bluuebunny/crossref_metadata_2025 huggingface dataset:
Design principles for photonic crystals based on plasmonic nanoparticle superlattices
Authors: Sun Lin , Lin Haixin , Kohlstedt Kevin L. , Schatz George C. , Mirkin Chad A.
Published: June 2018

Significance

In this article, we derive a set of design principles for making photonic crystals with desired photonic stopband properties by taking advantage of spacer group, a design parameter enabled by recent advances in bottom-up assembly processes. The concept of spacer groups is experimentally realized through DNA-programmable assembly of Au nanoparticles, showing that highly reflective structures can be generated with cubic lattices and flexible spacer groups that can enable lighter and more compact 3D photonic crystals with precisely designed and even reconfigurable photonic properties. It also allows one to explore the combined effects of both photonic bandgap and the plasmonic properties of NPs, which may prove useful in fields spanning plasmonic cavity structures, optical nanocircuits, subwavelength imaging, and low-loss metamaterials.
Large-scale replicated field study of maize rhizosphere identifies heritable microbes
Authors: Walters William A. , Jin Zhao , Youngblut Nicholas , Wallace Jason G. , Sutter Jessica , Zhang Wei , González-Peña Antonio , Peiffer Jason , Koren Omry , Shi Qiaojuan , Knight Rob , Glavina del Rio Tijana , Tringe Susannah G. , Buckler Edward S. , Dangl Jeffery L. , Ley Ruth E.
Published: June 2018

Significance

In this very large-scale longitudinal field study of the maize rhizosphere microbiome, we identify heritable taxa. These taxa display variance in their relative abundances that can be partially explained by genetic differences between the maize lines, above and beyond the strong influences of field, plant age, and weather on the diversity of the rhizosphere microbiome. If these heritable taxa are associated with beneficial traits, they may serve as phenotypes in future breeding endeavors.
Developmental prosopagnosics have widespread selectivity reductions across category-selective visual cortex
Authors: Jiahui Guo , Yang Hua , Duchaine Bradley
Published: June 2018

Significance

People with developmental prosopagnosia (DP) have extremely poor face recognition and even have problems recognizing the faces of family and close friends. We carried out a comprehensive investigation of the neural basis of DP by comparing brain responses to multiple visual categories in DPs and people with normal face processing. The DPs showed widespread abnormalities in areas specialized for face processing and areas that respond preferentially to scenes and bodies. The abnormalities in scene and body areas indicate cortical problems in many DPs extend beyond face areas and open the door to investigations of developmental disorders impacting recognition of categories other than faces.
How gender determines the way we speak about professionals
Authors: Atir Stav , Ferguson Melissa J.
Published: June 2018

Significance

Across eight studies combining archival and experimental methods, we report evidence for a gender bias in how people speak about professionals. Men and women were, on average across studies, more than twice as likely to describe a male (vs. female) professional by surname in domains, such as science, literature, and politics. We find that this simple difference in reference affects judgments of eminence, with participants judging those professionals described by surname as more eminent and 14% more deserving of a career award. This gender bias may contribute to the gender gap in perceived eminence as well as in actual recognition and may partially explain the persistent state of women’s underrepresentation in high-status fields, including science, technology, engineering, and math.
Phosphatases control PKA-dependent functional microdomains at the outer mitochondrial membrane
Authors: Burdyga Alex , Surdo Nicoletta C. , Monterisi Stefania , Di Benedetto Giulietta , Grisan Francesca , Penna Elisa , Pellegrini Luca , Zaccolo Manuela , Bortolozzi Mario , Swietach Pawel , Pozzan Tullio , Lefkimmiatis Konstantinos
Published: June 2018

Significance

The selective phosphorylation of spatially distinct PKA targets is key for the pleiotropy of the cAMP cascade. This characteristic of the pathway is currently attributed to the ability of phosphodiesterases or adenylate cyclases to create subcellular sites (microdomains) where the concentration of cAMP is distinct from that of the surrounding areas. The role of phosphatases in this process has not been tested. Here we show that limited access of phosphatases to the PKA targets present at the outer mitochondrial membrane generates distinct microdomains of PKA phosphorylated proteins despite there being no differences in the local cAMP levels. These results describe an alternative mechanism capable of generating functional cAMP/PKA-dependent microdomains and may be extrapolated to the compartmentalization of other kinase-dependent events.
Formation of HONO from the NH3-promoted hydrolysis of NO2dimers in the atmosphere
Authors: Li Lei , Duan Zhiyao , Li Hui , Zhu Chongqin , Henkelman Graeme , Francisco Joseph S. , Zeng Xiao Cheng
Published: June 2018

Significance

As the primary source of “detergent” OH radicals, nitrous acid (HONO) plays an essential role in the chemistry of the atmosphere. Despite extensive studies, the source of HONO is still elusive. Although recent studies have shown the importance of reactive nitrogen compounds during aerosol formation, mechanistic insight into how these compounds react is still missing. Herein, based on Born–Oppenheimer molecular-dynamics simulations and free-energy sampling, we identified a formation mechanism for HONO via the NH3-promoted hydrolysis of NO2dimer (ONONO2) on water clusters/droplets. The near-spontaneous formation of HONO at the water–air interface sheds light on the catalytic role of water droplets in atmospheric chemistry. This finding provides not only a missing HONO source but also insight into HONO chemistry.
Marginalising homœopathy: an Australian case study
Authors: Greenland Joanne
Published: June 2018

