bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultra-high fatigue life of NiTi cylinders for compression-based elastocaloric cooling
Authors: Chen Junyu , Zhang Kuo , Kan Qianhua , Yin Hao , Sun Qingping
Published: August 2019

We investigated the fatigue behavior of superelastic polycrystalline NiTi cylinders during reversible partial transformation under cyclic adiabatic compression at 20 Hz with a maximum stress of 800 MPa. A fatigue life of ∼70 million cycles is recorded for the cylinder with a reliable load carrying capacity until ultimate failure. Surface morphology and fractograph observations show that such an ultrahigh fatigue life is realized by the extremely low average fatigue crack growth rates (0.15 nm/cycle for the longitudinal main crack and 0.03 nm/cycle for the transverse main crack) under cyclic compression. The intersection of the longitudinal and transverse cracks causes a fatigue failure mode of spalling. The cylinders under adiabatic partial transformation with a temperature drop of 9.9 K have a coefficient of performance of the material (COPmat) of 18.8 which is about 78% of the Carnot cycle COP. The extraordinary fatigue and cooling performances of the superelastic NiTi cylinder pave the way for future compression-based solid-state green refrigeration.
Examining solvent effects on the ultrafast dynamics of catechol
Authors: Turner M. A. P. , Turner R. J. , Horbury M. D. , Hine N. D. M. , Stavros V. G.
Published: August 2019

We consider the effect of a polar, hydrogen bond accepting, solvent environment on the excited state decay of catechol following excitation to its first excited singlet state (S1). A comparison of Fourier transform infrared spectroscopy and explicit-solvent ab initio frequency prediction suggests that 5 mM catechol in acetonitrile is both nonaggregated and in its “closed” conformation, contrary to what has been previously proposed. Using ultrafast transient absorption spectroscopy, we then demonstrate the effects of aggregation on the photoexcited S1 lifetime: at 5 mM catechol (nonaggregated) in acetonitrile, the S1 lifetime is 713 ps. In contrast at 75 mM catechol in acetonitrile, the S1 lifetime increases to 1700 ps. We attribute this difference to aggregation effects on the excited-state landscape. This work has shown that explicit-solvent methodology is key when calculating the vibrational frequencies of molecules in a strongly interacting solvent. Combining this with highly complementary steady-state and transient absorption spectroscopy enables us to gain key dynamical insights into how a prominent eumelanin building block behaves when in polar, hydrogen bond accepting solvents both as a monomer and as an aggregated species.
Full and fragmented permutationally invariant polynomial potential energy surfaces for trans and cis N-methyl acetamide and isomerization saddle points
Authors: Nandi Apurba , Qu Chen , Bowman Joel M.
Published: August 2019

We report full and fragmented potential energy surfaces (PESs) for N-methyl acetamide that contain the cis and trans isomers and the saddle points separating them. The full PES uses Permutationally Invariant Polynomials (PIPs) in reduced symmetry which describe the three-fold symmetry of each methyl rotor. A more efficient PES is an extension of the fragmented PIP approach we reported recently. In this approach, the set of Morse variables is partitioned and the fragmented PIP basis is the union of the PIP basis for each set of variables. This approach is general and can be used with neural network fits. The fits are done using roughly 250 000 electronic energies and gradients obtained from direct dynamics, using the B3LYP/cc-pVDZ level of theory. The full PIP basis in 66 Morse variables, with a maximum polynomial order of 3, contains 8040 linear coefficients. The fragmented PIP basis, also with a maximum polynomial order of 3, contains 6121 coefficients. The root-mean-square errors of both PESs are roughly 100 cm−1 for energies and 15 cm−1/bohr per atom for gradients, for energies up to roughly 45 000 cm−1, relative to the trans minimum. Energies and normal mode frequencies of the cis and trans isomers for the full and fragmented PESs agree well with direct calculations. The energies of the two saddle points separating these minima are precisely given by both PESs. Diffusion Monte Carlo calculations of the zero-point energies of the two isomers are also reported.
Computational study of the ro-vibrational spectrum of CO–CO2
Authors: Castro-Juárez Eduardo , Wang Xiao-Gang , Carrington Tucker , Quintas-Sánchez Ernesto , Dawes Richard
Published: August 2019

An accurate ab initio ground-state intermolecular potential energy surface (PES) was determined for the CO–CO2 van der Waals dimer. The Lanczos algorithm was used to compute rovibrational energies on this PES. For both the C-in and O-in T-shaped isomers, the fundamental transition frequencies agree well with previous experimental results. We confirm that the in-plane states previously observed are geared states. In addition, we have computed and assigned many other vibrational states. The rotational constants we determine from J = 1 energy levels agree well with their experimental counterparts. Planar and out-of-plane cuts of some of the wavefunctions we compute are quite different, indicating strong coupling between the bend and torsional modes. Because the stable isomers are T-shaped, vibration along the out-of-plane coordinates is very floppy. In CO–CO2, when the molecule is out-of-plane, interconversion of the isomers is possible, but the barrier height is higher than the in-plane geared barrier height.
Genome-wide association mapping and candidate gene analysis for seed shape in soybean (Glycine max)
Authors: Zhao Xue , Li Wenjing , Zhao Xiaoyue , Wang Jinyang , Liu Zhiyang , Han Yingpeng , Li Wenbin
Published: August 2019

