bluuebunny/crossref_metadata_2025 huggingface dataset:
Cowpea aphid–plant interactions: endosymbionts and related salivary protein patterns
Authors: Bayendi Loudit Sandrine Mariella , Bauwens Julien , Francis Frédéric
Published: June 2018

The specificity of plant use by aphids is related to symbiont diversity of some aphid models. Aphis craccivora Koch (Hemiptera: Aphididae, Aphidini) is a well‐known aphid that feeds on species of Fabaceae, but has also been recorded recently on Amaranthus species (Amaranthaceae) in Gabon (Africa). Aphis craccivora strains used in this study were originally collected from crop Vigna unguiculata L. Walp. (Fabaceae) from Togba in Benin (Africa) and Amaranthus hybridus L. from Libreville in Gabon, for a comparative study of symbionts. Saliva composition, potentially including bacterial proteins, also contributes to the phytotoxic effect of aphid attacks. Both, endosymbiont bacteria and saliva protein diversity should be targeted to investigate the feeding behavior of aphids and to explain plant–aphid interactions. Bacteria‐targeted PCR was conducted on six symbionts in A. craccivora. The obligate symbiont Buchnera aphidicola Munson et al. (Enterobacteriaceae) was identified in all aphids collected. In comparison, the facultative symbiont Serratia symbiotica Moran et al. (Enterobacteriaceae) was only found in A. craccivora from Gabon, whereas Rickettsia sp. (Rickettsiaceae) was only found in aphids from Benin. Using nano‐LC‐MS/MS (liquid chromatography‐tandem mass spectrometry), some proteins were only found in solid or soluble saliva, whereas others originated from S. symbiotica. Two of the identified proteins are involved in plant–pathogen interactions: calmodulin and elongation factor Tu. This information on endosymbionts and related salivary proteomes from A. craccivora in Gabon helps improve our understanding of aphid–plant interactions.
Cholinergic control of striatal neurons to modulate L‐dopa‐induced dyskinesias
Authors: Bordia Tanuja , Perez Xiomara A.
Published: June 2018

L‐dopa induced dyskinesias (LIDs) are a disabling motor complication of L‐dopa therapy for Parkinson's disease (PD) management. Treatment options remain limited and the underlying network mechanisms remain unclear due to a complex pathophysiology. What is well‐known, however, is that aberrant striatal signaling plays a key role in LIDs development. Here, we discuss the specific contribution of striatal cholinergic interneurons (ChIs) and GABAergic medium spiny projection neurons (MSNs) with a particular focus on how cholinergic signaling may integrate multiple striatal systems to modulate LIDs expression. Enhanced ChI transmission, altered MSN activity and the associated abnormal downstream signaling responses that arise with nigrostriatal damage are well known to contribute to LIDs development. In fact, enhancing M4 muscarinic receptor activity, a receptor favorably expressed on D1 dopamine receptor‐expressing MSNs dampens their activity to attenuate LIDs. Likewise, ChI activation via thalamostriatal neurons is shown to interrupt cortical signaling to enhance D2 dopamine receptor‐expressing MSN activity via M1 muscarinic receptors, which may interrupt ongoing motor activity. Notably, numerous preclinical studies also show that reducing nicotinic cholinergic receptor activity decreases LIDs. Taken together, these studies indicate the importance of cholinergic control of striatal neuronal activity and point to muscarinic and nicotinic receptors as significant pharmacological targets for alleviating LIDs in PD patients.
Quantification and statistical analysis of the transient visual evoked potential to a contrast‐reversing pattern: A frequency‐domain approach
Authors: Zemon Vance M. , Gordon James
Published: June 2018

Visual function is often assessed by recording transient visual evoked potentials to contrast reversal of spatial patterns (tVEP‐CR). This technique relies on measurements of amplitudes and peak times of a few points in the time‐domain waveform, which require subjective selection of appropriate time points in a possibly noisy waveform and ignores much of the informational content in the response. Here, we introduce a set of frequency‐domain measures that capture the full content of the response. Magnitude‐squared coherence is used to determine the significance and reliability of magnitude measures; estimates of time delay are based on frequency‐domain phase measures. In Study 1, extensive testing of a small number of observers revealed response details, and in Study 2, testing of a larger sample verified the novel frequency‐domain measures and demonstrated the validity of a short‐duration technique to produce reliable tVEP‐CRs. In addition, Study 2 revealed adaptation effects present under prolonged stimulation conditions. Principal component analyses provided evidence for six distinct frequency mechanisms, and comparisons with time‐domain measures indicated that power in high‐frequency bands may be used as objective measures of excitatory input to visual cortex. A middle‐frequency band captures the major peaks in the tVEP‐CR waveform, and its power is highly correlated with the standard peak‐to‐trough amplitude measure. These novel frequency‐domain indices may serve as more precise and powerful tools to assess visual function in healthy and diseased states.
High‐frequency peripheral vibration decreases completion time on a number of motor tasks
Authors: Macerollo Antonella , Palmer Clare , Foltynie Thomas , Korlipara Prasad , Limousin Patricia , Edwards Mark , Kilner James M.
Published: June 2018

