bluuebunny/crossref_metadata_2025 huggingface dataset:
Circadian rhythms in Per1, PER2 and Ca2+ of a solitary SCN neuron cultured on a microisland
Authors: Hirata Yoshihiro , Enoki Ryosuke , Kuribayashi-Shigetomi Kaori , Oda Yoshiaki , Honma Sato , Honma Ken-ichi
Published: December 2019

Circadian rhythms in Per1, PER2 expression and intracellular Ca2+ were measured from a solitary SCN neuron or glial cell which was physically isolated from other cells. Dispersed cells were cultured on a platform of microisland (100–200 μm in diameter) in a culture dish. Significant circadian rhythms were detected in 57.1% for Per1 and 70.0% for PER2 expression. When two neurons were located on the same island, the circadian rhythms showed desynchronization, indicating a lack of oscillatory coupling. Circadian rhythms were also detected in intracellular Ca2+ of solitary SCN neurons. The ratio of circadian positive neurons was significantly larger without co-habitant of glial cells (84.4%) than with it (25.0%). A relatively large fraction of SCN neurons generates the intrinsic circadian oscillation without neural or humoral networks. In addition, glial cells seem to interrupt the expression of the circadian rhythmicity of intracellular Ca2+ under these conditions.
Transcriptome changes in undifferentiated Caco-2 cells exposed to food-grade titanium dioxide (E171): contribution of the nano- and micro- sized particles
Authors: Proquin Héloïse , Jonkhout Marloes C. M. , Jetten Marlon J. , van Loveren Henk , de Kok Theo M. , Briedé Jacob J.
Published: December 2019

The food additive titanium dioxide (TiO2), or E171, is a white food colorant. Recent studies showed after E171 ingestion a significantly increased number of colorectal tumours in a colorectal cancer mouse model as well as inflammatory responses and dysregulation of the immune system in the intestine of rats. In the mouse colon, E171 induced gene expression changes related to oxidative stress, impairment of the immune system, activation of signalling and cancer-related processes. E171 comprises nanoparticles (NPs) and microparticles (MPs). Previous in vitro studies showed that E171, NPs and MPs induced oxidative stress responses, DNA damage and micronuclei formation. This study aimed to investigate the relative contribution of the NPs and MPs to effects of E171 at the transcriptome level in undifferentiated Caco-2 cells by genome wide microarray analysis. The results showed that E171, NPs, and MPs induce gene expression changes related to signalling, inflammation, immune system, transport and cancer. At the pathway level, metabolism of proteins with the insulin processing pathway and haemostasis were specific to E171 exposure. The gene expression changes associated with the immune system and inflammation induced by E171, MPs, and NPs suggest the creation of a favourable environment for colon cancer development.
Association of pre-existing depression with all-cause, cancer-related, and noncancer-related mortality among 5-year cancer survivors: a population-based cohort study
Authors: Ko Ahryoung , Kim Kyuwoong , Sik Son Joung , Park Hye Yoon , Park Sang Min
Published: December 2019

Previous studies on the association between mental health and mortality in patients with cancer have reported contradictory results. We conducted a population-based cohort study to determine whether pre-existing depression is associated with all-cause and cause-specific mortality after cancer diagnosis. We included 5-year cancer survivors, identified from the National Health Insurance Scheme Health Screening Cohort between January 1, 2004 and December 31, 2009. Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals (CI) to assess the association between pre-existing depression and all-cause, cancer-related, and noncancer-related mortality among 5-year cancer survivors. After adjustment for sociodemographics, lifestyle, and clinical status, the multivariable adjusted hazard ratios (95% CIs) for all-cause, cancer-related, and noncancer-related mortality among 5-year cancer survivors with pre-existing depression were 1.52 (1.13–2.05), 1.17 (0.75–1.81), and 2.07 (1.38–3.10) compared with those without pre-existing depression, respectively. Significant associations between pre-existing depression and mortalities (all-cause and noncancer-related mortality) were only observed among male cancer survivors. Our findings suggest that depression is associated with all-cause mortality after cancer diagnosis and that greater efforts should be focused on the long-term survival of patients with cancer with pre-existing depression, especially in male cancer survivors.
Hydrophobic ligands influence the structure, stability, and processing of the major cockroach allergen Bla g 1
Authors: Foo Alexander C. Y. , Thompson Peter M. , Perera Lalith , Arora Simrat , DeRose Eugene F. , Williams Jason , Mueller Geoffrey A.
Published: December 2019

The cockroach allergen Bla g 1 forms a novel fold consisting of 12 amphipathic alpha-helices enclosing an exceptionally large hydrophobic cavity which was previously demonstrated to bind a variety of lipids. Since lipid-dependent immunoactivity is observed in numerous allergens, understanding the structural basis of this interaction could yield insights into the molecular determinants of allergenicity. Here, we report atomic modelling of Bla g 1 bound to both fatty-acid and phospholipids ligands, with 8 acyl chains suggested to represent full stoichiometric binding. This unusually high occupancy was verified experimentally, though both modelling and circular dichroism indicate that the general alpha-helical structure is maintained regardless of cargo loading. Fatty-acid cargoes significantly enhanced thermostability while inhibiting cleavage by cathepsin S, an endosomal protease essential for antigen processing and presentation; the latter of which was found to correlate to a decreased production of known T-cell epitopes. Both effects were strongly dependent on acyl chain length, with 18–20 carbons providing the maximal increase in melting temperature (~20 °C) while completely abolishing proteolysis. Diacyl chain cargoes provided similar enhancements to thermostability, but yielded reduced levels of proteolytic resistance. This study describes how the biophysical properties of Bla g 1 ligand binding and digestion may relate to antigen processing, with potential downstream implications for immunogenicity.
Symbionts do not affect the mating incompatibility between the Brazilian-1 and Peruvian morphotypes of the Anastrepha fraterculus cryptic species complex
Authors: Devescovi Francisco , Conte Claudia A. , Augustinos Antonios , Martinez Elena I. Cancio , Segura Diego F. , Caceres Carlos , Lanzavecchia Silvia B. , Bourtzis Kostas
Published: December 2019

