bluuebunny/crossref_metadata_2025_split huggingface dataset:
TheBorrelia burgdorferiadenylyl cyclase, CyaB, is important for virulence factor production and mammalian infection
Authors: Ante Vanessa M. , Farris Lauren C. , Saputra Elizabeth P. , Hall Allie J. , O’Bier Nathaniel S. , Chavez Adela S. Oliva , Marconi Richard T. , Lybecker Meghan C. , Hyde Jenny A. 
Published: March 2021

AbstractBorrelia burgdorferi,the causative agent of Lyme disease, traverses through vastly distinct environments between the tick vector and the multiple phases of the mammalian infection that requires genetic adaptation for the progression of pathogenesis. Borrelial gene expression is highly responsive to changes in specific environmental signals that initiate the RpoS regulon for mammalian adaptation, but the mechanism(s) for direct detection of environmental cues has yet to be identified. Secondary messenger cyclic adenosine monophosphate (cAMP) produced by adenylate cyclase is responsive to environmental signals, such as carbon source and pH, in many bacterial pathogens to promote virulence by altering gene regulation.B. burgdorferiencodes a single non-toxin class IV adenylate cyclase (bb0723, cyaB). This study investigatescyaBexpression along with its influence on borrelial virulence regulation and mammalian infectivity. Expression ofcyaBwas specifically induced with co-incubation of mammalian host cells that was not observed with cultivated tick cells suggesting thatcyaBexpression is influenced by cellular factor(s) unique to mammalian cell lines. The 3’ end ofcyaBalso encodes a small RNA, SR0623, in the same orientation that overlaps withbb0722. The differential processing ofcyaBand SR0623 transcripts may alter the ability to influence function in the form of virulence determinant regulation and infectivity. Two independentcyaBdeletion B31 strains were generated in 5A4-NP1 and ML23 backgrounds and complemented with thecyaBORF alone that truncates SR0623,cyaBwith intact SR0623, orcyaBwith a mutagenized full length SR0623 to evaluate the influence on transcriptional and post-transcriptional regulation of borrelial virulence factors and infectivity. In the absence ofcyaB,expression and production ofospCwas significantly reduced, while the protein levels for BosR and DbpA were substantially lower than parental strains. Infectivity studies with both independentcyaBmutants demonstrated an attenuated phenotype with reduced colonization of tissues during early disseminated infection. This work suggests thatB. burgdorferiutilizescyaBand potentially cAMP as a regulatory pathway to modulate borrelial gene expression and protein production to promote borrelial virulence and dissemination in the mammalian host.
Reduced D-serine levels drive enhanced non-ionotropic NMDA receptor signaling and destabilization of dendritic spines in a mouse model for studying schizophrenia
Authors: Park Deborah K. , Petshow Samuel , Anisimova Margarita , Barragan Eden V. , Gray John A. , Stein Ivar S. , Zito Karen 
Published: March 2021

AbstractSchizophrenia is a psychiatric disorder that affects over 20 million people globally. Notably, schizophrenia is associated with decreased density of dendritic spines and decreased levels of D-serine, a co-agonist required for opening of theN-methyl-D-aspartate receptor (NMDAR). We hypothesized that lowered D-serine levels associated with schizophrenia would enhance ion flux-independent signaling by the NMDAR, driving destabilization and loss of dendritic spines. We tested our hypothesis using the serine racemase knockout (SRKO) mouse model, which lacks the enzyme for D-serine production. We show that activity-dependent spine growth is impaired in SRKO mice, but can be acutely rescued by exogenous D-serine. Moreover, we find a significant bias of synaptic plasticity toward spine shrinkage in the SRKO mice as compared to wild-type littermates. Notably, we demonstrate that enhanced ion flux-independent signaling through the NMDAR contributes to this bias toward spine destabilization, which is exacerbated by an increase in synaptic NMDARs in hippocampal synapses of SRKO mice. Our results support a model in which lowered D-serine levels associated with schizophrenia enhance ion flux-independent NMDAR signaling and bias toward spine shrinkage and destabilization.
Initial topical monotherapy may increase the risk of recurrence in patients with extramammary Paget’s disease
Authors: Choi Sooyie , Oh Yeongjoo , Roh Mi Ryung , Chung Kee Yang , Oh Byung Ho 
Published: March 2021

