bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure-guided function discovery of an NRPS-like glycine betaine reductase for choline biosynthesis in fungi
Authors: Hai Yang , Huang Arthur , Tang Yi 
Published: February 2019

ABSTRACTNonribosomal peptide synthetases (NRPS) and NRPS-like enzymes have diverse functions in primary and secondary metabolism. By using a structure-guided approach, we uncovered the function of an NRPS-like enzyme with unusual domain architecture, catalyzing two sequential two-electron reductions of glycine betaine to choline. Structural analysis based on homology model suggests cation-π interactions as the major substrate specificity determinant, which was verified using substrate analogs and inhibitors. Bioinformatic analysis indicates this NRPS-like glycine betaine reductase is highly conserved and widespread in fungi kingdom. Genetic knockout experiments confirmed its role in choline biosynthesis and maintaining glycine betaine homeostasis in fungi. Our findings demonstrate that the oxidative choline-glycine betaine degradation pathway can operate in a fully reversible fashion and provide new insights in understanding fungal choline metabolism. The use of an NRPS-like enzyme for reductive choline formation is energetically efficient compared to known pathways. Our discovery also underscores the capabilities of structure-guided approach in assigning function of uncharacterized multidomain proteins, which can potentially aid functional discovery of new enzymes by genome mining.
A small viral potassium ion channel with an inherent inward rectification
Authors: Eckert Denise , Schulze Tobias , Stahl Julian , Rauh Oliver , Van Etten James L , Hertel Brigitte , Schroeder Indra , Moroni Anna , Thiel Gerhard 
Published: February 2019

ABSTRACTSome algal viruses have coding sequences for K+channels with structural and functional characteristics of pore modules of complex K+channels. Here we exploit the immense structural diversity of natural channel orthologs to discover new basic principles of structure/function correlates in K+channels. The comparative analysis of three similar K+channels with monomer sizes ≤ 86 amino acids (AA) shows that one channel (Kmpv1) generates an ohmic conductance in HEK293 cells while the other two channels (KmpvSP1, KmpvPL1) exhibit typical features of canonical Kir channels. Like Kir channels, the rectification of the viral channels is a function of the K+driving force. Reconstitution of KmpvSP1and KmpvPL1in planar lipid bilayers showed rapid channel fluctuations only at voltages negative of the K+reversal voltage. This rectification was maintained in KCl buffer with 1 mM EDTA, which excludes blocking cations as the source of rectification. This means that rectification of the viral channels must be, unlike Kir channels, an inherent property of the channel proteins. The structural basis for rectification was investigated by a chimera between rectifying and non-rectifying channels as well as point mutations, which made the rectifying channels similar to the ohmic conducting channel. The results of these experiments exclude the domain, which connects the two transmembrane helixes and which includes the pore helix and the selectivity filter, as playing a major role in rectification; inward rectification must be conferred by the transmembrane domains. The finding that a swapping of the AA, which is typical for the two inward rectifiers, with the respective AA from Kmpv1did not compromise rectification suggests that tertiary or quaternary structural interactions are responsible for this type of gating.
HH-suite3 for fast remote homology detection and deep protein annotation
Authors: Steinegger Martin , Meier Markus , Mirdita Milot , Vöhringer Harald , Haunsberger Stephan J. , Söding Johannes 
Published: February 2019

