bluuebunny/crossref_metadata_2025_split huggingface dataset:
Offshoring the Border: The 1981 United States–Haiti Agreement and the Origins of Extraterritorial Maritime Interdiction
Authors: Tennis Katherine H. 
Published: January 2019

AbstractExtraterritorial maritime interdiction is a common tactic used by destination states to keep unwanted migrants from reaching their borders. But it is problematic, raising legal concerns about refoulement as well as political concerns about sovereignty. Where did extraterritorial interdiction come from, and how has it become so widespread? This article draws on archival sources and contemporaneous legal opinions from within the Reagan administration to tell the origin story of the pivotal 1981 United States–Haiti agreement that pioneered this model of border control. Even at the time of adoption, this agreement faced legal challenges, and was viewed as a solution of last resort. Yet many of the legal challenges of modern extraterritorial interdiction trace back to the unique circumstances shaping this first agreement—including the need to cooperate with countries of embarkation, anticipatory determination of attempted entry and the offshoring of protection responsibilities. They were locked in by path-dependent feedback mechanisms domestically and then diffused internationally.
Middleman Minorities and Ethnic Violence: Anti-Jewish Pogroms in the Russian Empire
Authors: Grosfeld Irena , Sakalli Seyhun Orcan , Zhuravskaya Ekaterina 
Published: January 2019

AbstractUsing detailed panel data from the Pale of Settlement area between 1800 and 1927, we document that anti-Jewish pogroms—mob violence against the Jewish minority—broke out when economic shocks coincided with political turmoil. When this happened, pogroms primarily occurred in places where Jews dominated middleman occupations, i.e., moneylending and grain trading. This evidence is inconsistent with the scapegoating hypothesis, according to which Jews were blamed for all misfortunes of the majority. Instead, the evidence is consistent with the politico-economic mechanism, in which Jewish middlemen served as providers of insurance against economic shocks to peasants and urban grain buyers in a relationship based on repeated interactions. When economic shocks occurred in times of political stability, rolling over or forgiving debts was an equilibrium outcome because both sides valued their future relationship. In contrast, during political turmoil, debtors could not commit to paying in the future, and consequently, moneylenders and grain traders had to demand immediate (re)payment. This led to ethnic violence, in which the break in the relationship between the majority and Jewish middlemen was the igniting factor.
Ecological causes of uneven mammal diversity
Authors: Upham Nathan S. , Esselstyn Jacob A. , Jetz Walter 
Published: January 2019

ABSTRACTThe uneven distributions of species over geography (e.g., tropical versus temperate regions) and phylogeny (e.g., rodents and bats versus the aardvark) are prominent biological patterns for which causal interconnections remain enigmatic. Here we investigate this central issue for living mammals using time-sliced clades sampled from a comprehensive recent phylogeny (N=5,911 species, ∼70% with DNA) to assess how different levels of unsampled extinction impact the inferred causes of species richness variation. Speciation rates are found to strongly exceed crown age as a predictor of clade species richness at every time slice, rejecting a clock-like model in which the oldest clades are the most speciose. Instead, mammals that are low-vagility or daytime-active show the fastest recent speciation and greatest extant richness. This suggests primary roles for dispersal limitation leading to geographic speciation (peripatric isolation) and diurnal adaptations leading to ecological speciation (time partitioning). Rates of speciation are also faster in temperate than tropical lineages, but only among older clades, consistent with the idea that many temperate lineages are ephemeral. These insights, enabled by our analytical framework, offer straightforward support for ecological effects on speciation-rate variation among clades as the primary cause of uneven phylogenetic richness patterns.
The BD2 domain of BRD4 is a determinant in EndoMT and vein graft neointima formation
Authors: Zhang Mengxue , Wang Bowen , Urabe Go , Huang Yitao , Plutzky Jorge , Kent K. Craig , Guo Lian-Wang 
Published: January 2019