A recent theoretical account of motor control proposes that modulation of afferent information plays a role in affecting how readily we can move. Increasing the estimate of uncertainty surrounding the afferent input is a necessary step in being able to move. It has been proposed that an inability to modulate the gain of this sensory information underlies the cardinal symptoms of Parkinson's disease (PD). We aimed to test this theory by modulating the uncertainty of the proprioceptive signal using high‐frequency peripheral vibration, to determine the subsequent effect on motor performance. We investigated if this peripheral stimulus might modulate oscillatory activity over the sensorimotor cortex in order to understand the mechanism by which peripheral vibration can change motor performance. We found that 80 Hz peripheral vibration applied to the right wrist of a total of 54 healthy human participants reproducibly improved performance across four separate randomised experiments on a number of motor control tasks (nine‐hole peg task, box and block test, reaction time task and finger tapping). Improved performance on all motor tasks (except the amplitude of finger tapping) was also seen for a sample of 18PD patients ON medication. EEG data investigating the effect of vibration on oscillatory activity revealed a significant decrease in beta power (15–30 Hz) over the contralateral sensorimotor cortex at the onset and offset of 80 Hz vibration. This finding is consistent with a novel theoretical account of motor initiation, namely that modulating uncertainty of the proprioceptive afferent signal improves motor performance potentially by gating the incoming sensory signal and allowing for top‐down proprioceptive predictions.
Remodeling of the number and structure of dendritic spines in the medial amygdala: From prepubertal sexual dimorphism to puberty and effect of sexual experience in male rats
Authors: Zancan Mariana , da Cunha Rick Shandler R. , Schroeder Francielle , Xavier Léder L. , Rasia‐Filho Alberto A.
Published: June 2018

The posterodorsal medial amygdala (MePD) is a sexually dimorphic area and plays a central role in the social behavior network of rats. Dendritic spines modulate synaptic processing and plasticity. Here, we compared the number and structure of dendritic spines in the MePD of prepubertal males and females and postpubertal males with and without sexual experience. Spines were classified and measured after three‐dimensional image reconstruction using DiI fluorescent labeling and confocal microscopy. Significantly differences are as follows: (a) Prepubertal males have more proximal spines, stubby/wide spines with long length and large head diameter and thin and mushroom spines with wide neck and head diameters than prepubertal females, whereas (b) prepubertal females have more mushroom spines with long neck length than age‐matched males. (c) In males, the number of thin spines reduces after puberty and, compared to sexually experienced counterparts, (d) naive males have short stubby/wide spines as well as mushroom spines with reduced neck diameter. In addition, (e) sexually experienced males have an increase in the number of mushroom spines, the length of stubby/wide spines, the head diameter of thin and stubby/wide spines and the neck diameter of thin and mushroom spines. These data indicate that a sexual dimorphism in the MePD dendritic spines is evident before adulthood and a spine‐specific remodeling of number and shape can be brought about by both puberty and sexual experience. These fine‐tuned ontogenetic, hormonally and experience‐dependent changes in the MePD are relevant for plastic synaptic processing and the reproductive behavior of adult rats.
Supportive Coparenting, Parenting Stress, Harsh Parenting, and Child Behavior Problems in Nonmarital Families
Authors: Choi Jeong‐Kyun , Becher Emily H.
Published: June 2018

Supportive coparenting is an identified protective factor for child development and behavioral outcomes. What is less known is how supportive coparenting dynamically links with other aspects of parenting and parent well‐being, particularly in multi‐stressed nonmarital families. This study used data from the Fragile Families and Child Wellbeing study, analyzed within a structural equation model, to explore how mothers’ experience of maternal depression, maternal age, father education, andSESinteracted with their parenting stress and supportive coparenting to impact child behavioral problems and harsh parenting practices. Among the findings, more supportive coparenting was found to be significantly associated with fewer child behavioral problems and less harsh parenting. Transmitted through supportive coparenting and parenting stress acting as mediator, maternal depressive symptoms were indirectly and positively related to harsh parenting practices and child behavior problems. These findings are discussed within the context of the broader literature and next steps for research are discussed.
Acceptance, Psychiatric Symptoms, and Migraine Disability: An Observational Study in a Headache Center
Authors: Seng Elizabeth K. , Kuka Alexander J. , Mayson Sarah Jo , Smitherman Todd A. , Buse Dawn C.
Published: June 2018

Objective

To evaluate relationships between psychiatric symptoms, acceptance, and migraine‐related disability in a sample of people with migraine presenting at a tertiary care headache center.

Background

Migraine is a chronic disease that can be severely disabling. Despite a strong theoretical basis and evidence in other pain conditions, little is known about relationships between acceptance, psychiatric symptoms, and migraine‐related disability.

Methods

Ninety patients with physician‐diagnosed migraine completed surveys assessing demographics, headache symptoms, severe migraine‐related disability (Migraine Disability Assessment Scale total score dichotomized at ≥ 21), depression (Patient Health Questionnaire‐9) and anxiety symptoms (Generalized Anxiety Disorder‐7), and acceptance (Chronic Pain Acceptance Questionnaire; subscales: Pain Willingness and Activity Engagement).

Results

Participants (77.8% white, non‐Hispanic; 85.6% women; and 50.0% with a graduate level education) reported an average headache pain intensity of 6.7/10 (SD = 2.0). One‐third (36.0%) reported chronic migraine, and half (51.5%) reported severe migraine‐related disability. Lower acceptance was associated with severe migraine‐related disability, t(54) = 4.13, P < .001. Higher activity engagement was associated with lower average headache pain intensity (r = −.30, P = .011). Higher acceptance was associated with lower levels of depression (r = −.48, P < .001) and anxiety symptoms (r = −.37, P = .003). Pain willingness and activity engagement serially mediated relationships between depression symptoms and severe migraine‐related disability (indirect effect = 0.05, 95% CI = 0.01, 0.15), and between anxiety symptoms and severe migraine‐related disability (indirect effect = 0.12, 95% CI = 0.02, 0.31).

