bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk Factors for Septicemia Deaths and Disparities in a Longitudinal US Cohort
Authors: Kempker Jordan A , Kramer Michael R , Waller Lance A , Martin Greg S
Published: November 2018

Background

There are few longitudinal data on the risk factors and mediators of racial disparities in sepsis among community- dwelling US adults.

Methods

This is a longitudinal study of adult participants in the 1999–2005 National Health Interview Survey with data linked to the 1999–2011 National Death Index. We utilized National Vital Statistics System’s ICD-10 schema to define septicemia deaths (A40-A41), utilizing influenza and pneumonia deaths (J09-J11) and other causes of death as descriptive comparators. All statistics utilized survey design variables to approximate the US adult population.

Results

Of 206 691 adult survey participants, 1523 experienced a septicemia death. Factors associated with a >2-fold larger hazard of septicemia death included need for help with activities of daily living; self-reported “poor” and “fair” general health; lower education; lower poverty index ratio; self-reported emphysema, liver condition, stroke, and weak or failing kidneys; numerous measures of disability; general health worse than the year prior; >1 pack per day cigarette use; and higher utilization of health care. Blacks had age- and sex-adjusted hazards that were higher for septicemia deaths (hazard ratio [HR], 1.92; 95% confidence interval [CI], 1.65–2.23) than for other causes of death (HR, 1.32; 95% CI, 1.25–1.38). The strongest mediators of the septicemia disparity included self-reported general health condition, family income-poverty ratio, and highest education level achieved.

Conclusions

In this cohort, the major risk factors for septicemia death were similar to those for other causes of death, there was approximately a 2-fold black-white disparity in septicemia deaths, and the strongest mediators of this disparity were across domains of socioeconomic status.
A Dissociation in Effects of Risperidone Monotherapy on Functional and Anatomical Connectivity Within the Default Mode Network
Authors: Zong Xiaofen , Hu Maolin , Pantazatos Spiro P , Mann J John , Wang Gaohua , Liao Yanhui , Liu Zhong-Chun , Liao Wei , Yao Tao , Li Zongchang , He Ying , Lv Luxian , Sang Deen , Tang Jinsong , Chen Huafu , Zheng Junjie , Chen Xiaogang
Published: November 2018

Respective changes in functional and anatomical connectivities of default mode network (DMN) after antipsychotic treatment have been reported. However, alterations in structure–function coupling after treatment remain unknown. We performed diffusion tensor imaging (DTI) and resting-state functional magnetic resonance imaging in 42 drug-naive first-episode schizophrenia patients (FESP) both at baseline and after 8-weeks risperidone monotherapy, and in 38 healthy volunteers. Independent component analysis was used to assess voxel-wise DMN synchrony. A 3-step procedure was used to trace fiber paths between DMN components. Structure–function couplings were assessed by Pearson’s correlations between mean fractional anisotropy and temporal correlation coefficients in major tracts of DMN. Pretreatment, FESP showed impaired functional connectivity in posterior cingulate cortex/precuneus (PCC/PCUN) and medial prefrontal cortex (mPFC), but no abnormalities in fibers connecting DMN components. After treatment, there were significant increases in functional connectivities of PCC/PCUN. Increases in functional connectivity between PCC/PCUN and mPFC correlated with improvement in positive symptoms. The structure–function coupling in tracts connecting PCC/PCUN and bilateral medial temporal lobes decreased after treatment. No alterations in DMN fiber integrity were detected. This combination of functional and anatomical findings in FESP contributes novel evidence related to neurobehavioral treatment effects. Increased functional connectivities between PCC/PCUN and mPFC may be treatment response biomarkers for positive symptoms. Increases in functional connectivities, no alterations in fiber integrity, combined with decreases in structural–functional coupling, suggest that DMN connectivities may be dissociated by modality after 8-week treatment. Major limitations of this study, however, include lack of repeat scans in healthy volunteers and control group of patients taking placebo or comparator antipsychotics.
A Feed-Forward Subnetwork Emerging from Integrated TOR- and cAMP/PKA-Signaling Architecture Reinforces Magnaporthe oryzae Appressorium Morphogenesis
Authors: Sun Guangchao , Qi Xiaobo , Wilson Richard A.
Published: November 2018

Appressoria are important mediators of plant–microbe interactions. In the devastating rice blast pathogen Magnaporthe oryzae, appressorial morphogenesis from germ tube tips requires activated cAMP/PKA signaling and inactivated TOR signaling (TORoff). TORoff temporarily arrests G2 at a metabolic checkpoint during the single round of mitosis that occurs following germination. G2 arrest induces autophagy and appressorium formation concomitantly, allowing reprogression of the cell cycle to G1/G0 quiescence and a single appressorial nucleus. Inappropriate TOR activation abrogates G2 arrest and inhibits cAMP/PKA signaling downstream of cPKA. This results in multiple rounds of germ tube mitosis and the loss of autophagy and appressoria formation. How cAMP/PKA signaling connects to cell cycle progression and autophagy is not known. To address this, we interrogated TOR and cAMP/PKA pathways using signaling mutants, different surface properties, and specific cell cycle inhibitors and discovered a feed-forward subnetwork arising from TOR- and cAMP/PKA-signaling integration. This adenylate cyclase-cAMP-TOR-adenylate cyclase subnetwork reinforces cAMP/PKA-dependent appressorium formation under favorable environmental conditions. Under unfavorable conditions, the subnetwork collapses, resulting in reversible cell cycle-mediated germ tube growth regardless of external nutrient status. Collectively, this work provides new molecular insights on germ tube morphogenetic decision-making in response to static and dynamic environmental conditions.
Development of a Pseudomonas syringae–Arabidopsis Suspension Cell Infection System for Investigating Host Metabolite-Dependent Regulation of Type III Secretion and Pattern-Triggered Immunity
Authors: Yan Qing , Rogan Conner J. , Anderson Jeffrey C.
Published: November 2018