AbstractBackgroundVein-graft bypass is commonly performed to overcome atherosclerosis but is limited by high failure rates, principally due to neointimal wall thickening. Recent studies reveal that endothelial-mesenchymal transition (EndoMT) is critical for vein-graft neointima formation. BETs are a family of Bromo/ExtraTerminal domains-containing epigenetic reader proteins (BRD2, BRD3, BRD4). They bind acetylated histones through their unique tandem bromodomains (BD1, BD2), facilitating transcriptional complex formation and cell-state transitions. The role for BETs, including individual BRDs and their unique BDs, is not well understood in EndoMT and neointimal formation.Methods and ResultsRepression of BRD4 expression abrogated TGFβ1-induced EndoMT, with greater effects than BRD2 or BRD3 knockdown. An inhibitor selective for BD2 in all BETs, but not that for BD1, blocked EndoMT. Moreover, expression of a dominant-negative BRD4-specific BD2 fully abolished EndoMT. Concordantly, BRD4 knockdown repressed TGFβ1-stimulated increase of ZEB1 protein – a transcription factor integral in EndoMT. In vivo, lentiviral gene transfer of either BRD4 shRNA or dominant negative BRD4-specific BD2 mitigated neointimal development in rat jugular veins grafted to carotid arteries.ConclusionsOur data reveal the BD2 domain of BRD4 as a determinant driving EndoMT in vitro and neointimal formation in vivo. These findings provide new insight into BET biology, while offering prospects of specific BET domain targeting as an approach to limiting neointima and extending vein graft patency.
Specific domains of early parenting, their heritability and differential association with adolescent behavioural and emotional disorders and academic achievement
Authors: Culpin Iryna , Bornstein Marc H. , Putnick Diane L. , Sallis Hannah , Lee Ruby , Cordero Miguel , Rajyaguru Priya , Kordas Katarzyna , Cadman Tim , Pearson Rebecca M. 
Published: January 2019

AbstractBackgroundVariations in parenting across large populations have rarely been described. It also remains unclear which specific domains of parenting are important for which specific offspring developmental outcomes. The study describes different domains of early parenting behaviours, their genetic heritability, and then determines the extent to which specific domains of parenting are associated with later offspring outcomes.MethodsParenting behaviours (birth to 3 years) were extracted from self-reported questionnaires administered to 12,358 mothers from the UK-based birth cohort study, the Avon Longitudinal Study of Parents and Children, and modelled as a latent factor using Confirmatory Factor Analysis. Genetic heritability and correlations between parenting factors were estimated using wide complex trait analysis. Offspring emotional, behavioural and academic outcomes were assessed at age 16 years using the self-reported Short Mood and Feelings Questionnaire, the Development and Well-Being Assessment, and grades achieved in national English Language examination.ResultsThree parenting factors were derived: parental enjoyment, conflictual relationships and stimulation; all showed low genetic heritability. There was no evidence of associations between parenting factors and offspring depressed mood. Stimulation was associated with better English grades after controlling for maternal education (standardised β=0.058, p=0.007), and enjoyment was negatively associated with English grades (β=-0.082, p=0.002). Conflictual relationships were associated with higher risk of offspring behavioural disorders after controlling for behavioural problems at age 3 years (β=0.227, p=0.007). Higher enjoyment reduced the association between conflict and behavioural problems (interaction term β=0.113, p<0.001).ConclusionsWe found evidence for predictive specificity of early parenting domains for offspring outcomes in adolescence. Early stimulation, unlike enjoyment, promoted later educational achievement. Conflictual relationships were associated with greater risk of behavioural problems, buffered by increased enjoyment. These findings hold implications for parenting interventions, guiding their focus according to specificity of parenting domains and their long-term outcomes in children.
The future of a partially effective HIV vaccine: assessing limitations at the population level
Authors: Selinger Christian , Dimitrov Dobromir T. , Welkhoff Philip , Bershteyn Anna 
Published: January 2019

AbstractObjectivesMathematical models have unanimously predicted that a first-generation HIV vaccine would be useful and cost-effective to roll out, but that its overall impact would be insufficient to reverse the epidemic. Here, we explore what factors contribute most to limiting the impact of such a vaccine.MethodsRanging from a theoretical ideal to a more realistic regimen, mirroring the one used in the currently ongoing trial in South Africa (HVTN 702), we model a nested hierarchy of vaccine attributes such as speed of roll-out, efficacy, and retention of booster doses.ResultsThe predominant reasons leading to a substantial loss of vaccine impact on the HIV epidemic are the time required to scale up mass vaccination, limited durability and waning of efficacy.ConclusionsA partially effective HIV vaccine will be a critical milestone for the development of a highly effective, durable, and scalable next-generation vaccine. Accelerated development, expedited vaccine availability, and improved immunogenicity are the main attributes of a vaccine that could dramatically reverse the course of the epidemic in highly endemic countries.
Automation for the identification of Pseudomonas aeruginosa: Comparison of TDR-300B, VITEK®2 and VITEK®-MS
Authors: Moehario Lucky H , Boestami Hans P , Edbert Daniel , Tjoa Enty , Robertus T 
Published: January 2019