AbstractBackgroundHH-suite is a widely used open source software suite for sensitive sequence similarity searches and protein fold recognition. It is based on pairwise alignment of profile Hidden Markov models (HMMs), which represent multiple sequence alignments of homologous sequences.ResultsWe developed a single-instruction multiple-data (SIMD) vectorized implementation of the Viterbi algorithm for profile HMM alignment and introduced various other speed-ups. This accelerated HHsearch by a factor 4 and HHblits by a factor 2 over the previous version 2.0.16. HHblits3 is ~10× faster than PSI-BLAST and ~20× faster than HMMER3. Jobs to perform HHsearch and HHblits searches with many query profile HMMs can be parallelized over cores and over servers in a cluster using OpenMP and message passing interface (MPI). The free, open-source, GNU GPL(v3)-licensed software is available at https://github.com/soedinglab/hh-suite.ConclusionThe added functionalities and increased speed of HHsearch and HHblits should facilitate their use in large-scale protein structure and function prediction, e.g. in metagenomics and genomics projects.
Antibiotic production is organized by a division of labour inStreptomyces
Authors: Zhang Zheren , de Barsy Frederique , Liem Michael , Liakopoulos Apostolos , Choi Young H. , Claessen Dennis , Rozen Daniel E. 
Published: February 2019

AbstractOne of the hallmark behaviors of social groups is division of labour, where different group members become specialized to carry out complementary tasks. By dividing labour, cooperative groups of individuals increase their efficiency, thereby raising group fitness even if these specialized behaviors reduce the fitness of individual group members. Here we provide evidence that antibiotic production in colonies of the multicellular bacteriumStreptomyces coelicoloris coordinated by a division of labour. We show thatS. coelicolorcolonies are genetically heterogenous due to massive amplifications and deletions to the chromosome. Cells with gross chromosomal changes produce an increased diversity of secondary metabolites and secrete significantly more antibiotics; however, these changes come at the cost of dramatically reduced individual fitness, providing direct evidence for a trade-off between secondary metabolite production and fitness. Finally, we show that colonies containing mixtures of mutant strains and their parents produce significantly more antibiotics, while colony-wide spore production remains unchanged. Our work demonstrates that by generating mutants that are specialized to hyper-produce antibiotics, streptomycetes reduce the colony-wide fitness costs of secreted secondary metabolites while maximizing the yield and diversity of these products.
Pleiotropic requirements for human TDP-43 in the regulation of cell and organelle homeostasis
Authors: Roczniak-Ferguson Agnes , Ferguson Shawn M. 
Published: February 2019

AbstractTDP-43 is an RNA-binding protein that forms cytoplasmic aggregates in multiple neurodegenerative diseases. Although the loss of normal TDP-43 functions likely contributes to disease pathogenesis, the cell biological consequences of human TDP-43 depletion are not well understood. We therefore generated human TDP-43 knockout cells and subjected them to parallel cell biological and transcriptomic analyses. These efforts yielded three important discoveries. First, complete loss of TDP-43 resulted in widespread morphological defects related to multiple organelles including: Golgi, endosomes, lysosomes, mitochondria and the nuclear envelope. Second, we identified a new role for TDP-43 in controlling mRNA splicing of Nup188 (nuclear pore protein). Third, analysis of multiple amyotrophic lateral sclerosis (ALS) causing TDP-43 mutations revealed a broad ability to support splicing of TDP-43 target genes. However, as some TDP-43 disease causing mutants failed to support the regulation of specific target transcripts, our results raise the possibility of mutation-specific loss-of-function contributions to disease pathology.
Anosognosia for Hemiplegia as a tripartite disconnection syndrome
Authors: Pacella V. , Foulon C. , Jenkinson P.M. , Scandola M. , Bertagnoli S. , Avesani R. , Fotopoulou A. , Moro V. , Thiebaut De Schotten M. 
Published: February 2019

AbstractThe rare syndrome of Anosognosia for Hemiplegia (AHP) can provide unique insights into the neurocognitive processes of motor awareness. Yet, prior studies have only explored predominately discreet lesions. Using advanced structural neuroimaging methods in 174 patients with a right-hemisphere stroke, we were able to identify three neural networks that contribute to AHP, when disconnected: the (1) premotor loop (2) limbic system, and (3) ventral attention network. Our results suggest that human motor awareness is contingent on the joint contribution of these three systems.
Uniaxial loading induces a scalable switch in cortical actomyosin flow polarization and reveals mechanosensitive regulation of cytokinesis
Authors: Singh Deepika , Odedra Devang , Pohl Christian 
Published: February 2019

