bluuebunny/crossref_metadata_2025 huggingface dataset:
Amisulpride and l‐DOPA modulate subcortical brain nuclei connectivity in resting‐state pharmacologic magnetic resonance imaging
Authors: Grimm Oliver , Kopfer Vera , Küpper‐Tetzel Lea , Deppert Vera , Kuhn Magdalena , de Greck Moritz , Reif Andreas
Published: December 2019

The precise understanding of the dopaminergic (DA) system and its pharmacological modifications is crucial for diagnosis and treatment of neuropsychiatric disorders, as well as for understanding basic processes, such as motivation and reward. We probed the functional connectivity (FC) of subcortical nuclei related to the DA system according to seed regions defined according to an atlas of subcortical nuclei. We conducted a large pharmaco‐fMRI study using a double‐blind, placebo‐controlled design, where we examined the effect of l
‐DOPA, a dopamine precursor, and amisulpride, a D2/D3‐receptor antagonist on resting‐state FC in 45 healthy young adults using a cross‐over design. We examined the FC of subcortical nuclei with connection to the reward system and their reaction to opposing pharmacological probing. Amisulpride increased FC from the putamen to the precuneus and from ventral striatum to precentral gyrus. l
‐DOPA increased FC from the ventral tegmental area (VTA) to the insula/operculum and between ventral striatum and ventrolateral prefrontal cortex and it disrupted ventral striatal and dorsal caudate FC with the medial prefrontal cortex. In an exploratory analysis, we demonstrated that higher self‐rated impulsivity goes together with a significant increase in VTA‐mid‐cingulate gyrus FC during l
‐DOPA‐challenge. Therefore, our DA challenge modulated distinct large‐scale subcortical connectivity networks. A dopamine‐boost can increase midbrain DA nuclei connectivity to the cortex. The involvement of the VTA‐cingulum connectivity in dependence of impulsivity has implications for diagnosis and therapy in disorders like ADHD.
Anatomy based corridors to the infratemporal fossa: Implications for endoscopic approaches
Authors: Li Lifeng , London Nyall R. , Prevedello Daniel M. , Carrau Ricardo L.
Published: December 2019

Background

The infratemporal fossa (ITF) represents an area densely packed with neurovascular structures within irregular boundaries. The goal of this study was to classify the ITF into zones corresponding to its anatomical spaces and the order in which they are encountered during an endonasal approach (anteroposterior axis).

Methods

Six cadaveric specimens (12 sides) with injected colored latex were dissected. Following an endoscopic medial maxillectomy and Denker's approach, a progressive exploration of the masticator space and upper parapharyngeal space was completed. A classification of the ITF based on well‐defined spaces was ascertained.

Results

The ITF was divided into five zones:

Zone 1 (retromaxillary space)—space lying between the posterolateral wall of the maxillary sinus and the temporalis and pterygoid muscles.

Zone 2 (superior interpterygoid space)—area including the superior head of the lateral pterygoid muscle, V3, and foramen ovale.

Zone 3 (inferior interpterygoid space)—includes the inferior head of lateral pterygoid muscle, medial pterygoid, and temporalis muscles, and the space enclosed by these muscles.

Zone 4 (temporo‐masseteric space)—space lateral to the temporalis muscle (comprising fat mostly).

Zone 5 (tubopharyngeal space)—includes the Eustachian tube, tensor, and levator veli palatini muscles, and structures in upper parapharyngeal space.

Conclusion

The ITF can be visualized as five zones based on spaces enclosed by the masticator muscles and upper parapharyngeal structures. This novel classification system is useful to guide endoscopic approaches to the ITF, while decreasing the potential for injury of neurovascular structures and pterygoid muscles.
The rodent hippocampus as a bilateral structure: A review of hemispheric lateralization
Authors: Jordan Jake T.
Published: December 2019

The left and right rodent hippocampi exhibit striking lateralization in some of the very neural substrates considered to be critical for hippocampal cognitive function. Despite this, there is an overwhelming lack of consideration for hemispheric differences in studies of the rodent hippocampus. Asymmetries identified so far suggest that a bilateral model of the hippocampus will be essential for an understanding of this brain region, and perhaps of the brain more widely. Although hypotheses have been proposed to explain how the left and right hippocampi contribute to behavior and cognition, these hypotheses have either been refuted by more recent studies or have been limited in the scope of data they explain. Here, I will first review data on human and rodent hippocampal lateralization. The implications of these data suggest that considering the hippocampus as a bilateral structure with functional lateralization will be critical moving forward in understanding the function and mechanisms of this brain region. In exploring these implications, I will then propose a hypothesis of the hippocampus as a bilateral structure. This discrete‐continuous hypothesis proposes that the left and right hippocampi contribute to spatial memory and navigation in a complementary manner. Specifically, the left hemisphere stores spatial information as discrete, salient locations, and the right hemisphere represents space continuously, contributing to route computation and flexible spatial navigation. Consideration of hippocampal lateralization in designing future studies may provide insight into the function of the hippocampus and resolve debates concerning its function.
Neural underpinnings of the relationships between sensation seeking and emotion regulation in adolescents
Authors: Deng Xinmei , Zhang Lin
Published: December 2019