AbstractAlthough topical therapies are used to treat extramammary Paget's disease (EMPD), reliable treatment outcomes and the effects of these therapies on subsequent surgical treatments are unclear. To assess the clinical outcomes of topical treatment of EMPD and establish the treatment guidelines the medical records of 166 patients diagnosed with EMPD were retrospectively reviewed. The recurrence rate was evaluated according to the previous use of topical agents. Thirty‐four patients (34/166, 20.5%) were initially treated with topical agents such as imiquimod, 5‐fluorouracil, and ingenol mebutate. Three patients (3/34, 8.8%) showed clinical response, while 31 patients required subsequent therapy owing to treatment failure. Analysis of the prognostic factors of recurrence in 166 patients revealed that initial topical treatment increased the hazard ratio (HR) in both univariate and multiple Cox proportional hazards models (HR = 3.770, 95% confidence interval [CI] = 1.768–8.037, P = 0.001, and adjusted HR = 3.628, 95% CI = 1.558–8.450, P = 0.003). Patients treated with topical agents showed significantly poorer 3‐year recurrence‐free survival than the nontreated group (66.3% vs 88.6%, P < 0.001). Topical treatment may be deleterious for some EMPD patients, thus increasing the recurrence risk.
Land‐use change erodes trophic redundancy in tropical forest streams: Evidence from amino acid stable isotope analysis
Authors: Chua Kenny W. J. , Liew Jia Huan , Wilkinson Clare L. , Ahmad Amirrudin B. , Tan Heok Hui , Yeo Darren C. J. 
Published: March 2021

Abstract

Studies have shown that food chain length is governed by interactions between species richness, ecosystem size and resource availability. While redundant trophic links may buffer impacts of species loss on food chain length, higher extinction risks associated with predators may result in bottom‐heavy food webs with shorter food chains.

The lack of consensus in earlier empirical studies relating species richness and food chain length reflects the need to account robustly for the factors described above. In response to this, we conducted an empirical study to elucidate impacts of land‐use change on food chain length in tropical forest streams of Southeast Asia.

Despite species losses associated with forest loss at our study areas, results from amino acid isotope analyses showed that food chain length was not linked to land use, ecosystem size or resource availability. Correspondingly, species losses did not have a significant effect on occurrence likelihoods of all trophic guilds except herbivores.

Impacts of species losses were likely buffered by initial high levels of trophic redundancy, which declined with canopy cover. Declines in trophic redundancy were most drastic amongst invertivorous fishes. Declines in redundancy across trophic guilds were also more pronounced in wider and more resource‐rich streams.

While our study found limited evidence for immediate land‐use impacts on stream food chains, the potential loss of trophic redundancy in the longer term implies increasing vulnerability of streams to future perturbations, as long as land conversion continues unabated.
Location of recurrent cardiovascular events and anticardiolipin antibodies
Authors: Galán‐González Javier , Rico‐Martín Sergio , Calderón‐García Julián F. , Antón Joaquín , Ramírez‐Moreno José M. , Álvarez‐Rodríguez Lorenzo R. , Sánchez Muñoz‐Torrero Juan F. ,   for FRENA Investigators
Published: March 2021

