bluuebunny/crossref_metadata_2025_split huggingface dataset:
Astrocytic modulation of glutamatergic synaptic transmission is reduced in NTS of rats submitted to short-term sustained hypoxia
Authors: Accorsi-Mendonça Daniela , Bonagamba Leni G. H. , Machado Benedito H. 
Published: March 2019

Sustained hypoxia (SH) activates chemoreceptors to produce cardiovascular and respiratory responses to bring the arterial partial pressure of O2back to the physiological range. We evaluated the effect of SH (fraction of inspired O2 = 0.10, 24 h) on glutamatergic synaptic transmission and the interaction neuron-astrocyte in neurons of the nucleus tractus solitarii (NTS). Tractus solitarius (TS) fiber stimulation induced glutamatergic currents in neurons and astrocytes. SH increased α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate (AMPA/kainate) [−183 ± 122 pA ( n = 10) vs. −353 ± 101 pA ( n = 10)] and N-methyl-d-aspartate (NMDA) current amplitude [61 ± 10 pA ( n = 7) vs. 102 ± 37 pA ( n = 10)]. To investigate the effects of SH, we used fluoroacetate (FAC), an astrocytic inhibitor, which revealed an excitatory modulation on AMPA/kainate current and an inhibitory modulation of NMDA current in control rats. SH blunted the astrocytic modulation of AMPA [artificial cerebrospinal fluid (aCSF): −353 ± 101 pA vs. aCSF + FAC: −369 ± 76 pA ( n = 10)] and NMDA currents [aCSF: 102 ± 37 pA vs. aCSF + FAC: 108 ± 32 pA ( n = 10)]. SH increased AMPA current density [control: −6 ± 3.5 pA/pF ( n = 6) vs. SH: −20 ± 12 pA/pF ( n = 7)], suggesting changes in density, conductance, or affinity of AMPA receptors. SH produced no effect on astrocytic resting membrane potential, input resistance, and AMPA/kainate current. We conclude that SH decreased the neuron-astrocyte interaction at the NTS level, facilitating the glutamatergic transmission, which may contribute to the enhancement of cardiovascular and respiratory responses to baro- and chemoreflexes activation in SH rats.NEW & NOTEWORTHY Using an electrophysiological approach, we have shown that in nucleus tractus solitarii (NTS) from control rats, astrocytes modulate the AMPA and NMDA currents in NTS neurons, changing their excitability. Sustained hypoxia (SH) increased both glutamatergic currents in NTS neurons due to 1) a reduction in the astrocytic modulation and 2) an increase in the density of AMPA receptors. These new findings show the importance of neuron-astrocyte modulation in the excitatory synaptic transmission in NTS of control and SH rats.
Direction of action of presynaptic GABAA receptors is highly dependent on the level of receptor activation
Authors: Khatri Shailesh N. , Wu Wan-Chen , Yang Ying , Pugh Jason R. 
Published: March 2019

Many synapses, including parallel fiber synapses in the cerebellum, express presynaptic GABAA receptors. However, reports of the functional consequences of presynaptic GABAA receptor activation are variable across synapses, from inhibition to enhancement of transmitter release. We find that presynaptic GABAA receptor function is bidirectional at parallel fiber synapses depending on GABA concentration and modulation of GABAA receptors in mice. Activation of GABAA receptors by low GABA concentrations enhances glutamate release, whereas activation of receptors by higher GABA concentrations inhibits release. Furthermore, blocking GABAB receptors reduces GABAA receptor currents and shifts presynaptic responses toward greater enhancement of release across a wide range of GABA concentrations. Conversely, enhancing GABAA receptor currents with ethanol or neurosteroids shifts responses toward greater inhibition of release. The ability of presynaptic GABAA receptors to enhance or inhibit transmitter release at the same synapse depending on activity level provides a new mechanism for fine control of synaptic transmission by GABA and may explain conflicting reports of presynaptic GABAA receptor function across synapses. NEW & NOTEWORTHY GABAA receptors are widely expressed at presynaptic terminals in the central nervous system. However, previous reports have produced conflicting results on the function of these receptors at different synapses. We show that presynaptic GABAA receptor function is strongly dependent on the level of receptor activation. Low levels of receptor activation enhance transmitter release, whereas higher levels of activation inhibit release at the same synapses. This provides a novel mechanism by which presynaptic GABAA receptors fine-tune synaptic transmission.
Negative Regulation of p53-Induced Senescence by N-WASP Is Crucial for DMBA/TPA-Induced Skin Tumor Formation
Authors: Li Hui , Petersen Simon , Garcia Mariscal Alberto , Brakebusch Cord 
Published: March 2019