Conclusion

Results provided preliminary support for a theoretical pathway by which psychiatric symptoms may influence migraine‐related disability, in part, through their relationships with pain willingness and activity engagement.
The “three‐in‐one” formulation of bismuth quadruple therapy for Helicobacter pylori eradication with or without probiotics supplementation: Efficacy and safety in daily clinical practice
Authors: Zagari Rocco Maurizio , Romiti Alessandra , Ierardi Enzo , Gravina Antonietta G. , Panarese Alba , Grande Giuseppe , Savarino Edoardo , Maconi Giovanni , Stasi Elisa , Eusebi Leonardo Henry , Farinati Fabio , Conigliaro Rita , Bazzoli Franco , Romano Marco
Published: June 2018

Background

Clinical trials have shown a good efficacy of the “three‐in‐one” formulation of bismuth quadruple therapy (BQT) for Helicobacter (H.) pylori eradication. We aimed to assess the efficacy and safety of the three‐in‐one BQT in clinical practice, and investigate the effect of probiotic supplementation, in Italy.

Materials and Methods

A retrospective database, multicentre observational study was conducted in seven Italian Hospitals. Consecutive H. pylori‐positive patients who received the three‐in‐one BQT for 10 days were included in the analysis. H. pylori eradication was assessed by histology, 13C‐urea breath test, or stool antigen test. Compliance and adverse events were evaluated by interview.

Results

A total of 376 patients were included in the intention‐to‐treat (ITT) and 352 in the per protocol (PP) analyses. One hundred and ninety‐three subjects received probiotics supplementation. Overall, eradication rates were 90.2% (95% Confidence Interval (CI):86.7‐93.0) in ITT and 94.6% (95% CI: 91.7‐96.7) in PP analyses. The compliance was good (≥90% of treatment taken) in 94.9% of patients. The proportion of patients with a good compliance was not different with and without probiotics supplementation (94.8% vs 95.1%). Eradication rates were equally high for first‐line (91.4%), second‐line (87.5%), and third‐line treatments (91.7%) in the ITT analysis (P = .48). Adverse events were reported by 32.4% of patients, but only 6.1% of patients discontinued treatment.

Conclusions

The three‐in‐one BQT is highly effective and well tolerated for H. pylori eradication in daily clinical practice. Probiotics supplementation fails to improve compliance.
Spermine oxidase is upregulated and promotes tumor growth in hepatocellular carcinoma
Authors: Hu Tingting , Sun Dalong , Zhang Jie , Xue Ruyi , Janssen Harry L.A. , Tang Wenqing , Dong Ling
Published: June 2018

Aim

The polyamine catabolic enzyme, spermine oxidase (SMOX) is upregulated in chronic inflammatory conditions and linked to increased reactive oxygen species and DNA damage in various forms of cancers. The present study aims to explore the expression pattern and biological function of SMOX in hepatocellular carcinoma (HCC).

Methods

We used quantitative real‐time polymerase chain reaction, Western blotting, and immunohistochemistry to examine SMOX expression in four HCC cell lines and 120 HCC clinical samples, and the clinical significance of SMOX was analyzed. The biological function of SMOX on HCC cells was detected both in vitro and in vivo.

Results

Results showed that SMOX was overexpressed in HCC cell lines and clinical HCC tissues. Moreover, SMOX expression levels were gradually increased in normal liver, chronic hepatitis, and HCC tissues. Increased SMOX expression was correlated with poor clinical features of HCC. Patients with positive SMOX expression in tumor tissues indicated worse overall survival (P = 0.008) and shorter relapse‐free survival (P = 0.002). Knockdown of SMOX inhibited HCC cell proliferation, arrested cell cycle at S phase, and resulted in an increase of apoptosis. The in vivo study showed that inhibition of SMOX in HCC cells significantly repressed tumor growth in nude mice. Furthermore, we showed that SMOX might exert its function by regulating the phosphatidylinositol 3′‐kinase/protein kinase B signaling pathway.

Conclusion

Our data indicated that SMOX upregulation could be a critical oncogene in HCC and might serve as a valuable prognostic marker and potential therapeutic target for HCC.
Towards elimination of HIV transmission, AIDS and HIV‐related deaths in the UK
Authors: Brown AE , Nash S , Connor N , Kirwan PD , Ogaz D , Croxford S , De Angelis D , Delpech VC
Published: June 2018

Objectives

Our objective was to present recent trends in the UK HIV epidemic (2007–2016) and the public health response.

Methods

HIV diagnoses and clinical markers were extracted from the HIV and AIDS Reporting System; HIV testing data in sexual health services (SHS) were taken from GUMCAD STI Surveillance System. HIV data were modelled to estimate the incidence in men who have sex with men (MSM) and post‐migration HIV acquisition in heterosexuals. Office for National Statistics (ONS) data enabled mortality rates to be calculated.