AbstractQuick and precise methods have always been needed in the medical field to correctly identify the agent of infection. Automated systems for diagnosis of infectious pathogen such Pseudomonas aeruginosa from critical patients with infections in the Intensive Care Unit is essential. This study aimed to compare the capability of automated biochemistry-based identification system, TDR-300B and VITEK®2, to the one of Matrix-Assisted Laser Desorption/Ionization - Time of Flight (MALDI-TOF), VITEK®-MS, in the identification of P. aeruginosa.Samples were P. aeruginosa isolates collection from Laboratory of Microbiology, Faculty of Medicine and Health Science UNIKA Atma Jaya. These isolates were refreshed; one single colony of oxidase-positive Gram-negative rods was further inoculated in TDR-300B NF-64 cards and VITEK®2 GN cassettes. The bacterial identification was also carried out using VITEK®-MS as gold-standard. Positivity of TDR-300B and VITEK®2 in the identification of P. aeruginosa was 87.09% (27/31) and 90.32% (28/31) in the species level, and 87.09%, 96.77% in the genus level respectively. The congruity of TDR-300B/ VITEK®2 in the species and genus level was 83.87% and 87.09%. When compared to VITEK®-MS, congruence of VITEK®2 was 93.30% (24/26) and TDR-300B was 80.76% (21/26). Sensitivity value for TDR-300B and VITEK®2 was high, 95.45% and 100%, positive predictive value and accuracy were lower in TDR-300B than VITEK®2; Fisher’ exact value was >0.05, thus there were no significant differences in the capability of TDR-300B and VITEK®2 in the identification of P. aeruginosa.
Kinetics of enzymatic mercury methylation at nanomolar concentrations catalyzed by HgcAB
Authors: Date Swapneeta S. , Parks Jerry M. , Rush Katherine W. , Wall Judy D. , Ragsdale Stephen W. , Johs Alexander 
Published: January 2019

ABSTRACTMethylmercury (MeHg) is a potent neurotoxin that bioaccumulates in fish. MeHg is generated by anaerobic bacteria and archaea possessing the gene pair hgcAB. Although bacterial mercury (Hg) methylation has been characterized in vivo, the specific role of HgcAB in catalyzing Hg methylation is not well understood. Here we report the kinetics of HgcAB-mediated Hg methylation in cell lysates of Desulfovibrio desulfuricans ND132 at nanomolar Hg concentrations. The enzymatic Hg methylation mediated by HgcAB is highly oxygen-sensitive, irreversible, and follows Michaelis-Menten kinetics with an apparent KM of 3.2 nM and Vmax of 19.7 fmol·min-1·mg-1 total protein for the substrate Hg(II). Although the abundance of HgcAB in the cell lysates is extremely low, Hg(II) was quantitatively converted to MeHg at subnanomolar substrate concentrations. Supplementation with ATP, methyltetrahydrofolate, or pyruvate did not enhance MeHg production under the experimental conditions. Insight into the kinetics of Hg methylation catalyzed by HgcAB advances our understanding of the complex global Hg cycle.
Tombusvirusp19 captures RNase III-cleaved double-stranded RNAs formed by overlapping sense and antisense transcripts inE. coli
Authors: Huang Linfeng , Deighan Padraig , Jin Jingmin , Li Yingxue , Lee Elaine , Mo Shirley S. , Hoover Heather , Abubucker Sahar , Finkel Nancy , McReynolds Larry , Hochschild Ann , Lieberman Judy 
Published: January 2019

