bluuebunny/crossref_metadata_2025 huggingface dataset:
HDAC1 links early life stress to schizophrenia-like phenotypes
Authors: Bahari-Javan Sanaz , Varbanov Hristo , Halder Rashi , Benito Eva , Kaurani Lalit , Burkhardt Susanne , Anderson-Schmidt Heike , Anghelescu Ion , Budde Monika , Stilling Roman M. , Costa Joan , Medina Juan , Dietrich Detlef E. , Figge Christian , Folkerts Here , Gade Katrin , Heilbronner Urs , Koller Manfred , Konrad Carsten , Nussbeck Sara Y. , Scherk Harald , Spitzer Carsten , Stierl Sebastian , Stöckel Judith , Thiel Andreas , von Hagen Martin , Zimmermann Jörg , Zitzelsberger Antje , Schulz Sybille , Schmitt Andrea , Delalle Ivana , Falkai Peter , Schulze Thomas G. , Dityatev Alexander , Sananbenesi Farahnaz , Fischer André
Published: May 2017

Significance

Early life stress (ELS) is an important risk factor for schizophrenia. Our study shows that ELS in mice increases the levels of histone-deacetylase (HDAC) 1 in brain and blood. Although altered
Hdac1
expression in response to ELS is widespread, increased
Hdac1
levels in the prefrontal cortex are responsible for the development of schizophrenia-like phenotypes. In turn, administration of an HDAC inhibitor ameliorates ELS-induced schizophrenia-like phenotypes. We also show that
Hdac1
levels are increased in the brains of patients with schizophrenia and in blood from patients who suffered from ELS, suggesting that the analysis of
Hdac1
expression in blood could be used for patient stratification and individualized therapy.
Extraordinarily rapid speciation in a marine fish
Authors: Momigliano Paolo , Jokinen Henri , Fraimout Antoine , Florin Ann-Britt , Norkko Alf , Merilä Juha
Published: May 2017

Significance

Divergent selection can lead to the evolution of distinct species, a process known as ecological speciation. Evidence for ecological speciation in the marine environment is scarce, and the few known examples have happened within a time frame of hundreds of thousands to millions of years. We present evidence that European flounders in the Baltic Sea exhibiting different breeding behaviors are a species pair arising from a recent event of ecological speciation. The two lineages diverged within less than 3,000 generations. This is the fastest event of speciation ever reported for any marine vertebrate. Extraordinarily rapid speciation driven by natural selection can therefore happen even in the marine environment.
Emergence of categorical face perception after extended early-onset blindness
Authors: Gandhi Tapan K. , Singh Amy Kalia , Swami Piyush , Ganesh Suma , Sinha Pawan
Published: May 2017

Significance

The results of this study help resolve an important open question regarding visual learning: Can the human brain acquire face classification skill late in life, or is such learning limited only to a critical period early in development? Working with a group of congenitally blind children in whom we were able to surgically initiate sight, we tracked their face/nonface categorization ability over several months. The data reveal that although the newly sighted children do not possess innately specified face schemas, they are able to learn this distinction to a high degree of proficiency through natural visual experience. These findings have implications for visual learning, brain plasticity, and prognoses for late treatments of blindness.
Mental models accurately predict emotion transitions
Authors: Thornton Mark A. , Tamir Diana I.
Published: May 2017

Significance

People naturally understand that emotions predict actions: angry people aggress, tired people rest, and so forth. Emotions also predict future emotions: for example, tired people become frustrated and guilty people become ashamed. Here we examined whether people understand these regularities in emotion transitions. Comparing participants’ ratings of transition likelihood to others’ experienced transitions, we found that raters’ have accurate mental models of emotion transitions. These models could allow perceivers to predict others’ emotions up to two transitions into the future with above-chance accuracy. We also identified factors that inform—but do not fully determine—these mental models: egocentric bias, the conceptual properties of valence, social impact, and rationality, and the similarity and co-occurrence between different emotions.
Behavioral and neural correlates to multisensory detection of sick humans
Authors: Regenbogen Christina , Axelsson John , Lasselin Julie , Porada Danja K. , Sundelin Tina , Peter Moa G. , Lekander Mats , Lundström Johan N. , Olsson Mats J.
Published: May 2017

Significance

In the perpetual race between evolving organisms and pathogens, the human immune system has evolved to reduce the harm of infections. As part of such a system, avoidance of contagious individuals would increase biological fitness. The present study shows that we can detect both facial and olfactory cues of sickness in others just hours after experimental activation of their immune system. The study further demonstrates that multisensory integration of these olfactory and visual sickness cues is a crucial mechanism for how we detect and socially evaluate sick individuals. Thus, by motivating the avoidance of sick conspecifics, olfactory–visual cues, both in isolation and integrated, may be important parts of circuits handling imminent threats of contagion.
Unique clade of alphaproteobacterial endosymbionts induces complete cytoplasmic incompatibility in the coconut beetle
Authors: Takano Shun-ichiro , Tuda Midori , Takasu Keiji , Furuya Naruto , Imamura Yuya , Kim Sangwan , Tashiro Kosuke , Iiyama Kazuhiro , Tavares Matias , Amaral Acacio Cardoso
Published: May 2017

