependent interaction between acute cold exposure and flight performance in adult T. leucotreta, which may be used to enhance the efficacy of the sterile insect technique under cooler environmental conditions.
Stricture rate after chemoradiotherapy and radiotherapy for oesophageal squamous cell carcinoma: a 20‐year experience
Authors: Hamer Peter W. , Hight Stephanie C. , Ward Ian G. , Harris Dean L. , Woodham Benjamin L. , Flint Richard S.
Published: February 2019

Background

Definitive chemoradiation for oesophageal squamous cell carcinoma (SCC) is the first‐line treatment in many centres. However, it is not without morbidity. We assess outcomes for patients treated with definitive chemoradiotherapy and radiotherapy.

Methods

A retrospective review of a prospectively maintained database (Radiotherapy Department, Canterbury District Health Board) was undertaken. All patients who underwent definitive radiotherapy for oesophageal SCC between October 1996 and April 2015 were included.

Results

Sixty patients underwent chemoradiotherapy with curative intent and 17 underwent definitive radiotherapy with curative intent. Median age was 69 years (44–84 years) for those undergoing chemoradiotherapy and 73 years (36–85 years) for those who underwent definitive radiotherapy. Tumour location in all patients was upper third in 14 (18%), middle third in 39 (51%), lower third in 22 (29%) cases and junctional tumour in two (3%). Staging information was complete for 73 of 77 patients (stage I 16/77 (21%), stage II 40/77 (52%), stage III 17/77 (22%)). Median dose of external beam radiotherapy for those who underwent definitive chemotherapy was 50.4 Gy (30–63 Gy) and 60 Gy (50–64 Gy) for definitive radiotherapy. Median length of follow‐up was 39 months (range 4–120 months). Strictures developed in 58% of all patients (52% chemoradiotherapy and 76% definitive radiotherapy). Twenty‐four (32%) patients were dilated and 14 (18%) stented. The chemoradiotherapy group had higher 5‐year survival than definitive radiotherapy group (34% versus 6%, P = 0.0034).

Conclusion

Oesophageal SCC treated with chemoradiation has a 5‐year survival rate of 34%. Post‐treatment strictures occur in 52% of patients with chemoradiotherapy and 76% with definitive radiotherapy.
Vaginal or laparoscopic hysterectomy: Do perioperative outcomes differ? A propensity score‐matched analysis
Authors: Rademaker Doortje , Einarsson Jon I. , Huirne Judith A. F. , Gu XiangMei , Cohen Sarah L.
Published: February 2019

Introduction

There are assertions that vaginal mode may be the preferred approach of minimally invasive hysterectomy, yet rates of laparoscopic hysterectomy (LH) continue to rise while vaginal hysterectomy (VH) rate remains relatively unchanged. The aim of this study is to compare the perioperative outcomes of LH vs VH.

Material and methods

We identified women who underwent either LH or VH for benign indications between 2009 and 2015 at a large academic institution. A propensity score‐matched analysis was used to adjust for differences between women undergoing VH vs LH. Outcome parameters were perioperative complications (both intraoperative and postoperative), operative time, blood loss, hospital length of stay, conversion and readmission.

Results

A total of 1921 patients underwent either LH or VH during the study period. In all, 155 patients from each group were successfully matched using propensity score match analysis. While most intra‐ and postoperative characteristics did not differ between groups, LH was associated with lower blood loss during surgery (102.8 ± 166.5 mL vs 185.0 ± 179.0 mL, P < 0.001) and shorter hospital stay (0.9 ± 1 days vs 1.2 ± 0.9 days, P < 0.0001). Concomitant adnexal surgery was performed more frequently during LH (47.7% vs 12.3%, P < 0.0001), and concomitant prolapse surgery was performed more frequently at the time of VH (14.2% vs 68.4%, P < 0.0001).

