bluuebunny/crossref_metadata_2025 huggingface dataset:
Apurinic endonuclease-1 preserves neural genome integrity to maintain homeostasis and thermoregulation and prevent brain tumors
Authors: Dumitrache Lavinia C. , Shimada Mikio , Downing Susanna M. , Kwak Young Don , Li Yang , Illuzzi Jennifer L. , Russell Helen R. , Wilson David M. , McKinnon Peter J.
Published: December 2018

Significance

The nervous system consumes a large quotient of oxygen and as such is at risk for high levels of oxidative DNA damage. A key DNA-repair factor, apurinic/apyrimidinic endonuclease 1 (APE1), is essential for repair of oxidative DNA lesions, although the specific role(s) for this enzyme in the nervous system is unknown. Surprisingly, mice lacking APE1 throughout neurogenesis were viable and showed little discernible phenotype at birth. However, after birth, when tissue oxygenation shifts from the placenta to respiration, loss of APE1 led to rapid and pronounced genome instability, resulting in widespread apoptosis, demyelination, thermoregulation defects, and brain tumors. Our findings reveal unrestrained oxidative DNA damage in the nervous system can result in specific pathology implicated in many human diseases.
Vision for a systems architecture to integrate and transform population health
Authors: Madhavan Guruprasad , Phelps Charles E. , Rouse William B. , Rappuoli Rino
Published: December 2018

Entities involved in population health often share a common mission while acting independently of one another and perhaps redundantly. Population health is in everybody’s interest, but nobody is really in charge of promoting it. Across governments, corporations, and frontline operations, lack of coordination, lack of resources, and lack of reliable, current information have often impeded the development of situation-awareness models and thus a broad operational integration for population health. These deficiencies may also affect the technical, organizational, policy, and legal arrangements for information sharing, a desired practice of high potential value in population health. In this article, we articulate a vision for a next-generation modeling effort to create a systems architecture for broadly integrating and visualizing strategies for advancing population health. This multipurpose systems architecture would enable different views, alerts, and scenarios to better prepare for and respond to potential degradations in population health. We draw inspiration from systems engineering and visualization tools currently in other uses, including monitoring the state of the economy (market performance), security (classified intelligence), energy (power generation), transportation (global air traffic control), environment (weather monitoring), jobs (labor market dynamics), manufacturing and supply chain (tracking of components, parts, subassemblies, and products), and democratic processes (election analytics). We envision the basic ingredients for a population health systems architecture and its visualization dashboards to eventually support proactive planning and joint action among constituents. We intend our ambitious vision to encourage the work needed for progress that the population deserves.
Cofactors are essential constituents of stable and seeding-active tau fibrils
Authors: Fichou Yann , Lin Yanxian , Rauch Jennifer N. , Vigers Michael , Zeng Zhikai , Srivastava Madhur , Keller Timothy J. , Freed Jack H. , Kosik Kenneth S. , Han Songi
Published: December 2018

Significance

The tau protein is involved in Alzheimer’s and other neurodegenerative diseases, where the location, morphology, and quantity of amyloid fibrils composed of tau correlate with the disease type and stage. While tau fibrillary aggregates have been colocalized in brains together with several cofactors, their role in fibril formation, structure, and seeding has been largely neglected. We show that seeding of tau aggregation is facilitated by polyanionic cofactors, and that seeded or recombinant mature fibrils depolymerize into monomers when their cofactor is removed. We show that cofactor-assisted seeding with mouse brain-derived tau fibrils yielded tau fibrils with distinct and narrowed structural properties compared with heparin-induced fibrils, suggesting that the fibrillar templates tuned the structure of the seeded fibril.
Eigenvector centrality for characterization of protein allosteric pathways
Authors: Negre Christian F. A. , Morzan Uriel N. , Hendrickson Heidi P. , Pal Rhitankar , Lisi George P. , Loria J. Patrick , Rivalta Ivan , Ho Junming , Batista Victor S.
Published: December 2018

Significance

Allosteric processes are ubiquitous in macromolecules and regulate biochemical information transfer between spatially distant sites. Despite decades of study, allosteric processes remain generally poorly understood at the molecular level. Here, we introduce the eigenvector centrality measure of mutual information to disentangle the complex interplay of amino acid interactions giving rise to allosteric signaling. The analysis of eigenvector centrality is tested in imidazole glycerol phosphate synthase (IGPS), a prototypical V-type allosteric enzyme. The resulting insights allow us to pinpoint key amino acids in terms of their relevance in the allosteric process, suggesting protein-engineering strategies for control of enzymatic activity.
Transgenerational hypocortisolism and behavioral disruption are induced by the antidepressant fluoxetine in male zebrafishDanio rerio
Authors: Vera-Chang Marilyn N. , St-Jacques Antony D. , Gagné Rémi , Martyniuk Chris J. , Yauk Carole L. , Moon Thomas W. , Trudeau Vance L.
Published: December 2018

