bluuebunny/crossref_metadata_2025 huggingface dataset:
Kant's Racism as a Philosophical Problem
Authors: Ramsauer Laurenz
Published: September 2023

Immanuel Kant was possibly both the most influential racist and the most influential moral philosopher of modern, Western thought. So far, authors have either interpreted Kant as an “inconsistent egalitarian” or as a “consistent inegalitarian.” On the former view, Kant failed to draw the necessary conclusions about persons from his own moral philosophy; on the latter view, Kant did not consider non‐White people as persons at all. However, both standard interpretations face significant textual difficulties; instead, I argue that Kant's moral egalitarianism is so thin as to remain almost entirely useless as an antidote to racism.
Graded and ungraded expectation patterns: Prediction dynamics during active comprehension
Authors: Lai Melinh K. , Payne Brennan R. , Federmeier Kara D.
Published: September 2023

Language comprehension can be facilitated by the accurate prediction of upcoming words, but prediction effects are not ubiquitous, and comprehenders likely use predictive processing to varying degrees depending on task demands. To ascertain the processing consequences of prioritizing prediction, we here compared ERPs elicited when young adult participants simply read for comprehension with those collected in a subsequent block that required active prediction. We were particularly interested in frontally‐distributed post‐N400 effects for expected and unexpected words in strongly constraining contexts, which have previously been documented as two distinct patterns: an enhanced positivity (“anterior positivity”) observed for prediction violations compared to words that are merely unpredictable (because they occur in weakly constraining sentences) and a distinction between expected endings in more constraining contexts and those same weakly constrained words (“frontal negativity” to the strongly predicted words). We found that the size of the anterior positivity effect was unchanged between passive comprehension and active prediction, suggesting that some processes related to prediction may engage state‐like networks. On the other hand, the frontal negativity showed graded patterns from the interaction of task and sentence type. These differing patterns support the hypothesis that there are two separate effects with frontal scalp distributions that occur after the N400 and further suggest that the impact of violating predictions (as long as prediction is engaged at all) is largely stable across varying levels of effort/attention directed toward prediction, whereas other comprehension processes can be modulated by task demands.
Negotiating civic identity across different political contexts: Immigrant participation in social movements and political incorporation
Authors: Chow Cheng , Ren Lifeiyang
Published: September 2023

This article examines the understudied intersection between migration and contentious politics, focusing specifically on immigrant participation in social movements within their host societies. Drawing upon data from the Anti‐Extradition Law Amendment Bill (Anti‐ELAB) Movement in Hong Kong, it illuminates the process through which Chinese immigrants become politicized, evolve collective identities, and mobilize against civil dominance. Further, it underscores the transformative potential of social movements in facilitating immigrant political incorporation. However, it also recognizes the unilateral acceptance determined by mainstream society, which often leaves immigrants sidelined in discussions regarding their qualifications for unconventional political participation. To address civil inequality, immigrants establish their civil identities, challenge dominance, and amass political capital for future incorporation. This study extends the migration and social movements literature by shedding light on the political dynamics of immigrant participation and the hurdles they encounter during their journey toward political incorporation. It also underscores the significant role of progressive social movements in fostering immigrant political participation. Furthermore, the research highlights the unique immigrant political identity that emerges and evolves through participation in social movements, contesting exclusion and monopolistic dominance over democratic realization.
Automatic partner attitudes: Sources, implications, and future directions
Authors: Faure Ruddy , McNulty James K. , Karremans Johan C.
Published: September 2023

Satisfying romantic relationships offer numerous social and health benefits, making it critical to understand the trajectory of relationship satisfaction. In recent years, research has begun to examine the role of automatic processes in relationship contexts. In particular, a growing number of studies have incorporated indirect (implicit) measures developed by socio‐cognitive researchers to capture people's automatic partner attitudes—the spontaneous affective reactions toward their partner that people may at times be unable to access or unwilling to self‐report in more direct (explicit) measures like questionnaires. In this paper, we review work illustrating how automatic partner attitudes can help explain, predict, and promote both the functioning and the well‐being of romantic couples. That is, we integrate theoretical perspectives on interdependence, attachment, and attitudes to discuss empirical evidence relative to why automatic partner attitudes differ from self‐reported judgments of relationship satisfaction, how such attitudes form in the context of real‐world relationship experiences, and under which conditions they affect dyadic interactions in everyday life. Further, we identify important questions that remain unanswered and provide recommendations that may benefit future work on couples and beyond.
Social protection and state‐citizen relations: A review of the literature
Authors: Ulriksen Marianne S. , Plagerson Sophie
Published: September 2023

It is frequently assumed that social protection can play a key role in positively transforming state‐citizen relations in the global South. We examine the evidence with a focus on recipients and non‐recipients, both citizens and non‐citizens. Based on a systematic literature review, we identify three levels of analysis: activity, perceptions and expectations. A common thread through these levels is the bifurcated and hierarchical nature of relationships between social protection recipients on the one side and the state and non‐recipients on the other. Thus, the cross‐section of evidence does not conclusively support the oft‐assumed transformative potentials of social protection. Arguably, theoretical frameworks on activities, perceptions and expectations allow us to explore further the differentiated relationships shaped by social protection.
On Boltyanski and Gohberg's partition conjecture
Authors: Wang Jun , Xue Fei , Zong Chuanming
Published: September 2023