Conclusions

Both VH and LH have overall favorable perioperative outcomes; however, LH is associated with lower blood loss and a shorter hospital stay. The results support the trend toward increasing rates of laparoscopic approach to hysterectomy when appropriate.
Wuzhi capsule regulates chloroacetaldehyde pharmacokinetics behaviour and alleviates high‐dose cyclophosphamide‐induced nephrotoxicity and neurotoxicity in rats
Authors: Chen Li , Xiong Xiaojuan , Hou Xingyun , Wei Hua , Zhai Jianxiu , Xia Tianyi , Gong Xiaobin , Gao Shouhong , Feng Ge , Tao Xia , Zhang Feng , Chen Wansheng
Published: February 2019

High‐dose cyclophosphamide (HD‐CTX) treatment often leads to severe nephrotoxicity and neurotoxicity, which are mainly caused by one of its metabolites, chloroacetaldehyde (CAA). However, there are no effective antidotes to prevent these side effects. The objective of this study was to evaluate the effect of Wuzhi Capsule (WZC) on the pharmacokinetics of CTX and its metabolites in rats, and the attenuation of CAA induced kidney and brain injuries, which was produced at equimolar with 2‐dechloroethylcyclophosphamide. Rats were treated with single‐ or multiple‐dose of WZC when giving HD‐CTX, and the plasma concentration of CTX and its metabolites were quantitated by UHPLC‐MS/MS Single‐dose, not multiple‐dose of WZC co‐administration (300 mg/kg) significantly reduced Cmax and AUC0→24 h of DC‐CTX by 33.10% and 35.51%, respectively. Biochemical assay suggested oxidative stress was involved in kidney and brain injuries by HD‐CTX, which were attenuated by single‐dose WZC (300 mg/kg) pre‐treatment, with increased glutathione, glutathione peroxidase and superoxide dismutase contents/or activities in both tissues and plasma (P < 0.05). Meanwhile, WZC pre‐treatment could also significantly decrease the plasma levels of creatinine, blood urea nitrogen and malondialdehyde (P < 0.05). Additionally, WZC treatment improved the morphology and pathology condition of the kidneys and brains in rats. In conclusion, single‐dose WZC co‐administration decreased CAA production and exerted protective effect on CTX‐induced oxidative stress in kidney and brain, whereas repetitive WZC co‐administration with CTX was probably not recommended.
CDKL5 deficiency predisposes neurons to cell death through the deregulation of SMAD3 signaling
Authors: Fuchs Claudia , Medici Giorgio , Trazzi Stefania , Gennaccaro Laura , Galvani Giuseppe , Berteotti Chiara , Ren Elisa , Loi Manuela , Ciani Elisabetta
Published: February 2019

CDKL5 deficiency disorder (CDD) is a rare encephalopathy characterized by early onset epilepsy and severe intellectual disability. CDD is caused by mutations in the X‐linked cyclin‐dependent kinase‐like 5 (CDKL5) gene, a member of a highly conserved family of serine‐threonine kinases. Only a few physiological substrates of CDKL5 are currently known, which hampers the discovery of therapeutic strategies for CDD. Here, we show that SMAD3, a primary mediator of TGF‐β action, is a direct phosphorylation target of CDKL5 and that CDKL5‐dependent phosphorylation promotes SMAD3 protein stability. Importantly, we found that restoration of the SMAD3 signaling through TGF‐β1 treatment normalized defective neuronal survival and maturation in Cdkl5 knockout (KO) neurons. Moreover, we demonstrate that Cdkl5 KO neurons are more vulnerable to neurotoxic/excitotoxic stimuli. In vivo treatment with TGF‐β1 prevents increased NMDA‐induced cell death in hippocampal neurons from Cdkl5 KO mice, suggesting an involvement of the SMAD3 signaling deregulation in the neuronal susceptibility to excitotoxic injury of Cdkl5 KO mice. Our finding reveals a new function for CDKL5 in maintaining neuronal survival that could have important implications for susceptibility to neurodegeneration in patients with CDD.
Termite diversity in Neotropical dry forests of Colombia and the potential role of rainfall in structuring termite diversity
Authors: Casalla Robin , Korb Judith
Published: February 2019