The importance of pattern-triggered immunity (PTI) in plant defense has been clearly established through genetic studies of mutants lacking functional pattern recognition receptors (PRRs) and signaling components downstream of PRR activation. Despite extensive knowledge of PRR-mediated signaling responses to pathogen-associated molecular patterns (PAMPs), little is known about which of these responses, if any, are directly responsible for limiting bacterial growth. In this work, we established a protocol for coculturing the bacterial pathogen Pseudomonas syringae pv. tomato DC3000 and Arabidopsis suspension cells. The system closely mirrors infection processes that occur in leaves, with bacteria relying on the type III secretion system (T3SS) for maximal growth and PAMP-induced plant defenses effectively limiting bacterial growth. To demonstrate the utility of this system, we investigated the molecular basis of PAMP-induced growth inhibition and discovered that T3SS-associated genes are inhibited when DC3000 is cocultured with PAMP-treated plant suspension cells. To determine the underlying mechanism of decreased T3SS gene expression, we performed metabolomics and biochemical analyses of suspension cell exudates and identified 14 metabolites that significantly increased or decreased following PAMP treatment. Citric acid, a known inducer of T3SS gene expression in DC3000, was among several organic acids decreased in exudates from PAMP-treated plant cells. Exogenous addition of citric acid increased T3SS gene expression and partially recovered growth of DC3000 in the presence of PAMP-treated cells, indicating that a portion of PAMP-induced defense in this system is decreased extracellular release of this metabolite. We envision that the well-defined infection conditions of this coculture system will be valuable for quantitative studies of type III effector delivery by P. syringae. Furthermore, this system provides a unique ‘top-down’ approach to unravel the molecular basis of PTI against P. syringae.
Association of Histologic Chorioamnionitis With Perinatal Brain Injury and Early Childhood Neurodevelopmental Outcomes Among Preterm Neonates
Authors: Bierstone Daniel , Wagenaar Nienke , Gano Dawn L. , Guo Ting , Georgio Gregory , Groenendaal Floris , de Vries Linda S. , Varghese Jojy , Glass Hannah C. , Chung Catherine , Terry Jefferson , Rijpert Maarten , Grunau Ruth E. , Synnes Anne , Barkovich A. James , Ferriero Donna M. , Benders Manon , Chau Vann , Miller Steven P.
Published: November 2018

(Abstracted from JAMA Pediatr 2018;172(6):534–541)

Acute chorioamnionitis refers to the neutrophilic inflammation of the placental tissues thought to result from an ascending bacterial infection. It is considered a major factor associated with preterm birth and has been estimated to occur in 40% to 80% of preterm deliveries.
Vemurafenib impairs the repair of ultraviolet radiation-induced DNA damage
Authors: Kimeswenger Susanne , Mann Ulrike , Hoeller Christoph , Foedinger Dagmar , Jantschitsch Christian
Published: November 2018

Targeted therapy with the BRAF inhibitors vemurafenib and dabrafenib is an effective treatment regimen in patients with advanced melanoma carrying the BRAF V600E mutation. A common side effect is an enhanced rate of nonmelanoma skin cancer (NMSC). BRAF inhibition leads to a paradoxical enhanced MAPK signalling in BRAF wild-type cells, which might in part be responsible for the enhanced NMSC burden. It is known that disturbances of DNA repair result in an increased rate of NMSC. In the present study, it was investigated whether BRAF inhibitors might interfere with the repair of ultraviolet radiation-induced DNA damage in vitro. Epidermal keratinocytes of 11 Caucasian donors were treated with vemurafenib or dabrafenib and, 24 h later, exposed to ultraviolet A. DNA damage and repair capacity were analysed using south-western slot blot detecting cyclobutane pyrimidine dimers. Using PCR and DNA sequencing, RAS mutations and human papilloma virus genes were investigated. RNA expression was determined using a Gene Expression Chip and qRT-PCR. In 36% of keratinocytes, vemurafenib hampers the repair of ultraviolet A-induced DNA damage. No changes in DNA repair were observed with dabrafenib, indicating a possible substance-specific effect of vemurafenib. In none of the keratinocytes, pre-existing RAS mutations or human papilloma virus-associated DNA sequences were detected. The expression of the interferon-related damage resistance signature is decreased upon vemurafenib treatment in 36% of donors. The enhanced rate of NMSC in patients treated with vemurafenib might be partly related to a vemurafenib-driven impaired capacity for DNA repair.
Absorbable Implant Foreign Body Reaction Masquerading as Orbital Cellulitis
Authors: Shaughness Gabrielle J. , Segal Kira L. , Kahana Alon
Published: November 2018