In 1965, Boltyanski and Gohberg made the following conjecture: Every bounded set in an ‐dimensional normed space can be divided into subsets of smaller diameters. In this paper, we prove the following result: Every bounded set in an ‐dimensional normed space can be divided into subsets of smaller diameters.
Convergent escape behaviour from distinct visual processing of impending collision in fish and grasshoppers
Authors: Dewell Richard B. , Carroll‐Mikhail Terri , Eisenbrandt Margaret R. , Mendoza Alexander F. , Halder Bidisha , Preuss Thomas , Gabbiani Fabrizio
Published: September 2023

In animal species ranging from invertebrate to mammals, visually guided escape behaviours have been studied using looming stimuli, the two‐dimensional expanding projection on a screen of an object approaching on a collision course at constant speed. The peak firing rate or membrane potential of neurons responding to looming stimuli often tracks a fixed threshold angular size of the approaching stimulus that contributes to the triggering of escape behaviours. To study whether this result holds more generally, we designed stimuli that simulate acceleration or deceleration over the course of object approach on a collision course. Under these conditions, we found that the angular threshold conveyed by collision detecting neurons in grasshoppers was sensitive to acceleration whereas the triggering of escape behaviours was less so. In contrast, neurons in goldfish identified through the characteristic features of the escape behaviours they trigger, showed little sensitivity to acceleration. This closely mirrored a broader lack of sensitivity to acceleration of the goldfish escape behaviour. Thus, although the sensory coding of simulated colliding stimuli with non‐zero acceleration probably differs in grasshoppers and goldfish, the triggering of escape behaviours converges towards similar characteristics. Approaching stimuli with non‐zero acceleration may help refine our understanding of neural computations underlying escape behaviours in a broad range of animal species.

image

Key points

A companion manuscript showed that two mathematical models of collision‐detecting neurons in grasshoppers and goldfish make distinct predictions for the timing of their responses to simulated objects approaching on a collision course with non‐zero acceleration.

Testing these experimental predictions showed that grasshopper neurons are sensitive to acceleration while goldfish neurons are not, in agreement with the distinct models proposed previously in these species using constant velocity approaches.

Grasshopper and goldfish escape behaviours occurred after the stimulus reached a fixed angular size insensitive to acceleration, suggesting further downstream processing in grasshopper motor circuits to match what was observed in goldfish.

Thus, in spite of different sensory processing in the two species, escape behaviours converge towards similar solutions.

The use of object acceleration during approach on a collision course may help better understand the neural computations implemented for collision avoidance in a broad range of species.
Community-Based Joint Business Model Design for Solutions to Implementing Technology Innovation in Small Farmers
Authors: Rustandi Yudi , Wulandari Restu , Savitri Mirna
Published: September 2023

In general, small-scale farmers in rural areas often experience obstacles in implementing technological innovations offered by agricultural extension workers. Obstacles can come from within the individual breeder himself. The theory of small farmers and the theory of collective action is expected to solve the obstacles to implementing these technological innovations. This study aims to analyze and find solutions to the obstacles to implementing technological innovation at the individual level of small farmers in rural areas. Researchers took case study research with a research and development (RD) method approach to find the construction of a joint venture model. Qualitative methods are used in Focus Group Discussion (FGD) activities. At the same time, the quantitative descriptive research method is to evaluate the results of implementing the joint venture model. The population and the evaluation research sample were members of the Ampelsari Makmur Jaya farmer group in Pasuruan Regency and the La Tulip Farmer/Women Group in Lamongan Regency. The number of respondents for the perception evaluation was 68, determined as a total sample. Data was collected through participation techniques, in-depth interviews, FGDs and surveys. The evaluation perception was analyzed using descriptive analysis and Score T. The evaluation of respondents’ perceptions resulted in the farmers accepting the establishment of community-based business units (complete feed and pastured chicken business). The solution is also considered effective in solving the obstacles to applying technological innovation by rural and small-scale farmers in Indonesia.
Dynamic phases induced by two-level system defects on driven qubits
Authors: Wang Yanxiang , You Ziyang , Ian Hou
Published: September 2023

Recent experimental evidences point to two-level defects, located in the oxides and on the interfaces of the Josephson junctions, as the major constituents of decoherence in superconducting qubits. How these defects affect the qubit evolution with the presence of external driving is less well understood since the semiclassical qubit-field coupling renders the Jaynes–Cummings model for qubit-defect coupling undiagonalizable. We analyze the decoherence dynamics in the continuous coherent state space induced by the driving and solve the master equation endowed with an extra decay-cladded driving term via a Fokker–Planck equation. The solutions for diffusion propagators as Gaussian distributions show four distinct dynamic phases: four types of convergence paths to limit cycles of varying radius by the distribution mean, which are determined by the competing external driving and the defect decays. The qubit trajectory resulted from these solutions is a super-Poissonian over displaced Fock states, which reduces to a Gibbs state of effective temperature decided by the defect at zero driving limit. Furthermore, the Poincare map shows the dependence of the rate of convergence on the initial state. In other words, the qubit evolution can serve as an indicator of the defect coupling strength through the variation of the driving strength as a parameter.
Changes in the Force–Velocity Relationship of Knee Muscles After Anterior Cruciate Ligament Reconstruction Using the Isokinetic 2-Point Model
Authors: Drigny Joffrey , Calmès Anaelle , Reboursière Emmanuel , Hulet Christophe , Gauthier Antoine
Published: September 2023