The South American fruit fly, Anastrepha fraterculus, is clearly undergoing a speciation process. Among others, two of their morphotypes, the Brazilian-1 and Peruvian, have accumulated differences in pre- and post-zygotic mechanisms resulting in a degree of reproductive isolation. Both harbor a different strain of Wolbachia, which is a widespread endosymbiotic bacterium among many invertebrates producing a range of reproductive effects. In this paper, we studied the role of this bacterium as one of the factors involved in such isolation process. Infected and cured laboratory colonies were used to test pre- and post-zygotic effects, with special emphasis in uni- and bi-directional cytoplasmic incompatibility (CI). We showed that Wolbachia is the only known reproductive symbiont present in these morphotypes. Wolbachia reduced the ability for embryonic development in crosses involving cured females and infected males within each morphotype (uni-directional CI). This inhibition showed to be more effective in the Peruvian morphotype. Bi-directional CI was not evidenced, suggesting the presence of compatible Wolbachia strains. We conclude that Wolbachia is not directly involved in the speciation process of these morphotypes. Other mechanisms rather than CI should be explored in order to explain the reduced mating compatibility between the Brazilian-1 and Peruvian morphotypes.
Beta rhythm events predict corticospinal motor output
Authors: Hussain Sara J. , Cohen Leonardo G. , Bönstrup Marlene
Published: December 2019

The beta rhythm (15–30 Hz) is a prominent signal of sensorimotor cortical activity. This rhythm is not sustained but occurs non-rhythmically as brief events of a few (1–2) oscillatory cycles. Recent work on the relationship between these events and sensorimotor performance suggests that they are the biologically relevant elements of the beta rhythm. However, the influence of these events on corticospinal excitability, a mechanism through which the primary motor cortex controls motor output, is unknown. Here, we addressed this question by evaluating relationships between beta event characteristics and corticospinal excitability in healthy adults. Results show that the number, amplitude, and timing of beta events preceding transcranial magnetic stimulation (TMS) each significantly predicted motor-evoked potential (MEP) amplitudes. However, beta event characteristics did not explain additional MEP amplitude variance beyond that explained by mean beta power alone, suggesting that conventional beta power measures and beta event characteristics similarly captured natural variation in human corticospinal excitability. Despite this lack of additional explained variance, these results provide first evidence that endogenous beta oscillatory events shape human corticospinal excitability.
Development of Novel Silyl Cyanocinnamic Acid Derivatives as Metabolic Plasticity Inhibitors for Cancer Treatment
Authors: Nelson Grady L. , Ronayne Conor T. , Solano Lucas N. , Jonnalagadda Sravan K. , Jonnalagadda Shirisha , Rumbley Jon , Holy Jon , Rose-Hellekant Teresa , Drewes Lester R. , Mereddy Venkatram R.
Published: December 2019

Novel silyl cyanocinnamic acid derivatives have been synthesized and evaluated as potential anticancer agents.In vitrostudies reveal that lead derivatives2aand2bhave enhanced cancer cell proliferation inhibition properties when compared to the parent monocarboxylate transporter (MCT) inhibitor cyano-hydroxycinnamic acid (CHC). Further, candidate compounds exhibit several-fold more potent MCT1 inhibition properties as determined by lactate-uptake studies, and these studies are supported by MCT homology modeling and computational inhibitor-docking studies.In vitroeffects on glycolysis and mitochondrial metabolism also illustrate that the lead derivatives2aand2blead to significant effects on both metabolic pathways.In vivosystemic toxicity and efficacy studies in colorectal cancer cell WiDr tumor xenograft demonstrate that candidate compounds are well tolerated and exhibit good single agent anticancer efficacy properties.
Investigation of the preservation effect of canagliflozin on pancreatic beta cell mass using SPECT/CT imaging with 111In-labeled exendin-4
Authors: Hamamatsu Keita , Fujimoto Hiroyuki , Fujita Naotaka , Murakami Takaaki , Shiotani Masaharu , Toyoda Kentaro , Inagaki Nobuya
Published: December 2019