Significance

Maternally inherited bacterial endosymbionts in arthropods manipulate host reproduction to increase the number of infected females. Cytoplasmic incompatibility (CI) is one such manipulation, in which infected females can produce offspring by mating with both infected and uninfected males, but uninfected females cannot or seldom produce offspring with infected males. Two bacterial endosymbionts,
Wolbachia
and
Cardinium
, are known CI inducers. Here we report a third CI inducer that belongs to a unique clade of Alphaproteobacteria. This bacterial clade was found to cause complete CI between two clades of the coconut beetle, a serious invasive pest of coconut palms. We discuss the potential use of this bacterium as a biological control agent and its effects on speciation of the coconut beetle.
Engineering Cu surfaces for the electrocatalytic conversion of CO
2
: Controlling selectivity toward oxygenates and hydrocarbons
Authors: Hahn Christopher , Hatsukade Toru , Kim Youn-Geun , Vailionis Arturas , Baricuatro Jack H. , Higgins Drew C. , Nitopi Stephanie A. , Soriaga Manuel P. , Jaramillo Thomas F.
Published: May 2017

Significance

Anthropogenic global warming necessitates the development of renewable carbon-free and carbon-neutral technologies for the future. Electrochemical CO
2
reduction is one such technology that has the potential to impact climate change by enabling sustainable routes for the production of fuels and chemicals. Whereas the field of CO
2
reduction has attracted great interest, current state-of-the-art electrocatalysts must be improved in product selectivity and energy efficiency to make this pathway viable for the future. Here, we investigate how controlling the surface structure of copper electrocatalysts can guide CO
2
reduction activity and selectivity. We show how the coordination environment of Cu surfaces influences oxygenate vs. hydrocarbon formation, providing insights on how to improve selectivity and energy efficiency toward more valuable CO
2
reduction products.
Nanomechanics of the substrate binding domain of Hsp70 determine its allosteric ATP-induced conformational change
Authors: Mandal Soumit Sankar , Merz Dale R. , Buchsteiner Maximilian , Dima Ruxandra I. , Rief Matthias , Žoldák Gabriel
Published: May 2017

Significance

Hsp70 is a protein nanometer-sized molecular machine operating similar like a macroscopic engine: Combustion of fuel (ATP in the case of Hsp70) triggers mechanical motion for its function. However, in contrast to macroscopic engines, protein machines face additional limitations imposed by thermal fluctuations and by the low stability of the individual components. Using single-molecule force spectroscopy, we drive the passive machine through its mechanical states that allows us to detect its relevant parts. Applying this approach for the substrate binding domain (SBD) of Hsp70, we identified mechanical subunits and hinges of the SBD. Interestingly, these parts are involved in an ATP-fueled biological conformational change of Hsp70. In summary, single-molecule manipulation gives insight into the operating principles of nanoscale molecular machines.
Facial appearance affects science communication
Authors: Gheorghiu Ana I. , Callan Mitchell J. , Skylark William J.
Published: May 2017

Significance

The dissemination of scientific findings to the wider public is increasingly important to public opinion and policy. We show that this process is influenced by the facial appearance of the scientist. We identify the traits that engender interest in a scientist’s work and the perception that they do high-quality work, and show that these face-based impressions influence both the selection and evaluation of science news. These findings inform theories of person perception and illuminate a potential source of bias in the public’s understanding of science.
Data-driven modeling reveals cell behaviors controlling self-organization during
Myxococcus xanthus
development
Authors: Cotter Christopher R. , Schüttler Heinz-Bernd , Igoshin Oleg A. , Shimkets Lawrence J.
Published: May 2017

Significance

Coordinated cell movement is critical for a broad range of multicellular phenomena, including microbial self-organization, embryogenesis, wound healing, and cancer metastasis. Elucidating how these complex behaviors emerge within cell populations is frequently obscured by randomness in individual cell behavior and the multitude of internal and external factors coordinating cells. This work describes a technique of combining fluorescent cell tracking with computational simulations driven by the tracking data to identify cell behaviors contributing to an emergent phenomenon. Application of this technique to the model social bacterium
Myxococcus xanthus
suggested key aspects of cell coordination during aggregation without complete knowledge of the underlying signaling mechanisms.
B
12
-dependent photoresponsive protein hydrogels for controlled stem cell/protein release
Authors: Wang Ri , Yang Zhongguang , Luo Jiren , Hsing I-Ming , Sun Fei
Published: May 2017

Significance

Photoresponsive hydrogels have lately received ample attention because of their great potential in biomedical applications. However, the use of an entirely recombinant protein-based hydrogel with light-sensing abilities for stem cell applications has rarely been shown. Here, we created a B
12
-dependent light-sensing hydrogel by covalently stitching together the photoreceptor C-terminal adenosylcobalamin binding domain (CarH
C
) proteins under mild conditions. The polymeric CarH
C
proteins self-assemble into an elastic hydrogel in the presence of adenosylcobalamin in the dark and disassemble rapidly on light exposure. Such a photoresponsive protein hydrogel system enabled facile release/recovery of stem cells and protein molecules. This direct assembly of stimuli-responsive proteins into hydrogels represents a versatile strategy for designing “smart” materials and opens up enormous opportunities for future material biology.
Perceived social presence reduces fact-checking
Authors: Jun Youjung , Meng Rachel , Johar Gita Venkataramani
Published: May 2017