Seed shape (SS) of soybean (Glycine max (L.) Merr.) is an important morphological trait that significantly affects the quality of marketable seed. Study of the genetic architecture of SS is important and basic to soybean molecular breeding. In the present study, a natural soybean population of 202 diverse accessions mainly from China was used to analyse the genetic basis of SS via genome-wide association analysis (GWAS), which was based on single-nucleotide polymorphisms (SNP) generated by specific-locus amplified fragment sequencing method. In total, 27335 SNPs were finally identified with minor allele frequencies >5%. By using GWAS, 14 quantitative trait nucleotides (QTNs) were identified to be associated with seed length, 13 with seed width and 21 with seed thickness in four tested environments. Among these QTNs, 21 QTNs overlapped or were located in the linked genomic regions of the reported quantitative trait loci related to SS or seed weight; and the other 27 QTNs were novel loci for SS. Ten QTNs showed environmental stability and were detected under at least two environments. In total, 83 genes were predicted in the 200-kbp flanking region of six stable QTNs that could be detected under >three environments. Gene-based association analysis was performed by using 38 accessions of diverse SS; 778 SNPs were found in the 83 genes based on 38 accessions, and 270 SNPs from 41 genes were found significantly associated with SS. Twenty-eight genes were environmentally stable and/or pleiotropic in controlling two or more SS-related traits at the same time. The identified loci along with the candidate genes could be of great value for studying the molecular mechanisms underlying SS and improving the potential seed yield of soybean.
Ef-cd
locus shortens rice maturity duration without yield penalty
Authors: Fang Jun , Zhang Fantao , Wang Hongru , Wang Wei , Zhao Fei , Li Zijuan , Sun Changhui , Chen Faming , Xu Fan , Chang Shuoqi , Wu Liang , Bu Qingyun , Wang Pingrong , Xie Jiankun , Chen Fan , Huang Xuehui , Zhang Yijing , Zhu Xinguang , Han Bin , Deng Xiaojian , Chu Chengcai
Published: August 2019

The contradiction between “high yielding” and “early maturing” hampers further improvement of annual rice yield. Here we report the positional cloning of a major maturity duration regulatory gene,
Early flowering-completely dominant
(
Ef-cd
), and demonstrate that natural variation in
Ef-cd
could be used to overcome the above contradictory. The
Ef-cd
locus gives rise to a long noncoding RNA (lncRNA) antisense transcript overlapping the
OsSOC1
gene.
Ef-cd
lncRNA expression positively correlates with the expression of
OsSOC1
and H3K36me3 deposition. Field test comparisons of early maturing
Ef-cd
near-isogenic lines with their wild types as well as of the derivative early maturing hybrids with their wild-type hybrids conducted under different latitudes determined that the early maturing
Ef-cd
allele shortens maturity duration (ranging from 7 to 20 d) without a concomitant yield penalty.
Ef-cd
facilitates nitrogen utilization and also improves the photosynthesis rate. Analysis of 1,439 elite hybrid rice varieties revealed that the 16 homozygotes and 299 heterozygotes possessing
Ef-cd
matured significantly earlier. Therefore,
Ef-cd
could be a vital contributor of elite early maturing hybrid varieties in balancing grain yield with maturity duration.
The expanded specificity and physiological role of a widespread N-degron recognin
Authors: Gao Xiaohui , Yeom Jinki , Groisman Eduardo A.
Published: August 2019

Significance

Proteases control a variety of cellular processes. The protease adaptor ClpS recognizes substrates bearing particular amino acids at the N terminus of proteins in bacteria and bacteria-derived organelles. By identifying and characterizing natural ClpS substrates, we dramatically expand the specificity and physiological role of ClpS. We determined that ClpS recognizes a degron in proteins harboring isoleucine, leucine, phenylalanine, tryptophan, tyrosine, or valine at the fourth position from their N terminus and retaining the N-terminal methionine. Identified ClpS substrates have a variety of functions, including response to different stresses.
The uric acid crystal receptor Clec12A potentiates type I interferon responses
Authors: Li Kai , Neumann Konstantin , Duhan Vikas , Namineni Sukumar , Hansen Anne Louise , Wartewig Tim , Kurgyis Zsuzsanna , Holm Christian K. , Heikenwalder Mathias , Lang Karl S. , Ruland Jürgen
Published: August 2019

The detection of microbes and damaged host cells by the innate immune system is essential for host defense against infection and tissue homeostasis. However, how distinct positive and negative regulatory signals from immune receptors are integrated to tailor specific responses in complex scenarios remains largely undefined. Clec12A is a myeloid cell-expressed inhibitory C-type lectin receptor that can sense cell death under sterile conditions. Clec12A detects uric acid crystals and limits proinflammatory pathways by counteracting the cell-activating spleen tyrosine kinase (Syk). Here, we surprisingly find that Clec12A additionally amplifies type I IFN (IFN-I) responses in vivo and in vitro. Using retinoic acid-inducible gene I (RIG-I) signaling as a model, we demonstrate that monosodium urate (MSU) crystal sensing by Clec12A enhances cytosolic RNA-induced IFN-I production and the subsequent induction of IFN-I–stimulated genes. Mechanistically, Clec12A engages Src kinase to positively regulate the TBK1-IRF3 signaling module. Consistently, Clec12A-deficient mice exhibit reduced IFN-I responses upon lymphocytic choriomeningitis virus (LCMV) infection, which affects the outcomes of these animals in acute and chronic virus infection models. Thus, our results uncover a previously unrecognized connection between an MSU crystal-sensing receptor and the IFN-I response, and they illustrate how the sensing of extracellular damage-associated molecular patterns (DAMPs) can shape the immune response.
Multiple sensory neurons mediate starvation-dependent aversive navigation in
Caenorhabditis elegans
Authors: Jang Moon Sun , Toyoshima Yu , Tomioka Masahiro , Kunitomo Hirofumi , Iino Yuichi
Published: August 2019