Purpose: After anterior cruciate ligament reconstruction (ACL-R), knee muscle strength symmetry is used as part of the return-to-sport criteria. However, little is known about the changes in the force–velocity (F–V) relationship, which could affect athletic performance. This study investigated the F–V relationship of knee muscles at 4 and 8 months after ACL-R, using the 2-point method tested by isokinetic dynamometry. Methods: A total of 103 physically trained individuals (24.6 [9.3] y, 59.2% male) who underwent primary ACL-R were included. Demographic information and surgery characteristics were collected at 6 weeks postoperatively. Isokinetic knee flexors’ and extensors’ peak torques were measured at 60° and 240° per second in the concentric mode at 4 and 8 months postoperative. Peak torques and angular velocities were converted to force and linear velocity for calculating maximum isometric force (F0) and the slope of the regression line (F–V slope). Results: At 4 and 8 months postoperative, F0 was significantly lower and F–V slope was significantly less steep (less negative) on the operated leg compared with the nonoperated leg for knee extensors (P < .001) and flexors (P < .001–.002). The limb symmetry index calculated using F0 was lower than the limb symmetry indexes assessed at 60° and 240° per second, especially for knee flexors (P < .001). The use of patellar tendon grafts was associated with lower F0 and a less steep F–V slope compared with hamstring tendon grafts (P < .010). Conclusion: The isokinetic 2-point model assessing the F–V relationship provides additional and relevant insight for evaluating knee muscle strength after ACL-R.
Avidity-based biosensors for ubiquitylated PCNA reveal choreography of DNA damage bypass
Authors: Yakoub George , Choi Yun-Seok , Wong Ronald P. , Strauch Tina , Ann Kezia J. , Cohen Robert E. , Ulrich Helle D.
Published: September 2023

In eukaryotes, the posttranslational modifier ubiquitin is used to regulate the amounts, interactions, or activities of proteins in diverse pathways and signaling networks. Its effects are mediated by monoubiquitin or polyubiquitin chains of varying geometries. We describe the design, validation, and application of a series of avidity-based probes against the ubiquitylated forms of the DNA replication clamp, proliferating cell nuclear antigen (PCNA), in budding yeast. Directed against total ubiquitylated PCNA or specifically K63-polyubiquitylated PCNA, the probes are tunable in their activities and can be used either as biosensors or as inhibitors of the PCNA-dependent DNA damage bypass pathway. Used in live cells, the probes revealed the timing of PCNA ubiquitylation during damage bypass and a particular susceptibility of the ribosomal DNA locus to the activation of the pathway. Our approach is applicable to a wide range of ubiquitin-conjugated proteins, thus representing a generalizable strategy for the design of biosensors for specific (poly)ubiquitylated forms of individual substrates.
HIV-1 Vpr induces ciTRAN to prevent transcriptional repression of the provirus
Authors: Bhardwaj Vipin , Singh Aman , Choudhary Aditi , Dalavi Rishikesh , Ralte Lalchhanhima , Chawngthu Richard L. , Senthil Kumar Nachimuthu , Vijay Nagarjun , Chande Ajit
Published: September 2023

The functional consequences of circular RNA (circRNA) expression on HIV-1 replication are largely unknown. Using a customized protocol involving direct RNA nanopore sequencing, here, we captured circRNAs from HIV-1–infected T cells and identified ciTRAN, a circRNA that modulates HIV-1 transcription. We found that HIV-1 infection induces ciTRAN expression in a Vpr-dependent manner and that ciTRAN interacts with SRSF1, a protein known to repress HIV-1 transcription. Our results suggest that HIV-1 hijacks ciTRAN to exclude serine/arginine-rich splicing factor 1 (SRSF1) from the viral transcriptional complex, thereby promoting efficient viral transcription. In addition, we demonstrate that an SRSF1-inspired mimic can inhibit viral transcription regardless of ciTRAN induction. The hijacking of a host circRNA thus represents a previously unknown facet of primate lentiviruses in overcoming transmission bottlenecks.
Magic-angle helical trilayer graphene
Authors: Devakul Trithep , Ledwith Patrick J. , Xia Li-Qiao , Uri Aviram , de la Barrera Sergio C. , Jarillo-Herrero Pablo , Fu Liang
Published: September 2023

We propose magic-angle helical trilayer graphene (HTG), a helical structure featuring identical rotation angles between three consecutive layers of graphene, as a unique and experimentally accessible platform for realizing exotic correlated topological states of matter. While nominally forming a supermoiré (or moiré-of-moiré) structure, we show that HTG locally relaxes into large regions of a periodic single-moiré structure realizing flat topological bands carrying nontrivial valley Chern number. These bands feature near-ideal quantum geometry and are isolated from remote bands by a very large energy gap, making HTG a promising platform for experimental realization of correlated topological states such as integer and fractional quantum anomalous Hall states.
Human herpesvirus 6A nuclear matrix protein U37 interacts with heat shock transcription factor 1 and activates the heat shock response
Authors: Huang Jing Rin , Arii Jun , Hirai Mansaku , Nishimura Mitsuhiro , Mori Yasuko
Published: September 2023

