bluuebunny/crossref_metadata_2025_split huggingface dataset:
The minimum metallicity of globular clusters and its physical origin – implications for the galaxy mass–metallicity relation and observations of proto-globular clusters at high redshift
Authors: Kruijssen J M Diederik 
Published: April 2019

ABSTRACT
In the local Universe, globular clusters (GCs) with metallicities [Fe/H] &lt; −2.5 are extremely rare. In this Letter, the close connection between GC formation and galaxy evolution is used to show that this GC metallicity ‘floor’ results from the galaxy mass–metallicity relation of ultra low-luminosity galaxies (ULLGs) at high redshift, where the most metal-poor GCs must have formed. Galaxies with metallicities [Fe/H] ≲ −2.5 have too low masses to form GCs with initial masses Mi ≳ 105 M⊙ needed to survive for a Hubble time. This translates the galaxy mass–metallicity relation into a maximum initial cluster mass–metallicity relation for [Fe/H] ≲ −1.8, which naturally leads to the observed colour–magnitude relation of metal-poor GCs at z = 0 (the ‘blue tilt’). Its strength traces the slope of the gas phase mass–metallicity relation of ULLGs. Based on the observed blue tilt of GCs in the Virgo and Fornax Clusters, the galaxy mass–metallicity relation is predicted to have a slope of α = 0.4 ± 0.1 for 105 ≲ M⋆/M⊙ ≲ 107 at z ≳ 2. The GC metallicity floor implies a minimum host galaxy mass and a maximum redshift for GC formation. Any proto-GCs that may be detected at z &gt; 9 are most likely to end up in galaxies presently more massive than the Milky Way, whereas GCs in low-mass galaxies such as the Fornax dSph (M⋆ ≈ 4 × 107 M⊙) formed at z ≲ 3.
Explaining the enhanced star formation rate of Jellyfish galaxies in galaxy clusters
Authors: Safarzadeh Mohammadtaher , Loeb Abraham 
Published: April 2019

ABSTRACT
We study the recently observed JellyFish galaxies (JFGs), which are found to have their gas content ram pressure stripped away in galaxy clusters. These galaxies are observed to have an enhanced star formation rate of about 0.2 dex compared with a control sample of the same stellar mass in their discs. We model the increase in the star formation efficiency as a function of intracluster medium pressure and parametrize the cold gas content of the galaxies as a function of cluster-centric distance. We show that regarding the external pressure as a positive feedback results in agreement with the observed distribution of enhanced star formation in the JFGs if clouds are shielded from evaporation by magnetic fields. Our results predict that satellites with halo mass $\lt 10^{11}{\rm \, M_\odot }$ moving with Mach numbers $\mathcal {M}\approx 2$, and inclination angles below 60 deg, are more likely to be detected as JFGs.
Colloid Cysts: Evolution of Surgical Approach Preference and Management of Recurrent Cysts
Authors: Heller Robert S , Heilman Carl B 
Published: April 2019

Abstract

BACKGROUND
Optimal management of third ventricular colloid cysts remains debated. While microsurgery offers greater resection rates and lower recurrences, endoscopy offers a perceived less invasive option.

OBJECTIVE
To describe the evolution of our practice to favor microsurgery and determine the optimal management of recurrent colloid cysts

METHODS
Any patient having undergone surgery for a colloid cyst by the senior author was identified and included in the study cohort. Clinical, radiographic, and operative records were reviewed, with attention paid to those patients requiring recurrent surgery.

RESULTS
Thirty-three patients were treated for intracranial colloid cysts between 1995 and 2017. Two patients had initial surgical treatment at an outside institution prior to presentation at our institution. Microsurgery was used in 15/31 initial cases, endoscopy in 13 cases, and ventriculoperitoneal shunting in 3 cases. Between 1995 and 2005, 89% of colloid cysts (8/9 cases) were resected endoscopically, whereas 74% of colloid cysts (14/19 cases) were resected by microsurgery after 2005. Of the 13 patients treated endoscopically, 6 (46%) required surgery for recurrent cysts. Incomplete cyst wall resection at the initial operation increased the recurrence rate to 55%. There were no recurrences in the microsurgery cohort.

