bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of an embedded contact sensor to study nanoscale heat transfer in heat assisted magnetic recording
Authors: Wu Haoyu , Bogy David
Published: January 2017

A near field transducer is employed in the heat assisted magnetic recording technology in order to focus the light energy into a nanoscale spot on the disk. This is necessary to heat the high coercivity magnetic media to their Curie temperature, so the write transducer can record the data. However, the heat transfer mechanism across the head disk interface (HDI) is still not well understood. The current perpendicular media recording systems have a thermal fly-height control means in the air bearing slider near the read/write transducers for placing the transducers within 1 to 2 nm of the rotating disk. In order to monitor this near contact spacing, this system also uses an embedded contact sensor (ECS). Here, we investigate how this ECS can be used to study the heat transfer across the nanoscale gap between the read/write transducer and the disk. This study shows that the self heating effect of the ECS is strong when its current bias is too high. But this self heating effect can be isolated from other heat sources, which allows us to use the ECS for the desired heat transfer measurements. The experiments show that the heat transfer across the HDI is a strong function of the head-disk spacing.
Observation of charge coupling in InGaP/InGaAs/Ge triple-junction solar cells by electric modulus spectroscopy
Authors: Huang Chun-Ying , Shu Gia-Wei , Lai Kuan-Yu , Lei Bi-Cheng , Chien Forest Shih-Sen
Published: January 2017

Observation of charge coupling effect is important to characterize the electrical behaviors of triple-junction solar cells (TJSCs). Electric modulus (M) spectroscopy incorporated with adequate lasers is demonstrated to be an effective approach to investigate the internal electrical characteristics of the individual subcells in InGaP/InGaAs/Ge TJSCs. The distinct characteristic peaks of imaginary part of M corresponding to three individual subcells are identified, as specific lasers are applied. The charge coupling between the excited subcell and neighboring subcell is observed, which causes the expansion of the depletion region in the latter. This approach provides the information of charge coupling for the design of TJSCs.
Phase-domain photoacoustic sensing
Authors: Gao Fei , Zhang Ruochong , Feng Xiaohua , Liu Siyu , Ding Ran , Kishor Rahul , Qiu Lei , Zheng Yuanjin
Published: January 2017

As one of the fastest-growing imaging modalities in recent years, photoacoustic imaging has attracted tremendous research interest for various applications including anatomical, functional, and molecular imaging. The majority of the photoacoustic imaging systems are based on the time-domain pulsed photoacoustic method, which utilizes a pulsed laser source to induce a wideband photoacoustic signal, revealing optical absorption contrast. An alternative way is the frequency-domain photoacoustic method utilizing the chirping modulation of laser intensity to achieve lower system cost. In this paper, we report another way of the photoacoustic method, called phase-domain photoacoustic sensing, which explores the phase difference between two consequent intensity-modulated laser pulse induced photoacoustic measurements to reveal the optical properties. The basic principle is introduced, modeled, and experimentally validated in this paper, which opens another potential pathway to perform photoacoustic sensing and imaging, eliminating acoustic detection variations beyond the conventional time-domain and frequency-domain photoacoustic methods.
Ultra-high sensitive acetylene detection using quartz-enhanced photoacoustic spectroscopy with a fiber amplified diode laser and a 30.72 kHz quartz tuning fork
Authors: Ma Yufei , He Ying , Zhang Ligong , Yu Xin , Zhang Jingbo , Sun Rui , Tittel Frank K.
Published: January 2017

An ultra-high sensitive acetylene (C2H2) Quartz-enhanced photoacoustic spectroscopy (QEPAS) sensor based on a high power laser and a quartz tuning fork with a resonance frequency f0 of 30.72 kHz was demonstrated. An erbium-doped fiber amplifier (EDFA) amplified distributed feedback diode laser with a center wavelength of 1.53 μm was used as the exciting source. A 33.2 ppb minimum detection limit (MDL) at 6534.37 cm−1 was achieved, and the calculated normalized noise equivalent absorption coefficient was 3.54 × 10−8 cm−1 W/√Hz when the laser output power was 1500 mW. The ppb-level detection sensitivity of C2H2 validated the reported QEPAS method.
Stress granule-associated protein G3BP2 regulates breast tumor initiation
Authors: Gupta Nisha , Badeaux Mark , Liu Yiqian , Naxerova Kamila , Sgroi Dennis , Munn Lance L. , Jain Rakesh K. , Garkavtsev Igor
Published: January 2017

Significance

Malignant breast tumors consist of supporting stromal cells and epithelial cancerous cells. The cancer cell population is fueled by a reservoir of tumor-initiating cells, and these cells can give rise to the bulk of the tumor. Some breast cancer cell populations with vast proliferative potential may be intrinsically resistant to standard anticancer therapy. This intrinsic resistance may partially explain the limitations of these therapies in curing cancer patients and suggest a reason for relapse. In this study, we demonstrate that loss of GTPase-activating protein (SH3 domain)-binding protein 2 (G3BP2) inhibits breast tumor initiation, a finding that may lead to improved cancer treatments.
Drivers of Rift Valley fever epidemics in Madagascar
Authors: Lancelot Renaud , Béral Marina , Rakotoharinome Vincent Michel , Andriamandimby Soa-Fy , Héraud Jean-Michel , Coste Caroline , Apolloni Andrea , Squarzoni-Diaw Cécile , de La Rocque Stéphane , Formenty Pierre B. H. , Bouyer Jérémy , Wint G. R. William , Cardinale Eric
Published: January 2017

