bluuebunny/crossref_metadata_2025 huggingface dataset:
Barriers in Neurogastroenterology and Motility Training Experience for Pediatric Gastroenterology Fellows
Authors: Graham Kahleb , Belkind‐Gerson Jaime , Darbari Anil , Boyle John T.
Published: January 2019

Background:

Neurogastroenterology and motility (NGM) disorders are common and have a high health care burden. Although pediatric gastroenterology fellows are expected to obtain comprehensive training in the diagnosis and management of NGM disorders, there is ongoing concern for unmet training needs and lack of exposure in treating patients who suffer from NGM problems.

Methods:

We conducted a cross‐section survey of trainees listed as pediatric gastroenterology fellows in North American training programs in 2018 via direct E‐mail and the pediatric gastroenterology listserv. Eighty‐one pediatric gastroenterology fellows responded to the anonymous survey.

Results:

A total of 53.1% of the fellows reported interest in NGM; however, 75.1% of the fellows believed they had not been adequately trained in NGM during their fellowship. Eighty percent of fellows with 2 weeks or less of dedicated motility training reported that they received inadequate NGM training, compared to 46.2% fellows who received 1 or more months of dedicated motility training (P = 0.0148). The majority of fellows reported not being comfortable in performing gastrointestinal (GI) motility studies. The majority of fellows also reported not being comfortable in interpreting GI motility studies.

Conclusions:

Although most pediatric gastroenterology fellows expressed interest in NGM, the lack of exposure and dedicated training in motility during fellowship were identified as barriers to pursuing motility‐focused careers. Furthermore, most fellows reported limited comfort with performing and/or interpreting motility studies. Changes are needed to encourage fellows to develop their interest and expertise in NGM.
Psychotherapy With Suicidal Patients Part 2: An Alliance Based Intervention for Suicide
Authors: PLAKUN ERIC M.
Published: January 2019

This column, which is the second in a 2-part series on the challenge of treating patients struggling with suicide, reviews one psychodynamic approach to working with suicidal patients that is consistent with the elements shared across evidence-based approaches to treating suicidal patients that were the focus of the first column in this series. Alliance Based Intervention for Suicide is an approach to treating suicidal patients developed at the Austen Riggs Center that is not manualized or a stand-alone treatment, but rather it is a way of establishing and maintaining an alliance with suicidal patients that engages the issue of suicide and allows the rest of psychodynamic therapy to unfold.
Therapeutic Risk Management: Chain Analysis of Suicidal Ideation and Behavior
Authors: BORGES LAUREN M. , NAZEM SARRA , MATARAZZO BRIDGET B. , BARNES SEAN M. , WORTZEL HAL S.
Published: January 2019

Structural approaches to suicide risk assessment (eg, evaluating the frequency and intensity of suicidal ideation and classifying types of suicidal behavior) often fall short of providing an idiographic and dynamic analysis of the factors driving and maintaining an individual’s suicide risk. Structural approaches can be bolstered through chain analysis which facilitates an exploration of the factors maintaining suicidal ideation and behavior based on positive and negative reinforcement. By uncovering the factors causing suicidal ideation and behavior to persist, efficient intervention strategies can be selected to target these pathways. In this column, the authors delineate the use of chain analysis to guide suicide risk assessment and inform treatment planning.
From “Coordinated” to “Integrated” Residency Training: Evaluating Changes and the Current State of Plastic Surgery Programs
Authors: Rifkin William J. , Cammarata Michael J. , Kantar Rami S. , DeMitchell-Rodriguez Evellyn , Navarro Carla M. , Diaz-Siso J. Rodrigo , Ceradini Daniel J. , Stranix John T. , Saadeh Pierre B.
Published: January 2019

Background:

Since the inception of the integrated model, educational leaders have predicted its ongoing evolution, as the optimal plastic surgery curriculum remains a source of debate. With the now complete elimination of the “coordinated” pathway, the total number of integrated programs has arguably reached a plateau. Accordingly, this study examines the current state of training in integrated residencies and reevaluates the variability in the first 3 years of training observed previously.

Methods:

Program information was obtained for all 68 integrated plastic surgery programs, and rotation schedules were available for 59. Plastic, general, and subspecialty surgery exposures were quantified and compared. Inclusion of rotations “strongly suggested” by the Residency Review Committee was also examined.

Results:

Plastic surgery exposure ranged from 3.5 to 25 months (mean, 13.9 ± 5.4 months). General surgery ranged from 5 to 22.5 months (mean, 12.8 ± 4.7 months). Subspecialty rotations ranged from 0 to 8 months (mean, 3.6 ± 1.8 months). There was no difference in mean plastic surgery exposure between programs based within departments versus divisions (15.4 months versus 13.3 months; p = 0.184). There remained significant variability in the inclusion of 18 non–plastic surgery rotations, including the “strongly suggested” rotations.