Significance

The dissemination of unverified content (e.g., “fake” news) is a societal problem with influence that can acquire tremendous reach when propagated through social networks. This article examines how evaluating information in a social context affects fact-checking behavior. Across eight experiments, people fact-checked less often when they evaluated claims in a collective (e.g., group or social media) compared with an individual setting. Inducing momentary vigilance increased the rate of fact-checking. These findings advance our understanding of whether and when people scrutinize information in social environments. In an era of rapid information diffusion, identifying the conditions under which people are less likely to verify the content that they consume is both conceptually important and practically relevant.
Histone-binding of DPF2 mediates its repressive role in myeloid differentiation
Authors: Huber Ferdinand M. , Greenblatt Sarah M. , Davenport Andrew M. , Martinez Concepcion , Xu Ye , Vu Ly P. , Nimer Stephen D. , Hoelz André
Published: May 2017

Significance

Double plant homeodomain finger 2 (DPF2) is a regulator of myeloid differentiation and implicated in a range of human cancers, including acute myelogenous leukemia. Recruitment of DPF2 to chromatin has been shown to alter the expression of target genes and inhibit myeloid differentiation. Here, we present the crystal structure of the human DPF2 tandem plant homeodomain finger domain and comprehensive structure-guided biochemical and in vivo analyses. Combined, our data delineate the determinants of DPF2’s chromatin recruitment and establish its regulatory role in human hematopoietic stem/progenitor cell differentiation.
Metabolic basis to Sherpa altitude adaptation
Authors: Horscroft James A. , Kotwica Aleksandra O. , Laner Verena , West James A. , Hennis Philip J. , Levett Denny Z. H. , Howard David J. , Fernandez Bernadette O. , Burgess Sarah L. , Ament Zsuzsanna , Gilbert-Kawai Edward T. , Vercueil André , Landis Blaine D. , Mitchell Kay , Mythen Monty G. , Branco Cristina , Johnson Randall S. , Feelisch Martin , Montgomery Hugh E. , Griffin Julian L. , Grocott Michael P. W. , Gnaiger Erich , Martin Daniel S. , Murray Andrew J.
Published: May 2017

Significance

A relative fall in tissue oxygen levels (hypoxia) is a common feature of many human diseases, including heart failure, lung diseases, anemia, and many cancers, and can compromise normal cellular function. Hypoxia also occurs in healthy humans at high altitude due to low barometric pressures. Human populations resident at high altitude in the Himalayas have evolved mechanisms that allow them to survive and perform, including adaptations that preserve oxygen delivery to the tissues. Here, we studied one such population, the Sherpas, and found metabolic adaptations, underpinned by genetic differences, that allow their tissues to use oxygen more efficiently, thereby conserving muscle energy levels at high altitude, and possibly contributing to the superior performance of elite climbing Sherpas at extreme altitudes.
Inducible CTCF insulator delays the
IgH
3′ regulatory region-mediated activation of germline promoters and alters class switching
Authors: Braikia Fatima-Zohra , Oudinet Chloé , Haddad Dania , Oruc Zeliha , Orlando Domenico , Dauba Audrey , Le Bert Marc , Khamlichi Ahmed Amine
Published: May 2017

Significance

The spatial and temporal control of complex loci’s expression is often effected by distant regulatory elements. At the
IgH
locus, class switch recombination (CSR) is preceded by transcription of the recombining genes and is controlled by the 3′ regulatory region (3′RR) in a stimulus-dependent manner. Why the 3′RR-mediated up-regulation of transcription is delayed to the mature B-cell stage is unknown. We show that an inducible CTCF insulator is involved in this process. Deletion of the insulator led to specific deregulation of transcription and CSR at earlier developmental stages. Insertion of a promoter downstream of the insulator led to its premature activation. Thus, the 3′RR has developmentally controlled potential to constitutively activate target promoters, but its activity is blocked by the insulator.
Selective regulation of Notch ligands during angiogenesis is mediated by vimentin
Authors: Antfolk Daniel , Sjöqvist Marika , Cheng Fang , Isoniemi Kimmo , Duran Camille L. , Rivero-Muller Adolfo , Antila Christian , Niemi Rasmus , Landor Sebastian , Bouten Carlijn V. C. , Bayless Kayla J. , Eriksson John E. , Sahlgren Cecilia M.
Published: May 2017

Significance

Angiogenesis, the formation of new blood vessels from existing ones, is essential for embryonic development and necessary for tumor growth and invasion. The Notch signaling pathway regulates angiogenesis where the two Notch ligands, Dll4 and Jagged 1, exert opposite functions on sprouting. We found that the intermediate filament vimentin balances angiogenesis by binding specifically to the proangiogenic Jagged ligands. This binding provides a force-generating mechanism on the Jagged–Notch complex to ensure efficient transendocytosis and Notch activation. The interaction between vimentin and Jagged constitutes a mechanism behind selective regulation of Notch ligands during angiogenesis. The interaction may be amendable by therapeutic intervention and can facilitate strategies targeting a variety of diseases related to Jagged deregulation.
Prognostic and biological significance of the proangiogenic factor EGFL7 in acute myeloid leukemia
Authors: Papaioannou Dimitrios , Shen Changxian , Nicolet Deedra , McNeil Betina , Bill Marius , Karunasiri Malith , Burke Matthew H. , Ozer Hatice Gulcin , Yilmaz Selen A. , Zitzer Nina , Behbehani Gregory K. , Oakes Christopher C. , Steiner Damian J. , Marcucci Guido , Powell Bayard L. , Kolitz Jonathan E. , Carter Thomas H. , Wang Eunice S. , Mrózek Krzysztof , Croce Carlo M. , Caligiuri Michael A. , Bloomfield Clara D. , Garzon Ramiro , Dorrance Adrienne M.
Published: May 2017