AbstractDuring animal development, it is crucial that cells can sense and adapt to mechanical forces from their environment. Ultimately, these forces are transduced through the actomyosin cortex. How the cortex can simultaneously respond to and create forces during cytokinesis is not well understood. Here we show that under mechanical stress, cortical actomyosin flow switches its polarization during cytokinesis in theC. elegansembryo. In unstressed embryos, longitudinal cortical flows contribute to contractile ring formation, while rotational cortical flow is additionally induced in uniaxially loaded embryos. Rotational cortical flow is required for the redistribution of the actomyosin cortex in loaded embryos. Rupture of longitudinally aligned cortical fibers during cortex rotation releases tension, initiates orthogonal longitudinal flow and thereby contributes to furrowing in loaded embryos. A targeted screen for factors required for rotational flow revealed that actomyosin regulators involved in RhoA regulation, cortical polarity and chirality are all required for rotational flow and become essential for cytokinesis under mechanical stress. In sum, our findings extend the current framework of mechanical stress response during cell division and show scaling of orthogonal cortical flows to the amount of mechanical stress.
Modification of T cells function after restoration of spontaneous circulation in a rat model of cardiac arrest
Authors: Xing Chunlin , Chen Yang , Zhu Xuemei , Lu Guoping , Chen Weiming 
Published: February 2019

AbstractCardiac arrest (CA) is a prominent cause of mortality worldwide. A large number of patients after post-cardiac arrest is often associated with a phase of impaired immunity. Through an asphyxial cardiac arrest rat model, we investigate the peripheral blood T cells subsets and the expressions of surface molecules after restoration of spontaneous circulation (ROSC). Sprague-Dawley rats (weight, 300-400 g) were randomly divided into cardiac arrest (CA) group and sham-operated group. CA group rats were induced by 6 minutes of asphyxia. After successful ROSC, 24 surviving rats in two groups were randomly assigned to be sacrificed (n = 8 per subgroup) at 3, 24 and 72 h. The proportion of T cells and CD4+, CD8+ subsets as well as the expression of surface molecules (CTLA-4, PD-1, CD28) on T cells were identified by flow cytometry. The protein concentrations of cytokines (TNF-α, IL-6, IL-10, IL-4, IFN-γ, IL-17A) in serum were measured by ELISA. Compared with sham-operated control group, CD3+ lymphocytes in CA group were significantly decreased at 24 and 72 h post-ROSC. The expression levels of CD28, PD-1, and CTLA-4 on T cells were markedly increased in CA groups at 24 h post-ROSC. Additionally, the concentrations of IFN-γ were significantly declined, while IL-4 was markedly elevated in the CA group at 24 and 72 h post-ROSC. T cells function is moderately changed after CA, which is associated with decreased percentage of T cells, the upregulation of co-inhibitory molecules, and the shift from T helper (Th) 1 to Th2.
TCF4 induces enzalutamide resistance via neuroendocrine differentiation in prostate cancer
Authors: Lee Geun Taek , Kim Won Tae , Kwon Young Suk , Palapattu Ganesh , Mehra Rohit , Kim Wun-Jae , Kim Isaac Yi 
Published: February 2019

AbstractIn treating patients with castration resistant prostate cancer (CRPC), enzalutamide, the second-generation androgen receptor (AR) antagonist, is an accepted standard of care. However, clinical benefits are limited to a median time of 4.8 months because resistance inevitably emerges. To determine the mechanism of treatment resistance, we carried out a RNA sequence analysis and found increased expression levels of neuroendocrine markers in the enzalutamide-resistant LNCaP human prostate cancer (CaP) cell line when compared to the parental cell line. Subsequent studies demonstrated that TCF4, a transcription factor implicated in Wnt signaling, mediated neuroendocrine differentiation (NED) in response to enzalutamide treatment and was elevated in the enzalutamide-resistant LNCaP. In addition, we observed that PTHrP mediated enzalutamide resistance in tissue culture and inducible TCF4 overexpression resulted in enzalutamide-resistance in a mouse xenograft model. Finally, small molecule inhibitors of TCF4 or PTHrP partially reversed enzalutamide resistance in CaP cells. When tissues obtained from men who died of metastatic CaP were examined, a positive correlation was found between the expression levels of TCF4 and PTHrP. Taken together, the current results indicate that TCF4 induces enzalutamide resistance via NED in CaP.
No evidence for kin recognition in a passerine bird
Authors: Lattore Martina , Nakagawa Shinichi , Burke Terry , Plaza Mireia , Schroeder Julia 
Published: February 2019