There is little neurological evidence linking sensation seeking and emotion regulation in adolescence, which is characterised as an emotionally fluctuant period. The present study examined the relationship between sensation seeking and emotion regulation in adolescents. Electroencephalograms were recorded from 22 high sensation‐seeking adolescents (HSSs, Mage = 12.36) and 24 low sensation‐seeking adolescents (LSSs, Mage = 12.84) during the reactivity and regulation‐image task. Group differences in event‐related brain potentials (ERPs) associated with the regulation of negative and neutral stimuli were analysed. The results showed that (a) the P2 of HSSs were larger than LSSs during emotion regulation; (b) in down‐regulation conditions, the LPP in all time windows were smaller than no‐regulation in LSSs. However, there was no significant difference in HSSs; (c) the LPP 300–600 and LPP 1000–1500 of down‐regulation were smaller in LSSs than HSSs; (d) for LPP 600–1000, HSSs induced larger LPP than LSSs in the negative down‐regulation and negative no‐regulation conditions. The results provide neurological evidence that higher sensation seeking is related to the high reactivity to emotional stimuli and poor cognitive control during the regulation of emotions.
Literacy Leadership Learnings From a Large‐Scale Program With Mixed Results
Authors: Wilson Aaron , McNaughton Stuart
Published: December 2019

This department focuses on literacy leaders, including school and instructional leaders, teachers, and external partners, who are working to improve outcomes for adolescent and adult learners in a wide range of education settings. Columns investigate the challenges and complexities inherent in such work and share lessons learned, impactful strategies and approaches, and promising pathways forward.
Effect of multipurpose care solutions upon physical dimensions of silicone hydrogel contact lenses
Authors: Smith Stephanie M. , Zhu Dongkai , Pierre David , Gilbert Jeremy L. , Chinn Joseph A.
Published: December 2019

Interactions between contact lens multipurpose solution (MPS) components and the contact lenses with which they are used are both lens and solution dependent. As such, lens dimensional changes may arise after cleaning and immersion cycling in different lens care solutions over different time courses. In this study, the dimensional stability of five planned‐replacement silicone hydrogel lenses (lotrafilcon B, comfilcon A, senofilcon A, senofilcon C, and samfilcon A) over 30 cycles in three different MPSs (Biotrue, OPTI‐FREE Express, and OPTI‐FREE Puremoist) was evaluated. Measurements of diameter, sagittal depth, power, roundness, and center thickness were obtained prior to, during, and after 30 cycles of cleaning and storage. Diameters of all lenses increased when soaked in Express or Biotrue but held the International Standards Organization (ISO) tolerance over the full course of 30 disinfection cycles; however, the diameters of comfilcon A, senofilcon A, senofilcon C, and samfilcon A lenses soaked in Puremoist exceeded ISO tolerance after between 4 and 9 immersion cycles. In contrast, the diameter of lotrafilcon B held tolerance. Similarly, all lenses cycled in Express or Biotrue held tolerance for sagittal depth, while in Puremoist only lotrafilcon B held tolerance. All lenses became less round in all MPSs but held tolerance for both power and central thickness. Given the lack of reported clinical issues with Puremoist when used with lenses other than lotrafilcon B, we propose that it may be appropriate to revisit the ISO test methods and tolerances to determine if they are still applicable for silicone hydrogel lenses.
Disorder of Iron Metabolism Inhibits the Recovery of Unloading-Induced Bone Loss in Hypomagnetic Field
Authors: Xue Yanru , Yang Jiancheng , Luo Jie , Ren Li , Shen Ying , Dong Dandan , Fang Yanwen , Hu Lijiang , Liu Mengyu , Liao Zhongcai , Li Jun , Fang Zhicai , Shang Peng
Published: December 2019

Exposure of humans and animals to microgravity in spaceflight results in various deleterious effects on bone health. In addition to microgravity, the hypomagnetic field (HyMF) is also an extreme environment in space, such as on the Moon and Mars; magnetic intensity is far weaker than the geomagnetic field (GMF) on Earth. Recently, we showed that HyMF promoted additional bone loss in hindlimb unloading–induced bone loss, and the underlying mechanism probably involved an increase of body iron storage. Numerous studies have indicated that bone loss induced by mechanical unloading can be largely restored after skeletal reloading in GMF conditions. However, it is unknown whether this bone deficit can return to a healthy state under HyMF condition. Therefore, the purpose of this study is to examine the effects of HyMF on the recovery of microgravity-induced bone loss, and illustrates the changes of body iron storage in this process. Our results showed that there was lower bone mineral content (BMC) in the HyMF reloading group compared to the GMF reloading group. Reloaded mice in the HyMF condition had a worse microstructure of femur than in the GMF condition. Femoral mechanical properties, including elastic modulus, stiffness, and ultimate stress, were poorer and toughness was higher in the HyMF group compared with the GMF group. Simultaneously, more iron content in serum, the tibia, liver, and spleen was found under HyMF reloading than GMF reloading. The iron chelator deferoxamine mesylate (DFO) decreased the iron content in the bone, liver, and spleen, and significantly relieved unloading-induced bone loss under HyMF reloading. These results showed that HyMF inhibits the recovery of microgravity-induced bone loss, probably by suppressing the elevated iron levels’ return to physiological level. © 2019 American Society for Bone and Mineral Research.
Propranolol Reverses Impaired Fracture Healing Response Observed With Selective Serotonin Reuptake Inhibitor Treatment
Authors: Lee Sooyeon , Remark Lindsey H , Buchalter Daniel B , Josephson Anne M , Wong Madeleine Z , Litwa Hannah P , Ihejirika Rivka , Leclerc Kevin , Markus Danielle , Yim Nury L , Tejwani Ruchi , Bradaschia-Correa Vivian , Leucht Philipp
Published: December 2019

