bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protein disulfide isomerase PDI8 is indispensable for parasite growth and associated with secretory protein processing in
Toxoplasma gondii
Authors: Wang Chaoyue , Sun Pei , Jia Yonggen , Tang Xinming , Liu Xianyong , Suo Xun , Peng Hongjuan 
Published: August 2024

ABSTRACT

Protein disulfide isomerase, containing thioredoxin (Trx) domains, serves as a vital enzyme responsible for oxidative protein folding (the formation, reduction, and isomerization of disulfide bonds in newly synthesized proteins) in the endoplasmic reticulum (ER). However, the role of ER-localized PDI proteins in parasite growth and their interaction with secretory proteins remain poorly understood. In this study, we identified two ER-localized PDI proteins, TgPDI8 and TgPDI6, in
Toxoplasma gondii
. Conditional knockdown of TgPDI8 resulted in a significant reduction in intracellular proliferation and invasion abilities, leading to a complete block in plaque formation on human foreskin fibroblast monolayers, whereas parasites lacking TgPDI6 did not exhibit any apparent fitness defects. The complementation of TgPDI8 with mutant variants highlighted the critical role of the CXXC active site cysteines within its Trx domains for its enzymatic activity. By utilizing TurboID-based proximity labeling, we uncovered a close association between PDI proteins and canonical secretory proteins. Furthermore, parasites lacking TgPDI8 showed a significant reduction in the expression of secretory proteins, especially those from micronemes and dense granules. In summary, our study elucidates the roles of TgPDI8 and sets the stage for future drug discovery studies.

IMPORTANCE

Apicomplexans, a phylum of intracellular parasites, encompass various zoonotic pathogens, including
Plasmodium
,
Cryptosporidium
,
Toxoplasma
, and
Babesia
, causing a significant economic burden on human populations. These parasites exhibit hypersensitivity to disruptions in endoplasmic reticulum (ER) redox homeostasis, necessitating the presence of ER-localized thioredoxin (Trx) superfamily proteins, particularly protein disulfide isomerase (PDI), for proper oxidative folding. However, the functional characteristics of ER-localized PDI proteins in
Toxoplasma gondii
remain largely unexplored. In this study, we identified two ER-localized proteins, namely, TgPDI8 and TgPDI6, and demonstrated the indispensable role of TgPDI8 in parasite survival. Through a comprehensive multi-omics analysis, we elucidated the crucial role of TgPDI8 in the processing of secretory proteins in
T. gondii
. Additionally, we introduced a novel ER-anchored TurboID method to label and identify canonical secretory proteins in
T. gondii
. This research opens up new avenues for understanding oxidative folding and the secretory pathway in apicomplexan parasites, laying the groundwork for future advancements in antiparasitic drug development.
Complete genome of a rare
Salmonella enterica
subsp.
enterica
serovar Hessarek from human stool
Authors: Selway Caitlin A. , May Jacob P. , Goonetilleke Shenoi M. A. , Hocking Helen , Turra Mark , Leong Lex E. X. 
Published: August 2024

ABSTRACT

We present a complete genome of
Salmonella enterica
subsp.
enterica
serovar Hessarek isolated from a human stool from an outbreak linked to egg consumption in South Australia. Orientation of the
rrn
operon and characteristics of the
Salmonella
virulence plasmid indicates that this serovar is virulent toward humans and birds.
Nanopore sequencing of IPNV vp2 gene in Peruvian Andean trout (
Oncorhynchus mykiss
) cultures
Authors: Tapia Stephanie , Orellana Joseph , Duran Yerson , Rodriguez Jose , Angulo Derly , Dominguez-Mendoza Luz , Grabiel Sandra , Silva Jose , Caballero Romina , Zapata Katherine , Gómez Muriel , Tataje-Lavanda Luis , Velazco Rodolfo 
Published: August 2024