Results

New HIV diagnoses have declined in heterosexuals as a result of decreasing numbers of migrants from high HIV prevalence countries entering the UK. Among MSM, the number of HIV diagnoses fell from 3570 in 2015 to 2810 in 2016 (and from 1554 to 1096 in London). Preceding the decline in HIV diagnoses, modelled estimates indicate that transmission began to fall in 2012, from 2800 [credible interval (CrI) 2300–3200] to 1700 (CrI 900–2700) in 2016. The crude mortality rate among people promptly diagnosed with HIV infection was comparable to that in the general population (1.22 vs. 1.39 per 1000 aged 15–59 years, respectively). The number of MSM tested for HIV at SHS increased annually; 28% of MSM who were tested in 2016 had been tested in the preceding year. In 2016, 76% of people started antiretroviral therapy within 90 days of diagnosis (33% in 2007).

Conclusions

The dual successes of the HIV transmission decline in MSM and reduced mortality are attributable to frequent HIV testing and prompt treatment (combination prevention). Progress towards the elimination of HIV transmission, AIDS and HIV‐related deaths could be achieved if combination prevention, including pre‐exposure prophylaxis, is replicated for all populations.
Psoriasis: implication to disease and therapeutic strategies, with an emphasis on drug delivery approaches
Authors: Todke Pooja , Shah Viral H.
Published: June 2018

Skin is the most visible and vulnerable organ of the integumentary system. Psoriasis is a chronic inflammatory skin disorder with an equal prevalence rate in males and females globally. Psoriasis is seen today beyond a cosmetic turmoil as it significantly impacts the socioeconomic life of the patients. Patients with severe psoriasis report feeling denounced and isolated. Despite detailed understanding of the molecular mechanisms and pathogenesis of psoriasis, issues like the autoimmune cause of inflammation and role of external, genetic, cutaneous, and systemic factors on initiation, progression, and treatment of psoriasis are still ambiguous. The present review summarizes immunogenic pathophysiology of psoriasis with a cascade of events from stimuli‐based release of self‐nucleotides to the hyperproliferation of keratinocytes leading to psoriasis. The review emphasizes challenges and hurdles toward the efficient treatment of psoriasis. The review also provides a detailed understanding of conventional and novel treatment strategies including drug delivery approaches and patented technologies for therapeutic and preventive approaches leading to improved outcome for psoriasis patients. The review summarizes a brief insight on biologics and gene therapy that has resulted in a paradigm shift in the treatment strategies for psoriasis management.
One‐seller assignment markets with multi‐unit demands: Core and competitive equilibrium
Authors: Robles Francisco , Núñez Marina
Published: June 2018

We consider an assignment market with one seller who owns several indivisible heterogeneous goods and many buyers each willing to buy up to a given capacity. In this market, the core contains the Vickrey payoff vector. However, core allocations may not be supported by competitive equilibrium prices, even in a finite replication of the market. We first characterize the convexity of the associated coalitional game and we show that it is a sufficient condition so that the buyers‐optimal core allocation is competitive. With respect to the seller‐optimal core allocation, we provide a characterization of competitiveness by means of buyers’ valuations. In addition, we characterize in terms of the valuation matrix the coincidence between the core and the set of competitive equilibrium payoff vectors.
Standardization and comparison of nonautomated assays to measure the collagen binding activity of von Willebrand factor
Authors: Oliveira L. M. M. , Amorim M. V. A. , Corsini C. A. , Neto C. C. A. , Chaves D. G.
Published: June 2018

Introduction

Diagnosis of von Willebrand disease (VWD) is difficult due to the heterogenic phenotype of patients and to the complex tests that are required for an adequate investigation. The collagen binding assay (VWF:CB) reveals the adhesion capacity of von Willebrand factor (VWF) to collagen and can be useful to reduce the misleading diagnosis ofVWD. This study aimed the standardization of 2 nonautomatedVWF:CBassays based onELISAand flow cytometry.

Methods

Plasma samples from 87 patients previously diagnosed withVWDand 22 healthy controls were analyzed. Measurement of theVWF‐collagen binding activity was performed using a commercial assay and the 2 tests proposed.VWF:CB/VWF:Ag ratio was calculated for samples and the differentiation between types 1, 2A, and 2M was analyzed.

Results

ELISAand flow cytometry tests presented strong correlation with the gold standard test (r2 = .8976 andr2 = .8143, respectively). Tests based onELISAand flow cytometry presented a bias of +7.2% and −3.6%, respectively.

Conclusion

TheELISAtest demonstrated better performance to detectVWF‐collagen binding activity in healthy individuals andVWDpatients. This test could differentiate 2A and 2M subtypes using a feasible protocol that can be easily implemented.
Yonsei nomogram: A predictive model of new‐onset chronic kidney disease after on‐clamp partial nephrectomy in patients with T1 renal tumors
Authors: Abdel Raheem Ali , Shin Tae Young , Chang Ki Don , Santok Glen Denmer R , Alenzi Mohamed Jayed , Yoon Young Eun , Ham Won Sik , Han Woong Kyu , Choi Young Deuk , Rha Koon Ho
Published: June 2018

Objectives

To develop a predictive nomogram for chronic kidney disease‐free survival probability in the long term after partial nephrectomy.

Methods

A retrospective analysis was carried out of 698 patients with T1 renal tumors undergoing partial nephrectomy at a tertiary academic institution. A multivariable Cox regression analysis was carried out based on parameters proven to have an impact on postoperative renal function. Patients with incomplete data, <12 months follow up and preoperative chronic kidney disease stage III or greater were excluded. The study end‐points were to identify independent risk factors for new‐onset chronic kidney disease development, as well as to construct a predictive model for chronic kidney disease‐free survival probability after partial nephrectomy.

