bluuebunny/crossref_metadata_2025 huggingface dataset:
Where to forage when afraid: Does perceived risk impair use of the foodscape?
Authors: Dwinnell Samantha P. H. , Sawyer Hall , Randall Jill E. , Beck Jeffrey L. , Forbey Jennifer S. , Fralick Gary L. , Monteith Kevin L.
Published: July 2019

The availability and quality of forage on the landscape constitute the foodscape within which animals make behavioral decisions to acquire food. Novel changes to the foodscape, such as human disturbance, can alter behavioral decisions that favor avoidance of perceived risk over food acquisition. Although behavioral changes and population declines often coincide with the introduction of human disturbance, the link(s) between behavior and population trajectory are difficult to elucidate. To identify a pathway by which human disturbance may affect ungulate populations, we tested the Behaviorally Mediated Forage‐Loss Hypothesis, wherein behavioral avoidance is predicted to reduce use of available forage adjacent to disturbance. We used GPS collar data collected from migratory mule deer (Odocoileus hemionus) to evaluate habitat selection, movement patterns, and time‐budgeting behavior in response to varying levels of forage availability and human disturbance in three different populations exposed to a gradient of energy development. Subsequently, we linked animal behavior with measured use of forage relative to human disturbance, forage availability, and quality. Mule deer avoided human disturbance at both home range and winter range scales, but showed negligible differences in vigilance rates at the site level. Use of the primary winter forage, sagebrush (Artemisia tridentata), increased as production of new annual growth increased but use decreased with proximity to disturbance. Consequently, avoidance of human disturbance prompted loss of otherwise available forage, resulting in indirect habitat loss that was 4.6‐times greater than direct habitat loss from roads, well pads, and other infrastructure. The multiplicative effects of indirect habitat loss, as mediated by behavior, impaired use of the foodscape by reducing the amount of available forage for mule deer, a consequence of which may be winter ranges that support fewer animals than they did before development.
Disappearing Kilimanjaro snow—Are we the last generation to explore equatorial glacier biodiversity?
Authors: Zawierucha Krzysztof , Shain Daniel H.
Published: July 2019

Glaciation accompanied our human ancestors in Africa throughout the Pleistocene. Regrettably, equatorial glaciers and snow are disappearing rapidly, and we are likely the last generation who will get to know these peculiar places. Despite the permanently harsh conditions of glacier/snow habitats, they support a remarkable diversity of life ranging from bacteria to animals. Numerous papers have been devoted to microbial communities and unique animals on polar glaciers and high mountains, but only two reports relate to glacial biodiversity in equatorial regions, which are destined to melt completely within the next few decades. Equatorial glaciers constitute “cold islands” in tropics, and discovering their diversity might shed light on the biogeography, dispersal, and history of psychrophiles. Thus, an opportunity to protect biota of equatorial glaciers hinges on ex situ conservation. It is timely and crucial that we should investigate the glacial biodiversity of the few remaining equatorial glaciers.
Nickel Carbodicarbene Catalyzes Kumada Cross‐Coupling of Aryl Ethers with Grignard Reagents through C–O Bond Activation
Authors: Ambre Ram , Yang Hsuan , Chen Wen‐Ching , Yap Glenn P. A. , Jurca Titel , Ong Tiow‐Gan
Published: July 2019

The development of a cross‐coupling reaction protocol between aryl ethers and Grignard reagents catalyzed by carbodicarbene (CDC) nickel complexes to afford biaryl compounds through C–O cleavage is reported. Aromatic substrates featuring a broad range of electron neutral, donating, or withdrawing groups are introduced at the desired position. The method has proven effective over a wide range of naphthyl methyl ethers, anisoles, and Grignard reagents. The robustness of the protocol is validated by performing multiple cleavage reactions, gram scale synthesis, and arylation of a dimethoxy esterdiol derivative.
Considerations for the Use of Mutation as a Regulatory Endpoint in Risk Assessment
Authors: Klapacz Joanna , Gollapudi B. Bhaskar
Published: July 2019

Assessment of a chemical's potential to cause permanent changes in the genetic code has been a common practice in the industry and regulatory settings for decades. Furthermore, the genetic toxicity battery of tests has typically been employed during the earliest stages of the research and development programs of new product development. A positive outcome from such battery has a major impact on the chemical's utility, industrial hygiene, product stewardship practices, and product life cycle analysis, among many other decisions that need to be taken by the industry, even before the registration of a chemical is undertaken. Under the prevailing regulatory paradigm, the dichotomous (yes/no) evaluation of the chemical's genotoxic potential leads to a conservative, linear no‐threshold (LNT) risk assessment, unless compelling and undeniable data to the contrary can be provided to satisfy regulators, typically in a number of different global jurisdictions. With the current advent of predictive methods, new testing paradigms, mode‐of‐action/adverse outcome pathways, and quantitative risk assessment approaches, various stakeholders are starting to employ these state‐of‐the‐science methodologies to further the conversation on decision making and advance the regulatory paradigm beyond the dominant LNT status quo. This commentary describes these novel methodologies, relevant biological responses, and how these can affect internal and regulatory risk assessment approaches. Environ. Mol. Mutagen. 61:84–93, 2020. © 2019 Wiley Periodicals, Inc.
Transcriptional regulation of homeostatic and disease‐associated‐microglial genes by IRF1, LXRβ, and CEBPα
Authors: Gao Tianwen , Jernigan Janna , Raza Syed Ali , Dammer Eric B. , Xiao Hailian , Seyfried Nicholas T. , Levey Allan I. , Rangaraju Srikant
Published: July 2019