Termites are ecosystem engineers that play an important role in the biotransformation and re‐distribution of nutrients in soil. The dry forests are endemic repositories, but at same time, they are most threatened by extensive livestock and crop farming, fires, and climate change. In Colombia, the best‐protected dry forests are located in the north. The termite fauna of dry forests are poorly known. The aim was to identify the termite species occurring in tropical dry forests of the Colombian Caribbean coast in relation to diet and precipitation, temperature, elevation, and soil properties. A total of 32 species in 1,103 occurrences were found. Termitidae accounted for 78% of the species richness with the Anoplotermes‐group, Microcerotermes, and Nasutitermes being the dominant genera. Differences in species composition and abundance were found across sites. These differences may be linked to anthropogenic disturbance and polygyny and polydomy. Strikingly, our highest elevation site (334 m) had the highest species richness much higher than the two lower elevation sites. This implies an inversion of the common elevation‐diversity gradient, also found for termites which can be explained by increasing precipitation with elevation in the dry forest. An analysis of termite species richness at the global scale confirms that termite species richness correlates positively with rainfall. Hence, rainfall seems to positively affect termite diversity. In line, the studied Colombian tropical dry forests had low diversity compared to rain forests. A decline of species‐rich soil‐feeding termites with increasing aridity may explain why the highest termite diversity occurs in humid tropical rain forests.

Abstract in Spanish is available with online material.
Lessons learned about steered molecular dynamics simulations and free energy calculations
Authors: Boubeta Fernando Martín , Contestín García Rocío María , Lorenzo Ezequiel Norberto , Boechi Leonardo , Estrin Dario , Sued Mariela , Arrar Mehrnoosh
Published: February 2019

The calculation of free energy profiles is central in understanding differential enzymatic activity, for instance, involving chemical reactions that require QM‐MM tools, ligand migration, and conformational rearrangements that can be modeled using classical potentials. The use of steered molecular dynamics (sMD) together with the Jarzynski equality is a popular approach in calculating free energy profiles. Here, we first briefly review the application of the Jarzynski equality to sMD simulations, then revisit the so‐called stiff‐spring approximation and the consequent expectation of Gaussian work distributions and, finally, reiterate the practical utility of the second‐order cumulant expansion, as it coincides with the parametric maximum‐likelihood estimator in this scenario. We illustrate this procedure using simulations of CO, both in aqueous solution and in a carbon nanotube as a model system for biologically relevant nanoheterogeneous environments. We conclude the use of the second‐order cumulant expansion permits the use of faster pulling velocities in sMD simulations, without introducing bias due to large dispersion in the non‐equilibrium work distribution.
Expression and function of macrophage-inducible C-type lectin (Mincle) in inflammation driven parturition in fetal membranes and myometrium
Authors: Lim R , Lappas M
Published: February 2019

The pivotal role of inflammatory processes in human parturition is well known, but not completely understood. We have performed a study to examine the role of macrophage-inducible C-type lectin (Mincle) in inflammation-associated parturition. Using human samples, we show that spontaneous labour is associated with up-regulated Mincle expression in the myometrium and fetal membranes. Mincle expression was also increased in fetal membranes and myometrium in the presence of pro-labour mediators, the proinflammatory cytokines interleukin (IL)-1B and tumour necrosis factor (TNF), and Toll-like receptor (TLR) ligands fsl-1, poly(I:C), lipopolysaccharide (LPS) and flagellin. These clinical studies are supported by mouse studies, where an inflammatory challenge in a mouse model of preterm birth increased Mincle expression in the uterus. Importantly, elimination of Mincle decreased the effectiveness of proinflammatory cytokines and TLR ligands to induce the expression of pro-labour mediators; namely, proinflammatory cytokines and chemokines, contraction-associated proteins and prostaglandins, and extracellular matrix remodelling enzymes, matrix metalloproteinases. The data presented in this study suggest that Mincle is required when inflammatory activation precipitates parturition.
Mental illness and obesity among Veterans undergoing percutaneous coronary intervention: Insights from the VA CART program
Authors: Brostow Diana P. , Warsavage Theodore J. , Abbate Lauren M. , Starosta Amy J. , Brenner Lisa A. , Plomondon Mary E. , Valle Javier A.
Published: February 2019