AbstractAntisense transcription is widespread in bacteria. By base pairing with overlapping sense RNAs, antisense RNAs (asRNA) can form long double-stranded RNAs (dsRNA), which are cleaved by RNase III, a dsRNA endoribonuclease. Ectopic expression of plant tombusvirus p19 inE. colistabilizes ~21 bp dsRNA RNase III decay intermediates, which enabled us to characterize otherwise highly unstable asRNA by deep sequencing of p19-captured dsRNA and total RNA. dsRNA formed at most bacterial genes in the bacterial chromosome and in a plasmid. The most abundant dsRNA clusters were mostly formed by divergent transcription of sense and antisense transcripts overlapping at their 5’-ends. The most abundant clusters included small RNAs, such asryeA/ryeB, 4 toxin-antitoxin genes, and 3 tRNAs, and some longer coding genes, includingrsdandcspD. The sense and antisense transcripts in abundant dsRNA clusters were more plentiful and had longer half-lives in RNase III mutant strains, suggesting that formation of dsRNAs promoted RNA decay at these loci. However, widespread changes in protein levels did not occur in RNase III mutant bacteria. Nonetheless, some proteins involved in antioxidant responses and glycolysis changed reproducibly. dsRNAs accumulated in bacterial cells lacking RNase III, increasing in stationary phase, and correlated with increased cell death in RNase III mutant bacteria in late stationary phase. The physiological importance of widespread antisense transcription in bacteria remains unclear but it may become important during environmental stress. Ectopic expression of p19 is a sensitive method for identifying antisense transcripts and RNase III cleavage sites in bacteria.
Avian ANP32B does not support influenza A virus polymerase and influenza A virus relies exclusively on ANP32A in chicken cells
Authors: Long Jason S. , Idoko-Akoh Alewo , Mistry Bhakti , Goldhill Daniel H. , Staller Ecco , Schreyer Jocelyn , Ross Craig , Goodbourn Steve , Shelton Holly , Skinner Michael A. , Sang Helen M. , McGrew Mike J. , Barclay Wendy S. 
Published: January 2019

SummaryInfluenza A viruses (IAV) are subject to species barriers that prevent frequent zoonotic transmission and pandemics. One of these barriers is the poor activity of avian IAV polymerases in human cells. Differences between avian and mammalian ANP32 proteins underlie this host range barrier. Human ANP32A and ANP32B homologues both support function of human-adapted influenza polymerase but do not support efficient activity of avian IAV polymerase which requires avian ANP32A. We show here that avian ANP32B is evolutionarily distinct from mammalian ANP32B, and that chicken ANP32B does not support IAV polymerase activity even of human-adapted viruses. Consequently, IAV does not replicate in chicken cells that lack ANP32A. Amino acid differences in LRR5 domain accounted for the inactivity of chicken ANP32B. Transfer of these residues to chicken ANP32A abolished support of IAV polymerase. Understanding ANP32 function will help develop antiviral strategies and aid the design of influenza virus resistant genome edited chickens.
Characterizing gene tree conflict in plastome-inferred phylogenies
Authors: Walker Joseph F. , Stull Gregory W. , Walker-Hale Nathanael , Vargas Oscar M. , Larson Drew A. 
Published: January 2019

ABSTRACTPremise of the studyEvolutionary relationships among plants have been inferred primarily using chloroplast data. To date, no study has comprehensively examined the plastome for gene tree conflict.MethodsUsing a broad sampling of angiosperm plastomes, we characterized gene tree conflict among plastid genes at various time scales and explore correlates to conflict (e.g., evolutionary rate, gene length, molecule type).Key resultsWe uncover notable gene tree conflict against a backdrop of largely uninformative genes. We find gene length is the strongest correlate to concordance, and that nucleotides outperform amino acids. Of the most commonly used markers, matK greatly outperforms rbcL; however, the rarely used gene rpoC2 is the top-performing gene in every analysis. We find that rpoC2 reconstructs angiosperm phylogeny as well as the entire concatenated set of protein-coding chloroplast genes.ConclusionsOur results suggest that longer genes are superior for phylogeny reconstruction. The alleviation of some conflict through the use of nucleotides suggests that systematic error is likely the root of most of the observed conflict, but further research on biological conflict within plastome is warranted given the documented cases of heteroplasmic recombination. We suggest rpoC2 as a useful marker for reconstructing angiosperm phylogeny, reducing the effort and expense of assembling and analyzing entire plastomes.
Rtn4a promotes exocytosis in mammalian cells while ER morphology does not necessarily affect exocytosis and translation
Authors: Mukherjee Richik Nilay , Zhang Zhaojie , Levy Daniel L. 
Published: January 2019