The global prevalence of depression is high during childbearing. Due to the associated risks to the mother and baby, the selective serotonin reuptake inhibitor fluoxetine (FLX) is often the first line of treatment. Given that FLX readily crosses the placenta, a fetus may be susceptible to the disruptive effects of FLX during this highly plastic stage of development. Here, we demonstrate that a 6-day FLX exposure to a fetus-relevant concentration at a critical developmental stage suppresses cortisol levels in the adult zebrafish (F0). This effect persists for three consecutive generations in the unexposed descendants (F1to F3) without diminution and is more pronounced in males. We also show that the in vivo cortisol response of the interrenal (fish “adrenal”) to an i.p. injection of adrenocorticotropic hormone was also reduced in the males from the F0and F3FLX lineages. Transcriptomic profiling of the whole kidney containing the interrenal cells revealed that early FLX exposure significantly modified numerous pathways closely associated with cortisol synthesis in the male adults from the F0and F3generations. We also show that the low cortisol levels are linked to significantly reduced exploratory behaviors in adult males from the F0to F2FLX lineages. This may be a cause for concern given the high prescription rates of FLX to pregnant women and the potential long-term negative impacts on humans exposed to these therapeutic drugs.
Exploiting correlated molecular-dynamics networks to counteract enzyme activity–stability trade-off
Authors: Yu Haoran , Dalby Paul A.
Published: December 2018

Significance

Rigidifying flexible sites is a powerful method to improve enzyme stability. However, if the highly flexible regions form the active site, modifying them risks losing activity due to the activity–stability trade-off. We hypothesized here that regions outside the active site whose dynamics were highly correlated to flexible active sites, would provide good targets for stabilizing mutations. To test this hypothesis, six variants were constructed in the 3M variant of
Escherichia coli
transketolase. The best variant had a 10.8-fold improved half-life at 55 °C, and increased the
T
m
and
T
agg
by 3 °C and 4.3 °C, respectively. The variants even increased the activity, by up to threefold. This study highlights how protein engineering strategies could be potentially improved by considering long-range dynamics.
Pervasive iron limitation at subsurface chlorophyll maxima of the California Current
Authors: Hogle Shane L. , Dupont Christopher L. , Hopkinson Brian M. , King Andrew L. , Buck Kristen N. , Roe Kelly L. , Stuart Rhona K. , Allen Andrew E. , Mann Elizabeth L. , Johnson Zackary I. , Barbeau Katherine A.
Published: December 2018

Subsurface chlorophyll maximum layers (SCMLs) are nearly ubiquitous in stratified water columns and exist at horizontal scales ranging from the submesoscale to the extent of oligotrophic gyres. These layers of heightened chlorophyll and/or phytoplankton concentrations are generally thought to be a consequence of a balance between light energy from above and a limiting nutrient flux from below, typically nitrate (NO
3
). Here we present multiple lines of evidence demonstrating that iron (Fe) limits or with light colimits phytoplankton communities in SCMLs along a primary productivity gradient from coastal to oligotrophic offshore waters in the southern California Current ecosystem. SCML phytoplankton responded markedly to added Fe or Fe/light in experimental incubations and transcripts of diatom and picoeukaryote Fe stress genes were strikingly abundant in SCML metatranscriptomes. Using a biogeochemical proxy with data from a 40-y time series, we find that diatoms growing in California Current SCMLs are persistently Fe deficient during the spring and summer growing season. We also find that the spatial extent of Fe deficiency within California Current SCMLs has significantly increased over the last 25 y in line with a regional climate index. Finally, we show that diatom Fe deficiency may be common in the subsurface of major upwelling zones worldwide. Our results have important implications for our understanding of the biogeochemical consequences of marine SCML formation and maintenance.
Symbiotic unicellular cyanobacteria fix nitrogen in the Arctic Ocean
Authors: Harding Katie , Turk-Kubo Kendra A. , Sipler Rachel E. , Mills Matthew M. , Bronk Deborah A. , Zehr Jonathan P.
Published: December 2018

Biological dinitrogen (N
2
) fixation is an important source of nitrogen (N) in low-latitude open oceans. The unusual N
2
-fixing unicellular cyanobacteria (UCYN-A)/haptophyte symbiosis has been found in an increasing number of unexpected environments, including northern waters of the Danish Straight and Bering and Chukchi Seas. We used nanoscale secondary ion mass spectrometry (nanoSIMS) to measure
15
N
2
uptake into UCYN-A/haptophyte symbiosis and found that UCYN-A strains identical to low-latitude strains are fixing N
2
in the Bering and Chukchi Seas, at rates comparable to subtropical waters. These results show definitively that cyanobacterial N
2
fixation is not constrained to subtropical waters, challenging paradigms and models of global N
2
fixation. The Arctic is particularly sensitive to climate change, and N
2
fixation may increase in Arctic waters under future climate scenarios.
PCNA-mediated stabilization of E3 ligase RFWD3 at the replication fork is essential for DNA replication
Authors: Lin Yo-Chuen , Wang Yating , Hsu Rosaline , Giri Sumanprava , Wopat Susan , Arif Mariam K. , Chakraborty Arindam , Prasanth Kannanganattu V. , Prasanth Supriya G.
Published: December 2018

Significance

Ubiquitination of several DNA replication–repair proteins is a critical mechanism by which cellular DNA replication and DNA damage repair pathways are controlled. The E3 ligase RING finger and WD repeat domain-containing protein 3 (RFWD3) has emerged as an important regulator of genome stability. We propose that the association of RFWD3 to proliferating cell nuclear antigen stabilizes RFWD3 at the fork, enabling ubiquitination of replication protein A and its subsequent removal to facilitate DNA replication.
RNA-mediated gene fusion in mammalian cells
Authors: Gupta Sachin Kumar , Luo Liming , Yen Laising
Published: December 2018