Selective serotonin reuptake inhibitors (SSRIs) are one of the most commonly prescribed antidepressants worldwide and recent data show significant impairment of fracture healing after treatment with the SSRI fluoxetine in mice. Here, we provide evidence that the negative effects of SSRIs can be overcome by administration of the beta-blocker propranolol at the time of fracture. First, in vitro experiments established that propranolol does not affect osteogenic differentiation. We then used a murine model of intramembranous ossification to study the potential rescue effect of propranolol on SSRI-induced impaired fracture healing. Micro-CT analysis revealed that fluoxetine treatment resulted in a smaller bony regenerate and that this decrease in bone formation can be overcome by co-treatment with propranolol. We then tested this in a clinically relevant model of endochondral ossification. Fluoxetine-treated mice with a femur fracture were treated with propranolol initiated at the time of fracture, and a battery of analyses demonstrated a reversal of the detrimental effect of fluoxetine on fracture healing in response to propranolol treatment. These experiments show for the first time to our knowledge that the negative effects of SSRIs on fracture healing can be overcome by co-treatment with a beta-blocker. © 2019 American Society for Bone and Mineral Research.
Coexpression of Human Hepatic Uridine Diphosphate Glucuronosyltransferase Proteins: Implications for Ontogenetic Mechanisms and Isoform Coregulation
Authors: Liu Yuejian , Badée Justine , Takahashi Ryan H. , Schmidt Stephan , Parrott Neil , Fowler Stephen , Mackenzie Peter I. , Coughtrie Michael W. H. , Collier Abby C.
Published: December 2019

Uridine diphosphate glucuronosyltransferases (UGTs) catalyze glucuronidation to facilitate systemic and local clearance of numerous chemicals and drugs. To investigate whether UGT expression is coregulated in human liver, we analyzed the protein expression of UGTs 1A1, 1A3, 1A4, 1A6, 1A9, 2B7, 3A1, and 3A2 using western blots from 164 healthy human liver samples, comparing expression with age and sex. UGT1A6 levels were significantly higher in children than adults, and UGT3A1 and 3A2 expression significantly increased with age from childhood to age >65 yearas. In children aged <18 years, UGT1A4/1A9 protein expression was significantly correlated, but not for adults aged >18 years. UGT1A3 expression was always significantly correlated with other UGT1A isoforms in all adults aged >18 years. In individuals aged ≥12 years, expression of UGT1A1/1A4, UGT1A1/1A6, UGT1A1/1A9, and UGT1A4/1A6 significantly correlated, which was not observed in children aged <12 years. In contrast, UGT1A4/2B7 showed significant correlation in children aged <12 years, but not in individuals aged ≥12 years, and this was observed in female but not male individuals. Expression of UGT1A6/1A9 and UGT3A1/3A2 correlated in the entire sample population, but UGT3As did not correlate with other UGTs. These correlations were sex dependent, as UGT1A3/1A1, UGT1A4/2B7 and UGT3A1/3A2 correlated more highly in male than female individuals, while UGT1A4/1A6 protein correlated more significantly in female than male individuals. This is the first report on the ontogeny of UGT3A isoforms, showing maximal expression in the elderly, and is the first demonstration that UGT isoforms commonly coexpress in vivo, in both age‐dependent and sex‐dependent manners.
Longitudinal serum biomarker screening identifies malate dehydrogenase 2 as candidate prognostic biomarker for Duchenne muscular dystrophy
Authors: Signorelli Mirko , Ayoglu Burcu , Johansson Camilla , Lochmüller Hanns , Straub Volker , Muntoni Francesco , Niks Erik , Tsonaka Roula , Persson Anja , Aartsma‐Rus Annemieke , Nilsson Peter , Al‐Khalili Szigyarto Cristina , Spitali Pietro
Published: December 2019

Background

Duchenne muscular dystrophy (DMD) is a fatal disease for which no cure is available. Clinical trials have shown to be largely underpowered due to inter‐individual variability and noisy outcome measures. The availability of biomarkers able to anticipate clinical benefit is highly needed to improve clinical trial design and facilitate drug development.

Methods

In this study, we aimed to appraise the value of protein biomarkers to predict prognosis and monitor disease progression or treatment outcome in patients affected by DMD. We collected clinical data and 303 blood samples from 157 DMD patients in three clinical centres; 78 patients contributed multiple blood samples over time, with a median follow‐up time of 2 years. We employed linear mixed models to identify biomarkers that are associated with disease progression, wheelchair dependency, and treatment with corticosteroids and performed survival analysis to find biomarkers whose levels are associated with time to loss of ambulation.

Results

Our analysis led to the identification of 21 proteins whose levels significantly decrease with age and nine proteins whose levels significantly increase. Seven of these proteins are also differentially expressed in non‐ambulant patients, and three proteins are differentially expressed in patients treated with glucocorticosteroids. Treatment with corticosteroids was found to partly counteract the effect of disease progression on two biomarkers, namely, malate dehydrogenase 2 (MDH2, P = 0.0003) and ankyrin repeat domain 2 (P = 0.0005); however, patients treated with corticosteroids experienced a further reduction on collagen 1 serum levels (P = 0.0003), especially following administration of deflazacort. A time to event analysis allowed to further support the use of MDH2 as a prognostic biomarker as it was associated with an increased risk of wheelchair dependence (P = 0.0003). The obtained data support the prospective evaluation of the identified biomarkers in natural history and clinical trials as exploratory biomarkers.