AbstractTheory predicts that individuals behave altruistically towards their relatives. Hence, some form of kin recognition is useful for individuals to optimize their behaviour. In species displaying bi-parental care and subject to extra-pair matings, kin recognition theoretically allows cuckolded fathers to reduce their parental investment, and thus optimize their fitness, but whether this is possible remains unclear in birds. This study investigates the ability of male sparrows to recognize their own chicks, using a large cross-foster experiment, parental care as an indicator and House Sparrows (Passer domesticus) as a model organism. We cross-fostered chicks after hatching, and then expected that fathers would show a decrease in their parental efforts when tending to a clutch of unrelated offspring. However, there was no significant effect of relatedness on provisioning rates. This suggests that sparrows may not be capable of kin recognition, or at least do not display kin discrimination despite its apparent evolutionary advantage.
“Aesthetic regime” in urban entrepreneurialism: public art venues in Shanghai
Authors: Zheng Jane 
Published: February 2019

Purpose
The purpose of this paper is to understand urban sculpture venues that emerged in the recent decade and their connections to the on-going entrepreneurial urban policies and urban strategies in Shanghai. How does this phenomenon relate to Shanghai’s urban policies? How does urban sculpture development reflect the nature and characteristics of the urban sculpture authority?

Design/methodology/approach
Case study is the major research method used to achieve an in-depth understanding of the developmental processes, mechanisms and characteristics of urban sculpture projects. Three cases were selected and studied using purposeful sampling methods, including Duolun Road Sculpture Project (2002), the Shanghai International Sculpture Center (2006) and the Jing’an Sculpture Park (2009).

Findings
A twofold main argument is established in this paper. Urban sculpture venues emerged as a new type of instrument to advance urban entrepreneurial policies; the use of this instrument, however, also involves politics in that art politically transforms the features and functions of open spaces in Shanghai.

Originality/value
Although scholarly interest in exploring cultural development through urban planning in the Chinese context is evident, urban sculpture planning (termed as “urban sculpture” in the Chinese ideological context) in Chinese metropolitan cities, in particular, is an unexplored topic, and thus leaves a gap in the knowledge. This paper introduces a new conceptual model, i.e., “aesthetic regime,” to describe the role of the urban sculpture authority in the development of the urban sculpture scene. It looks at the artistic representation of artworks, design of the sculpture venues, functionality of the artworks and social mechanisms for the actualization of these projects. An evolutional trend of the three sites across the decade is concerned.
Vlog and brand evaluations: the influence of parasocial interaction
Authors: Liu Matthew Tingchi , Liu Yongdan , Zhang Lida L. 
Published: February 2019

Purpose
The purpose of this paper is to investigate the marketing results of video blogging (vlogging). In particular, the authors are interested in understanding which video bloggers (vloggers) can better help marketers develop their brand image, which vlog viewers tend to evaluate vlogger-endorsed brands more positively, and how these effects occur.

Design/methodology/approach
A questionnaire survey was conducted with a convenience sample online. A total of 401 valid responses were collected. Regression analyses and bootstrapping were used to test the hypotheses.

Findings
The authors found that vloggers’ physical and social attractiveness and the audience’s viewing motives (entertainment motive and relationship-building motive) and behavior (time spent on the media) increased the audience’s evaluations of the brands endorsed by the vloggers (perceived brand quality, brand affect and brand preference). The authors also found that these relationships were mediated by the parasocial interaction (PSI) between the vloggers and the audience.