Significance

In this work we report on the previously uncharacterized clinical and biological role for EGFL7 in acute myeloid leukemia (AML). Patients with increased
EGFL7
mRNA expression had lower complete remission rates and shorter overall and event-free survival, demonstrating the clinical relevance of
EGFL7
expression in cytogenetically normal AML. Our results show that AML blasts are able to synthesize and secrete EGFL7 protein, promoting autocrine blast cell growth. Inhibition of EGFL7 results in decreased proliferation and induces apoptosis of AML cells. Taken together, our data provide the rationale for targeting EGFL7 using blocking antibodies as a therapy for patients with AML.
Mechanosensing of shear by
Pseudomonas aeruginosa
leads to increased levels of the cyclic-di-GMP signal initiating biofilm development
Authors: Rodesney Christopher A. , Roman Brian , Dhamani Numa , Cooley Benjamin J. , Katira Parag , Touhami Ahmed , Gordon Vernita D.
Published: May 2017

Significance

It is well established that mechanical inputs, such as strain and elasticity, can be sensed by eukaryotic cells and can impact phenotype and behavior. In contrast, very little is known about how prokaryotes may respond to mechanical inputs. Here, we show that bacteria can sense shear and can respond by initiating biofilms. This is an important advance in fundamental microbiology and mechanobiology. Biofilms are difficult to prevent using extant approaches. Our knowledge points the way to a hitherto-undeveloped type of antibiofilm surface that thwarts mechanosensing by not sustaining sufficiently high shear. This would prevent bacteria from sensing surface attachment, activating cyclic-di-GMP signaling, and forming a biofilm.
Repression of phosphatidylinositol transfer protein α ameliorates the pathology of Duchenne muscular dystrophy
Authors: Vieira Natassia M. , Spinazzola Janelle M. , Alexander Matthew S. , Moreira Yuri B. , Kawahara Genri , Gibbs Devin E. , Mead Lillian C. , Verjovski-Almeida Sergio , Zatz Mayana , Kunkel Louis M.
Published: May 2017

Significance

Duchenne muscular dystrophy (DMD) is a genetic X-linked neuromuscular disease characterized by severe muscle degeneration caused by absence of the protein dystrophin. In the golden retriever muscular dystrophy dog model of DMD, two atypical dogs exhibited significantly milder phenotypes compared with their severely affected littermates despite lacking dystrophin. These two notable dogs were found to have decreased expression of phosphatidylinositol transfer protein-α (PITPNA) compared with severely affected dogs. Decreased expression ofPITPNAin dystrophin-deficient zebrafish and in human DMD myogenic cells ameliorated several aspects of the dystrophic phenotype, improving muscle structure, increasing survival, and increasing levels of phosphorylated Akt. Our findings presentPITPNAas a genetic modifier of DMD and potential target for future therapies.
Bio-inspired self-healing structural color hydrogel
Authors: Fu Fanfan , Chen Zhuoyue , Zhao Ze , Wang Huan , Shang Luoran , Gu Zhongze , Zhao Yuanjin
Published: May 2017

Significance

Structural color hydrogels have been widely studied and used in different applications, such as in switches, optical devices, etc. However, because the deterioration and accumulation of damage of these materials are inevitable during applications, the creation of bio-inspired structure color materials with increased survivability is still desired for both fundamental research and practical applications. In this study, inspired by creatures in nature with spontaneous healing from injury and recovering of functionality, we demonstrated a self-healing structural color hydrogel by filling a healable protein hydrogel into an inverse opal scaffold. A series of new structural color materials with 1D linear microfiber, 2D pattern, and 3D photonic path structures could be constructed by assembling and healing the composite structural color hydrogel elements.
Manipulating DNA damage-response signaling for the treatment of immune-mediated diseases
Authors: McNally Jonathan P. , Millen Scott H. , Chaturvedi Vandana , Lakes Nora , Terrell Catherine E. , Elfers Eileen E. , Carroll Kaitlin R. , Hogan Simon P. , Andreassen Paul R. , Kanter Julie , Allen Carl E. , Henry Michael M. , Greenberg Jay N. , Ladisch Stephan , Hermiston Michelle L. , Joyce Michael , Hildeman David A. , Katz Jonathan D. , Jordan Michael B.
Published: May 2017

Significance

Therapeutic immune suppression is essential for treating a variety of immune conditions, including autoimmune diseases, immunoregulatory disorders, and in transplantation. Reliance on broadly acting drugs carries substantial risks, and even pathway-specific agents are problematic, because most immune pathways have essential functions. The ideal form of immune suppression would be antigen-specific, suppressing an undesired immune response but sparing all others. We describe a unique strategy for therapeutic immune suppression, relying on targeted manipulation of DNA damage-response signaling, that exploits unique aspects of lymphocyte biology. This approach allows for highly selective suppression of recently activated T cells, displays clear therapeutic benefits, and has less off-target toxicity than conventional DNA-damaging drugs.
Collective action and the evolution of social norm internalization
Authors: Gavrilets Sergey , Richerson Peter J.
Published: May 2017