Poly-dl-lactide polymer implants absorb over a period of 6 to 12 months and have been used with increasing frequency for repair of orbital fractures. The authors describe the case of a 7-year-old boy who presented with orbital inflammation 10 months following repair of a white-eyed blowout fracture with a poly-dl-lactide implant. Rapid improvement in symptoms followed initiation of oral steroids, with excellent long-term result. Clinical presentation and treatment response implicated a foreign body inflammatory reaction as the underlying etiology of symptoms. Ophthalmologists and orbital surgeons should be aware that absorbable implants can demonstrate this late idiosyncratic complication.
Variations in Insurance Policies Regarding Adherence to the AGA Guideline for Therapeutic Drug Monitoring in IBD
Authors: Yadav Abhijeet , Vasquez Pamela , Dolgin Natasha H. , Falchuk Kenneth R. , Feuerstein Joseph D.
Published: November 2018

Background:

The American Gastroenterological Association (AGA) published guidelines on therapeutic drug monitoring (TDM) in inflammatory bowel disease (IBD) in August 2017 recommending use of reactive TDM to guide treatment changes in patients with active IBD who are being treated with anti-tumor necrosis factor (anti-TNF) agents or thiopurines. We sought to determine if changes in national clinical practice guidelines result in changes in health care insurance policies within 6 months of publication.

Methods:

Using the National Association of Insurance Commissioners Market Share Reports of the top 125 insurance companies by market share in 2016, we reviewed the largest 50 companies for their publicly available online policies regarding TDM of anti-TNF and thiopurine in IBD. For those with available policies, we looked for whether proactive and/or reactive TDM was covered. Policies were also looked for genetic or enzymatic activity of thiopurine methyltransferase (TPMT) testing before use of thiopurine. All these policies were reviewed within the week of publication of the AGA guideline. They were reviewed again 1, 3, and 6 months later for evaluation of any policy changes after the published AGA guidelines.

Results:

Fifty of the largest insurance company policies were included. With regards to TDM policy for anti-TNF, we did not find a difference between baseline and 6 months values (P=0.38). With regards to TDM policy for thiopurine, we did not find a difference between baseline and 6 months values (P=1.00). About half of the companies did not have a policy regarding TPMT testing for thiopurine use. Of those with available policies for TPMT testing, there was no difference between baseline and 6 months values (P=0.13).

Conclusions:

Even after publication of national guidelines, a large number of the largest health insurance companies do not have a policy regarding reactive TDM for anti-TNF and/or thiopurines. Majority of those with a policy, fail to meet the current standards set forth by the practice guidelines. A significant gap remains between the insurance policies and AGA guidelines. Further studies are needed to determine how to effectuate change to improve insurance company adherence to clinical practice guidelines.
Validation of the short form of the International Crowding Measure in Emergency Departments: an international study
Authors: Boyle Adrian , Atkinson Paul , Basaure Verdejo Carlos , Chan Edward , Clouston Robin , Gilligan Paedar , Grewal Karan , Higginson Ian , Liston Paul , Newcombe Virginia , Norton Valerie , Richter Sophie , Stoica George , Wakai Abel
Published: November 2018

Objective

There is little consensus on the best way to measure emergency department (ED) crowding. We have previously developed a consensus-based measure, the International Crowding Measure in Emergency Departments. We aimed to externally validate a short form of the International Crowding Measure in Emergency Department (sICMED) against emergency physician’s perceptions of crowding and danger.

Methods

We performed an observational validation study in seven EDs in five different countries. We recorded sICMED observations and the most senior available emergency physician’s perceptions of crowding and danger at the same time. We performed a times series regression model.

Results

A total of 397 measurements were analysed. The sICMED showed moderate positive correlations with emergency physician’s perceptions of crowding, r = 0.4110, P < 0.05) and safety (r = 0.4566, P < 0.05). There was considerable variation in the performance of the sICMED between different EDs. The sICMED was only slightly better than measuring occupancy or ED boarding time.

Conclusion

The sICMED has moderate face validity at predicting clinician’s concerns about crowding and safety, but the strength of this validity varies between different EDs and different countries.
Template for uniform reporting of emergency department measures, consensus according to the Utstein method
Authors: Hruska Katrin , Castrén Maaret , Banerjee Jay , Behringer Wilhelm , Bjørnsen Lars P. , Cameron Peter , Einav Sharon , Holroyd Brian R. , Jones Peter , Lassen Annmarie , Truesdale Melinda , Kurland Lisa
Published: November 2018

Objective

To develop a template for uniform reporting of standardized measuring and describing of care provided in the emergency department (ED).

Methods

An international group of experts in emergency medicine, with broad experience from different clinical settings, met in Utstein, Norway. Through a consensus process, a limited number of measures that would accurately describe an ED were chosen and a template was developed.

Results

The final measures to be reported and their definitions were grouped into six categories: Structure, Staffing and governance, Population, Process times, Hospital and healthcare system and Outcomes. The template for Utstein-style uniform reporting is presented.