Microglia transform from homeostatic to disease‐associated‐microglia (DAM) profiles in neurodegeneration. Within DAM, we recently identified distinct pro‐inflammatory and anti‐inflammatory sub‐profiles although transcriptional regulators of homeostatic and distinct DAM profiles remain unclear. Informed by these studies, we nominated CEBPα, IRF1, and LXRβ as likely regulators of homeostatic, pro‐inflammatory and anti‐inflammatory DAM states and performed in‐vitro siRNA studies in primary microglia to identify roles of each transcriptional factor (TF) in regulating microglial activation, using an integrated transcriptomics, bioinformatics and experimental validation approach. Efficient (>70%) silencing of TFs in microglia revealed reciprocal regulation between each TF specifically following pro‐inflammatory activation. Neuroinflammatory transcriptomic profiling of microglia coupled with qPCR validation revealed distinct gene clusters with unique patterns of regulation by each TF, which were independent of LPS stimulation. While all three TFs (especially IRF1 and LXRβ) positively regulated core DAM genes (Apoe, Axl, Clec7a, Tyrobp, and Trem2) as well as homeostatic and pro‐inflammatory DAM genes, LPS, and IFNγ increased pro‐inflammatory DAM but suppressed homeostatic and anti‐inflammatory DAM gene expression via an Erk1/2‐dependent signaling pathway. IRF1 and LXRβ silencing suppressed microglial phagocytic activity for polystyrene microspheres as well as fAβ42 while IRF1 silencing strongly suppressed production of pro‐inflammatory cytokines in response to LPS. Our studies reveal complex transcriptional regulation of homeostatic and DAM profiles whereby IRF1, LXRβ, and CEBPα positively regulate both pro‐ and anti‐inflammatory DAM genes while activating stimuli independently augment pro‐inflammatory DAM responses and suppress homeostatic and anti‐inflammatory responses via Erk signaling. This framework can guide development of therapeutic immuno‐modulatory strategies for neurodegeneration.
Audio–visual and olfactory–visual integration in healthy participants and subjects with autism spectrum disorder
Authors: Stickel Susanne , Weismann Pauline , Kellermann Thilo , Regenbogen Christina , Habel Ute , Freiherr Jessica , Chechko Natalya
Published: July 2019

The human capacity to integrate sensory signals has been investigated with respect to different sensory modalities. A common denominator of the neural network underlying the integration of sensory clues has yet to be identified. Additionally, brain imaging data from patients with autism spectrum disorder (ASD) do not cover disparities in neuronal sensory processing. In this fMRI study, we compared the underlying neural networks of both olfactory–visual and auditory–visual integration in patients with ASD and a group of matched healthy participants. The aim was to disentangle sensory‐specific networks so as to derive a potential (amodal) common source of multisensory integration (MSI) and to investigate differences in brain networks with sensory processing in individuals with ASD. In both groups, similar neural networks were found to be involved in the olfactory–visual and auditory–visual integration processes, including the primary visual cortex, the inferior parietal sulcus (IPS), and the medial and inferior frontal cortices. Amygdala activation was observed specifically during olfactory–visual integration, with superior temporal activation having been seen during auditory–visual integration. A dynamic causal modeling analysis revealed a nonlinear top‐down IPS modulation of the connection between the respective primary sensory regions in both experimental conditions and in both groups. Thus, we demonstrate that MSI has shared neural sources across olfactory–visual and audio–visual stimulation in patients and controls. The enhanced recruitment of the IPS to modulate changes between areas is relevant to sensory perception. Our results also indicate that, with respect to MSI processing, adults with ASD do not significantly differ from their healthy counterparts.
Home enteral nutrition may prevent myelosuppression of patients with nasopharyngeal carcinoma treated by concurrent chemoradiotherapy
Authors: Li Xuemei , Zhou Jidan , Chu Ci , You Qian , Zhong Renming , Rao Zhiyong , Hu Wen
Published: July 2019

Background

The aim of this study is to assess the effect of home enteral nutrition (HEN) on the myelosuppression of patients with nasopharyngeal cancer (NPC) during the course of concurrent chemoradiotherapy (CCRT).

Methods

A total of 18 outpatients with NPC administered oral nutritional supplementation intervention at home during the course of CCRT were designated as the HEN group, whereas 36 patients with NPC who had previously completed CCRT were retrospectively included as the control group. Patient Generated Subjective Global Assessment, body mass index (BMI), and blood test were evaluated prior to CCRT. During the course of CCRT, blood test was assessed every 2 weeks.

Results

In male patients, hemoglobin (HB) and red blood cell were decreased (P < .05) in both HEN and control group after CCRT, whereas white blood cell (WBC) started to decrease since week 2 of CCRT in the control group but maintained in the HEN group which was significantly higher than the control (5.05 ± 1.29 vs 3.77 ± 1.5, P < .05). In female patients, HB and WBC were reduced in control group during CCRT, whereas these indicators also maintained in the HEN group. Surprisingly, all patients with lower BMI (<24 kg/m2) had a significant increase in platelet (PLT) after CCRT (200.78 ± 58.03 vs 253.00 ± 69.82, P < .05), while had steady HB and WBC values in the HEN group. At the end of CCRT, WBC and PLT of the HEN group were both higher than those in the control group (5.21 ± 1.07 vs 3.37 ± 1.52), (253.00 ± 69.82 vs 165.57 ± 59.56) (P < .05 for both). Our findings suggest that HEN is effective in preventing myelosuppression during CCRT for patients with NPC.