Significance

People often ignore material costs they incur when following existing social norms. Some individuals and groups are often willing to pay extremely high costs to enact, defend, or promulgate specific values and norms that they consider important. Such behaviors, often decreasing biological fitness, represent an evolutionary puzzle. We study theoretically the evolutionary origins of human capacity to internalize and follow social norms. We focus on two general types of collective actions our ancestors were regularly involved in: cooperation to overcome nature’s challenges and conflicts with neighboring groups. We show that norm internalization evolves under a wide range of conditions, making cooperation “instinctive.” We make testable predictions about individual and group behavior.
Selective lowering of synapsins induced by oligomeric α-synuclein exacerbates memory deficits
Authors: Larson Megan E. , Greimel Susan J. , Amar Fatou , LaCroix Michael , Boyle Gabriel , Sherman Mathew A. , Schley Hallie , Miel Camille , Schneider Julie A. , Kayed Rakez , Benfenati Fabio , Lee Michael K. , Bennett David A. , Lesné Sylvain E.
Published: May 2017

Significance

Alzheimer’s disease (AD) is the most common form of dementia affecting an estimated 5.3 million Americans based on the 2015 Report of the Alzheimer Association. Our current understanding of the pathogenesis of AD suggests that soluble, nonfibrillar forms of amyloid proteins [e.g. amyloid-β, tau, and α-synuclein (αSyn)] may be responsible for impairing cognition and have therefore been advanced to be the most bioactive species in this brain disorder. We sought to determine the potential contribution of αSyn oligomers to AD-associated cognitive decline. We found that selective αSyn oligomers are elevated in AD brains and that genetically elevating oligomeric αSyn in an AD mouse model led to a selective decrease in presynaptic proteins and cognitive performance.
Interplay of catalysis, fidelity, threading, and processivity in the exo- and endonucleolytic reactions of human exonuclease I
Authors: Shi Yuqian , Hellinga Homme W. , Beese Lorena S.
Published: May 2017

Significance

Human exonuclease 1 (hExo1) is a 5′-structure–specific nuclease and a member of the RAD2/XPG superfamily that plays important roles in many aspects of genome maintenance. The means by which individual family members process multiple, structurally disparate substrates has been a long-standing question. The reaction intermediate structures reported here reveal that this remarkable feat is achieved by a series of orchestrated conformational changes that guide disparate substrates into a common, catalytically competent conformation, where they are cleaved by an enhanced variant of the two-metal, in-line hydrolysis mechanism. The observed motions not only enable exo- and endonucleolytic cleavage of gapped and 5′-flap substrates, respectively, but also encode unanticipated features, including mechanisms that enhance processing fidelity and account for processivity.
Bidirectional regulation of Aβ levels by Presenilin 1
Authors: Bustos Victor , Pulina Maria V. , Kelahmetoglu Yildiz , Sinha Subhash C. , Gorelick Fred S. , Flajolet Marc , Greengard Paul
Published: May 2017

Significance

Alzheimer’s disease is the most common neurodegenerative disorder, affecting more than 5 million people in the United States. Multiple lines of evidence suggest that the accumulation of toxic oligomers and aggregates of β-amyloid (Aβ) peptide are the primary causes of neurodegeneration. Aβ originates from sequential cleavage of the amyloid precursor protein (APP). The APP first cleavage is by β-secretase and yields β-C-terminal fragment (βCTF). In turn, βCTF is cleaved by Presenilin 1 (PS1) to produce Aβ. In this work, we show that PS1, in addition to generating Aβ, can also decrease Aβ levels by directing βCTF degradation through autophagy. This previously unrecognized mechanism of regulation of Aβ by Presenilin 1 could provide an attractive target for potential Alzheimer’s disease therapies.
Blue fluorescent amino acid for biological spectroscopy and microscopy
Authors: Hilaire Mary Rose , Ahmed Ismail A. , Lin Chun-Wei , Jo Hyunil , DeGrado William F. , Gai Feng
Published: May 2017

Significance

Herein, we report a tryptophan-based fluorophore that emits in the visible spectral region when excited with 355-nm light. Because this blue fluorescent amino acid has a small size and affords unique photophysical properties, we expect that it will find use in various biological studies, especially in spectroscopic and/or microscopic measurements where an amino acid-sized fluorescence reporter is required.
Visualization and characterization of individual type III protein secretion machines in live bacteria
Authors: Zhang Yongdeng , Lara-Tejero María , Bewersdorf Jörg , Galán Jorge E.
Published: May 2017

Significance

Type III protein secretion systems are essential virulence factors for many bacterial pathogens. Cryo-electron microscopy has provided important details about the architecture and molecular organization of the type III secretion machine in isolation or in fixed samples. However, little information is available about the organization of the type III secretion machine and its individual substructures in live bacteria. Using 2D and 3D single-molecule switching superresolution microscopy, we have visualized individual type III secretion machines in live bacteria and obtained unique insight into the assembly and function of these machines. These studies bridge a major resolution gap in the visualization of type III secretion machines and may serve as a paradigm for the examination of other bacterially encoded molecular machines.
Applicability of ribosome engineering to vitamin B12 production by Propionibacterium shermanii
Authors: Tanaka Yukinori , Kasahara Ken , Izawa Masumi , Ochi Kozo
Published: May 2017