Conclusion

The suggested template is intended for use in studies carried out in EDs to improve comparability and knowledge translation.
The Failure of United States Maternal Mortality Reporting and Its Impact on Women’s Lives
Authors: MacDorman Marian F. , Declercq Eugene
Published: November 2018

(Abstracted from Birth 2018;45:105–108)

Maternal mortality is a significant public health problem and an important indicator of the quality of health care both nationally and internationally. The death of a mother during pregnancy, childbirth, or postpartum is one of the greatest tragedies that can occur within a family, with wide-ranging consequences for the index child, other family members, and the larger society.
Prospective Assessment of Follicular Growth and the Oocyte Cohort After Ovarian Stimulation for Fertility Preservation in 90 Cancer Patients Versus 180 Matched Controls
Authors: Decanter Christine , Robin Geoffroy , Mailliez Audrey , Sigalaa Julien , Morschhauser Franck , Ramdane Nassima , Devos Patrick , Dewailly Didier , Leroy-Martin Brigitte , Keller Laura
Published: November 2018

(Abstracted from Reprod Biomed Online 2018;36:543–551)

With the increasing incidence of cancer and survival rates among young women, the development of fertility preservation techniques is of critical importance for those who desire future pregnancy. The pattern of ovarian response and oocyte quality after ovarian stimulation in cancer patients of reproductive age has been studied in several retrospective studies, which often compared cancer patients with a historical control; results were mixed.
생 및 데친 야콘 분말의 등온흡습 모델링
Authors: Choi Ji Eun , Lee Jun Ho
Published: November 2018

Information on moisture adsorption isotherms, which describe the inherent relationship between water activity (aw) and moisture content in food materials, is essential for drying, storing, packaging, and predicting shelf-life for successful application of yacon tuber flour in various fields of the food industry. The moisture sorption isotherms of fresh and blanched yacon tuber flours were obtained at 25℃, 35℃, and 45℃ and aw in the range of 0.11-0.75 by the static gravimetric method. Six different isotherm models were used to fit the experimental data and to analyze water vapor sorption. The results showed that water vapor sorption of both fresh and blanched yacon flours followed a type III shape over the humidity range. The blanched samples exhibited lower equilibrium moisture content than fresh samples. The monolayer moisture content estimated by the Guggenheim, Anderson, and De Boer (GAB) model was lower than that estimated by the Brunauer, Emmett, and Teller model. By quantifying the relative percent error and the coefficient of determination of the isotherm models relative to data, the GAB and Halsey models were identified to be the best-fitting isotherm to describe the water sorption process of both fresh and blanched yacon flours.
Physicochemical characteristics and antioxidant activities of rice bran extracts according to extraction solvent and cultivar
Authors: Gu Yul Ri , Kim Ju Hyeon , Cho Jun-Hyeon , Seo Woo-Duck , Hong Joo-Heon , Youn Kwang-Sup
Published: November 2018

Rice bran is widely used in various types of food supplement as oil, functional materials. In this study, we compared the physicochemical characteristics and antioxidant activities of rice bran extracts according to extraction solvent (water, 80% ethanol, and 80% methanol) and cultivar (Bukkyeong 2012-2, Han-ahreum, and Jasmin 85) to develop a useful food processing materials. The moisture content of rice bran powder was 8.19-9.00% depend on cultivars. Its color variables ranged as follows: L value, 50.06-55.18; a value, 2.35-2.97; and b value 11.65-13.88. The total polyphenol and total flavonoid content of 80% ethanol extract of Bukkyeong rice bran (E-BRB) extract were 6.75 and 5.18 g/100 g, respectively, which were higher than those of other extracts. Whereas, the total protein content of hot-water extract of Bukkyeong rice bran (H-BRB) was the highest, with 18.46 g/100 g. The DPPH and ABTS radical scavenging activities of E-BRB extract at 10 mg/mL concentration were 95.94% and 96.47%, respectively. The ferric-reducing antioxidant power and reducing power of E-BRB extract at 10 mg/mL concentration were 1.39 mM and 1.97, respectively. These results suggest that 80% ethanol extract of Bukkyeong rice bran can be used as a physiologically active substance for functional materials and functional food in food industry.
Anti-adipogenic effect of 1-O-feruloyl-β-D-glucose on 3T3-L1 preadipocytes
Authors: Kwak Sang Hee , Kim Yoon Hee
Published: November 2018

Obesity is the most common metabolic disease and is caused by an excess accumulation of body fat. 1-O-Feruloyl-β-D-glucose (FG) is a phenolic compound isolated from the corks of Euonymus alatus (Thunb.) Sieb. This study was designed to investigate the effect of FG on adipogenesis using 3T3-L1 preadipocyte. First, we evaluated the effects of FG on cell proliferation and cytotoxicity. Up to 5 μM, FG did not affect the proliferation of or cause cytotoxicity in 3T3-L1 preadipocytes. Therefore, we used FG at 0-5 μM for subsequent experiments. FG inhibited the accumulation of lipid droplets in differentiated 3T3-L1 adipocytes in a concentration-dependent manner. To understand the mechanism underlying the anti-adipogenic effect of FG, western blot analyses were performed. We found that FG suppressed peroxisome proliferator-activated receptor (PPAR) γ protein expression, a representative adipogenesis-related transcription factor. In addition, FG inhibited aP2/fatty acid binding protein 4 (FABP4) protein expression, a target gene of PPARγ. In conclusion, these data suggest that FG inhibits adipogenesis in 3T3-L1 adipocytes by inhibiting the expression of PPARγ and FABP4.
Injury-free priming: induction of Primary Afferent Collateral Sprouting in uninjured sensory neurons in vivo primes them for enhanced axon outgrowth in vitro
Authors: Soleman Sara , Petruska Jeffrey C. , Moon Lawrence D.F.
Published: November 2018