Significance

Rift Valley fever (RVF) is an emerging, mosquito-borne viral infection of ruminants, transmissible to people, and linked to rainfall. By investigating a wider range of possible drivers this study confirms the assumption that RVF occurrence can also be dependent on nonenvironmental drivers. In Madagascar, human and ruminant infections were geographically distinct, with introduction and long-distance disease spread linked to livestock trading. Human infections were highest in those involved with slaughtering and handling fresh meat. The identification of possible introduction routes, major cattle trade hubs, and areas of high risk to ruminants has shown how multidisciplinary analyses are needed to properly understand disease dynamics and spread, thereby improving early detection and prevention of RVF in humans.
Scene-selective coding by single neurons in the human parahippocampal cortex
Authors: Mormann Florian , Kornblith Simon , Cerf Moran , Ison Matias J. , Kraskov Alexander , Tran Michelle , Knieling Simeon , Quian Quiroga Rodrigo , Koch Christof , Fried Itzhak
Published: January 2017

Significance

Neurons in the human parahippocampal cortex explicitly code for scenes, rather than people, animals, or objects. More specifically, they respond to outdoor pictures, rather than to indoor pictures, and to stimuli with rather than without spatial layout. These scene-selective neurons are spatially clustered and receive spatially clustered inputs reflected by an event-related local field potential (LFP). Furthermore, these neurons form a distributed population code that is less sparse than codes found elsewhere in the human medial temporal lobe. Our findings thus provide insight into the electrophysiological (single unit and LFP) substrates underlying the parahippocampal place area, a structure well-known from neuroimaging.
β-Catenin haploinsufficiency promotes mammary tumorigenesis in an ErbB2-positive basal breast cancer model
Authors: Bui Tung , Schade Babette , Cardiff Robert D. , Aina Olulanu H. , Sanguin-Gendreau Virginie , Muller William J.
Published: January 2017

Significance

Although the oncogenic potential of β-catenin as a transcriptional factor is well-established, its role as a critical component of adherens junctions during tumorigenesis remains elusive. Using two transgenic mouse models of ErbB2-induced mammary tumorigenesis that recapitulate either luminal or basal human breast cancer, we show that β-catenin is required for proper adherens junction formation and that, consequently, β-catenin haploinsufficiency promotes aggressive mammary tumorigenesis. This haploinsufficient phenotype is unique to a basal ErbB2-driven model with a preexisting aberrant activation of β-catenin signaling, highlighting a tumor suppressor role of β-catenin, similar to other adherens junction proteins, in maintaining junctional integrity and a complex interplay between its junctional and transcriptional roles in facilitating tumor progression.
Atrial natriuretic peptide regulates adipose tissue accumulation in adult atria
Authors: Suffee Nadine , Moore-Morris Thomas , Farahmand Patrick , Rücker-Martin Catherine , Dilanian Gilles , Fradet Magali , Sawaki Daigo , Derumeaux Geneviève , LePrince Pascal , Clément Karine , Dugail Isabelle , Puceat Michel , Hatem Stéphane N.
Published: January 2017

Significance

Atrial fibrillation is the most frequent cardiac arrhythmia and is a major cause of stroke. Recently, it has been shown that the adipose tissue that accumulates at the surface of the heart contributes to the pathogenesis of atrial fibrillation by favoring fibrosis of the neighboring myocardium. However, the cellular origin of adult cardiac fat tissue is unknown. Here, we show that resident progenitor cells of the external layer of the heart, referred to as the “epicardium,” are a source of adipocytes through an epithelial-to-mesenchymal transition process. The atrial natriuretic peptide, which is secreted by atrial myocytes, is a potent factor in the differentiation of epicardial progenitors in adipocytes. Our data uncover cross-talk between myocardial mechanical properties and adipose tissue expansion.
Unlocking Tn3-family transposase activity in vitro unveils an asymetric pathway for transposome assembly
Authors: Nicolas Emilien , Oger Cédric A. , Nguyen Nathan , Lambin Michaël , Draime Amandine , Leterme Sébastien C. , Chandler Michael , Hallet Bernard F. J.
Published: January 2017

Significance

The Tn3 family of transposons, discovered in the early 1970s, represents a serious threat to human health because of its prevalence in the dissemination of antibiotic resistance and, indirectly, because of its involvement in xenobiotic metabolism and in the transmission of plant pathogenicity determinants. Astonishingly, their transposition mechanism has yet to be elucidated. We have started to unravel this mechanism by reconstituting the transposition reaction of the Tn3-family transposon Tn4430 in a cell-free in vitro system. The assays also were used to characterize transposase mutants affected in target immunity, a phenomenon whereby a given transposon avoids inserting more than once into the same DNA target. The data support a tentative model linking target immunity with transposition complex assembly and activation.
Selection against variants in the genome associated with educational attainment
Authors: Kong Augustine , Frigge Michael L. , Thorleifsson Gudmar , Stefansson Hreinn , Young Alexander I. , Zink Florian , Jonsdottir Gudrun A. , Okbay Aysu , Sulem Patrick , Masson Gisli , Gudbjartsson Daniel F. , Helgason Agnar , Bjornsdottir Gyda , Thorsteinsdottir Unnur , Stefansson Kari
Published: January 2017