Ribosome engineering has been widely utilized for strain improvement, especially for the activation of bacterial secondary metabolism. This study assessed ribosome engineering technology to modulate primary metabolism, taking vitamin B12 production as a representative example. The introduction into Propionibacterium shermanii of mutations conferring resistance to rifampicin, gentamicin, and erythromycin, respectively, increased per cell production (μg/L/OD600) of vitamin B12 5.2-fold, although net production (μg/L) was unchanged, as the cell mass of the mutants was reduced. Real-time qPCR analysis demonstrated that the genes involved in vitamin B12 fermentation by P. shermanii were activated at the transcriptional level in the drug-resistant mutants, providing a mechanism for the higher yields of vitamin B12 by the mutants. These results demonstrate the efficacy of ribosome engineering for the production of not only secondary metabolites but of industrially important primary metabolites.
Effects of Brood Density and Spawning Substrate Type and Orientation on the Reproductive Output of Seminole Killifish in Tanks
Authors: Joseph Lindsay M V , Ohs Cortney L , DiMaggio Matthew A , Broach Jason S
Published: May 2017

Aquaculture of baitfish has the potential to produce and supply desired species and sizes to meet year-round market demand. The Seminole Killifish Fundulus seminolis is native to Florida and has recently emerged as a candidate for marine baitfish aquaculture because of its ability to survive acclimation to seawater, fast growth, and resilient larvae. Experiments were conducted to identify which spawning substrate materials and orientations were preferred by Seminole Killifish and to evaluate effects of broodfish stocking density on reproductive output. Results indicated that Seminole Killifish required a suitable substrate to be present for successful spawning and egg deposition. Broodstock spawned nearly all eggs onto fiber spawning mats when offered both mat and sand substrates. There was no significant difference in the number of eggs recorded among spawning mats regardless of orientation. Seminole Killifish held in outdoor tanks at a 2:1 (female : male) sex ratio had similar total egg production per tank per week irrespective of stocking density (10, 20, or 30 fish/m3). Consequently, the mean number of eggs produced per female was significantly different among the treatment densities, and an inverse relationship was noted between egg production and stocking density. Causes of observed fecundity differences among treatment densities are discussed along with other observations relevant to production.
Role of objectively measured sedentary behaviour in physical performance, frailty and mortality among older adults: A short systematic review
Authors: Mañas Asier , del Pozo‐Cruz Borja , García‐García Francisco José , Guadalupe‐Grau Amelia , Ara Ignacio
Published: May 2017

Sedentary behaviour (SB) has recently emerged as an independent risk factor for different health outcomes. Older adults accumulate long time in SB. Understanding the role that SB plays on health is crucial for a successful aging. This short systematic review summarizes the current evidence related to the effects of objectively measured SB on frailty, physical performance and mortality in adults ≥60 years old. The literature search produced 271 records for physical performance (n = 119), frailty (n = 31), and mortality (n = 121). Finally, only 13 articles fulfilled the inclusion criteria and were included in this review. All articles but one included in the physical performance section (n = 9) showed a negative association between longer time spent in SB and physical performance. A significant association of SB with higher odds of frailty was found, however this association disappeared after adjusting for cognitive status. Lastly, two of the three included studies showed positive associations between SB and mortality, but this effect decreased or even disappeared in the more adjusted models. In conclusion, there is consistency that SB is negatively associated with physical performance. However, the relationship between objectively measured SB and frailty incidence and mortality rates remains unclear and deserves further research. The use of homogenous criteria to assess SB and the inclusion of more robust research designs will help clarifying the independent effects that SB could have on physical performance, frailty, and mortality. This will ultimately help designing more efficient and comprehensive physical activity guidelines for older adults.
Familiarity with images affects how dogs (Canis familiaris) process life-size video projections of humans
Authors: Pongrácz Péter , Péter András , Miklósi Ádám
Published: May 2017

A central problem of behavioural studies providing artificial visual stimuli for non-human animals is to determine how subjects perceive and process these stimuli. Especially in the case of videos, it is important to ascertain that animals perceive the actual content of the images and are not just reacting to the motion cues in the presentation. In this study, we set out to investigate how dogs process life-sized videos. We aimed to find out whether dogs perceive the actual content of video images or whether they only react to the videos as a set of dynamic visual elements. For this purpose, dogs were presented with an object search task where a life-sized projected human was hiding a target object. The videos were either normally oriented or displayed upside down, and we analysed dogs’ reactions towards the projector screen after the video presentations, and their performance in the search task. Results indicated that in the case of the normally oriented videos, dogs spontaneously perceived the actual content of the images. However, the ‘Inverted’ videos were first processed as a set of unrelated visual elements, and only after some exposure to these videos did the dogs show signs of perceiving the unusual configuration of the depicted scene. Our most important conclusion was that dogs process the same type of artificial visual stimuli in different ways, depending on the familiarity of the depicted scene, and that the processing mode can change with exposure to unfamiliar stimuli.
Spindle assembly checkpoint satisfaction occurs via end-on but not lateral attachments under tension
Authors: Kuhn Jonathan , Dumont Sophie
Published: May 2017