Homœopathy, once an accepted form of medicine, is currently under attack in Australia, so much so that its very existence is threatened. To illustrate techniques of marginalisation of homœopathy in Australia, the Australian National Health and Medical Research Council’s (NHMRC) report of 2015 is examined. As there is no standard framework or classification of marginalisation techniques, boundary work ideas were used to suggest techniques used in the process of marginalisation. To condemn homœopathy, the NHMRC used at least eight techniques: authority, asserting protection of autonomy, exclusion, double standards, normalisation, denigration, censorship, expansion and diversion. The NHMRC report is a revealing example of how biomedicine uses various tactics to marginalise alternative therapies, thereby maintaining biomedicine’s dominant position.
A timer for analyzing temporally dynamic changes in transcription during differentiation in vivo
Authors: Bending David , Martín Paz Prieto , Paduraru Alina , Ducker Catherine , Marzaganov Erik , Laviron Marie , Kitano Satsuki , Miyachi Hitoshi , Crompton Tessa , Ono Masahiro
Published: June 2018

Understanding the mechanisms of cellular differentiation is challenging because differentiation is initiated by signaling pathways that drive temporally dynamic processes, which are difficult to analyze in vivo. We establish a new tool, Timer of cell kinetics and activity (Tocky; or toki [time in Japanese]). Tocky uses the fluorescent Timer protein, which spontaneously shifts its emission spectrum from blue to red, in combination with computer algorithms to reveal the dynamics of differentiation in vivo. Using a transcriptional target of T cell receptor (TCR) signaling, we establish Nr4a3-Tocky to follow downstream effects of TCR signaling. Nr4a3-Tocky reveals the temporal sequence of events during regulatory T cell (Treg) differentiation and shows that persistent TCR signals occur during Treg generation. Remarkably, antigen-specific T cells at the site of autoimmune inflammation also show persistent TCR signaling. In addition, by generating Foxp3-Tocky, we reveal the in vivo dynamics of demethylation of the Foxp3 gene. Thus, Tocky is a tool for cell biologists to address previously inaccessible questions by directly revealing dynamic processes in vivo.
Mortality and Risk of Cancer After Prophylactic Bilateral Oophorectomy in Women With a Family History of Cancer
Authors: Abildgaard Julie , Ahlström Magnus Glindvad , Daugaard Gedske , Nielsen Dorte Lisbet , Pedersen Anette Tønnes , Lindegaard Birgitte , Obel Niels
Published: June 2018

Background

Current international guidelines recommend systemic hormone therapy (HT) to oophorectomized women until the age of natural menopause. Despite an inherited predisposition to estrogen-dependent malignancies, the guidelines also apply to women oophorectomized because of a family history of cancer. The objective of this study was to investigate the impact of HT on mortality and risk of cancer in women oophorectomized because of a family history of cancer.

Methods

A nationwide, population-based cohort was used to study women oophorectomized because of a family history of cancer (n = 2002). Comparison cohorts included women from the background population individually matched on age (n = 18 018). Oophorectomized women were subdivided into three groups: oophorectomized at 1) age 45 years or younger not using HT, 2) age 45 years or younger using HT, 3) older than age 45 years, and their respective population comparison cohorts.

Results

Women oophorectomized at age 45 years or younger using HT had increased overall mortality (mortality rate ratio [MRR] = 3.45, 95% confidence interval [CI] = 1.53 to 7.79), mortality because of cancer (MRR = 5.67, 95% CI = 1.86 to 17.34), and risk of overall cancer (incidence rate ratio [IRR] = 3.68, 95% CI = 1.93 − 6.98), primarily reflected in an increased risk of breast cancer (IRR = 4.88, 95% CI = 2.19 − 10.68). Women oophorectomized at age 45 years or younger not using HT and women oophorectomized at older than age 45 years did not have increased mortality, mortality because of cancer, or risk of overall cancer, but they had increased risk of breast cancer (IRR = 2.64, 95% CI = 1.14 to 6.13, and IRR = 1.72, 95% CI = 1.14 to 2.59, respectively).

Conclusions

Use of HT in women oophorectomized at age 45 years or younger with a family history of cancer is associated with increased mortality and risk of overall cancer and breast cancer. Our study warrants further investigation to establish the impact of HT on mortality and cancer risk in oophorectomized women with a family history of cancer.
ALMA view of the circumnuclear disk of the Galactic Center: tidally disrupted molecular clouds falling to the Galactic Center
Authors: Tsuboi Masato , Kitamura Yoshimi , Uehara Kenta , Tsutsumi Takahiro , Miyawaki Ryosuke , Miyoshi Makoto , Miyazaki Atsushi
Published: June 2018