Significance

Epidemiological studies suggest that educational attainment is affected by genetic variants. Results from recent genetic studies allow us to construct a score from a person’s genotypes that captures a portion of this genetic component. Using data from Iceland that include a substantial fraction of the population we show that individuals with high scores tend to have fewer children, mainly because they have children later in life. Consequently, the average score has been decreasing over time in the population. The rate of decrease is small per generation but marked on an evolutionary timescale. Another important observation is that the association between the score and fertility remains highly significant after adjusting for the educational attainment of the individuals.
Genomic analysis reveals major determinants ofcis-regulatory variation inCapsella grandiflora
Authors: Steige Kim A. , Laenen Benjamin , Reimegård Johan , Scofield Douglas G. , Slotte Tanja
Published: January 2017

Significance

Despite long-standing interest in the contribution ofcis-regulatory changes to adaptation, we still have a limited understanding of the selective importance and genomic determinants ofcis-regulatory variation in natural populations. We use a combination of analyses of allele-specific expression and population genomic analyses to investigate the selective forces and genomic determinants ofcis-regulatory variation in the outcrossing plant speciesCapsella grandiflora. We conclude that gene-specific functional constraints shapecis-regulatory variation and that genes withcis-regulatory variation are under relaxed purifying selection compared with other genes. Finally, we identify a link between gene body methylation and the extent ofcis-regulatory constraint in natural populations.
α-Actinin/titin interaction: A dynamic and mechanically stable cluster of bonds in the muscle Z-disk
Authors: Grison Marco , Merkel Ulrich , Kostan Julius , Djinović-Carugo Kristina , Rief Matthias
Published: January 2017

Significance

Muscle is the tissue in our body experiencing most extreme mechanical forces. The mechanism of active force generation has been investigated for more than 50 y and is fairly well understood. However, despite its physiological significance, it is still unknown what mechanical linkages hold together the muscle machinery under passive stretching forces. In this paper, we show with direct mechanical single-molecule measurements that an array of titin/α-actinin bonds composes a dynamic network that can provide stable anchoring, maintaining the integrity of the muscle Z-disk even under load. This dynamic network explains how components of the Z-disk are able to rapidly rearrange and, at the same time, form a long-term stable mechanical structure.
Myofibril breakdown during atrophy is a delayed response requiring the transcription factor PAX4 and desmin depolymerization
Authors: Volodin Alexandra , Kosti Idit , Goldberg Alfred Lewis , Cohen Shenhav
Published: January 2017

Significance

Muscle wasting as occurs with disuse, spinal injuries, aging, and many diseases (including cancer, sepsis, and renal failure) results primarily from the accelerated destruction of the myofibrillar apparatus, although the molecular mechanisms for this effect are largely unclear. To gain insight into the sequence of events leading to myofibril destruction, we studied the atrophy induced by denervation. We found that phosphorylation and ubiquitination of the desmin cytoskeleton precede its depolymerization, which eventually causes myofibril destruction. We further uncovered a delayed phase in the atrophy process, which involves the induction of genes that facilitate myofibril breakdown, including the AAA-ATPase p97/VCP, by the transcription factor paired box 4 (PAX4). Consequently, desmin phosphorylation, p97/VCP, and PAX4 may represent new therapeutic targets to reduce myofibril breakdown during atrophy.
Active MLKL triggers the NLRP3 inflammasome in a cell-intrinsic manner
Authors: Conos Stephanie A. , Chen Kaiwen W. , De Nardo Dominic , Hara Hideki , Whitehead Lachlan , Núñez Gabriel , Masters Seth L. , Murphy James M. , Schroder Kate , Vaux David L. , Lawlor Kate E. , Lindqvist Lisa M. , Vince James E.
Published: January 2017

Significance

Necroptotic cell death is mediated by activation of the mixed-lineage kinase domain-like protein (MLKL). The inflammation associated with this form of cell death is thought to be due to the release of proinflammatory cellular contents after plasma membrane rupture. In contrast to this prevailing view, we show that MLKL activates the innate immune receptor nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) in a cell-intrinsic manner. Importantly, we show that MLKL-mediated NLRP3 and caspase-1 activation and the secretion of the proinflammatory cytokine IL-1β is a major determinant of necroptotic-derived inflammatory signals. These findings suggest that NLRP3 and IL-1β may be relevant therapeutic targets in MLKL-driven diseases.
Modeling the role of voyaging in the coastal spread of the Early Neolithic in the West Mediterranean
Authors: Isern Neus , Zilhão João , Fort Joaquim , Ammerman Albert J.
Published: January 2017

Significance

The Neolithic expansion in Europe took place at an average rate of 1 km⋅y
−1
. In the West Mediterranean, the archaeological record yields a much faster rate of spread, one that cannot be explained by classical overland models. Voyaging has been put forward as an alternative line of explanation. Here, we develop a computational model to identify the key elements and mechanisms and to estimate the values that yield outcomes that fit the observations. The results show that voyaging is indeed required to explain the pattern. We have also found that interactions with local hunter-gatherers played a lesser part in the fast rate of spread.
Thermal-driven domain and cargo transport in lipid membranes
Authors: Talbot Emma L. , Parolini Lucia , Kotar Jurij , Di Michele Lorenzo , Cicuta Pietro
Published: January 2017

Significance

Giant phospholipid and sterol vesicles can separate into coexisting phase domains, observable by fluorescence microscopy. The morphology and motility of these domains provides a simplified model for processes in the plasma membrane of cells. Previous studies maintained a uniform temperature across a vesicle and showed that the morphology of the domains depends on the membrane composition and temperature. We observed the nonequilibrium behavior of domains due to a temperature gradient, revealing domain migration toward higher temperatures. This motion provides a method for controlling the localization of each phase. Species that associate with the sterol-rich regions, such as DNA constructs, can also be actively transported on the vesicle surface, allowing control over the distribution and confinement of that species via vesicle morphology.
Elucidating the mechanism of fluorinated extender unit loading for improved production of fluorine-containing polyketides
Authors: Ad Omer , Thuronyi B. W. , Chang Michelle C. Y.
Published: January 2017