AbstractMice with a keratinocyte-restricted deletion of the actin polymerization–promoting molecule, N-WASP, display cyclic hair loss and skin inflammation. Here, we showed that these mice were also resistant to 7,12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)–induced skin tumor formation. This resistance correlated with decreased expression of the senescence regulator, DNMT1, and increased expression of the senescence marker, p16Ink4a, in N-WASP–deficient epidermis. Moreover, primary N-WASP–null keratinocytes displayed a premature senescence phenotype in vitro. Expression and activation of p53, a major inducer of senescence, was not significantly altered in N-WASP–null keratinocytes. However, impairment of p53 function effectively rescued the senescence phenotype, indicating that N-WASP was an inhibitor of p53-induced senescence. Mechanistically, N-WASP regulated senescence by preventing p53-dependent degradation of the H3K9 methyltransferases, G9a/GLP, and the DNA methyltransferase, DNMT1, which both control keratinocyte senescence. This pathway collaborated with other N-WASP–independent, senescence-promoting signaling downstream of p53 and allowed the fine tuning of p53-induced senescence by N-WASP. Collectively, these data reveal N-WASP as an inhibitor of p53-induced senescence, which might be of importance for skin tumor formation and cellular aging of keratinocytes.Significance:These findings demonstrate that N-WASP regulates p53-dependent senescence in keratinocytes in vitro and in vivo.
Inhibition of EphB4–Ephrin-B2 Signaling Reprograms the Tumor Immune Microenvironment in Head and Neck Cancers
Authors: Bhatia Shilpa , Oweida Ayman , Lennon Shelby , Darragh Laurel B. , Milner Dallin , Phan Andy V. , Mueller Adam C. , Van Court Benjamin , Raben David , Serkova Natalie J. , Wang Xiao-Jing , Jimeno Antonio , Clambey Eric T. , Pasquale Elena B. , Karam Sana D. 
Published: March 2019

Abstract

Identifying targets present in the tumor microenvironment that contribute to immune evasion has become an important area of research. In this study, we identified EphB4–ephrin-B2 signaling as a regulator of both innate and adaptive components of the immune system. EphB4 belongs to receptor tyrosine kinase family that interacts with ephrin-B2 ligand at sites of cell–cell contact, resulting in bidirectional signaling. We found that EphB4–ephrin-B2 inhibition alone or in combination with radiation (RT) reduced intratumoral regulatory T cells (Tregs) and increased activation of both CD8+ and CD4+Foxp3− T cells compared with the control group in an orthotopic head and neck squamous cell carcinoma (HNSCC) model. We also compared the effect of EphB4–ephrin-B2 inhibition combined with RT with combined anti-PDL1 and RT and observed similar tumor growth suppression, particularly at early time-points. A patient-derived xenograft model showed reduction of tumor-associated M2 macrophages and favored polarization towards an antitumoral M1 phenotype following EphB4–ephrin-B2 inhibition with RT. In vitro, EphB4 signaling inhibition decreased Ki67-expressing Tregs and Treg activation compared with the control group. Overall, our study is the first to implicate the role of EphB4–ephrin-B2 in tumor immune response. Moreover, our findings suggest that EphB4–ephrin-B2 inhibition combined with RT represents a potential alternative for patients with HNSCC and could be particularly beneficial for patients who are ineligible to receive or cannot tolerate anti-PDL1 therapy.