Results

The median age was 52 years, median tumor size was 2.5 cm and mean warm ischemia time was 28 min. A total of 91 patients (13.1%) developed new‐onset chronic kidney disease at a median follow up of 60 months. The chronic kidney disease‐free survival rates at 1, 3, 5 and 10 year were 97.1%, 94.4%, 85.3% and 70.6%, respectively. On multivariable Cox regression analysis, age (1.041, P = 0.001), male sex (hazard ratio 1.653, P < 0.001), diabetes mellitus (hazard ratio 1.921, P = 0.046), tumor size (hazard ratio 1.331, P < 0.001) and preoperative estimated glomerular filtration rate (hazard ratio 0.937, P < 0.001) were independent predictors for new‐onset chronic kidney disease. The C‐index for chronic kidney disease‐free survival was 0.853 (95% confidence interval 0.815–0.895).

Conclusion

We developed a novel nomogram for predicting the 5‐year chronic kidney disease‐free survival probability after on‐clamp partial nephrectomy. This model might have an important role in partial nephrectomy decision‐making and follow‐up plan after surgery. External validation of our nomogram in a larger cohort of patients should be considered.
Clinical correlates of severe thrombocytopenia from temozolomide in glioblastoma patients
Authors: Arulananda Surein , Lynam James , Sem Liew Mun , Wada Morikatsu , Cher Lawrence , Gan Hui K.
Published: June 2018

Background/Aim

This study was conducted retrospectively to evaluate rates of thrombocytopenia and their clinical impact during chemo‐radiotherapy for glioblastomas and to elucidate associated clinical factors.

Methods

A total of 64 patients who received temozolomide chemotherapy at our institution was included; 35 patients received full‐dose chemo‐radiotherapy as per the STUPP protocol (Group A), and 9 patients received abbreviated radiotherapy with concurrent chemotherapy (Group B). Twenty patients received temozolomide alone with an intended 12 cycles of therapy for first relapse at least 6 months after completion of adjuvant chemotherapy (Group C).

Results

In Group A, 27 of 35 (77%) patients completed the chemo‐radiotherapy phase; 14% had grade 3–4 thrombocytopenia leading to discontinuation. Of 27 patients, 16 (59%) completed adjuvant chemotherapy. There were no grade 3–4 thrombocytopenias, but 4% discontinued due to grade 2 thrombocytopenias. In Group B, four of nine (45%) patients completed the chemo‐radiotherapy phase; 11% had grade 3–4 thrombocytopenias and discontinued treatment. Three of four (75%) patients completed adjuvant chemotherapy. Of these, 75% had grade 3–4 thrombocytopenias, but none discontinued. Finally, in Group C, 8 of 20 (40%) patients completed, with 10% discontinuing due to thrombocytopenias and the rest due to disease progression. In exploratory analyses, being female increased the risk of myelosuppresion, and there was a trend noticed in patients having a higher body surface area.

Conclusion

Our toxicity data were within range of the literature. We identified the group of patients that have increased thrombocytopenia risk. Larger pooled retrospective series and prospective studies are required.
Male reproductive system of the arrow crab Stenorhynchus seticornis (Inachoididae)
Authors: Antunes Mariana , Zara Fernando J. , López Greco Laura S. , Negreiros‐Fransozo Maria L.
Published: June 2018

Our aim was to describe the reproductive system of males and the formation of sperm packages in the seminal receptacle (SR) of recently mated females of the arrow crab Stenorhynchus seticornis. The male reproductive system was analyzed, and was described using light microscopy and histological and histochemical methods. The first pair of gonopods was described by means of scanning electron microscopy. Additionally, the dehiscence of spermatophores was tested using samples obtained from the vas deferens of males and from the seminal receptacle of recently mated females. Testes were tubular type, and each vas deferens consisted of three regions: the anterior vas deferens (AVD), including a proximal portion that was filled with free spermatozoa and a distal portion contained developing spermatophores; the median vas deferens (MVD) that contained completely formed spermatophores; and the posterior vas deferens (PVD), which contained only granular secretions. The accessory gland, which was filled with secretions, was located in the transition region between the MVD and the PVD. The spermatophores from the MVD were of different sizes, and none of them showed dehiscence in seawater, whereas those spermatophores in contact with the seminal receptacle were immediately broken. The ultrastructure of the gonopods revealed the presence of denticles at the distal portion, which contribute to the mechanical rupture of the spermatophore wall during the transfer of sperm. The contents of the PVD and accessory gland of males are transferred together with the spermatophores, and are responsible for the secretions observed among the sperm packets in the SR of the female. We suggest that these secretions formed the layers found in the SR of recently mated females, and may play a role in sperm competition in arrow crabs.
Near‐field confocal optical spectroscopy (NCOS): subdiffraction optical resolution for biological systems
Authors: HAYDON P. G. , MARCHESE-RAGONA S. , BASARSKY T. A. , SZULCZEWSKI M. , McCLOSKEY M.
Published: June 2018