Practical implications
The findings of this study suggest that marketers can develop relationships with consumers and enhance their brand evaluations via vloggers. This strategy is more effective when brand managers use more attractive vloggers and target viewers who spend a lot of time on vlogs seeking entertainment or hoping to build relationships.

Originality/value
This study contributes to the literature by showing that vlogging can affect brand evaluations through the development of PSI between vloggers and viewers. The authors extended the focus of vlog marketing research from consumers’ watching and sharing behaviors and their perception of vloggers to brand evaluations, from vloggers’ characteristics to viewers’ characteristics and from the Western to the Eastern context.
Do letters to shareholders have information content?
Authors: Kiattikulwattana Prapaporn 
Published: February 2019

PurposeThe purpose of this paper is to investigate the information content in letters to shareholders in terms of business content, tone and types of business vocabulary.Design/methodology/approachThe study uses multiple regression models to test the information content concerning business content, tone, and types of business vocabulary in letters to shareholders. Two textual analyses in accounting research dictionaries are used. Loughran and McDonald’s (2011) dictionary is used as a scheme to identify the positive and negative words, and Kothariet al.’s (2009) dictionary is used to identify the business vocabulary.FindingsLetters to shareholders contain incremental information for investors. First, the results show that the market reacts negatively to the content of these letters. The more that business content is disclosed, the lower the abnormal returns. It can be seen that investors catch additional information from letters to shareholders. Second, investors in negative unexpected earnings firms tend to not trust the concentration of positive tone in the letters. Third, some types of business vocabulary in the letters have an influence on investors’ decisions. In addition, larger amounts of business content are seen to be negatively related to firms’ future performance.Practical implicationsDue to the effect of the content of letters to shareholders, the Securities Exchange Commission may wish to consider the results of this study before setting new disclosure regulations. Specifically, some inside information might have a negative effect on market returns.Originality/valueThe study indicates that letters to shareholders are a disclosure venue between companies and investors, where investors react to certain business vocabulary. Some business words are associated with lower future performance. Therefore, the market reacts negatively when these words are reported in the letters.
Customer engagement with brands in social media platforms
Authors: Carlson Jamie , Gudergan Siegfried P. , Gelhard Carsten , Rahman Mohammad Mahfuzur 
Published: February 2019

Purpose
Social media brand platforms have become a popular means for engaged customers to share information and experiences with brands and other customers. However, empirical research on how customer engagement (CE) relates to customers’ sharing intentions with the brand is limited. This study aims to investigate causal patterns of four CE dimensions – focused attention, absorption, enthusiasm and interaction – together with two cognitive structure properties in stimulating sharing intentions with the brand.

Design/methodology/approach
Using data from 782 Chinese customers of brand pages on the social media platform Weibo, this paper is the first to use both finite mixture partial least squares (FIMIX-PLS) analysis and fuzzy-set qualitative comparative analysis (fsQCA) to empirically assess the impact of CE configurations on sharing intentions.

Findings
The findings imply that not all of the CE dimensions co-occur necessarily and that different configurations of them can produce superior sharing intentions, conditional on the cognitive structure of customers, including their level of brand knowledge and avant-gardism.

Research limitations/implications
Although restricted to customers on Weibo, the results inform practice about how social media technology can facilitate different CE configurations and customer sharing intentions.

Practical implications
The results inform brand managers’ segmentation efforts and CE content marketing initiatives that can induce different CE configurations and customer sharing intentions with customers that possess high avant-gard and brand knowledge characteristics.

Originality/value
This study is the first to substantiate how different CE configurations (as gestalts) affect sharing intentions in social media and to challenge conventional net-effects thinking about CE dimensions. Understanding how such conditional configurations foster sharing via a social media platform is advantageous because it can improve segmentation efforts to strengthen brand relationships.