Significance

Processing and integrating multiple sensory inputs are essential for generating appropriate behavioral output, where sensory information of food is particularly important. The soil nematode
Caenorhabditis elegans
remembers salt concentrations that they have experienced under starvation conditions and learn to avoid them by monitoring current salt concentrations with the salt-sensory neuron called ASER. Here, we described how a sensory neuron pair that was not previously implicated, called ASG, plays a pivotal role in driving food-related navigation; sensory input to these 2 sensory neurons is required for navigation to avoid salt concentrations associated with starvation. Our results show how integrated sensory information determines the bias of turning behaviors to efficiently navigate toward food in starved worms.
IFITM3 protects the heart during influenza virus infection
Authors: Kenney Adam D. , McMichael Temet M. , Imas Alexander , Chesarino Nicholas M. , Zhang Lizhi , Dorn Lisa E. , Wu Qian , Alfaour Omar , Amari Foued , Chen Min , Zani Ashley , Chemudupati Mahesh , Accornero Federica , Coppola Vincenzo , Rajaram Murugesan V. S. , Yount Jacob S.
Published: August 2019

Significance

We discovered that IFITM3 prevents efficient dissemination and replication of influenza virus in heart tissue, thereby limiting cardiac fibrosis and electrical dysfunction during infection. Since IFITM3 polymorphisms are among the only human genetic factors that have been reproducibly associated with hospitalization and mortality during influenza virus infection, our findings are relevant to the serious threat of influenza virus infection to human health. Furthermore, IFITM3 KO mice provide one of the first models for studying cardiac complications of influenza.
Excessive CD11c
+
Tbet
+
B cells promote aberrant T
FH
differentiation and affinity-based germinal center selection in lupus
Authors: Zhang Wenqian , Zhang Huihui , Liu Shujun , Xia Fucan , Kang Zijian , Zhang Yan , Liu Yaoyang , Xiao Hui , Chen Lei , Huang Chuanxin , Shen Nan , Xu Huji , Li Fubin
Published: August 2019

Excessive self-reactive and inadequate affinity-matured antigen-specific antibody responses have been reported to coexist in lupus, with elusive cellular and molecular mechanisms. Here, we report that the antigen-specific germinal center (GC) response―a process critical for antibody affinity maturation―is compromised in murine lupus models. Importantly, this defect can be triggered by excessive autoimmunity-relevant CD11c
+
Tbet
+
age-associated B cells (ABCs). In B cell-intrinsic Ship-deficient (ShipΔB) lupus mice, excessive CD11c
+
Tbet
+
ABCs induce deregulated follicular T-helper (T
FH
) cell differentiation through their potent antigen-presenting function and consequently compromise affinity-based GC selection. Excessive CD11c
+
Tbet
+
ABCs and deregulated T
FH
cell are also present in other lupus models and patients. Further, over-activated Toll-like receptor signaling in Ship-deficient B cells is critical for CD11c
+
Tbet
+
ABC differentiation, and blocking CD11c
+
Tbet
+
ABC differentiation in ShipΔB mice by ablating MyD88 normalizes T
FH
cell differentiation and rescues antigen-specific GC responses, as well as prevents autoantibody production. Our study suggests that excessive CD11c
+
Tbet
+
ABCs not only contribute significantly to autoantibody production but also compromise antigen-specific GC B-cell responses and antibody-affinity maturation, providing a cellular link between the coexisting autoantibodies and inadequate affinity-matured antigen-specific antibodies in lupus models and a potential target for treating lupus.
Idiosyncratic neural coding and neuromodulation of olfactory individuality in
Drosophila
Authors: Honegger Kyle S. , Smith Matthew A.-Y. , Churgin Matthew A. , Turner Glenn C. , de Bivort Benjamin L.
Published: August 2019

Significance

Individuality is a fundamental feature of behavior. For instance, the same smell or song may evoke very different responses in 2 individuals. What is the biological basis for these differences? While behavioral differences likely originate with differences in neural activity, little is known about how idiosyncratic behavioral differences are reflected in neural activity. We used statistical behavioral analysis and live brain imaging to assess idiosyncratic odor responses in fruit flies, and found that the same odors produce different behavioral responses across flies and that these odors evoke subtly different patterns of brain activity across flies. Moreover, neuromodulators and sets of neurons in the olfactory region of the fly’s brain directly modulate the degree of fly-to-fly behavioral variability in a flexible way.
Human-modified landscapes alter mammal resource and habitat use and trophic structure
Authors: Magioli Marcelo , Moreira Marcelo Zacharias , Fonseca Renata Cristina Batista , Ribeiro Milton Cezar , Rodrigues Márcia Gonçalves , Ferraz Katia Maria Paschoaletto Micchi de Barros
Published: August 2019

Significance

Knowledge of resource and habitat use by wildlife is essential to support conservation actions. Stable isotope analysis (SIA) is a useful method for the acquisition of this type of information. Samples for SIA can be obtained through indirect and noninvasive methods, which is favorable for studies of threatened species. We used SIA to compare the resource and habitat use and trophic structure of mammals between preserved areas and human-modified landscapes in a tropical rainforest. Our study shows that mammals in human-modified landscapes present an altered trophic structure and use food items from the agricultural matrix, while they depend on forest resources in preserved areas. Our findings stress the need for favorable management of the agricultural matrix to support wildlife survival.
A Rubisco-binding protein is required for normal pyrenoid number and starch sheath morphology in
Chlamydomonas reinhardtii
Authors: Itakura Alan K. , Chan Kher Xing , Atkinson Nicky , Pallesen Leif , Wang Lianyong , Reeves Gregory , Patena Weronika , Caspari Oliver , Roth Robyn , Goodenough Ursula , McCormick Alistair J. , Griffiths Howard , Jonikas Martin C.
Published: August 2019