Significance

This report provides striking evidence that expression of a chimeric RNA mimicking a fusion RNA can drive the formation of gene fusions in mammalian cells. However, it is the antisense rather than sense chimeric RNAs that effectively drive gene fusion. The discovery that the cellular
AZI1
RNA, not
AZI1
protein, can act as an “initiator” RNA to induce
TMPRSS2–ERG
gene fusion indicates that this mechanism may have important biological relevance to oncogenesis. RNA-mediated gene fusion, a mechanism that relies on sequence-specific interactions, can account for the “specificity” of genes that were selected to undergo gene fusion. The results could also have fundamental implications in mammalian genome stability, as well as gene-editing technology via mechanisms native to mammalian cells.
Spatiotemporal activation of the C/EBPβ/δ-secretase axis regulates the pathogenesis of Alzheimer’s disease
Authors: Wang Hualong , Liu Xia , Chen Shengdi , Ye Keqiang
Published: December 2018

Significance

Our most recent reports demonstrate that δ-secretase (AEP) cleaves both APP and Tau, promoting Ab and neurofibrillary tangle formation. Depletion of δ-secretase diminishes Alzheimer’s disease (AD) pathologies and restores cognitive functions in AD mouse models. Moreover, we found that C/EBPβ, an inflammatory cytokine or Ab-activated transcription factor, dictates δ-secretase expression during aging. Overexpression of C/EBPβ facilitates AD pathologies via upregulating δ-secretase, whereas depletion of C/EBPβ reduces AD pathologies. In the current study, we examined the pathological roles of the C/EBPβ/δ-secretase axis in different AD mouse models, at different time points, and in different brain regions and found that this pathway plays a critical role in mediating AD pathologies and cognitive function. Hence, C/EBPβ/δ-secretase spatiotemporally mediates AD pathogenesis.
Nuclear receptor HNF4A transrepresses CLOCK:BMAL1 and modulates tissue-specific circadian networks
Authors: Qu Meng , Duffy Tomas , Hirota Tsuyoshi , Kay Steve A.
Published: December 2018

Either expression level or transcriptional activity of various nuclear receptors (NRs) have been demonstrated to be under circadian control. With a few exceptions, little is known about the roles of NRs as direct regulators of the circadian circuitry. Here we show that the nuclear receptor HNF4A strongly transrepresses the transcriptional activity of the CLOCK:BMAL1 heterodimer. We define a central role for HNF4A in maintaining cell-autonomous circadian oscillations in a tissue-specific manner in liver and colon cells. Not only transcript level but also genome-wide chromosome binding of HNF4A is rhythmically regulated in the mouse liver. ChIP-seq analyses revealed cooccupancy of HNF4A and CLOCK:BMAL1 at a wide array of metabolic genes involved in lipid, glucose, and amino acid homeostasis. Taken together, we establish that HNF4A defines a feedback loop in tissue-specific mammalian oscillators and demonstrate its recruitment in the circadian regulation of metabolic pathways.
Optical stimulation of cardiac cells with a polymer-supported silicon nanowire matrix
Authors: Parameswaran Ramya , Koehler Kelliann , Rotenberg Menahem Y. , Burke Michael J. , Kim Jungkil , Jeong Kwang-Yong , Hissa Barbara , Paul Michael D. , Moreno Kiela , Sarma Nivedina , Hayes Thomas , Sudzilovsky Edward , Park Hong-Gyu , Tian Bozhi
Published: December 2018

Significance

Cardiac conduction disorders are potentially fatal illnesses caused by abnormalities in the heart’s electrical conduction system. Current treatments for these disorders, such as pacemakers, are effective but are bulky, rigid, and invasive. Here we develop a method to optically modulate cardiac beating frequency in primary cultured cardiomyocytes and adult rat hearts ex vivo, to a specified target frequency. Specifically, we use a low-irradiance moving laser stimulus and a biocompatible polymer–silicon nanowire composite material to achieve this modulation. This work has implications for future bioelectric studies of the cardiac conduction system as well as therapeutics for cardiac conduction disorders in the clinic.
Nanotechnology-mediated crossing of two impermeable membranes to modulate the stars of the neurovascular unit for neuroprotection
Authors: Surnar Bapurao , Basu Uttara , Banik Bhabatosh , Ahmad Anis , Marples Brian , Kolishetti Nagesh , Dhar Shanta
Published: December 2018

Significance

Neurodegenerative disorders touch many lives in the form of various diseases. Therapeutic interventions of such disorders are limited due to the difficulty in reaching the neurons by crossing the impermeable blood–brain barrier. Scientists have created nanoscopic particles to take therapeutics to the brain; however, the results have not been very encouraging due to the inefficient ability of the nanoplatforms in crossing the blood–brain barrier and to accumulate in the target neuron cells effectively as uptake of nanomaterials by neurons is difficult to achieve. We provide a biodegradable nanoparticle platform with efficient brain astrocyte accumulation properties to provide an alternative approach to tackle neurodegenerative processes by improving and enhancing astrocyte’s natural protection ability toward neurons for neuromedicine.
Structural–functional interactions of NS1-BP protein with the splicing and mRNA export machineries for viral and host gene expression
Authors: Zhang Ke , Shang Guijun , Padavannil Abhilash , Wang Juan , Sakthivel Ramanavelan , Chen Xiang , Kim Min , Thompson Matthew G. , García-Sastre Adolfo , Lynch Kristen W. , Chen Zhijian J. , Chook Yuh Min , Fontoura Beatriz M. A.
Published: December 2018