Conclusion

Our findings suggest that HEN is effective in preventing myelosuppression during CCRT for patients with NPC.
Twitter As a Noninvasive Bio‐Marker for Trends in Liver Disease
Authors: Da Ben L. , Surana Pallavi , Schueler Samuel A. , Jalaly Niloofar Y. , Kamal Natasha , Taneja Sonia , Vittal Anusha , Gilman Christy L. , Heller Theo , Koh Christopher
Published: July 2019

With the success of hepatitis C virus (HCV) direct‐acting antiviral therapies, there has been a shift in research focus to the other major chronic liver diseases (CLDs). The use of social media, specifically Twitter, has become a popular platform for understanding public health trends and for performing health care research. To evaluate this, we studied the areas of public interest and social media trends of the following three major CLDs: hepatitis B virus (HBV), HCV, and nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH). Twitter activity data from January 1, 2013, through January 1, 2019, for HBV, HCV, and NAFLD/NASH were collected using the social media analytic tool Symplur Signals (Symplur LLC) software. Content and regression analyses were performed to understand and predict Twitter activity for each of the CLDs. Over the study period, there were 810,980 tweets generating 4,452,939,516 impressions. HCV tweet activity peaked in 2015 at 243,261 tweets, followed by a decline of 52.4% from 2015 to 2016 with a subsequent plateau through 2018. Meanwhile, NAFLD/NASH and HBV tweet activity has continued to increase, with projections that these two CLDs will surpass HCV by the second half of 2023 and 2024, respectively. Treatment and Management was the most popular content category for HCV and NAFLD/NASH, while Prevention was the most popular content category for HBV. Conclusion: Twitter is a useful social media tool to gauge public interest in liver disease over time. The information provided by Twitter can be used to identify gaps in public knowledge or highlight areas of interest that may need further research. Future studies on the use of Twitter in liver disease are warranted.
Balanced synaptic currents underlie low‐frequency oscillations in the subiculum
Authors: Royzen Feliks , Williams Sylvain , Fernandez Fernando R. , White John A.
Published: July 2019

Numerous synaptic and intrinsic membrane mechanisms have been proposed for generating oscillatory activity in the hippocampus. Few studies, however, have directly measured synaptic conductances and membrane properties during oscillations. The time course and relative contribution of excitatory and inhibitory synaptic conductances, as well as the role of intrinsic membrane properties in amplifying synaptic inputs, remains unclear. To address this issue, we used an isolated whole hippocampal preparation that generates autonomous low‐frequency oscillations near the theta range. Using 2‐photon microscopy and expression of genetically encoded fluorophores, we obtained on‐cell and whole‐cell patch recordings of pyramidal cells and fast‐firing interneurons in the distal subiculum. Pyramidal cell and interneuron spiking shared similar phase‐locking to local field potential oscillations. In pyramidal cells, spiking resulted from a concomitant and balanced increase in excitatory and inhibitory synaptic currents. In contrast, interneuron spiking was driven almost exclusively by excitatory synaptic current. Thus, similar to tightly balanced networks underlying hippocampal gamma oscillations and ripples, balanced synaptic inputs in the whole hippocampal preparation drive highly phase‐locked spiking at the peak of slower network oscillations.
Place cell firing cannot support navigation without intact septal circuits
Authors: Bolding Kevin A. , Ferbinteanu Janina , Fox Steven E. , Muller Robert U.
Published: July 2019

Though it has been known for over half a century that interference with the normal activity of septohippocampal neurons can abolish hippocampal theta rhythmicity, a definitive answer to the question of its function has remained elusive. To clarify the role of septal circuits and theta in location‐specific activity of place cells and spatial behavior, three drugs were delivered to the medial septum of rats: Tetracaine, a local anesthetic; muscimol, a GABA‐A agonist; and gabazine, a GABA‐A antagonist. All three drugs disrupted normal oscillatory activity in the hippocampus. However, tetracaine and muscimol both reduced spatial firing and interfered with the rat's ability to navigate to a hidden goal. After gabazine, location‐specific firing was preserved in the absence of theta, but rats were unable to accurately locate the hidden goal. These results indicate that theta is unnecessary for location‐specific firing of hippocampal cells, and that place cell activity cannot support accurate navigation when septal circuits are disrupted.
Degeneracy in hippocampal physiology and plasticity
Authors: Rathour Rahul K. , Narayanan Rishikesh
Published: July 2019

Degeneracy, defined as the ability of structurally disparate elements to perform analogous function, has largely been assessed from the perspective of maintaining robustness of physiology or plasticity. How does the framework of degeneracy assimilate into an encoding system where the ability to change is an essential ingredient for storing new incoming information? Could degeneracy maintain the balance between the apparently contradictory goals of the need to change for encoding and the need to resist change towards maintaining homeostasis? In this review, we explore these fundamental questions with the mammalian hippocampus as an example encoding system. We systematically catalog lines of evidence, spanning multiple scales of analysis that point to the expression of degeneracy in hippocampal physiology and plasticity. We assess the potential of degeneracy as a framework to achieve the conjoint goals of encoding and homeostasis without cross‐interferences. We postulate that biological complexity, involving interactions among the numerous parameters spanning different scales of analysis, could establish disparate routes towards accomplishing these conjoint goals. These disparate routes then provide several degrees of freedom to the encoding‐homeostasis system in accomplishing its tasks in an input‐ and state‐dependent manner. Finally, the expression of degeneracy spanning multiple scales offers an ideal reconciliation to several outstanding controversies, through the recognition that the seemingly contradictory disparate observations are merely alternate routes that the system might recruit towards accomplishment of its goals.
Nanofluid flow over three different geometries under viscous dissipation and thermal radiation using the local linearization method
Authors: Shaw Sachin , Motsa Sandile S. , Sibanda Precious
Published: July 2019