Polyketides are a large family of bioactive natural products synthesized by polyketide synthase (PKS) enzyme complexes predominantly from acetate and propionate. Given the structural diversity of compounds produced using these two simple building blocks, there has been longstanding interest in engineering the incorporation of alternative extender units. We have been investigating the mechanism of fluorinated monomer insertion by three of the six different modules of the PKS involved in erythromycin biosynthesis (6-deoxyerythronolide B synthase, DEBS) to begin understanding the contribution of different steps, such as enzyme acylation, transacylation, C–C bond formation, and chain transfer, to the overall selectivity and efficiency of this process. In these studies, we observe that inactivation of a
cis
-acyltransferase (AT) domain to circumvent its native extender unit preference leads concurrently to a change of mechanism in which chain extension with fluorine-substituted extender units switches largely to an acyl carrier protein (ACP)-independent mode. This result suggests that the covalent linkage between the growing polyketide chain and the enzyme is lost in these cases, which would limit efficient chain elongation after insertion of a fluorinated monomer. However, use of a standalone
trans
-acting AT to complement modules with catalytically deficient AT domains leads to enzyme acylation with the fluoromalonyl-CoA extender unit. Formation of the canonical ACP-linked intermediate with fluoromalonyl-CoA allows insertion of fluorinated extender units at 43% of the yield of the wild-type system while also amplifying product yield in single chain-extension experiments and enabling multiple chain extensions to form multiply fluorinated products.
Dynamic PIN-FORMED auxin efflux carrier phosphorylation at the plasma membrane controls auxin efflux-dependent growth
Authors: Weller Benjamin , Zourelidou Melina , Frank Lena , Barbosa Inês C. R. , Fastner Astrid , Richter Sandra , Jürgens Gerd , Hammes Ulrich Z. , Schwechheimer Claus
Published: January 2017

Significance

The distribution of the hormone auxin controls most processes in plant development. Auxin distribution within the plant requires PIN transporters and efficient PIN-mediated transport requires PIN phosphorylation. Phosphorylation seemingly also controls auxin transport by targeting PINs to specific sides of the cell. Understanding how auxin is directed and activated through phosphorylation is essential to understand plant growth. Two different protein kinases targeting the same phosphosites in PIN1 can activate auxin efflux. Surprisingly, however, only one affects PIN1 polar distribution. Here, we show that the differential effects of the two kinases on PIN1 cannot be explained by phosphorylation at the established phosphosites, and suggest that a more complex model is needed to explain the effects of the kinase on PIN1 polarity.
Establishment of expression-state boundaries by Rif1 and Taz1 in fission yeast
Authors: Toteva Tea , Mason Bethany , Kanoh Yutaka , Brøgger Peter , Green Daniel , Verhein-Hansen Janne , Masai Hisao , Thon Geneviève
Published: January 2017

Significance

In recent years, high-throughput studies have revealed the organization of eukaryotic genomes into chromatin domains, topologically associated domains, and replication domains, laying out important principles for the spatiotemporal organization of the nucleus. Our work shows how customized genetic screens with model organisms can help delineate functional relationships between the different layers of organization and identify the
cis
- and
trans
-acting elements underpinning them. Here, such approaches revealed that DNA elements and proteins that regulate replication-origin firing in yeasts and other eukaryotes can help partition the genome into expressed and repressed domains. We expect this insight acquired with fission yeast will inspire research in other organisms where the proteins we identified, the Shelterin component Rif1 and its effectors, are intensively studied.
Ornithine decarboxylase regulates M1 macrophage activation and mucosal inflammation via histone modifications
Authors: Hardbower Dana M. , Asim Mohammad , Luis Paula B. , Singh Kshipra , Barry Daniel P. , Yang Chunying , Steeves Meredith A. , Cleveland John L. , Schneider Claus , Piazuelo M. Blanca , Gobert Alain P. , Wilson Keith T.
Published: January 2017

Significance

The pathogenesis of many bacteria is enhanced by the ability to establish persistent infection. Macrophages, particularly classically activated M1 macrophages, provide essential functions in the initiation of antibacterial immune responses. The regulation of macrophage activation is still poorly understood. Here, we demonstrate that ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine synthesis, regulates M1 activation duringHelicobacter pyloriandCitrobacter rodentiuminfection. Deletion ofOdcin macrophages resulted in increased inflammation and decreased bacterial persistence in mouse models. The enhanced M1 response was due to alterations in histone modifications, resulting in changes in chromatin structure and up-regulated transcription. These findings represent a novel mechanism by which ODC directly regulates macrophage activation and provides new insights into understanding bacterial persistence.
Recognition of protein-linked glycans as a determinant of peptidase activity
Authors: Noach Ilit , Ficko-Blean Elizabeth , Pluvinage Benjamin , Stuart Christopher , Jenkins Meredith L. , Brochu Denis , Buenbrazo Nakita , Wakarchuk Warren , Burke John E. , Gilbert Michel , Boraston Alisdair B.
Published: January 2017