Significance

Many cellular structures are assembled via phase separation, forming liquid-like droplets in a manner analogous to oil in water. How can the cell control whether there is 1 droplet or many? Here, we provide insights into this question by studying the pyrenoid, an algal liquid-like organelle that mediates a substantial portion of global CO
2
fixation. Whereas most algae have just 1 pyrenoid, we characterize a mutant that has approximately 10 pyrenoids per cell. Our results suggest a model where imposing an increased surface area on the liquid-like pyrenoid matrix favors the formation of multiple pyrenoids, with a concomitant loss of photosynthetic efficiency. Our findings advance our basic understanding of the biogenesis of the pyrenoid and of phase-separated organelles in general.
Therapeutic genome editing of triple-negative breast tumors using a noncationic and deformable nanolipogel
Authors: Guo Peng , Yang Jiang , Huang Jing , Auguste Debra T. , Moses Marsha A.
Published: August 2019

Significance

Triple-negative breast cancer (TNBC), which represents 12% of all breast cancers, is a devastating breast cancer subtype that occurs more frequently in women under 50 y of age, in African American women, and in individuals carrying a BRCA1 gene mutation. Because of the lack of therapeutic targets and limited treatment options, the prognosis for patients with TNBC remains the poorest of all patients with breast cancer. Here we report the synthesis and application of a novel CRISPR nanotherapeutic to effectively knock out Lipocalin 2 (Lcn2), a breast cancer-promoting gene, in TNBC tumors via in vivo genome editing, leading to a significant suppression of TNBC tumor growth. Our studies demonstrate that CRISPR genome editing is a promising targeted gene therapy approach for TNBC.
Encounter complexes and hidden poses of kinase-inhibitor binding on the free-energy landscape
Authors: Re Suyong , Oshima Hiraku , Kasahara Kento , Kamiya Motoshi , Sugita Yuji
Published: August 2019

Significance

Molecular recognition via protein–ligand binding is essential for biomolecular functions. Current understanding of ligand recognition is mostly brought from a bound state structure resolved by X-ray crystallography. Using molecular dynamics simulation with enhanced sampling techniques, we here characterize multiple bound poses and transient encounter complexes of an inhibitor kinase on the statistically converged free-energy landscapes. Our simulations propose parallel binding pathways connected through encounter complexes, highlighting the importance of early binding processes. Determination of transient encounter complexes is still difficult experimentally, and the present finding helps to understand the process and widens the possibility of drug compound design.
Allosteric modulation of β-cell M3muscarinic acetylcholine receptors greatly improves glucose homeostasis in lean and obese mice
Authors: Zhu Lu , Rossi Mario , Cohen Amanda , Pham Jonathan , Zheng Hongchao , Dattaroy Diptadip , Mukaibo Taro , Melvin James E. , Langel Jennifer L. , Hattar Samer , Matschinsky Franz M. , Appella Daniel H. , Doliba Nicolai M. , Wess Jürgen
Published: August 2019

Significance

Type 2 diabetes (T2D) has emerged as a major threat to human health worldwide. In T2D, pancreatic β cells are unable to release sufficient amounts of insulin to maintain physiological blood glucose levels. Acetylcholine (ACh) stimulates insulin release from mouse and human pancreatic β cells by activating a cell surface receptor known as M3muscarinic ACh receptor (M3R). In the present study, we show that a drug that binds to an allosteric site on the M3R (a site distinct from the ACh-binding site) greatly enhances ACh-induced, M3R-mediated insulin release and improves glucose homeostasis in obese, glucose-intolerant mice. This proof-of-concept study strongly suggests that positive allosteric modulators of M3R function may prove beneficial for the treatment of T2D.
LRRC52 regulates BK channel function and localization in mouse cochlear inner hair cells
Authors: Lingle Christopher J. , Martinez-Espinosa Pedro L. , Yang-Hood Aizhen , Boero Luis E. , Payne Shelby , Persic Dora , V-Ghaffari Babak , Xiao Maolei , Zhou Yu , Xia Xiao-Ming , Pyott Sonja J. , Rutherford Mark A.
Published: August 2019

Significance

Hair cells of the cochlea transduce mechanical energy into electrical signals. Acoustic stimulation of mechanotransduction channels generates a graded receptor potential that elicits glutamate release from hair cells onto postsynaptic auditory nerve fibers. The amplitude and time course of the receptor potential is shaped by activation of Ca
2+
- and voltage-dependent K
+
channels (BK channels). Hair cell BK channels are unusual in that, even in the absence of Ca
2+
, they are activated at more negative potentials than any other known BK channel. Here we show that a specific regulatory gamma subunit, LRRC52, is a key determinant in inner hair cells of the negative activation range of BK channels. Furthermore, the absence of LRRC52 disrupts BK channel clustering and localization.
A promising bioconjugate vaccine against hypervirulent
Klebsiella pneumoniae
Authors: Feldman Mario F. , Mayer Bridwell Anne E. , Scott Nichollas E. , Vinogradov Evgeny , McKee Samuel R. , Chavez Sthefany M. , Twentyman Joy , Stallings Christina L. , Rosen David A. , Harding Christian M.
Published: August 2019