Radiolabeled exendin derivatives are promising for non-invasive quantification of pancreatic beta cell mass (BCM); longitudinal observation of BCM for evaluation of therapeutic effects has not been achieved. The aim of this study is to demonstrate the usefulness of our developing method using [Lys12(111In-BnDTPA-Ahx)]exendin-4 to detect longitudinal changes in BCM. We performed a longitudinal study with obese type 2 diabetes model (db/db) mice administered canagliflozin, which is reported to preserve BCM. Six-week-old mice were assigned to a canagliflozin-administered group or a control group. Blood glucose levels of the canagliflozin group were significantly lower than those of the control group. Plasma insulin levels, insulin secretion during OGTT and insulin content in the pancreas were preserved in the canagliflozin group in comparison with those in the control group. According to SPECT/CT imaging analysis using [Lys12(111In-BnDTPA-Ahx)]exendin-4, pancreatic uptake was significantly decreased in the control group, whereas there was no significant change in the canagliflozin group. After nine weeks, both pancreatic uptake and BCM of the canagliflozin group were significantly higher than those of the control group, and a correlation between them was observed. In conclusion, our imaging method confirmed the BCM-preservation effect of canagliflozin, and demonstrated its potential for longitudinal evaluation of BCM.
Author Correction: Cardiac glycoside/aglycones inhibit HIV-1 gene expression by a mechanism requiring MEK1/2-ERK1/2 signaling
Authors: Wong Raymond W. , Lingwood Clifford A. , Ostrowski Mario A. , Cabral Tyler , Cochrane Alan
Published: December 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Combined use of satellite and surface observations to study aerosol optical depth in different regions of China
Authors: Filonchyk Mikalai , Yan Haowen , Zhang Zhongrong , Yang Shuwen , Li Wei , Li Yanming
Published: December 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Effects of early dialysis on the outcomes of critically ill patients with acute kidney injury: a systematic review and meta-analysis of randomized controlled trials
Authors: Lin Wei-Ting , Lai Chih-Cheng , Chang Shen-Peng , Wang Jian-Jhong
Published: December 2019

The appropriate timing for initiating renal replacement therapy (RRT) in critically ill patients with acute kidney injury (AKI) remains unknown. This meta-analysis aims to assess the efficacy of early initiation of RRT in critically ill patients with AKI. The Pubmed, Embase and Cochrane databases were searched up to August 13, 2019. Only randomized controlled trials (RCTs) comparing the effects of early and late RRT on AKI patients were included. The primary outcome was 28-day mortality. Eleven RCTs including 1131 and 1111 AKI patients assigned to early and late RRT strategies, respectively, were enrolled in this meta-analysis. The pooled 28-day mortality was 38.1% (431/1131) and 40.7% (453/1111) in the patients assigned to early and late RRT, respectively, with no significant difference between groups (risk ratio (RR), 0.95; 95% CI, 0.78–1.15, I2 = 63%). No significant difference was found between groups in terms of RRT dependence in survivors on day 28 (RR, 0.90; 95% CI, 0.67–1.25, I2 = 0%), and recovery of renal function (RR, 1.03; 95% CI, 0.89–1.19, I2 = 56%). The early RRT group had higher risks of catheter-related infection (RR, 1.7, 95% CI, 1.01–2.97, I2 = 0%) and hypophosphatemia (RR, 2.5, 95% CI, 1.25–4.99, I2 = 77%) than the late RRT group. In conclusion, an early RRT strategy does not improve survival, RRT dependence, or renal function recovery in critically ill patients with AKI in comparison with a late RRT strategy. However, clinicians should be vigilant because early RRT can carry higher risks of catheter-related infection and hypophosphatemia during dialysis than late RRT.
The optimal timing of additional surgery after non-curative endoscopic resection to treat early gastric cancer: long-term follow-up study
Authors: Cha Jae Hwang , Kim Jie-Hyun , Kim Hyoung-Il , Jung Da Hyun , Park Jae Jun , Youn Young Hoon , Park Hyojin , Choi Seung Ho , Cheong Jae-Ho , Hyung Woo Jin , Noh Sung Hoon
Published: December 2019

Patients with early gastric cancer (EGC) who undergo non-curative endoscopic resection (ER) require additional surgery. The aim of the study was to validate surgical and oncological outcomes according to the timing of additional surgery after non-curative endoscopic resection. We retrospectively analyzed long-term follow-up data on the 302 patients enrolled between January 2007 and December 2014. We validated our earlier suggestion that the optimal time interval from non-curative ER to additional surgery was 29 days. All patients were divided into two groups by reference to time intervals from ER to additional surgery of ≤29days (n = 133; group A) and >29 days (n = 169; group B). The median follow-up duration was 41.98 ± 21.23 months. As in our previous study, group B exhibited better surgical outcomes. A total of 10 patients developed locoregional or distant recurrences during the follow-up period, but no significant difference was evident between the two groups. Interestingly, the survival rate was better in group B. Group B (>29 days) exhibited better surgical and oncological outcomes. Thus, additional gastrectomy after non-curative ER should be delayed for 1 month to ensure optimal surgical and oncological outcomes.
Chitosan Encapsulation of FerrateVI for Controlled Release to Water:Mechanistic Insights and Degradation of Organic Contaminant
Authors: Chen Bo-Yen , Kuo Hsuen-Wen , Sharma Virender K. , Den Walter
Published: December 2019

Tetraoxy-anion of iron in +6 oxidation state (FeVIO42−, FeVI), commonly called ferrate, has shown tremendous potential as a green oxidative agent for decontaminating water and air. Encapsulation of solid potassium salt of ferrate (K2FeO4) circumvents the inherent drawbacks of the instability of ferrate under humid conditions. In the encapsulated strategy, controlled release without exposing the solid ferrate to the humid environment avoids self-decomposition of the oxidant by water in the air, and the ferrate is mostly used to decontaminate water efficiently. This study demonstrated the formulation of oxidative microcapsules with natural materials present in chitosan, whose release rate of the core material can be controlled by the type of intermediate hydrocarbon layer and the pH-dependent swelling of chitosan shell. The pH played a pivotal role in swelling chitosan shell and releasing the core oxidant. In a strong acidic solution, chitosan tended to swell quickly and release FeVI at a faster rate than under neutral conditions. Additionally, among the several long-chain hydrocarbon compounds, oleic acid exhibited the strongest “locking” effect when applied as the intermediate layer, giving rise to the slow release of FeVI. Coconut oil and mineral oil, in comparison, allowed FeVI to penetrate the layer within shorter lengths of time and showed comparable degrees of degradation of target contaminant, methylene orange, under ambient temperature and near-neutral conditions. These findings have practical ramifications for remediating environmental and industrial processes.
Short-term effects of sound localization training in virtual reality
Authors: Steadman Mark A. , Kim Chungeun , Lestang Jean-Hugues , Goodman Dan F. M. , Picinali Lorenzo
Published: December 2019