Significance

Protein glycosylation is one of the most abundant and important posttranslational modifications where the protein-linked glycans can impart specific physiochemical properties to the glycoprotein and/or the glycans themselves can mediate particular biological functions. The degradation of glycosylated proteins in normal or pathogenic processes, therefore, is an important biological process. This study reveals the molecular basis of how peptidases can use the O-glycans present on glycoproteins as a critical determinant of peptidase activity and, in doing so, provides unique insight into how peptidases may directly use posttranslational modifications present on their substrates to influence recognition and peptide bond cleavage.
Rhythm judgments reveal a frequency asymmetry in the perception and neural coding of sound synchrony
Authors: Wojtczak Magdalena , Mehta Anahita H. , Oxenham Andrew J.
Published: January 2017

Significance

Why music developed in the way it did is of fundamental interest across the sciences, arts, and humanities. A recent study reported that rhythm perception was enhanced for low-pitch sounds, and suggested that this enhancement may provide a biological explanation for why low-pitch instruments generally provide the beat in music. Our results refute this hypothesis, but reveal a robust asymmetry in the perception and cortical coding of synchrony between low and high tones. Synchrony is an important and ubiquitous property of sounds emanating from the same source. Our findings suggest a way in which the veridical perception of simultaneous events is maintained in the face of delays produced both by cochlear processing and by the inherent properties of acoustic sources.
Eight-coordinate fluoride in a silicate double-four-ring
Authors: Goesten Maarten G. , Hoffmann Roald , Bickelhaupt F. Matthias , Hensen Emiel J. M.
Published: January 2017

Significance

Although strain and bonding are often antagonists in chemistry, they may also work together. When fluoride enters a silicate double-four-ring (D4R), their conjoined effect leads to fluoride binding to 8 silicon atoms. The strain comes from D4R, a molecular unit that acts (and looks) like a box. And, as we can expect from that geometrical constraint, it experiences strain when being deformed. Avoiding such deformation, the box pushes fluoride toward its center. Yet even there, fluoride engages in orbital overlap (hypervalent bonding) with the highly delocalized antibonding orbitals of D4R, and significant charge transfer occurs. The unusual number of bonds, around the smallest existing anion, leaves us pondering the limits of hypervalence.
Catalytic oxidation of Li
2
S on the surface of metal sulfides for Li−S batteries
Authors: Zhou Guangmin , Tian Hongzhen , Jin Yang , Tao Xinyong , Liu Bofei , Zhang Rufan , Seh Zhi Wei , Zhuo Denys , Liu Yayuan , Sun Jie , Zhao Jie , Zu Chenxi , Wu David Sichen , Zhang Qianfan , Cui Yi
Published: January 2017

Significance

A series of metal sulfides were systematically investigated as polar hosts to reveal the key parameters correlated to the energy barriers and polysulfide adsorption capability in Li−S batteries. The investigation demonstrates that the catalyzing oxidation capability of metal sulfides is critical in reducing the energy barrier and contributing to the remarkably improved battery performance. Density functional theory simulation allows us to identify the mechanism for how binding energy and polysulfides trapping dominate the Li
2
S decomposition process and overall battery performance. The understanding can serve as a general guiding principle for the rational design and screening of advanced materials for high-energy Li−S batteries.
Trogocytosis of peptide–MHC class II complexes from dendritic cells confers antigen-presenting ability on basophils
Authors: Miyake Kensuke , Shiozawa Nozomu , Nagao Toshihisa , Yoshikawa Soichiro , Yamanishi Yoshinori , Karasuyama Hajime
Published: January 2017

Significance

Recent studies have revealed that basophils, the rarest granulocytes, have crucial roles in various immune responses. Among their properties, the MHC class II (MHC-II) expression and their function as antigen-presenting cells are matters of considerable controversy. Here we show that basophils indeed express MHC-II on the cell surface, but with little transcription of corresponding genes. This could be achieved by the acquisition of peptide–MHC-II complexes from dendritic cells via cell contact-dependent trogocytosis in vitro and in vivo. The acquired complexes enabled basophils to stimulate and differentiate T cells toward Th2 cells. Thus, the present study clarified the mechanism by which basophils display MHC-II on the cell surface and appears to reconcile some discrepancies observed in previous studies.
Measurement of cortical elasticity in
Drosophila melanogaster
embryos using ferrofluids
Authors: Doubrovinski Konstantin , Swan Michael , Polyakov Oleg , Wieschaus Eric F.
Published: January 2017

Significance

A physically realistic understanding of any morphogenetic process requires the knowledge of material properties of the tissue, almost all of which we currently lack. This paper introduces a technique that allows measuring physical properties of the interior constituents of a fruit fly embryo. To interpret our measurements, we developed a computational framework that allowed us to deduce underlying material properties of embryonic tissues from the measured data. Using our protocol we have determined a number of key physical properties of embryonic tissue (e.g., cytoplasmic viscosity and the timescale of elastic stress relaxation). Finally, we used pharmacological perturbations to examine which cellular structures are responsible for the observed elastic response.
RFamide-related peptide-3 (RFRP-3) suppresses sexual maturation in a eusocial mammal
Authors: Peragine Diana E. , Pokarowski Martha , Mendoza-Viveros Lucia , Swift-Gallant Ashlyn , Cheng Hai-Ying M. , Bentley George E. , Holmes Melissa M.
Published: January 2017