To ensure accurate chromosome segregation, the spindle assembly checkpoint (SAC) prevents anaphase until all kinetochores attach to the spindle. What signals the SAC monitors remains unclear. We do not know the contributions of different microtubule attachment features or tension from biorientation to SAC satisfaction nor how these possible cues change during attachment. In this study, we quantify concurrent Mad1 intensity and report on SAC silencing, real-time attachment geometry, occupancy, and tension at individual mammalian kinetochores. We show that Mad1 loss from the kinetochore is switch-like with robust kinetics and that tension across sister kinetochores is established just before Mad1 loss events at the first sister. We demonstrate that CenpE-mediated lateral attachment of the second sister can persistently generate this metaphase-like tension before biorientation, likely stabilizing sister end-on attachment, yet cannot induce Mad1 loss from that kinetochore. Instead, Mad1 loss begins after several end-on microtubules attach. Thus, end-on attachment provides geometry-specific molecular cues or force on specific kinetochore linkages that other attachment geometries cannot provide.
Jonathan Kagan: A cell biologist’s view of immunity
Authors: O’Donnell Marie Anne
Published: May 2017

Kagan studies how organelles control innate immunity.
Tolerogenic insulin peptide therapy precipitates type 1 diabetes
Authors: Bergman Marie-Louise , Lopes-Carvalho Thiago , Martins Ana-Catarina , Grieco Fabio A. , Eizirik Décio L. , Demengeot Jocelyne
Published: May 2017

Daniel et al. (https://doi.org/10.1084/jem.20110574) have previously published in JEM a study on the preventive effect of tolerogenic vaccination with a strong agonist insulin mimetope in type 1 diabetes. Our study now challenges these results and shows that osmotic pump delivery of the modified insulin peptide R22E did not prevent hyperglycemia, accelerated disease onset, increased its incidence, and worsened insulitis.
The Holy Maid of Wales: Visions, Imposture and Catholicism in Elizabethan Britain
Authors: Walsham Alexandra
Published: May 2017

This article explores the case of Elizabeth Orton of Overton in Flintshire, a young girl who experienced two ecstatic visions in February and March 1581 and was later exposed as a fraud. First, it uses this intriguing incident to illuminate the precarious stability of the Elizabethan polity at a moment of acute political crisis, when the fate of the Reformation itself seemed to be balanced on a knife-edge. It contends that religious developments in north Wales and the Marches were far more significant than has previously been recognised and investigates how far they were inflected by Welsh patriotism. Secondly, it focuses attention on the rhetorical strategies by which Elizabeth Orton was discredited—on the modes of argument that were utilised in the ensuing contest about her own authenticity and about the truth of the Catholic religion. Setting aside the question of whether or not she was guilty of faking her trances and revelations, it suggests that the incident sheds fresh light on the nature and evolution of the entangled concepts of imposture, hypocrisy and fraud. It shows how anxiety about the status and source of Elizabeth’s ecstatic experiences converged with intense concern about a second species of deceit and dissimulation: religious conformity.
The draft genome of blunt snout bream (Megalobrama amblycephala) reveals the development of intermuscular bone and adaptation to herbivorous diet
Authors: Liu Han , Chen Chunhai , Gao Zexia , Min Jiumeng , Gu Yongming , Jian Jianbo , Jiang Xiewu , Cai Huimin , Ebersberger Ingo , Xu Meng , Zhang Xinhui , Chen Jianwei , Luo Wei , Chen Boxiang , Chen Junhui , Liu Hong , Li Jiang , Lai Ruifang , Bai Mingzhou , Wei Jin , Yi Shaokui , Wang Huanling , Cao Xiaojuan , Zhou Xiaoyun , Zhao Yuhua , Wei Kaijian , Yang Ruibin , Liu Bingnan , Zhao Shancen , Fang Xiaodong , Schartl Manfred , Qian Xueqiao , Wang Weimin
Published: May 2017

The blunt snout bream Megalobrama amblycephala is the economically most important cyprinid fish species. As an herbivore, it can be grown by eco-friendly and resource-conserving aquaculture. However, the large number of intermuscular bones in the trunk musculature is adverse to fish meat processing and consumption. As a first towards optimizing this aquatic livestock, we present a 1.116-Gb draft genome of M. amblycephala, with 779.54 Mb anchored on 24 linkage groups. Integrating spatiotemporal transcriptome analyses, we show that intermuscular bone is formed in the more basal teleosts by intramembranous ossification and may be involved in muscle contractibility and coordinating cellular events. Comparative analysis revealed that olfactory receptor genes, especially of the beta type, underwent an extensive expansion in herbivorous cyprinids, whereas the gene for the umami receptor T1R1 was specifically lost in M. amblycephala. The composition of gut microflora, which contributes to the herbivorous adaptation of M. amblycephala, was found to be similar to that of other herbivores. As a valuable resource for the improvement of M. amblycephala livestock, the draft genome sequence offers new insights into the development of intermuscular bone and herbivorous adaptation.
Far-infrared metallicity diagnostics: application to local ultraluminous infrared galaxies
Authors: Pereira-Santaella M. , Rigopoulou D. , Farrah D. , Lebouteiller V. , Li J.
Published: May 2017