Nascent nucleocapsids of herpesviruses acquire a primary envelope during their nuclear export by budding through the inner nuclear membrane into the perinuclear space between the inner and outer nuclear membranes. This process is mediated by a conserved viral heterodimeric complex designated the nuclear egress complex, which consists of the nuclear matrix protein and the nuclear membrane protein. In addition to its essential roles during nuclear egress, the nuclear matrix protein has been shown to interact with intracellular signaling pathway molecules including NF-κB and IFN-β to affect viral or cellular gene expression. The human herpesvirus 6A (HHV-6A) U37 gene encodes a nuclear matrix protein, the role of which has not been analyzed. Here, we show that HHV-6A U37 activates the heat shock element promoter and induces the accumulation of the molecular chaperone Hsp90. Mechanistically, HHV-6A U37 interacts with heat shock transcription factor 1 (HSF1) and induces its phosphorylation at Ser-326. We report that pharmacological inhibition of HSF1, Hsp70, or Hsp90 decreases viral protein accumulation and viral replication. Taken together, our results lead us to propose a model in which HHV-6A U37 activates the heat shock response to support viral gene expression and replication.

IMPORTANCE

Human herpesvirus 6A (HHV-6A) is a dsDNA virus belonging to the
Roseolovirus
genus within the
Betaherpesvirinae
subfamily. It is frequently found in patients with neuroinflammatory disease, although its pathogenetic role, if any, awaits elucidation. The heat shock response is important for cell survival under stressful conditions that disrupt homeostasis. Our results indicate that HHV-6A U37 activates the heat shock element promoter and leads to the accumulation of heat shock proteins. Next, we show that the heat shock response is important for viral replication. Overall, our findings provide new insights into the function of HHV-6A U37 in host cell signaling and identify potential cellular targets involved in HHV-6A pathogenesis and replication.
HIV-1 reverse transcriptase stability correlates with Gag cleavage efficiency: reverse transcriptase interaction implications for modulating protease activation
Authors: Hsieh Shih-Han , Yu Fu-Hsien , Huang Kuo-Jung , Wang Chin-Tien
Published: September 2023

Proteolytic processing of human immunodeficiency virus type 1 particles mediated by viral protease (PR) is essential for acquiring virus infectivity. Activation of PR embedded in Gag-Pol is triggered by Gag-Pol dimerization during virus assembly. We previously reported that amino acid substitutions at the RT tryptophan repeat motif destabilize virus-associated RT and attenuate the ability of efavirenz (EFV, an RT dimerization enhancer) to increase PR-mediated Gag cleavage efficiency. Furthermore, a single amino acid change at RT significantly reduces virus yields due to enhanced Gag cleavage. These data raise the possibility of the RT domain contributing to PR activation by promoting Gag-Pol dimerization. To test this hypothesis, we investigated the putative involvement of a hydrophobic leucine repeat motif (LRM) spanning RT L282 to L310 in RT/RT interactions. We found that LRM amino acid substitutions led to RT instability and that RT is consequently susceptible to degradation by PR. The LRM mutants exhibited reduced Gag cleavage efficiencies while attenuating the EFV enhancement of Gag cleavage. In addition, an RT dimerization-defective mutant, W401A, reduced enhanced Gag cleavage via a leucine zipper (LZ) motif inserted at the deleted Gag-Pol region. Importantly, the presence of RT and integrase domains failed to counteract the LZ enhancement of Gag cleavage. A combination of the Gag cleavage enhancement factors EFV and W402A markedly impaired Gag cleavage, indicating a disruption of W402A Gag-Pol dimerization following EFV binding to W402A Gag-Pol. Our results support the idea that RT modulates PR activation by affecting Gag-Pol/Gag-Pol interaction.

IMPORTANCE

A stable reverse transcriptase (RT) p66/51 heterodimer is required for HIV-1 genome replication in host cells following virus entry. The activation of viral protease (PR) to mediate virus particle processing helps viruses acquire infectivity following cell release. RT and PR both appear to be major targets for inhibiting HIV-1 replication. We found a strong correlation between impaired p66/51RT stability and deficient PR-mediated Gag cleavage, suggesting that RT/RT interaction is critical for triggering PR activation via the promotion of adequate Gag-Pol dimerization. Accordingly, RT/RT interaction is a potentially advantageous method for anti-HIV/AIDS therapy if it is found to simultaneously block PR and RT enzymatic activity.
Complete genome sequence of phi29-like
Microbacterium foliorum
podovirus phage PineapplePizza
Authors: LaBianca Kylie , Butura Jessica , McKnight Arden , Pan Karin , Whelan Sean , Punska Elizabeth , Pause Robert , Igbinosa Bright , Ribbe Alexander , Chien Peter , Russell Daniel , Garlena Rebecca , Hatfull Graham , Jacobs-Sera Deborah , Rocheleau Jessica
Published: September 2023