ABSTRACT

Nanopore sequencing of the infectious pancreatic necrosis virus (IPNV) vp2 gene from Andean trout cultures in Peru reveals genogroups 1 and 5. This insight aids in understanding strain diversity and pathogenicity, vital for effective disease surveillance, and control measures in aquaculture.
Transcriptomic analyses of a
Salmonella enterica-Escherichia coli
pair following exposure to tetracycline during
in vitro
conjugation experiments
Authors: Algarni Suad , Gudeta Dereje D. , Sopovski Danielle , Han Jing , Feye Kristina M. , Foley Steven L. 
Published: August 2024

ABSTRACT

Antimicrobial exposure can potentially lead to increased antimicrobial resistance plasmid transfer. Sequencing data were collected from the RNA of pairs of
Salmonella enterica
and
Escherichia coli
exposed or not exposed to tetracycline over time to determine differences in transcription-associated tetracycline exposure during
in vitro
conjugation experiments.
Genome sequences of 36
Streptococcus pneumoniae
strains optimized for the multiplexed opsonophagocytosis killing assay
Authors: Graffice Emma , Meewes Chloe , Ganaie Feroze A. , Nahm Moon H. , Calix Juan J. 
Published: August 2024

ABSTRACT

A multiplexed opsonophagocytosis assay (MOPA) was developed as a cost-effective, high-throughput biological assay to evaluate the efficacy of pneumococcal vaccines by
in vitro
measurement of opsonophagocytic activity of anti-capsular antibodies. Here, we report draft genomes of the 36 strains of
Streptococcus pneumoniae
developed for use in the reference pneumococcal MOPA.
Draft genome sequence of
Acinetobacter haemolyticus
strain MUWRP1017 isolated from the pus of a female inpatient at Bwera General Hospital in Uganda
Authors: Wokorach Godfrey , Erima Bernard , Alafi Stephen , Kabatesi Hope O. , Muhindo Julius T. , Najjuka Florence , Kiyengo James , Kibuuka Hannah , Musinguzi Ambrose K. , Wabwire-Mangen Fred , Byarugaba Denis K. 
Published: August 2024

ABSTRACT

The bacterium
Acinetobacter haemolyticus
, with a genome size of 3.4 Mb, was isolated from a pus swab of a wound on the left lower limb above the ankle joint of a female patient. This strain carries the antimicrobial resistance genes cephalosporinase
blaADC-25
, oxallinase
blaOXA-264
,
floR
, and
sul2
and other resistance and virulence genes.
Genomic and functional divergence of
Staphylococcus aureus
strains from atopic dermatitis patients and healthy individuals: insights from global and local scales
Authors: Wang Zhongjie , Hülpüsch Claudia , Foesel Bärbel , Traidl-Hoffmann Claudia , Reiger Matthias , Schloter Michael 
Published: August 2024

ABSTRACT

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease worldwide and is characterized by a complex interplay with skin microbiota, with
Staphylococcus aureus
often abnormally more abundant in AD patients than in healthy individuals (HE).
S. aureus
harbors diverse strains with varied genetic compositions and functionalities, which exhibit differential connections with the severity of AD. However, the differences in
S. aureus
strains between AD and HE remain unclear, with most variations seen at a specific geographic level, implying spontaneous adaptations rather than systematic distinctions. This study presents genomic and functional differences between these
S. aureus
strains from AD and HE on both global and local levels. We observed reduced gene content diversity but increased functional variation in the global AD-associated strains. Two additional AD-dominant clusters emerged, with Cluster 1 enriched in transposases and Cluster 2 showcasing genes linked to adaptability and antibiotic resistance. Particularly, robust evidence illustrates that the lantibiotic operon of
S. aureus
, involved in the biosynthesis of lantibiotics, was acquired
via
horizontal gene transfer from environmental bacteria. Comparisons of the gene abundance profiles in functional categories also indicate limited zoonotic potential between human and animal isolates. Local analysis mirrored global gene diversity but showed distinct functional variations between AD and HE strains. Overall, this research provides foundational insights into the genomic evolution, adaptability, and antibiotic resistance of
S. aureus
, with significant implications for clinical microbiology.