ABSTRACTER tubules and sheets conventionally correspond to smooth and rough ER, respectively. The ratio of ER tubules-to-sheets varies in different cell types and changes in response to cellular conditions, potentially impacting the functional output of the ER. To directly test if ER morphology impacts ER function, we increased the tubule-to-sheet ratio by Rtn4a overexpression and monitored effects on protein translation and trafficking. While expression levels of several cell surface and secreted proteins were unchanged, their exocytosis was increased. Rtn4a depletion reduced cell surface trafficking without affecting ER morphology, and increasing the tubule-to-sheet ratio by other means did not affect trafficking. These data suggest that Rtn4a enhances exocytosis independently of changes in ER morphology. We demonstrate that Rtn4a enhances ER-to-Golgi trafficking and co-localizes with COPII vesicles. We propose that Rtn4a promotes COPII vesicle formation by inducing membrane curvature. Taken together, we show that altering ER morphology does not necessarily affect protein synthesis or trafficking, but that Rtn4a specifically enhances exocytosis.
TMEM98 is a negative regulator of FRAT mediated Wnt/β-catenin signalling
Authors: van der Wal Tanne , Lambooij Jan-Paul , van Amerongen Renée 
Published: January 2019

SummaryWnt/β-catenin signalling is crucial for maintaining the balance between cell proliferation and differentiation, both during tissue morphogenesis and during tissue maintenance in postnatal life. Whereas the signalling activities of the core Wnt/β-catenin pathway components are understood in great detail, far less is known about the precise role and regulation of the many different modulators of Wnt/β-catenin signalling that have been identified to date.Here we describe TMEM98, a putative transmembrane protein of unknown function, as an interaction partner and regulator of the GSK3-binding protein FRAT2. We show that TMEM98 reduces FRAT2 protein levels and, accordingly, inhibits the FRAT2-mediated induction of β-catenin/TCF signalling. We also characterize the intracellular trafficking of TMEM98 in more detail and show that it is recycled between the plasma membrane and the Golgi. Together, our findings not only reveal a new layer of regulation for Wnt/β-catenin signalling, but also a new biological activity for TMEM98.
A pitfall for machine learning methods aiming to predict across cell types
Authors: Schreiber Jacob , Singh Ritambhara , Bilmes Jeffrey , Noble William Stafford 
Published: January 2019

AbstractMachine learning models used to predict phenomena such as gene expression, enhancer activity, transcription factor binding, or chromatin conformation are most useful when they can generalize to make accurate predictions across cell types. In this situation, a natural strategy is to train the model on experimental data from some cell types and evaluate performance on one or more held-out cell types. In this work, we show that when the training set contains examples derived from the same genomic loci across multiple cell types, the resulting model can be susceptible to a particular form of bias related to memorizing the average activity associated with each genomic locus. Consequently, the trained model may appear to perform well when evaluated on the genomic loci that it was trained on but tends to perform poorly on loci that it was not trained on. We demonstrate this phenomenon by using epigenomic measurements and nucleotide sequence to predict gene expression and chromatin domain boundaries, and we suggest methods to diagnose and avoid the pitfall. We anticipate that, as more data and computing resources become available, future projects will increasingly risk suffering from this issue.
The Replication-Competent HIV-1 Latent Reservoir is Primarily Established Near the Time of Therapy Initiation
Authors: Abrahams Melissa-Rose , Joseph Sarah B. , Garrett Nigel , Tyers Lynn , Moeser Matthew , Archin Nancie , Council Olivia D. , Matten David , Zhou Shuntai , Doolabh Deelan , Anthony Colin , Goonetilleke Nilu , Karim Salim Abdool , Margolis David M. , Pond Sergei Kosakovsky , Williamson Carolyn , Swanstrom Ronald 
Published: January 2019

AbstractAlthough antiretroviral therapy (ART) is highly effective at suppressing HIV-1 replication, the virus persists as a latent reservoir in resting CD4+ T cells during therapy. Little is known about the dynamics of reservoir formation and this reservoir forms even when ART is initiated early after infection. The reservoir of individuals who initiate therapy in chronic infection is generally larger and genetically more diverse than that of individuals who initiate in acute infection, suggesting the reservoir is formed continuously throughout untreated infection. To determine when viruses enter the latent reservoir, we compared sequences of replication-competent viruses from resting CD4+ T cells from nine women on therapy to viral sequences circulating in blood collected longitudinally prior to therapy. We found that 78% of viruses from the latent reservoir were most genetically similar to viruses replicating just prior to therapy initiation. This proportion is far greater than expected if the reservoir forms continuously and is always long-lived. Thus, therapy alters the host environment in a way that allows the formation of a majority of the long-lived latent HIV-1 reservoir.One Sentence SummaryMost of the long-lived, replication-competent HIV-1 reservoir is formed at the time of therapy initiation.