Significance

Naked mole rats exhibit the most profound case of socially induced infertility among mammals. They live in sizable colonies where breeding is monopolized by two to four dominant animals; all other colony members retain prepubertal gonadal quiescence until death or removal from the colony. Proximate mechanisms underlying this phenomenon are unknown but presumably involve integration of environmental cues by the brain into neuroendocrine signals that impact the gonadotropin-releasing hormone (GnRH) system. The role of RFamide-related peptide-3 (RFRP-3) in modulating the reproductive axis in vertebrates has been well documented, making it a prime candidate as a gatekeeper for puberty onset. Here, we present evidence for RFRP-3–mediated social delay of puberty and define a previously unidentified neuroendocrine component of social control of sexual maturation.
Helical structure, stability, and dynamics in human apolipoprotein E3 and E4 by hydrogen exchange and mass spectrometry
Authors: Chetty Palaniappan S. , Mayne Leland , Lund-Katz Sissel , Englander S. Walter , Phillips Michael C.
Published: January 2017

Significance

Apoliprotein E (apoE) serves as a cholesterol transport protein in both the peripheral circulation and the brain. In humans, the less common apoE4 isoform, which differs from the most abundant parent apoE3 by a single C112R substitution, is associated with increased incidence of cardiovascular disease and Alzheimer’s disease. To understand the structural basis for the altered functionality, we used hydrogen exchange mass spectrometry to compare the structure, stability, and molecular dynamics of these isoforms. The C112R substitution in apoE4 leads to unfolding of certain helical segments that reduces self-association and is expected to enhance the binding of apoE4 to triglyceride-rich lipoprotein particles in plasma and to amyloid-β deposits in the brain.
Evolution of antibiotic resistance is linked to any genetic mechanism affecting bacterial duration of carriage
Authors: Lehtinen Sonja , Blanquart François , Croucher Nicholas J. , Turner Paul , Lipsitch Marc , Fraser Christophe
Published: January 2017

Significance

The relationship between a population’s antibiotic consumption and the frequency of antibiotic resistance among bacteria colonizing that population is not fully understood. Antibiotic resistant and sensitive strains compete for available hosts—we would therefore expect the fitter strain to dominate. Instead, we observe stable coexistence of both strains. In this work, we propose an explanation for this coexistence by showing the fitness advantage of resistance depends on a bacterial strain’s duration of carriage. This finding ties the evolution of resistance to any genetic mechanism affecting duration of carriage. These insights could allow more accurate prediction of future resistance levels and play a role in informing strategies to prevent the spread of resistance.
Transmembrane protein 108 is required for glutamatergic transmission in dentate gyrus
Authors: Jiao Hui-Feng , Sun Xiang-Dong , Bates Ryan , Xiong Lei , Zhang Lei , Liu Fang , Li Lei , Zhang Hong-Sheng , Wang Shun-Qi , Xiong Ming-Tao , Patel Mihir , Stranahan Alexis M. , Xiong Wen-Cheng , Li Bao-Ming , Mei Lin
Published: January 2017

Significance

Dentate gyrus (DG) dysfunction has been implicated in schizophrenia, a disabling psychiatric disorder. However, underlying pathophysiological mechanisms are not clear. We provide evidence that Tmem108, a novel schizophrenia-associated gene, is highly enriched in DG granule neurons. Tmem108 is required for spine development and glutamatergic transmission. Further investigations indicate a critical role of Tmem108 for AMPA receptor expression in postsynaptic compartments. Mutation ofTmem108leads to schizophrenia-related behavioral deficits. These results provide insight into a potential pathophysiological mechanism for DG dysfunction in schizophrenia.
Kinetic assay shows that increasing red cell volume could be a treatment for sickle cell disease
Authors: Li Quan , Henry Eric R. , Hofrichter James , Smith Jeffrey F. , Cellmer Troy , Dunkelberger Emily B. , Metaferia Belhu B. , Jones-Straehle Stacy , Boutom Sarah , Christoph Garrott W. , Wakefield Terri H. , Link Mary E. , Staton Dwayne , Vass Erica R. , Miller Jeffery L. , Hsieh Matthew M. , Tisdale John F. , Eaton William A.
Published: January 2017

Significance

Sickle cell disease can be treated by preventing polymerization of the mutant hemoglobin to form fibers during the time that red cells are transiting the smallest vessels of the tissues. However, most drugs in clinical trials are aimed at reducing the sequelae of fiber formation, such as inflammation and adhesion to the vascular endothelium. Searching for drugs that increase the delay before polymerization, which allows more cells to escape the small vessels before fibers form, has been hampered by the lack of a quantitative and sensitive assay, which we describe in this work. With this assay, we show that increasing the delay time by increasing red cell volume to reduce the intracellular hemoglobin concentration is a viable approach to therapy.
Antiviral screening identifies adenosine analogs targeting the endogenous dsRNALeishmaniaRNA virus 1 (LRV1) pathogenicity factor
Authors: Kuhlmann F. Matthew , Robinson John I. , Bluemling Gregory R. , Ronet Catherine , Fasel Nicolas , Beverley Stephen M.
Published: January 2017

Significance

The endogenous double-stranded RNA virusLeishmaniavirus(LRV1) has been implicated as a pathogenicity factor for leishmaniasis in rodent models and human disease, and associated with drug-treatment failures. As a first step toward the identification of therapeutic LRV1 inhibitors, we identified two adenosine analogs that selectively inhibited LRV1 replication. These analogs were used as tools to confirm that viral inheritance is by random segregation, as well as to generate LRV1-cured lines ofLeishmania guyanensis,which correspondingly lost the increased pathogenicity conferred by LRV1. These compounds hold promise as leads to ameliorate the severity of LRV1-bearingLeishmaniainfections, and raise the possibility of targeting other protozoal infections whose pathogenicity may be exacerbated by similar endogenous viruses.
Continual renewal and replication of persistentLeishmania majorparasites in concomitantly immune hosts
Authors: Mandell Michael A. , Beverley Stephen M.
Published: January 2017