Significance

Klebsiella pneumoniae
is considered a nosocomial pathogen, usually infecting immunocompromised patients. However, a pathotype of
K. pneumoniae
, termed hypervirulent
K. pneumoniae
(hv
Kp
), has emerged and is spreading throughout the community, causing severe, often fatal, disease in healthy individuals. Moreover, reports on multidrug-resistant hv
Kp
isolates are increasing in frequency. It is imperative that strategies to combat hv
Kp
begin immediately to prevent further dissemination of this new class of “superbugs.” Here, we show that bioconjugate vaccines targeting the capsule of hv
Kp
can provide immunity and protection against extremely lethal hv
Kp
strains. Further, we demonstrate that bioconjugation is a promising technology for rapid development of efficacious vaccines against emerging bacterial threats.
Single-cell imaging reveals unexpected heterogeneity of telomerase reverse transcriptase expression across human cancer cell lines
Authors: Rowland Teisha J. , Dumbović Gabrijela , Hass Evan P. , Rinn John L. , Cech Thomas R.
Published: August 2019

Significance

Telomerase, which extends DNA at chromosome ends, is composed of an RNA template and a catalytic protein subunit, telomerase reverse transcriptase (TERT).
TERT
gene expression has been of great interest because it is required for proliferation of most cancers, but expression investigations have been limited due to low endogenous mRNA levels. Here, we employ single-molecule RNA fluorescent in situ hybridization (FISH) in 10 human cancer cell lines and make findings that are unanticipated based upon bulk TERT mRNA measurements. For example, there is great cell-to-cell variation in the number of transcription sites, and spliced TERT mRNA has greater nuclear localization than cytoplasmic. Overall, our findings provide insights regarding TERT expression, localization patterns, and variability in cancer on a single-cell level.
Identification of multiple male reproductive tract-specific proteins that regulate sperm migration through the oviduct in mice
Authors: Fujihara Yoshitaka , Noda Taichi , Kobayashi Kiyonori , Oji Asami , Kobayashi Sumire , Matsumura Takafumi , Larasati Tamara , Oura Seiya , Kojima-Kita Kanako , Yu Zhifeng , Matzuk Martin M. , Ikawa Masahito
Published: August 2019

Significance

While the emergence of gene modification technologies has produced major discoveries in biomedical sciences, the recent development of the CRISPR/Cas9 system has dramatically altered the trajectory of phenotypic analysis in animal models. In this study, we identified male-specific gene clusters (CstandPate) and family genes (GdpdandLypd) and found specific members to be required for male fertility, especially for sperm fertilizing ability. Our findings support the important roles of these proteins in sperm function and could be used to develop novel infertility treatments as well as contraceptives.
Positive selection in dNTPase SAMHD1 throughout mammalian evolution
Authors: Monit Christopher , Morris Elizabeth R. , Ruis Christopher , Szafran Bart , Thiltgen Grant , Tsai Ming-Han Chloe , Mitchison N. Avrion , Bishop Kate N. , Stoye Jonathan P. , Taylor Ian A. , Fassati Ariberto , Goldstein Richard A.
Published: August 2019

Significance

Animals defend themselves from viral infection using innate immunity proteins that disrupt various stages of the virus life cycle. In response, viruses produce proteins that bind these host factors and compromise their activity, resulting in evolutionary conflict as immunity and virus proteins adapt to prevent and restore binding, respectively. We report that evolutionary conflict involving the host innate immunity protein SAMHD1 has occurred throughout mammalian evolution. We observe adaptation in a region of SAMHD1 that regulates its activity, and we demonstrate how mutations here influence its enzymatic properties, suggesting that evolutionary conflict has involved modulation of SAMHD1 regulation and function. This correlates with reduced restriction of HIV-1, indicating that positive selection has influenced both SAMHD1’s dNTPase and antiviral activities.
Carbon-13 dynamic nuclear polarization in diamond via a microwave-free integrated cross effect
Authors: Henshaw Jacob , Pagliero Daniela , Zangara Pablo R. , Franzoni María B. , Ajoy Ashok , Acosta Rodolfo H. , Reimer Jeffrey A. , Pines Alexander , Meriles Carlos A.
Published: August 2019

Significance

Optical spin pumping of color centers promises to revolutionize the practice of nuclear magnetic resonance via efficient dynamic nuclear polarization protocols. Significant progress has been attained with systems such as the nitrogen-vacancy (NV) center in diamond, but extreme spectral broadening and nuclear spin-lattice relaxation from coexisting paramagnetic defects are hurdles still difficult to circumvent. The present technique addresses both issues through the implementation of magnetic-field-sweep–induced NV cross-relaxation with ancilla point defects, here acting as proxies to mediate the transfer of polarization to the nuclear spin ensemble. The governing spin dynamics is robust to field misalignment and ideally suited for shallow NVs, indirectly coupled to outside nuclei through paramagnetic defects at the diamond surface.
Human cytomegalovirus induces and exploits Roquin to counteract the IRF1-mediated antiviral state
Authors: Song Jaewon , Lee Sanghyun , Cho Dong-Yeon , Lee Sungwon , Kim Hyewon , Yu Namhee , Lee Sanghyuk , Ahn Kwangseog
Published: August 2019