Head-related transfer functions (HRTFs) capture the direction-dependant way that sound interacts with the head and torso. In virtual audio systems, which aim to emulate these effects, non-individualized, generic HRTFs are typically used leading to an inaccurate perception of virtual sound location. Training has the potential to exploit the brain’s ability to adapt to these unfamiliar cues. In this study, three virtual sound localization training paradigms were evaluated; one provided simple visual positional confirmation of sound source location, a second introduced game design elements (“gamification”) and a final version additionally utilized head-tracking to provide listeners with experience of relative sound source motion (“active listening”). The results demonstrate a significant effect of training after a small number of short (12-minute) training sessions, which is retained across multiple days. Gamification alone had no significant effect on the efficacy of the training, but active listening resulted in a significantly greater improvements in localization accuracy. In general, improvements in virtual sound localization following training generalized to a second set of non-individualized HRTFs, although some HRTF-specific changes were observed in polar angle judgement for the active listening group. The implications of this on the putative mechanisms of the adaptation process are discussed.
Carbamylation and glycation compete for collagen molecular aging in vivo
Authors: Nicolas Camille , Jaisson Stéphane , Gorisse Laëtitia , Tessier Frédéric J. , Niquet-Léridon Céline , Jacolot Philippe , Pietrement Christine , Gillery Philippe
Published: December 2019

Tissue aging is a complex phenomenon involving molecular aging of matrix proteins, which mainly results from their progressive alteration by nonenzymatic post-translational modifications (NEPTMs) such as glycation and carbamylation. These two reactions, which correspond to the binding of reactive metabolites (i.e. reducing sugars and urea-derived cyanate, respectively) on amino groups of proteins, occur during aging and are amplified in various chronic diseases such as diabetes mellitus or chronic renal disease (CKD). Since these reactions target the same functional groups, they can reciprocally compete for protein modification. Determining which NEPTM is predominant in tissues is necessary to better understand their role in the development of long-term complications of chronic diseases. For that purpose, two different murine models were used for reproducing such a competitive context: a CKD-diabetic mice model and a cyanate-consuming mice model. The competition has been evaluated by quantifying glycation and carbamylation products by LC-MS/MS in skin and aorta total extracts as well as in skin type I collagen. The results showed that the simultaneous enhancement of glycation and carbamylation reactions resulted in a decrease of the formation of glycation products (especially Amadori products) whereas the concentrations of homocitrulline, a carbamylation product, remained similar. These results, which have been obtained in both tissues and in purified skin type I collagen, suggest that carbamylation takes precedence over glycation for the modification of tissue proteins, but only in pathological conditions favouring these two NEPTMs. While glycation has been considered for a long time the predominant NEPTM of matrix proteins, carbamylation seems to also play an important role in tissue aging. The existence of competition between these NEPTMs must be taken into account to better understand the consequences of molecular aging of matrix proteins in tissue aging.
Author Correction: Non-invasive, Brain-controlled Functional Electrical Stimulation for Locomotion Rehabilitation in Individuals with Paraplegia
Authors: Selfslagh Aurelie , Shokur Solaiman , Campos Debora S. F. , Donati Ana R. C. , Almeida Sabrina , Yamauti Seidi Y. , Coelho Daniel B. , Bouri Mohamed , Nicolelis Miguel A. L.
Published: December 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
A Prospective Observational Cohort of Clinical Outcomes in Medical Inpatients prescribed Pharmacological Thromboprophylaxis Using Different Clinical Risk Assessment Models(COMPT RAMs)
Authors: Chamoun Nibal , Matta Stephanie , Aderian Sandrine Sarine , Salibi Rami , Salameh Pascale , Tayeh Gaby , Haddad Elie , Ghanem Hady
Published: December 2019

The Caprini and Padua venous thromboembolism (VTE) risk assessment models (RAMs) are used to assess VTE risk in surgical and in medical patients respectively. This study aims to compare the proportion of medical inpatients eligible for VTE prophylaxis using the hospital Caprini-based RAM to using the Caprini and Padua RAMs and to assess the associated clinical outcomes. In a prospective observational study, we assessed 297 adult medical inpatients for whom VTE thromboprophylaxis was initiated according to the hospital Caprini-based RAM, referred to as the Lebanese American University Medical Center RAM (LAUMC-RAM). The Padua, Caprini and IMPROVE bleeding risk scores were also assessed for all patients. Bleeding and thromboembolism were evaluated at 14 and 30 days post VTE risk assessment. Pharmacologic thromboprophylaxis was warranted in 97.6%, 99.7%, and 52.9% of patients using the Caprini-based, Caprini, and Padua RAMs respectively. The Caprini-based and Caprini RAMs were highly correlated (r = 0.873 p < 0.001) and were significantly less correlated with the Padua RAM. Major and overall bleeding occurred in 1.4% and 9.2% respectively. VTE was reported in 0.4% with no VTE related mortality. In hospitalized medical patients, the Caprini-based RAM can accurately distinguish low and high VTE risk without resulting in increased risk of bleeding.
A New Tool for In Vivo Study of Astrocyte Connexin 43 in Brain
Authors: Droguerre Marine , Tsurugizawa Tomokazu , Duchêne Adeline , Portal Benjamin , Guiard Bruno P. , Déglon Nicole , Rouach Nathalie , Hamon Michel , Mouthon Franck , Ciobanu Luisa , Charvériat Mathieu
Published: December 2019