The influenza virulence factor NS1 protein interacts with the cellular NS1-BP protein to promote splicing and nuclear export of the viral M mRNAs. The viral M1 mRNA encodes the M1 matrix protein and is alternatively spliced into the M2 mRNA, which is translated into the M2 ion channel. These proteins have key functions in viral trafficking and budding. To uncover the NS1-BP structural and functional activities in splicing and nuclear export, we performed proteomics analysis of nuclear NS1-BP binding partners and showed its interaction with constituents of the splicing and mRNA export machineries. NS1-BP BTB domains form dimers in the crystal. Full-length NS1-BP is a dimer in solution and forms at least a dimer in cells. Mutations suggest that dimerization is important for splicing. The central BACK domain of NS1-BP interacts directly with splicing factors such as hnRNP K and PTBP1 and with the viral NS1 protein. The BACK domain is also the site for interactions with mRNA export factor Aly/REF and is required for viral M mRNA nuclear export. The crystal structure of the C-terminal Kelch domain shows that it forms a β-propeller fold, which is required for the splicing function of NS1-BP. This domain interacts with the polymerase II C-terminal domain and SART1, which are involved in recruitment of splicing factors and spliceosome assembly, respectively. NS1-BP functions are not only critical for processing a subset of viral mRNAs but also impact levels and nuclear export of a subset of cellular mRNAs encoding factors involved in metastasis and immunity.
The competitive dimension of comparative optimism / La dimensión competitiva del optimismo comparativo
Authors: Krzeminski Aurélie , Milhabet Isabelle , Priolo Daniel
Published: December 2018

We usually think that positive events are more likely to occur to us than to others and vice versa for negative events. This phenomenon, called comparative optimism, increases both social utility and the tendency to present oneself as above average. The literature highlights the same elements in competition. Our objective was to study the links between comparative optimism and competition and to argue that social utility can explain this relation. In our study, we presented participants with comparative optimistic, comparative pessimistic or neutral targets. We observed that a comparative optimistic target was perceived to fit better with a competitive situation than other targets because he/she was deemed socially useful (e.g., assertive, self-confident). Participants also felt that a comparative optimistic target pursued more performance goals than the other targets. This effect was mediated by the perception of this target as a competitive person. These results, consistent with our assumptions, highlight the competitive dimension of comparative optimism.
Characterization of the bagremycin biosynthetic gene cluster in Streptomyces sp. Tü 4128
Authors: Ye Jiang , Zhu Yunxia , Hou Bingbing , Wu Haizhen , Zhang Huizhan
Published: December 2018

Bagremycin A and bagremycin B isolated from Streptomyces sp. Tü 4128 have activities against Gram-positive bacteria, fungi and also have a weak antitumor activity, which make them have great potential for development of novel antibiotics. Here, we report a draft genome 8,424,112 bp in length of S. sp. Tü 4128 by Illumina Hiseq2000, and identify the bagremycins biosynthetic gene cluster (BGC) by bioinformatics analysis. The putative bagremycins BGC includes 16 open reading frames (ORFs) with the functions of biosynthesis, resistance and regulation. Disruptions of relative genes and HPLC analysis of bagremycins production demonstrated that not all the genes within the BGC are responsible for the biosynthesis of bagremycins. In addition, the biosynthetic pathways of bagremycins are proposed for deeper inquiries into their intriguing biosynthetic mechanism.
ATP13A2 facilitates HDAC6 recruitment to lysosome to promote autophagosome–lysosome fusion
Authors: Wang Ruoxi , Tan Jieqiong , Chen Tingting , Han Hailong , Tian Runyi , Tan Ya , Wu Yiming , Cui Jingyi , Chen Fang , Li Jie , Lv Lu , Guan Xinjie , Shang Shuai , Lu Jiahong , Zhang Zhuohua
Published: December 2018

Mutations in ATP13A2 cause Kufor-Rakeb syndrome, an autosomal recessive form of juvenile-onset atypical Parkinson’s disease (PD). Recent work tied ATP13A2 to autophagy and other cellular features of neurodegeneration, but how ATP13A2 governs numerous cellular functions in PD pathogenesis is not understood. In this study, the ATP13A2-deficient mouse developed into aging-dependent phenotypes resembling those of autophagy impairment. ATP13A2 deficiency impaired autophagosome–lysosome fusion in cultured cells and in in vitro reconstitution assays. In ATP13A2-deficient cells or Drosophila melanogaster or mouse tissues, lysosomal localization and activity of HDAC6 were reduced, with increased acetylation of tubulin and cortactin. Wild-type HDAC6, but not a deacetylase-inactive mutant, restored autophagosome–lysosome fusion, antagonized cortactin hyperacetylation, and promoted lysosomal localization of cortactin in ATP13A2-deficient cells. Mechanistically, ATP13A2 facilitated recruitment of HDAC6 and cortactin to lysosomes. Cortactin overexpression in cultured cells reversed ATP13A2 deficiency–associated impairment of autophagosome–lysosome fusion. PD-causing ATP13A2 mutants failed to rescue autophagosome–lysosome fusion or to promote degradation of protein aggregates and damaged mitochondria. These results suggest that ATP13A2 recruits HDAC6 to lysosomes to deacetylate cortactin and promotes autophagosome–lysosome fusion and autophagy. This study identifies ATP13A2 as an essential molecular component for normal autophagy flux in vivo and implies potential treatments targeting HDAC6-mediated autophagy for PD.
Drosophila kinesin-8 stabilizes the kinetochore–microtubule interaction
Authors: Edzuka Tomoya , Goshima Gohta
Published: December 2018