IMPORTANCE

Our study uncovers significant genomic variations in
Staphylococcus aureus
strains associated with atopic dermatitis. We observed adaptive evolution tailored to the disease microenvironment, characterized by a smaller pan-genome than strains from healthy skin both on the global and local levels. Key functional categories driving strain diversification include “replication and repair” and “transporters,” with transposases being pivotal. Interestingly, the local strains predominantly featured metal-related genes, whereas global ones emphasized antimicrobial resistances, signifying scale-dependent diversification nuances. We also pinpointed horizontal gene transfer events, indicating interactions between human-associated and environmental bacteria. These insights expand our comprehension of
S. aureus
’s genetic adaptation in atopic dermatitis, yielding valuable implications for clinical approaches.
Clinical outcomes of reperfusion therapy in patients with site-specific basilar artery occlusion
Authors: Žakelj Nina , Rigler Igor , Longo Alja , Frol Senta , Pretnar Oblak Janja 
Published: August 2024

BackgroundDespite its low incidence, basilar artery occlusion (BAO) remains a major therapeutic challenge since severe disability and death occur in about 80% of patients. Specific site of BAO (proximal, middle, or distal) has rarely been reported as a prognostic factor in reperfusion therapy. We aimed to explore the relationship between site-specific BAO and clinical outcomes in patients treated with reperfusion therapies.MethodsWe performed a single-centre retrospective study of all consecutive patients with acute BAO admitted to the University Medical Centre Ljubljana between January 2013 and August 2022 who were treated with reperfusion therapies. Patients were grouped according to the location of BAO and compared for baseline characteristics, differences in stroke aetiology, type of reperfusion therapy, success of recanalization, and clinical outcome after 90 days evaluated by the modified Rankin Scale (mRS) score. Statistical analysis was performed with the two-sided ANOVA t-tests for continuous measures, Chi-squared (χ2) tests for categorical measures and a multivariate ordinal logistic regression analysis.ResultsThe study included 103 patients (47% females, median age 74 years; confidence interval (CI) 72 to 98). Proximal BAO was found in 13%, middle in 13%, and distal in 74% of patients. Cardioembolic etiology was more common in distal (=0.01), and atherosclerotic etiology in proximal and middle BAO occlusions (P=0.02). While distal BAO was more likely to be recanalized using intravenous thrombolysis (IVT) compared with other sites of occlusion (P=0.05), we found no difference between different occlusion sites and the success of endovascular treatment (EVT). Lower age (odds ratio (OR) 0.89; CI 0.84 to 0.95; P<0.01) and shorter time to intervention (OR 0.71; CI 0.53 to 0.95; P=0.02), regardless of it being IVT or EVT, were predictors of an excellent clinical outcome (mRS 0–2). Distal occlusion (OR 28; CI 2.7 to 300; p<0.01) was a strong predictor of a favorable clinical outcome (mRS 0–3).ConclusionPrompt reperfusion, regardless of it being IVT or EVT, increases the chance of excellent clinical outcomes in patients with acute BAO. Distal BAO is more often associated with a favorable clinical outcome compared with the proximal and middle segments.
Multiple mantle metasomatism recorded by Triassic post-collisional ultrapotassic and tholeiitic magmatism in West Qinling, NW China
Authors: Tao Lu , Luo Biji , Zhang Hongfei , Xu Wangchun , Huang Hua , Yang He , Qiu Huaning , Bai Xiujuan , Lu Shansong , Guo Liang , Pan Fabin , Wang Lianxun , Li Zhanke 
Published: August 2024

Mantle properties and metasomatic processes, together with interlayer interactions, in orogenic belts are still under debate. Post-collisional magmatic rocks could provide secondhand constraints on these issues. We have conducted an integrated geochronological, geochemical and isotopic study on post-collisional Zhanwa dolerites, the Dashui granodiorite–monzonite–monzogabbro complex and the Jiuzigou pyroxenite–syenite complex at West Qinling. The Zhanwa dolerites, being tholeiitic with flat trace element patterns, were mixtures of melts from asthenospheric and oceanic slab-fluid-metasomatized lithospheric mantle. The Dashui monzonite–monzogabbro suite is ultrapotassic with strongly right-inclined trace element patterns and evolved isotopic composition with (
87
Sr/
86
Sr)
i
= 0.7066–0.7068,