We present high angular resolution and high sensitivity images of the “circumnuclear disk” (CND) and the surrounding region of the Milky Way Galaxy in the CS J = 2–1, SiO v = 0 J = 2–1, H13CO+J = 1–0, C34S J = 2–1, and CH3OH $J_{K_a, K_c}=2_{1,1}$–11, 0A−− emission lines using ALMA. The CND is recognized as a torus-like molecular gas with gaps in these emission lines, except for the CH3OH emission line. The inner and outer radii of the CND are estimated to be Rin ∼ 1.5 and Rout ∼ 2 pc, respectively. The velocities of the rotation and radial motion are estimated to be Vrot ∼ 115 km s−1 and Vrad ∼ 23 km s−1, respectively. The LTE molecular gas mass is estimated to be MLTE ∼ 3 × 104 M⊙. We also found some anomalous molecular clouds in the surrounding region. One of the molecular clouds is positionally connected to part of the CND adjacent to the “western arc.” However, the cloud is seen to rotate in the opposite direction to the CND, so it could currently be falling from the outer region to the CND and being disrupted by the tidal shear of Sagittarius A* (Sgr A*) because the velocity is not yet assimilated into that of the CND. Another molecular cloud is continuously connected to the tip of the “eastern arm” (EA). The velocity of this cloud is consistent with that of the ionized gas in the EA. These facts suggest that the molecular cloud is falling from the outer region to the vicinity of Sgr A*, being disrupted by the tidal shear, and ionized by strong UV emission from the central cluster because the impact parameter of the cloud is smaller than the first cloud. These falling clouds would play an important role in transferring material from the outer region to the CND and/or the vicinity of Sgr A*.
Associations between family and home-related factors and child’s snack consumption in a multi-ethnic population
Authors: van Grieken Amy , Wang Lu , van de Gaar Vivian M , Jansen Wilma , Raat Hein
Published: June 2018

Background

Energy-dense snacks are considered unhealthy due to their high concentrations of fat and sugar and low concentrations of micronutrients. The present study aimed to evaluate associations between family and home-related factors and children’s snack consumption. We explored associations within subgroups based on ethnic background of the child.

Methods

Cross-sectional data of 644 primary school children (mean age: 9.4 years, 53% girls) from the population-based ‘Water Campaign’ study conducted in the Netherlands were used. Logistic regression analyses were used to evaluate the associations between family and home-related factors and child’s snack intake.

Results

Of the children, 28.7% consumed more than one snack per day. Children of parents who expressed more restrictive parenting practices towards the child’s snack consumption (odds ratio (OR) = 2.5, P < 0.001), and who modelled snack eating less often (OR = 2.2, P < 0.001) had lower snack intake. Restrictive parenting practices and parental modelling of healthy snacking were significant for children with a Dutch or Moroccan/Turkish ethnic background, but not for children with a Surinamese/Antillean ethnic background.

Conclusions

We observed that parenting practices and parental modelling were independently associated with the child’s snack intake. Also, the relationships between these factors and the child’s snack consumption differed for children with distinct ethnic backgrounds.
Methamphetamine exposure triggers apoptosis and autophagy in neuronal cells by activating the C/EBPβ‐related signaling pathway
Authors: Xu Xiang , Huang Enping , Luo Baoying , Cai Dunpeng , Zhao Xu , Luo Qin , Jin Yili , Chen Ling , Wang Qi , Liu Chao , Lin Zhoumeng , Xie Wei‐Bing , Wang Huijun
Published: June 2018

Methamphetamine (Meth) is a widely abused psychoactive drug that primarily damages the nervous system, notably causing dopaminergic neuronal apoptosis. CCAAT‐enhancer binding protein (C/EBPβ) is a transcription factor and an important regulator of cell apoptosis and autophagy. Insulin‐like growth factor binding protein (IGFBP5) is a proapoptotic factor that mediates Meth‐induced neuronal apoptosis, and Trib3 (tribbles pseudokinase 3) is an endoplasmic reticulum (ER) stress‐inducible gene involved in autophagic cell death through the mammalian target of rapamycin (mTOR) signaling pathway. To test the hypothesis that C/EBPβ is involved in Meth‐induced IGFBP5‐mediated neuronal apoptosis and Trib3‐mediated neuronal autophagy, we measured the protein expression of C/EBPβ after Meth exposure and evaluated the effects of silencing C/EBPβ, IGFBP5, or Trib3 on Meth‐induced apoptosis and autophagy in neuronal cells and in the rat striatum after intrastriatal Meth injection. We found that, at relatively high doses, Meth exposure increased C/EBPβ protein expression, which was accompanied by increased neuronal apoptosis and autophagy; triggered the IGFBP5‐mediated, p53‐up–regulated modulator of apoptosis (PUMA)‐related mitochondrial apoptotic signaling pathway; and stimulated the Trib3‐mediated ER stress signaling pathway through the Akt‐mTOR signaling axis. We also found that autophagy is an early response to Meth‐induced stress upstream of apoptosis and plays a detrimental role in Meth‐induced neuronal cell death. These results suggest that Meth exposure induces C/EBPβ expression, which plays an essential role in the neuronal apoptosis and autophagy induced by relatively high doses of Meth; however, relatively low concentrations of Meth did not change the expression of C/EBPβ in vitro. Further studies are needed to elucidate the role of C/EBPβ in low‐dose Meth‐induced neurotoxicity.—Xu, X., Huang, E., Luo, B., Cai, D., Zhao, X., Luo, Q., Jin, Y., Chen, L., Wang, Q., Liu, C., Lin, Z., Xie, W.‐B., Wang, H. Methamphetamine exposure triggers apoptosis and autophagy in neuronal cells by activating the C/EBPβ‐related signaling pathway. FASEB J. 32, 6737–6759 (2018). www.fasebj.org
Lipin‐1 regulates Bnip3–mediated mitophagy in glycolytic muscle
Authors: Alshudukhi Abdullah A. , Zhu Jing , Huang Dengtong , Jama Abdulrahman , Smith Jeffrey D. , Wang Qing Jun , Esser Karyn A. , Ren Hongmei
Published: June 2018

