bluuebunny/crossref_metadata_2025 huggingface dataset:
Brain Metabolism and Arterial Acid-Base Balance Following Bilateral Carotid Occlusion in Normotensive and Experimental Hypertensive Rats
Authors: Fujishima M. , Morotomi Y. , Tamaki K. , Nakatomi Y. , Ogata J. , Takishita S. , Kumamoto K. , Fukiyama K. , Omae T.
Published: May 2019

The effects of bilateral common carotid artery occlusion en brain metabolism and arterial acid-base balance were studied in normotensive and experimental renovascular hypertensive rats.

One hour after carotid occlusion in hypertensive rats, supratentorial lactate increased to 383% and lactate-pyruvate ratio to 280% of the controls, while adenosine triphosphate (ATP) decreased to 69%. These metabolic changes were thought to be due to cerebral ischemia. Arterial pC02 was lowered and the pH was raised in the hypertensive animals due to cerebral ischemia induced hyperventilation. In the normotensive rats, carotid occlusion had minimal effects on cerebral metabolism and arterial acid-base balance.

These results suggest that hypertensive rats are more susceptible to cerebral ischemia caused by carotid occlusion than normotensive rats. Increased cerebrovascular resistance in hypertension is discussed as a casual factor in cerebral ischemia.
Cytochemical Localization of Adenylate Cyclase in Broken Cell Preparations of the Cerebral Cortex
Authors: French S. W. , Palmer D. S. , Caldwell M.
Published: May 2019

Broken cell preparations derived from rat cerebral cortical grey matter were studied cytochemically to localize adenylate cyclase (AC) activity in subcellular organelle membranes. AC activity was localized by visualizing reaction product in brain particulate fractions by electron microscopy. Activity was found in the endoplasmic reticulum, on the inside of the inner mitochondrial membrane and on both leaflets of the nuclear membrane. Reaction product was found in the postsynaptic density area of most synapses. The reaction product tended to be more prominent in the presence of flouride. A synaptosome-rich fraction was shown to have NE stimulated AC activity which was blocked in vitro by both a α-and an β-blocker and in vivo by propranolol.
HLA and Complement Typing in Olivo-ponto-cerebellar Atrophy
Authors: Wastiaux J. P. , Lamoureux G. , Bouchard J. P. , Durivage A. , Barbeau C. , Barbeau A.
Published: May 2019

HLA antigen typing was carried out in a family with an autosomal dominant form of spinocerebellar degeneration [possibly olivoponto cerebellar atrophy (O.P.C.A.) — Type 1] . Eleven ataxic patients, three possibly ataxic subjects, two unrelated spouses and 13 clinically normal at risk siblings were typed for ABO and Rh blood groups, HLA-A and HLA-B antigens, C4 component of the complement and a number of other serum proteins (Clq, (β -1A, (β-1C, C5, (β -lipoproteins). No solid evidence for linkage between the ataxia gene and the HLA or C4 loci could be demonstrated in this family. Certain serum proteins, and particularly β -lipoproteins were found to be significantly reduced in some sub-groups of subjects.
Lipoamide Dehydrogenase in Friedreich's Ataxia Fibroblasts
Authors: Melançon S. B. , Potier M. , Dallaire L. , Fontaine G. , Grenier B. , Lemieux B. , Geoffroy G. , Barbeau A.
Published: May 2019

Lipoamide dehydrogenase was measued in cultivated skin fibroblasts from twelve patients with Friedreich's ataxia and nine normal controls. No difference in specific activity, subcellular distribution and Vmax or Km was observed between patients and controls.
Cerebellar Ataxia Produced by 3-Acetyl Pyridine in Rat
Authors: Butterworth R. F. , Hamel E. , Landreville F. , Barbeau A.
Published: May 2019

A single intraperitoneal injection of 3-acetyl pyridine produces, within 24 hours of administration, signs of cerebellar ataxia and damage to the medulla oblongata and to the climbing fibers of the cerebellum. These changes are accompanied by changes in the concentration of certain amino acids in the appropriate areas. Glutamic acid is decreased in cerebellum, medulla, cortex, striatum, hippocampus, retina and olfactory bulbs, while taurine is specifically decreased in the cerebellum and medulla oblongata and aspartic acid in the retina. The concentrations of GABA and glycine are not modified in any of the areas studied. Glutamine is generally increased in concentration in areas of cell damage.
Antagonism by Taurine of Morphine Induced Growth Hormone Secretion
Authors: Collu R. , Charpenet G. , Clermont M. J.
Published: May 2019

The intraperitoneal (IP) or intraventricular (IVT) administration of small amounts of taurine did not modify pentobarbital-induced sleep or pituitary hormone release. However, the drastic increment in plasma GH values induced by morphine administration was completely blocked by the IVT injection of the amino acid. Whether taurine plays a physiological role in the control ofGH secretion is highly speculative.
Early socioemotional competence, psychopathology, and latent class profiles of reparative prosocial behaviors from preschool through early adolescence
Authors: Donohue Meghan Rose , Tillman Rebecca , Luby Joan
Published: May 2019