ε

Nd
(
t
) = −4.56 to −4.35,

ε

Hf
(
t
) = −3.14 to −2.35 and (
206
Pb/
204
Pb)
i
= 17.99–18.12. It was derived from melting of a mantle source metasomatized by continent-crustal materials. In contrast, the Dashui granodiorites are shoshonitic–calc-alkaline with more evolved isotopic compositions with (
87
Sr/
86
Sr)
i
,

ε

Nd
(
t
),

ε

Hf
(
t
), and (
206
Pb/
204
Pb)
i
of 0.7074–0.7091, −7.56 to −5.51, −5.61 to −3.53 and 18.18–18.46, respectively. They represent hybrids of mantle-derived K-rich and crustal-derived felsic melts. The Jiuzigou complex has extremely high trace element contents. Its mantle source was metasomatized by both oceanic crustal fluids and sedimentary melts. Generation of these rocks (
c.
235–223 Ma) not only recorded multiple mantle metasomatism, but also captured collective asthenospheric and lithospheric magmatic responses in a post-collisional setting.
Optimizing Garbage Collection for ZNS SSDs via In-storage Data Migration and Address Remapping
Authors: Tan Zhenhua , Long Linbo , Shen Jingcheng , Liu Renping , Gao Congming , Zhong Kan , Jiang Yi 
Published: August 2024

The NVMe Zoned Namespace (ZNS) is a high-performance interface for flash-based solid-state drives (SSDs), which divides the logical address space into fixed-size and sequential-write zones. Meanwhile, ZNS SSDs eliminate in-device garbage collection (GC) by shifting the responsibility of GC to the host. However, the host-side GC of ZNS SSDs is not efficient. On the one hand, data migration during GC first moves data to the host buffer and then writes back the transferred data to the new location in the SSD, resulting in an unnecessary end-to-end transfer overhead. On the other hand, due to the pre-configured mapping between zones and blocks, GC incurs a large block-to-block rewrite overhead, i.e., even if most of the data in a block of the victim zone is valid, the valid data will still be rewritten to another block in the target zone. To address these issues, this article proposes a novel ZNS SSD design that features dynamic zone mapping, termed
Brick-ZNS
.
Brick-ZNS
implements two key functionalities: in-storage data migration and address remapping. New ZNS commands are first designed to realize in-storage data migration to avoid the end-to-end transfer overhead of GC while ensuring performance predictability. Then, a remapping strategy exploiting parallel physical blocks is proposed to reduce the large block-to-block rewrite overhead while ensuring zone-level access parallelism. The basic idea of the strategy is to directly remap the parallel physical blocks with a sufficient amount of valid data in the victim zone to the target zone, hence avoiding the large block-to-block rewrite overhead. Based on a full-stack SSD emulator, the evaluation results show that
Brick-ZNS
improves write throughput by 25% and SSD lifetime by 1.41×.
Progression of Sclerouveitis to Endogenous Fusarium Endophthalmitis
Authors: Zhang Sairi , Chacko J. Anthony , Sanders Riley N. , Rosenbaum Eric R. , Dockery Philip W. , Sallam Ahmed B. 
Published: August 2024