Significance:
These findings present EphB4–ephrin-B2 inhibition as an alternative to anti-PDL1 therapeutics that can be used in combination with radiation to induce an effective antitumor immune response in patients with HNSCC.
Inhibition of miR-328–3p Impairs Cancer Stem Cell Function and Prevents Metastasis in Ovarian Cancer
Authors: Srivastava Amit K. , Banerjee Ananya , Cui Tiantian , Han Chunhua , Cai Shurui , Liu Lu , Wu Dayong , Cui Ri , Li Zaibo , Zhang Xiaoli , Xie Guozhen , Selvendiran Karuppaiyah , Patnaik Srinivas , Karpf Adam R. , Liu Jinsong , Cohn David E. , Wang Qi-En 
Published: March 2019

AbstractCancer stem cells (CSC) play a central role in cancer metastasis and development of drug resistance. miRNA are important in regulating CSC properties and are considered potential therapeutic targets. Here we report that miR-328–3p (miR-328) is significantly upregulated in ovarian CSC. High expression of miR-328 maintained CSC properties by directly targeting DNA damage binding protein 2, which has been shown previously to inhibit ovarian CSC. Reduced activity of ERK signaling in ovarian CSC, mainly due to a low level of reactive oxygen species, contributed to the enhanced expression of miR-328 and maintenance of CSC. Inhibition of miR-328 in mouse orthotopic ovarian xenografts impeded tumor growth and prevented tumor metastasis. In summary, our findings provide a novel mechanism underlying maintenance of the CSC population in ovarian cancer and suggest that targeted inhibition of miR-328 could be exploited for the eradication of CSC and aversion of tumor metastasis in ovarian cancer.Significance:These findings present inhibition of miR-328 as a novel strategy for efficient elimination of CSC to prevent tumor metastasis and recurrence in patients with epithelial ovarian cancer.
Characterization of insect galls from a vegetation area in Altinópolis, São Paulo State, Brazil
Authors: Ribeiro Amanda Das Neves , Balbi Maria Isabel Protti de Andrade , Urso-Guimarães Maria Virginia 
Published: March 2019

Herein, we studied the occurrence of insect galls from natural vegetation around the Itambé Cave, Altinópolis, SP, Brazil. A sampling effort of 7.5 hours resulted in 41 gall morphotypes on 21 host plant species from 14 families. The richest families of host plants in morphotypes were Fabaceae (N = 11), Euphorbiaceae (N = 7), and Malpighiaceae (N = 5). Copaifera langsdorffii Desf. (N = 8), Croton floribundus Spreng. (N = 7), Diplopterys pubipetala (A. Juss.) W.R. Anderson & C.C. Davis (N = 5), and Bauhinia holophylla (Bong.) Steud. (N = 4) were the super host plant species. Among the gall makers obtained, cecidomyiids were reared in 81% of cases and Hemiptera (Diaspididae), Hymenoptera (Eurytomidae), Coleoptera (Apion sp./Apionidae), and Lepidoptera in 4.5% of cases, each. The parasitoids belong to the Chalcidoidea superfamily (Hymenoptera). One new species of Camptoneuromyiia (Cecidomyiidae) was found in Smilax oblongifolia Pohl ex Griseb. (Smilacaceae) as inquiline and a new species of Lestodiplosis in Diplopterys pubipetala (Malpighiaceae) was a predator. We also present the first register of Bauhinia holophylla as host plants of Cecidomyiidae, and we expand the occurrence of Rochadiplosis tibouchinae Tavares and Couridiplosis vena to São Paulo State. The results of this paper are a continuation of the description of gall morphotypes from the vegetation in Northeastern São Paulo State, and they also increase knowledge about the diversity of host plant and gall-maker associations in the Neotropical region.
Practice Variation in Anticoagulation Prescription and Outcomes After Device-Detected Atrial Fibrillation
Authors: Perino Alexander C. , Fan Jun , Askari Mariam , Heidenreich Paul A. , Keung Edmund , Raitt Merritt H. , Piccini Jonathan P. , Ziegler Paul D. , Turakhia Mintu P. 
Published: March 2019