Prior “conditioning” nerve lesions can prime DRG neurons for enhanced axon regeneration. Here, we tested the hypothesis that adult DRG neurons can be primed for axon elongation in vitro without axonal injury by prior induction of Primary Afferent Collateral Sprouting (PACS) in vivo. Thoracic cutaneous nerves (T9, T10, T12, T13 but not T11) were transected to create zones of denervated skin. Neurons from the uninjured T11 DRG underwent PACS within the skin, as demonstrated by the expansion of its zones responsive to pinch up to 14 days. At 7 or 14 days after induction of collateral sprouting, DRG neurons were dissociated and cultured for 18 hours in defined media lacking neurotrophins and growth factors. Neurons from the uninjured T11 DRG had longer mean neurite lengths than neurons from naïve DRG. A larger proportion of neurons from the uninjured T11 DRG showed an elongating or arborizing phenotype than neurons from naïve DRG. Transcriptomic analysis of the uninjured T11 DRG and denervated/reinnervated skin reveal regulation of receptor/ligand systems and regulators of growth during collateral sprouting. For example, the glial cell-derived neurotrophic family ligands Artemin and Persephin were upregulated in denervated skin after 7 and/or 14 days. We suggest that extracellular cues in denervated skin modify the intrinsic growth program of uninjured DRG neurons that enhances their ability to elongate or arborize even after explantation. Collectively, these data confirm that induction of collateral sprouting does not induce an injury response yet primes many of these uninjured neurons for in vitro axon growth.
Bayesian Shrinkage Estimation of High Dimensional Causal Mediation Effects in Omics Studies
Authors: Song Yanyi , Zhou Xiang , Zhang Min , Zhao Wei , Liu Yongmei , Kardia Sharon L. R. , Diez Roux Ana V. , Needham Belinda L. , Smith Jennifer A. , Mukherjee Bhramar
Published: November 2018

Causal mediation analysis aims to examine the role of a mediator or a group of mediators that lie in the pathway between an exposure and an outcome. Recent biomedical studies often involve a large number of potential mediators based on high-throughput technologies. Most of the current analytic methods focus on settings with one or a moderate number of potential mediators. With the expanding growth of omics data, joint analysis of molecular-level genomics data with epidemiological data through mediation analysis is becoming more common. However, such joint analysis requires methods that can simultaneously accommodate high-dimensional mediators and that are currently lacking. To address this problem, we develop a Bayesian inference method using continuous shrinkage priors to extend previous causal mediation analysis techniques to a high-dimensional setting. Simulations demonstrate that our method improves the power of global mediation analysis compared to simpler alternatives and has decent performance to identify true non-null mediators. We also construct tests for natural indirect effects using a permutation procedure. The Bayesian method helps us to understand the structure of the composite null hypotheses. We applied our method to Multi-Ethnic Study of Atherosclerosis (MESA) and identified DNA methylation regions that may actively mediate the effect of socioeconomic status (SES) on cardiometabolic outcome.
Previewing a face in the periphery reduces the fN170: Combined EEG and eye-tracking suggests two stages of trans-saccadic predictive processes
Authors: Huber-Huber Christoph , Buonocore Antimo , Hickey Clayton , Melcher David
Published: November 2018

The world appears stable despite saccadic eye-movements. One possible explanation for this phenomenon is that the visual system predicts upcoming input across saccadic eye-movements, based on peripheral preview of the saccadic target. We tested this idea using concurrent electroencephalography (EEG) and eye-tracking. Participants made cued saccades to peripheral upright or inverted face stimuli that could change (invalid preview) or keep their orientation (valid preview) across the saccade. Experiment 1 demonstrated better discrimination performance and a reduced fixation-locked N170 (fN170) with valid than with invalid preview demonstrating integration of pre- and post-saccadic information. Moreover, the early fixation-locked EEG showed a preview face inversion effect suggesting that we perceive pre-saccadic input up to about 170 ms post fixation-onset, at least for face orientation. Experiment 2 replicated Experiment 1 and manipulated the proportion of valid and invalid trials (mostly valid versus mostly invalid, 66.6% to 33.3%) to test whether the preview effect reflected active expectations. A whole-scalp Bayes factor analysis provided evidence for no influence of proportion on the fN170 preview effect. Instead, before the saccade the preview face orientation effect declined earlier in the mostly invalid than in the mostly valid block suggesting some form of pre-saccadic expectations. We conclude that visual stability is achieved by two trans-saccadic integration processes: pre-saccadic prediction, reflected in the pre-saccadic proportion modulation, and early post-saccadic change-detection reflected in the fN170 preview effect.
Visual information is broadcast among cortical areas in discrete channels
Authors: Yu Yiyi , Stirman Jeffery N. , Dorsett Christopher R. , Smith Spencer LaVere
Published: November 2018