Children who have difficulty using reparative behaviors following transgressions display a wide range of poorer social and emotional outcomes. Despite the importance of reparative skills, no study has charted the developmental trajectory of these behaviors or pinpointed predictors of poorer reparative abilities. To address these gaps in the literature, this study applied growth mixture modeling to parent reports of children's reparative behaviors (N = 230) in a 9-year longitudinal data set spanning from preschool to early adolescence. Three distinct trajectories of reparative behaviors were found: a low-stable, moderate-stable, and high-stable latent class. Poorer emotion understanding, social withdrawal, social rejection, and maladaptive guilt in the preschool period predicted membership in a low-stable reparative trajectory. Externalizing diagnoses, particularly conduct disorder and oppositional defiant disorder, also predicted membership in a low-stable reparative trajectory. Preschool-onset depression predicted membership in a low-stable reparative trajectory through high levels of maladaptive guilt. The findings from this study suggest that socioemotional deficits in the preschool period set children on longstanding trajectories of impaired reparative responding. Thus, emotion understanding, social functioning, maladaptive guilt, and early psychiatric symptoms should be targeted in early preventive interventions.
Singular value automata and approximate minimization
Authors: Balle Borja , Panangaden Prakash , Precup Doina
Published: May 2019

The present paper uses spectral theory of linear operators to construct approximatelyminimal realizations of weighted languages. Our new contributions are: (i) a new algorithm for the singular value decomposition (SVD) decomposition of finite-rank infinite Hankel matrices based on their representation in terms of weighted automata, (ii) a new canonical form for weighted automata arising from the SVD of its corresponding Hankelmatrix, and (iii) an algorithmto construct approximateminimizations of given weighted automata by truncating the canonical form.We give bounds on the quality of our approximation.
Cerebrospinal fluid biomarkers in patients with central nervous system infections: a retrospective study
Authors: Di Stefano Alessandro , Alcantarini Chiara , Atzori Cristiana , Lipani Filippo , Imperiale Daniele , Burdino Elisa , Audagnotto Sabrina , Mighetto Lorenzo , Milia Maria Grazia , Di Perri Giovanni , Calcagno Andrea
Published: May 2019

Background

Central nervous system (CNS) may be infected by several agents, resulting in different presentations and outcomes. Analysis of cerebrospinal fluid (CSF) markers could be helpful to differentiate specific conditions and setting an appropriate therapy.

Methods

Patients presenting with signs and symptoms were enrolled if, before receiving a diagnostic lumbar puncture, signed a written informed consent. We analyzed CSF indexes of blood–brain barrier permeability (CSF to serum albumin ratio or CSAR), inflammation (CSF to serum IgG ratio, neopterin), amyloid deposition (1–42 β-amyloid), neuronal damage (Total tau (T-tau), Phosphorylated tau (P-tau), and 14.3.3 protein) and astrocyte damage (S-100β).

Results

Two hundred and eighty-one patients were included: they were mainly affected by herpesvirus encephalitis, enterovirus meningoencephalitis, bacterial meningitis (Neisseria meningitidis and Streptococcus pneumoniae), and infection by other etiological agents or unknown pathogen. Their CSF features were compared with HIV-negative patients and native HIV-positive individuals without CNS involvement. 14.3.3 protein was found in bacterial and HSV infections while T-tau and neopterin were abnormally high in the herpesvirus group. P-tau, instead, was elevated in enterovirus meningitis. S-100β was found to be high in patients with HSV-1 and HSV-2 infections but not in those with Varicella Zoster Virus (VZV). Thirty-day mortality was unexpectedly low (2.7%): patients who died had higher levels of T-tau and, significantly, lower levels of Aβ1–42.

Conclusion

This work demonstrates that CSF biomarkers of neuronal damage or inflammation may vary during CNS infections according to different causative agents. The prognostic value of these biomarkers needs to be assessed in prospective studies.
Neurocognitive heterogeneity across the spectrum of psychopathology: need for improved approaches to deficit detection and intervention
Authors: Kavanaugh Brian C. , Cancilliere Mary Kathryn , Spirito Anthony
Published: May 2019

Neurocognition is one of the strongest predictors of clinical and functional outcomes across the spectrum of psychopathology, yet there remains a dearth of unified neurocognitive nosology and available neurocognition-targeted interventions. Neurocognitive deficits manifest in a transdiagnostic manner, with no psychiatric disorder uniquely affiliated with one specific deficit. In fact, recent research has identified that essentially all investigated disorders are comprised of 3–4 neurocognitive profiles. This within-disorder neurocognitive heterogeneity has hampered the development of novel, neurocognition-targeted interventions, as only a portion of patients with any given disorder possess neurocognitive deficits that would warrant neurocognitive intervention. The development of criteria and terminology to characterize these neurocognitive deficit syndromes would provide clinicians with the opportunity to more systematically identify and treat their patients and provide researchers the opportunity to develop neurocognition-targeted interventions for patients. This perspective will summarize recent work and discuss possible approaches for neurocognition-focused diagnosis and treatment in psychiatry.
Multivariate Base Rates of Low Scores on Tests of Learning and Memory Among Latino Adult Populations
Authors: Rivera Diego , Olabarrieta-Landa Laiene , Brooks Brian L. , Ertl Melissa M. , Benito-Sánchez Itziar , Quijano Maria Cristina , Rodriguez-Irizarry Walter , Aguayo Arelis Adriana , Rodríguez-Agudelo Yaneth , Arango-Lasprilla Juan Carlos
Published: May 2019

Objective:

To determine the prevalence of low scores for two neuropsychological tests with five total scores that evaluate learning and memory functions.

Method:

N = 5402 healthy adults from 11 countries in Latin America and the commonwealth of Puerto Rico were administered the Rey–Osterrieth Complex Figure (ROCF) and the Hopkins Verbal Learning Test (HVLT-R). Two-thirds of the participants were women, and the average age was 53.5 ± 20.0 years. Z-scores were calculated for ROCF Copy and Memory scores and HVLT-R Total Recall, Delayed Recall, and Recognition scores, adjusting for age, age2, sex, education, and interaction variables if significant for the given country. Each Z-score was converted to a percentile for each of the five subtest scores. Each participant was categorized based on his/her number of low scoring tests in specific percentile cutoff groups (25th, 16th, 10th, 5th, and 2nd).