Kinesin-8 is required for proper chromosome alignment in a variety of animal and yeast cell types. However, it is unclear how this motor protein family controls chromosome alignment, as multiple biochemical activities, including inconsistent ones between studies, have been identified. Here, we find that Drosophila kinesin-8 (Klp67A) possesses both microtubule (MT) plus end–stabilizing and –destabilizing activity, in addition to kinesin-8's commonly observed MT plus end–directed motility and tubulin-binding activity in vitro. We further show that Klp67A is required for stable kinetochore–MT attachment during prometaphase in S2 cells. In the absence of Klp67A, abnormally long MTs interact in an “end-on” fashion with kinetochores at normal frequency. However, the interaction is unstable, and MTs frequently become detached. This phenotype is rescued by ectopic expression of the MT plus end–stabilizing factor CLASP, but not by artificial shortening of MTs. We show that human kinesin-8 (KIF18A) is also important to ensure proper MT attachment. Overall, these results suggest that the MT-stabilizing activity of kinesin-8 is critical for stable kinetochore–MT attachment.
Going the distance: Neocentromeres make long-range contacts with heterochromatin
Authors: McNulty Shannon M. , Sullivan Beth A.
Published: December 2018

Neocentromeres are ectopic centromeres that form at noncanonical, usually nonrepetitive, genomic locations. Nishimura et al. (2019. J. Cell Biol. https://doi.org/10.1083/jcb.201805003) explore the three-dimensional architecture of vertebrate neocentromeres, leading to a model for centromere function and maintenance via nuclear clustering with heterochromatin.
Interplanting Different Varieties of a Sweet Potato Crop to Reduce Damage by Oligophagous Insect Pests
Authors: Ichinose K , Reddy G V P , Shrestha G , Sharma A , Okada Y , Yoshida M , Sakai Tetsufumi
Published: December 2018

One complementary or alternative control measure to chemical insecticide is interplanting of plants that affect insect behavior. While few successes are known based on interplanting of different varieties of the same crop, such intra-crop interplanting may be effective against insects that feed on a limited range of plants and have persistent preference to one cultivar. Here, we report three field trials that examined the efficacy of intra-crop interplanting of sweet potato varieties, Ipomoea batatas (L.) Lamarck (Solanales: Convolvulaceae), on an oligophagous weevil, Euscepes postfasciatus (Fairmaire) (Coleoptera: Curculionidae), planting a preferred variety, Beni-masari, together with a less preferred one, Kyushu 166. In the first experiment, Beni-masari was planted as a border around Kyushu 166 and this arrangement decreased tuber damage in the main crop (Kyushu 166), although damage reduction was not statistically significant from monoculture plantings of Kyushu 166. In the second experiment, both varieties were planted in plots spaced 3 m apart to test the attractiveness of Beni-masari to weevils from Kyushu 166. No attractive effects of Beni-masari were observed. In the third experiment, the two varieties were planted in separate plots that were contiguous to each other, and in this experiment Beni-masari preferentially attracted weevils away from Kyushu 166 within 3 m distance, and tuber damage in Kyushu 166 within that zone was reduced owing to the attractiveness of Beni-masari. We discuss the potential of the intra-crop interplanting in pest management.
Utility of a Simple and Robust Flow Cytometry Assay for Rapid Clonality Testing in Mature Peripheral T-Cell Lymphomas
Authors: Novikov Natasha D , Griffin Gabriel K , Dudley Graham , Drew Mai , Rojas-Rudilla Vanesa , Lindeman Neal I , Dorfman David M
Published: December 2018

Objectives

Flow cytometry immunophenotyping is limited by poor resolution of T-cell clones. A newly described antibody was recently used to distinguish normal peripheral blood T cells from malignant T-cell clones. Here, we evaluate this antibody as a new diagnostic tool for detecting T-cell clonality in mature peripheral T-cell lymphomas.

Methods

Immunostaining for the T-cell receptor β chain constant region 1 (TRBC1) along with routine T-cell markers was performed on 51 peripheral blood and two bone marrow samples submitted to the flow cytometry laboratory for suspected T-cell malignancy.

Results

TRBC immunophenotyping identified malignant T-cell clones with 97% sensitivity and 91% specificity. Findings correlated with molecular T-cell clonality testing. In cases with equivocal molecular results, TRBC1 immunophenotyping provided additional diagnostic information.

Conclusions

TRBC1 flow cytometric immunophenotyping is a robust and inexpensive method for identifying T-cell clonality that could easily be incorporated into routine flow cytometric practice.
Genetic associations and regulation of expression indicate an independent role for 14q32 snoRNAs in human cardiovascular disease
Authors: Håkansson Kjell E J , Goossens Eveline A C , Trompet Stella , van Ingen Eva , de Vries Margreet R , van der Kwast Reginald V C T , Ripa Rasmus S , Kastrup Jens , Hohensinner Philipp J , Kaun Christoph , Wojta Johann , Böhringer Stefan , Le Cessie Saskia , Jukema J Wouter , Quax Paul H A , Nossent A Yaël
Published: December 2018

Aims

We have shown that 14q32 microRNAs are highly involved in vascular remodelling and cardiovascular disease. However, the 14q32 locus also encodes 41 ‘orphan’ small nucleolar RNAs (snoRNAs). We aimed to gather evidence for an independent role for 14q32 snoRNAs in human cardiovascular disease.

Methods and results

We performed a lookup of the 14q32 region within the dataset of a genome wide association scan in 5244 participants of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). Single nucleotide polymorphisms (SNPs) in the snoRNA-cluster were significantly associated with heart failure. These snoRNA-cluster SNPs were not linked to SNPs in the microRNA-cluster or in MEG3, indicating that snoRNAs modify the risk of cardiovascular disease independently. We looked at expression of 14q32 snoRNAs throughout the human cardio-vasculature. Expression profiles of the 14q32 snoRNAs appeared highly vessel specific. When we compared expression levels of 14q32 snoRNAs in human vena saphena magna (VSM) with those in failed VSM-coronary bypasses, we found that 14q32 snoRNAs were up-regulated. SNORD113.2, which showed a 17-fold up-regulation in failed bypasses, was also up-regulated two-fold in plasma samples drawn from patients with ST-elevation myocardial infarction directly after hospitalization compared with 30 days after start of treatment. However, fitting with the genomic associations, 14q32 snoRNA expression was highest in failing human hearts. In vitro studies show that the 14q32 snoRNAs bind predominantly to methyl-transferase Fibrillarin, indicating that they act through canonical mechanisms, but on non-canonical RNA targets. The canonical C/D-box snoRNA seed sequences were highly conserved between humans and mice.