CONCLUSION
Surgical resection of recurrent colloid cysts should focus on complete removal of the cyst wall to minimize the chance of recurrence. Microsurgery has been shown to provide the highest success rates for cyst wall resection and lowest rates of recurrence and is therefore recommended for patients undergoing surgery for primary and recurrent colloid cysts.
Sounds of Loss: Church Bells, Place, and Time in the Habsburg Empire During the First World War*
Authors: Morelon Claire 
Published: April 2019

Abstract
This article examines the rupture created by the First World War in towns and villages of the Habsburg Empire by focusing on the requisition of church bells, which were melted for the production of munitions. Bells performed an important social function for both rural and urban populations in the early twentieth century. They gathered communities at important times, stood as symbols of local identity, and gave a structure to the days and lives of rural inhabitants. Their removal generated an intense emotional response among parishioners, which is documented in newspapers, parish newsletters or chronicles, and petitions to the Ministry of Religion. These various reactions shed light on the difficult conciliation between local identity, religiosity, and imperial patriotism during the war. The requisitions contributed to the de-legitimization process experienced by the Habsburg Empire at the end of the war, as well as in the disruption of soundscapes in the region. The sense of time was also disturbed as daily rhythms, religious celebrations, and death rituals changed. This exploration of material culture draws on insights from the history of emotions and sensory history to study the changes in the sense of place that the war provoked in local communities.
Enhanced formation of transparent exopolymer particles (TEP) under turbulence during phytoplankton growth
Authors: Burns Wilton G , Marchetti Adrian , Ziervogel Kai 
Published: April 2019

AbstractSmall-scale turbulence in the surface ocean is ubiquitous, influencing phytoplankton dynamics with consequences for energy flow. The underlying mechanisms that drive changes in phytoplankton dynamics under turbulence are not well constrained. We investigated growth of four phytoplankton species at different turbulence levels in oscillating grid tanks. We also measured transparent exopolymer particles (TEP) from phytoplankton exudates, which play a major role in biogeochemical fluxes in the ocean. Turbulence levels in the tanks reflected in situ conditions in surface waters from the open ocean to higher turbulent environments such as estuaries. Growth rates were unaffected by turbulence while TEP concentrations as xanthan gum (XG) equivalents normalized to algal cells showed generally higher levels in the high turbulence compared to the low turbulence treatments particularly during initial algal growth. Results from a mixing experiment without algal cells and XG also revealed enhanced formation of TEP-like particles under high mixing conditions, indicating that TEP formation in the phytoplankton turbulence treatments was mainly driven by physical processes, such as enhanced encounter rates of TEP-precursors under high mixing. Our results underline the importance of small-scale turbulence on TEP formation with possible consequences for particle aggregation and vertical carbon fluxes in the ocean.
Cancer Chemoprevention: Preclinical In Vivo Alternate Dosing Strategies to Reduce Drug Toxicities
Authors: Mohammed Altaf , Fox Jennifer T , Miller Mark Steven 
Published: April 2019

AbstractCancer chemopreventive agents inhibit the formation of precursor lesions and/or the progression of these lesions to late stage disease. This approach to disease control has the potential to reduce the physical and financial costs of cancer in society. Several drugs that have been approved by the FDA for other diseases and have been extensively evaluated for their safety and pharmacokinetic/pharmacodynamic characteristics have the potential to be repurposed for use as cancer chemopreventive agents. These agents often mechanistically inhibit signaling molecules that play key roles in the carcinogenic process. The safety profile of agents is a primary concern when considering the administration of drugs for chemoprevention, as the drugs will be given chronically to high-risk, asymptomatic individuals. To decrease drug toxicity while retaining efficacy, several approaches are currently being explored. In this short review, we describe studies that use preclinical in vivo models to assess efficacy of alternative drug dosing strategies and routes of drug administration on chemopreventive drug efficacy. In vivo drug dosing strategies that reduce toxicity while retaining efficacy will pave the way for future cancer prevention clinical trials.
Investigation of the pathogenic RFC1 repeat expansion in a Canadian and a Brazilian ataxia cohort: identification of novel conformations
Authors: Akçimen Fulya , Ross Jay P. , Bourassa Cynthia V. , Liao Calwing , Rochefort Daniel , Gama Maria Thereza Drumond , Dicarie Marie-Josée , Barsottini Orlando G. , Brais Bernard , Pedroso José Luiz , Dion Patrick A. , Rouleau Guy A. 
Published: April 2019