Results:

Between 57.3% (El Salvador) and 64.6% (Bolivia) of the sample scored below the 25th percentile on at least one of the five scores. Between 27.1% (El Salvador) and 33.9% (Puerto Rico) scored below the 10th percentile on at least one of the five subtests. Between 5.9% (Chile, El Salvador, Peru) and 10.3% (Argentina) scored below the 2nd percentile on at least one of the five scores.

Conclusions:

Results are consistent with other studies that found that low scores are common when multiple neuropsychological outcomes are evaluated in healthy individuals. Clinicians should consider the higher probability of low scores when evaluating learning and memory using various sets of scores to reduce false-positive diagnoses of cognitive deficits.
Availability of neighbourhood supermarkets and convenience stores, broader built environment context, and the purchase of fruits and vegetables in US households
Authors: Peng Ke , Kaza Nikhil
Published: May 2019

Objective:

To determine whether neighbourhood supermarket and convenience store availability and broader built environment context are associated with food purchasing behaviour in a national population.

Design:

We used observational data to perform a cross-sectional study of food purchases for US households in 2010. We used three-level mixed-effect regression models to determine whether the associations between the number of neighbourhood supermarkets and convenience stores and the self-reported annual household expenditures for fruits and vegetables were affected by regional destination accessibility, neighbourhood destination diversity, availability of neighbourhood destinations and neighbourhood street connectivity.

Setting:

Metropolitan statistical areas (n 378) in the USA.

Participants:

Households (n 22 448).

Results:

When we controlled for broader built environment context, there was no significant association between availability of neighbourhood supermarkets and expenditures on fruits and vegetables; instead, we observed an inverse association between the number of convenience stores and expenditures for fruits (P = 0·001). The broader built environment context was associated with food purchase, although the magnitude was small: (i) higher regional destination accessibility was associated with higher expenditures for fruits (P < 0·001); (ii) higher neighbourhood destination diversity was associated with lower expenditures for vegetables (P = 0·002); and (iii) higher neighbourhood street connectivity was associated with higher expenditures for fruits (P < 0·001).

Conclusions:

The broader built environment factors contributed to understanding how people use neighbourhood food stores. However, there was only a small relationship between the broader environment context and fruit and vegetable expenditures. Policy interventions that focus exclusively on increasing the availability of neighbourhood supermarkets likely will not promote fruit and vegetable consumption.
Investigation of ORR Performances on Graphene/Phthalocyanine Nanocomposite in Neutral Medium
Authors: Mukherjee Moumita , Samanta Madhupriya , Das Gour P. , Chattopadhyay Kalyan K.
Published: May 2019

The drive to replace scarce and expensive Pt-based electrocatalysts for oxygen reduction reaction (ORR) has led to the development of a group of electrocatalysts composed of transition-metal ion centers coordinated with four nitrogen groups (M-N4). Among these, metal phthalocyanines (MPcs), due to low cost of preparation, highly conjugated structure as well as high thermal and chemical stability, have received a great interest. The catalytic activity of MPcs can be improved by employing conducting supports. Here, in this report, we have solvothermally synthesized graphene-supported zinc phthalocyanine nanostructures, and their ORR kinetics and mechanism have been investigated in neutral solution (pH = 7) by using the rotating disk electrode technique. The as-synthesized nanocomposite followed a 4e− reduction pathway. The onset potential (−0.04 V versus Ag/AgCl) found in this work can be comparable with other state-of-the-art material, demonstrating good performance in neutral solution. The fascinating performance leads the nanocomposite material toward future energy applications.
Post-operative stereotactic radiosurgery of brain metastases: A single-center retrospective review of clinical outcomes
Authors: Smith Zachary T. , Ashruf Syed U. , Mylander Charles , Thompson Kerry J. , Geraghty Charles , Hasson Brian , Burke Timothy G. , Dad Luqman K.
Published: May 2019

Aim:

We sought to retrospectively report our outcomes using post-operative stereotactic radiosurgery (SRS)/stereotactic radiotherapy (SRT) in place of whole-brain radiation therapy (WBRT) following resection of brain metastases from our hospital-based community practice.

Materials and Methods:

A retrospective review of 23 patients who underwent post-operative SRS at our single institution from 2013 to 2017 was undertaken. Patient records, treatment plans and diagnostic images were reviewed. Local failure, distant intracranial failure and overall survival were studied. Categorical variables were analyzed using Fisher’s exact tests. Continuous variables were analyzed using Mann–Whitney tests. The Kaplan–Meier method was used to estimate survival times.

Results:

16 (70%) were single-fraction SRS, whereas the remaining 7 patients received a five-fraction treatment course. The median single-fraction dose was 16 Gy (range, 16–18). The median total dose for fractionated treatments was 25 Gy (range, 25–35). Overall survival at 6 and 12 months was 95 and 67%, respectively. Comparison of SRS versus SRT local control rates at 6 and 12 months revealed control rates of 92 and 78% versus 29 and 14%, respectively. Every patient with dural/pial involvement at the time of surgery had distant intracranial failure at the 12-month follow-up.