Conclusions

We identified a number of serum biomarkers associated with disease progression, loss of ambulation, and treatment with corticosteroids. The identified biomarkers are promising candidate prognostic and surrogate biomarkers, which may support drug developers if confirmed in prospective studies. The serum levels of MDH2 are of particular interest, as they correlate with disease stage and response to treatment with corticosteroids, and are also associated with the risk of wheelchair dependency and pulmonary function.
SBA‐15‐Pr‐SO3H catalyzed one‐pot synthesis of indole derivatives via Fischer indole pathway
Authors: Ghiyasabadi Zahra , Bahadorikhalili Saeed , Saeedi Mina , Karimi‐Niyazagheh Mona , Mirfazli Seyedeh Sara
Published: December 2019

In this work, an efficient, user‐friendly, and simple procedure was reported for the preparation of indole derivatives catalyzed by the heterogeneous SBA‐15‐Pr‐SO3H via Fischer indole pathway. The title compounds were synthesized from various arylhydrazines and ketones in the presence of 3 mol% of the catalyst in the refluxing ethanol.
Late locoregional complications associated with adjuvant radiotherapy in the treatment of breast cancer: Systematic review and meta‐analysis
Authors: Kanda Márcia Helena , da Costa Vieira René Aloisio , Lima João Paulo S. N. , Paiva Carlos Eduardo , de Araujo Raphael Leonardo Cunha
Published: December 2019

This systematic review with meta‐analysis addressed late locoregional complications associated with adjuvant radiotherapy (RT) in breast cancer. Among 2120 titles, ten comparative studies in patients undergoing surgery vs surgery and radiotherapy reporting complications were evaluated. RT was associated with an increased risk of capsular contracture and decreased the mobility of the upper limb. A borderline association of lymphedema risk using RT was noted in the random‐effects model but was significant in the fixed‐effects model.
Characterization of a Type‐2 Diacylglycerol Acyltransferase from Haematococcus pluvialis Reveals Possible Allostery of the Recombinant Enzyme
Authors: Nguyen Trinh , Xu Yang , Abdel‐Hameed Mona , Sorensen John L. , Singer Stacy D. , Chen Guanqun
Published: December 2019

Haematococcus pluvialis is a green microalga used in the algal biotechnology industry that can accumulate considerable amounts of storage triacylglycerol (TAG) and astaxanthin, which is a high‐value carotenoid with strong antioxidant activity, under stress conditions. Diacylglycerol acyltransferase (DGAT) catalyzes the last step of the acyl‐CoA‐dependent TAG biosynthesis and appears to represent a bottleneck in algal TAG formation. In this study, putative H. pluvialis DGAT2 cDNA (HpDGAT2A, B, D and E) were identified from a transcriptome database and were subjected to sequence‐based in silico analyses. The coding sequences of HpDGAT2B, D, and E were then isolated and characterized through heterologous expression in a TAG‐deficient Saccharomyces cerevisiae strain H1246. The expression of HpDGAT2D allowed the recovery of TAG biosynthesis in this yeast mutant, and further in vitro enzymatic assays confirmed that the recombinant HpDGAT2D possessed strong DGAT activity. Interestingly, the recombinant HpDGAT2D displayed sigmoidal kinetics in response to increasing acyl‐CoA concentrations, which has not been reported in plant or algal DGAT2 in previous studies.
Chitosan Microspheres as Carriers for pH‐Indicating Species in Corrosion Sensing
Authors: Sousa Isabel , Quevedo Marcela C. , Sushkova Alesia , Ferreira Mário G. S. , Tedim João
Published: December 2019

Chitosan microspheres containing bromocresol green, cresol red, and phenolphthalein for corrosion detection, through pH change, are synthesized in order to be used in protective coatings for aluminium alloys. Microspheres containing corrosion detection species are characterized morphologically (SEM) and physico‐chemically (FTIR, TGA). Release studies (UV–vis) are performed in corrosion‐promoting conditions (pH, NaCl), and detection studies by immersion in media associated with corrosion activity while microspheres' sensing activity is evaluated visually. Electrochemical characterization of AA2024 substrates in the presence of chitosan spheres is performed to understand material performance, and a color change is observed as a result of local pH increase in cathodic areas when corrosion takes place. These findings can be correlated with the results from release studies and seem a promising approach for corrosion sensing purposes, not only because pH increase is possible to detect due to corrosion, but also because chitosan is considered an environmentally friendly material.
Large deviations for intersection measures of some Markov processes
Authors: Mori Takahiro
Published: December 2019

Consider an intersection measure of p independent (possibly different) m‐symmetric Hunt processes up to time t in a metric measure space E with a Radon measure m. We derive a Donsker–Varadhan type large deviation principle for the normalized intersection measure on the set of finite measures on E as , under the condition that t is smaller than life times of all processes. This extends earlier work by W. König and C. Mukherjee [16], in which the large deviation principle was established for the intersection measure of p independent N‐dimensional Brownian motions before exiting some bounded open set . We also obtain the asymptotic behavior of logarithmic moment generating function, which is related to the results of X. Chen and J. Rosen [7] on the intersection measure of independent Brownian motions or stable processes.