Conclusions:

Plastic surgery exposure remains highly variable with a greater than 7-fold difference between programs. This suggests that programs are still sorting out the ideal curriculum. However, there is an overall trend toward earlier and increased plastic surgery exposure, which now exceeds the average time spent on general surgery rotations.
A Flow Dynamic Rationale for Accelerated Vascularized Composite Allotransplant Rejection
Authors: Robbins Nicholas L. , Wordsworth Matthew J. , Parida Bijaya K. , Kaplan Bruce , Gorantla Vijay S. , Weitzel Col Erik K. , Breidenbach Warren C.
Published: January 2019

Background:

From 1996 to 2000, Diefenbeck et al. carried out six knee vascularized composite allotransplants. The allotransplants were composed of bone, soft tissue, and femoral vascular pedicle (25 to 40 cm). All rejected between 14 and 56 months. Failures were attributed to chronic rejection. In 2008, the Louisville team lost their fourth patient’s hand transplant at 8 months. During the rejection workup, intraoperative findings noted a thickened arterial pedicle attributed to intimal hyperplasia with significant fibrotic perivascular tissue and a near “no-flow phenomenon.” No cutaneous rejection was appreciated and failure was attributed to chronic rejection.

Methods:

Data were collected from two teams, one in Germany and the other in Louisville, Kentucky. The population under study consisted of the six knee and one hand transplants. The factor of interest was the long donor arterial pedicle. The outcome measurements were transplant survival time and histopathologic results.

Results:

There are only seven published vascularized composite allotransplant cases where a donor artery longer than 25 cm was used. This cohort represents a 100 percent accelerated failure rate. The cause of these losses remains unexplained. The donor arteries suffered from T-cell–mediated rejection and ischemia-induced media/adventitial necrosis.

Conclusions:

We hypothesize that the donor artery rejected at an accelerated rate because of ischemia caused by disruption of the external vasa vasorum in conjunction with intimal hyperplasia induced by T-cell–mediated rejection that led to disruption of the Windkessel effect. Loss of this effect presented as intimal hyperplasia accelerated by ischemia causing an expedited transplant failure.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, V.
Review of the Use of Stainless Wires in Craniosynostosis Surgery
Authors: Natghian Hamidreza , Song Marie , Wall Steven , Johnson David
Published: January 2019

Background:

Controversy exists as to the ideal form of bone fixation in craniosynostosis surgery with the use of resorbable plates predominating in most craniofacial units. However, the use of stainless steel wires has been the preferred fixation method at the Oxford Craniofacial Unit (OCU) since its establishment. Wires have the advantage of being malleable, inexpensive, and quick and easy to use.

Methods:

A retrospective review of all patients who underwent craniosynostosis surgery at the OCU between February 1995 and February 2017 was undertaken. Average follow-up period was 141 months (11.7 years), with a minimum of 6 months.

Results:

A total number of 1226 craniosynostosis procedures were performed. A minimum of 16,160 wires were inserted. No complications were identified resulting from transdural migration of wires. One hundred fifty-six wires were removed in 92 patients during 109 general anesthetic day-care procedures. This was due to discomfort on palpation in the majority of cases. The average time from primary surgery to removal of wires was 37 months (3.1 years). The most common site for wire removal was in the supraorbital and lateral forehead regions, and occurred most frequently in children who had undergone fronto-orbital advancement and remodeling.

Conclusion:

The use of wires in craniofacial surgery is safe. One percent of all wires that were inserted had to be removed. Children undergoing primary craniosynostosis surgery have a 9% chance of needing a subsequent day-care procedure to have a wire removed. Taking into account the cost of this additional surgical procedure, the primary use of wires in craniosynostosis surgery is still significantly cheaper than the use of resorbable plates.
Efficacy of Single-incision Laparoscopic Totally Extraperitoneal Inguinal Hernia Repair for Overweight or Obese Patients
Authors: Wakasugi Masaki , Nakahara Yujiro , Hirota Masaki , Matsumoto Takashi , Kusu Takashi , Takemoto Hiroyoshi , Takachi Ko , Oshima Satoshi
Published: January 2019

Aim:

To evaluate the efficacy of single-incision laparoscopic surgery for totally extraperitoneal repair in overweight or obese patients.

Materials and Methods:

For outcome analyses, patients were subdivided by body mass index (BMI) as normal-weight (18.5≤BMI<25 kg/m2), overweight (25≤BMI<30 kg/m2) or obese (≥30 kg/m2) and compared.

Results:

In total, 201 patients were divided into a normal-weight group (n=152) and an overweight/obese group (n=49). Median operative time for unilateral hernia was 72 minutes in the normal-weight group and 95 minutes in the overweight/obese group (P<0.05). No significant differences in operative time for bilateral hernia, bleeding volume, peritoneal injury, conversion to a different procedure, postoperative hospital stay, follow-up duration, complications, or recurrence were identified.

Conclusions:

Single-incision laparoscopic surgery for totally extraperitoneal repair, which offers good cosmetic outcomes, seems feasible and safe for overweight or obese patients, although the operation takes longer.
Laparoscopy Versus Open Incarcerated Inguinal Hernia Repair in Octogenarians: Single-Center Experience With World Review
Authors: Payiziwula Jiangduosi , Zhao Pei-Ji , Aierken Amina , Yao Gang , Apaer Shadike , Li Tao , Tuxun Tuerhongjiang
Published: January 2019

Objectives:

The clinical study is aiming to discuss the therapeutic benefit of laparoscopic hernia (LH) repair with comparing conventional open hernia (OH) repair in incarcerated hernia in octogenarians.