Background:
Device-detected atrial fibrillation (AF) is associated with increased risk of stroke; however, there are no clearly defined thresholds of AF burden at which to initiate oral anticoagulation (OAC). We sought to describe OAC prescription practice variation in response to new device-detected AF and the association with outcomes.

Methods:

We performed a retrospective cohort study using data from the Veterans Health Administration linked to remote monitoring data that included day-level AF burden. We included patients with cardiac implantable electronic devices and remote monitoring from 2011 to 2014, CHA
2
DS
2
-VASc score ≥2, and no prior stroke or OAC receipt in the preceding 2 years. We determined the proportion of patients prescribed OAC within 90 days after new device-detected AF across a range of AF thresholds (≥6 minutes to >24 hours) and examined site variation in OAC prescription. We used multivariable Cox proportional hazards regressions to determine the association of OAC prescription with stroke by device-detected AF burden.

Results:

Among 10 212 patients with cardiac implantable electronic devices, 4570 (45%), 3969 (39%), 3263 (32%), and 2469 (24%) had device-detected AF >6 minutes, >1 hour, >6 hours, and >24 hours, respectively. For device-detected AF >1 hour, 1712 patients met inclusion criteria (72±10 years; 1.5% female; CHA
2
DS
2
-VASc score 4.0±1.4; HAS-BLED score 2.6±1.1). The proportion receiving OAC varied based on device-detected AF burden (≥6 minutes: 272/2101 [13%]; >1 hour: 273/1712 [16%]; >6 hours: 263/1279 [21%]; >24 hours: 224/818 [27%]). Across 52 sites (N=1329 patients), there was substantial site-level variation in OAC prescription after device-detected AF >1 hour (median, 16%; range, 3%–67%; median odds ratio, 1.56 [95% credible interval, 1.49–1.71]). In adjusted models, OAC prescription after device-detected AF >24 hours was associated with reduced stroke risk (hazard ratio, 0.28; 95% CI, 0.10–0.81;
P
=0.02), although the propensity-adjusted model was significant when AF lasted at least 6 minutes.

Conclusions:
Among veterans with cardiac implantable electronic devices, device-detected AF is common. There is large practice variation in 90-day OAC initiation after new device-detected AF, with low rates of treatment overall, even for episodes that last >24 hours. The strongest association of OAC with reduction in stroke was observed after device-detected AF >24 hours. Randomized trials are needed to confirm these observational findings.
Mitophagy Reduces Oxidative Stress Via Keap1 (Kelch-Like Epichlorohydrin-Associated Protein 1)/Nrf2 (Nuclear Factor-E2-Related Factor 2)/PHB2 (Prohibitin 2) Pathway After Subarachnoid Hemorrhage in Rats
Authors: Zhang Tongyu , Wu Pei , Budbazar Enkhjargal , Zhu Qiquan , Sun Chengmei , Mo Jun , Peng Jianhua , Gospodarev Vadim , Tang Jiping , Shi Huaizhang , Zhang John H. 
Published: March 2019

Background and Purpose—
Mitoquinone has been reported as a mitochondria-targeting antioxidant to promote mitophagy in various chronic diseases. Here, our aim was to study the role of mitoquinone in mitophagy activation and oxidative stress–induced neuronal death reduction after subarachnoid hemorrhage (SAH) in rats.