Conclusion

14q32 snoRNAs appear to play an independent role in cardiovascular pathology. 14q32 snoRNAs are specifically regulated throughout the human vasculature and their expression is up-regulated during cardiovascular disease. Our data demonstrate that snoRNAs merit increased effort and attention in future basic and clinical cardiovascular research.
Alliance and Public Preference for Nuclear Forbearance: Evidence from South Korea
Authors: Ko Jiyoung
Published: December 2018

How does a patron state dampen a client state's domestic aspirations for developing nuclear weapons? What nonproliferation tools most effectively induce a client state's domestic preference for nuclear forbearance? This article assesses the relative effectiveness of three nonproliferation tools available to a nuclear patron: a declaration of extended deterrence, forward deployment of nuclear weapons, and a conditional threat of punishment. More specifically, using experimental data on the South Korean public, this article examines whether nuclear forward-deployment and a conditional threat of punishment are more effective than a declaratory policy in enhancing the credibility of extended deterrence and curbing public aspirations for nuclearization. The experimental results show that neither nuclear forward-deployment nor a conditional threat of punishment reduces public support for nuclear armament significantly more than a declaratory policy. They also reveal that compared to when a nuclear ally does not exist, the three nonproliferation tools do not necessarily dampen the public's preference for developing indigenous nuclear weapons. The robustness of the findings is assessed using an experiment on a small sample of government officials. Taken together, this study provides the first experimental evidence on public perception of different nonproliferation tools in a client state.
The Political Class and Redistributive Policies
Authors: Corvalan Alejandro , Querubín Pablo , Vicente Sergio
Published: December 2018

We study the relationship between the composition of the political class and the size of government. First, we use a citizen-candidate model to show that the extension of suffrage is inconsequential for government spending when stricter eligibility requirements are in place. The removal of eligibility requirements, on the other hand, leads to the election of less wealthy politicians and the enactment of more redistributive policies. We test these predictions empirically using data from the 13 U.S. original states. We find no robust correlation between the extension of the franchise and government spending or the composition of the political class. However, the subsequent elimination of eligibility restrictions is associated with an increase in government spending and the election of state senators with a less elite background.
Neutrino emission from BL Lac objects: the role of radiatively inefficient accretion flows
Authors: Righi C , Tavecchio F , Inoue S
Published: December 2018

The origin of the astrophysical high-energy neutrinos discovered by IceCube is currently a major mystery. The recent detection of IceCube-170922A, an ∼300 TeV neutrino potentially correlated with the flaring γ-ray source TXS 0506+056, directs attention towards BL Lac objects (BL Lacs), the subclass of blazars with weak emission lines. While high-energy neutrinos can be produced via photohadronic interactions between protons accelerated in their jets and ambient low-energy photons, the density of the latter in such objects had generally been thought to be too low for efficient neutrino emission. Here we consider the role of radiatively inefficient accretion flows (RIAFs), which can plausibly exist in the nuclei of BL Lacs, as the source of target photons for neutrino production. Based on simple model prescriptions for the spectra of RIAFs at different accretion rates, we find that they can be sufficiently intense to allow appreciable neutrino emission for the class of low-synchrotron-peak BL Lacs such as TXS 0506+056. In contrast, for high-synchrotron-peak BL Lacs, including Mkn 421 and Mkn 501, the contribution of RIAFs is subdominant and their neutrino production efficiency can remain low, consistent with their non-detection by IceCube to date.
Work–family reconciliation policies and women’s and mothers’ labor market outcomes in rich democracies
Authors: Brady David , Blome Agnes , Kmec Julie A
Published: December 2018

Prominent research has claimed that work–family reconciliation policies trigger ‘tradeoffs’ and ‘paradoxes’ in terms of gender equality with adverse labor market consequences for women. These claims have greatly influenced debates regarding social policy, work, family and gender inequality. Motivated by limitations of prior research, we analyze the relationship between the two most prominent work–family reconciliation policies (paid parental leave and public childcare coverage) and seven labor market outcomes (employment, full-time employment, earnings, full-time earnings, being a manager, being a lucrative manager and occupation percent female). We estimate multilevel models of individuals nested in a cross-section of 21 rich democracies near 2005, and two-way fixed effects models of individuals nested in a panel of 12 rich democracies over time. The vast majority of coefficients for work–family policies fail to reject the null hypothesis of no effects. The pattern of insignificance occurs regardless of which set of models or coefficients one compares. Moreover, there is as much evidence that significantly contradicts the ‘tradeoff hypothesis’ as is consistent with the hypothesis. Altogether, the analyses undermine claims that work–family reconciliation policies trigger trade-offs and paradoxes in terms of gender equality with adverse labor market consequences for women.
A coordinate-based meta-analysis comparing brain activation between attention deficit hyperactivity disorder and total sleep deprivation
Authors: Saletin Jared M , Jackvony Stephanie , Rodriguez Katherina A , Dickstein Daniel P
Published: December 2018

Study Objectives

Sleep disruption is common in attention deficit hyperactivity disorder (ADHD). Likewise, deficits in attention are a hallmark of sleep deprivation in healthy individuals. Whether ADHD and sleep deprivation modulate common, or disparate, neural systems is unknown. No study has yet utilized functional magnetic resonance imaging (fMRI) to investigate sleep loss in ADHD. We address this gap by performing a novel meta-analysis to compare patterns of fMRI activation during sleep deprivation and ADHD.