Materials and Methods:

The clinical data of 29 octogenarian incarcerated hernia patients who underwent hernia repair from November 2013 to March 2017 were retrospectively analyzed. The variables analyzed include baseline, operation characteristics, and clinical outcomes. The patients were divided into LH and OH according to the surgical approach and their clinical parameters were compared. Descriptive statistics were calculated, and outcomes were compared using the Fisher exact test and the student t test, a P≤0.05 was considered significant.

Results:

Of reported 18 octogenarian patients, 7 patients underwent LH, whereas the remaining 11 patients underwent OH. The median age of the patients was 86 (81 to 97). All patients in LH group and 3 patients in OH group underwent nonmesh repair. In total, 8 patients in OH group underwent mesh repair. Simultaneous intestinal resection was needed in 4 patients (2 in LH, 2 in OH) due to the necrotic bowel. No mortality was observed in all subjects. The results showed significantly shorter operation time (50±5 vs. 110±3 min; P=0.000), hospital stay (6±1 vs. 12±3 d; P=0.04). There were no noteworthy postoperative complications and during the follow-up period, no patient experienced recurrent hernia in both groups.

Conclusions:

LH nonmesh repair has not increased the morbidity and mortality but showed shorter hospital stay and fast recovery and no recurrence in octogenarian incarcerated hernia patients. Therefore, LH in octogenarian incarcerated hernia patients might be preferred approach in sophisticated hands with acceptable outcomes.
White matter regions with low microstructure in young adults are associated with white matter hyperintensities in late life
Authors: Lao Patrick J. , Vorburger Robert S. , Narkhede Atul , Gazes Yunglin , Igwe Kay C. , Guzman Vanessa A. , Last Briana , Habeck Christian , Stern Yaakov , Brickman Adam M.
Published: January 2019

Background

White matter hyperintensities (WMH) are areas of increased signal observed on T2-weighted magnetic resonance imaging (MRI) that reflect macrostructural white matter damage frequently observed in aging. The extent to which diminished microstructure precedes or results from white matter damage is unknown. The aim of this study was to evaluate the hypothesis that white matter areas that show normatively lower microstructure are most susceptible to develop WMH.

Methods

Five hundred fifty-seven older adults (age: 73.9±5.7yrs) underwent diffusion weighted imaging (DWI) and T2-weighted magnetic resonance imaging (MRI). Diffusion weighted imaging scans were processed into parametric maps of fractional anisotropy (FA) and T2-weighted MRI scans were segmented into WMH. All images were spatially normalized to standard space. A FA template was created to represent normative values from a separate, independent sample of young, healthy adults (N=49, age: 25.8±2.8yrs) and a WMH frequency template was created from the segmented WMH in the older adults. We compared FA values between areas defined as WMH with those defined as normal appearing white matter (NAWM) in the older participants. White matter hyperintensity frequency was binned (0-5%, 5-10%, 10-15%, 15-20%, >20%) and we determined whether WMH frequency bins were different by normative FA values defined in the younger group.

Results

Fractional anisotropy values were lower (p<0.001) in WMH regions compared with NAWM regions in the older sample. Areas with higher WMH frequency in older adults had lower FA values in younger adults (5-10%>10-15%>15-20%; p<0.001).

Discussion

Low FA values are observed in frank WMH, but FA is also normatively low in regions with high WMH frequency prior to damage. Regions with normatively lower microstructure are more susceptible to future damage from factors such as chronic hypoperfusion or pathology.
Induction of the HIF pathway: Differential regulation by chemical hypoxia and oxygen glucose deprivation
Authors: Novak Alicia E. , Jones Susan M. , Elliott J. Paul
Published: January 2019

The Hypoxia Inducible Factor (HIF) proteins are the master regulators in the cellular response to varying oxygen levels, including hypoxia. The HIF complex is stabilized and accumulates when oxygen levels drop through inhibition of a degradative enzyme. An active HIF complex can act as a transcriptional regulator of hundreds of genes. In turn, these genes determine the response of the cell by inducing pathways which can promote survival, or result in cell death. However, little is known about the regulation of the transcriptional process. We were interested in learning more about the time dependence of transcriptional activation in order to target those pathways which could enhance cell survival after ischemia. Using mouse hippocampal organotypic cultures (HOTCs), we compared oxygen-glucose deprivation with the hypoxia mimetic cobalt, which inhibits the oxygen dependent prolyl hydroylase and blocks degradation of the HIF proteins. We demonstrated that two of the most studied HIF target genes (VEGF, EPO) as well as HIF structural genes show complex time and dose-dependent expression patterns in response to the two different insults. Understanding of these molecular responses is crucial for the development of future treatments to enhance recovery from hypoxia and stroke.
Microbial networks in SPRING - Semi-parametric rank-based correlation and partial correlation estimation for quantitative microbiome data
Authors: Yoon Grace , Gaynanova Irina , Müller Christian L.
Published: January 2019