Bacteriophage PineapplePizza is a podovirus infecting
Microbacterium foliorum
NRRL B-24224. The genome is 16,662 bp long and contains 23 predicted protein-coding genes. Interestingly, PineapplePizza shows amino acid similarities to well-studied
Bacillus subtilis
phage phi29.
Emergence of KPC-113 and KPC-114 variants in ceftazidime-avibactam-resistant
Klebsiella pneumoniae
belonging to high-risk clones ST11 and ST16 in South America
Authors: Vásquez-Ponce Felipe , Bispo Jessica , Becerra Johana , Fontana Herrison , Pariona Jesus G. M. , Esposito Fernanda , Fuga Bruna , Oliveira Flavio A. , Brunetti Florencia , Power Pablo , Gutkind Gabriel , Schreiber Angelica Zaninelli , Lincopan Nilton
Published: September 2023

Two novel variants of
Klebsiella pneumoniae
carbapenemase (KPC) associated with resistance to ceftazidime-avibactam (CZA) and designated as KPC-113 and KPC-114 by NCBI were identified in 2020, in clinical isolates of
Klebsiella pneumoniae
in Brazil. While
K. pneumoniae
of ST16 harbored the
bla
KPC-113
variant on an IncFII-IncFIB plasmid,
K. pneumoniae
of ST11 carried the
bla
KPC-114
variant on an IncN plasmid. Both isolates displayed resistance to broad-spectrum cephalosporins, β-lactam inhibitors, and ertapenem and doripenem, whereas
K. pneumoniae
producing KPC-114 showed susceptibility to imipenem and meropenem. Whole-genome sequencing and
in silico
analysis revealed that KPC-113 presented a Gly insertion between Ambler positions 264 and 265 (R264_A265insG), whereas KPC-114 displayed two amino acid insertions (Ser-Ser) between Ambler positions 181 and 182 (S181_P182insSS) in KPC-2, responsible for CZA resistance profiles. Our results confirm the emergence of novel KPC variants associated with resistance to CZA in international clones of
K. pneumoniae
circulating in South America.

IMPORTANCE

KPC-2 carbapenemases are endemic in Latin America. In this regard, in 2018, ceftazidime-avibactam (CZA) was authorized for clinical use in Brazil due to its significant activity against KPC-2 producers. In recent years, reports of resistance to CZA have increased in this country, limiting its clinical application. In this study, we report the emergence of two novel KPC-2 variants, named KPC-113 and KPC-114, associated with CZA resistance in
Klebsiella pneumoniae
strains belonging to high-risk clones ST11 and ST16. Our finding suggests that novel mutations in KPC-2 are increasing in South America, which is a critical issue deserving active surveillance.
The bovine leukemia virus-derived long non-coding RNA AS1-S binds to bovine hnRNPM and alters the interaction between hnRNPM and host mRNAs
Authors: Andoh Kiyohiko , Nishimori Asami , Matsuura Yuichi
Published: September 2023

Viruses utilize several strategies to cause latent infection and evade host immune responses. Long non-coding RNA (lncRNA), a class of non-protein-encoding RNA that regulates various cellular functions by interacting with RNA-binding proteins, plays important roles for viral latency in several viruses, such as herpesviruses and retroviruses, due to its lack of antigenicity. Bovine leukemia virus (BLV), which belongs to the family Retroviridae, encodes the BLV-derived lncRNA AS1-S, which is a major transcript expressed in latently infected cells. We herein identified bovine heterogeneous nuclear ribonucleoprotein M (hnRNPM), an RNA-binding protein located in the nucleus, as the binding partner of AS1-S using an RNA-protein pull-down assay. The pull-down assay using recombinant hnRNPM mutants showed that RNA recognition motifs (RRMs) 1 and 2, located in the N-terminal region of bovine hnRNPM, were responsible for the binding to AS1-S. Furthermore, RNA immunoprecipitation (RIP) assay results showed that the expression of AS1-S increased the number of mRNAs that co-immunoprecipitated with bovine hnRNPM in MDBK cells. These results suggested that AS1-S could alter the interaction between hnRNPM and host mRNAs, potentially interfering with cellular functions during the initial phase of mRNA maturation in the nucleus. Since most of the identified mRNAs that exhibited increased binding to hnRNPM were correlated with the KEGG term “Pathways in cancer,” AS1-S might affect the proliferation and expansion of BLV-infected cells and contribute to tumor progression.

IMPORTANCE

BLV infects bovine B cells and causes malignant lymphoma, a disease that greatly affects the livestock industry. Due to its low incidence and long latent period, the molecular mechanisms underlying the progression of lymphoma remain enigmatic. Several non-coding RNAs (ncRNAs), such as miRNA and lncRNA, have recently been discovered in the BLV genome, and the relationship between BLV pathogenesis and these ncRNAs is attracting attention. However, most of the molecular functions of these transcripts remain unidentified. To the best of our knowledge, this is the first report describing a molecular function for the BLV-derived lncRNA AS1-S. The findings reported herein reveal a novel mechanism underlying BLV pathogenesis that could provide important insights for not only BLV research but also comparative studies of retroviruses.
A prebiotic diet modulates the oral microbiome composition and results in the attenuation of oropharyngeal candidiasis in mice
Authors: Vazquez-Munoz Roberto , Thompson Angela , Sobue Takanori , Dongari-Bagtzoglou Anna
Published: September 2023