Astrocytes are glial cells organized in dynamic and structured networks in the brain. These plastic networks, involving key proteins such as connexin 43 (Cx43), are engaged in fine neuronal tuning and have recently been considered as emerging therapeutic targets in central nervous system disorders. We developed and validated a new application of the manganese-enhanced magnetic resonance imaging (MEMRI) technique allowing in vivo investigations of astrocyte-neuron interactions through quantification of brain Cx43 functional activity. The proof of concept has been achieved by quantification of MEMRI signals in brain after either local astrocyte-specific Cx43 knockdown with shRNA or systemic administration of Cx43 blockers. Unilateral hippocampal Cx43 genetical silencing was associated with an ipsilateral local increase of MEMRI signal. Furthermore, Cx43 blockers also enhanced MEMRI signal responses in hippocampus. Altogether, these data reveal the MEMRI technique as a tool for quantitative imaging of in vivo Cx43-dependent function in astrocytes under physiological and pathological conditions.
The effects of temperature and dispersal on species diversity in natural microbial metacommunities
Authors: Parain Elodie C. , Gray Sarah M. , Bersier Louis-Félix
Published: December 2019

Dispersal is key for maintaining biodiversity at local- and regional scales in metacommunities. However, little is known about the combined effects of dispersal and climate change on biodiversity. Theory predicts that alpha-diversity is maximized at intermediate dispersal rates, resulting in a hump-shaped diversity-dispersal relationship. This relationship is predicted to flatten when competition increases. We anticipate that this same flattening will occur with increased temperature because, in the rising part of the temperature performance curve, interspecific competition is predicted to increase. We explored this question using aquatic communities of Sarracenia purpurea from early- and late-successional stages, in which we simulated four levels of dispersal and four temperature scenarios. With increased dispersal, the hump shape was observed consistently in late successional communities, but only in higher temperature treatments in early succession. Increased temperature did not flatten the hump-shape relationship, but decreased the level of alpha- and gamma-diversity. Interestingly, higher temperatures negatively impacted small-bodied species. These metacommunity-level extinctions likely relaxed interspecific competition, which could explain the absence of flattening of the diversity-dispersal relationship. Our findings suggest that climate change will cause extinctions both at local- and global- scales and emphasize the importance of intermediate levels of dispersal as an insurance for local diversity.
Sphingosine kinase-2 prevents macrophage cholesterol accumulation and atherosclerosis by stimulating autophagic lipid degradation
Authors: Ishimaru Kazuhiro , Yoshioka Kazuaki , Kano Kuniyuki , Kurano Makoto , Saigusa Daisuke , Aoki Junken , Yatomi Yutaka , Takuwa Noriko , Okamoto Yasuo , Proia Richard L. , Takuwa Yoh
Published: December 2019

Atherosclerosis is the major cause of ischemic coronary heart diseases and characterized by the infiltration of cholesterol-accumulating macrophages in the vascular wall. Although sphingolipids are implicated in atherosclerosis as both membrane components and lipid mediators, the precise role of sphingolipids in atherosclerosis remains elusive. Here, we found that genetic deficiency of sphingosine kinase-2 (SphK2) but not SphK1 aggravates the formation of atherosclerotic lesions in mice with ApoE deficiency. Bone marrow chimaera experiments show the involvement of SphK2 expressed in bone marrow-derived cells. In macrophages, deficiency of SphK2, a major SphK isoform in this cell type, results in increases in cellular sphingosine and ceramides. SphK2-deficient macrophages have increases in lipid droplet-containing autophagosomes and autolysosomes and defective lysosomal degradation of lipid droplets via autophagy with an impaired luminal acidic environment and proteolytic activity in the lysosomes. Transgenic overexpression of SphK1 in SphK2-deficient mice rescued aggravation of atherosclerosis and abnormalities of autophagosomes and lysosomes in macrophages with reductions of sphingosine, suggesting at least partial overlapping actions of two SphKs. Taken together, these results indicate that SphK2 is required for autophagosome- and lysosome-mediated catabolism of intracellular lipid droplets to impede the development of atherosclerosis; therefore, SphK2 may be a novel target for treating atherosclerosis.
Comparison of 3T and 7T MRI for the visualization of globus pallidus sub-segments
Authors: Maruyama Shuki , Fukunaga Masaki , Fautz Hans-Peter , Heidemann Robin , Sadato Norihiro
Published: December 2019