Introduction: We describe a unique case of sclerouveitis that progressed to endogenous Fusarium endophthalmitis in a 69‐year‐old male with chronic lymphocytic leukemia (CLL). We highlight the risk of treating sclerouveitis with oral corticosteroids, which can exacerbate an infection and contribute to disease progression.Case Presentation: A 69‐year‐old male with CLL on zanubrutinib, a second‐generation Bruton’s tyrosine kinase inhibitor, was admitted to the hospital for osteomyelitis of the left foot. At presentation, the patient also reported right eye pain for 1 week and vision loss over the course of 1 month. Vision in the right eye was hand motion. Slit lamp examination revealed scleral inflammation in the right eye with violaceous injection, chemosis, inflammation in the anterior chamber, and diffuse subconjunctival hemorrhage. There was significant corneal edema preventing fundus examination. B‐scan ultrasonography demonstrated a flat retina with no vitritis or scleral thickening. Forty‐eight hours after treatment with oral and topical corticosteroids, the patient’s eye pain improved but his vision worsened. Repeat B‐scan showed new‐onset vitritis. Fungal culture obtained by diagnostic pars plana vitrectomy (PPV) revealed growth of Fusarium. The patient was treated with oral and intravitreal voriconazole in addition to intravenous voriconazole and amphotericin B for systemic therapy. Corticosteroids were discontinued. Despite aggressive therapy, the patient’s disposition declined to the point of transitioning to comfort‐focused care, and he passed away.Conclusion: Endogenous fungal endophthalmitis is most commonly seen in immunocompromised patients, and oral corticosteroid therapy for such patients should be used with caution as it can worsen an infection. In cases of fusarial endophthalmitis, visual prognosis is poor.
Novel ERBB2 Variant Potentially Associated with Resistance against Anti-HER2 Monoclonal Antibody–Based Therapy in ERBB2-Amplified Metastatic Colorectal Cancer
Authors: Iida Naoko , Imai Mitsuho , Okamoto Wataru , Kato Takeshi , Esaki Taito , Kato Ken , Komatsu Yoshito , Yuki Satoshi , Masuishi Toshiki , Nishina Tomohiro , Ebi Hiromichi , Taniguchi Hiroya , Nonomura Norio , Sunakawa Yu , Shiozawa Manabu , Yamazaki Kentaro , Boku Shogen , Bando Hideaki , Shiraishi Yuichi , Kobayashi Maki , Goto Hiroki , Sato Akihiro , Fujii Satoshi , Yoshino Takayuki , Nakamura Yoshiaki 
Published: August 2024

Abstract

Purpose:
HER2-targeted therapies in ERBB2-amplified metastatic colorectal cancer (mCRC) are effective; however, a notable portion of patients do not respond to treatment, and secondary resistance occurs in most patients receiving these treatments. The purpose of this study was to investigate determinants of treatment efficacy and resistance in patients with ERBB2-amplified mCRC who received HER2-targeted therapy by analyzing multiomics data.

Experimental Design:
We investigated genomic data from a nationwide large cancer genomic screening project, the SCRUM-Japan project. We analyzed paired genome and transcriptome data of tissue and genomic data of ctDNA collected pre- and postprogression in patients enrolled in the related trial, TRIUMPH, in ERBB2-amplified mCRC.

Results:
In 155 patients with ERBB2-amplified solid tumors who received HER2-targeted therapy based on the SCRUM-Japan project, the objective response rate was 50%, 51%, and 35% in ERBB2 wild-type, variant of unknown significance, and pathogenic variant groups, respectively. In the paired genome and transcriptome data analyses in TRIUMPH, we identified the novel splicing-associated variant c.644-66_-2del in one of the 11 patients with paired whole-exome sequencing and whole-transcriptome sequencing data sets, which lacks the binding domain of pertuzumab, in progressed metastatic tumor as a variant with potential pathogenicity. The time-course ctDNA analysis detected c.644-66_-2del as an acquired variant.

Conclusions:
This study highlighted the importance of ERBB2 genomic status when evaluating the efficacy of HER2-targeted therapies in ERBB2-amplified mCRC. The identification of a novel splicing-associated variant may provide insights into potential mechanisms of treatment resistance. Furthermore, we demonstrated the utility of ctDNA to follow the acquired genomic status of mCRC tumors.
Chemotherapy Drives Tertiary Lymphoid Structures That Correlate with ICI-Responsive TCF1+CD8+ T Cells in Metastatic Ovarian Cancer
Authors: Lanickova Tereza , Hensler Michal , Kasikova Lenka , Vosahlikova Sarka , Angelidou Artemis , Pasulka Josef , Griebler Hannah , Drozenova Jana , Mojzisova Katerina , Vankerckhoven Ann , Laco Jan , Ryska Ales , Dundr Pavel , Kocian Roman , Cibula David , Brtnicky Tomas , Skapa Petr , Jacob Francis , Kovar Marek , Praznovec Ivan , McNeish Iain A. , Halaska Michal J. , Rob Lukas , Coosemans An , Orsulic Sandra , Galluzzi Lorenzo , Spisek Radek , Fucikova Jitka 
Published: August 2024