High-throughput microbial sequencing techniques, such as targeted amplicon-based and metagenomic profiling, provide low-cost genomic survey data of microbial communities in their natural environment, ranging from marine ecosystems to host-associated habitats. While standard microbiome profiling data can provide sparserelativeabundances of operational taxonomic units or genes, recent advances in experimental protocols give a more quantitative picture of microbial communities by pairing sequencing-based techniques with orthogonal measurements of microbial cell counts from the same sample. These tandem measurements provide absolute microbial count data albeit with a large excess of zeros due to limited sequencing depth. In this contribution we consider the fundamental statistical problem of estimating correlations and partial correlations from such quantitative microbiome data. To this end, we propose a semi-parametric rank-based approach to correlation estimation that can naturally deal with the excess zeros in the data. Combining this estimator with sparse graphical modeling techniques leads to theSemi-ParametricRank-based approach forINference inGraphical model (SPRING). SPRING enables inference of statistical microbial association networks from quantitative microbiome data which can serve as high-level statistical summary of the underlying microbial ecosystem and can provide testable hypotheses for functional species-species interactions. Due to the absence of verified microbial associations we also introduce a novel quantitative microbiome data generation mechanism which mimics empirical marginal distributions of measured count data while simultaneously allowing user-specified dependencies among the variables. SPRING shows superior network recovery performance on a wide range of realistic benchmark problems with varying network topologies and is robust to misspecifications of the total cell count estimate. To highlight SPRING’s broad applicability we infer taxon-taxon associations from the American Gut Project data and genus-genus associations from a recent quantitative gut microbiome dataset. We believe that, as quantitative microbiome profiling data will become increasingly available, the semi-parametric estimators for correlation and partial correlation estimation introduced here provide an important tool for reliable statistical analysis of quantitative microbiome data.
MaXLinker: proteome-wide cross-link identifications with high specificity and sensitivity
Authors: Yugandhar Kumar , Wang Ting-Yi , Leung Alden King-Yung , Lanz Michael Charles , Motorykin Ievgen , Liang Jin , Shayhidin Elnur Elyar , Smolka Marcus Bustamante , Zhang Sheng , Yu Haiyuan
Published: January 2019

Protein-protein interactions play a vital role in nearly all cellular functions. Hence, understanding their interaction patterns and three-dimensional structural conformations can provide crucial insights about various biological processes and underlying molecular mechanisms for many disease phenotypes. Cross-linking mass spectrometry has the unique capability to detect protein-protein interactions at a large scale along with spatial constraints between interaction partners. However, the current cross-link search algorithms follow an “MS2-centric” approach and, as a result, suffer from a high rate of mis-identified cross-links (~15%). We address this urgent problem, by designing a novel “MS3-centric” approach for cross-link identification and implemented it as a search engine called MaXLinker. MaXLinker significantly outperforms the current state of the art search engine with up to 18-fold lower false positive rate. Additionally, MaXLinker results in up to 31% more cross-links, demonstrating its superior sensitivity and specificity. Moreover, we performed proteome-wide cross-linking mass spectrometry using K562 cells. Employing MaXLinker, we unveiled the most comprehensive set of 9,319 unique cross-links at 1% false discovery rate, comprising 8,051 intraprotein and 1,268 interprotein cross-links. Finally, we experimentally validated the quality of a large number of novel interactions identified in our study, providing a conclusive evidence for MaXLinker’s robust performance.
Posttraumatic Stress Disorder and the Social Brain: Affect-Related Disruption of the Default and Mirror Networks
Authors: Tan Kevin M. , Burklund Lisa J. , Craske Michelle G. , Lieberman Matthew D.
Published: January 2019

Background

Social impairments, specifically in mentalizing and emotion recognition, are common and debilitating symptoms of posttraumatic stress disorder (PTSD). Despite this, little is known about the neural underpinnings of these impairments, as there have been no published neuroimaging investigations of social inference in PTSD.

Methods

Trauma-exposed veterans with and without PTSD (N = 20 each) performed the Why/How social inference task during functional magnetic resonance imaging (fMRI). The PTSD group had two fMRI sessions, between which they underwent affect labeling training. We probed the primary networks of the “social brain”—the default mode network (DMN) and mirror neuron system (MNS)—by examining neural activity evoked by mentalizing and action identification prompts, which were paired with emotional and non-emotional targets.

Results

Hyperactivation to emotional stimuli differentiated PTSD patients from controls, correlated with symptom severity, and predicted training outcomes. Critically, these effects were generally non-significant for non-emotional stimuli. PTSD-related effects were widely distributed throughout DMN and MNS. Effects were strongest in regions associated with the dorsal attention, ventral attention, and frontoparietal control networks. Unexpectedly, effects were non-significant in core affect regions.

Conclusions

The array of social cognitive processes subserved by DMN and MNS may be inordinately selective for emotional stimuli in PTSD. This selectivity may be tightly linked with attentional processes, as effects were strongest in attention-related regions. Putatively, we propose an attentional account of social inference dysfunction in PTSD, in which affective attentional biases drive widespread affect-selectivity throughout the social brain. This account aligns with numerous findings of affect-biased attentional processing in PTSD.
Can grid cell ensembles represent multiple spaces?
Authors: Spalla Davide , Dubreuil Alexis , Rosay Sophie , Monasson Remi , Treves Alessandro
Published: January 2019