This study deals with the transfer of mass and heat of nanofluid flow over three different geometries of the non‐Darcy permeable vertical cone/wedge/vertical plate. Influence of the Brownian motion and thermophoresis takes place due to the nanofluid. Boundary condition on the temperature is introduced at the surface where the thermal conductivity of the fluid obeys a linear relation with the temperature. The local linearization method is introduced for solving the governing equations, and is based on spectral discretization. To verify the numerical scheme, we compared our results with those in the existing literature. The impact of the governing parameters on the fluid velocity, temperature distribution, and concentration distribution of nanoparticles along with the Nusselt number and Sherwood number is discussed. Some important outcomes of the present study are that the Nusselt number is higher for the plane plate than that for the vertical cone and it significantly decreases with introduction of the radiation parameter. The nanofluid Lewis number decreases the diffusivity of mass of the nanofluid, and as a result it helps enhance the Sherwood number.
Free convective MHD micropolar fluid flow with thermal radiation and radiation absorption: A numerical study
Authors: Pradhan S. R. , Baag S. , Mishra S. R. , Acharya M. R.
Published: July 2019

An analysis is carried out for the free convective flow of an electrically conducting micropolar fluid through permeable stretching sheet in the presence of porous medium. Inclusion of thermal radiation to the energy equation enhances the thermal properties of polar fluid. In addition to that the radiation absorption parameter occurs due to the interaction of solutal concentration difference also considered in the heat transfer equation. Suitable similar transformation is used to convert the governing partial differential equations to ordinary differential equations. Furthermore, though analytical solutions of these complex nonlinear coupled equations are more complicated therefore, numerical solution such as Runge‐Kutta fourth order method associated with shooting technique is adopted. Behavior of characterizing parameters for the flow phenomena are presented via graphs and computed values of physical quantities of interest are obtained and shown in tabular form. Present result validates with that of earlier results in particular case which confirms the existence of present solution methodology. However, the main findings of contributing parameters are laid down as; angular velocity profile contributes a dual character from the point of contact at the middle of the channel. Fluid temperature is affected by the inclusion of absorption coefficient.
Cervical ripening balloon: An off‐label but effective use to manage massive hemorrhage during outpatient cervical conization
Authors: Giannella Luca , D'Ippolito Giovanni
Published: July 2019

A double‐balloon catheter may be very helpful in managing a major hemorrhage following outpatient conization.
P2Y11 receptor antagonist NF340 ameliorates inflammation in human fibroblast‐like synoviocytes: An implication in rheumatoid arthritis
Authors: Gao Feng , Li Xin
Published: July 2019

Rheumatoid arthritis is a common chronic inflammatory joint disease. Fibroblast‐like synoviocytes‐mediated inflammation is closely associated with the development of rheumatoid arthritis. In this study, we report that P2Y11 receptor activity is required for cytokine‐induced inflammation in primary fibroblast‐like synoviocytes (FLS). P2Y11R is fairly expressed in primary FLS isolated from healthy subjects and is elevated to around three‐ to four‐fold in rheumatoid arthritis‐derived FLS. The expression of P2Y11R is inducible upon IL‐1β treatment. Blockage of P2Y11R by its antagonist suppresses IL‐1β‐induced TNF‐α and IL‐6 induction and ameliorates oxidative stress as determined by levels of cellular ROS and the oxidative byproduct 4‐HNE. Moreover, blockage of P2Y11R by NF340 inhibits IL‐1β‐induced matrix metalloproteinase protein expression as indicated by the levels of MMP‐1, MMP‐3, and MMP‐13. Mechanistically, blockage of P2Y11R mitigates IL‐1β‐activated NFκB signaling, which was revealed by reduced IκBα phosphorylation, nuclear p65 accumulation, and NFκB promoter activity. Our study provides evidence of a protective mechanism of P2Y11R antagonist NF340 against cytokine‐induced inflammation. Therefore, targeting P2Y11R could have potential therapeutic implication in the treatment of RA.
Cholinergic and peptidergic neurotransmission in the adrenal medulla: A dynamic control of stimulus‐secretion coupling
Authors: Guérineau Nathalie C.
Published: July 2019

Synaptic neurotransmission at the splanchnic nerve‐chromaffin cell synapse is a chief element of the stimulus‐secretion coupling in the adrenal medullary tissue, managing and regulating the secretion of catecholamines. Making the state of play more intricate than initially envisioned, the synaptic vesicles of nerve terminals innervating the medulla contain various compounds, including various neurotransmitters and neuropeptides. Under basal conditions associated with a low splanchnic nerve discharge rate, neurotransmission is ensured by the synaptic release of the primary neurotransmitter acetylcholine (ACh). Under sustained and repetitive stimulations of the splanchnic nerve, as triggered in response to stressors, the synaptic release of neuropeptides, such as the pituitary adenylate cyclase‐activating polypeptide PACAP, supplants ACh release. The anatomical and functional changes that occur presynaptically at the preganglionic splanchnic nerve, combined with changes occurring postsynaptically at nicotinic acetylcholine receptors (nAChRs), confer the adrenomedullary synapses a solid and persistent aptitude to functional remodeling, from birth to aging. The present review focuses on the composite cholinergic and noncholinergic nature of neurotransmission occurring at the splanchnic nerve‐chromaffin cell synapse and its remodeling in response to physiological or pathological stimuli.
Secreted frizzled‐related protein 4 and its implication in obesity and type‐2 diabetes
Authors: Bukhari Shazia Anwer , Yasmin Aysha , Zahoor Muhammad Asif , Mustafa Ghulam , Sarfraz Iqra , Rasul Azhar
Published: July 2019