AbstractBackgroundThe relationship between anticardiolipin (aCL) antibodies and cardiovascular events is uncertain and may vary according to arterial location.Materials and methodsFRENA is an ongoing registry of stable outpatients with symptomatic coronary artery disease (CAD), cerebrovascular disease (CVD) or peripheral artery disease (PAD). The rate of subsequent ischaemic events was cross‐referenced with the presence of aCL antibodies (any isotype, IgG or IgM).ResultsAs of June 2017, 1387 stable outpatients were recruited. Of these, 120 (8.7%) showed positive levels of aCL antibodies. Over an average follow‐up of 18 months, 250 patients developed subsequent events: 101 myocardial infarction, 57 ischaemic stroke and 92 critical leg events. Patients with positive aCL antibodies had a higher risk of distal artery events (a composite of ischaemic stroke or critical leg events) than patients with undetectable or low levels (rate ratio: 1.66; 95% CI: 1.07‐2.60). However, an association with central coronary events was not found. The multivariate Cox analysis after adjustment for relevant clinical covariates showed that positivity of aCL antibodies is an independent risk factor for distal events (hazard ratio: 1.60; 95% CI: 1.01‐2.55; P < .05).ConclusionsPositivity of aCL antibodies is associated with an increased risk of subsequent distal artery ischaemic events (cerebral or leg arteries) but not coronary artery events. Anticardiolipin antibodies appear to have a different relationship on the localisation of ischaemic events in patients with symptomatic artery disease.
The sociology of Catholicism: A review of research and scholarship
Authors: Conway Brian 
Published: March 2021

AbstractThis article seeks to review recent research and scholarship in the sociology of Catholicism, as well as focusing on areas needing greater attention. In taking stock of this literature, I identify institutional change, church‐society interactions, institutional resources and influence, and the church as international actor as four key topics that have engaged scholarship. I review existing research under each, as well as highlighting gaps and blind spots that invite further inquiry of this specific religious group.
Generalized Models of Design Iteration Using Signal Flow Graphs
Authors: Nukala Murthy V. , Eppinger Steven D. , Whitney Daniel E. 
Published: March 2021

Abstract
Changing customer preferences, demand for quality and new technologies have led to very short product life cycles. This requires firms to have short product development lead times while keeping product cost low and quality high in order to stay competitive. In this context, we focus on improved understanding of design iterations. We are creating tools for modeling product development projects in order to predict the performance of product development organizations. In this paper, signal flow graphs are presented as a flexible tool for design process modeling. Illustrated using an industrial example, key project performance metrics including the probability distribution of lead time, and to identify key drivers of lead time.
A Methodology of Perspective Browsing to Support Concurrent Design
Authors: Ito Teruaki , Fukuda Shuichi 
Published: March 2021

Abstract
A methodology of perspective browsing to support concurrent design is presented using the concept of perspective and a new idea called hypergraph. Our approach uses the idea of browsing design for concurrent work, where a designer can proceed designing sessions using navigational operations. Browsing design uses the view as a trigger for obtaining information, which strongly supports the natural sequence of a designer’s thought with the minimum interruption. The view is represented by the concept of perspective. We applied a model called PERMO, which encompasses the view and includes a navigational function using a new data structure called hypergraph. We developed a prototype system HYDRA based on the model to demonstrate the usefulness of our browsing methodology for design support system. The paper describes some examples of browsing design using HYDRA.
Dynamics of High Speed Roller Chain Drives
Authors: Fritz Peter , Pfeiffer Friedrich 
Published: March 2021

Abstract
This paper deals with roller chain drives applied in combustion engines. In order to find characteristics for an optimal design, all components of a chain drive are taken into account. For a detailed analysis of the chain strand vibrations and the contact configurations each chain link, sprocket and guide is treated as a separate body. A nonlinear force element describes the joint forces, including elasticity, damping, backlash and oil-displacement. To determine real contact forces between a link and a sprocket or a guide, the exact contour and the mutual dependence of the contacts are considered. The impact of one link may influence the other links in such a manner that their contact configuration may change. In the mechanical model these contacts are represented by unilateral constraints. Applying the formulation of the linear complementarities including additional inequality conditions, the determination of a valid contact configuration after a change in the system structure is simplified.
Self Excited Multi-Mode Vibrations of Aircraft Brakes With Nonlinear Negative Damping
Authors: Black Raymond J. 
Published: March 2021

Abstract
This paper shows how vibratory modes of a brake/landing gear system can interact strongly when there is nonlinear negative damping being generated at the brake’s friction interface. The approach first considers the normal modes of the linearized system. The nonlinear frictional interface force is then added to the modal equations of motion. The energy added to each of the modes, per cycle of the lowest frequency mode, is then determined. From these functions an amplitude path map and limit cycle amplitudes are determined. Multiple limit cycles are found to exist for certain combinations of damping. Amplitude modulation of the higher-frequency mode at multiples of the lower frequency mode is explained. Time solutions of the motion are obtained and compared to computer simulation results. Results compare closely.
The method yields a global view of the stability and modal interactions caused by nonlinear negative damping at the brake’s friction interface.
Barrel-Stave Flextensional Transducers for Sonar Applications
Authors: Jones D. F. , Lewis D. J. , Reithmeier C. G. , Brownell G. A. 
Published: March 2021