The way grid cells represent space in the rodent brain has been a striking discovery, with theoret-ical implications still unclear. Differently from hippocampal place cells, which are known to encode multiple, environment-dependent spatial maps, grid cells have been widely believed to encode space through a single low dimensional manifold, in which coactivity relations between different neurons are preserved when the environment is changed. Does it have to be so? Here, we compute - using two alternative mathematical models - the storage capacity of a population of grid-like units, em-bedded in a continuous attractor neural network, for multiple spatial maps. We show that distinct representations of multiple environments can coexist, as existing models for grid cells have the po-tential to express several sets of hexagonal grid patterns, challenging the view of a universal grid map. This suggests that a population of grid cells can encode multiple non-congruent metric rela-tionships, a feature that could in principle allow a grid-like code to represent environments with a variety of different geometries and possibly conceptual and cognitive spaces, which may be expected to entail such context-dependent metric relationships.
Characterization of a thaumarchaeal symbiont that drives incomplete nitrification in the tropical spongeIanthella basta
Authors: Moeller Florian U. , Webster Nicole S. , Herbold Craig W. , Behnam Faris , Domman Daryl , Albertsen Mads , Mooshammer Maria , Markert Stephanie , Turaev Dmitrij , Becher Dörte , Rattei Thomas , Schweder Thomas , Richter Andreas , Watzka Margarete , Nielsen Per Halkjaer , Wagner Michael
Published: January 2019

Marine sponges represent one of the few eukaryotic groups that frequently harbor symbiotic members of theThaumarchaeota, which are important chemoautotrophic ammonia-oxidizers in many environments. However, in most studies, direct demonstration of ammonia-oxidation by these archaea within sponges is lacking, and little is known about sponge-specific adaptations of ammonia-oxidizing archaea (AOA). Here, we characterized the thaumarchaeal symbiont of the marine spongeIanthella bastausing metaproteogenomics, fluorescencein situhybridization, qPCR and isotope-based functional assays. “CandidatusNitrosospongia bastadiensis” is only distantly related to cultured AOA. It is an abundant symbiont that is solely responsible for nitrite formation from ammonia inI. bastathat surprisingly does not harbor nitrite-oxidizing microbes. Furthermore, this AOA is equipped with an expanded set of extracellular subtilisin-like proteases, a metalloprotease unique among archaea, as well as a putative branched-chain amino acid ABC transporter. This repertoire is strongly indicative of a mixotrophic lifestyle and is (with slight variations) also found in other sponge-associated, but not in free-living AOA. We predict that this feature as well as an expanded and unique set of secreted serpins (protease inhibitors), a unique array of eukaryotic-like proteins, and a DNA-phosporothioation system, represent important adaptations of AOA to life within these ancient filter-feeding animals.

Originality-Significance Statement

Many marine sponges harbor symbiotic members of theThaumarchaeota, but there is generally only indirect evidence available about their functional role within these filter-feeding animals. Furthermore, the specific adaptations of thaumarchaeal symbionts to their sponge hosts are incompletely understood. In this study, we thoroughly characterized a thaumarchaeal symbiont residing in the reef spongeIanthella bastaand demonstrate by using a combination of molecular tools and isotope techniques, that it is the only ammonia-oxidizer in its host. In contrast to other sponges,I. bastadoes not contain nitrite-oxidizing microbes and thus excretes considerable amounts of nitrite. Furthermore, using metagenomics and metaproteomics we reveal important adaptations of this symbiont, that represents a new genus within theThaumarchaeota, and conclude that it most likely lives as a mixotroph in its sponge host.
What do I do now? Intolerance of uncertainty is associated with discrete patterns of anticipatory physiological responding to different uncertain contexts
Authors: Morriss Jayne
Published: January 2019

Heightened physiological responses to uncertainty are a common hallmark of anxiety disorders. Many separate studies have examined the relationship between individual differences in intolerance of uncertainty (IU) and physiological responses to uncertainty during different contexts. Despite this, little is known about the extent to which physiological responses during different uncertain contexts covary within individuals based on IU. Anticipatory physiological responses to uncertainty were assessed in three different contexts (associative threat learning, basic threat uncertainty, decision-making) within the same sample (n = 45). During these tasks, behavioural responses (i.e. reaction times, choices), skin conductance and corrugator supercilli activity were recorded. In addition, self-reported IU and trait anxiety were measured. IU made different contributions to the physiological measures during each task. IU was found to modulate both skin conductance and corrugator supercilii activity for the associative threat learning and decision-making contexts. However, trait anxiety was found to modulate corrugator supercilii activity during the basic threat uncertainty context. Ultimately, this research helps us further tease apart the role of IU in different uncertain contexts, which will be relevant for future IU-related models of psychopathology.
Rapid Reconfiguration of the Functional Connectome after Chemogenetic Locus Coeruleus Activation
Authors: Zerbi Valerio , Floriou-Servou Amalia , Markicevic Marija , Vermeiren Yannick , Sturman Oliver , Privitera Mattia , von Ziegler Lukas , Ferrari Kim David , Weber Bruno , De Deyn Peter Paul , Wenderoth Nici , Bohacek Johannes
Published: January 2019