Methods

We performed a coordinate-based activation likelihood estimate (ALE) meta-analysis using the GingerALE software. A systematic review of task-based fMRI studies of sleep deprivation vs. rested and also ADHD vs. healthy controls (HC) yielded 134 articles. fMRI coordinates were extracted for each contrast (i.e. “ADHD vs. HC,” “TSD vs. Rested”) and normalized to the Talairach-atlas. Separate ALE analyses were performed for ADHD and sleep deprivation. We directly compared these initial estimates to determine shared vs. distinct areas of fMRI neural activation in ADHD and sleep deprivation.

Results

Conjunction analyses revealed overlapping hypoactivations between ADHD and sleep loss in executive function regions, notably the dorsal anterior cingulate cortex. Sleep deprivation, however, was associated with significantly exaggerated hyperactivation in the thalamus.

Conclusions

Our study indicates that ADHD and sleep deprivation share a common neural signature: hypoactivation of executive function neuroanatomy. In contrast, sleep loss, but not ADHD, was associated with thalamic hyperactivations, intimating a potential compensatory response in sleep loss not present in ADHD. By elucidating shared and distinct patterns of functional neuroanatomy, these data provide novel targets for future experimental investigations of sleep loss in ADHD.
miR156/SPL9 Regulates Reactive Oxygen Species Accumulation and Immune Response in Arabidopsis thaliana
Authors: Yin Hongbiao , Hong Gaojie , Li Linying , Zhang Xueying , Kong Yaze , Sun Zongtao , Li Junmin , Chen Jianping , He Yuqing
Published: December 2018

The functions of microRNA156 (miR156) and its targeted SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) transcription factor genes in plant development have been widely investigated. However, the role of the miR156/SPLs regulatory network in plant immune systems remains obscure. Here, we found that the accumulation of reactive oxygen species (ROS) and the transcripts of basal salicylic acid (SA) signaling pathway genes were lower in Arabidopsis Pro35S:MIR156 seedlings (miR156 overexpression mutants) but higher in Pro35S:MIM156 (miR156 repression mutants) and ProSPL9:rSPL9 (SPL9 overexpression mutants) seedlings compared with wild-type Col-0 plants (WT). As a result, Pro35S:MIR156 mutants induced greater susceptibility to Pseudomonas syringae pv. tomato DC3000 following syringe infiltration than WT, while Pro35S:MIM156 and ProSPL9:rSPL9 mutants showed enhanced resistance. In addition, foliar H2O2 application resulted in activation of SA-mediated defense response and ablation of miR156-induced susceptibility to P. syringae pv. tomato DC3000 infection. Collectively, our results provide new insights into the function of the miR156/SPL network in Arabidopsis immune response by regulating ROS accumulation and activating the SA signaling pathway.
Pitfalls in Cardiac CT: Causes and Solutions
Authors: Saxena Deepali , Rajiah Prabhakar , Quadri Rehan , Saboo Sachin S.
Published: December 2018

Cardiac CT is used increasingly in the evaluation of cardiac abnormalities, particularly for coronary artery diseases. Cardiac CT mainly provides morphological information, but it also can generate some functional information. Cardiac CT can be performed either with prospective electrocardiogram (ECG) triggering or retrospective ECG gating. Several pitfalls can be seen in cardiac CT, and these can be confused for abnormal cardiac lesions. In this article, we provide solutions to avoid their misdiagnosis.
Minimal change disease
Authors: Mitchell-Brown Fay M. , Veisze Tiernan
Published: December 2018

Although minimal change disease (MCD) is a major cause of nephrotic syndrome in children, it's less common in adults. It develops from damage to the glomeruli with a loss of large amounts of protein in the urine. Early recognition and treatment is the key to a good outcome. This article describes the diagnosis, treatment, and nursing care of an adult with MCD.
Nursing Knowledge in the 21st Century
Authors: Roy Callista
Published: December 2018

Some have described that nursing is at a crossroads that necessitates finding ways to balance knowledge development that is philosophical and conceptual/theoretical with the empirical inquiry, particularly of the developing related biologic sciences. This article sets a direction for nursing knowledge development that is domain-driven. The central role of nursing theory in attaining the common goals of nursing is envisioned. Recommendations include that grand theories, middle-range theories, and practice theories in tree-like fashion feed into the common goal of humanization; that all teaching tools in nursing begin with common goals and describe nursing theories as contributing to these goals; that theory-practice alliances are central in filling out the envisioned domain-driven knowledge and integrating this with practice-shaped basic sciences.
Understanding Mi'kmaq Women's Experiences Accessing Prenatal Care in Rural Nova Scotia
Authors: Burns Laura , Whitty-Rogers Joanne , MacDonald Cathy
Published: December 2018

Indigenous women experience a higher incidence of maternal complications compared with non-Indigenous women. Despite this, little is known about access to prenatal care for Mi'kmaq women in Nova Scotia. The intent of this study was to gain a more comprehensive understanding of Mi'kmaq women's experiences accessing prenatal care. The findings from this study highlight key implications for nursing practice such as promoting the nurse's role in supporting and advocating for Mi'kmaq women's health and for providing culturally safe care. This research will highlight that access to prenatal care is a complex issue for some women.
Intravenous and Oral Tranexamic Acid Are Equivalent at Reducing Blood Loss in Thoracolumbar Spinal Fusion
Authors: Yu Charles C. , Kadri Omar , Kadado Allen , Buraimoh Morenikeji , Pawloski Jacob , Bartol Stephen , Graziano Gregory
Published: December 2018

Study Design.