AbstractA homozygous pentanucleotide expansion in the RFC1 gene has been shown to be a common cause of late-onset ataxia. In the general population a total of four different repeat conformations have been observed: a wild type sequence AAAAG (11 repeats), and longer expansions of AAAAG, AAAGG and AAGGG sequences. However, in ataxia cases only the AAGGG expansion has been shown to be pathogenic. In this study, we assessed the prevalence and nature of RFC1 repeat expansions in three adult-onset ataxia cohorts: Brazilian (n = 23) and Canadian (n = 26) cases that tested negative for other known ataxia mutations, as well as a cohort of randomly selected Canadian cases (n = 128) without regard to a genetic diagnosis. We identified the homozygous AAGGG pathogenic expansion in only one Brazilian family with two affected siblings, and in one Canadian case. The RFC1 expansion may therefore not be a common cause of adult-onset ataxia in these populations. Interestingly we observed two new repeat motifs, AAGAG and AGAGG, which indicates the dynamic nature of the pentanucleotide expansion sequence. To assess the frequency of these two new repeat conformations in the general population we screened 163 healthy individuals. These novel motifs were more frequent in patients versus controls. While we cannot be certain that the homozygous genotypes of the novel expanded conformations are pathogenic, their occurrence should nonetheless be taken into consideration in future studies.
Arbovirus emergence in temperate climates: the case of Córdoba, Argentina, 2009-2018
Authors: Robert Michael A. , Tinunin Daniela Tatiana , Benitez Elisabet Marina , Ludueña-Almeida Francisco , Romero Moory , Stewart-Ibarra Anna M. , Estallo Elizabet Lilia 
Published: April 2019

AbstractThe distribution of arbovirus disease transmission is expanding from the tropics and subtropics into temperate regions worldwide. The aim of this study was to characterize the emergence of arboviruses in the temperate city of Córdoba, Argentina (2009-2018), including dengue virus (DENV) serotypes and origins of imported cases. The first cases of dengue fever were reported in 2009, followed by outbreaks in 2013, 2015, and 2016, each outbreak having greater incidence than the previous. DENV1 was the predominant serotype. Cases were imported from Venezuela, Brazil, Bolivia, Mexico, Costa Rica, and northern Argentina. The first imported cases of chikungunya were reported in 2014 and the first imported and autochthonous of Zika fever in 2016. Regional efforts are needed to strengthen surveillance, due to the key role of human movement in arbovirus introductions.
Loss of adipocyte identity through synergistic repression of PPARγ by TGF-β and mechanical stress
Authors: Bielczyk-Maczyńska Ewa , Taylor Brooks , Miller Cayla M , Zhao Michael L , Shah Arnav , Bahrami-Nejad Zahra , Dunn Alexander R , Teruel Mary N 
Published: April 2019

ABSTRACTAdipocytes convert into myofibroblasts in a TGF-β-dependent mouse model of fibrosis. The molecular steps and timing underlying this conversion are poorly understood, hindering development of antifibrotic therapies. Here we used two single-cell approaches, lineage tracing and live-cell imaging of an adipocyte marker PPARγ, to track the fate of adipocytes induced to convert by TGF-β. We found that TGF-β alone was not sufficient to activate the TGF-β pathway and to induce myofibroblast conversion in cells with high PPARγ expression. However, robust conversion was observed when an additional PPARγ-inhibiting stimulus, mechanical stress applied by increasing adhesion area on a stiff matrix, was applied simultaneously with TGF-β. We show that the PPARγ downregulation in response to increased adhesion area required both fibronectin and a sufficiently stiff extracellular matrix (ECM) and was partially mediated by Rho. Our results show for the first time the order of the molecular processes driving fat tissue fibrosis and the requirement for signal convergence for the loss of adipocyte identity.
Shifting from fear to safety through deconditioning-update: a novel approach to attenuate fear memories
Authors: Popik Bruno , Amorim Felippe E. , Amaral Olavo B. , de Oliveira Alvares Lucas 
Published: April 2019

AbstractAversive memories are at the heart of psychiatric disorders such as phobias and post-traumatic stress disorder (PTSD). Here, we present a new behavioral approach in rats that robustly attenuates aversive memories. This method consists of “deconditioning” animals previously trained to associate a tone with a strong footshock by replacing it with a much weaker one during memory retrieval. Our results indicate that deconditioning-update is more effective than traditional extinction in reducing fear responses; moreover, such effects are long lasting and resistant to renewal and spontaneous recovery. Remarkably, this strategy overcame important boundary conditions for memory updating, such as remote or very strong traumatic memories. The same beneficial effect was found in other types of fear-related memories. Deconditioning was mediated by L-type voltage-gated calcium channels and is consistent with computational accounts of mismatch-induced memory updating. Our results suggest that shifting from fear to safety through deconditioning-update is a promising approach to attenuate traumatic memories.
Acquired FGFR and FGF alterations confer resistance to estrogen receptor (ER) targeted therapy in ER+ metastatic breast cancer
Authors: Mao Pingping , Cohen Ofir , Kowalski Kailey J. , Kusiel Justin G. , Buendia-Buendia Jorge E. , Cuoco Michael S. , Exman Pedro , Wander Seth A. , Waks Adrienne G. , Nayar Utthara , Chung Jon , Freeman Samuel , Rozenblatt-Rosen Orit , Miller Vincent A. , Piccioni Federica , Root David E. , Regev Aviv , Winer Eric P. , Lin Nancy U. , Wagle Nikhil 
Published: April 2019