The abundance of metals in galaxies is a key parameter that permits to distinguish between different galaxy formation and evolution models. Most of the metallicity determinations are based on optical line ratios. However, the optical spectral range is subject to dust extinction and, for high-z objects (z > 3), some of the lines used in optical metallicity diagnostics are shifted to wavelengths not accessible to ground-based observatories. For this reason, we explore metallicity diagnostics using far-infrared (far-IR) line ratios which can provide a suitable alternative in such situations. To investigate these far-IR line ratios, we modelled the emission of a starburst with the photoionization code cloudy. The most sensitive far-IR ratios to measure metallicities are the [O iii]52 μm and 88 μm to [N iii]57 μm ratios. We show that this ratio produces robust metallicities in the presence of an active galactic nucleus and is insensitive to changes in the age of the ionizing stellar. Another metallicity-sensitive ratio is the [O iii]88 μm/[N ii]122 μm ratio, although it depends on the ionization parameter. We propose various mid- and far-IR line ratios to break this dependence. Finally, we apply these far-IR diagnostics to a sample of 19 local ultraluminous IR galaxies (ULIRGs) observed with Herschel and Spitzer. We find that the gas-phase metallicity in these local ULIRGs is in the range $0.7<Z_{\rm gas}/$ Z⊙ < 1.5, which corresponds to $8.5 <12 + \log ({\rm O / H}) < 8.9$. The inferred metallicities agree well with previous estimates for local ULIRGs and this confirms that they lie below the local mass–metallicity relation.
Preoperative Nomograms Predict Patient-Specific Cervical Spine Surgery Clinical and Quality of Life Outcomes
Authors: Lubelski Daniel , Alentado Vincent , Nowacki Amy S , Shriver Michael , Abdullah Kalil G , Steinmetz Michael P , Benzel Edward C , Mroz Thomas E
Published: May 2017

BACKGROUND

Clinical and quality of life (QOL) outcomes vary depending on the patient's demographics, comorbidities, presenting symptoms, pathology, and surgical treatment used. While there have been individual predictors identified, no comprehensive method incorporates a patient's complex clinical presentation to predict a specific individual postoperative outcome.

OBJECTIVE

To create tool that predicts patient-specific outcomes among those undergoing cervical spine surgery.

METHODS

A total of 952 patients at a single tertiary care institution who underwent anterior or posterior cervical decompression/fusion between 2007 and 2013 were retrospectively reviewed. Outcomes included postoperative emergency department visit or readmission within 30 d, reoperation within 90 d for infection, and changes in QOL outcomes. Nomograms were modeled based on patient demographics and surgical variables. Bootstrap was used for internal validation.

RESULTS

Bias-corrected c-index for emergency department visits, readmission, and reoperation were 0.63, 0.78, and 0.91, respectively. For the QOL metrics, the bias-corrected adjusted R-squared was EQ-5D (EuroQOL): 0.43, for PHQ-9 (Patient Health Questionnaire-9): 0.35, and for PDQ (Pain/Disability Questionnaire): 0.47. Variables predicting the clinical outcomes varied, but included race and median income, body mass index, comorbidities, presenting symptoms, indication for surgery, surgery type, and levels. For the QOL nomograms, the predictors included similar variables, but were significantly more affected by the preoperative QOL of the patient.

CONCLUSION

These prediction models enable referring physicians and spine surgeons to provide patients with personalized expectations regarding postoperative clinical and QOL outcomes following a cervical spine surgery. After appropriate validation, use of patient-specific prediction tools, such as nomograms, has the potential to lead to superior spine surgery outcomes and more cost effective care.
Evaluation of Prognostic Factors for Early Mortality After Stereotactic Radiosurgery for Brain Metastases: a Single Institutional Retrospective Review
Authors: Bennett E Emily , Vogelbaum Michael A , Barnett Gene H , Angelov Lilyana , Chao Samuel , Murphy Erin , Yu Jennifer , Suh John H , Elson Paul , Stevens Glen H J , Mohammadi Alireza M
Published: May 2017

BACKGROUND

Stereotactic radiosurgery (SRS) is used commonly for patients with brain metastases (BM) to improve intracranial disease control. However, survival of these patients is often dictated by their systemic disease course. The value of SRS becomes less clear in patients with anticipated short survival.

OBJECTIVE

To evaluate prognostic factors, which may predict early death (within 90 d) after SRS.

METHODS

A total of 1427 patients with BM were treated with SRS at our institution (2000-2012). There were 1385 cases included in this study; 1057 patients underwent upfront SRS and 328 underwent salvage SRS. The primary endpoint of the study was all-cause mortality within 90 d after first SRS. Multivariate analyses were performed to develop prognostic indices.

RESULTS

Two hundred sixty-six patients (19%, 95% confidence interval 17%-21%) died within 90 d after SRS. Multivariate analysis of upfront SRS patients showed that Karnofsky Performance Status, primary tumor type, extracranial metastases, age at SRS, boost treatment, total tumor volume, prior surgery, and interval from primary to BM were independent prognostic factors for 90-d mortality. The first 4 factors were also independent predictors in patients treated with salvage SRS. Based on these factors, an index was defined for each group that categorized patients into 3 and 2 prognostic groups, respectively. Ninety-day mortality was 5% to 7% in the most favorable cohort and 36% to 39% in the least favorable.

CONCLUSION

Indices based on readily available patient, clinical, and treatment factors that are highly predictive of early death in patients treated with upfront or salvage SRS can be calculated and used to define well-separated prognostic groups.
Risk Factors Associated With Outpatient Parenteral Antibiotic Therapy Program Failure Among Intravenous Drug Users
Authors: Buehrle Deanna J. , Shields Ryan K. , Shah Neel , Shoff Christopher , Sheridan Kathleen
Published: May 2017

Sixty-one percent of intravenous drug users (IVDUs) who received outpatient parenteral antibiotic therapy (OPAT) failed treatment. Hospital readmission and adverse drug reactions occurred in 25%. By multivariate analysis, time since last IVDU was associated with failure (P = .04). Intravenous drug users requiring OPAT are at high risk for failure; additional studies are needed to explore alternatives.