Mental illness and obesity are highly prevalent in patients with coronary disease and are frequently comorbid. While mental illness is an established risk factor for major adverse cardiac and cerebrovascular events (MACCEs), prior studies suggest improved outcomes in people with obesity. It is unknown if obesity and mental illness interact to affect cardiac outcomes or if they independently influence MACCE. We identified 55 091 patients undergoing percutaneous coronary intervention (PCI) between 2009 and 2014, using the Veterans Affairs (VA) Clinical Assessment Reporting and Tracking (CART) program. Cox methods were used to assess the risk of MACCE by weight status and psychiatric diagnosis, and assessed for interaction. Compared to normal weight status, higher weight was associated with reduced MACCE events after PCI (mean follow‐up of 2 years) for both stable angina and acute coronary syndromes (ACSs; reduction of >13% in stable angina, >17% in ACS; P < 0.01 for both after adjustment). Having a non‐substance abuse mental illness diagnosis increased risk of MACCE compared to patients without mental illness in stable angina over 17%; P < 0.05, but not in ACS. When analysed for interaction, obesity and mental illness did not significantly impact MACCE over their independent influences. These results suggest that mental illness along with weight status have significant impact on MACCE, post‐PCI. Clinicians should be aware of patients' mental health status as a significant cardiovascular risk factor after PCI, independent of weight status.
Multiyear monitoring of survival following mitigation‐driven translocation of a long‐lived threatened reptile
Authors: Dickson Brett G. , Scherer Rick D. , Kissel Amanda M. , Wallace Bryan P. , Langin Kathryn M. , Gray Miranda E. , Scheib Amanda F. , Weise Bruce
Published: February 2019

Translocation is used by managers to mitigate the negative impacts of development on species. Moving individuals to a new location is challenging, and many translocation attempts have failed. Robust, posttranslocation monitoring is therefore important for evaluating effects of translocation on target species. We evaluated the efficacy of a translocation designed to mitigate the effects of a utility‐scale solar energy project on the U.S. federally listed Mojave desert tortoise (Gopherus agassizii). The species is a long‐lived reptile threatened by a variety of factors, including habitat loss due to renewable energy development in the Mojave Desert and portions of the Colorado Desert in southern California (southwestern United States). We translocated 58 individual tortoises away from the project's construction site and intensively monitored them over 5 years (2012–2017). We monitored these individuals and tortoises located in the translocation release area (resident tortoises; n = 112) and control tortoises (n = 149) in a nearby location. We used our tortoise encounter data and known‐fate survival models to estimate annual and cumulative survival. Translocated tortoises in each of 2 size classes (120–160 mm, >160 mm) did not survive at lower rates than resident and control tortoises over the study period. For models with different sets of biotic and abiotic covariates, annual and cumulative estimates of survival were always >0.87 and >0.56, respectively. Larger tortoises tended to have higher survival, but translocated tortoises were not differentially affected by the covariates used to model variation in survival. Based on these findings, our translocation design and study protocols could inform other translocation projects for desert species. Our case study highlights the benefits of combining rigorous scientific monitoring with well‐designed, mitigation‐driven management actions to reduce the negative effects of development on species of conservation concern.
Ecology of wood‐inhabiting fungi in northern forests of Iran
Authors: Bari Ehsan , Aghajani Hamed , Ohno Katie M. , Shahi Roya , Hale Mike D. C. , Bahmani Mohsen
Published: February 2019

Wood‐decay fungi are important in forest ecosystems and play an important role in nutrient and carbon recycling. The scope of this research was to identify wood‐inhabiting and wood‐decay macrofungi and determine their ecology. We sampled standing trees and dead wood of oak and hornbeam in the northern forests of Iran, specifically in Mazandaran and Golestan provinces. We assessed the influence of field slope, elevation, site direction and the height of fungal sporocarp position on the tree. The species of wood‐inhabiting and wood‐decay fungi belonged to 11 families: Polyporaceae; Stereaceae; Ganodermataceae; Physalacriaceae; Agaricaceae; Xylariaceae; Pluteaceae; Coprinaceae; Strophariaceae; Pleurotaceae; and Hydnaceae. The most common fungal species identified belonged to the Polyporaceae and Ganodermataceae and predominantly grew on trees growing on a slope of 20%, at an altitude of 700–900 m, 0–3 m from the ground a southwesterly site direction and the northern sides of both tree species. These results indicated that field slope was the most important factor in determining fungal sporocarp abundance.
Oxidative lipoprotein markers predict poor functional outcome in patients with minor stroke or transient ischaemic attack
Authors: Wang A. , Zhang X. , Li S. , Zhao X. , Liu L. , Johnston S. C. , Meng X. , Lin J. , Zuo Y. , Li H. , Wang Y. , Wang Y. ,   the CHANCE Study Group
Published: February 2019

Background and purpose

Oxidative stress plays an important role in acute ischaemic stroke. However, the association of oxidative lipoprotein markers, including oxidized low‐density lipoprotein (oxLDL), oxLDL:high‐density lipoprotein (HDL) and oxLDL:low‐density lipoprotein (LDL), with functional outcome of minor stroke or transient ischaemic attack (TIA) remains unclear. We aimed to investigate the association between oxidative lipoprotein markers and poor functional outcome in patients with minor stroke or TIA.