Abstract
Barrel-stave flextensional transducers are low frequency underwater projectors that can be used as active components in long-range sonar systems or as versatile sound sources in oceanographic applications. The advantages offered by this type of flextensional transducer include low frequency, high power, small size, low weight, post-assembly frequency tuning, and low cost due to simplicity in its design and assembly. The construction of three barrel-stave projectors, investigated at the Defence Research Establishment Atlantic (DREA) in recent years, is briefly described. The performance goals for each of these projectors are shown to be consistent with the criteria that distinguish the first three classes in the Brigham-Royster classification scheme for flextensional transducers. Important in-water performance parameters, such as the resonance frequencies, transmitting voltage responses, source levels, mechanical quality factors, and electroacoustic efficiencies, are presented. In addition, these parameters are compared to those of other experimental and commercial barrel-stave flextensional designs.
Fast Total Variation-Based Image Reconstruction
Authors: Vogel Curtis R. , Oman Mary Ellen 
Published: March 2021

Abstract
We apply a total variation minimization technique for two tasks in image processing: denoising, which is the reconstruction of an image from noisy observations of the image; and deblurring, which is the reconstruction of an image which is convolved with a smooth kernel function and then contaminated with error. Total Variation minimization yields a nonlinear elliptic partial differential equation (PDE). In this paper we discuss numerical techniques for the efficient solution of this PDE.
Physiological response of the moderately halophilic psychrotolerant strain Chromohalobacter sp. N1 to salinity change and low temperature
Authors: Anan’ina Lyudmila N. , Gorbunov Aleksey A. , Pyankova Anna A. 
Published: March 2021

The available information on de novo synthesized compatible solutes in response to high medium salinity by bacteria of the Chromohalobacter genus is limited to studies of the mesophilic moderately halophilic strain Chromohalobacter salexigens DSM 3043T. Therefore, there is a need for studies of representatives of other species of the Chromohalobacter genus of the Halomonadaceae family. A moderately halophilic psychrotolerant bacterium, strain N1, closely related to the species Chromohalobacter japonicus was isolated from the salt crust of a rock salt waste pile in Berezniki, Perm Krai, Russia. An intracellular pool of compatible solutes of strain N1 was investigated by NMR spectroscopy. Cells grown in the presence of 5% NaCl at optimal growth temperature (28 °C) accumulated ectoine, glutamate, N(4)-acetyl-l-2,4-diaminobutyrate (NADA), alanine, trehalose, hydroxyectoine, and valine. Such a combination of compatible solutes is unique and distinguishes the strain from C. salexigens DSM 3043T. Hyperosmotic stress induced by 15% NaCl caused the accumulation of ectoine, NADA, and hydroxyectoine but led to a decrease in the amount of alanine, valine, and trehalose. The intracellular pool of glutamate was not significantly changed. A reduction of the growth temperature from 28 to 5 °C led to an increase in the amount of ectoine, NADA, trehalose, and hydroxyectoine. Ectoine was the major compatible solute.
The Emerging Roles of RNA m6A Methylation and Demethylation as Critical Regulators of Tumorigenesis, Drug Sensitivity, and Resistance
Authors: Lan Qing , Liu Pei Y. , Bell Jessica L. , Wang Jenny Y. , Hüttelmaier Stefan , Zhang Xu Dong , Zhang Lirong , Liu Tao 
Published: March 2021