AbstractBeyond acquired mutations in the estrogen receptor (ER), mechanisms of resistance to ER-directed therapies in ER+ breast cancer have not been clearly defined. We conducted a genome-scale functional screen spanning 10,135 genes to investigate genes whose overexpression confer resistance to selective estrogen receptor degraders. Pathway analysis of candidate resistance genes demonstrated that the FGFR, ERBB, insulin receptor, and MAPK pathways represented key modalities of resistance. In parallel, we performed whole exome sequencing in paired pre-treatment and post-resistance biopsies from 60 patients with ER+ metastatic breast cancer who had developed resistance to ER-targeted therapy. The FGFR pathway was altered via FGFR1, FGFR2, or FGF3 amplifications or FGFR2 mutations in 24 (40%) of the post-resistance biopsies. In 12 of the 24 post-resistance tumors exhibiting FGFR/FGF alterations, these alterations were not detected in the corresponding pre-treatment tumors, suggesting that they were acquired or enriched under the selective pressure of ER-directed therapy. In vitro experiments in ER+ breast cancer cells confirmed that FGFR/FGF alterations led to fulvestrant resistance as well as cross-resistance to the CDK4/6 inhibitor palbociclib. RNA sequencing of resistant cell lines treated with different drug combinations demonstrated that FGFR/FGF induced resistance through ER reprogramming and activation of the MAPK pathway. The resistance phenotypes were reversed by FGFR inhibitors, a MEK inhibitor, and/or a SHP2 inhibitor, suggesting potential treatment strategies. The detection of targetable, clonally acquired genetic alterations in the FGFR pathway in metastatic tumor biopsies highlights the value of serial tumor testing to dissect mechanisms of resistance in human breast cancer and its potential application in directing clinical management.
Spontaneous isomerization of long-lived proteins provides a molecular mechanism for the lysosomal failure observed in Alzheimer’s disease
Authors: Lambeth Tyler R. , Riggs Dylan L. , Talbert Lance E. , Tang Jin , Coburn Emily , Kang Amrik S. , Noll Jessica , Augello Catherine , Ford Byron D. , Julian Ryan R. 
Published: April 2019

AbstractProteinaceous aggregation is a well-known observable in Alzheimer’s disease (AD), but failure and storage of lysosomal bodies within neurons is equally ubiquitous and actually precedes bulk accumulation of extracellular amyloid plaque. In fact, AD shares many similarities with certain lysosomal storage disorders though establishing a biochemical connection has proven difficult. Herein, we demonstrate that isomerization and epimerization, which are spontaneous chemical modifications that occur in long-lived proteins, prevent digestion by the proteases in the lysosome (namely the cathepsins). For example, isomerization of aspartic acid into L-isoAsp prevents digestion of the N-terminal portion of Aβ by cathepsin L, one of the most aggressive lysosomal proteases. Similar results were obtained after examination of various target peptides with a full series of cathepsins, including endo-, amino-, and carboxy-peptidases. In all cases peptide fragments too long for transporter recognition or release from the lysosome persisted after treatment, providing a mechanism for eventual lysosomal storage and bridging the gap between AD and lysosomal storage disorders. Additional experiments with microglial cells confirmed that isomerization disrupts proteolysis in active lysosomes. These results are easily rationalized in terms of protease active sites, which are engineered to precisely orient the peptide backbone and cannot accommodate the backbone shift caused by isoaspartic acid or side chain dislocation resulting from epimerization. Although Aβ is known to be isomerized and epimerized in plaques present in AD brains, we further establish that the rates of modification for aspartic acid in positions 1 and 7 are fast and could accrue prior to plaque formation. Spontaneous chemistry can therefore provide modified substrates capable of inducing gradual lysosomal failure, which may play an important role in the cascade of events leading to the disrupted proteostasis, amyloid formation, and tauopathies associated with AD.
Dynamic cerebral autoregulation of endurance-trained men following 6 weeks of high-intensity interval training to exhaustion
Authors: Drapeau Audrey , Labrecque Lawrence , Imhoff Sarah , Paquette Myriam , Le Blanc Olivier , Malenfant Simon , Brassard Patrice 
Published: April 2019