Findings:

Single-fraction frameless SRS proved to be an effective modality with excellent local control rates. However, the five-fraction SRT course was associated with an increased rate of local recurrence. Dural/pial involvement may portend a high risk for distant intracranial disease; therefore, it may be prudent to consider alternative approaches in these cases.
Attitudes and completion of advance care planning: Assessing the contribution of health beliefs about Alzheimer's disease among Israeli laypersons
Authors: Werner Perla , Schiffman Ile Kermel
Published: May 2019

Objectives

The purpose of this study was to assess laypersons’ attitudes and completion of advance care planning (ACP) and to examine associations with sociodemographic characteristics and health beliefs on Alzheimer's disease.

Methods

A cross-sectional telephone survey was conducted during April and May 2017, with a sample of 514 Israeli adults, aged 18 years and above. A structured, pretested questionnaire assessing participants’ awareness, attitudes, and completion of ACP, as well as health beliefs on Alzheimer's disease (subjective knowledge, susceptibility, and worry), and sociodemographic factors, was used.

Results

Two-fifths of the participants had heard of at least one of the terms: advance directives or durable power of attorney. Overall, participants expressed positive attitudes toward ACP. Results of regression models showed that gender, religiosity, and subjective knowledge of Alzheimer's disease were statistically significant correlates of attitudes toward ACP. Adding health beliefs on Alzheimer's disease doubled the amount of the variance explained, from 3% to 6%.

Significance of results

Our results support the use of cognitive models of health behavior by assessing intra-personal beliefs and knowledge to understand ACP attitudes and completion. Specifically, we demonstrated the importance of knowledge of Alzheimer's disease for ACP attitudes, suggesting the importance of including a module on the topic to ACP interventions.
Influence of carrier water pH, foliar fertilizer, and ammonium sulfate on 2,4-D and 2,4-D plus glyphosate efficacy
Authors: Devkota Pratap , Johnson William G.
Published: May 2019

Carrier water pH is an important factor for enhancing herbicide efficacy. Coapplying agrochemical products with the herbicide might save time and resources; however, the negative effect of foliar fertilizers on herbicide efficacy should be thoroughly evaluated. In greenhouse studies, the effect of carrier water pH (4, 6.5, and 9), foliar fertilizer (zinc [Zn], manganese [Mn], or without fertilizer), and ammonium sulfate (AMS) at 0% or 2.5% vol/vol was evaluated on 2,4-D and premixed 2,4-D plus glyphosate efficacy for giant ragweed, horseweed, and Palmer amaranth control. In addition, a field study was conducted to evaluate the effect of carrier water pH (4, 6.5, and 9); and Zn or Mn foliar fertilizer on premixed 2,4-D plus glyphosate efficacy for horseweed and Palmer amaranth control. In the greenhouse study, 2,4-D and premixed 2,4-D plus glyphosate provided 5% greater weed control at acidic compared with alkaline carrier water pH. Coapplied Mn foliar fertilizer reduced 2,4-D and premixed 2,4-D plus glyphosate efficacy at least 5% for weed control. Addition of AMS enhanced 2,4-D and premixed 2,4-D plus glyphosate efficacy at least 6% for giant ragweed, horseweed, and Palmer amaranth control. In the field study, few significant differences occurred between coapplied Zn or Mn foliar fertilizer for any treatment variables. Therefore, carrier water pH, coapplied foliar fertilizer, and water-conditioning adjuvants have potential to influence herbicide performance. However, weed species could play a role in the differential response of these factors on herbicide efficacy.
Believe It or Not? Partisanship, Preferences, and the Credibility of Campaign Promises
Authors: Fernandez-Vazquez Pablo , Theodoridis Alexander G.
Published: May 2019

We use a novel survey experiment with a broadly representative sample to reveal an important phenomenon in voter integration of campaign communications: preference-mediated partisan motivation. When evaluating the credibility of candidate position changes on minimum wage policy (a readily quantifiable and salient issue domain), partisans do not take a new stance at face value, apply universal skepticism, or simply afford more credibility to co-partisans. Instead, they process a candidate’s stance through an interaction between the voter’s partisan allegiance and their own policy preference. Partisans update more when a co-partisan moves closer to them than when the candidate shifts away from them. The opposite pattern emerges with the other party’s candidates: partisans tend to be more receptive if the candidate moves away from them. This feature of campaign message acceptance has profound implications for political communication and our understanding of partisan cognition.
Gaming Disorder and Computer-Mediated Communication in Children and Adolescents with Autism Spectrum Disorder
Authors: Paulus Frank W. , Sander Charlotte S. , Nitze Monika , Kramatschek-Pfahler Anne-Rose , Voran Anette , von Gontard Alexander
Published: May 2019

Abstract. Background: This study investigates how children and adolescents with autism spectrum disorder (ASD) make use of computer gaming and computer-mediated communication (CMC) in comparison to their nonautistic peers. Method: Parents filled out a standardized questionnaire on media use, gaming disorder (GD), and CMC. Sixty-two boys with a diagnosis of ASD aged 4 to 17 years (mean = 11.5; SD = 3.2) were compared to 31 healthy control boys (mean = 11.5; SD = 3.7). Results: Children and adolescents with ASD used CMC less frequently than their nonautistic peers but played video games for longer times than the controls. They preferred playing alone rather than in company of others and less frequently in multiplayer mode. Levels of GD symptoms were higher in boys with ASD. Conclusions: Children and adolescents with ASD seem to be an especially vulnerable subpopulation for GD. For them, the gaming situation (alone and in single-player mode) and CMC behavior seem to correspond to social patterns in real life. Our findings also provide support for the inclusion of offline gaming in the GD definition.
A Qualitative Metasynthesis of Reasons for the Use or Nonuse of	Assistive Technologies in the Aging Population
Authors: Abrilahij Afsaneh , Boll Thomas
Published: May 2019