Our results rely on assumptions about the heat kernels and the 1‐order resolvents of the processes, hence include rich examples. For example, the assumptions hold for with when the processes enjoy (sub‐)Gaussian type or jump type heat kernel estimates, where is determined by the Hausdorff dimension of E and the so‐called walk dimensions of the processes.
Organic–Inorganic Nanocomposite Film for High‐Performance Stretchable Resistive Memory Device
Authors: Wu Ping‐Han , Lin Yan‐Cheng , Laysandra Livy , Lee Meng‐Hsien , Chiu Yu‐Cheng , Isono Takuya , Satoh Toshifumi , Chen Wen‐Chang
Published: December 2019

A compatible organic/inorganic nanocomposite film for a stretchable resistive memory device with high performance is demonstrated using poly(4‐vinylpyridine)‐block‐poly(propyl methacrylate) (P4VP‐b‐PPMA) with zinc oxide (ZnO) nanoparticle. The PPMA soft segment is designed for reducing the rigidity of the active layer, while the P4VP block serves as a charge‐trapping component to induce conductive filament and also a compatible moiety for inorganic nanoparticles through hydrogen bonding. The experimental results show that the P4VP‐b‐PPMA‐based electrical memory device exhibits write‐once‐read‐many‐times memory behavior and an excellent ON/OFF current ratio of over 105 with a stable turn‐on voltage (Vset) around −2.0 V and stable memory behavior upon stretching up to 60% strain. On the other hand, P4VP‐b‐PPMA/ZnO nanocomposite film switches the memory characteristic to the dynamic random access memory behavior. The stretchable memory device prepared from the nanocomposite film can have a stretching durability over 40% strain and up to 1000 times cycling stretch–relaxation test. This work demonstrates a new strategy using nanocomposite films with tunable electrical characteristics and enhanced mechanical properties for stretchable electrical devices.
An Efficient Ring‐Closure Method for Preparing Well‐Defined Cyclic Polynorbornenes
Authors: Zhang Minghui , Wu Ying , Liu Zhengping , Li Jun , Huang Liyan , Zhang Ke
Published: December 2019

An efficient bimolecular ring‐closure method is developed to prepare the well‐defined cyclic polynorbornenes by combining the living ring‐opening metathesis polymerization (ROMP) with the self‐accelerating double strain‐promoted azide–alkyne cycloaddition (DSPAAC) reaction. In this method, ROMP is used to synthesize the well‐defined linear polynorbornenes with both azide terminals by virtue of a N‐hydroxysuccinimide‐ester‐functionalized Grubbs initiator following the modification of polymer end groups. DSPAAC click reaction is then used to ring‐close the linear polymer precursors and prepare the corresponding well‐defined cyclic polynorbornenes using the sym‐dibenzo‐1,5‐cyclooctadiene‐3,7‐diyne (DIBOD) as small linkers. The self‐accelerating DSPAAC ring‐closing reaction facilitates this method to efficiently prepare pure cyclic polynorbornenes in the presence of a molar excess of DIBOD small linkers to the linear polynorbornene precursors. This is the first report to prepare well‐defined polynorbornenes with cyclic topology based on the ring‐closure strategy for cyclic polymers.
Nonconforming quadrilateral finite element method for nonlinear Kirchhoff‐type equation with damping
Authors: Shi Dongyang , Wu Yanmi
Published: December 2019

Nonconforming quadrilateral
finite element method (FEM) of nonlinear Kirchhoff‐type equation with damping is studied on anisotropic meshes. Based on the property of the nonlocal term of this equation, unconditional optimal error estimates of
and
(
, the spatial parameter, and
, the time step) in the broken
norm are deduced for the semidiscrete and a linearized fully discrete schemes without any restrictions of
through a distinct approach compared with the methods used for other partial differential equations, respectively. Besides, the damping term appearing in the Kirchhoff‐type equation is solved with a novel technique, which is the major difficulty in the theoretical analysis. Finally, some numerical results are provided to verify the theoretical analysis.
Single‐nucleotide polymorphism c.474G>A in the SEPT12 gene is a predisposing factor in male infertility
Authors: Rafaee Alemeh , Mohseni Meybodi Anahita , Yaghmaei Parichehreh , Hosseini Seyedeh Hanieh , Sabbaghian Marjan
Published: December 2019

SEPT12 is a testis‐specific gene involved in the terminal differentiation of male germ cells. SEPT12 protein is required for sperm head‐tail formation and acts as a fundamental constituent of sperm tail annulus. In this study, we screened genetic variations in exons 5, 6, 7 of the SEPT12 and assessed the annulus status in teratozoospermic, globozoospermic, and patients with immotile short tail sperm.

DNA sequencing was performed for 90 teratozoospermic and 30 normozoospermic individuals. Immunocytochemistry, transmission electron microscopy and western blotting were conducted to evaluate annulus status and the expression level of SEPT12 in patients with a distinct exonic variation (c.474G>A), respectively.