Autophagy of mitochondria (mitophagy) is essential for maintaining muscle mass and healthy skeletal muscle. Patients with heritable phosphatidic acid phosphatase lipin‐1–null mutations present with severe rhabdomyolysis and muscle atrophy in glycolytic muscle fibers, which are accompanied with mitochondrial aggregates and reduced mitochondrial cytochrome c oxidase activity. However, the underlying mechanisms leading to muscle atrophy as a result of lipin‐1 deficiency are still not clear. In this study, we found that lipin‐1 deficiency in mice is associated with a marked accumulation of abnormal mitochondria and autophagic vacuoles in glycolytic muscle fibers. Our studies using lipin‐1–deficient myoblasts suggest that lipin‐1 participates in B‐cell leukemia (BCL)‐2 adenovirus E1B19 kDa protein–interacting protein 3 (Bnip3)–regulated mitophagy by interacting with microtubule‐associated protein 1A/1B‐light chain (LC)3, which is an important step in the recruitment of mitochondria to nascent autophagosomes. The requirement of lipin‐1 for Bnip3–mediated mitophagy was further verified in vivo in lipin‐1–deficient green fluorescent protein‐LC3 transgenic mice (lipin‐1–/–‐GFP‐LC3). Finally, we showed that lipin‐1 deficiency in mice resulted in defective mitochondrial adaptation to starvation‐induced metabolic stress and impaired contractile muscle force in glycolytic muscle fibers. In summary, our study suggests that deregulated mitophagy arising from lipin‐1 deficiency is associated with impaired muscle function and may contribute to muscle rhabdomyolysis in humans.—Alshudukhi, A. A., Zhu, J., Huang, D., Jama, A., Smith, J. D., Wang, Q. J., Esser, K. A., Ren, H. Lipin‐1 regulates Bnip3–mediated mitophagy in glycolytic muscle. FASEB J. 32, 6796–6807 (2018). www.fasebj.org
Andreev bound states at spin-active interfaces
Authors: Beckmann D. , Hübler F. , Wolf M. J. , Löhneysen H. v.
Published: June 2018

Andreev bound states are ubiquitous in superconducting hybrid structures. They are formed near impurities, in Josephson junctions, in vortex cores and at interfaces. At spin-active superconductor–ferromagnet interfaces, Andreev bound states are formed due to spin-dependent scattering phases. Spin-dependent phase shifts are an important ingredient for the generation of triplet Cooper pairs in superconductor–ferromagnet hybrid structures. Spectroscopy of Andreev bound states is a powerful probe of superconducting order parameter symmetry, as well as spin-dependent interface scattering and the triplet proximity effect.

This article is part of the theme issue ‘Andreev bound states’.
Gene editing can generate fragile bivalents in mouse oocytes
Authors: Manil-Ségalen Marion , Łuksza Małgorzata , Kannaan Joanne , Marthiens Véronique , Lane Simon I.R , Jones Keith T. , Terret Marie-Emilie , Basto Renata , Verlhac Marie-Hélène
Published: June 2018

Mouse female meiotic spindles assemble from acentriolar MTOCs (aMTOCs) that fragment into discrete foci. These are further sorted and clustered to form spindle poles, thus providing balanced forces for faithful chromosome segregation. To assess the impact of aMTOCs biogenesis on spindle assembly, we genetically induced their precocious fragmentation in mouse oocytes using conditional overexpression of Plk4, a master MTOC regulator. Excessive microtubule nucleation from these fragmented aMTOCs accelerated spindle assembly dynamics. Prematurely formed spindles promoted the breakage of three different fragilized bivalents, generated by the presence of recombined Lox P sites. Reducing the density of microtubules diminished the extent of chromosome breakage. Thus, improper spindle forces can lead to widely described yet unexplained chromosomal structural anomalies with disruptive consequences on the ability of the gamete to transmit an uncorrupted genome.
Regulatory T-cells are required for neonatal heart regeneration
Authors: Li Jiatao , Yang Kevin Y. , Yee Tam Rachel Chun , Chan Vicken W. , Sheng Bao , Hori Shohei , Zhou Bin , Dennis Lo Yuk Ming , Lui Kathy O.
Published: June 2018

Previous work has elegantly demonstrated that, unlike adult mammalian heart, the neonatal heart is able to regenerate after injury from postnatal day (P) 1 to 7. Recently, macrophages are found to be required in the repair process as depletion of which abolishes endogenous regenerative capability of the neonatal heart. Nevertheless, whether innate immunity alone is sufficient for neonatal heart regeneration is obscure. Here, we investigate a hitherto novel role of FOXP3+ regulatory T-cells (Treg) in neonatal heart regeneration. Unlike their wild type counterparts, NOD/SCID mice that are deficient for T-cells but innate immune cells including macrophages fail to regenerate their injured heart as early as P3. In wild type mice, both conventional CD4+ T-cells and Treg are recruited to cardiac muscle within the first week after injury. Treatment with the lytic anti-CD4 antibody that specifically depletes conventional CD4+ T-cells leads to reduced cardiac fibrosis; while treatment with the lytic anti-CD25 antibody that specifically depletes CD4+CD25hiFOXP3+ Treg contributes to increased fibrosis of the neonatal heart after injury. Moreover, adoptive transfer of Treg to NOD/SCID mice results in mitigated fibrosis and increased proliferation and function of cardiac muscle of the neonatal heart after injury. Mechanistically, single cell transcriptomic profiling reveals that Treg are a source of chemokines and cytokines that attract monocytes and macrophages previously known to drive neonatal heart regeneration. Furthermore, Treg directly promote proliferation of both mouse and human cardiomyocytes in a paracrine manner. Our findings uncover an unappreciated mechanism in neonatal heart regeneration; and offer new avenues for developing novel therapeutics targeting Treg-mediated heart regeneration.
Healthspan pathway maps in C. elegans and humans highlight transcription, proliferation/biosynthesis and lipids
Authors: Möller Steffen , Saul Nadine , Cohen Alan A. , Köhling Rüdiger , Sender Sina , Escobar Hugo Murua , Junghanss Christian , Cirulli Francesca , Berry Alessandra , Antal Peter , Adler Priit , Vilo Jaak , Boiani Michele , Jansen Ludger , Repsilber Dirk , Grabe Hans Jörgen , Struckmann Stephan , Barrantes Israel , Hamed Mohamed , Wouters Brecht , Schoofs Liliane , Luyten Walter , Fuellen Georg
Published: June 2018