Abstract. Models of the use of assistive technologies (ATs) have only moderate value for predicting older people’s actual use of ATs. To find further predictors, we performed a systematic literature review and – applying an action-theoretical approach – a metasynthesis of seven qualitative studies about the reasons older people use or fail to use ATs. We found 25 reasons referring to user’s beliefs and desires (e.g., related to demand, act of using ATs, its consequences), 18 of which were not contained in existing AT use models. Some reasons generalized across ATs (e.g., perceived unreliability), whereas others (e.g., privacy concerns, desire to avoid burden to others) appeared specific to telealarm or smart-home technology. We discuss findings with respect to improving AT use models and developmental counseling.
Dynamics of Mesoscale Eddies Interacting With a Western Boundary Current Flowing by a Gap
Authors: Yuan Dongliang , Song Xinxin , Yang Ya , Dewar William K.
Published: May 2019

The propagation of cyclonic and anticyclonic mesoscale eddies through a wide meridional gap with a crossing western boundary current (WBC) is studied using a 1.5‐layer quasi‐geostrophic ocean circulation model. The results of the numerical experiments suggest that a steady, leaping WBC blocks nearly completely all eddies from propagating westward through the gap. In comparison, both cyclonic and anticyclonic eddies propagate westward nearly uninterrupted through the gap if the WBC is in a penetrating state. Interactions of mesoscale eddies with a critical‐state WBC trigger regime transitions of the WBC between leaping and penetrating states, resulting in dramatic changes of the circulation west of the gap. The radiation of the circulation plumes from the gap into the western basin due to the WBC regime transition is found to be independent of the size and the initial location of the perturbing eddy in the eastern basin, provided that the WBC path shift is induced successfully by the eddy.
Contrasted Summer Processes in the Sea Ice for Two Neighboring Floes North of 84°N: Surface and Basal Melt and False Bottom Formation
Authors: Provost Christine , Sennéchael Nathalie , Sirven Jérôme
Published: May 2019

We report continuous observations in the high Arctic (north of 84°N) over the full 2013 summer season at two nearby sites with distinct initial snow depth, ice thickness, and altitude with respect to the local ice topography. The two sites, subject to similar atmospheric conditions that did not favor strong ice melt, showed contrasting evolutions. One site, with initially thin sea ice (1.40 m) at a relatively low location of the floe, witnessed the formation of a spectacular 1.20‐m‐deep melt pond, a pond‐enhanced erosion of the ice surface, and a sudden pond drainage into the ocean. Then, the outpoured fresh water rapidly froze, heated the old ice from below, and also acted as a temporary shield from the ocean heat flux while it was progressively ablated through dissolution. Eventually, the site almost recovered its initial ice thickness. In contrast, the other site, with initially thicker sea ice (1.75 m) at a relatively high location on its floe, did not support any significant meltwater and underwent over 0.5 m of continuous basal ablation. The two sites experienced formation of superimposed and interposed ice. Sea ice survived summer melt at the two sites, which entered the refreezing season with similar snow and ice thicknesses. For the first time, processes associated with the formation of a deep melt pond and subsequent false bottom evolution are continuously documented with ice mass balance instruments.
Heterogeneous GM-CSF signaling in macrophages is associated with control of Mycobacterium tuberculosis
Authors: Bryson Bryan D. , Rosebrock Tracy R. , Tafesse Fikadu G. , Itoh Christopher Y. , Nibasumba Armel , Babunovic Gregory H. , Corleis Bjorn , Martin Constance , Keegan Caroline , Andrade Priscila , Realegeno Susan , Kwon Douglas , Modlin Robert L. , Fortune Sarah M.
Published: May 2019

Variability in bacterial sterilization is a key feature of Mycobacterium tuberculosis (Mtb) disease. In a population of human macrophages, there are macrophages that restrict Mtb growth and those that do not. However, the sources of heterogeneity in macrophage state during Mtb infection are poorly understood. Here, we perform RNAseq on restrictive and permissive macrophages and reveal that the expression of genes involved in GM-CSF signaling discriminates between the two subpopulations. We demonstrate that blocking GM-CSF makes macrophages more permissive of Mtb growth while addition of GM-CSF increases bacterial control. In parallel, we find that the loss of bacterial control that occurs in HIV-Mtb coinfected macrophages correlates with reduced GM-CSF secretion. Treatment of coinfected cells with GM-CSF restores bacterial control. Thus, we leverage the natural variation in macrophage control of Mtb to identify a critical cytokine response for regulating Mtb survival and identify components of the antimicrobial response induced by GM-CSF.
Heading direction with respect to a reference point modulates place-cell activity
Authors: Jercog P. E. , Ahmadian Y. , Woodruff C. , Deb-Sen R. , Abbott L. F. , Kandel E. R.
Published: May 2019