The success of deep brain stimulation (DBS) targeting the internal globus pallidus (GPi) depends on the accuracy of electrode localization inside the GPi. In this study, we sought to compare visualization of the medial medullary lamina (MML) and accessory medullary lamina (AML) between proton density-weighted (PDW) and T2-weighted (T2W) sequences on 3T and 7T MRI scanners. Eleven healthy participants (five men and six women; age, 19–28 years; mean, 21.5) and one 61-year-old man were scanned using two-dimensional turbo spin-echo PDW and T2W sequences on 3T and 7T MRI scanners with a 32-channel receiver head coil and a single-channel transmission coil. Profiles of signal intensity were obtained from the pixel values of straight lines over the GP regions crossing the MML and AML. Contrast ratios (CRs) for GPe/MML, GPie/MML, GPie/AML, and GPii/AML were calculated. Qualitatively, 7T visualized both the MML and AML, whereas 3T visualized the MML less clearly and hardly depicted the AML. The T2W sequence at 7T yielded significantly higher CRs for GPie/MML, GPie/AML, and GPii/AML than the PDW sequence at 7T or 3T. The T2W sequence at 7T allows visualization of the internal structures of GPi segments with high signal intensity and contrast.
Selection of candidate reference genes for RT-qPCR analysis in Argulus siamensis and their validation through screening of drugs and drug targets
Authors: Sahoo Pramoda Kumar , Parida Sonali , Mohapatra Amruta , Mohanty Jyotirmaya
Published: December 2019

Argulusspp. are economically important fish ectoparasites. The development of antiparasitic drugs is thus important and real time PCR is an indispensable tool in drug development. The analytical potential of RT-PCR depends upon accurate normalisation by the use of stable reference genes. Here, we identified stable reference genes ofArgulus siamensisfor validation of efficacy of drugs and drug targets. Seven candidate genes were evaluated by evaluating their expression under different states ofArgulususing the RefFinder tool. The four algorithms together generated a comprehensive ranking with elongation factor-1 alpha (EF-1α) being the most stable and 18S ribosomal protein (18S) the least stable gene. Taking EF-1α and 18S genes as references, the effectiveness of six anti-parasitic compounds againstArguluswas evaluated by studying their effect on the expression pattern of few ion channel genes; this was to understand their mode of action, besides validating the reference genes. EF-1α was found to be the most stable gene in the validation. Collectively, this study is the first report to validate the optimal reference genes ofA.siamensisfor normalisation, and the potential of the ion channel genes for evaluating effective drug targets in parasite control.
The role of CRP and Pentraxin 3 in the prediction of systemic inflammatory response syndrome and death in acute pancreatitis
Authors: Staubli Sebastian M. , Schäfer Juliane , Rosenthal Rachel , Zeindler Jasmin , Oertli Daniel , Nebiker Christian A.
Published: December 2019

Pentraxin 3 (PTX3) is an acute phase protein. Our goal was to assess PTX3 as a predictor of systemic inflammatory response syndrome (SIRS), death and disease severity in acute pancreatitis (AP) in comparison to C-reactive protein (CRP) and the APACHE II score. From April 2011 to January 2015, 142 patients with AP were included in this single center post hoc analysis of prospectively collected data at the University Hospital Basel, Switzerland. Disease severity was rated by the revised Atlanta criteria (rAC). Inflammatory response was measured by the SIRS criteria. PTX3, CRP and APACHE II score were measured. Patients median PTX3 plasma concentrations in AP were higher in moderate (3.311 ng/ml) and severe (3.091 ng/ml) than in mild disease (2.461 ng/ml). Overall, 59 occurrences of SIRS or death were observed. In the prediction of SIRS or death, PTX3 was inferior to CRP and APACHE II, with modest predictive discriminatory ability of all three markers and AUC of 0.54, 0.69 and 0.69, respectively. Upon combination of CRP with PTX3, AUC was 0.7. PTX3 seems to be inferior to CRP and APACHE II in the prediction of SIRS or death in AP and does not seem to improve the predictive value of CRP upon combination of both parameters.
Syndecan-1 Predicts Outcome in Patients with ST-Segment Elevation Infarction Independent from Infarct-related Myocardial Injury
Authors: Wernly Bernhard , Fuernau Georg , Masyuk Maryna , Muessig Johanna Maria , Pfeiler Susanne , Bruno Raphael Romano , Desch Steffen , Muench Phillip , Lichtenauer Michael , Kelm Malte , Adams Volker , Thiele Holger , Eitel Ingo , Jung Christian
Published: December 2019

Syndecan-1 (sdc1) is a surface protein part of the endothelial glycocalyx (eGC). Soluble sdc1 is derived from shedding and indicates damaged eGC. We assessed the predictive value of plasma sdc1 concentrations for future cardiovascular events in acute reperfused ST-segment elevation myocardial infarction (STEMI) patients. A total of 206 patients admitted for STEMI were included in this study (29% female; age 65 ± 12 years) and followed-up for six months. Plasma samples were obtained post-intervention and analyzed for sdc1 by Enzyme-linked Immunosorbent Assay (ELISA). Primary outcome was six-month-mortality. Sdc1 did not correlate with biomarkers such as creatine kinase (CK) (r = 0.11; p = 0.01) or troponin (r = −0.12; p = 0.09), nor with infarct size (r = −0.04; p = 0.67) and myocardial salvage index (r = 0.11; p = 0.17). Sdc-1 was associated with mortality (changes per 100 ng/mL sdc-1 concentration; HR 1.08 95% 1.03–1.12; p = 0.001). An optimal cut-off was calculated at >120 ng/mL. After correction for known risk factors sdc1 >120 ng/mL was independently associated with mortality after 6 months. In our study, sdc1 is independently associated with six-month-mortality after STEMI. Combining clinical evaluation and different biomarkers assessing both infarct-related myocardial injury and systemic stress response might improve the accuracy of predicting clinical prognosis in STEMI patients.
Suppressing aberrant phospholipase D1 signaling in 3xTg Alzheimer’s disease mouse model promotes synaptic resilience
Authors: Bourne Krystyn Z. , Natarajan Chandramouli , Perez Carlos X. Medina , Tumurbaatar Batbayar , Taglialatela Giulio , Krishnan Balaji
Published: December 2019