The molecular basis of aging and of aging-associated diseases is being unraveled at an increasing pace. An extended healthspan, and not merely an extension of lifespan, has become the aim of medical practice. However, a precise definition of health and healthspan is not straightforward, and the causal molecular basis of health “per se” is largely unknown. Here, we define health based on the absence of diseases and dysfunctions. Based on an extensive review of the literature, in particular for humans and C. elegans, we compile a list of features of health and of the genes associated with them. Clusters of these genes based on molecular interaction data give rise to maps of healthspan pathways for humans, featuring the themes transcription initiation, proliferation and cholesterol/lipid processing, and for C. elegans, featuring the themes immune response, mitochondrion and biosynthesis based on genetic and compound intervention data, and lipids, biosynthesis and transcription based on WormBase compound intervention data. Overlaying healthspan-related gene expression data (describing effects of metabolic intervention associated with improvements in health) onto the aforementioned healthspan pathway maps, we observe the downregulation of Notch signalling in humans and of proliferation/cell-cycle in C. elegans. The former reflects the proinflammatory role of the Notch pathway. We identify transcription, proliferation/biosynthesis and lipids as a common theme on the annotation level, and proliferation-related kinases on the gene/protein level. Our literature-based data corpus, including visualization, is available as a reference for future investigations, at http://www.h2020awe.eu/index.php/pathways/.
IFN-γ induces epithelial-to-mesenchymal transition of cancer cells via an unique microRNA processing
Authors: Lo U-Ging , Pong Rey-Chen , Yang Diane , Gandee Leah , Hernandez Elizabeth , Dang Andrew , Lin Chung-Jung , Santoyo John , Ma Shi-Hong , Sonavane Rajni , Huang Jun , Tseng Shu-Fen , Moro Loredana , Arbini Arnaldo A. , Kapur Payal , Raj Ganesh , He Dalin , Lai Chih-ho , Lin Ho , Hsieh Jer-Tsong
Published: June 2018

Interferon-γ (IFNγ) is a potent cytokine in modulating tumor immunity and tumoricidal effects. We demonstrate a new function of IFNγ in inducing epithelial-to-mesenchymal transition (EMT) in normal and cancer cells from different cell types. IFNγ activates JAK-STAT signaling pathway leading to the transcription of IFN-stimulated genes (ISGs), such as interferon-induced tetratricopeptide repeat 5 (IFIT5). We unveil a new function of IFIT5 complex in degrading precursor microRNAs (pre-miRNA) that include pre-miR-363 from the miR-106a-363 cluster, as well as pre-miR-101 and pre-miR-128 with a similar 5’-end structure with pre-miR-363. Noticeably, these suppressive miRNAs have similar functions by targeting EMT transcription factors in prostate cancer (PCa) cells. We further demonstrated that IFIT5 plays a critical role in IFNγ-induced cell invasivenessin vitroand lung metastasisin vivo. Clinically, IFIT5 is highly elevated in high-grade PCa and its expression inversely correlates with these suppressive miRNAs. Altogether, this study unveils pro-tumorigenic role of the IFN pathway via a new mechanism of action, which certainly raises concern about its clinical application.
PTK2 regulates the UPS impairment via p62 phosphorylation in TDP-43 proteinopathy
Authors: Lee Shinrye , Jeon Yu-Mi , Kim Seyeon , Kwon Younghwi , Jo Myungjin , Jang You-Na , Lee Seongsoo , Kim Jaekwang , Kim Sang Ryong , Lee Kea Joo , Lee Sung Bae , Kim Kiyoung , Kim Hyung-Jun
Published: June 2018