The tuning of neurons in area CA1 of the hippocampus emerges through a combination of non-spatial input from different sensory modalities and spatial information about the animal’s position and heading direction relative to the spatial enclosure being navigated. The positional modulation of CA1 neuronal responses has been widely studied (e.g. place tuning), but less is known about the modulation of these neurons by heading direction. Here, utilizing electrophysiological recordings from CA1 pyramidal cells in freely moving mice, we report that a majority of neural responses are modulated by the heading-direction of the animal relative to a point within or outside their enclosure that we call a reference point. The finding of heading-direction modulation relative to reference points identifies a novel representation encoded in the neuronal responses of the dorsal hippocampus.
The viral protein corona directs viral pathogenesis and amyloid aggregation
Authors: Ezzat Kariem , Pernemalm Maria , Pålsson Sandra , Roberts Thomas C. , Järver Peter , Dondalska Aleksandra , Bestas Burcu , Sobkowiak Michal J. , Levänen Bettina , Sköld Magnus , Thompson Elizabeth A. , Saher Osama , Kari Otto K. , Lajunen Tatu , Sverremark Ekström Eva , Nilsson Caroline , Ishchenko Yevheniia , Malm Tarja , Wood Matthew J. A. , Power Ultan F. , Masich Sergej , Lindén Anders , Sandberg Johan K. , Lehtiö Janne , Spetz Anna-Lena , EL Andaloussi Samir
Published: May 2019

Artificial nanoparticles accumulate a protein corona layer in biological fluids, which significantly influences their bioactivity. As nanosized obligate intracellular parasites, viruses share many biophysical properties with artificial nanoparticles in extracellular environments and here we show that respiratory syncytial virus (RSV) and herpes simplex virus type 1 (HSV-1) accumulate a rich and distinctive protein corona in different biological fluids. Moreover, we show that corona pre-coating differentially affects viral infectivity and immune cell activation. In addition, we demonstrate that viruses bind amyloidogenic peptides in their corona and catalyze amyloid formation via surface-assisted heterogeneous nucleation. Importantly, we show that HSV-1 catalyzes the aggregation of the amyloid β-peptide (Aβ42), a major constituent of amyloid plaques in Alzheimer’s disease, in vitro and in animal models. Our results highlight the viral protein corona as an acquired structural layer that is critical for viral–host interactions and illustrate a mechanistic convergence between viral and amyloid pathologies.
The valley Zeeman effect in inter- and intra-valley trions in monolayer WSe2
Authors: Lyons T. P. , Dufferwiel S. , Brooks M. , Withers F. , Taniguchi T. , Watanabe K. , Novoselov K. S. , Burkard G. , Tartakovskii A. I.
Published: May 2019

Monolayer transition metal dichalcogenides (TMDs) hold great promise for future information processing applications utilizing a combination of electron spin and valley pseudospin. This unique spin system has led to observation of the valley Zeeman effect in neutral and charged excitonic resonances under applied magnetic fields. However, reported values of the trion valley Zeeman splitting remain highly inconsistent across studies. Here, we utilize high quality hBN encapsulated monolayer WSe2 to enable simultaneous measurement of both intervalley and intravalley trion photoluminescence. We find the valley Zeeman splitting of each trion state to be describable only by a combination of three distinct g-factors, one arising from the exciton-like valley Zeeman effect, the other two, trion specific, g-factors associated with recoil of the excess electron. This complex picture goes significantly beyond the valley Zeeman effect reported for neutral excitons, and eliminates the ambiguity surrounding the magneto-optical response of trions in tungsten based TMD monolayers.
Human mobility patterns and malaria importation on Bioko Island
Authors: Guerra Carlos A. , Kang Su Yun , Citron Daniel T. , Hergott Dianna E. B. , Perry Megan , Smith Jordan , Phiri Wonder P. , Osá Nfumu José O. , Mba Eyono Jeremías N. , Battle Katherine E. , Gibson Harry S. , García Guillermo A. , Smith David L.
Published: May 2019

Malaria burden on Bioko Island has decreased significantly over the past 15 years. The impact of interventions on malaria prevalence, however, has recently stalled. Here, we use data from island-wide, annual malaria indicator surveys to investigate human movement patterns and their relationship to Plasmodium falciparum prevalence. Using geostatistical and mathematical modelling, we find that off-island travel is more prevalent in and around the capital, Malabo. The odds of malaria infection among off-island travelers are significantly higher than the rest of the population. We estimate that malaria importation rates are high enough to explain malaria prevalence in much of Malabo and its surroundings, and that local transmission is highest along the West Coast of the island. Despite uncertainty, these estimates of residual transmission and importation serve as a basis for evaluating progress towards elimination and for efficiently allocating resources as Bioko makes the transition from control to elimination.
Ocean predation and mortality of adult Atlantic salmon
Authors: Strøm John Fredrik , Rikardsen Audun Håvard , Campana Steven E. , Righton David , Carr Jonathan , Aarestrup Kim , Stokesbury Michael J. W. , Gargan Patrick , Javierre Pablo Caballero , Thorstad Eva Bonsak
Published: May 2019

Predation and mortality are often difficult to estimate in the ocean, which hampers the management and conservation of marine fishes. We used data from pop-up satellite archival tags to investigate the ocean predation and mortality of adult Atlantic salmon (Salmo salar) released from 12 rivers flowing into the North Atlantic Ocean. Data from 156 tagged fish revealed 22 definite predation events (14%) and 38 undetermined mortalities (24%). Endothermic fish were the most common predators (n = 13), with most of these predation events occurring in the Gulf of St. Lawrence and from the Bay of Biscay to the Irish Shelf. Predation by marine mammals, most likely large deep-diving toothed whales (n = 5), and large ectothermic fish (n = 4) were less frequent. Both the estimated predation rates (ZP) and total mortality rates (ZM) where higher for Atlantic salmon from Canada, Ireland, and Spain (ZP = 0.60–1.32 y−1, ZM = 1.73–3.08 y−1) than from Denmark and Norway (ZP = 0–0.13 y−1, ZM = 0.19–1.03 y−1). This geographical variation in ocean mortality correlates with ongoing population declines, which are more profound for southern populations, indicating that low ocean survival of adults may act as an additional stressor to already vulnerable populations.
CHA2DS2-VASc score and left atrial volume dilatation synergistically predict incident atrial fibrillation in hypertension: an observational study from the Campania Salute Network registry
Authors: Rapacciuolo Antonio , Mancusi Costantino , Canciello Grazia , Izzo Raffaele , Strisciuglio Teresa , de Luca Nicola , Ammirati Giuseppe , de Simone Giovanni , Trimarco Bruno , Losi Maria-Angela
Published: May 2019