Oral bacteria can influence the ability of
Candida albicans
to cause oropharyngeal candidiasis (OPC). We recently reported that a
Lactobacillus johnsonii
-enriched oral microbiota reduced
C. albicans
virulence in an immunosuppressed OPC mouse model. As a follow-up, in this work, we aimed to enrich the resident oral
Lactobacillus
communities with a prebiotic diet to further assess their effect on the severity of OPC. We tested the effect of a prebiotic xylo-oligosaccharides (XOS)-enriched diet in the oral global bacterial composition and severity of OPC. We assessed changes in the oral microbiome composition via 16S-rRNA gene high-throughput sequencing, validated by qPCR. The impact of the prebiotic diet on
Candida
infection was assessed by quantifying changes in oral fungal and bacterial biomass and scoring tongue lesions. Contrary to expectations, oral
Lactobacillus
communities were not enriched by the XOS-supplemented diet. Yet, XOS modulated the oral microbiome composition, increasing
Bifidobacterium
abundance and reducing enterococci and staphylococci. In the OPC model, the XOS diet attenuated
Candida
virulence and bacterial dysbiosis, increasing lactobacilli and reducing enterococci on the oral mucosa. We conclude that XOS attenuates
Candida
virulence by promoting a bacterial microbiome structure more resilient to
Candida
infection.

IMPORTANCE

This is the first study on the effects of a prebiotic diet on the oral mucosal bacterial microbiome and an oropharyngeal candidiasis (OPC) mouse model. We found that xylo-oligosaccharides change the oral bacterial community composition and attenuate OPC. Our results contribute to the understanding of the impact of the oral bacterial communities on
Candida
virulence.
Erythronate utilization activates VdtR regulating its metabolism to promote
Brucella
proliferation, inducing abortion in mice
Authors: Yin Yi , Fang Tian , Lian Zhengmin , Zuo Dong , Hu Hai , Zhang Guangdong , Ding Chan , Tian Mingxing , Yu Shengqing
Published: September 2023

Brucella
is a facultative intracellular pathogen that preferentially colonizes reproductive organs and utilizes erythritol as a preferred carbon source for its survival and proliferation. In this study, we identified a
v
irulence-related
D
eoR-family
t
ranscriptional
r
egulator (VdtR) and an erythronate metabolic pathway responsible for four-carbon acid sugar metabolism of D-erythronate and L-threonate in
Brucella
. We found that VdtR plays an important role in
Brucella
intracellular survival and trafficking to the endoplasmic reticulum in RAW 264.7 macrophages and in virulence in a mouse model. More importantly, we found that VdtR negatively regulates the erythronate metabolic pathway to promote extracellular proliferation of
Brucella
, depending on utilization of D-erythronate, an oxidative product of erythritol in the host. In a pregnant mouse model, the erythronate metabolic pathway was shown to cooperate with erythritol metabolism and play a crucial role in
Brucella
proliferation in the placenta, inducing placentitis and finally resulting in abortion or stillbirth. Our results demonstrate that, in addition to erythritol, erythronate is a preferred carbon source for
Brucella
utilization to promote its extracellular proliferation. This discovery updates the information on the preferential colonization of reproductive organs by
Brucella
and provides a novel insight into the
Brucella
-associated induction of abortion in pregnant animals.

IMPORTANCE

Brucella
is an intracellular parasitic bacterium causing zoonosis, which is distributed worldwide and mainly characterized by reproductive disorders. Erythritol is found in allantoic fluid, chorion, and placenta of aborted animals, preferentially utilized by
Brucella
to cause infertility and abortion. However, the erythritol metabolism-defected mutant was unable to function as a vaccine strain due to its residual virulence. Here, we found that erythronate, an oxidative product of erythritol in the host, was also preferentially utilized by
Brucella
relying on the function of a deoxyribonucleoside regulator-family transcriptional regulator VdtR. Erythronate utilization activates VdtR regulation of the erythronate metabolic pathway to promote
Brucella
extracellular proliferation, inducing placentitis/abortion in mice. Double mutations on
Brucella
erythritol and D-erythronate metabolisms significantly reduced bacterial virulence. This study revealed a novel mechanism of
Brucella
infection-induced abortion, thus providing a new clue for the study of safer
Brucella
attenuated vaccines.
Deciphering the regulatory mechanisms of the cAMP/protein kinase A pathway and their roles in the pathogenicity of
Candida auris
Authors: Kim Ji-Seok , Lee Kyung-Tae , Bahn Yong-Sun
Published: September 2023

The emergence of multidrug-resistant fungal pathogens is a significant concern for global public health.
Candida auris
poses a considerable threat as a multidrug-resistant fungal pathogen. Our recent study revealed that the adenylyl cyclase Cyr1 and protein kinase A (PKA) pathways play distinct and redundant roles in drug resistance and pathogenicity of
C. auris
. However, the upstream and negative feedback regulatory mechanisms of
C. auris
are not yet fully understood. In this study, we discovered that the small GTPase Ras1, along with its nucleotide exchange factor Cdc25 and GTPase-activating protein Ira2, plays a major role in regulating cAMP/PKA-dependent traits, while G-protein-coupled receptor Gpr1 and heterotrimeric G-protein α subunit Gpa2 play a minor role. Pde2 plays a major role in negative feedback regulation of the cAMP/PKA pathway, while Pde1 plays a minor role. Hyperactivation of the Ras/cAMP/PKA pathway by deleting
PDE2
or
BCY1
renders
C. auris
cells thermosensitive and susceptible to nutrient deficiency, which leads to attenuated virulence. Our study demonstrates the distinct contributions of hyperactivation of the Ras/cAMP/PKA signaling pathway to
C. auris
pathogenesis and suggests potential therapeutic targets for
C. auris-
mediated candidiasis.