Current approaches in treatment of Alzheimer’s disease (AD) is focused on early stages of cognitive decline. Identifying therapeutic targets that promote synaptic resilience during early stages may prevent progressive memory deficits by preserving memory mechanisms. We recently reported that the inducible isoform of phospholipase D (PLD1) was significantly increased in synaptosomes from post-mortem AD brains compared to age-matched controls. Using mouse models, we reported that the aberrantly elevated neuronal PLD1 is key for oligomeric amyloid driven synaptic dysfunction and underlying memory deficits. Here, we demonstrate that chronic inhibition using a well-tolerated PLD1 specific small molecule inhibitor is sufficient to prevent the progression of synaptic dysfunction during early stages in the 3xTg-AD mouse model. Firstly, we report prevention of cognitive decline in the inhibitor-treated group using novel object recognition (NOR) and fear conditioning (FC). Secondly, we provide electrophysiological assessment of better synaptic function in the inhibitor-treated group. Lastly, using Golgi staining, we report that preservation of dendritic spine integrity as one of the mechanisms underlying the action of the small molecule inhibitor. Collectively, these studies provide evidence for inhibition of PLD1 as a potential therapeutic strategy in preventing progression of cognitive decline associated with AD and related dementia.
Author Correction: Verbascoside: Identification, Quantification, and Potential Sensitization of Colorectal Cancer Cells to 5-FU by Targeting PI3K/AKT Pathway
Authors: Attia Yasmeen M. , El-Kersh Dina M. , Wagdy Hebatallah A. , Elmazar Mohamed M.
Published: December 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Publisher Correction: Intrinsic activation of cell growth and differentiation in ex vivo cultured human hair follicles by a transient endogenous production of ROS
Authors: Calvo-Sánchez María I. , Fernández-Martos Sandra , Montoya Juan José , Espada Jesús
Published: December 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Characterization of the dielectric properties of water and methanol in the D-band using a quasi-optical spectroscopy
Authors: Liu Xiaoming , Yu Junsheng
Published: December 2019

This work presents the measurement of the permittivities of water and methanol in the D-band. Water is a reference medium for dielectric measurement. The dielectric permittivity of water in the millimeter wave range is a fundamental parameter in many applications, and needs to be investigated systematically. The measurement is conducted using a quasi-optical spectroscopy, which is an improved free-space method more suitable for the millimeter wave range. The theoretical formulae are derived using the signal-flow chart method, which is developed specially for multi-layer operation. This model enables one measure liquid samples. A non-calibration method has been developed to retrieve the permittivity. Water and methanol are measured at several temperatures. The measured results agree with published results in a 4% discrepancy. This work will add new measured data to the permittivities of water and methanol over the whole D-band.
Author Correction: Single-trial classification of awareness state during anesthesia by measuring critical dynamics of global brain activity
Authors: Alonso Leandro M. , Solovey Guillermo , Yanagawa Toru , Proekt Alex , Cecchi Guillermo A. , Magnasco Marcelo O.
Published: December 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Preparation of Lauroyl Grafted Alginate-Psyllium Husk Gel Composite Film with Enhanced Physicochemical, Mechanical and Antimicrobial Properties
Authors: Fernandes Clara , Acharya Pratap Chandra , Bhatt Shikha
Published: December 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Publisher Correction: Identification of microRNAs and relative target genes in Moringa oleifera leaf and callus
Authors: Pirrò Stefano , Matic Ivana , Guidi Arianna , Zanella Letizia , Gismondi Angelo , Cicconi Rosella , Bernardini Roberta , Colizzi Vittorio , Canini Antonella , Mattei Maurizio , Galgani Andrea
Published: December 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Organisation of Toxicological Data in Databases
Authors: Bower David , Cross Kevin , Myatt Glenn
Published: December 2019

There are a wide variety of established toxicity databases being routinely used to support hazard and risk assessment. The increasing number and size of toxicology databases and methods for automatically recording toxicology studies has led to a diverse series of formats for organisation of the information. Currently, such approaches span from simple one-to-one data exchange formats to complex formats incorporating semantic representations and data models covering additional information (such as experimental design, results and findings). Such developments support the volume, variety and value of (big) data and the transition from insular, isolated and simple structures to big data technologies for big toxicology data resources. This chapter reviews current solutions for the most known resources and identifies opportunities and gaps that such resources show in the era of big data. It covers a variety of approaches to data exchange and database design for organising toxicity and related data, highlights a number of databases with toxicity data as well as information on alternative approaches, and discusses project management and regulatory compliance databases. The chapter concludes with reflections on how these systems can integrate diverse toxicology-related data in preparation for the adoption of new big data technologies.
Toxicogenomics and Toxicoinformatics: Supporting Systems Biology in the Big Data Era
Authors: Souza Terezinha M. , Kleinjans Jos C. S. , Jennen Danyel G. J.
Published: December 2019