Arterial hypertension is a leading risk factor for developing atrial fibrillation. CHA2DS2-VASc score can help to decide if patients with atrial fibrillation need anticoagulation. Whether CHA2DS2-VASc may predicts incident atrial fibrillation and how it interacts with left atrial dilatation is unknown. We tested this hypothesis in a large registry of treated hypertensive patients. From 12154 hypertensive patients we excluded those with prevalent atrial fibrillation (n 51), without follow-up (n 3496), or carotid ultrasound (n 1891), and low ejection fraction (i.e. <50%, n 119). A CHA2DS2-VASc score ≥3 was compared with CHA2DS2-VASc score ≤2. Incident symptomatic or occasionally detected atrial fibrillation was the end-point of the present analysis. At baseline, 956 (15%) patients exhibited high CHA2DS2-VASc; they were older, most likely to be women, obese and diabetic, with lower glomerular filtration rate, and higher prevalence of left ventricular hypertrophy, left-atrial dilatation and carotid plaque (all p < 0.005). Prevalent Stroke/TIA was found only in the subgroup with high CHA2DS2-VASc. During follow-up (median = 54 months) atrial fibrillation was identified in 121 patients, 2.57-fold more often in patients with high CHA2DS2-VASc (95% Cl 1.71–4.86 p < 0.0001). In multivariable Cox analysis, CHA2DS2-VASc increased incidence of atrial fibrillation by 3-fold, independently of significant effect of left-atrial dilatation (both p < 0.0001) and other markers of organ damage. Incident AF is more than doubled in hypertensive patients with CHA2DS2-VASc ≥3. Coexisting CHA2DS2-VASc score >3 and LA dilatation identify high risk subjects potentially needing more aggressive management to prevent AF and associated cerebrovascular ischemic events.
Viscoelastic and shear-thinning effects of aqueous exopolymer solution on disk and sphere settling
Authors: Mrokowska Magdalena M. , Krztoń-Maziopa Anna
Published: May 2019

In this study, xanthan gum is used as a model exopolymer to demonstrate potential effects of non-Newtonian properties of natural aquatic systems on settling dynamics of particles. Rheological measurements combined with settling experiments using visualization methods revealed that instantaneous velocity fluctuations and a flow pattern formed around a particle are the effects of solution viscoelasticity and shear-thinning properties and that the average settling velocity depends on the exopolymer concentration and particle size. Our study showed that in the considered conditions a disk-shaped particle settles preferably in vertical position with a negative wake behind. The understanding of these processes is essential in technology and engineering and is necessary to improve prediction accuracy of large-scale sedimentation processes and biogeochemical cycles in the ocean involving settling of minerals, marine snow, microplastics, and locomotion of microorganisms.
The origin of rare alkali metals in geothermal fluids of southern Tibet, China: A silicon isotope perspective
Authors: Wang Wei , Wei Hai-Zhen , Jiang Shao-Yong , Tan Hong-Bing , Eastoe Christopher J. , Williams-Jones Anthony E. , Hohl Simon V. , Wu He-Pin
Published: May 2019

Geothermal waters from the Semi, Dagejia and Kawu hot springs in the Shiquanhe-Yarlung Zangbo geothermal field of southern Tibet (China) are highly enriched in rare alkali metals (RAM). However, the enrichment mechanism is still hotly debated. Here, we report the first silicon isotope data of these geothermal waters to unravel the origin of the extreme RAM enrichments. Sinter precipitation in the spring vents and water-rock interaction in the deep reservoir controlled both the silicon budget and silicon isotope fractionation. The rates of water-rock interaction and sinter precipitation in three spring sites decrease in the sequences Semi > Kawu > Dagejia, and Dagejia > Kawu > Semi respectively. Silicon isotope fractionation during sinter precipitation (i.e. Δ30Siprecipitate-solution < −0.1‰) is less than that due to water-rock interaction (i.e. Δ30Sisolution-rocks at least as high as −0.47‰), which makes it possible to use the δ30Si signatures of springs to evaluate the intensity of water-rock interaction. Based on the available evidence, a conceptual model of RAM enrichment is proposed: (i) persistent magmatic activity in southern Tibet provided the initial enrichment of the RAM in host rocks and a heat sources for the deep reservoirs of geothermal systems; (ii) the high Cl− content and long residence time (thousands of years) promote the leaching of RAM from the silicate host rocks.
Target identification, screening and in vivo evaluation of pyrrolone-fused benzosuberene compounds against human epilepsy using Zebrafish model of pentylenetetrazol-induced seizures
Authors: Tanwar Garima , Mazumder Arindam Ghosh , Bhardwaj Vijay , Kumari Savita , Bharti Richa , Yamini  , Singh Damanpreet , Das Pralay , Purohit Rituraj
Published: May 2019