Methods

All patients with minor stroke or TIA were recruited from the Clopidogrel in High‐Risk Patients With Acute Non‐Disabling Cerebrovascular Events (CHANCE) trial. The poor functional outcome included modified Rankin Scale (mRS) score 2–6 and 3–6 at 90‐day and 12‐month follow‐up. Multivariate logistic regression was used to investigate the associations of oxLDL, oxLDL:HDL and oxLDL:LDL with poor functional outcome.

Results

Among 3019 patients included in this study, the median (interquartile range) oxLDL, oxLDL:HDL and oxLDL:LDL were 13.96 (6.65–28.81), 4.52 (2.08–9.32) and 11.73 (5.27–24.85) μg/dL, respectively. After adjusted for confounding factors, patients in the highest oxLDL quartile had a higher proportion of mRS score 2–6 at 90 days [hazard ratio (HR), 1.78; 95% confidence interval (CI), 1.26–2.52] and 12 months (HR, 1.42; 95% CI, 1.01–1.99), and mRS score 3–6 at 90 days (HR, 1.98; 95% CI, 1.29–3.04) and 12 months (HR, 1.77; 95% CI, 1.09–2.89) when compared with the lowest oxLDL quartile (P < 0.05). Similar results were found for oxLDL:HDL and oxLDL:LDL.

Conclusions

Higher levels of oxidative lipoprotein markers are independent predictors of poor functional outcome in patients with minor stroke or TIA at 90 days and 12 months.
Phytosanitary management of Citrus germplasm in France
Authors: Legrand P.
Published: February 2019

It is important to assess the phytosanitary status of plants for planting as many pests are transmitted with plant propagating material. The phytosanitary management of Citrus germplasm in France, in application of the European phytosanitary regulations, is described in this article. Import of Citrus germplasm into France is strictly regulated and only possible through the post‐entry quarantine station for plants, which receives plant material from all over the world. Subsequently, the French Citrus biological resource centre maintains and distributes plant material to the scientific community and to partners for production of graft‐sticks and plants for planting in nurseries. The continuous assessment of the phyto sanitary status of plants for planting throughout the production chain involves different stakeholders to ensure the high quality plant health status of Citrus orchards.
Tropical joint syndrome: Exostosis on the dorsal aspect of the proximal phalanx in racing Thoroughbreds in Asia
Authors: Shaw D. J. , Rosanowski S. M.
Published: February 2019

Tropical joint syndrome (TJS) is poorly documented in the published literature but appears to be associated with horses undergoing intensive training in tropical areas: South East Asia and Northern Australia. Tropical joint syndrome is characterised by a firm, often nonpainful swelling at the front of the fetlock, which has a slow and insidious onset. Swelling associated with TJS can reach an alarming size, with a marked loss of fetlock flexion. Radiographs reveal varying degrees of exostosis, initially on the dorsolateral aspect of proximal phalanx (P1) but, as the condition progresses, onto the dorsomedial P1 and distal dorsal third metacarpal bone. A survey of equine veterinarians employed in racing practices in Southeast Asia and Australia (n = 10) was undertaken to estimate the prevalence of this condition and treatment methods. Additionally, a retrospective study of clinical records was undertaken at the Singapore Turf Club to identify horses with TJS, with racing performance post‐diagnosis compared with matched controls. All 10 racing veterinarians responded to the survey. All respondents recognised TJS in horses in their practice as ‘new bone deposits of unknown origin’, with most estimating prevalence between 1 and 10% in their population of horses. The most common treatment for TJS was intra‐articular medication (n = 9) and/or shockwave therapy. In total, 79 horses had TJS diagnosed by equine veterinarians at the Singapore Turf Club between 2008 and 2015, 64 of which had complete race records. There was no significant difference in racing performance between horses with and without TJS. However, 29 cases that were retired from racing were retired with chronic, severe and irreversible fetlock pain. The high number of horses retired with fetlock pain due to TJS is a welfare concern. More research is required to identify management and treatment strategies to aid in dealing with this condition.