ABSTRACTElevated cardiorespiratory fitness (CRF) is associated with reduced dynamic cerebral autoregulation (dCA), but the impact of exercise trainingper seon dCA remains equivocal. In addition, resting cerebral blood flow (CBF) and dCA after high-intensity interval training (HIIT) in individuals with already high CRF is unknown. We examined to what extent 6 weeks of HIIT affect resting CBF and dCA in cardiorespiratory fit men and explored if potential changes are intensity-dependent. Endurance-trained men were assigned to group HIIT85(85% of maximal aerobic power, 1 to 7 min effort bouts, n = 8) and HIIT115(115% of maximal aerobic power, 30 s to 1 min effort bouts, n = 9). Training sessions were completed until exhaustion 3 times/week over 6 weeks. Mean arterial pressure (MAP) and middle cerebral artery mean blood velocity (MCAvmean) were measured continuously at rest and during repeated squat-stands (0.05 and 0.10 Hz). Transfer function analysis (TFA) was used to characterize dCA on driven blood pressure oscillations during repeated squat-stands. Neither training nor intensity had an effect on resting MAP and MCAvmean(bothP> 0.05). TFA phase during 0.10 Hz squat-stands decreased after HIIT irrespective of intensity (HIIT85: 0.77 ± 0.22 vs. 0.67 ± 0.18 radians; HIIT115: pre: 0.62 ± 0.19 vs. post: 0.59 ± 0.13 radians, time effectP= 0.048). These results suggest that HIIT over 6 weeks have no apparent benefits on resting CBF, but a subtle attenuation in dCA is seen posttraining irrespective of intensity training in endurance-trained men.NEW & NOTEWORTHYThe novel findings of this study are that 6 weeks of submaximal and supramaximal high-intensity interval exercise to exhaustion reduce dynamic cerebral autoregulation irrespective of training intensity in endurance-trained men. However, these HIIT protocols do not influence resting cerebral blood flow in these individuals. The results indicate the cerebrovasculature of endurance-trained men has an attenuated ability to react to large and rapid changes in blood pressure following HIIT.
Complex responses to inflammatory oxidants by the probiotic bacteriumLactobacillus reuteri
Authors: Thakur Poulami Basu , Long Abagail R. , Nelson Benjamin J. , Kumar Ranjit , Rosenberg Alexander F. , Gray Michael J. 
Published: April 2019

ABSTRACTInflammatory diseases of the gut are associated with increased intestinal oxygen concentrations and high levels of inflammatory oxidants, including hydrogen peroxide (H2O2) and hypochlorous acid (HOCl), which are antimicrobial compounds produced by the innate immune system. This contributes to dysbiotic changes in the gut microbiome, including increased populations of pro-inflammatory enterobacteria (Escherichia coliand related species) and decreased levels of health-associated anaerobic Firmicutes and Bacteroidetes. The pathways for H2O2and HOCl resistance inE. colihave been well-studied, but little is known about how commensal and probiotic bacteria respond to inflammatory oxidants. In this work, we have characterized the transcriptomic response of the anti-inflammatory, gut-colonizing Gram-positive probioticLactobacillus reuterito both H2O2and HOCl.L. reuterimounts distinct responses to each of these stressors, and both gene expression and survival were strongly affected by the presence or absence of oxygen. Oxidative stress response inL. reuterirequired several factors not found in enterobacteria, including the small heat shock protein Lo18, polyphosphate kinase 2, and RsiR, anL. reuteri-specific regulator of anti-inflammatory mechanisms. These results raise the intriguing possibility of developing treatments for inflammatory gut diseases that could sensitize pro-inflammatory enterobacteria to killing by the immune system while sparing anti-inflammatory, health-associated species.IMPORTANCEIt is becoming increasingly clear that effective treatment of inflammatory gut diseases will require modulation of the gut microbiota. Preventing pro-inflammatory bacteria from blooming while also preserving anti-inflammatory and commensal species is a considerable challenge, but our results suggest that it may be possible to take advantage of differences in the way different species of gut bacteria resist inflammatory oxidants to accomplish this goal.