Within Toxicology, Toxicogenomics stands out as a unique research field aiming at the investigation of molecular alterations induced by chemical exposure. Toxicogenomics comprises a wide range of technologies developed to measure and quantify the '-omes (transcriptome, (epi)genome, proteome and metalobome), offering a human-based approach in contrast to traditional animal-based toxicity testing. With the growing acceptance and continuous improvements in high-throughput technologies, we observed a fast increase in the generation of ‘omics outputs. As a result, Toxicogenomics entered a new, challenging era facing the characteristic 4 Vs of Big Data: volume, velocity, variety and veracity. This chapter addresses these challenges by focusing on computational methods and Toxicoinformatics in the scope of Big ‘omics Data. First, we provide an overview of current technologies and the steps involved in storage, pre-processing and integration of high-throughput datasets, describing databases, standard pipelines and routinely used tools. We show how data mining, pattern recognition and mechanistic/pathway analyses contribute to elucidate mechanisms of adverse effects to build knowledge in Systems Toxicology. Finally, we present the recent progress in tackling current computational and biological limitations. Throughout the chapter, we also provide relevant examples of successful applications of Toxicoinformatics in predicting toxicity in the Big Data era.
Role of Toxicological Big Data to Support Read-across for the Assessment of Chemicals
Authors: Cronin Mark T. D. , Richarz Andrea-Nicole
Published: December 2019

The toxicity of similar chemicals can be read across to fill data gaps. As such, read-across provides a pragmatic solution to data gap filling and is of considerable interest to reduce the reliance on animal testing for regulatory purposes, or where testing may not be practical or possible. Weaknesses of read-across can be addressed, at least partially, by the use of toxicological data increasingly generated by new approach methodologies on a large scale in the big data era, to provide evidence to support a justification of similarity which extends the current paradigm from chemical to biological and toxicological similarity. This chapter illustrates how these toxicological big data, such as from high-throughput in vitro screening, high content omics technologies and other large-scale bioactivity data compilations, can be used to undertake read-across based on biological and chemical similarity, supporting read-across justifications and mechanistic interpretation, as well as contribute to tackling challenges such as how to perform hazard assessment on mixtures and nanomaterials.
Correction: A colorimetric probe for the real-time naked eye detection of cyanide and hydroxide ions in tap water: experimental and theoretical studies
Authors: Uahengo Veikko , Naimhwaka Johannes , Daniel Likius S. , Rahman Ateeq , Elzagheid Mohamed I. , Rhyman Lydia , Ramasami Ponnadurai , Cai Ping
Published: December 2019

Correction for ‘A colorimetric probe for the real-time naked eye detection of cyanide and hydroxide ions in tap water: experimental and theoretical studies’ by Veikko Uahengo et al., Analyst, 2019, 144, 6422–6431.
A gold nanoparticles-assisted multiplex PCR assay for simultaneous detection of Salmonella typhimurium, Listeria monocytogenes and Escherichia coli O157:H7
Authors: Du Juan , Wu Shujing , Niu Liyuan , Li Junguang , Zhao Dianbo , Bai Yanhong
Published: December 2019

Unfunctionalized flower-shaped AuNPs is used as colorimetric sensor for PCR product detection by naked eyes.
“Swiss roll”-like bioactive hybrid scaffolds for promoting bone tissue ingrowth and tendon-bone healing after anterior cruciate ligament reconstruction
Authors: Zhang Peng , Han Fei , Chen Tianwu , Wu Ziying , Chen Shiyi
Published: December 2019

The choice of grafts for anterior cruciate ligament (ACL) reconstruction is a critical issue in sports medicine.
Preventing Pd–NHC bond cleavage and switching from nano-scale to molecular catalytic systems: amines and temperature as catalyst activators
Authors: Khazipov Oleg V. , Shevchenko Maxim A. , Pasyukov Dmitry V. , Chernenko Andrey Yu. , Astakhov Alexander V. , Tafeenko Victor A. , Chernyshev Victor M. , Ananikov Valentine P.
Published: December 2019

Heating Pd/NHC complexes with aliphatic amines induces Pd–NHC bond cleavage, while treating the complexes with primary or secondary aliphatic amines in the presence of strong bases promotes the activation of molecular Pd/NHC catalysis.
Reduction of reverse solute flux induced solute buildup in the feed solution of forward osmosis
Authors: Ferby Matthew , Zou Shiqiang , He Zhen
Published: December 2019

Accumulation of solutes in the feed solutions of forward osmosis due to reverse solute flux should be reduced.
Lysine blockage of milk proteins in infant formula impairs overall protein digestibility and peptide release
Authors: Zenker Hannah E. , van Lieshout Glenn A. A. , van Gool Martine P. , Bragt Marjolijn C. E. , Hettinga Kasper A.
Published: December 2019

High levels of blocked lysine in infant formula lead to increasing average peptide length after in vitro digestion in infants.
Effect of transglutaminase cross-linking on the allergenicity of tofu based on a BALB/c mouse model
Authors: Bai Jing , Hui Junyu , Lu Qiaoling , Yang Anshu , Yuan Juanli , Gao Jinyan , Wu Zhihua , Li Xin , Tong Ping , Chen Hongbing
Published: December 2019

This paper investigated the effect of enzymatic cross-linking on the potential allergenicity of tofu in vivo.
Addressing the plasmonic hotspot region by site-specific functionalization of nanostructures
Authors: Goerlitzer Eric S. A. , Speichermann Lutz E. , Mirza Talha A. , Mohammadi Reza , Vogel Nicolas
Published: December 2019

We provide a simple and parallel method to selectively functionalize the hot-spot regions of plasmonic nanostructures, allowing to deposit molecules or particles directly at the most active sites.
Bright, stable, and efficient red light-emitting electrochemical cells using contorted nanographenes
Authors: Fresta Elisa , Baumgärtner Kevin , Cabanillas-Gonzalez Juan , Mastalerz Michael , Costa Rubén D.
Published: December 2019

A red-emitting contorted hexabenzoovalene yielded bright and stable light-emitting electrochemical cells showing electric-field dependent emission.