Secreted frizzled‐related protein 4 (SFRP4) is a member of secreted protein family with sequence similarity to frizzled receptors of wingless‐related integration site (Wnt) signaling pathways. These proteins control diverse functions from embryonic development to adults in many organisms including humans. Initially, SFRPs were recognized as antagonists of Wnt signaling and supposed to interact with Wnts. Further research demonstrated their interactions to frizzled receptors and a functional diversity was related to these proteins, Wnt signaling potentiation in addition to modulation. SFRP4 is the largest member of SFRP family and is implicated in many diseases including obesity, type 2 diabetes (T2D), and cancer. SFRP4 acts as a biomarker for T2D and was expressed several years before clinical diagnosis of disease. This review mainly focusses on the role of SFRP4 in obesity and how it can lead to β‐cell failure and ultimately to T2D. The role of SFRP4 in adipose tissues causing increased production of adipokines lead to the oxidative stress in pancreas that particularly have low amount of antioxidant enzymes in pancreatic β‐cells leading to failure in exocytosis of insulin containing granules causing T2D. Obesity‐induced inflammation is a principal factor in pathogenesis of insulin resistance as well as metabolic syndrome. Pro‐inflammatory cytokines have potential to cause insulin resistance in skeletal muscles, adipose tissue, and liver via inhibition of insulin signal transduction. Secretion of SFRP4 is mediated by interleukin 1‐β (IL1‐β). This review highlights the molecular mechanisms by which SFRP4 leads to T2D. Understanding of molecular mechanism and targeting SFRP4 could help to eradicate or reduce chances of developing T2D.
Development of Nonbonded Models for Metal Cations Using the Electronic Continuum Correction
Authors: Nikitin Alexei , Del Frate Gianluca
Published: July 2019

The parametrization of classical nonbonded models of metal ions has been widely addressed in the recent years. Despite the continuous development of novel and more physically inspired functional forms, the 12‐6 Lennard‐Jones plus Coulomb potential is still the most adopted force field in molecular dynamics (MD) codes, owing to its simple form and easy implementation. However, due to the integer formal charge, unpolarizable force fields of ions may suffer from overestimated interatomic electrostatic interactions, leading to nonphysical clustering or repulsion between such full charges. The electronic continuum correction (ECC) can fix this problem through a simple inclusion of solvent polarization effects via ionic charge rescaling. In this work, the development of novel nonbonded models for mono, divalent, and highly charged metal ions is presented. For each metal species, the ionic charge has been scaled, according to the ECC. Lennard‐Jones parameters have been optimized using experimental structural and thermodynamic properties as target quantities. Performances of the proposed models are discussed and compared with the literature data, while transferability attitudes among different and well‐known water models are evaluated. © 2019 Wiley Periodicals, Inc.
Ab Initio Ground‐State Potential Energy Function and Vibration‐Rotation Energy Levels of Aluminum Monohydride
Authors: Koput Jacek
Published: July 2019

The accurate ground‐state potential energy function of aluminum monohydride (AlH) has been determined from ab initio calculations using the multireference averaged coupled‐pair functional (MR‐ACPF) method in conjunction with the correlation‐consistent core‐valence basis sets up to septuple‐zeta quality. The vibration‐rotation energy levels of the two isotopologues, AlH and AlD, were predicted to near the “spectroscopic” accuracy. The importance of electron correlation beyond the MR‐ACPF level of approximation, the scalar relativistic, spin‐orbit, adiabatic, and nonadiabatic effects was discussed. © 2019 Wiley Periodicals, Inc.
TacoxDNA: A user‐friendly web server for simulations of complex DNA structures, from single strands to origami
Authors: Suma Antonio , Poppleton Erik , Matthies Michael , Šulc Petr , Romano Flavio , Louis Ard A. , Doye Jonathan P. K. , Micheletti Cristian , Rovigatti Lorenzo
Published: July 2019

Simulations of nucleic acids at different levels of structural details are increasingly used to complement and interpret experiments in different fields, from biophysics to medicine and materials science. However, the various structural models currently available for DNA and RNA and their accompanying suites of computational tools can be very rarely used in a synergistic fashion. The tacoxDNA webserver and standalone software package presented here are a step toward a long‐sought interoperability of nucleic acids models. The webserver offers a simple interface for converting various common input formats of DNA structures and setting up molecular dynamics (MD) simulations. Users can, for instance, design DNA rings with different topologies, such as knots, with and without supercoiling, by simply providing an XYZ coordinate file of the DNA centre‐line. More complex DNA geometries, as designable in the cadnano, CanDo and Tiamat tools, can also be converted to all‐atom or oxDNA representations, which can then be used to run MD simulations. Though the latter are currently geared toward the native and LAMMPS oxDNA representations, the open‐source package is designed to be further expandable. TacoxDNA is available at http://tacoxdna.sissa.it. © 2019 Wiley Periodicals, Inc.
Trans‐philicity (trans‐influence/trans‐effect) ladders for square planar platinum(II) complexes constructed by 35Cl NMR probe
Authors: Tsipis Athanassios C.
Published: July 2019