Optical resolution is limited by diffraction. However. in near‐field microscopes sample illumination is provided through a subwavelength aperture to increase optical resolution. In this study we have evaluated the usefulness of this technique for living biological systems and report two significant improvements in this form of microscopy to enhance optical resolution for biological studies. We report a unique feedback method, photon‐density feedback, which is used to monitor the registration of a near‐field illumination probe with living cell membranes. In this method, the fluorescence intensity of a uniformly distributed fluorochrome is monitored while the sample is moved in the z‐axis towards the probe. Upon contact between the cell membrane and the near‐field probe a maximum intensity is detected. A problem with near‐field microscopy is that enhanced optical resolution is only achieved within the near‐field of the illuminating aperture. Thick biological specimens also fluoresce in the far‐field reducing optical resolution. To reduce this problem we incorporated a confocal pinhole together with the near‐field probe to enhance the resolution of this form of near‐field microscopy. Finally, we demonstrate that near‐field confocal optical spectroscopy does not impair physiological properties of neurons, astrocytes or mast cells, indicating that this high‐resolution optical methodology will permit a new approach to the study of molecular distribution and action within living specimens.
Editorial Perspective: From schizophrenia polygenic risk score to vulnerability (endo‐)phenotypes: translational pathways in child and adolescent mental health
Authors: Poletti Michele , Raballo Andrea
Published: June 2018

The Polygenic Risk Scores (PRS) approach is becoming increasingly prominent in psycho‐behavioral research, however, its translational potential is still relatively underconceptualized. Indeed, PRS paradigm (which capitalizes on the combination of multiple genetic markers into a single proxy score to predict lifetime outcomes) has the potential to unravel some of the developmental complexities leading to severe mental disorders. With respect to schizophrenia, the application of PRS approach to child–adolescent cohorts from the general population, provides a crucial vantage point for understanding how presumed genetic predisposition is manifested during developmental years. Clearly, this is essential for etiological research as well as for the timely identification of the earliest stages of those specific psychopathological trajectories leading to psychosis. Therefore, the translational import of the PRS approach could improve our etiopathogenetic understanding of schizophrenia (e.g., allowing the disentanglement of the respective contribution of genetic and environmental risk factors along neurodevelopment) and further refine current staging models for early detection of vulnerability to psychosis (e.g., providing the rationale for more developmentally oriented reformulations of clinical high‐risk criteria).
Altered perception‐action binding modulates inhibitory control in Gilles de la Tourette syndrome
Authors: Petruo Vanessa , Bodmer Benjamin , Brandt Valerie C. , Baumung Leoni , Roessner Veit , Münchau Alexander , Beste Christian
Published: June 2018

Background

Gilles de la Tourette Syndrome (GTS) is a multifaceted neuropsychiatric developmental disorder with onset in childhood or adolescence and frequent remissions in early adulthood. A rather new emerging concept of this syndrome suggests that it is a disorder of purposeful actions, in which sensory processes and their relation to motor responses (actions) play a particularly important role. Thus, this syndrome might be conceived as a condition of altered ‘perception‐action binding’. In the current study, we test this novel concept in the context of inhibitory control.

Methods

We examined N = 35 adolescent GTS patients and N = 39 healthy controls in a Go/Nogo‐task manipulating the complexity of sensory information triggering identical actions; i.e. to inhibit a motor response. This was combined with event‐related potential recordings, EEG data decomposition and source localization.

Results

GTS patients showed worse performance compared to controls and larger performance differences when inhibitory control had to be exerted using unimodal visual compared to bimodal auditory‐visual stimuli. This suggests increased binding between bimodal stimuli and responses leading to increased costs of switching between responses instructed by bimodal and those instructed by unimodal stimuli. The neurophysiological data showed that this was related to mechanisms mediating between stimulus evaluation and response selection; i.e. perception‐action binding processes in the right inferior parietal cortex (BA40).

Conclusions

Stimulus‐action inhibition binding is stronger in GTS patients than healthy controls and affects inhibitory control corroborating the concept suggesting that GTS might be a condition of altered perception‐action integration (binding); i.e. a disorder of purposeful actions.
Effects of sodium–glucose cotransporter 2 inhibitors in addition to insulin therapy on cardiovascular risk factors in type 2 diabetes patients: A meta‐analysis of randomized controlled trials
Authors: Wu Bingshu , Zheng Hongzhi , Gu Jianqiu , Guo Yan , Liu Yixuan , Wang Yingfang , Chen Feng , Yang Aolin , Wang Jiabei , Wang Hailong , Liu Ying , Wang Difei
Published: June 2018

Aims/Introduction

In the present meta‐analysis, we aimed to determine the effects of sodium–glucose cotransporter 2 inhibitor (SGLT‐2i) in addition to insulin therapy on cardiovascular risk factors in type 2 diabetes patients.

Materials and Methods

Randomized controlled trials were identified by searching the PubMed, Embase and Cochrane Library databases published before September 2017. The intervention group received SGLT‐2i as add‐on treatment to insulin therapy, and the control group received placebos in addition to insulin. We assessed pooled data, including weighted mean differences and 95% confidence intervals (CIs) using a random‐effects model.