RNA represents a pivotal component of host–pathogen interactions. Human cytomegalovirus (HCMV) infection causes extensive alteration in host RNA metabolism, but the functional relationship between the virus and cellular RNA processing remains largely unknown. Through loss-of-function screening, we show that HCMV requires multiple RNA-processing machineries for efficient viral lytic production. In particular, the cellular RNA-binding protein Roquin, whose expression is actively stimulated by HCMV, plays an essential role in inhibiting the innate immune response. Transcriptome profiling revealed Roquin-dependent global down-regulation of proinflammatory cytokines and antiviral genes in HCMV-infected cells. Furthermore, using cross-linking immunoprecipitation (CLIP)-sequencing (seq), we identified IFN regulatory factor 1 (
IRF1
), a master transcriptional activator of immune responses, as a Roquin target gene. Roquin reduces IRF1 expression by directly binding to its mRNA, thereby enabling suppression of a variety of antiviral genes. This study demonstrates how HCMV exploits host RNA-binding protein to prevent a cellular antiviral response and offers mechanistic insight into the potential development of CMV therapeutics.
Diverse conjugative elements silence natural transformation in
Legionella
species
Authors: Durieux Isabelle , Ginevra Christophe , Attaiech Laetitia , Picq Kévin , Juan Pierre-Alexandre , Jarraud Sophie , Charpentier Xavier
Published: August 2019

Natural transformation (i.e., the uptake of DNA and its stable integration in the chromosome) is a major mechanism of horizontal gene transfer in bacteria. Although the vast majority of bacterial genomes carry the genes involved in natural transformation, close relatives of naturally transformable species often appear not competent for natural transformation. In addition, unexplained extensive variations in the natural transformation phenotype have been reported in several species. Here, we addressed this phenomenon by conducting a genome-wide association study (GWAS) on a panel of isolates of the opportunistic pathogen
Legionella pneumophila
. GWAS revealed that the absence of the transformation phenotype is associated with the conjugative plasmid pLPL. The plasmid inhibits transformation by simultaneously silencing the genes required for DNA uptake and recombination. We identified a small RNA (sRNA), RocRp, as the sole plasmid-encoded factor responsible for the silencing of natural transformation. RocRp is homologous to the highly conserved and chromosome-encoded sRNA RocR which controls the transient expression of the DNA uptake system. Assisted by the ProQ/FinO-domain RNA chaperone RocC, RocRp acts as a substitute of RocR, ensuring that the bacterial host of the conjugative plasmid does not become naturally transformable. Distinct homologs of this plasmid-encoded sRNA are found in diverse conjugative elements in other
Legionella
species. Their low to high prevalence may result in the lack of transformability of some isolates up to the apparent absence of natural transformation in the species. Generally, our work suggests that conjugative elements obscure the widespread occurrence of natural transformability in bacteria.
Neurodevelopmental mutation of giant ankyrin-G disrupts a core mechanism for axon initial segment assembly
Authors: Yang Rui , Walder-Christensen Kathryn K. , Lalani Samir , Yan Haidun , García-Prieto Irene Díez , Álvarez Sara , Fernández-Jaén Alberto , Speltz Laura , Jiang Yong-Hui , Bennett Vann
Published: August 2019

Significance

Axon initial segments of vertebrate neurons integrate thousands of dendritic inputs and generate a single outgoing action potential. Giant ankyrin-G associates with most of the molecular components of axon initial segments and is required for their assembly. This study identified 3 human mutations of giant ankyrin-G resulting in impaired neurodevelopment in compound heterozygotes. These mutations prevent transition of giant ankyrin-G from a closed to an open conformation, which normally is regulated by phosphorylation of giant ankyrin-G during maturation of axon initial segments. Giant ankyrin-G thus functions in a signaling pathway that may contribute to activity-dependent plasticity of the axon initial segment as well as provide a therapeutic target for treatment of patients bearing giant ankyrin-G mutations.
Identifying roles for peptidergic signaling in mice
Authors: Powers Kathryn G. , Ma Xin-Ming , Eipper Betty A. , Mains Richard E.
Published: August 2019

Despite accumulating evidence demonstrating the essential roles played by neuropeptides, it has proven challenging to use this information to develop therapeutic strategies. Peptidergic signaling can involve juxtacrine, paracrine, endocrine, and neuronal signaling, making it difficult to define physiologically important pathways. One of the final steps in the biosynthesis of many neuropeptides requires a single enzyme, peptidylglycine α-amidating monooxygenase (PAM), and lack of amidation renders most of these peptides biologically inert. PAM, an ancient integral membrane enzyme that traverses the biosynthetic and endocytic pathways, also affects cytoskeletal organization and gene expression. While mice, zebrafish, and flies lacking
Pam
(

Pam
KO/KO

) are not viable, we reasoned that cell type-specific elimination of
Pam
expression would generate mice that could be screened for physiologically important and tissue-specific deficits. Conditional

Pam
cKO/cKO

mice, with loxP sites flanking the 2 exons deleted in the global

Pam
KO/KO

mouse, were indistinguishable from wild-type mice. Eliminating
Pam
expression in excitatory forebrain neurons reduced anxiety-like behavior, increased locomotor responsiveness to cocaine, and improved thermoregulation in the cold. A number of amidated peptides play essential roles in each of these behaviors. Although atrial natriuretic peptide (ANP) is not amidated,
Pam
expression in the atrium exceeds levels in any other tissue. Eliminating
Pam
expression in cardiomyocytes increased anxiety-like behavior and improved thermoregulation. Atrial and serum levels of ANP fell sharply in PAM myosin heavy chain 6 conditional knockout mice, and RNA sequencing analysis identified changes in gene expression in pathways related to cardiac function. Use of this screening platform should facilitate the development of therapeutic approaches targeted to peptidergic pathways.
Assemblies of calcium/calmodulin-dependent kinase II with actin and their dynamic regulation by calmodulin in dendritic spines
Authors: Wang Qian , Chen Mingchen , Schafer Nicholas P. , Bueno Carlos , Song Sarah S. , Hudmon Andy , Wolynes Peter G. , Waxham M. Neal , Cheung Margaret S.
Published: August 2019