Significance

Persistent parasites contribute to the maintenance of protective immune responses through concomitant immunity, but our understanding of how they do so has been limited by the difficulties associated with their low numbers. Our studies indicate that forLeishmaniasubstantial parasite replication occurs in persistent infections, with most parasites found within activated antigen-presenting cells. Parasite replication serves to maintain the infection and likely also provides a constant source of parasite antigens for immune stimulation and the maintenance of protective immunity. Collectively, these studies suggest a framework to understand concomitant immunity that may be applicable to other persistent pathogens.
Uncovering hidden variation in polyploid wheat
Authors: Krasileva Ksenia V. , Vasquez-Gross Hans A. , Howell Tyson , Bailey Paul , Paraiso Francine , Clissold Leah , Simmonds James , Ramirez-Gonzalez Ricardo H. , Wang Xiaodong , Borrill Philippa , Fosker Christine , Ayling Sarah , Phillips Andrew L. , Uauy Cristobal , Dubcovsky Jorge
Published: January 2017

Comprehensive reverse genetic resources, which have been key to understanding gene function in diploid model organisms, are missing in many polyploid crops. Young polyploid species such as wheat, which was domesticated less than 10,000 y ago, have high levels of sequence identity among subgenomes that mask the effects of recessive alleles. Such redundancy reduces the probability of selection of favorable mutations during natural or human selection, but also allows wheat to tolerate high densities of induced mutations. Here we exploited this property to sequence and catalog more than 10 million mutations in the protein-coding regions of 2,735 mutant lines of tetraploid and hexaploid wheat. We detected, on average, 2,705 and 5,351 mutations per tetraploid and hexaploid line, respectively, which resulted in 35–40 mutations per kb in each population. With these mutation densities, we identified an average of 23–24 missense and truncation alleles per gene, with at least one truncation or deleterious missense mutation in more than 90% of the captured wheat genes per population. This public collection of mutant seed stocks and sequence data enables rapid identification of mutations in the different copies of the wheat genes, which can be combined to uncover previously hidden variation. Polyploidy is a central phenomenon in plant evolution, and many crop species have undergone recent genome duplication events. Therefore, the general strategy and methods developed herein can benefit other polyploid crops.
Loss of GET pathway orthologs in
Arabidopsis thaliana
causes root hair growth defects and affects SNARE abundance
Authors: Xing Shuping , Mehlhorn Dietmar Gerald , Wallmeroth Niklas , Asseck Lisa Yasmin , Kar Ritwika , Voss Alessa , Denninger Philipp , Schmidt Vanessa Aphaia Fiona , Schwarzländer Markus , Stierhof York-Dieter , Grossmann Guido , Grefen Christopher
Published: January 2017

Significance

Root hairs are unicellular extensions of the rhizodermis, providing anchorage and an increase in surface area for nutrient and water uptake. Their fast, tip-focused growth showcases root hairs as an excellent genetic model to study physiological and developmental processes on the cellular level. We uncovered a root hair phenotype that is dependent on putative
Arabidopsis
orthologs of the Guided Entry of Tail-anchored (TA) proteins (GET) pathway, which facilitates membrane insertion of TA proteins in yeast and mammals. We found that plants have evolved multiple paralogs of specific GET pathway components, albeit in a compartment-specific manner. In addition, we show that differential expression of pathway components causes pleiotropic growth defects, suggesting alternative pathways for TA insertion and additional functions of GET in plants.
The NBS-LRR architectures of plant R-proteins and metazoan NLRs evolved in independent events
Authors: Urbach Jonathan M. , Ausubel Frederick M.
Published: January 2017

Significance

Instances of convergent evolution in innate immune systems can reveal fundamental principles of immunity. We use phylogenetic reconstruction and tests of alternative evolutionary hypotheses combined with ancestral state reconstruction and an analysis of the phylogenetic distribution of the nucleotide binding site–leucine rich repeat (NBS-LRR) architecture to demonstrate that most likely, two distinct and separate evolutionary events gave rise to the NBS-LRR architecture in plant resistance proteins (R-proteins) and metazoan NOD-like receptors (NLRs), and furthermore, the STAND NTPase of both protein families was likely inherited from ancestral proteins with an NBS–tetratricopeptide (TPR) architecture. The implication is that the NBS-LRR architecture has special functionality for innate immune receptors.
High Coulombic efficiency aluminum-ion battery using an AlCl
3
-urea ionic liquid analog electrolyte
Authors: Angell Michael , Pan Chun-Jern , Rong Youmin , Yuan Chunze , Lin Meng-Chang , Hwang Bing-Joe , Dai Hongjie
Published: January 2017

Significance

To relieve humanity’s dependence on fossil fuels, grid-scale storage of renewable energy must be implemented. This requires cheap, high-rate, and long cycle life energy storage mechanisms. This work presents the development of an Al-ion battery using earth-abundant aluminum and graphite as anode and cathode, respectively, and an ionic liquid analog electrolyte composed of AlCl
3
and urea that is very low-cost and eco-friendly. The battery exhibits ∼99.7% Coulombic efficiency and a substantial rate capability, with a cathode capacity of 73 mA g
-1
at 100 mA g
-1
(1.4 C).
Network-based integration of systems genetics data reveals pathways associated with lignocellulosic biomass accumulation and processing
Authors: Mizrachi Eshchar , Verbeke Lieven , Christie Nanette , Fierro Ana C. , Mansfield Shawn D. , Davis Mark F. , Gjersing Erica , Tuskan Gerald A. , Van Montagu Marc , Van de Peer Yves , Marchal Kathleen , Myburg Alexander A.
Published: January 2017

