bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dual therapy with Atazanavir/ritonavir plus Raltegravir versus triple therapy with Atazanavir/ritonavir plus Tenofovir-Emtricitabine after failure to an NNRTI regimen: 48-week results of the randomized pilot study ARTE trial
Authors: Inés Figueroa María , Sued Omar , Cesar Carina , Patterson Patricia , Yamamoto Cleyton , Fink Valeria , Luna Norma , Camiro-Zúñiga Antonio , Gun Ana , Cahn Pedro 
Published: July 2022

AbstractBackgroundDual therapy has emerged as a novel concept for HIV treatment. The ARTE study was aimed at comparing a nucleoside-sparing dual regimen consisting of ATV/r + RAL (DT) vs standard therapy of ATV/r + TDF/FTC (TT) among individuals failing first NNRTI-containing treatment.MethodsRandomized multicenter open-label pilot study. Primary outcome: proportion of subjects with plasma HIV-1 RNA below the limit of detection (<50 copies/mL) at 48 weeks (W48). Secondary outcomes: proportion of discontinuation due to adverse events (AEs), time until viral suppression, time until loss of virological response, development of integrase resistance mutations, and absolute change in CD4 counts. The primary outcome was analyzed using the FDA snapshot analysis.ResultsOut of 57 participants screened, 34 were randomized to receive: DT (n: 18) or TT (n: 16). At W48, virological response was achieved in 67% (n: 12/18) of participants receiving DT and 88% (n: 14/16) receiving TT by FDA snapshot analysis (p = NS) and, 73% and 93% by per-protocol analysis (p = NS). CD4 cell count median change from baseline to W48 was +119 and + 52 cell/μL in DT and TT, respectively. Four participants receiving DT and one TT presented virological failure at W48, with low pVL. One participant developed an integrase resistance mutation (155H) and suppressed later on TT.ConclusionATV/r+RAL as second-line therapy showed a trend to more frequent virological failure, compared to TT, although the study was unpowered to prove this difference. No major differences were seen in tolerance or toxicity.This study is registered with ClinicalTrials.gov, Number: NCT01829802
Looking for a needle in a haystack: magnetotactic bacteria help in “rare biosphere” investigations
Authors: Uzun Maria , Koziaeva Veronika , Dziuba Marina , Alekseeva Lolita , Krutkina Maria , Sukhacheva Marina , Baslerov Roman , Grouzdev Denis 
Published: July 2022

ABSTRACTStudying the minor part of the uncultivated microbial majority (“rare biosphere”) is difficult even with modern culture-independent techniques. The enormity of microbial diversity creates particular challenges for investigating low-abundance microbial populations in soils. Strategies for selective sample enrichment to reduce community complexity can aid in studying the rare biosphere. Magnetotactic bacteria, apart from being a minor part of the microbial community, are also found in poorly studied bacterial phyla and certainly belong to a rare biosphere. The presence of intracellular magnetic crystals within magnetotactic bacteria allows for their significant enrichment using magnetic separation techniques for studies using a metagenomic approach. This work investigated the microbial diversity of a black bog soil and its magnetically enriched fraction. The poorly studied phylum representatives in the magnetic fraction were enriched compared to the original soil community. Two new magnetotactic species,CandidatusLiberimonas magnetica DUR002 andCandidatusObscuribacterium magneticum DUR003, belonging to different classes of the relatively little-studied phylumElusimicrobiota, were proposed. Their genomes contain clusters of magnetosome genes that differ from the previously described ones by the absence of genes encoding magnetochrome-containing proteins and the presence of uniqueElusimicrobiota-specific genes, termedmae. The predicted obligately fermentative metabolism in DUR002 and lack of flagellar motility in the magnetotacticElusimicrobiotabroadens our understanding of the lifestyles of magnetotactic bacteria and raises new questions about the evolutionary advantages of magnetotaxis. The findings presented here increase our understanding of magnetotactic bacteria, soil microbial communities, and the rare biosphere.
UPF1 mutants with intact ATPase but deficient helicase activities promote efficient nonsense-mediated mRNA decay
Authors: Chapman Joseph H. , Craig Jonathan M. , Wang Clara D. , Gundlach Jens H. , Neuman Keir C. , Hogg J. Robert 
Published: July 2022