Among brain areas, axonal projections carry channels of information that can be mixed to varying degrees. Here, we assess the rules for the network consisting of the primary visual cortex and higher visual areas (V1-HVA) in mice. We use large field-of-view two-photon calcium imaging to measure correlated variability (i.e., noise correlations, NCs) among thousands of neurons, forming over a million unique pairs, distributed across multiple cortical areas simultaneously. The amplitude of NCs is proportional to functional connectivity in the network, and we find that they are robust, reproducible statistical measures, and are remarkably similar across stimuli, thus providing effective constraints to network models. We used these NCs to measure the statistics of functional connectivity among tuning classes of neurons in V1 and HVAs. Using a data-driven clustering approach, we identify approximately 60 distinct tuning classes found in V1 and HVAs. We find that NCs are higher between neurons from the same tuning class, both within and across cortical areas. Thus, in the V1-HVA network, mixing of channels is avoided. Instead, distinct channels of visual information are broadcast within and across cortical areas, at both the micron and millimeter length scales. This principle for the functional organization and correlation structure at the individual neuron level across multiple cortical areas can inform and constrain computational theories of neocortical networks.
What’s in Your Gamma? Activation of The Ventral Fronto-Parietal Attentional Network in Response to Distracting Sounds
Authors: ElShafei Hesham A. , Fornoni Lesly , Masson Rémy , Bertrand Olivier , Bidet-Caulet Aurélie
Published: November 2018

Auditory attention operates through top-down (TD) and bottom-up (BU) mechanisms that are supported by dorsal and ventral brain networks, respectively, with the main overlap in the lateral prefrontal cortex (lPFC). A good TD/BU balance is essential to be both task-efficient and aware of our environment, yet it is rarely investigated. Oscillatory activity is a novel method to probe the attentional dynamics with evidence that gamma activity (>30Hz) could signal BU processing and thus would be a good candidate to support the activation of the ventral BU network. MEG data were collected from 21 young adults performing the Competitive Attention Task which enables simultaneous investigation of BU and TD attentional mechanisms. Distracting sounds elicited an increase in gamma activity in regions of the BU ventral network. TD attention modulated these gamma responses in regions of the inhibitory cognitive control system: the medial prefrontal and anterior cingulate cortices. Finally, distracting-sound-induced gamma activity was synchronous between the auditory cortices and several distant brain regions, notably the lPFC. We provide novel insight into the role of gamma activity (1) in supporting the activation of the BU ventral network, and (2) in subtending the TD/BU attention balance in the prefrontal cortex.
Place cell firing cannot support navigation without intact septal circuits
Authors: Bolding Kevin A. , Ferbinteanu Janina , Fox Steven E. , Muller Robert U.
Published: November 2018

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.
DNA Extraction Method Optimized for Nontuberculous Mycobacteria Long-Read Whole Genome Sequencing
Authors: Bouso Jennifer M. , Planet Paul J.
Published: November 2018

Nontuberculous mycobacteria (NTM) are a major cause of pulmonary and systemic disease in at-risk populations. Gaps in knowledge about transmission patterns, evolution, and pathogenicity during infection have prompted a recent surge in genomic NTM research. Increased availability and affordability of whole genome sequencing (WGS) techniques, including the advent of Oxford Nanopore Technologies, provide new opportunities to sequence complete NTM genomes at a fraction of the previous cost. However, extracting large quantities of pure genomic DNA is particularly challenging with NTM due to their slow growth and recalcitrant cell wall. Here we report a DNA extraction protocol that is optimized for long-read WGS of NTM, yielding large quantities of highly pure DNA. Our refined method was compared to 6 other methods with variations in timing of mechanical and enzymatic digestion, quantity of matrix material, and reagents used in extraction and precipitation. We also demonstrate the ability of our optimized protocol to produce sufficient DNA to yield near-complete NTM genome assemblies using Oxford Nanopore Technologies long-read sequencing.
Noncontractile tissue forces mask muscle fiber forces underlying muscle spindle Ia afferent firing rates in stretch of relaxed rat muscle
Authors: Blum Kyle P. , Nardelli Paul , Cope Timothy C. , Ting Lena H.
Published: November 2018

Stretches of relaxed cat and rat muscle elicit similar history-dependent muscle spindle Ia firing rates that resemble history-dependent forces seen in single activated muscle fibers (Nichols and Cope, 2004). During stretch of relaxed cat muscle, whole musculotendon forces exhibit history-dependence that mirror history-dependent muscle spindle firing rates, where both muscle force and muscle spindle firing rates are elevated in the first stretch in a series of stretch-shorten cycles (Blum et al., 2017). By contrast, rat musculotendon are only mildly history-dependent and do not mirror history-dependent muscle spindle firing rates in the same way (Haftel et al., 2004). We hypothesized that history-dependent muscle spindle firing rates elicited in stretch of relaxed rat muscle would mirror history-dependent muscle fiber forces, which are masked by noncontractile tissue at the level of whole musculotendon force. We removed noncontractile tissue force contributions from the recorded musculotendon force using an exponentially-elastic tissue model. We then show that the remaining estimated muscle fiber force resembles history-dependent muscle spindle firing rates recorded simultaneously. These forces also resemble history-dependent forces recorded in stretch of single activated fibers and attributed to muscle cross-bridge mechanisms (Campbell and Moss, 2000). Our results suggest that history-dependent muscle spindle firing in both rats and cats arise from stretch of cross-bridges in muscle fibers.
Tcf4 encodescortical differentiation during development
Authors: Mesman Simone , Bakker Reinier , Smidt Marten P.
Published: November 2018