The locus coeruleus (LC) supplies norepinephrine (NE) to the entire forebrain, regulates many fundamental brain functions, and is implicated in several neuropsychiatric diseases. Although selective manipulation of the LC is not possible in humans, studies have suggested that strong LC activation might shift network connectivity to favor salience processing. To test this hypothesis, we use a mouse model to study the impact of LC stimulation on large-scale functional connectivity by combining chemogenetic activation of the LC with resting-state fMRI, an approach we term “chemo-connectomics”. LC activation rapidly interrupts ongoing behavior and strongly increases brain-wide connectivity, with the most profound effects in the salience and amygdala networks. We reveal a direct correlation between functional connectivity changes and transcript levels of alpha-1, alpha-2, and beta-1 adrenoceptors across the brain, and a positive correlation between NE turnover and functional connectivity within select brain regions. These results represent the first brain-wide functional connectivity mapping in response to LC activation, and demonstrate a causal link between receptor expression, brain states and functionally connected large-scale networks at rest. We propose that these changes in large-scale network connectivity are critical for optimizing neural processing in the context of increased vigilance and threat detection.
Maternal age alters offspring lifespan, fitness, and lifespan extension under caloric restriction
Authors: Bock Martha J. , Jarvis George C. , Corey Emily L. , Stone Emily E. , Gribble Kristin E.
Published: January 2019

Maternal age has a negative effect on offspring lifespan in a range of taxa and is hypothesized to influence the evolution of aging. However, the mechanisms of maternal age effects are unknown, and it remains unclear if maternal age alters offspring response to therapeutic interventions to aging. Here, we evaluate maternal age effects on offspring lifespan, reproduction, and the response to caloric restriction, and investigate maternal investment as a source of maternal age effects using the rotifer,Brachionus manjavacas, an aquatic invertebrate. We found that offspring lifespan and fecundity decline with increasing maternal age. Caloric restriction increases lifespan in all offspring, but the magnitude of lifespan extension is greater in the offspring from older mothers. The trade-off between reproduction and lifespan extension under low food conditions expected by life history theory is observed in young-mother offspring, but not in old-mother offspring. Age-related changes in maternal resource allocation to reproduction do not drive changes in offspring fitness or plasticity under caloric restriction inB. manjavacas. Our results suggest that the declines in reproduction in old-mother offspring negate the evolutionary fitness benefits of lifespan extension under caloric restriction.
Anhedonia following mild traumatic brain injury in rats: A behavioral economic analysis of positive and negative reinforcement
Authors: Avcu Pelin , Fortress Ashley M. , Fragale Jennifer E. , Spiegler Kevin M. , Pang Kevin C.H.
Published: January 2019

Psychiatric disorders affect nearly 50% of individuals who have experienced a traumatic brain injury (TBI). Anhedonia is a major symptom of numerous psychiatric disorders and is a diagnostic criterion for depression. Recently, anhedonia has been divided into consummatory, motivational and decisional components, all of which may be affected differently in disease. Although anhedonia is typically assessed using positive reinforcement, the importance of stress in psychopathology suggests the study of negative reinforcement (removal or avoidance of aversive events) may be equally important. The present study investigated positive and negative reinforcement following a rat model of mild TBI (mTBI) using lateral fluid percussion. Hedonic value of and motivation for reinforcement was determined by behavioral economic analyses. Following mTBI, the hedonic value of avoiding foot shock was reduced. In contrast, the hedonic value of escaping foot shock or obtaining a sucrose pellet was not altered by mTBI. Moreover, neither motivation to avoid or escape foot shock nor motivation to acquire sucrose was modified by mTBI. Our results suggest that individuals experiencing mTBI may experience more stress because of poor proactive control of stress resulting from reduced hedonic value of avoiding aversive events.
Subcortical Anatomy of the Default Mode Network: a functional and structural connectivity study
Authors: Alves Pedro Nascimento , Foulon Chris , Karolis Vyacheslav , Bzdok Danilo , Margulies Daniel S. , Volle Emmanuelle , de Schotten Michel Thiebaut
Published: January 2019

Most existing research into the default-mode network (DMN) has taken a corticocentric approach. Despite the resemblance of the DMN with the unitary model of the limbic system, the anatomy and contribution of subcortical structures to the network may be underappreciated due to methods limitation. Here, we propose a new and more comprehensive neuroanatomical model of the DMN including the basal forebrain and anterior and mediodorsal thalamic nuclei and cholinergic nuclei. This has been achieved by considering functional territories during interindividual brain alignment. Additionally, tractography of diffusion-weighted imaging was employed to explore the structural connectivity of the DMN and revealed that the thalamus and basal forebrain had high importance in term of values of node degree and centrality in the network. The contribution of these neurochemically diverse brain nuclei reconciles previous neuroimaging with neuropathological findings in diseased brain and offers the potential for identifying a conserved homologue of the DMN in other mammalian species.
High-affinity free ubiquitin sensors as quantitative probes of ubiquitin homeostasis and deubiquitination
Authors: Choi Yun-Seok , Bollinger Sarah A. , Prada Luisa F. , Scavone Francesco , Yao Tingting , Cohen Robert E.
Published: January 2019