Significance

Carbon fixation and accumulation as lignocellulosic biomass is of global ecological and industrial importance and most significantly occurs in the form of wood development in trees. Traits of importance in biomass accumulation are highly complex and, aside from environmental factors, are affected by many pathways and thousands of genes. We have applied a network-based data integration method for a systems genetics analysis of genes, processes, and pathways underlying biomass and bioenergy-related traits using segregating
Eucalyptus
hybrid tree populations. We could link biologically meaningful sets of genes to complex traits and at the same time reveal the molecular basis of trait variation. Such a holistic view of the biology of wood formation will contribute to genetic improvement and engineering of plant biomass.
Myosin-driven transport network in plants
Authors: Kurth Elizabeth G. , Peremyslov Valera V. , Turner Hannah L. , Makarova Kira S. , Iranzo Jaime , Mekhedov Sergei L. , Koonin Eugene V. , Dolja Valerian V.
Published: January 2017

Significance

A key feature of plant cells is rapid cytoplasmic streaming that is driven by myosin motors. However, specific mechanisms of myosin-dependent streaming are poorly understood. Here, we characterize a dense network of plant myosins and their receptors and adaptors that, jointly with myosins, appear to mediate cytoplasmic streaming through distinct endomembrane compartments. We additionally present data suggestive of a myosin-dependent nucleocytoplasmic trafficking pathway. The myosin network is an ancient functional module that was already present in the common ancestor of green algae and land plants but underwent a major expansion in the latter, probably contributing to land colonization by plants.
Transcriptomic, proteomic, and metabolomic landscape of positional memory in the caudal fin of zebrafish
Authors: Rabinowitz Jeremy S. , Robitaille Aaron M. , Wang Yuliang , Ray Catherine A. , Thummel Ryan , Gu Haiwei , Djukovic Danijel , Raftery Daniel , Berndt Jason D. , Moon Randall T.
Published: January 2017

Significance

In vertebrates, proper patterning during appendage regeneration is regulated by positional memory—a cellular property hypothesized to rely on gradients of molecules present in uninjured limbs. Only one gene, exclusive to salamanders, has been shown to regulate positional memory and be expressed in a gradient in the uninjured limb. To identify new candidate effectors of positional memory, we mapped the abundance of RNAs, proteins, and metabolites along the uninjured zebrafish tail fin. We identified hundreds of molecular gradients and generated a high-confidence list of 32 genes and 42 metabolites that are candidate effectors of positional memory in zebrafish. Furthermore, expression patterns discovered here may help to explain how size-homeostasis and patterning are maintained in a complex adult tissue.
A functional endonuclease Q exists in the bacterial domain: identification and characterization of endonuclease Q from Bacillus pumilus
Authors: Shiraishi Miyako , Ishino Sonoko , Cann Isaac , Ishino Yoshizumi
Published: January 2017

DNA base deamination occurs spontaneously under physiological conditions and is promoted by high temperature. Therefore, hyperthermophiles are expected to have efficient repair systems of the deaminated bases in their genomes. Endonuclease Q (EndoQ) was originally identified from the hyperthermophlic archaeon, Pyrococcus furiosus, as a hypoxanthine-specific endonuclease recently. Further biochemical analyses revealed that EndoQ also recognizes uracil, xanthine, and the AP site in DNA, and is probably involved in a specific repair process for damaged bases. Initial phylogenetic analysis showed that an EndoQ homolog is found only in the Thermococcales and some of the methanogens in Archaea, and is not present in most members of the domains Bacteria and Eukarya. A better understanding of the distribution of the EndoQ-mediated repair system is, therefore, of evolutionary interest. We showed here that an EndoQ-like polypeptide from Bacillus pumilus, belonging to the bacterial domain, is functional and has similar properties with the archaeal EndoQs.
Isolation and identification of a humanTRPV1 activating compound from soy sauce
Authors: Oshida Mayu , Matsuura Yasunori , Hotta Shinnosuke , Watanabe Jun , Mogi Yoshinobu , Watanabe Tatsuo
Published: January 2017

Transient receptor potential vanilloid 1 (TRPV1) was identified as a receptor of capsaicin, which is a pungent ingredient in hot red peppers. Due to its relevance for nociception, a physiological and pharmacological study of TRPV1 has also been developed. Therefore, it is important to enrich scientific knowledge regarding the TRPV1 activating or inhibiting compounds. In this study, we fractionated soy sauce based on the human TRPV1 (hTRPV1) activity using column chromatography and purified 5-(9H-pyrido[3,4-b]indol-1-yl)-2-furanmethanol (perlolyrine) as an hTRPV1-activating compound. Additionally, perlolyrine activates the human transient receptor potential ankyrin 1 (hTRPA1). The EC50 of hTRPV1 and hTRPA1 were 2.87 and 1.67 μmol L−1, respectively. HPLC quantification of soy sauces showed that they contain 2.22–12.13 μmol L−1 of perlolyrine. The sensory evaluation revealed that perlolyrine has taste modification effect. The results of this study, for the first time, suggest that perlolyrine induces the activation of hTRPV1 and hTRPA1.