Tcf4 has been linked to autism, schizophrenia, and Pitt-Hopkins Syndrome (PTHS) in humans, however, the mechanisms behind its role in disease development is still elusive. In the present study, we provide evidence that Tcf4 has a critical function in the differentiation of cortical regions during development.

We show that Tcf4 is present throughout the developing brain at the peak of neurogenesis. Deletion of Tcf4 results in mis-specification of the cortical layers, malformation of the corpus callosum and hypoplasia of the hippocampus. RNA-sequencing on E14.5 cortex material shows that Tcf4 functions as a transcriptional activator and loss of Tcf4 results in downregulation of genes linked to the emergence of other neurodevelopmental disorders. Taken together, we show that neurogenesis and differentiation are severely affected in Tcf4 mutants, phenocopying morphological brain defects detected in PTHS patients. The presented data identifies new leads to understand the mechanism of human brain defects and will assist in genetic counseling programs.
Subcellular orchestration of alpha-synuclein variants in Parkinson’s disease brains revealed by 3D multicolor STED microscopy
Authors: Moors Tim E. , Maat Christina A. , Niedieker Daniel , Mona Daniel , Petersen Dennis , Timmermans-Huisman Evelien , Kole Jeroen , El-Mashtoly Samir F. , Spycher Liz , Zago Wagner , Barbour Robin , Mundigl Olaf , Kaluza Klaus , Huber Sylwia , Hug Melanie N. , Kremer Thomas , Ritter Mirko , Dziadek Sebastian , Geurts Jeroen J.G. , Gerwert Klaus , Britschgi Markus , van de Berg Wilma D.J.
Published: November 2018

Post-translational modifications of alpha-synuclein (aSyn), particularly phosphorylation at Serine 129 (Ser129-p) and truncation of its C-terminus (CTT), have been implicated in Parkinson’s disease (PD) pathology. To gain more insight in the relevance of Ser129-p and CTT aSyn under physiological and pathological conditions, we investigated their subcellular distribution patterns in normal aged and PD brains using highly-selective antibodies in combination with 3D multicolor STED microscopy. We show that CTT aSyn localizes in mitochondria in PD patients and controls, whereas the organization of Ser129-p in a cytoplasmic network is strongly associated with pathology. Nigral Lewy bodies show an onion skin-like architecture, with a structured framework of Ser129-p aSyn and neurofilaments encapsulating CTT aSyn in their core, which displayed high content of proteins and lipids by label-free CARS microscopy. The subcellular phenotypes of antibody-labeled pathology identified in this study provide evidence for a crucial role of Ser129-p aSyn in Lewy body formation.
Quantifying the mechanics and growth of cells and tissues in 3D using high resolution computational models
Authors: Liedekerke Paul Van , Neitsch Johannes , Johann Tim , Warmt Enrico , Valverde Ismael Gonzales , Höhme Stefan , Grosser Steffen , Käs Josef , Drasdo Dirk
Published: November 2018

Mathematical models are increasingly designed to guide experiments in biology, biotechnology, as well as to assist in medical decision making. They are in particular important to understand emergent collective cell behavior. For this purpose, the models, despite still abstractions of reality, need to be quantitative in all aspects relevant for the question of interest. The focus in this paper is to study the regeneration of liver after drug-induced depletion of hepatocytes, in which surviving dividing and migrating hepatocytes must squeeze through a blood vessel network to fill the emerged lesions. Here, the cells’ response to mechanical stress might significantly impact on the regeneration process. We present a 3D high-resolution cell-based model integrating information from measurements in order to obtain a refined quantitative understanding of the cell-biomechanical impact on the closure of drug-induced lesions in liver. Our model represents each cell individually, constructed as a physically scalable network of viscoelastic elements, capable of mimicking realistic cell deformation and supplying information at subcellular scales. The cells have the capability to migrate, grow and divide, and infer the nature of their mechanical elements and their parameters from comparisons with optical stretcher experiments. Due to triangulation of the cell surface, interactions of cells with arbitrarily shaped (triangulated) structures such as blood vessels can be captured naturally. Comparing our simulations with those of so-called center-based models, in which cells have a rigid shape and forces are exerted between cell centers, we find that the migration forces a cell needs to exert on its environment to close a tissue lesion, is much smaller than predicted by center-based models. This effect is expected to be even more present in chronic liver disease, where tissue stiffens and excess collagen narrows pores for cells to squeeze through.
Dietary salt promotes cognitive impairment through tau phosphorylation
Authors: Faraco Giuseppe , Hochrainer Karin , Segarra Steven G. , Schaeffer Samantha , Santisteban Monica M. , Menon Ajay , Jiang Hong , Holtzman David M. , Anrather Josef , Iadecola Costantino
Published: November 2018