The unified term of trans‐philicity is proposed to cover the trans‐effect/trans‐influence concepts. NMR trans‐philicity ladders are built for a broad series of square planar trans‐Pt(NH3)2(Cl)L and trans‐Pt(CO)2(Cl)L complexes employing 35Cl NMR probe and quantified by calculation of NMR trans‐philicity indicators. The trans‐philicity is linearly correlated with the ligand electronic PL constant, a measure of the net donor power of the ligand. The nature of cis‐ligands does not affect trans‐philicity ladders but strongly affects trans‐philicity strength. Solvent has significant effect on the σcalcd 35Cl shielding constants, with the polar Dimethylformamide (DMF) solvent inducing downfield shifts relative to σcalcd 35Cl with nonpolar benzene solvent. Good correlations between σcalcd 35Cl shielding constants and the estimated R(Pt‐Cl) bond distances demonstrate the relation of trans‐philicity with trans‐influence and trans‐effect phenomena and put the grounds for the establishment of the new concept of trans‐philicity in the realm of square planar Pt(II) and other transition metal complexes. © 2019 Wiley Periodicals, Inc.
Potential role of circulating long noncoding RNA MALAT1 in predicting disease risk, severity, and patients' survival in sepsis
Authors: Geng Feng , Liu Wei , Yu Li
Published: July 2019

Background

This study aimed to investigate the plasma long noncoding RNA metastasis‐associated lung adenocarcinoma transcript 1 (lncRNA MALAT1) expression with risk, severity, inflammation level, and prognosis in sepsis.

Methods

One hundred and ninety sepsis patients and 190 health controls (HCs) were consecutively recruited. Blood samples within 24 hours after admission of sepsis patients and those on enrollment of HCs were collected, and then, plasma was separated for lncRNA MALAT1 and miR‐125b expressions detections by RT‐qPCR. In sepsis patients, clinical data and 28‐day mortality were recorded, and plasma inflammatory cytokines expressions were detected by ELISA.

Results

Plasma lncRNA MALAT1 expression was elevated in sepsis patients than HCs (P < 0.001), and ROC curve disclosed that it had a good value in predicting sepsis risk with an area under curve (AUC) of 0.823 (95% CI: 0.783‐0.864). Additionally, lncRNA MALAT1 expression was positively correlated with Scr (P = 0.005), WBC (P = 0.017), CRP (P < 0.001), PCT (P < 0.001), TNF‐α (P < 0.001), IL‐8 (P < 0.001), IL‐17 (P = 0.001), APACHE II score (P < 0.001), and SOFA score (P < 0.001). LncRNA MALA1 expression was elevated in deaths compared with survivors (P < 0.001) and could predict the risk of 28‐day mortality with an AUC of 0.755 (95% CI: 0.682‐0.828). Accumulating survival was worse in patients with lncRNA MALAT1 high expression compared with patients who had lncRNA MALAT1 low expression (P < 0.001). Moreover, lncRNA MALAT1 expression was negatively correlated with miR‐125b level in both sepsis patients (P < 0.001) and HCs (P < 0.001).

Conclusion

LncRNA MALAT1 could be developed as a potential biomarker for facilitating diagnosis and management in sepsis patients.
Preactivation of β‐catenin in osteoblasts improves the osteoanabolic effect of PTH in type 1 diabetic mice
Authors: Chen Sixu , Yang Lei , He Sihao , Yang Jiazhi , Liu Daocheng , Bao Quanwei , Qin Hao , Du Wenqiong , Zhong Xin , Chen Can , Zong Zhaowen
Published: July 2019

Type 1 diabetes (T1D) is correlated with osteopenia primarily due to low bone formation. Parathyroid hormone (PTH) is a known anabolic agent for bone, the anabolic effects of which are partially mediated through the Wnt/β‐catenin signaling pathway. In the present study, we first determined the utility of intermittent PTH treatment in a streptozotocin‐induced T1D mouse model. It was shown that the PTH‐induced anabolic effects on bone mass and bone formation were attenuated in T1D mice compared with nondiabetic mice. Further, PTH treatment failed to activate β‐catenin signaling in osteoblasts of T1D mice and was unable to improve osteoblast proliferation and differentiation. Next, the Col1–3.2 kb‐CreERTM; β‐cateninfx(ex3) mice were used to conditionally activate β‐catenin in osteoblasts by injecting tamoxifen, and we addressed whether or not preactivation of β‐catenin boosted the anabolic action of PTH on T1D‐related bone loss. The results demonstrated that pretreatment with activation of osteoblastic β‐catenin followed by PTH treatment outperformed PTH or β‐catenin activation monotherapy and led to greatly improved bone structure, bone mass, and bone strength in this preclinical model of T1DM. Further analysis demonstrated that osteoblast proliferation and differentiation, as well as osteoprogenitors in the marrow, were all improved in the combination treatment group. These findings indicated a clear advantage of developing β‐catenin as a target to improve the efficacy of PTH in the treatment of T1D‐related osteopenia.
Adenosine triphosphate enhances osteoblast differentiation of rat dental pulp stem cells via the PLC–IP3 pathway and intracellular Ca2+ signaling
Authors: Stovall Kelsie E. , Tran Tran D.N. , Suantawee Tanyawan , Yao Shaomian , Gimble Jeffrey M. , Adisakwattana Sirichai , Cheng Henrique
Published: July 2019