Abstract

Purpose:
Patients with high-grade serous ovarian carcinoma (HGSOC) are virtually insensitive to immune checkpoint inhibitors (ICI) employed as standalone therapeutics, at least in part reflecting microenvironmental immunosuppression. Thus, conventional chemotherapeutics and targeted anticancer agents that not only mediate cytotoxic effects but also promote the recruitment of immune effector cells to the HGSOC microenvironment stand out as promising combinatorial partners for ICIs in this oncological indication.

Experimental Design:
We harnessed a variety of transcriptomic, spatial, and functional assays to characterize the differential impact of neoadjuvant paclitaxel-carboplatin on the immunological configuration of paired primary and metastatic HGSOC biopsies as compared to neoadjuvant chemotherapy (NACT)-naïve HGSOC samples from five independent patient cohorts.

Results:
We found NACT-driven endoplasmic reticulum stress and calreticulin exposure in metastatic HGSOC lesions culminates with the establishment of a dense immune infiltrate including follicular T cells (TFH cells), a prerequisite for mature tertiary lymphoid structure (TLS) formation. In this context, TLS maturation was associated with an increased intratumoral density of ICI-sensitive TCF1+PD1+ CD8+ T cells over their ICI-insensitive TIM-3+PD1+ counterparts. Consistent with this notion, chemotherapy coupled with a PD1-targeting ICI provided a significant survival benefit over either therapeutic approach in syngeneic models of HGSOC bearing high (but not low) tumor mutational burden.

Conclusions:
Altogether, our findings suggest that NACT promotes TLS formation and maturation in HGSOC lesions, de facto preserving an intratumoral ICI-sensitive T-cell phenotype. These observations emphasize the role of rational design, especially relative to the administration schedule, for clinical trials testing chemotherapy plus ICIs in patients with HGSOC.
See related commentary by Bravo Melgar and Laoui, p. 10
Public Governance and Democracy: the role of Brazil’s Office of The Comptroller General in the promotion of Social Accountability
Authors: Teixeira Graziela Dias , Sena Lucas , Silva Suylan de Almeida Midlej e 
Published: August 2024

Este artigo busca analisar a atuação da Controladoria Geral da União (CGU) no governo Bolsonaro, no que se refere ao incentivo à accountability social, bem como identificar as perspectivas de construção de processos democráticos com a sociedade civil a partir da nova estrutura da CGU, que está sendo alterada desde o início do governo Lula. Diante disso, são estudadas três organizações da sociedade civil que têm atuado em parceria com a CGU: o Instituto de Fiscalização e Controle (IFC), o Observatório Social do Brasil (OSB) e os Amigos Associados de Ribeirão Bonito (Amarribo). Além disso, utiliza-se metodologia qualitativa baseada em análise documental, revisão bibliográfica e entrevistas semiestruturadas realizadas com burocratas da CGU e com representantes das organizações da sociedade civil. A governança pública tem sido uma preocupação compartilhada na relação entre Estado e sociedade, em especial com a CGU se destacando na promoção do controle social. Apesar dos avanços observados, há desafios gerados por problemas estruturais, dificuldades de financiamento e desarticulação das ações em rede, o que se agravou com a pandemia de Covid-19 e o desmonte de políticas gerado pelo governo anterior. Porém, a partir de 2023, a CGU, com uma nova estrutura institucional, tem atuado no sentido de se reaproximar da sociedade civil, procurando formas e estratégias para estimular a accountability social.