AbstractThe conserved RNA helicase UPF1 coordinates nonsense-mediated mRNA decay (NMD) by engaging with mRNAs, RNA decay machinery, and the terminating ribosome. UPF1 ATPase activity is necessary for mRNA target discrimination and completion of decay, but the mechanisms through which UPF1 enzymatic activities such as helicase, translocase, RNP remodeling, and ATPase-stimulated dissociation influence NMD remain poorly defined. Using high-throughput biochemical assays to quantify UPF1 enzymatic activities, we show that UPF1 is only moderately processive (< 200 nt) in physiological contexts and undergoes ATPase-stimulated dissociation from RNA. We combine an in silico screen with these assays to identify and characterize known and novel UPF1 mutants with altered helicase, ATPase, and RNA binding properties. We find that UPF1 mutants with substantially impaired processivity, slower unwinding rate, and reduced mechanochemical coupling (i.e. the ability to harness ATP hydrolysis for work) still support efficient NMD in human cells. These data are consistent with a central role for UPF1 ATPase activity in driving cycles of RNA binding and dissociation to ensure accurate NMD target selection.
A population modification gene drive targeting bothSaglinandLipophorinimpairsPlasmodiumtransmission inAnophelesmosquitoes
Authors: Green Emily , Jaouen Etienne , Klug Dennis , Olmo Roenick Proveti , Gautier Amandine , Blandin Stéphanie , Marois Eric 
Published: July 2022

AbstractLipophorin is an essential, highly expressed lipid transport protein that is secreted and circulates in insect hemolymph. We hijacked theAnopheles coluzzii Lipophoringene to make it co-express a single-chain version of antibody 2A10, which binds sporozoites of the malaria parasitePlasmodium falciparum. The resulting transgenic mosquitoes show a markedly decreased ability to transmitPlasmodium bergheiexpressing theP. falciparumcircumsporozoite protein. To force the spread of this anti-malarial transgene in a mosquito population, we designed and tested several CRISPR/Cas9-based gene drives. One of these is installed in, and disrupts, the pro-parasitic geneSaglinand also cleaves wild-typeLipophorin,causing the anti-malarial modifiedLipophorinversion to replace the wild type and hitch-hike together with theSaglindrive. Although generating drive-resistant alleles and showing instability in its gRNA-encoding multiplex array, theSaglin-based gene drive reached high levels in caged mosquito populations and efficiently promoted the simultaneous spread of the antimalarialLipophorin::Sc2A10allele. This combination is expected to decrease parasite transmission via two different mechanisms. This work contributes to the design of novel strategies to spread antimalarial transgenes in mosquitoes, and illustrates some expected and unexpected outcomes encountered when establishing a population modification gene drive.
Transient T cell expansion, activation, and proliferation in therapeutically vaccinated SIV+ macaques treated with N-803
Authors: Harwood Olivia E. , Balgeman Alexis J. , Weaver Abigail J. , Ellis-Connell Amy L. , Weiler Andrea M. , Erickson Katrina N. , Matschke Lea M. , Golfinos Athena E. , Vezys Vaiva , Skinner Pamela J. , Safrit Jeffrey T. , Edlefsen Paul T. , Reynolds Matthew R. , Friedrich Thomas C. , O’Connor Shelby L. 
Published: July 2022