Intracellular Ca2+ signals are essential for stem cell function and play a significant role in the differentiation process. Dental pulp stem cells (DPSCs) are a potential source of stem cells; however, the mechanisms controlling cell differentiation remain largely unknown. Utilizing rat DPSCs, we examined the effect of adenosine triphosphate (ATP) on osteoblast differentiation and characterized its mechanism of action using real‐time Ca
2+ imaging analysis. Our results revealed that ATP enhanced osteogenesis as indicated by Ca
2+ deposition in the extracellular matrix via Alizarin Red S staining. This was consistent with upregulation of osteoblast genes BMP2, Mmp13, Col3a1, Ctsk, Flt1, and Bgn. Stimulation of DPSCs with ATP (1–300 µM) increased intracellular Ca
2+ signals in a concentration‐dependent manner, whereas histamine, acetylcholine, arginine vasopressin, carbachol, and stromal‐cell‐derived factor‐1α failed to do so. Depletion of intracellular Ca
2+ stores in the endoplasmic reticulum by thapsigargin abolished the ATP responses which, nevertheless, remained detectable under extracellular Ca
2+ free condition. Furthermore, the phospholipase C (PLC) inhibitor U73122 and the inositol triphosphate (IP
3) receptor inhibitor 2‐aminoethoxydiphenyl borate inhibited the Ca
2+ signals. Our findings provide a better understanding of how ATP controls osteogenesis in DPSCs, which involves a Ca
2+‐dependent mechanism via the PLC‐IP
3 pathway. This knowledge could help improve osteogenic differentiation protocols for tissue regeneration of bone structures.
Umbilical cord‐derived mesenchymal stromal/stem cells expressing IL‐24 induce apoptosis in gliomas
Authors: Fan Shaochen , Gao Huasong , Ji Wei , Zhu Fengwei , Sun Lingzheng , Liu Yuankun , Zhang Siming , Xu Yanran , Yan Yaohua , Gao Yilu
Published: July 2019

Although much progress has been made in the treatment of gliomas, the prognosis for patients with gliomas is still very poor. Stem cell‐based therapies may be promising options for glioma treatment. Recently, many studies have reported that umbilical cord‐derived mesenchymal stromal/stem cells (UC‐MSCs) are ideal gene vehicles for tumor gene therapy. Interleukin 24 (IL‐24) is a pleiotropic immunoregulatory cytokine that has an apoptotic effect on many kinds of tumor cells and can inhibit the growth of tumors specifically without damaging normal cells. In this study, we investigated UC‐MSCs as a vehicle for the targeted delivery of IL‐24 to tumor sites. UC‐MSCs were transduced with lentiviral vectors carrying green fluorescent protein (GFP) or IL‐24 complementary DNA. The results indicated that UC‐MSCs could selectively migrate to glioma cells in vitro and in vivo. Injection of IL‐24‐UC‐MSCs significantly suppressed tumor growth of glioma xenografts. The restrictive efficacy of IL‐24‐UC‐MSCs was associated with the inhibition of proliferation as well as the induction of apoptosis in tumor cells. These findings indicate that UC‐MSC‐based IL‐24 gene therapy may be able to suppress the growth of glioma xenografts, thereby suggesting possible future therapeutic use in the treatment of gliomas.
Asymptomatic ceftriaxone‐associated pseudolithiasis
Authors: Sasaki Osamu , Sugimura Kazunori , Shinoda Masahiro , Shinkai Masaharu
Published: July 2019

An 88‐year‐old woman with a history of meningioma and dementia was admitted with high fever, loss of appetite, and nausea in July. Urinary tract infection was suspected. Computed tomography (CT) showed no significant findings. Urinary findings improved with administration of ceftriaxone. However, high fever appeared on hospital day 28, and CT identified a gallbladder stone without any abdominal symptoms. We considered the possibility of ceftriaxone‐associated pseudolithiasis and changed pharmacotherapy to cefmetazole. CT on day 34 showed a reduction in the size of the gallbladder stone. Ceftriaxone‐associated pseudolithiasis might arise in the absence of abdominal symptoms, and clinicians should take the patient background and season into account when using this agent.
Long non‐coding RNAs (CASC2 and TUG1) in hepatocellular carcinoma: Clinical significance
Authors: Refai Noha S. , Louka Manal L. , Halim Hany Y. , Montasser Iman
Published: July 2019

Background

The biology of hepatocellular carcinoma remains poorly understood. Long non‐coding RNAs (lncRNAs) have been confirmed to be key regulators of most cell processes and cancer. The lncRNA cancer susceptibility candidate 2 (CASC2) was originally identified as a downregulated gene in endometrial cancer and acted as a tumor suppressor. The lncRNA taurine up‐regulated gene 1 (TUG1) has been shown to play an oncogenic role in various cancers. However, the relative expression of CASC2 and TUG1 in hepatocellular carcinoma (HCC) on top of hepatitis C virus (HCV) and the relationship between both remains unclear. The present study aimed to evaluate both lncRNA CASC2 and TUG1 relative gene expression in whole blood of HCC/HCV patients in relation to HCV and healthy subjects and to relate them to each other and to different clinicopathological factors.