IMPORTANCE

Candida auris
is a major concern as a multidrug-resistant fungal pathogen. While our previous studies highlighted the crucial roles of the cAMP/protein kinase A (PKA) pathway in regulating drug resistance, stress responses, morphogenesis, ploidy change, biofilm formation, and pathogenicity in this pathogen, their regulatory mechanism remains unclear. In our study, we provided evidence that the cAMP/PKA signaling pathway in
C. auris
is primarily governed by the small GTPase RAS rather than a G-protein-coupled receptor. Additionally, we discovered that the negative feedback regulation of cAMP, controlled by phosphodiesterases, is vital for
C. auris
virulence by promoting resistance to high temperatures and nutrient deficiencies. These findings underscore the diverse pathobiological significance of the Ras/cAMP/PKA signaling pathway in
C. auris
, shedding light on potential therapeutic targets and strategies for combating this multidrug-resistant fungal pathogen.
Structural geometry and kinematic evolution of the central Canadian Rocky Mountain Foothills fold-and-thrust belt: Complex kinematic relationships controlled by detachment utilization
Authors: McMechan M.E.
Published: September 2023

Balanced regional cross sections based on surface, seismic, and subsurface data show that the thin-skinned fold-and-thrust belt in the Rocky Mountain Foothills of the Kakwa area of the central Canadian Rockies consists of a lower buried thrust belt developed in Paleozoic and Triassic strata and an upper exposed faulted fold belt of Jurassic to Cretaceous strata. Changes in fold wavelength, amplitude, and geometry with stratigraphic level indicate that multiple detachments were utilized in the upper faulted fold belt. Exposed folds are chevron or box shaped. Most appear to be detachment or fault propagation folds formed by fault-to-fold displacement transfer. Geometric and kinematic relationships in the upper faulted fold belt vary from thrust faults congruently folded by underlying folds (early fault) to folds abruptly truncated by thrust faults (late fault). In contrast, folding of thrust sheets in the buried thrust belt is consistent with in-sequence deformation for all faults except one. A sequential restoration of the balanced regional cross section shows that the variable kinematic relationships observed in the upper faulted fold belt can be explained by changes in the detachment level utilized by successive faults as they climbed out of the buried thrust belt. Chevron-folded thrust faults indicate a younger fault with associated fault displacement transfer folds formed in the footwall of an older fault. These folded thrusts formed by in-sequence faulting and utilization of successively higher detachment levels. Late faults that truncate preexisting folds required out-of-sequence (hinterlandward) utilization of a higher detachment level, and they illustrate another mechanism by which critical taper is maintained in a fold-and-thrust belt.
Supplemental Material: Products and dynamics of lava-snow explosions: The 16 March 2017 explosion at Mount Etna, Italy
Authors: Cioni Raffaello , et al.
Published: September 2023

Table S1: Sample list. Figure S1: Effects of the explosions. Figure S2: Relative abundance of the different clast lithologies in the different samples. Figure S3. Shape parameters relative to the grain-size class. Figure S4: Density distribution for the different lithologies of the coarse material. Figure S5: Pre-eruption topography of the area invaded by the lava flow. Supplemental Video S1: UAS video footage of the lava flow and the deposit of the explosion. Supplemental Data S1: Field and laboratory data.
Association of baseline fasting plasma glucose with 1-year mortality in non-diabetic patients with acute cerebral infarction: a multicentre observational cohort study
Authors: Zhang Dandan , Liu Zhongzhong , Liu Pei , Zhang Huan , Guo Weiyan , Lu Qingli , Huang Congli , Wang Jing , Chang Qiaoqiao , Zhang Mi , Huo Yan , Wang Yan , Lin Xuemei , Wang Fang , Wu Songdi
Published: September 2023

Objectives

Evidence on the association between fasting blood glucose and mortality in non-diabetic patients who had a stroke is limited. We aimed to investigate the association of baseline fasting plasma glucose (FPG) with 1 year all-cause mortality in non-diabetic patients with acute cerebral infarction (ACI).

Design

A multicentre prospective cohort study.

Setting

Four grade A tertiary hospitals in the Xi'an district of China.

Participants

A total of 1496 non-diabetic patients within 7 days of ACI were included.

Main outcome measures

The outcome was 1 year all-cause mortality. Baseline FPG was analysed as a continuous variable and was divided into four quartiles (group Q1–group Q4). We used multivariable Cox regression analyses, curve fitting and Kaplan–Meier (K-M) analyses to explore the association of baseline FPG with 1 year all-cause mortality in non-diabetic patients with ACI.