Five polymorphisms identified within the desired regions of the SEPT12, among them c.474G>A had the potential to induce aberrant splicing results in the expression of a truncated protein. The annulus was detected in most of the spermatozoa from teratozoospermic and normozoospermic men with c.474G>A. In contrast, in the patient with short tail sperm defect carrying c.474G>A, 99% of spermatozoa were devoid of the annulus. Based on our findings there would be no association between exons 5, 6, 7 polymorphisms of the SEPT12 gene and the occurrence of mentioned disease but c.474G>A would be a predisposing factor in male infertility.
Exploitation of Velocity Gradients by Sympatric Stream Salmonids: Basic Insights and Implications for Instream Flow Management
Authors: Naman Sean M. , Rosenfeld Jordan S. , Jordison Eva , Kuzyk Melanie , Eaton Brett C.
Published: December 2019

Hydraulic heterogeneity can strongly influence habitat selection by stream fishes. Velocity gradients created by channel roughness and flow obstructions may be particularly important for species that feed on drifting invertebrates, where maintaining focal points in low-velocity microhabitats adjacent to faster water allows fish to scan a larger water volume for prey while minimizing swimming costs. However, these velocity gradients are rarely integrated into habitat suitability criteria used for defining instream flow requirements, which are generally based on mean column velocity measurements at the focal point location. It is also unclear how velocity gradient exploitation differs among sympatric drift-feeding species. We measured the use of velocity gradients by two sympatric juvenile salmonids, Coho Salmon Oncorhynchus kisutch and steelhead O. mykiss, in a midorder cobble–boulder-dominated river. We compared focal point velocities of fish to adjacent velocities within their foraging area and compared the magnitude of velocity and kinetic energy gradients between species. We then explored how lateral velocity gradients may bias instream flow assessments by deriving two sets of velocity habitat suitability curves (HSCs): conventional HSCs using average water column velocities measured at focal point locations and spatially averaged HSCs incorporating adjacent velocities (four body lengths from focal points). These contrasting HSCs were then used as input into the physical habitat simulation model to predict the influence of flow on habitat availability. Both species often used focal velocities that were lower than adjacent points, but the magnitude of these velocity gradients was higher for steelhead, consistent with known differences in foraging behavior, habitat selection, and physiology. Incorporating adjacent velocities into HSCs resulted in a ~40% (steelhead) and ~10% (Coho Salmon) increase in flows predicted to optimize habitat availability. Thus, small-scale heterogeneity in velocity used by drift-feeding fish can lead to large biases in flow assessments.
Network traffic identification of several open source secure proxy protocols
Authors: Zhang Yidan , Chen Jiageng , Chen Kaiming , Xu Ruoyan , Teh Jesen , Zhang Shuai
Published: December 2019

Secure proxy technique has a wide range of applications especially in the area of VPN to protect the private communication from being surveilled. However, the adversaries may also take advantage of the VPN services for other purposes. Thus, knowing the characteristics of the corresponding security protocols will benefit the administration to narrow down the targets. Also, given the various VPN services on the market, we also want to know whether there exists some security flaws from the cryptographic protocol's point of view, so that can be used to improve analyzing the protocol. In this paper, we first target several widely used open source secure proxy protocols and provide their weaknesses through the static analysis. Then we apply the deep learning technique to train all the related network traffic, and our results showed that all the secure proxy traffics can be successfully distinguished with high accuracy.
Perivascular Neuropilin‐1 expression is an independent marker of improved survival in renal cell carcinoma
Authors: Morin Eric , Lindskog Cecilia , Johansson Martin , Egevad Lars , Sandström Per , Harmenberg Ulrika , Claesson‐Welsh Lena , Sjöberg Elin
Published: December 2019

Renal cell carcinoma (RCC) treatment has improved in the last decade with the introduction of drugs targeting tumor angiogenesis. However, the 5‐year survival of metastatic disease is still only 10–15%. Here, we explored the prognostic significance of compartment‐specific expression of Neuropilin 1 (NRP1), a co‐receptor for vascular endothelial growth factor (VEGF). NRP1 expression was analyzed in RCC tumor vessels, in perivascular tumor cells, and generally in the tumor cell compartment. Moreover, complex formation between NRP1 and the main VEGF receptor, VEGFR2, was determined. Two RCC tissue microarrays were used; a discovery cohort consisting of 64 patients and a validation cohort of 314 patients. VEGFR2/NRP1 complex formation in cis (on the same cell) and trans (between cells) configurations was determined by in situ proximity ligation assay (PLA), and NRP1 protein expression in three compartments (endothelial cells, perivascular tumor cells, and general tumor cell expression) was determined by immunofluorescent staining. Expression of NRP1 in perivascular tumor cells was explored as a marker for RCC survival in the two RCC cohorts. Results were further validated using a publicly available gene expression dataset of clear cell RCC (ccRCC). We found that VEGFR2/NRP1 trans complexes were detected in 75% of the patient samples. The presence of trans VEGFR2/NRP1 complexes or perivascular NRP1 expression was associated with a reduced tumor vessel density and size. When exploring NRP1 as a biomarker for RCC prognosis, perivascular NRP1 and general tumor cell NRP1 protein expression correlated with improved survival in the two independent cohorts, and significant results were obtained also at the mRNA level using the publicly available ccRCC gene expression dataset. Only perivascular NRP1 expression remained significant in multivariable analysis. Our work shows that perivascular NRP1 expression is an independent marker of improved survival in RCC patients, and reduces tumor vascularization by forming complexes in trans with VEGFR2 in the tumor endothelium. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Association of autophagy status with amount of Fusobacterium nucleatum in colorectal cancer
Authors: Haruki Koichiro , Kosumi Keisuke , Hamada Tsuyoshi , Twombly Tyler S , Väyrynen Juha P , Kim Sun A , Masugi Yohei , Qian Zhi Rong , Mima Kosuke , Baba Yoshifumi , da Silva Annacarolina , Borowsky Jennifer , Arima Kota , Fujiyoshi Kenji , Lau Mai Chan , Li Peilong , Guo Chunguang , Chen Yang , Song Mingyang , Nowak Jonathan A , Nishihara Reiko , Yanaga Katsuhiko , Zhang Xuehong , Wu Kana , Bullman Susan , Garrett Wendy S , Huttenhower Curtis , Meyerhardt Jeffrey A , Giannakis Marios , Chan Andrew T , Fuchs Charles S , Ogino Shuji
Published: December 2019