Ubiquitin (Ub) conjugation is an essential post-translational modification that affects nearly all proteins in eukaryotes. The functions and mechanisms of ubiquitination are areas of extensive and ongoing study, and yet the dynamics and regulation of even free (i.e., unconjugated) Ub are poorly understood. A major impediment has been the lack of simple and robust techniques to quantify Ub levels in cells and to monitor Ub release from conjugates. Here we describe the development of avidity-based fluorescent sensors that address this need. The sensors bind specifically to free Ub, have Kd values down to 60 pM, and, in concert with a newly developed workflow, allow us to distinguish and quantify the pools of free, protein-conjugated, and thioesterified forms of Ub from cell lysates. Alternatively, free Ub in fixed cells can be visualized microscopically by staining with a sensor. Real-time assays using the sensors afford unprecedented flexibility and precision to measure deubiquitination of virtually any (poly)Ub conjugate.
Tanycyte-independent control of hypothalamic leptin signaling
Authors: Yoo Sooyeon , Cha David , Kim Dong Won , Hoang Thanh V. , Blackshaw Seth
Published: January 2019

Leptin is secreted by adipocytes to regulate appetite and body weight. Recent studies have reported that tanycytes actively transport circulating leptin across the brain barrier into the hypothalamus, and are required for normal levels of hypothalamic leptin signaling. However, direct evidence for leptin receptor (LepR) expression is lacking, and the effect of tanycyte-specific deletion of LepR has not been investigated. In this study, we analyze the expression and function of the tanycytic LepR in mice. Using single-molecule fluorescent in situ hybridization (smfISH), RT-qPCR, single-cell RNA sequencing (scRNA-Seq), and selective deletion of the LepR in tanycytes, we are unable to detect expression of LepR in the tanycytes. Tanycyte-specific deletion of LepR likewise did not affect leptin-induced pSTAT3 expression in hypothalamic neurons, regardless of whether leptin was delivered by intraperitoneal or intracerebroventricular injection. Finally, we use activity-regulated scRNA-Seq (act-Seq) to comprehensively profile leptin-induced changes in gene expression in all cell types in mediobasal hypothalamus. Clear evidence for leptin signaling is only seen in endothelial cells and subsets of neurons, although virtually all cell types show leptin-induced changes in gene expression. We thus conclude that LepR expression in tanycytes is either absent or undetectably low, that tanycytes do not directly regulate hypothalamic leptin signaling through a LepR-dependent mechanism, and that leptin regulates gene expression in diverse hypothalamic cell types through both direct and indirect mechanisms.
Cytokinetic furrowing and abscission dynamics during brain development revealed by live imaging
Authors: McNeely Katrina C. , Little Jessica Neville , Dwyer Noelle D.
Published: January 2019

McNeely et al. quantitatively analyze polarized cytokinetic furrow ingression and abscission in mouse neuroepithelium by live imaging. The findings show important differences from HeLa cells, and suggest abscission timing and midbody release may be developmentally regulated, to influence daughter cell fate during brain growth.

While mechanisms of cytokinesis have been identified in single cell models, the spatial and temporal regulation in developing tissues is less understood. Here we compare cytokinetic furrowing and abscission in mouse neuroepithelial stem cells (NESCs) at different developmental stages and in a cytokinesis mutant, including imaging abscission dynamics in a polarized epithelium for the first time. We find that asymmetric furrows of NESCs ingress at a constant but slow rate, and form the midbody at the apical membrane. Usually, bilateral abscission on each midbody flank releases the midbody remnant extracellularly. Interestingly, midbody remnants are more associated with early proliferative divisions. Unexpectedly, in the microcephalicKif20bmutant, abscission is accelerated and occurs when the midbody is wider. The daughter cells of mutant NESCs show increased cell cycle exit that is p53-independent. We suggest that abscission mechanisms are developmentally regulated. These results provide significant insight into adaptations of a fundamental cell biological process required for proper brain growth.
Site preference and tetragonal distortion in palladium-rich Heusler alloys
Authors: Wu Mengxin , Han Yilin , Bouhemadou A. , Cheng Zhenxiang , Khenata R. , Kuang Minquan , Wang Xiangjian , Yang Tie , Yuan Hongkuan , Wang Xiaotian
Published: January 2019

In this work, two kinds of competition between different Heusler structure types are considered, one is the competition between XA and L21 structures based on the cubic system of full-Heusler alloys, Pd2
YZ (Y = Co, Fe, Mn; Z = B, Al, Ga, In, Tl, Si, Ge, Sn, Pb, P, As, Sb). Most alloys prefer the L21 structure; that is, Pd atoms tend to occupy the a (0, 0, 0) and c (0.5, 0.5, 0.5) Wyckoff sites, the Y atom is generally located at site b (0.25, 0.25, 0.25), and the main group element Z has a preference for site d (0.75, 0.75, 0.75), meeting the well known site-preference rule. The difference between these two cubic structures in terms of their magnetic and electronic properties is illustrated further by their phonon dispersion and density-of-states curves. The second type of competition that was subjected to systematic study was the competitive mechanism between the L21 cubic system and its L10 tetragonal system. A series of potential tetragonal distortions in cubic full-Heusler alloys (Pd2
YZ) have been predicted in this work. The valley-and-peak structure at, or in the vicinity of, the Fermi level in both spin channels is mainly attributed to the tetragonal ground states according to the density-of-states analysis. ΔE
M is defined as the difference between the most stable energy values of the cubic and tetragonal states; the larger the value, the easier the occurrence of tetragonal distortion, and the corresponding tetragonal structure is stable. Compared with the ΔE
M values of classic Mn2-based tetragonal Heusler alloys, the ΔE
M values of most Pd2CoZ alloys in this study indicate that they can overcome the energy barriers between cubic and tetragonal states, and possess possible tetragonal transformations. The uniform strain has also been taken into consideration to further investigate the tetragonal distortion of these alloys in detail. This work aims to provide guidance for researchers to further explore and study new magnetic functional tetragonal materials among the full-Heusler alloys.
Penetration of dyes into protein crystals
Authors: McPherson Alexander
Published: January 2019