Dietary habits and vascular risk factors promote both Alzheimer’s disease and cognitive impairment caused by vascular factors1-3. Furthermore, accumulation of hyperphosphorylated tau, a microtubule associated protein and a hallmark of Alzheimer’s pathology, is also linked to vascular cognitive impairment4-7. In mice, a salt-rich diet leads to cognitive dysfunction associated with a nitric oxide deficit in cerebral endothelial cells and cerebral hypoperfusion8. Here we report that dietary salt induces tau hyperphosphorylation followed by cognitive dysfunction, effects prevented by restoring endothelial nitric oxide production. The nitric oxide deficiency reduces neuronal calpain nitrosylation resulting in enzyme activation, which, in turn, leads to tau phosphorylation by activating cyclin dependent kinase-5. Salt-induced cognitive impairment is not observed in tau-null mice or in mice treated with anti-tau antibodies, despite persistent cerebral hypoperfusion and neurovascular dysfunction. These findings unveil a causal link between dietary salt, endothelial dysfunction and tau pathology, independent of hemodynamic insufficiency. Avoiding excessive salt intake and maintaining vascular health may help stave off vascular and neurodegenerative pathologies underlying late-life dementia.
Duration-specific effects of outcome devaluation in temporal control are differentially sensitive to amount of training
Authors: Araiba Sho , El Massioui Nicole , Brown Bruce L. , Doyère Valérie
Published: November 2018

This study demonstrates that overtraining in temporal discrimination modifies temporal stimulus control in a bisection task and produces habitual responding, as evidenced through insensitivity to food devaluation. Rats were trained or overtrained in a 2- versus 8-sec temporal discrimination task, with each duration associated with a lever (left or right) and food (grain or sucrose). Overtraining produced a leftward shift in the bisection point. Devaluation treatment induced a differential loss of responding depending on stimulus duration (short versus long) and the level of training (training versus overtraining). The relationships between timing behavior and habitual behavior are discussed.
Polymorphism in some new bis-hydrazone compounds
Authors: Dwivedi Bhavna , Das Dinabandhu
Published: November 2018

We describe the polymorphism of four new bis-hydrazone compounds, namely butane-2,3-dione 2,3-bis{[bis(4-fluorophenyl)methylidene]hydrazone}, C30H22F4N4 (1), butane-2,3-dione 2,3-bis{[bis(4-chlorophenyl)methylidene]hydrazone}, C30H22Cl4N4 (2), butane-2,3-dione 2,3-bis{[bis(4-methylphenyl)methylidene]hydrazone}, C34H34N4 (3), and butane-2,3-dione 2,3-bis({bis[4-(dimethylamino)phenyl]methylidene}hydrazone), C38H46N8 (4), derived by the condensation reaction between substituted benzophenone hydrazone and butane-2,3-dione. Concomitant polymorphism has been observed in 1, 2 and 3. Overlays of molecules of the different polymorphs indicate that there is conformational adjustment in the crystal structures of the polymorphs of 1 and 2, i.e. packing polymorphism, which was confirmed by a computational study. On the other hand, conformational change was observed in the cases of the polymorphs of compounds 3 and 4, i.e. conformational polymorphism.
Conflict-resolution algorithms for RPAS in non-segregated airspace
Authors: Pérez-Castán Javier A. , Gómez Comendador Fernando , Rodríguez-Sanz Álvaro , Arnaldo Valdés Rosa M. , Torrecilla Jaime
Published: November 2018

Purpose

The purpose of this paper is to focus on the development of conflict-resolution algorithms between Remotely Piloted Aircraft System (RPAS) and conventional aircraft. The goal of the conflict-resolution algorithm is to estimate the minimum protection distance (MPD) which is required to avoid a potential conflict.

Design/methodology/approach

The conflict-resolution algorithms calculate the last location at which an RPAS must start climbing to avoid a separation minima infringement. The RPAS maneuvers to prevent the conventional aircraft based on the kinematic equations. The approach selects two parameters to model the conflict-geometry: the path-intersection angle and the Rate of Climb (ROCD).

Findings

Results confirmed that the aircraft pair flying in opposition was the worst scenario because the MPD reached its maximum value. The best value of the MPD is about 12 Nautical Miles to ensure a safe resolution of a potential conflict. Besides, variations of the ROCD concluded that the relation between the ROCD and the MPD is not proportional.

Research limitations/implications

The primary limitation is that the conflict-resolution algorithms are designed in a theoretical framework without bearing in mind other factors such as communications, navigation capacity, wind and pilot errors among others. Further work should introduce these concepts to determine how the MPD varies and affects air traffic safety. Moreover, the relation between an ROCD requirement and the MPD will have an impact on regulations.

Practical implications

The non-linear relation between the MPD and the ROCD could be the pillar to define a standardized MPD in the future for RPAS systematic integration. To accomplish this standard, RPAS could have to fulfil a requirement of minimum ROCD until a specified flight level.

Originality/value

This paper is the first approach to quantify the Minimum Protection Distance between RPAS and conventional aircraft, and it can serve the aeronautical community to define new navigation requirements for RPAS.