Fusobacterium nucleatum (F. nucleatum), which has been associated with colorectal carcinogenesis, can impair anti‐tumour immunity, and actively invade colon epithelial cells. Considering the critical role of autophagy in host defence against microorganisms, we hypothesised that autophagic activity of tumour cells might influence the amount of F. nucleatum in colorectal cancer tissue. Using 724 rectal and colon cancer cases within the Nurses' Health Study and the Health Professionals Follow‐up Study, we evaluated autophagic activity of tumour cells by immunohistochemical analyses of BECN1 (beclin 1), MAP1LC3 (LC3), and SQSTM1 (p62) expression. We measured the amount of F. nucleatum DNA in tumour tissue by quantitative polymerase chain reaction (PCR). We conducted multivariable ordinal logistic regression analyses to examine the association of tumour BECN1, MAP1LC3, and SQSTM1 expression with the amount of F. nucleatum, adjusting for potential confounders, including microsatellite instability status; CpG island methylator phenotype; long‐interspersed nucleotide element‐1 methylation; and KRAS, BRAF, and PIK3CA mutations. Compared with BECN1‐low cases, BECN1‐intermediate and BECN1‐high cases were associated with lower amounts of F. nucleatum with odds ratios (for a unit increase in three ordinal categories of the amount of F. nucleatum) of 0.54 (95% confidence interval, 0.29–0.99) and 0.31 (95% confidence interval, 0.16–0.60), respectively (Ptrend < 0.001 across ordinal BECN1 categories). Tumour MAP1LC3 and SQSTM1 levels were not significantly associated with the amount of F. nucleatum (Ptrend > 0.06). Tumour BECN1, MAP1LC3, and SQSTM1 levels were not significantly associated with patient survival (Ptrend > 0.10). In conclusion, tumour BECN1 expression is inversely associated with the amount of F. nucleatum in colorectal cancer tissue, suggesting a possible role of autophagy in the elimination of invasive microorganisms. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Translation of segment scale stiffening into macroscale reinforcement in polymer nanocomposites
Authors: Zboncak Marek , Ondreas Frantisek , Uhlir Vojtech , Lepcio Petr , Michalicka Jan , Jancar Josef
Published: December 2019

Structuring of polymer nanocomposites (PNCs) with an aid of relatively weak external magnetic fields has been studied as a method for control of the nano‐ and microstructure. Magnetic nanoparticles (NPs) were assembled into high aspect ratio one‐dimensional strings and unidirectionally oriented with the magnetic field (B = 0–50 mT) within the photopolymer matrix. The effect of the anisotropic MNPs assemblies on the mechanical properties was studied over a wide temperature range for the first time. The impact of various reinforcing mechanisms was distinguished with respect to the position of the glass transition temperature (Tg). The reinforcing effect exhibits temperature dependency with a maximum ~65°C above the glass transition and only negligible effect below the Tg. In addition, significant directional anisotropy of stiffness was observed. Composite micromechanics was applied to interpret the orientation and size‐dependent reinforcement of PNCs, and temperature‐dependent stiffness of the polymer‐MNP structures was quantified. The presence of polymer chains with altered dynamics surrounding the MNPs inside the anisotropic assemblies was proposed to be an essential nanoscale mechanism mediating the stress transfer and contributing to mechanical robustness of the hybrid structures and PNCs. POLYM. ENG. SCI., 60:587–596, 2020. © 2019 Society of Plastics Engineers
Ovonic Threshold Switching in Se‐Rich GexSe1−x Glasses from an Atomistic Point of View: The Crucial Role of the Metavalent Bonding Mechanism
Authors: Raty Jean-Yves , Noé Pierre
Published: December 2019

The ovonic threshold switching (OTS) phenomenon, a unique discontinuity of conductivity upon electric‐field application, has been observed in many chalcogenide glasses, some of which are presently used as selector elements in latest ultimate phase‐change memory devices. Herein, ab initio molecular dynamics is used to simulate the structure of two prototypical glasses that are shown to exhibit significantly different OTS properties and switching performance in OTS devices. The first glass, Ge30Se70 (GS), has a typical structure of connected Ge tetrahedra, whereas in the second GS‐based glass that contains antimony and nitrogen, the structure around Ge atoms is quite more complex. By the simulation of the excitation of electrons in the conduction band, slight modifications of the local order are shown to be sufficient to delocalize electronic states. The electron delocalization involving both Ge and Se (as well as Sb atoms in the case of Sb‐containing glass) ensures the percolation of conductive paths for electrons, giving, therefore, to the excited material a metallic behavior. These conductive channels result from the local formation of “metavalent” bonds in the amorphous structure as characterized geometrically and with associated Born effective charges.
The effects of grape seed extract on glycemic control, serum lipoproteins, inflammation, and body weight: A systematic review and meta‐analysis of randomized controlled trials
Authors: Asbaghi Omid , Nazarian Behzad , Reiner Željko , Amirani Elaheh , Kolahdooz Fariba , Chamani Maryam , Asemi Zatollah
Published: December 2019