Methods—
Endovascular perforation was used for SAH model of male Sprague-Dawley rats. Exogenous mitoquinone was injected intraperitoneally 1 hour after SAH. ML385, an inhibitor of Nrf2 (nuclear factor-E2-related factor 2), was given intracerebroventricularly 24 hours before SAH. Small interfering RNA for PHB2 (prohibitin 2) was injected intracerebroventricularly 48 hours before SAH. Nuclear, mitochondrial, and cytoplasmic fractions were gathered using nucleus and mitochondria isolation kits. SAH grade evaluation, short- and long- term neurological function tests, oxidative stress, and apoptosis measurements were performed. Pathway related proteins were investigated with Western blot and immunofluorescence staining.

Results—
Expression of Keap1 (Kelch-like epichlorohydrin-associated protein 1, 2.84× at 24 hours), Nrf2 (2.78× at 3 hours), and LC3II (light chain 3-II; 1.94× at 24 hours) increased, whereas PHB2 (0.46× at 24 hours) decreased after SAH compared with sham group. Mitoquinone treatment attenuated oxidative stress and neuronal death, both short-term and long-term. Administration of mitoquinone resulted in a decrease in expression of Keap1 (0.33×), Romo1 (reactive oxygen species modulator 1; 0.24×), Bax (B-cell lymphoma-2 associated X protein; 0.31×), Cleaved Caspase-3 (0.29×) and an increase in Nrf2 (2.13×), Bcl-xl (B-cell lymphoma-extra large; 1.67×), PINK1 (phosphatase and tensin-induced kinase 1; 1.67×), Parkin (1.49×), PHB2 (1.60×), and LC3II (1.67×) proteins compared with SAH+vehicle group. ML385 abolished the treatment effects of mitoquinone on behavior and protein levels. PHB2 small interfering RNA reversed the outcomes of mitoquinone administration through reduction in protein expressions downstream of PHB2.

Conclusions—
Mitoquinone inhibited oxidative stress–related neuronal death by activating mitophagy via Keap1/Nrf2/PHB2 pathway after SAH. Mitoquinone may serve as a potential treatment to relieve brain injury after SAH.
Indophyes yaromi, a new genus and species of Nanophyidae (Curculionoidea) from southern India
Authors: FRIEDMAN ARIEL-LEIB-LEONID 
Published: March 2019

A new monobasic genus of Nanophyidae, Indophyes, and a new species, I. yaromi, are described from southern India (type locality: Karnataka, Bilukoppa, 800 m, 40 km W Mudigere). The new genus is characterized by 5-segmented antennal funicle, strong sexual dimorphism of the rostrum, dentate femora, male tibiae unarmed, abdominal suture IV distinct in both sexes, male pygidium not foveate and 8th elytral interstria not crenulate. The subulate form of rostrum—abruptly narrowed apically—is unusual among the Nanophyidae.
Sliding bone graft combined with double locking plate fixation for the treatment of femoral shaft nonunion
Authors: Xing Wenzhao , Pan Zhenhua , Sun Lei , Sun Liang , Zhang Chunpu , Zhang Zhiguo , Feng Wenling , Liu Changcheng 
Published: March 2019

Objectives The aim of this study was to describe and evaluate a novel method of sliding bone graft combined with double locking plate fixation in treating femoral shaft nonunion. Methods Clinical data from patients with femoral shaft nonunion that was treated with sliding bone grafts combined with double locking plate fixation were retrospectively collected. Data included duration of surgery, blood loss, union rate, time to union and possible complications. Results Twenty-five patients included in the study were followed for a mean duration of 16.6 ± 2.6 months (range, 12–22 months). All of the fractures (100%) achieved bony union. Mean time to union was 6.0 ± 1.0 months (range, 4–8 months). No infections or medullary cavity occlusions were observed. Conclusions Sliding bone graft combined with double locking plate fixation was shown to be a safe, effective, and convenient surgical option for the treatment of nonunion, due to its high union rates with no complications. Further studies with larger sample sizes and longer-term follow-up are warranted.
Short-lasting retroorbital pain attacks as a form of ictal epileptic headache: Case report
Authors: Viana Pedro F , Hasegawa Harumoto , Jarosz Josef , Siddiqui Ata , Selway Richard P , Mullatti Nandini 
Published: March 2019