Methods

The relative expression of CASC2 and TUG1 was estimated by a quantitative reverse transcriptase‐polymerase chain reaction in 30 HCC/HCV patients and compared with 20 cases of HCV patients and 20 controls.

Results

CASC2 was downregulated in HCC/HCV patients, whereas TUG1 was overexpressed in relation to HCV and the control group, indicating their antagonistic effect. This suggests their role in the pathogenesis of HCC on top of HCV. Their expression was correlated to Barcelona Clinic Liver Cancer stage and serum alpha‐fetoprotein level.

Conclusions

CASC2 and TUG1 could be new potential biomarkers with a valid non‐invasive technique.
Morphological bases for intestinal paracellular absorption in bats and rodents
Authors: Brun Antonio , Fernández Marinone Guido , Price Edwin R. , Nell Lucas A. , Simões Beatriz M. V. , Castellar Alexandre , Gontero‐Fourcade Manuel , Cruz‐Neto Ariovaldo P. , Karasov William H. , Caviedes‐Vidal Enrique
Published: July 2019

Flying mammals present unique intestinal adaptations, such as lower intestinal surface area than nonflying mammals, and they compensate for this with higher paracellular absorption of glucose. There is no consensus about the mechanistic bases for this physiological phenomenon. The surface area of the small intestine is a key determinant of the absorptive capacity by both the transcellular and the paracellular pathways; thus, information about intestinal surface area and micro‐anatomical structure can help explain differences among species in absorptive capacity. In order to elucidate a possible mechanism for the high paracellular nutrient absorption in bats, we performed a comparative analysis of intestinal villi architecture and enterocyte size and number in microchiropterans and rodents. We collected data from intestines of six bat species and five rodent species using hematoxylin and eosin staining and histological measurements. For the analysis we added measurements from published studies employing similar methodology, making in total a comparison of nine species each of rodents and bats. Bats presented shorter intestines than rodents. After correction for body size differences, bats had ~41% less nominal surface area (NSA) than rodents. Villous enhancement of surface area (SEF) was ~64% greater in bats than in rodents, mainly because of longer villi and a greater density of villi in bat intestines. Both taxa exhibited similar enterocyte diameter. Bats exceeded rodents by ~103% in enterocyte density per cm2 NSA, but they do not significantly differ in total number of enterocytes per whole animal. In addition, there is a correlation between SEF and clearance per cm2 NSA of L‐arabinose, a nonactively transported paracellular probe. We infer that an increased enterocyte density per cm2 NSA corresponds to increased density of tight junctions per cm2 NSA, which provides a partial mechanistic explanation for understanding the high paracellular absorption observed in bats compared to nonflying mammals.
Automated deep learning method for whole‐breast segmentation in diffusion‐weighted breast MRI
Authors: Zhang Lei , Mohamed Aly A. , Chai Ruimei , Guo Yuan , Zheng Bingjie , Wu Shandong
Published: July 2019

Background

Diffusion‐weighted imaging (DWI) in MRI plays an increasingly important role in diagnostic applications and developing imaging biomarkers. Automated whole‐breast segmentation is an important yet challenging step for quantitative breast imaging analysis. While methods have been developed on dynamic contrast‐enhanced (DCE) MRI, automatic whole‐breast segmentation in breast DWI MRI is still underdeveloped.

Purpose

To develop a deep/transfer learning‐based segmentation approach for DWI MRI scans and conduct an extensive study assessment on four imaging datasets from both internal and external sources.

Study Type

Retrospective.

Subjects

In all, 98 patients (144 MRI scans; 11,035 slices) of four different breast MRI datasets from two different institutions.

Field Strength/Sequences

1.5T scanners with DCE sequence (Dataset 1 and Dataset 2) and DWI sequence. A 3.0T scanner with one external DWI sequence.

Assessment

Deep learning models (UNet and SegNet) and transfer learning were used as segmentation approaches. The main DCE Dataset (4,251 2D slices from 39 patients) was used for pre‐training and internal validation, and an unseen DCE Dataset (431 2D slices from 20 patients) was used as an independent test dataset for evaluating the pre‐trained DCE models. The main DWI Dataset (6,343 2D slices from 75 MRI scans of 29 patients) was used for transfer learning and internal validation, and an unseen DWI Dataset (10 2D slices from 10 patients) was used for independent evaluation to the fine‐tuned models for DWI segmentation. Manual segmentations by three radiologists (>10‐year experience) were used to establish the ground truth for assessment. The segmentation performance was measured using the Dice Coefficient (DC) for the agreement between manual expert radiologist's segmentation and algorithm‐generated segmentation.

Statistical Tests

The mean value and standard deviation of the DCs were calculated to compare segmentation results from different deep learning models.

Results

For the segmentation on the DCE MRI, the average DC of the UNet was 0.92 (cross‐validation on the main DCE dataset) and 0.87 (external evaluation on the unseen DCE dataset), both higher than the performance of the SegNet. When segmenting the DWI images by the fine‐tuned models, the average DC of the UNet was 0.85 (cross‐validation on the main DWI dataset) and 0.72 (external evaluation on the unseen DWI dataset), both outperforming the SegNet on the same datasets.

Data Conclusion

The internal and independent tests show that the deep/transfer learning models can achieve promising segmentation effects validated on DWI data from different institutions and scanner types. Our proposed approach may provide an automated toolkit to help computer‐aided quantitative analyses of breast DWI images.

Level of Evidence: 3

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2020;51:635–643.