Significance

The structural dynamics of the dendritic synapse, arising from the remodeling of actin cytoskeletons, has been widely associated with memory and cognition. The remodeling is regulated by intracellular Ca
2+
levels. Under low Ca
2+
concentration, actin filaments are bundled by a calcium signaling protein, CaMKII. When the Ca
2+
concentration is raised, CaMKII dissociates from actin and opens the window for actin remodeling. At present, the molecular details of the actin bundling and regulation are elusive. Herein we use experimental tools along with molecular simulations to construct a model of how CaMKII bundles actin and how the CaMKII–actin architecture is regulated by Ca
2+
signals. In this way, our results explain how Ca
2+
signals ultimately change the structure of the dendritic synapse.
Spontaneous generation of hydrogen peroxide from aqueous microdroplets
Authors: Lee Jae Kyoo , Walker Katherine L. , Han Hyun Soo , Kang Jooyoun , Prinz Fritz B. , Waymouth Robert M. , Nam Hong Gil , Zare Richard N.
Published: August 2019

Significance

Water is considered to be a stable and relatively inert molecule in bulk solution. We report an exceptional behavior of water: Water molecules are spontaneously oxidized to form hydrogen peroxide near the water−air interface of micron-sized water droplets. This process does not require any chemical reagent, catalyst, applied electric potential, or radiation. Only pure water in the form of microdroplets in air is necessary for the appearance of hydrogen peroxide. We suggest that this discovery opens various innovative opportunities including green and inexpensive production of hydrogen peroxide, green chemical synthesis, safe cleaning, and food processing.
15 years of collostructions
Authors: Gries Stefan Th.
Published: August 2019

This paper discusses a variety of potential shortcomings of most of the most widely-used association measures as used in collocation research and collostructional analyses. To address these shortcomings, I then discuss a research program calledtupleization, an approach that does away with the usual kinds of information conflation by keeping relevant corpus-linguistic dimensions of information – e.g. frequency, association/contingency, dispersion, entropy, etc. – separate and analyzing them in a multidimensional way; I conclude with pointers towards how these dimensions could, if deemed absolutely necessary, be conflated for the simplest kinds of of rankings as well as strategies for future research.
A corpus perspective on the development of verb constructions in second language learners
Authors: Römer Ute
Published: August 2019

This article reports initial findings from a study that uses written data from second language (L2) learners of English at different proficiency levels (CEFR A1 to C1) in a large-scale investigation of verb-argument construction (VAC) emergence. The findings provide insights into first VACs in L2 learner production, changes in the learners’ VAC repertoire from low to high proficiency levels, and changes in learners’ dominant verb-VAC associations from low to high proficiency levels. The article also addresses the question what role formulaic sequences play in the L2 acquisition of VACs. Data analyses indicate that, from lowest to highest proficiency levels, the VAC repertoire of L2 English learners shows an increase in VAC types, growth in VAC productivity and complexity, and a development from predominantly fixed sequences to more flexible and productive ones. The findings help to expand our understanding of the processes that underlie construction acquisition in an L2 context.
Construction Grammar and the corpus-based analysis of discourses
Authors: Groom Nicholas
Published: August 2019

Construction grammar (CxG) initially arose as a usage-based alternative to nativist theoretical accounts of language, and remains to this day strongly associated with cognitive linguistic theory and research. In this paper, however, I argue that CxG can be seen as offering an equally viable general framework for socially-oriented linguists whose work focuses on the corpus-based analysis of discourses (CBADs). The paper begins with brief reviews of CxG and CBADs as distinctive research traditions, before going on to identify synergies (both potential and actual) between them. I then offer a more detailed case study example, focusing on a usage-based analysis of a newly identified construction, the WAY IN WHICH construction, as it occurs in corpora representing six different academic discourses. The paper concludes by rebutting some anticipated objections to the approach advocated here, and by proposing a new conceptual model for constructionist approaches to CBADs.
Towards an English Constructicon using patterns and frames
Authors: Perek Florent , Patten Amanda L.
Published: August 2019

Recent research in construction grammar has been marked by increasing efforts to create constructicons: detailed
inventories of form-meaning pairs to describe the grammar of a given language, following the principles of construction grammar.
This paper describes proposals for building a new constructicon of English, based on the combination of the COBUILD Grammar
Patterns and the semantic frames of FrameNet. In this case study, the valency information from FrameNet was automatically matched
to the verb patterns of COBUILD, in order to identify the frames that each pattern is associated with. We find that the automatic
procedure must be complemented by a good deal of manual annotation. We examine the “V that” pattern in particular, illustrating
how the frame information can be used to describe this pattern in terms of constructions.
Impolite viewer responses in Arabic political TV talk shows on YouTube
Authors: Hassan Bahaa-eddin A.
Published: August 2019