AbstractVaccine strategies aimed at eliciting HIV-specific CD8+ T cells are one major target of interest in HIV functional cure strategies. We hypothesized that CD8+ T cells elicited by therapeutic vaccination during antiretroviral therapy (ART) would be recalled and boosted by treatment with the IL-15 superagonist N-803 after ART discontinuation. We intravenously immunized four SIV+ Mauritian cynomolgus macaques (MCM) receiving ART with vesicular stomatitis virus (VSV), modified vaccinia virus Ankara strain (MVA), and recombinant adenovirus serotype 5 (rAd-5) vectors all expressing SIVmac239 Gag. Immediately after ART cessation, these animals received three doses of N-803. Four control animals received no vaccines or N-803. The vaccine regimen generated a high magnitude of Gag-specific CD8+ T cells that were proliferative and biased toward an effector memory phenotype. We then compared cells elicited by vaccination (Gag-specific) to cells elicited by SIV infection and unaffected by vaccination (Nef-specific). We found that N-803 treatment enhanced both the frequencies of bulk and proliferating antigen-specific CD8+ T cells elicited by vaccination and the antigen-specific CD8+ T cells elicited by SIV infection. In sum, we demonstrate that a therapeutic heterologous prime-boost-boost (HPBB) vaccine can elicit antigen-specific effector memory CD8+ T cells that are boosted by N-803.
Rational synthesis of total damage during vitrification: modelling and experimental validation of osmotic, temperature, and cytotoxic damage in sea urchin (Paracentrotus lividus) oocytes
Authors: Olver Dominic J , Heres Pablo , Paredes Estefania , Benson James D 
Published: July 2022

ABSTRACTSea urchin (Paracentrotus lividus) oocytes are an important species for aquaculture and as a model species for multiple scientific fields. Despite their importance, methods of cryopreserved biobanking of oocytes are currently not possible. Optimized cryoprotectant loading may enable vitrification methods of cryopreservation and thus long-term storage of oocytes. Determining an optimized protocol requires membrane characteristics and models of damage associated with the vitrification loading protocol, namely osmotic, temperature, and cytotoxic damage. We present and experimentally evaluated state-of-the-art models alongside our novel models. We experimentally verify the damage models throughout time at difference treatment intensities. Osmotic damage experiments consisted of hypertonic solutions composed of seawater supplemented with NaCl or sucrose and hypotonic solutions composed of seawater diluted with deionized water. Treatment times ranged from 2 to 30 minutes. To test temperature damage (in particular chill injury), oocytes were exposed to 1.7 °C, 10 °C, and 20 °C (control) for exposure times ranging from 2 to 90 minutes. Cytotoxicity was investigated by exposing oocytes to solutions of Me2SO for exposure times ranging from 2 to 30 minutes. We identify appropriate models and use these to search for an optimal loading protocol, namely the time dependent osmotic damage model (for osmotic damage), the temperature dependent model (for temperature damage), and the external molality Arrhenius power model (for cytotoxicity). We combined these models to estimate total damage during a cryopreservation loading protocol and performed a exhaustive grid search for optimal loading for a given goal intracellular cryoprotectant concentration. Given our fitted models, we find sea urchin oocytes can only be loaded to 0.13 Me2SO v/v with a 50% survival, For reference, levels for vitrification are approximately 0.45 v/v. Our synthesis of damages is the first of its kind, and enables a fundamentally novel approach to modelling survival for cells in general.
Plant-specific armadillo repeat kinesin directs organelle transport and microtubule convergence to promote tip growth
Authors: Kanda Asaka , Otani Kento , Ueda Takashi , Takahashi Taku , Motose Hiroyasu 
Published: July 2022

AbstractTip growth is essential for plant growth and reproduction. However, it remains elusive how highly polarized tip-growing cells coordinate the organization of intracellular components. Here, we show that plant-specific armadillo-repeat containing kinesin, MpARK, mediates organelle transport and microtubule convergence in tip growing rhizoids in the early diverging land plantMarchantia polymorpha. MpARK is required for anterograde transport of organelles to maintain their position. Furthermore, MpARK participates in the formation of microtubule foci at the rhizoid apex to stabilize growth direction. MpARK-dependent rhizoid growth is essential for plant anchorage and soil holding capacity. Thus, ARK might be a principal organelle transporter and intracellular organizer in the primitive rooting cells for the adaptation to terrestrial environments. Our findings suggest that ARK is functionally comparable to canonical anterograde kinesins in animals and fungi.
An RNA binding protein, RNP1A, works with Contractility Kit proteins to facilitate macropinocytosis
Authors: Liu Yinan , Leng Jessica , Nguyen Ly TS , Robinson Douglas N. 
Published: July 2022