Results

A total of 10 randomized controlled trials (n = 5,159) were eligible. The weighted mean differences for systolic blood pressure and diastolic blood pressure were −3.17 mmHg (95% CI −4.53, −1.80, I2 = 0%) and −1.60 mmHg (95% CI −2.52, −0.69, I2 = 0%) in the intervention groups. Glycosylated hemoglobin, fasting plasma glucose, postprandial glucose and daily insulin were also lower in the intervention groups, with relative weighted mean differences of −0.49% (95% CI −0.71, −0.28%, I2 = 92%), −1.10 mmol/L (95% CI −1.69, −0.51 mmol/L, I2 = 84%), −3.63 mmol/L (95% CI −4.36, −2.89, I2 = 0%) and −5.42 IU/day (95% CI −8.12, −2.72, I2 = 93%). The transformations of uric acid and bodyweight were −26.16 μmol/L (95% CI −42.14, −10.17, I2 = 80%) and −2.13 kg (95% CI −2.66, −1.60, I2 = 83%). The relative risk of hypoglycemia was 1.09 (95% CI 1.02, 1.17, P < 0.01). The relative risks of urinary tract and genital infection were 1.29 (95% CI 1.03, 1.62, P = 0.03) and 5.25 (95% CI 3.55, 7.74, P < 0.01).

Conclusions

The results showed that in the intervention group, greater reductions were achieved for blood pressure, glucose control, uric acid and bodyweight. This treatment regimen might therefore provide beneficial effects on the occurrence and development of cardiovascular events.
Sex chromosome turnovers and genetic drift: a simulation study
Authors: Saunders Paul A. , Neuenschwander Samuel , Perrin Nicolas
Published: June 2018

The recent advances of new genomic technologies have enabled the identification and characterization of sex chromosomes in an increasing number of nonmodel species, revealing that many plants and animals undergo frequent sex chromosome turnovers. What evolutionary forces drive these turnovers remains poorly understood, but it was recently proposed that drift might play a more important role than generally assumed. We analysed the dynamics of different types of turnovers using individual‐based simulations and show that when mediated by genetic drift, turnovers are usually easier to achieve than substitutions at neutral markers, but that their dynamics and relative likelihoods vary with the type of the resident and emergent sex chromosome system (XY and/or ZW) and the dominance relationships among the sex‐determining factors. Focusing on turnovers driven by epistatically dominant mutations, we find that drift‐mediated turnovers that preserve the heterogamety pattern are 2–4× more likely than those along which the heterogametic sex changes. This ratio nevertheless decreases along with effective population size and can even reverse in case of extreme polygyny. This can be attributed to a ‘drift‐induced’ selective force, known to influence transitions between male and female heterogamety, but which according to our study does not affect turnovers that preserve the heterogametic sex.
High‐P metamorphism of rodingites during serpentinite dehydration (Cerro del Almirez, Southern Spain): Implications for the redox state in subduction zones
Authors: Laborda‐López Casto , López‐Sánchez‐Vizcaíno Vicente , Marchesi Claudio , Gómez‐Pugnaire María T. , Garrido Carlos J. , Jabaloy‐Sánchez Antonio , Padrón‐Navarta José A. , Hidas Károly
Published: June 2018

The transition between antigorite‐serpentinite and chlorite‐harzburgite at Cerro del Almirez (Betic Cordillera, Southern Spain) exceptionally marks in the field the front of antigorite breakdown at high pressure (~16–19 kbar) and temperature (~650°C) in a paleosubducted serpentinite. These ultramafic lithologies enclose three types of metarodingite boudins of variable size surrounded by metasomatic reaction rims. Type 1 Grandite‐metarodingite (garnet+chlorite+diopside+titanite±magnetite±ilmenite) mainly crops out in the antigorite‐serpentinite domain and has three generations of garnet. Grossular‐rich Grt‐1 formed during rodingitization at the seafloor (<2 kbar, ~150–325°C, ~FMQ buffer). During subduction, the alternating growth of Grt‐2b (richer in andradite and pyralspite components than Grt‐1) and Grt‐3 (very rich in andradite component) reflects the change from internally buffered metamorphic conditions (>10 kbar, ~350–650°C, ~FMQ buffer) to influx events of oxidizing fluids (fO2 ~HM buffer) released by brucite breakdown in the host antigorite‐serpentinite. Type 2 Epidote‐metarodingite (epidote+diopside+titanite±garnet) derives from Type 1 and is the most abundant metarodingite type enclosed in dehydrated chlorite‐harzburgite. Type 2 formed by increasing μSiO2 (from −884 to −860 kJ/mol) and decreasing μCaO (from −708 to −725 kJ/mol) triggered by the flux of high amounts of oxidizing fluids during the high‐P antigorite breakdown in serpentinite. The growth of Grt‐4, with low‐grandite and high‐pyralspite components, in Type 2 metarodingite accounts for progressive reequilibration of garnet with changing intensive variables. Type 3 Pyralspite‐metarodingite (garnet+epidote+amphibole+chlorite±diopside+rutile) crops out in the chlorite‐harzburgite domain and formed at peak metamorphic conditions (16–19 kbar, 660–684°C) from Type 2 metarodingite. This transformation caused the growth of a last generation of pyralspite‐rich garnet (Grt‐5) and the recrystallization of diopside into tremolitic amphibole at decreasing fO2 and μCaO (from −726 to −735 kJ/mol) and increasing μMgO (from −630 to −626 kJ/mol) due to chemical mixing between the metarodingite and the reaction rims. The different bulk Fe3+/FeTotal ratios of antigorite‐serpentinite and chlorite‐harzburgite, and of the three metarodingite types, reflect the highly heterogeneous oxidation state of the subducting slab and likely point to the transfer of localized oxidized reservoirs, such as metarodingites, into the deep mantle.
Comparison of the pregnancy outcomes and the incidence of fetal congenital abnormalities in infertile women treated with letrozole and clomiphene citrate
Authors: Akbari Sene Azadeh , Ghorbani Selma , Ashrafi Mahnaz
Published: June 2018

Objectives

The aim of the study was to evaluate the incidence of congenital fetal anomalies reported among infertile Iranian women treated with letrozole compared to those treated with Clomiphene Citrate (CC).