TDP-43 proteinopathy is a common feature in a variety of neurodegenerative disorders including Amyotrophic lateral sclerosis (ALS) cases, Frontotemporal lobar degeneration (FTLD), and Alzheimer’s disease. However, the molecular mechanisms underlying TDP-43-induced neurotoxicity are largely unknown. In this study, we demonstrated that TDP-43 proteinopathy induces impairment in ubiquitin-proteasome system (UPS) evidenced by an accumulation of ubiquitinated proteins and reduction of proteasome activity in neuronal cells. Through kinase inhibitor screening, we identified PTK2 as a suppressor of neurotoxicity induced by UPS impairment. Importantly, PTK2 inhibition significantly reduces ubiquitin aggregates and attenuated TDP-43-induced cytotoxicity inDrosophilamodel of TDP-43 proteinopathy. We further identified that phosphorylation of p62 at serine 403 (p-p62S403), a key component in the autophagic degradation of poly-ubiquitinated proteins, is increased upon TDP-43 overexpression and dependent on activation of PTK2 in neuronal cells. Moreover, expressing a non-phosphorylated form of p62 (p62S403A) significantly represses accumulation of polyubiquitinated proteins and neurotoxicity induced by TDP-43 overexpression in neuronal cells. In addition, inhibition of TBK1, a kinase which phosphorylates S403 of p62, ameliorates neurotoxicity upon UPS impairment in neuronal cells. Taken together, our data suggest that activation of PTK2-TBK1-p62 axis plays a critical role in the pathogenesis of TDP-43 by regulating neurotoxicity induced by UPS impairment. Therefore, targeting PTK2-TBK1-p62 axis may represent a novel therapeutic intervention for neurodegenerative diseases with TDP-43 proteinopathy.
CDK phosphorylation of Xenopus laevis M18BP1 promotes its metaphase centromere localization
Authors: French Bradley T. , Straight Aaron F.
Published: June 2018

Chromosome segregation requires the centromere, the site on chromosomes where kinetochores assemble in mitosis to attach chromosomes to the mitotic spindle. Centromere identity is defined epigenetically by the presence of nucleosomes containing the histone H3 variant CENP-A. New CENP-A nucleosome assembly occurs at the centromere every cell cycle during G1, but how CENP-A nucleosome assembly is spatially and temporally restricted remains poorly understood. Centromere recruitment of factors required for CENP-A assembly is mediated in part by the three-protein Mis18 complex (Mis18α, Mis18β, M18BP1). Here we show that Xenopus M18BP1 localizes to centromeres during metaphase - prior to CENP-A assembly - by binding to CENP-C using a highly conserved SANTA domain. We find that Cdk phosphorylation of M18BP1 is necessary for M18BP1 to bind CENP-C and localize to centromeres in metaphase. Surprisingly, mutations which disrupt the metaphase M18BP1/CENP-C interaction cause defective nuclear localization of M18BP1 in interphase, resulting in defective CENP-A nucleosome assembly. We propose that M18BP1 may identify centromeric sites in metaphase for subsequent CENP-A nucleosome assembly in interphase.
Multimodal evidence for delayed fear extinction in adolescence and young adulthood
Authors: Morriss Jayne , Christakou Anastasia , van Reekum Carien M.
Published: June 2018

Previous research in rodents and humans points to an evolutionarily conserved profile of blunted fear extinction during adolescence, underpinned by brain structures such as the amygdala and medial prefrontal cortex (mPFC). In this study, we examine age-related effects on the function and structural connectivity of this system in fear extinction in adolescence and young adulthood. Younger age was associated with greater amygdala activity and delayed mPFC engagement to learned threat cues as compared to safety cues. Furthermore, greater structural integrity of the uncinate fasciculus, a white matter tract that connects the amygdala and mPFC, mediated the relationship between age and acceleration of mPFC engagement during extinction. These findings suggest that age-related changes in the structure and function of amygdala-mPFC circuitry may underlie the protracted maturation of fear regulatory processes, rendering younger individuals more vulnerable to anxiety disorders, which emerge during development.
Structural characterization of free-state and product-stateMycobacterium tuberculosismethionyl-tRNA synthetase reveals an induced-fit ligand-recognition mechanism
Authors: Wang Wei , Qin Bo , Wojdyla Justyna Aleksandra , Wang Meitian , Gao Xiaopan , Cui Sheng
Published: June 2018

Mycobacterium tuberculosis(MTB) caused 10.4 million cases of tuberculosis and 1.7 million deaths in 2016. The incidence of multidrug-resistant and extensively drug-resistant MTB is becoming an increasing threat to public health and the development of novel anti-MTB drugs is urgently needed. Methionyl-tRNA synthetase (MetRS) is considered to be a valuable drug target. However, structural characterization ofM. tuberculosisMetRS (MtMetRS) was lacking for decades, thus hampering drug design. Here, two high-resolution crystal structures of MtMetRS are reported: the free-state structure (apo form; 1.9 Å resolution) and a structure with the intermediate product methionyl-adenylate (Met-AMP) bound (2.4 Å resolution). It was found that free-state MtMetRS adopts a previously unseen conformation that has never been observed in other MetRS homologues. The pockets for methionine and AMP are not formed in free-state MtMetRS, suggesting that it is in a nonproductive conformation. Combining these findings suggests that MtMetRS employs an induced-fit mechanism in ligand binding. By comparison with the structure of human cytosolic MetRS, additional pockets specific to MtMetRS that could be used for anti-MTB drug design were located.
Raising bank loss absorption capacity through equity capital or bail-in debt
Authors: Benink Harald A.
Published: June 2018

Purpose

Based upon recent statements made by the European Shadow Financial Regulatory Committee, a group of well-known professors coming from ten European countries, during the period 2012-2017, this paper aims to analyze from a European perspective the adequacy and credibility of the proposed framework.

Design/methodology/approach

This paper is a summary and interpretation of statements from the European Shadow Financial Regulatory Committee.

Findings

The authors argue that the credibility of the bail-in mechanism is likely to be limited. Because of this, unexpected losses may not be absorbed by unsecured debt holders. Therefore, there is still a need for relatively high equity capital buffers.