AbstractCell shape regulation is important for many biological processes. Some cell shape regulating proteins harbor mechanoresponsive properties that enable them to sense and respond to mechanical cues, allowing for cell adaptation. InDictyostelium discoideum, mechanoresponsive network proteins include Cortexillin I and IQGAP1, which assemble in the cytoplasm into macromolecular complexes, which we term Contractility Kits.In vivofluorescence cross-correlation spectroscopy revealed that Cortexillin I also interacts with an RNA-binding protein, RNP1A. Thernp1Aknockdown cells have reduced cell growth rate, reduced adhesion, defective cytokinesis, and a gene expression profile that indicatesrnp1Aknockdown cells shift away from the vegetative growth state. RNP1A binds to transcripts encoding proteins involved in macropinocytosis. One of these, DlpA, facilitates macropinosome maturation, similar to RNP1A. Loss of different CK proteins leads to macropinocytotic defects characterized by reduced macropinocytotic crown size. RNP1A interacts with IQGAP1in vivoand has cross-talk with IQGAP1 during macropinocytosis. Overall, RNP1A contributes to macropinocytosis, in part through interacting with transcripts encoding macropinocytotic proteins likedlpA, and does so in coordination with the Contractility Kit proteins.
“Remote adipose tissue-derived stromal cells of patients with lung adenocarcinoma generate a similar malignant microenvironment of the lung stromal counterpart”
Authors: De Falco Elena , Bordin Antonella , Menna Cecilia , Dhori Xhulio , Rosa Paolo , Rendina Erino , Ibrahim Mohsen , Calogero Antonella 
Published: July 2022

AbstractCancer alters both local and distant tissue by influencing the microenvironment. In this regard, the interplay with the stromal fraction is considered critical as this latter can either foster or hamper the progression of the disease. Accordingly, the modality by which tumor may alter distant niches of stromal cells is still unclear, expecially at early stages. In this short report we attempt to better understand the biology of this cross talk. In our “autologous stromal experimental setting”, we found that remote adipose tissue-derived mesenchymal stem cells (mediastinal AMSC) obtained from patients with lung adenocarcinoma sustain proliferation and clonogenic ability of A549 and human primary lung adenocarcinoma cells similarly to the autologous stromal lung counterpart (LMSC). This effect is not observed in lung benign diseases as the hamartochondroma. This finding was validated by conditioning benign AMSC with supernatants from LAC up to 21 days. The new reconditioned media of the stromal fraction so obtained, was able to increase cell proliferation of A549 cells at 14 and 21 days similarly to that derived from AMSC of patients with lung adenocarcinoma. The secretome generated by remote AMSC revealed overlapping to the corresponding malignant microenvironment of the autologous local LMSC. Among the plethora of 80 soluble factors analysed by arrays, a small pool of 5 upregulated molecules including IL1-β, IL-3, MCP-1, TNF-α and EGF, was commonly shared by both malignant-like autologous A- and LMSC derived microenvironments vs those benign. The bioinformatic analysis both revealed that these proteins were strictly and functionally interconnected to the lung fibrosis and proinflammation and that miR-126, 101, 486 and let-7-g were their main targets. Accordingly, we found that in lung cancer tissues and blood samples from the same set of patients here employed, miR-126 and miR-486 displayed the highest expression levels in tissue and blood, respectively.
The LH-DH module of the bacterial replicative helicases is the common binding site for DciA and other helicase loaders
Authors: Cargemel Claire , Marsin Stéphanie , Noiray Magali , Legrand Pierre , Bounoua Halil , Li de la Sierra-Gallay Inès , Walbott Hélène , Quevillon-Cheruel Sophie 
Published: July 2022

AbstractDuring the initiation step of bacterial genome replication, replicative helicases depend on specialized proteins for their loading onto oriC. DnaC and DnaI were the first loaders characterized. However, most bacteria do not contain any of these genes, which are domesticated phage elements that replaced the ancestral and unrelated loader gene dciA several times during evolution. To understand how DciA assists the loading of DnaB, we determined the crystal structure of the complex from Vibrio cholerae, in which two VcDciAs interact with a dimer of VcDnaB, without changing its canonical structure. Our data showed that the VcDciA binding site on VcDnaB is the conserved module formed by the linker helix LH of one monomer and the determinant helix DH of the second one. Interestingly, DnaC from Escherichia coli also targets this module onto EcDnaB. Thanks to their common target site, we showed that VcDciA and EcDnaC could be functionally interchanged in vitro, despite sharing no structural similarities. This is a milestone in understanding the mechanism employed by phage helicase loaders to hijack bacterial replicative helicases during evolution.
The association between public pension fund characteristics and pension accounting choices
Authors: Xu Guoquan , Liu Fang-Chun , Hsu Hsiao-Tang , Lin Jerry 
Published: July 2022