The aim of this systematic review and meta‐analysis was to analyze the effects of grape seed extract (GSE) on glycemic control and serum lipoproteins, inflammation and body weight. Two independent authors systematically searched online databases including EMBASE, Scopus, PubMed, Cochrane Library, and Web of Science from inception until May 30, 2019. Cochrane Collaboration risk of bias tool was applied to assess the methodological quality of included trials. The heterogeneity among the included studies was assessed using Cochrane's Q test and I‐square (I2) statistic. Data were pooled using a random‐effects model and weighted mean difference (WMD) was considered as the overall effect size. Fifty trials were included in this meta‐analysis. Pooling effect sizes from studies demonstrated a significant decrease in fasting plasma glucose (FPG) (WMD): −2.01; 95% confidence interval (CI): −3.14, −0.86), total cholesterol (TC; WMD: −6.03; 95% CI: −9.71, −2.35), low‐density lipoprotein (LDL) cholesterol (WMD: −4.97; 95% CI: −8.37, −1.57), triglycerides (WMD: −6.55; 95% CI: −9.28, −3.83), and C‐reactive protein (CRP) concentrations (WMD: −0.81; 95% CI: −1.25, −0.38) following GSE therapy. Grape seed did not influence HbA1c, HDL cholesterol levels, and anthropometric measurements. This meta‐analysis demonstrated that GSE intake significantly reduced FPG, TC, LDL cholesterol, triglycerides, and CRP levels.
How does knowledge of atmospheric gravity waves guide their parameterizations?
Authors: Plougonven Riwal , de la Cámara Alvaro , Hertzog Albert , Lott François
Published: December 2019

This note discusses the relation between our knowledge of gravity waves and the parameterization of their effects in global models. Improving these parameterizations represents a major motivation for current research on atmospheric gravity waves. Indeed, as a major portion of the gravity wave spectrum is on the subgrid scale, parameterizations are used to represent their impacts on large‐scale flow. Gravity wave parameterizations generally share a common framework, with assumptions on their propagation (columnar only) and their sources (tropospheric only). These assumptions are highly justified to leading order, and parameterizations have been successful in allowing models to reproduce a number of middle‐atmospheric features. Once this framework is set up, specifying the sources constitutes a poorly constrained step. In practice, sources are tuned to a large extent in order to improve the modelled atmospheric circulation, a process that includes compensating for model biases. Consequently, significant efforts have been made to better quantify the sources of gravity waves, combining observations, modelling and theory, stimulating ground‐breaking progress in our knowledge and understanding of atmospheric gravity waves. As emphasized in this note, however, the transfer to parameterizations is not straightforward: knowledge of the characteristics of lower‐stratospheric gravity waves does not directly translate into input parameters for parameterizations. The example of intermittency is used to illustrate the impact of a (minor) shift in the parameterization framework, leading to a redistribution of the resulting forcing in the middle atmosphere. Recent studies have highlighted a number of phenomena which fall outside of the classical framework of parameterizations, notably lateral propagation and secondary generation. This growing body of evidence calls for further investigations to determine which of these phenomena could have systematic and robust implications for the larger‐scale flow. To retain appropriate simplicity of the parameterizations, efforts to identify acceptable simplifications should also be undertaken in parallel, in a framework of a model hierarchy.
Stochastic robust finite‐time boundedness for semi‐Markov jump uncertain neutral‐type neural networks with mixed time‐varying delays via a generalized reciprocally convex combination inequality
Authors: Zhang Haiyang , Qiu Zhipeng , Liu Xinzhi , Xiong Lianglin
Published: December 2019

This article investigates the stochastic robust finite‐time boundedness problem for semi‐Markov jump uncertain (SMJU) neutral‐type neural networks with distributed and additive time‐varying delays (TDs). To derive less conservative stability criteria, a generalized reciprocally convex combination inequality (RCCI) is first proposed, which includes the existing RCCIs as its special cases. By taking full advantage of the characteristics of various TDs and SMJU parameters, a novel suitable Lyapunov‐Krasovskii functional is provided. Then, with the virtue of the new RCCI and other analysis approaches, some new criteria guaranteeing the underlying systems are stochastically robustly finite‐time bounded or stable and are derived in the form of linear matrix inequalities. Finally, three numerical examples are given to show the validity of the approaches presented in this article.
Self‐Assembled Collagen Microparticles by Aerosol as a Versatile Platform for Injectable Anisotropic Materials
Authors: Lama Milena , Fernandes Francisco M. , Marcellan Alba , Peltzer Juliette , Trouillas Marina , Banzet Sébastien , Grosbot Marion , Sanchez Clément , Giraud‐Guille Marie‐Madeleine , Lataillade Jean‐Jacques , Coulomb Bernard , Boissière Cédric , Nassif Nadine
Published: December 2019

Extracellular matrices (ECM) rich in type I collagen exhibit characteristic anisotropic ultrastructures. Nevertheless, working in vitro with this biomacromolecule remains challenging. When processed, denaturation of the collagen molecule is easily induced in vitro avoiding proper fibril self‐assembly and further hierarchical order. Here, an innovative approach enables the production of highly concentrated injectable collagen microparticles, based on collagen molecules self‐assembly, thanks to the use of spray‐drying process. The versatility of the process is shown by performing encapsulation of secretion products of gingival mesenchymal stem cells (gMSCs), which are chosen as a bioactive therapeutic product for their potential efficiency in stimulating the regeneration of a damaged ECM. The injection of collagen microparticles in a cell culture medium results in a locally organized fibrillar matrix. The efficiency of this approach for making easily handleable collagen microparticles for encapsulation and injection opens perspectives in active tissue regeneration and 3D bioprinted scaffolds.