Results

After controlling for confounders, multivariable Cox regression analyses indicated a 17% increase in 1 year all-cause mortality for every 1 mmol/L of baseline FPG increase (HR=1.17, 95% CI 1.02 to 1.35, p=0.030). Patients from the Q4 group had 2.08 times increased hazard of 1 year all-cause mortality compared with the Q1 group (HR=2.08, 95% CI 1.13 to 3.82, p=0.019), while the survival rate of patients in group Q4 was decreased compared with that in other groups (p<0.001). The curve fitting revealed a positive but non-linear association of baseline FPG with 1-year all-cause mortality in non-diabetic patients with ACI.

Conclusion

In non-diabetic patients with ACI, elevated baseline FPG is an independent risk factor for 1-year all-cause mortality, and the two are positively and non-linearly associated. These results suggest that high FPG should be seen as a concern in non-diabetic patients with ACI.
Sequential multiple assignment randomised controlled trial protocol for developing an adaptive intervention to improve depressive symptoms among family caregivers of people with dementia
Authors: Kor Patrick Pui Kin , Chou Kee Lee , Zarit Steven H , Gallagher Dolores , Galante Julieta , Wong Samuel Y S , Cheung Daphne Sze Ki , Leung Angela Y M , Chu Leung-Wing
Published: September 2023

Objectives

Family caregivers of people with dementia (FC-of-PWD) suffer from a high level of stress and depressive symptoms, which usually require different interventions at different stages. Although some standalone interventions such as behavioural activation (BA) and mindfulness practice (MP) have been shown to be potentially effective at reducing depressive symptoms, the best sequence and combination of these interventions for caregivers are unknown. This study aims to develop and identify a two-stage adaptive intervention with prespecified rules guiding whether, how or when to offer different interventions initially/over time to reduce depressive symptoms in FG-of-PWD.

Methods

A sequential multiple assignment randomised trial design will be adopted. 272 FG-of-PWD with mild to moderate depressive symptoms will be recruited from the community. Four two-stage, embedded adaptive interventions involving BA and MP of different sequences and dosages (eg, 8 weeks of BA followed by booster sessions for responders and 8 weeks of MP for non-responders) will be assigned to the participants following a set of decision rules. The primary outcomes will be depressive symptoms (measured using the Patient Health Questionnaire-9), assessed after the second stage of the intervention. Other outcomes, such as positive aspects of caregiving (measured using the Positive Aspects of Caregiving Scale), sleep quality (measured using the Pittsburgh Sleep Quality Index) and time points will also be assessed. The analyses will follow the intention-to-treat principle. Several process indicators (eg, engagement in meaningful activities and level of mindfulness) will also be assessed. The findings will have strong implications for the further development of psychosocial adaptive interventions to reduce depressive symptoms among FC-of-PWD.

Ethics and dissemination

This study has received ethical approval from the Human Research Ethics Committee at The Hong Kong Polytechnic University (HSEARS20211223001). The findings will be presented at academic conferences and submitted to peer-reviewed journals for publication.

Trial registration number

NCT05634317.
What matters most? A qualitative study exploring priorities for supportive interventions for people with tuberculosis in urban Viet Nam
Authors: Smith Isabel , Forse Rachel , Sidney Annerstedt Kristi , Thanh Nguyen Thi , Nguyen Lan , Phan Thi Hoang Yen , Nguyen Han , Codlin Andrew , Vo Luan Nguyen Quang , Nguyen Nga Thi Thuy , Khan Amera , Creswell Jacob , Pham Huy Minh , Basu Lopa , Lönnroth Knut , Nguyen Binh Hoa , Nguyen Viet Nhung , Atkins Salla
Published: September 2023

Introduction

The health and economic burden of tuberculosis (TB) in urban Viet Nam is high. Social protection and support interventions can improve treatment outcomes and reduce costs. However, evidence regarding optimal strategies in this context is lacking. This study aimed to increase understanding of what people with TB and healthcare providers (HCPs) perceive as important to improve TB treatment outcomes and reduce costs.

Methods

We conducted qualitative focus group discussions (seven groups, n=30) and key informant interviews (n=4) with people with drug-susceptible and multidrug-resistant TB and HCPs in Ha Noi and Ho Chi Minh City. Topic guides covered perspectives on and prioritisation of different forms of social protection and support. Data were analysed using reflexive thematic analysis and interpreted using a Framework for Transformative Social Protection.

Results

We identified three themes and seven subthemes. The first theme, ‘Existing financial safety nets are essential, but could go further to support people affected by TB’, highlights that support to meet the medical costs of TB treatment and flexible cash transfers are a priority for people with TB and HCPs. The second, ‘It is important to promote “physical and spiritual health” during TB treatment’, demonstrates that extended psychosocial and nutritional support would encourage people with TB during their treatment. The third, ‘Accessibility and acceptability are critical in designing social support interventions for people with TB’, shows the importance of ensuring that support is accessible and proportional to the needs of people with TB and their families.

Conclusions

Accessible interventions that incorporate financial risk protection, nutritional and psychosocial support matter most to people with TB and HCPs in urban Viet Nam to improve their treatment outcomes and reduce catastrophic costs. This study can inform the design of stronger person-centred interventions to advance progress towards the goals of the WHO’s End TB Strategy.