Originality/value

The issue of how to raise loss absorption capacity for banks is prominent on the international policy agenda. International regulators are aiming for a combination of equity capital, typically raised by issuing shares, retaining profits and issuing contingent convertible (CoCo) bonds and bail-in debt where unsecured creditors such as holders of subordinated and common bonds are supposed to take losses in case of a bankruptcy or restructuring of a bank.
Organizational tenure and knowledge-sharing behaviours
Authors: Sarti Daria
Published: June 2018

Purpose

This paper aims to contribute to research on the broad theme of knowledge-sharing (KS) behaviours and the impact that different organizational tenure may have on them. In this relationship, the relevance of the leader in enhancing sharing dynamics among employees is highlighted.

Design/methodology/approach

This study focuses on KS attitudes among employees with different numbers of years spent in the same organization, seen through the theoretical lens of a social exchange perspective. Specifically, the role of the leader in building a social exchange with co-workers is investigated as a managerial lever able to favour KS among a more experienced workforce. This paper starts by considering the relationship between organizational tenure and employees’ KS attitude. Furthermore, the specific role played by the leader–member social exchange with regard to this relation is described. The study’s hypotheses are tested on data collected from employees (N= 150) working in a non-profit organization located in central Italy.

Findings

The results suggest that a negative relationship exists between employees’ organizational tenure and KS attitude. In addition, the critical role of a leader’s support is demonstrated in moderating the effect of different organizational tenures on the KS attitude.

Research limitations/implications

This paper has both theoretical and managerial implications.

Originality/value

This paper contributes to the research on the important role of leaders in enhancing KS behaviors among co-workers when the number of years in the same organizations is a variable of interest.
Understanding public libraries’ challenges, motivators, and perceptions toward the use of social media for marketing
Authors: Choi Namjoo , Joo Soohyung
Published: June 2018

Purpose

The purpose of this paper is to identify challenges and motivators to social media adoption for marketing purposes in public libraries and to investigate how these libraries perceive the importance of social media marketing.

Design/methodology/approach

A nation-wide online survey on public libraries in the USA was conducted to carry out this study, and a total number of 470 responses were used for data analysis.

Findings

This study determined a range of challenges and motivators to implementing social media for marketing in public libraries. The results also showed that public libraries perceive social media as an important tool for their library marketing and intend to increase their use.

Practical implications

The findings from this study can serve as a guideline for public libraries when employing social media for marketing purposes in their libraries.

Originality/value

This study assessed the current state of social media use for marketing in the public library context, a context that has been under-researched in the literature, from three perspectives: challenges, motivators, and perceptions.
Altmetrics: “big data” that map the influence of New Zealand research
Authors: Konkiel Stacy , Guichard Stephanie
Published: June 2018

Purpose

Altmetrics can offer organizations a unique opportunity to understand the non-traditional scholarly and public influence of their institutions’ research. This paper aims to look at bibliometrics and altmetrics for New Zealand research published in 2016 to understand the country’s research’s reach in social media, mainstream media and public policy, as well as more traditional measures of research impact such as university rankings, citations and publications.

Design/methodology/approach

Research insights platform Dimensions was searched for author affiliations and publication dates for papers published in 2016 by New Zealand researchers (n = 10,934). The study then used Dimensions to perform citation analysis and Altmetric Explorer to find altmetrics for these journal articles, and to generate visualizations to better interrogate the data set.

Findings

Of the 10,934 papers published in 2016 by New Zealand (2016 NZ) researchers, 5,413 (49.5 per cent) were mentioned 86,915 times in one of the 16 sources that Altmetric tracks. Twitter, news outlets and Facebook were among the sources that showed the most engagement with New Zealand 2016 research. Citation analysis tools in Dimensions showed that New Zealand 2016 research had a higher than average Field Citation Ratio (1.51) and Relative Citation Ratio (1.29).

Originality/value

This study combines traditional bibliometric analysis with altmetrics to find new insights into the impact of recent New Zealand research. It suggests new means for organizations to demonstrate the value of the research they produce.
The established state and patient X’s rebellion
Authors: Voyce Andrew
Published: June 2018

Purpose

The purpose of this paper (anonymised case study) is to explore political perspectives on the detention of patients under the Mental Health Act.

Design/methodology/approach

The approach is ethnographic and narrative.

Findings

The essay offers an exploratory explanation using political theory, of a violent and rebellious act by a person detained as a formal mental health patient. The protest relates to the treatment offered to the patient.

Research limitations/implications

This essay offers a new explanation for a protest for a person detained as a compulsory mental health patient. The essay explores issues relating to political philosophy that the patient applies to their detention.

Practical implications

An understanding of how a patient with a background in academic politics is related in this essay. There is consideration of how an education in politics can be as valid in wellbeing, as a medical degree. It may be that more patients will be spared multiple hospital admissions by the use of effective therapies.

Social implications

There is consideration of the debate about the fitness of current mental health legislation to enable wellbeing, and the debate about the review of mental health law begun in 2017.