Methods

This retrospective case–control study was performed based on information available from infertile patients referred to the Akbar‐Abadi Hospital IVF Center, Tehran, Iran, undergoing ovulation induction (OI) or intrauterine insemination (IUI) cycles from 2007 to 2014.We compared sonographic findings, fertility results, pregnancy complications and congenital anomalies in two groups of women treated with letrozole and CC.

Results

Overall, the results of the 2009 cycles including 1237 CC cycles and 772 letrozole cycles were evaluated. In spite of a higher chance of ovulation following CC treatment, overall fertility rates were similar in the two treatment groups. The frequency of adverse outcomes of pregnancy was similar in the two groups, except for the incidence of first trimester abortion, which was significantly higher in the CC‐treated group. The frequency of fetal anomalies and major chromosomal abnormalities in the Letrozole group was 4.76% (five cases), and in the CC group, it was 2.12% (three cases). This difference was not statistically significant.

Conclusion

Based on the findings of this study, it seems that the incidence of congenital anomalies in offspring after OI with letrozole is not increased compared to the CC group.
Cardiovascular disease in diabetes type 2: current concepts
Authors: Rosengren A.
Published: June 2018

Type 2 diabetes is a major and accelerating public health challenge. Between 1980 and 2014, a period of just 35 years, the number of adults with diabetes globally is estimated to have increased from 108 to 422 million, due not only to sharply rising obesity rates, but also to increasing population size, longer life expectancy, and rising prevalence of diabetes worldwide. Overall, worldwide age‐standardized adult diabetes prevalence doubled from 4.3% to 9.0% in men and from 5.0% to 7.9% in women. The largest increases in diabetes type 2 have been demonstrated in low‐ and middle‐income countries, whilst rises in high‐income countries have been less marked, or even flat. Diabetes type 2 rates in low‐ and middle‐income countries now in many instances surpass those in high‐income countries, in response to changes in lifestyle. One factor of particular concern are the large relative increases in type 2 diabetes amongst young individuals observed in many countries, their higher overall risk factor burden, long exposure to hyperglycaemia and greater risk of complications over the life course. Type 2 diabetes is increasingly found to be a heterogeneous condition, where risk of cardiovascular disease that traditionally has been estimated at 2–4 times that of the nondiabetic population varies substantially with diabetes phenotype and accordingly diabetes does not confer the same increase in relative or absolute risk in all people. New research shows that excess risk varies substantially with type of outcome, age, glycaemic control, the presence of renal complications and other factors. Heart failure, previously less recognized that other cardiovascular conditions, is increasingly coming into focus, because of strong links with poor glycaemic control and obesity. The knowledge about risk of cardiovascular disease in diabetes is almost entirely derived from high‐income countries, whereas there is comparatively very little data from low‐ and middle income countries, where the majority of persons with type 2 diabetes live, and where management in many cases is far from optimal. The reductions in cardiovascular disease incidence and mortality now observed in high‐income countries are encouraging, because this reinforces the fact that improvement is possible and that a near‐normal, or even normal life‐expectancy can be achieved in subtypes of type 2 diabetes.
Nitidine chloride represses Mcl‐1 protein via lysosomal degradation in oral squamous cell carcinoma
Authors: Yang In‐Hyoung , Jung Won , Kim Lee‐Han , Shin Ji‐Ae , Cho Nam‐Pyo , Hong Seong Doo , Hong Kyoung‐Ok , Cho Sung‐Dae
Published: June 2018

Background

We have shown previously that nitidine chloride (NC) induces apoptosis via inhibition of signal transducer and activator of transcription 3 (STAT3). However, its downstream molecules are not fully understood yet. Here, we report that NC as STAT3 inhibitor downregulates myeloid cell leukemia‐1 (Mcl‐1) protein in HSC‐3 and HSC‐4 human oral squamous cell carcinoma (OSCC) cells and a nude mouse tumor xenograft model.

Methods

This study investigated the effects of NC on Mcl‐1 expression in HSC‐3 and HSC‐4 cells using Western blotting, RT‐PCR, and dual‐luciferase assay. Immunohistochemistry was employed to evaluate Mcl‐1 expression levels in mouse tumor tissues. Construction of Mcl‐1 overexpression vector and transient transfection was done to test the apoptosis of HSC‐3 cells.

Results

Nitidine chloride did not affect either mRNA level or promoter activity of Mcl‐1, and the decrease in Mcl‐1 protein by NC was caused by lysosome‐dependent degradation, but not proteasome‐dependent degradation. The overexpression of Mcl‐1 protein in OSCC cell lines was sufficient to block the induction of apoptosis. In addition, NC strongly reduced the expression level of Mcl‐1 protein compared with other STAT3 inhibitors such as cryptotanshione and S3I‐201 in OSCCs.

Conclusions

Our findings suggest that NC triggers apoptosis via lysosome‐dependent Mcl‐1 protein degradation and could be chosen as a promising chemotherapeutic candidate against human OSCCs.