The article deals with the features of impolite responses of YouTube Arab viewers of political TV talk shows.
YouTube comments are written discourse of live commentary, a new genre of computer-mediated communication. Based on data from
comments of Arabic viewers of political TV talk shows on YouTube, the article argues that impolite responses appear to be a common
feature in Arabic comments in political talk shows on YouTube. Identity and power are reconsidered in this paper as variables that
trigger impoliteness in Arabic online responses in political talk shows on YouTube. It argues that obscuring identity online
incites the use of conventionalized impoliteness to exercise power on the TV presenter or the TV episode’s guest. The article also
shows how communication variables such as context, commentator’s identity and models of communication influence the realization of
impolite responses in those online interactions. The study draws on Spencer-Oatey
(2007) to correlate identity, power, and impoliteness. It also utilized Culpeper’s
(2011) bottom-up model of impoliteness triggers.
Combinaciones entre operadores argumentativos
Authors: Fuentes Rodríguez Catalina
Published: August 2019

El trabajo analiza la fijación de una construcción,si cabe, como operador escalar. Se describe su comportamiento como regulador de la escala: señala la posición superior y exige la combinación con otro intensificador. Se analiza también la aparición de la estructura en diferentes contextos, ya sea como construcción libre o construcción con valor periférico en el enunciado. La descripción sigue una perspectiva pragmática y macrosintáctica, se centra en el estudio de la gramaticalización de operadores discursivos e incorpora a su estudio una dimensión combinatoria de la que surgen nuevos elementos. La investigación se apoya en los corpus de la RAE (CREA, CORPES y CORDE) así como en el corpus MEsA, de discurso digital.
‘Is it always so fast?’
Authors: Zhang Leticia Tian , Cassany Daniel
Published: August 2019

While much research has proved the benefits of subtitled audiovisuals for foreign language learning, few studies address such practices in out-of-classroom settings or focus on Asia-based video-sharing platforms. This study bridges this gap by introducing an increasingly popular viewing-commenting system in Japan and China, known asdanmuordanmaku, which displays viewers’ timeline-synchronized comments on video content. We analyse the metalinguistic comments which entail viewers’ knowledge of the language, their comprehension issues and sociolinguistic attitudes toward its use. Adopting an inductive or data-driven methodology, we extracted and manually coded 390 comments that are related to the Spanish language, Spanish–Chinese translation and learning Spanish. Results show that viewers are mostly interested in linguistic features that differ from Chinese or English (e.g. the complex grammar) and they usedanmuto access sociolinguistic issues that are central to daily communication such as the fast speech rate, language varieties, and frequent use of vulgarisms.
La campaña contra el ‘manspreading’ entre paisaje semiótico y eco mediático
Authors: Pontrandolfo Gianluca
Published: August 2019

El estudio analiza la campaña contra el ‘manspreading’ (el despatarre masculino en el transporte público) como
fenómeno semiótico. El punto de partida de la investigación es la decisión de la Empresa Municipal de Transportes de Madrid de
poner una pegatina contra el despatarre de los hombres en todos los autobuses madrileños. El tema despierta interés y desata
críticas desde distintas posiciones: la supuesta invasión del espacio público por parte de los varones engendra reflexiones acerca
del posicionamiento de los hombres y de las mujeres en la sociedad moderna; además, estos gestos de comunicación no verbal y los
signos lingüísticos a estos asociados revelan sesgos de género que es interesante observar bajo una perspectiva sociolingüística y
multimodal.

Desde el punto de vista metodológico, la investigación sienta sus bases en dos ejes: por un lado, los cimientos
teóricos del ‘paisaje lingüístico’, al analizar algunas imágenes contra el ‘manspreading’ como productos semióticos sociales de
corte multimodal; por el otro, el estudio del discurso enfocado bajo la perspectiva sociolingüística y pragmática, al examinar la
resonancia de la decisión en la prensa española.
Phosphorylation of CEP83 by TTBK2 is necessary for cilia initiation
Authors: Lo Chien-Hui , Lin I-Hsuan , Yang T. Tony , Huang Yen-Chun , Tanos Barbara E. , Chou Po-Chun , Chang Chih-Wei , Tsay Yeou-Guang , Liao Jung-Chi , Wang Won-Jing
Published: August 2019

Primary cilia are microtubule-based organelles that play important roles in development and tissue homeostasis. Tau-tubulin kinase-2 (TTBK2) is genetically linked to spinocerebellar ataxia type 11, and its kinase activity is crucial for ciliogenesis. Although it has been shown that TTBK2 is recruited to the centriole by distal appendage protein CEP164, little is known about TTBK2 substrates associated with its role in ciliogenesis. Here, we perform superresolution microscopy and discover that serum starvation results in TTBK2 redistribution from the periphery toward the root of distal appendages. Our biochemical analyses uncover CEP83 as a bona fide TTBK2 substrate with four phosphorylation sites characterized. We also demonstrate that CEP164-dependent TTBK2 recruitment to distal appendages is required for subsequent CEP83 phosphorylation. Specifically, TTBK2-dependent CEP83 phosphorylation is important for early ciliogenesis steps, including ciliary vesicle docking and CP110 removal. In summary, our results reveal a molecular mechanism of kinase regulation in ciliogenesis and identify CEP83 as a key substrate of TTBK2 during cilia initiation.
Boundary states for entanglement robustness under dephasing and bit flip channels*
Authors: Li Hong-Mei , Guo Miao-Di , Zhang Rui , Su Xue-Mei
Published: August 2019

We investigate the robustness of entanglement for a multiqubit system under dephasing and bit flip channels. We exhibit the difference between the entanglement evolution of the two forms of special states, which are locally unitarily equivalent to each other and therefore possess precisely the same entanglement properties, and demonstrate that the difference increases with the number of qubits n. Moreover, those two forms of states are either the most robust genuine entangled states or the most fragile ones, which confirm that local unitary (LU) operations can greatly enhance the entanglement robustness of n-qubit states.