Abstract
RNA N6-methyladenosine (m6A) modification occurs in approximately 25% of mRNAs at the transcriptome-wide level. RNA m6A is regulated by the RNA m6A methyltransferases methyltransferase-like 3 (METTL3), METTL14, and METTL16 (writers), demethylases FTO and ALKBH5 (erasers), and binding proteins YTHDC1–2, YTHDF1–3, IGF2BP1–3, and SND1 (readers). These RNA m6A modification proteins are frequently upregulated or downregulated in human cancer tissues and are often associated with poor patient prognosis. By modulating pre-mRNA splicing, mRNA nuclear export, decay, stability, and translation of oncogenic and tumor suppressive transcripts, RNA m6A modification proteins regulate cancer cell proliferation, survival, migration, invasion, tumor initiation, progression, metastasis, and sensitivity to anticancer therapies. Importantly, small-molecule activators of METTL3, as well as inhibitors of METTL3, FTO, ALKBH5, and IGF2BP1 have recently been identified and have shown considerable anticancer effects when administered alone or in combination with other anticancer agents, both in vitro and in mouse models of human cancers. Future compound screening and design of more potent and selective RNA m6A modification protein inhibitors and activators are expected to provide novel anticancer agents, appropriate for clinical trials in patients with cancer tissues harboring aberrant RNA m6A modification protein expression or RNA m6A modification protein–induced resistance to cancer therapy.
Neoadjuvant Chemotherapy Induces IL34 Signaling and Promotes Chemoresistance via Tumor-Associated Macrophage Polarization in Esophageal Squamous Cell Carcinoma
Authors: Nakajima Shotaro , Mimura Kosaku , Saito Katsuharu , Thar Min Aung Kyi , Endo Eisei , Yamada Leo , Kase Koji , Yamauchi Naoto , Matsumoto Takuro , Nakano Hiroshi , Kanke Yasuyuki , Okayama Hirokazu , Saito Motonobu , Neupane Prajwal , Saze Zenichiro , Watanabe Yohei , Hanayama Hiroyuki , Hayase Suguru , Kaneta Akinao , Momma Tomoyuki , Ohki Shinji , Ohira Hiromasa , Kono Koji 
Published: March 2021

Abstract

The tumor microenvironment (TME) plays a key role in the efficacy of neoadjuvant chemotherapy (NAC) in solid tumors including esophageal squamous cell carcinoma (ESCC). However, the TME profile of ESCC treated with NAC is not fully understood. In this study, we investigated the effect of NAC on the TME especially tumor-associated macrophages (TAM), the important immunosuppressive components of the TME, in ESCC. We quantified the expression of CD163, a crucial marker of TAM, in pretherapeutic biopsy and surgically resected ESCC specimens from patients who received NAC (n = 33) or did not receive NAC (n = 12). We found that NAC dramatically increased the expression of CD163 on TAMs in ESCC. Colony-stimulating factor 1 (CSF-1) and IL34 are crucial cytokines that recruit monocytes into tumor sites and differentiate them into TAMs. Interestingly, NAC significantly upregulated the expression of IL34 but not CSF-1 on tumor cells, and the frequencies of CD163+ TAMs were significantly correlated with IL34 expression in ESCC after NAC. The expression of IL34 in NAC-nonresponsive patients was significantly higher than that in NAC-responsive patients, and patients with IL34-high ESCC exhibited worse prognosis as compared with patients with IL34-low ESCC. We also demonstrated that 5-fluorouracil (5-FU)/cisplatin preferentially increased mRNA expression of IL34 on human ESCC cell lines. Human peripheral blood monocytes co-cultured with ESCC cells treated with 5-FU/cisplatin increased the expression of CD163, which was attenuated by the treatment with CSF-1R inhibitors. These data suggest that IL34 expression by NAC shifts the TME toward CD163+ TAM-rich immunosuppressive and chemo-insensitive microenvironment in ESCC.

Implications:
The blockade of IL34 signaling may offer a novel therapeutic strategy against chemoresistance in ESCC by inhibiting M2-TAM polarization.
Kathy McKeown Interviews Bonnie Webber
Authors: Webber Bonnie 
Published: March 2021

AbstractBecause the 2020 ACL Lifetime Achievement Award presentation could not be done in person, we replaced the usual LTA talk with an interview between Professor Kathy McKeown (Columbia University) and the recipient, Bonnie Webber. The following is an edited version of the interview, with added citations.