Experiments were carried out on 15 different protein crystals with the objective of estimating the rates of penetration of dye molecules into the crystals. The dyes were in the molecular-weight range 250–1000 Da and the protein crystals were of dimensions of 0.7 mm or greater. Experiments were also conducted on protein crystals grown between glass cover slips (separation 200 µm) that restricted the direction of diffusion. The rate of penetration of dyes into protein crystals depends very much on the degree of association between the dye and protein molecules. Dye penetration was not consistent with pure diffusion when the affinity of the protein for the dye was significant, and this was frequent. Penetration rates were less dependent on factors such as the molecular weight of the dye or the diffusion direction. For weakly interacting protein crystal/dye combinations, penetration was a fair measure of diffusivity and the observed rates were in the range 60–100 µm h−1. For strongly interacting combinations, the rates of penetration were of the order of 15–30 µm h−1.
Crystal structure of the aromatic-amino-acid aminotransferase fromStreptococcus mutans
Authors: Cong Xuzhen , Li Xiaolu , Li Shentao
Published: January 2019

Streptococcus mutans, a facultatively aerobic and Gram-positive bacterium, is the primary causative agent of dental caries and contributes to the multispecies biofilm known as dental plaque. In this study, the aromatic-amino-acid aminotransferase fromStreptococcus mutans(SmAroAT) was recombinantly expressed inEscherichia coli. An effective purification protocol was established. The recombinant protein was crystallized using the hanging-drop vapor-diffusion method with PEG 3350 as the primary precipitant. The crystal structure ofSmAroAT was solved at 2.2 Å resolution by the molecular-replacement method. Structural analysis indicated that the proteins of the aromatic-amino-acid aminotransferase family have conserved structural elements that might play a role in substrate binding. These results may help in obtaining a better understanding of the catabolism and biosynthesis of aromatic amino acids.
Levelling the playing field? Active labour market policies, educational attainment and unemployment
Authors: Benda Luc , Koster Ferry , van der Veen Romke J.
Published: January 2019

Purpose

The purpose of this paper is to investigate how active labour market policy (ALMP) training programmes and hiring subsidies increase or decrease differences in the unemployment risk between lesser and higher educated people during an economic downturn. A focus is put on potential job competition dynamics and cumulative (dis)advantages of the lesser and higher educated.

Design/methodology/approach

The paper uses multi-level data. The fifth wave (2010) of the European Social Survey was used and combined with macro-level data on labour market policies of the OECD. The sample consisted of 18,172 observations in 19 countries.

Findings

The results show that higher levels of participation and spending on training policies are related to a smaller difference in the unemployment risks of the educational groups. Higher training policy intensity is associated with a lower unemployment risk for the lesser educated and a higher unemployment risk for the higher educated. This implies that the lesser educated are better able to withstand downward pressure from the higher educated, thereby, reducing downward displacement during an economic downturn. Hiring subsidies do not seem to be associated with the impact of education on unemployment.

Originality/value

The paper adds to the discussion on ALMP training and hiring subsidies that are primarily rooted in the human capital theory and signalling theory. Both theories ignore the social context of labour market behaviour. The job competition theory and cumulative (dis)advantage theory add to these theories by focussing on the relative position of individuals and the characteristics that accompany the social position of the individual.
Stock prices, exchange rates and portfolio equity flows
Authors: Andriansyah Andriansyah , Messinis George
Published: January 2019

Purpose

The purpose of this paper is to develop a new framework to test the hypothesis that portfolio model predicts a negative correlation between stock prices and exchange rates in a trivariate transmission channel for foreign portfolio equity investment.

Design/methodology/approach

This paper utilizes panel data for eight economies to extend the Dumitrescu and Hurlin (2012) Granger non-causality test of heterogeneous panels to a trivariate model by integrating the Toda and Yamamoto (1995) approach to Granger causality.

Findings

The evidence suggests that stock prices Granger-cause exchange rates and portfolio equity flows Granger-cause exchange rates. However, the overall panel evidence casts doubt on the explicit trivariate model of portfolio balance model. The study shows that Indonesia may be the only case where stock prices affect exchange rates through portfolio equity flows.

Research limitations/implications

The proposed test does not account for potential asymmetries or structural shifts associated with the crisis period. To isolate the impact of the Asian Financial crisis, this paper rather splits the sample period into two sub-periods: pre- and post-crises. The sample period and countries are also limited due to the use of the balance of payment statistics.

Practical implications

The study casts doubt on the maintained hypothesis of a trivariate transmission channel, as posited by the portfolio model. Policy makers of an economy may integrate capital market and fiscal policies in order to maintain stable exchange rate.

Originality/value

This paper integrates a portfolio equity inflow variable into a single framework with stock price and exchange rate variables. It extends the Dumitrescu and Hurlin’s (2012) bivariate stationary Granger non-causality test in heterogeneous panels to a trivariate setting in the framework of Toda and Yamamoto (1995).