Pyrrolone-fused benzosuberene (PBS) compounds were semi-synthesized from α,β,γ-Himachalenes extracted from the essential oil of Cedrus deodara following amino-vinyl-bromide substituted benzosuberenes as intermediates. These PBSs compounds classified as an attractive source of therapeutics. The α-isoform of PI3K which is a pivotal modulator of PI3K/AKT/mTOR signaling pathway, responsible for neurological disorders like epilepsy, found as a potential target molecule against these 17 semi-synthesized PBS compounds using in silico ligand-based pharmacophore mapping and target screening. The compounds screened using binding affinities, ADMET properties, and toxicity that were accessed by in silico docking simulations and pharmacokinetics profiling. Ultimately two compounds viz., PBS-8 and PBS-9 were selected for further in vivo evaluation using a zebrafish (Danio rerio) model of pentylenetetrazol (PTZ)-induced clonic convulsions. Additionally, gene expression studies performed for the genes of the PI3K/AKT/mTOR pathway which further validated our results. In conclusion, these findings suggested that PBS-8 is a promising candidate that could bedeveloped as a potential antiepileptic.
Quantification of very low-abundant proteins in bacteria using the HaloTag and epi-fluorescence microscopy
Authors: Lepore Alessia , Taylor Hannah , Landgraf Dirk , Okumus Burak , Jaramillo-Riveri Sebastián , McLaren Lorna , Bakshi Somenath , Paulsson Johan , Karoui M. El
Published: May 2019

Cell biology is increasingly dependent on quantitative methods resulting in the need for microscopic labelling technologies that are highly sensitive and specific. Whilst the use of fluorescent proteins has led to major advances, they also suffer from their relatively low brightness and photo-stability, making the detection of very low abundance proteins using fluorescent protein-based methods challenging. Here, we characterize the use of the self-labelling protein tag called HaloTag, in conjunction with an organic fluorescent dye, to label and accurately count endogenous proteins present in very low numbers (<7) in individual Escherichia coli cells. This procedure can be used to detect single molecules in fixed cells with conventional epifluorescence illumination and a standard microscope. We show that the detection efficiency of proteins labelled with the HaloTag is ≥80%, which is on par or better than previous techniques. Therefore, this method offers a simple and attractive alternative to current procedures to detect low abundance molecules.
Effects of 1,8-cineole on neuropathic pain mediated by P2X2 receptor in the spinal cord dorsal horn
Authors: Zheng Xiao-bo , Zhang Ya-ling , Li Qing , Liu Yi-guo , Wang Xiang-dong , Yang Bao-lin , Zhu Gao-chun , Zhou Cong-fa , Gao Yun , Liu Zeng-xu
Published: May 2019

As an intractable health threat, neuropathic pain is now a key problem in clinical therapy, which can be caused by lesions affecting the peripheral nervous systems. 1,8-cineole is a natural monoterpene cyclic ether present in eucalyptus and has been reported to exhibit anti-inflammatory and antioxidant effects. Research has shown that 1,8-cineole inhibits P2X3 receptor-mediated neuropathic pains in dorsal root ganglion. The P2X2 and P2X3 receptors participate in the transmission of algesia and nociception information by primary sensory neurons. In the present study, We thus investigated in the spinal cord dorsal horn whether 1,8-cineole inhibits the expression of P2X2 receptor-mediated neuropathic pain. This study used rats in five random groups: group of chronic constriction injury(CCI) with dimethysulfoxide control (CCI + DMSO); group of CCI; sham group(Sham); group of CCI treated with a low dose 1,8-cineole (CCI + 50 mg/kg); group of CCI with a high dose (CCI + 100 mg/kg). We observed the effects of 1,8-cineole on thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT). We examined P2X2 receptors mRNA change in rat spinal cord dorsal horn by In situ nucleic acid hybridization(ISH) and Quantitative realtime polymerase chain reaction (qRT-PCR) methods. Western Blotting and Immunohistochemical staining methods were used to observe P2X2 receptor protein expressions in the rat spinal cord dorsal horn. It demonstrated that oral administration of 1,8-cineole inhibits over-expression of P2X2 receptor protein and mRNA in the spinal cord and dorsal horn in the CCI rats. And the study explored new methods for the prevention and treatment of neuropathic pain.
Cognitive and Microbiome Impacts of Experimental Ancylostoma ceylanicum Hookworm Infections in Hamsters
Authors: Pan Samuel C. , Ward Doyle V. , Yin Yunqiang , Hu Yan , Elfawal Mostafa A. , Clark Robert E. , Aroian Raffi V.
Published: May 2019

Hookworms are one of the most prevalent and important parasites, infecting ~500 million people worldwide. Hookworm disease is among the leading causes of iron-deficiency anemia in the developing world and is associated with significant growth stunting and malnutrition. In humans, hookworms appear to impair memory and other forms of cognition, although definitive data are hard to come by. Here we study the impact of a human hookworm parasite, Ancylostoma ceylanicum, on cognition in hamsters in a controlled laboratory setting. We developed tests that measure long-term memory in hamsters. We find that hookworm-infected hamsters were fully capable of detecting a novel object. However, hookworm-infected hamsters were impaired in detecting a displaced object. Defects could be discerned at even at low levels of infection, whereas at higher levels of infection, hamsters were statistically unable to distinguish between displaced and non-displaced objects. These spatial memory deficiencies could not be attributed to defects in infected hamster mobility or to lack of interest. We also found that hookworm infection resulted in reproducible reductions in diversity and changes in specific taxanomic groups in the hamster gut microbiome. These data demonstrate that human hookworm infection in a laboratory mammal results in a specific, rapid, acute, and measurable deficit in spatial memory, and we speculate that gut alterations could play some role in these cognitive deficits. Our findings highlight the importance of hookworm elimination and suggest that finer tuned spatial memory studies be carried out in humans.