A prospective randomized trial of patients enrolled at a university affiliated tertiary medical center between February and December 2017.

Objective.

To compare perioperative blood loss in patients undergoing elective posterior thoracolumbar fusion who were treated with intravenous (IV) versus oral (PO) tranexamic acid (TXA).

Summary of Background Data.

The use of antifibrinolytic agents such as TXA to decrease operative blood loss and allogenic blood transfusions is well documented in the literature. While evidence supports the use of IV and topical formulations of TXA in spine surgery, the use of PO TXA has not been studied.

Methods.

Eighty-three patients undergoing thoracolumbar fusion were randomized to receive 1.95 g of PO TXA 2 hours preoperatively or 2 g IV TXA (1 g before incision and 1 g before wound closure) intraoperatively. The sample was further stratified into three categories based on number of levels fused (1–2 level fusions, 3–5, and >5). The primary outcome was the reduction of hemoglobin. Secondary outcomes included calculated blood loss, drain output, postoperative transfusion, complications, and length of hospital stay. Equivalence analysis was performed with a two one-sided test (TOST). A P-value of <0.05 suggested equivalence between treatments.

Results.

Fourty three patients received IV TXA and 40 patients received PO TXA. Patient demographic factors were similar between groups except for body mass index (BMI). The mean reduction of hemoglobin was similar between IV and PO groups (3.36 g/dL vs. 3.43 g/dL, respectively; P = 0.01, equivalence). Similarly, the calculated blood loss was equivalent (1235 mL vs. 1312 mL, respectively; P = 0.02, equivalence). Eight patients (19%) in IV TXA group received a transfusion compared with five patients in PO TXA group (13%) (P = 0.44). One patient (2% and 3% in IV and PO, respectively) in each group experienced a deep venous thrombosis/pulmonary embolism (P = 0.96).

Conclusion.

Patients treated with IV and PO TXA experienced the same perioperative blood loss after spinal fusions. Given its lower cost, PO TXA represents an excellent alternative to IV TXA in patients undergoing elective posterior thoracolumbar fusion and may improve healthcare cost-efficiency in the studied population.

Level of Evidence: 1
High Prevalence of Spinal Magnetic Resonance Imaging Findings in Asymptomatic Young Adults (18–22 Yrs) Candidate to Air Force Flight
Authors: Romeo Valeria , Covello Mario , Salvatore Elena , Parente Chiara Anna , Abbenante Domenico , Biselli Roberto , Ciriello Mattia , Musolino Pasquale , Salvatore Marco , Cangiano Alessandro
Published: December 2018

Study Design.

Cross-sectional, retrospective, magnetic resonance (MR) imaging study, performed during cadets’ selection procedures of the Italian Air Force Academy.

Objective.

To assess the prevalence of spinal MR imaging findings in asymptomatic young adults (18–22 yrs) candidate to Air Force Flight.

Summary of Background Data.

Spinal MR imaging findings are frequently detected in asymptomatic subjects. Literature prevalence data come from studies that analyze different patient populations, in a wide age range and in different spinal tracts. Chronic degenerative disease of the vertebral column often occurs in pilots exposed to high flight acceleration forces, thus resulting crucial for Air Force Academy to exclude vertebral disease in cadets.

Methods.

Three hundred fifty asymptomatic young adults underwent a 3T MR examination of the entire spine. A structured radiological report was set up to classify and calculate the prevalence of spinal MR imaging findings.

Results.

Two hundred seventy of 350 subjects (77%) presented spinal MR findings, while 80 of 350 candidates (23%) had no detectable MR imaging findings. One hundred six of 350 (30%) candidates had at least one disc desiccation and 47 of 350 (13%) presented at least one disc narrowing. Disc bulging was found in 176 of 350 (49%) cadets. Sixty-two of 350 (18%) subjects showed disc protrusion while 28 of 350 (8%) had disc extrusion. Forty-five of 350 (13%) candidates presented low grade intervertebral spondylosis and of these 12 had also facet joints spondylosis. Asymptomatic vertebral fractures were observed in 2 of 350 (<1%) cadets.

Conclusion.

A high rate of MR spinal imaging findings, similar to that of the adult population, was detected in our population of young asymptomatic subjects. Our results suggest that the process of aging spine, which is supposed to begin in the second decade of life, is morphologically appreciable in the immediate postadolescent period and this issue is of crucial importance when selecting military pilots.

Level of Evidence: 4
Hypercellular Encapsulated Neuroma Imitating Desmoplastic Melanoma
Authors: May Caitlin , LeBoit Philip , McCalmont Timothy , Argenyi Zsolt
Published: December 2018

Palisaded encapsulated neuromas (PENs) are benign cutaneous nerve sheath proliferations that typically occur as flesh-colored papules solitarily on the head and neck in adults, with a slight predilection for females. Histopathologically, they are partially or completely encapsulated intradermal nodules with Schwann cells and axons in fascicles separated by clefts. Although these features are often characteristic, the hypercellular variant of PEN can pose a diagnostic challenge in distinguishing between other cellular neural and melanocytic lesions. We herein report a case of hypercellular PEN, which showed striking similarity to desmoplastic melanoma.