PurposeThe choice of accounting methods is critical in measuring the performance and sustainability of a public defined benefit pension (DBP) plan, and such measurement has an impact on the effectiveness of the entire pension system. Prior literature rarely discusses the choice and rationale of the accounting assumptions for public DBP plans. This study fills the gap by investigating whether crucial plan characteristics, including operational performance, financial health, sponsor fiscal stress, and audit quality, are associated with the accounting assumptions of public DBP plans.Design/methodology/approachThe sample includes 1,170 plan-years from the intersection of the Center for Retirement Research and public DBPs' annual financial reports for the years 2001–2013. This study develops regression models to examine the relationship between the characteristics of public DBP practices and DBP accounting choices.FindingsThe empirical results show that the public DBPs that have better investment performance, higher funding status, less fiscal stress, and that are audited by Big 4 accounting firms are more likely to adopt conservative accounting choices.Originality/valueThe study documents the impact of crucial pension plan characteristics on public DBP managers' accounting choices, which were not extensively discussed in pension literature. The findings help us understand the rationale for employing different accounting treatments in the context of public pension fund practices. In addition, the study sheds light on policy implications for the future reform of public pension regulations.
Towards a relational approach for understanding the multiplicity of sitting activities
Authors: Sharif Ahlam Ammar 
Published: July 2022

PurposeThis study aims at unpacking the multiplicity of the sitting activity in public spaces through the lens of actor-network theory. In line with previous urban research focussing on outdoor activities, such empirical investigation aims to show the importance of the physical aspects of spaces, including seating, in supporting sitting activities as a way of encouraging the use of public space.Design/methodology/approachThis study adopts the overlap between actor–network theory and affordances. It utilises ethnographic research involving frequent users in Dahiyat Al Hussein Park in Amman-Jordan. Data were gathered on the different seat–user relations and the translated sitting activity networks.FindingsAnalysis demonstrates different cases of alignment, misalignment and realignment between what is intended and experienced, and where these relations are maintained, disrupted or changed. These findings reveal the multiplicity of sitting activities; this is significant for understanding how they are maintained.Originality/valueThe research suggests a new way of conceptualising the relationship between the physical environment and users and an approach for examining sitting activities. Some studies have applied actor–network theory and/or the concept of “affordance” by highlighting relations between the object and its user and how they create sitting activities. However, only few studies have problematised the multiplicity of sitting when considering seating uses.
Team Around Me: a case coordination model for clients experiencing multiple disadvantage
Authors: Wright Scarlett A.A. , Campbell Lucy , Harries Morgan 
Published: July 2022

Purpose
This study aims to present a case study about the Team Around Me (TAM) model of case coordination which was developed by Fulfilling Lives Islington and Camden (FLIC) as an action experiment. The model is a standardised tool for running case conferences for clients experiencing multiple disadvantage (MD).

Design/methodology/approach
Deploying a case study approach, this study explores why a TAM-coordinated approach is beneficial for people experiencing MD.

Findings
The authors explore why the need for effective case coordination is integral for clients experiencing MD, and how current structures fail to facilitate effective case management. The authors put forward an argument for the four core principles underpinning the TAM model: strengths-based, action-focussed, systems thinking and client involvement. The barriers to embedding and upscaling this approach are discussed, alongside the obstacles presented by the wider system that prevent wider implementation.

Originality/value
The TAM model is a new approach to case conferences, designed and upscaled by FLIC, and has since been adopted across two London boroughs, and training has reached services across the UK. This paper highlights the need for innovative approaches to case coordination that centre client involvement, promote a strengths-based approach and recognise system blockages as a key barrier to client progress.