Background and objectivesIctal epileptic headache is a rare form of painful seizure, habitually consisting of migrainous or tension-type headache. We describe a case of a patient with short-lasting, severe retroorbital pain attacks caused by frontal lobe epilepsy.Case reportA 25-year-old male patient presented with recurrent attacks of paroxysmal, short-lasting, excruciating left periorbital and facial pain mainly occurring from sleep. After intracranial EEG exploration and resection of a right prefrontal focal cortical dysplasia, long-term seizure and headache remission was obtained.DiscussionOur case extends the clinical and neuroanatomical spectrum of ictal epileptic headache and suggests that long-term remission can be obtained by resective epilepsy surgery. It also reinforces the role of the prefrontal cortex in the pain matrix and pain generation.ConclusionDespite its rarity, ictal epileptic headache should be suspected in selected patients, particularly those with other ictal symptoms and signs, history of epileptic seizures, or neuroimaging abnormalities.
Random scaling factors in Bayesian distributional regression models with an application to real estate data
Authors: Razen Alexander , Lang Stefan 
Published: March 2019

Distributional structured additive regression provides a flexible framework for modelling each parameter of a potentially complex response distribution in dependence of covariates. Structured additive predictors allow for an additive decomposition of covariate effects with non-linear effects and time trends, unit- or cluster-specific heterogeneity, spatial heterogeneity and complex interactions between covariates of different type. Within this framework, we present a simultaneous estimation approach for multiplicative random effects that allow for cluster-specific heterogeneity with respect to the scaling of a covariate′s effect. More specifically, a possibly non-linear function f( z) of a covariate z may be scaled by a multiplicative and possibly spatially correlated cluster-specific random effect (1+αc). Inference is fully Bayesian and is based on highly efficient Markov Chain Monte Carlo (MCMC) algorithms. We investigate the statistical properties of our approach within extensive simulation experiments for different response distributions. Furthermore, we apply the methodology to German real estate data where we identify significant district-specific scaling factors. According to the deviance information criterion, the models incorporating these factors perform significantly better than standard models without (spatially correlated) random scaling factors.
Exercise training in women with cardiovascular disease: Differential response and barriers – review and perspective
Authors: Witvrouwen Isabel , Van Craenenbroeck Emeline M , Abreu Ana , Moholdt Trine , Kränkel Nicolle 
Published: March 2019

Abstract

Background
Exercise-based cardiac rehabilitation has a class 1A recommendation in coronary artery disease and heart failure based on its beneficial effects on mortality, morbidity and quality of life. However, the inter-individual response to exercise training is highly variable and influenced by both training and patient characteristics. Notably, men and women display a different training response, even when accounting for age, height and lean muscle mass. Most studies investigating exercise effects on various physiological outcomes focus on male patients. Because women are understudied, the scientific evidence for tailored exercise prescription in women is still limited.

Methods
This narrative review summarises: (a) the underlying physiological determinants of the response to exercise training in women with cardiovascular disease, in which women rely more on fat than on carbohydrate oxidation during exercise, have lower aerobic capacities and smaller increases in cardiac function during exercise; (b) the benefits and barriers of exercise in women, in whom improving cardiometabolic risk and quality of life is weighed against socioeconomic and psychological needs; and (c) the relevance of different clinical endpoints in exercise trials such as maximum oxygen uptake, morbidity, mortality, training characteristics, quality of life and metabolic or vascular endpoints.

Results
Finally, we provide a perspective on how to improve referral, enrolment and adherence to exercise training in women, with structured approaches to inform the referring physician as well as the patient, and offering more flexible, gender-tailored or tele/smartphone-based programmes while addressing the socioeconomic and psychological needs of the patients. This may ultimately improve the admission, adherence and outcome of exercise-based cardiac rehabilitation in women.