Originality/value

This is a perspective of how political theory can inform individual acts. The political inquiry is not of dogma or ideology, either critical or affirming. The discourse is of rebellion with a purpose, not of revolution, class war or national dispute. However, aspects of works that are critical of psychiatry are included in the considerations.
Evaluating the temporal dimension of legitimisation strategies
Authors: Maroun Warren
Published: June 2018

Purpose

The purpose of this study is to examine how social disclosures by one of the world’s largest producers of Platinum Group Metals are used to maintain and repair legitimacy in the context of South Africa’s prevailing socio-economic conditions and in response to the immediate challenge to legitimacy posed by violent worker demonstrations taking place at its operations in Marikana during August 2012. This is done to highlight how legitimacy strategies take account of the temporal characteristics of a threat to legitimacy and how these, in turn, may constrain the need for far-reaching organisational change.

Design/methodology/approach

Suchman’s (1995) outline of legitimacy theory and Laughlin’s (1991) model of organisational change provide a frame of reference for a detailed thematic content analysis which identifies the use of different strategies by an organization to respond to threats to its credibility and how these impact, resulting changes to business philosophies, policies and systems.

Findings

The study highlights the temporal dimension of legitimisation strategies. Social-related disclosures provided by the case entity in response to labour unrest are aimed at addressing both the episodic and continual threat to legitimacy resulting from the unfavourable event. These also have the effect of limiting the extent of internal changes to select business policies and sub-systems. Carefully managing legitimacy allows the case entity to avoid the need to reformulate its business ethos.

Research limitations/implications

The study deals only with a single case organisation. Although the emphasis is on highlighting themes and principles, results are not necessarily applicable in different contexts. Related to this, although the study deals with a major South African mining company, it does not prove the relevance of local cultural differences to the legitimisation process.

Originality/value

The study dispenses with the use of proxies, such as frequencies of disclosures, to demonstrate how organisations use non-financial reporting to secure legitimacy. Instead, it offers a detailed account of how different sub-sets of legitimacy are being mobilised in corporate reports response to long-term and episodic legitimacy considerations. In addition, the study offers one of the first interpretive accounts of how strategies used to manage legitimacy may constrain the potential of a material external shock resulting in internal organisational change. Finally, the study offers one of the first examples of the operation of legitimacy and organisational change theory from the African Continent.
Evidence-based management for today’s “ambidextrous” organizations
Authors: Jackson Nicole C. , Leung Opal M.C.
Published: June 2018

Purpose

This paper examines how evidence based management (EBM) can help managers build more flexible organizations. In the context of this article, we define the need to build for this capacity around the challenge of “ambidexterity”, or the need for companies to continue operations while also allowing for innovation. We present a framework to help managers create strategies that help them build ambidexterity in their organizations, whether they operate in highly regulated, compliance driven or un-regulated, non-compliance climates.

Design/methodology/approach

This paper identifies four organizational design strategies each of which represents a different leadership and organization consideration that may focus on how evidence based management practices are linked to competency building (i.e., exploitation), the need innovation, or an equal balance between the two (i.e., ambidexterity).

Findings

Our findings reveal that an organization’s use of data given these four strategic orientations reflect different uses of data (verifiability and codification concerns) and ways of embedding compliance and ambidexterity (exploitation vs. exploration) considerations.

Practical implications

These four strategies help managers expose biases in their current decision-making practices, and how they subsequently may affect lifecycle, change management, and data practice in ambidexterity development.

Originality/value

While EBM acknowledges the importance of utilizing evidence, it remains limited toward understanding how it might be used to build for ambidexterity in organizations.
Landscape structure and ecology influence the spread of a bat fungal disease
Authors: Lilley Thomas M. , Anttila Jani , Ruokolainen Lasse
Published: June 2018

White‐nose syndrome (WNS), affecting multiple North American bat species during the hibernation period, is a highly pathogenic disease caused by the psychrophilic fungus Pseudogymnoascus destructans (Pd). Because the fungal pathogen persists in the hibernation site environment independently of the hosts, previous theory on spatial disease dynamics cannot predict WNS epidemics. However, the ability to understand factors contributing to the spread of white‐nose syndrome (WNS) in North America is crucial to the management of infected and susceptible bat populations as well as the conservation of threatened and endangered bat species.

Utilizing recent theory on environmental opportunistic pathogens, we modelled the effect of (a) landscape clustering, (b) environmental conditions in hibernacula and (c) microbial competition on the spread of WNS. We used available, already published data to construct and parameterize our model, which takes into account the spatial distribution of hibernation sites, temperature conditions in both the outside ambient and hibernation site environment, bat population dynamics, dispersal and infection by the pathogen, which also has its host‐independent dynamics with the environment. We also consider the effect of outside‐host competition between the pathogen and other micro‐organisms on spatial disease dynamics.

Our model suggests that pathogen loads accumulate in poorly connected hibernacula at short host dispersal, which can help found the epidemic. In contrast, invasion of the landscape is most successful at long host dispersal distances, with homogenous hibernation site distribution and heterogeneous between‐hibernation site temperatures. Also, increasing the mean temperature across hibernacula increases fungal growth rate, leading to higher disease prevalence and faster invasion rate. Increasing spatial heterogeneity in hibernaculum temperatures results in the formation of disease hotspots in warmer hibernacula, facilitating more effective spread of the disease in the landscape. Cold‐adapted competing microbes can prevent invasion, and therefore, overwintering in cold hibernacula increases probability of host survival.

Sites that were suboptimal for overwintering prior to WNS may have importance in preventing local extirpations. Although the model is tailored for WNS, due to pressing need for results that can assist in planning conservation measures, these novel results can be broadly applied to other environmentally transmitted diseases.

A plain language summary is available for this article.