bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effective inhibition of PDCoV infection in chimeric APN gene-edited neonatal pigs
Authors: Li Jizong , Zhou Jian , Zhang Tianyi , Wu Heyong , Li Feng , Qi Chunyun , Fan Liyuan , Yuan Xuesong , Wang Wei , Guo Rongli , Fan Baochao , Tang Xiaochun , Pang Daxin , Ouyang Hongsheng , Xie Zicong , Li Bin 
Published: July 2024

ABSTRACT

Porcine deltacoronavirus (PDCoV), an emerging enteropathogenic coronavirus, is a serious threat to piglets and has zoonotic potential. Here, we aimed to further explore the role of aminopeptidase N (APN) as a receptor for PDCoV and test the inhibitory effect of a chimeric APN protein strategy on PDCoV infection. PK-15 cells and LLC-PK1 cells expressing chimeric APN were selected and infected with PDCoV. Viral replication was significantly decreased in these chimeric APN cells compared with that in control group cells. To further characterize the effect of the chimeric APN strategy on PDCoV infection
in vitro
, primary intestinal epithelial cells isolated from chimeric APN pigs were inoculated with PDCoV. Viral challenge of these cells led to decreased PDCoV infection. More importantly, virally challenged chimeric APN neonatal piglets displayed reduced viral load, significantly fewer microscopic lesions in the intestinal tissue, and no diarrhea. Taken together, these findings deepen our understanding of the mechanism of PDCoV infection and provide a valuable model for the production of disease-resistant animals.

IMPORTANCE
Porcine deltacoronavirus (PDCoV), an emerging enteropathogenic coronavirus, causes diarrhea in piglets and possesses the potential to infect humans. However, there are currently no effective measures for the prevention or control of PDCoV infection. Here, we have developed PK-15 cells, LLC-PK1 cells, and primary intestinal epithelial cells expressing chimeric APN, and viral challenge of these cells led to decreased PDCoV infection. Furthermore, virally challenged chimeric APN neonatal piglets displayed reduced viral load, significantly fewer microscopic lesions in the intestinal tissue, and no diarrhea. These data show that chimeric APN is a promising strategy to combat PDCoV infection.
cAMP signaling of
Bordetella
adenylate cyclase toxin blocks M-CSF triggered upregulation of iron acquisition receptors on differentiating CD14
+
monocytes
Authors: Ahmad Jawid Nazir , Sebo Peter 
Published: July 2024

ABSTRACT

Bordetella pertussis
infects the upper airways of humans and disarms host defense by the potent immuno-subversive activities of its pertussis (PT) and adenylate cyclase (CyaA) toxins. CyaA action near-instantly ablates the bactericidal activities of sentinel CR3-expressing myeloid phagocytes by hijacking cellular signaling pathways through the unregulated production of cAMP. Moreover, CyaA-elicited cAMP signaling also inhibits the macrophage colony-stimulating factor (M-CSF)-induced differentiation of incoming inflammatory monocytes into bactericidal macrophages. We show that CyaA/cAMP signaling via protein kinase A (PKA) downregulates the M-CSF-elicited expression of monocyte receptors for transferrin (CD71) and hemoglobin-haptoglobin (CD163), as well as the expression of heme oxygenase-1 (HO-1) involved in iron liberation from internalized heme. The impact of CyaA action on CD71 and CD163 levels in differentiating monocytes is largely alleviated by the histone deacetylase inhibitor trichostatin A (TSA), indicating that CyaA/cAMP signaling triggers epigenetic silencing of genes for micronutrient acquisition receptors. These results suggest a new mechanism by which
B. pertussis
evades host sentinel phagocytes to achieve proliferation on airway mucosa.

IMPORTANCE

To establish a productive infection of the nasopharyngeal mucosa and proliferate to sufficiently high numbers that trigger rhinitis and aerosol-mediated transmission, the pertussis agent
Bordetella pertussis
deploys several immunosuppressive protein toxins that compromise the sentinel functions of mucosa patrolling phagocytes. We show that cAMP signaling elicited by very low concentrations (22 pM) of
Bordetella
adenylate cyclase toxin downregulates the iron acquisition systems of CD14
+
monocytes. The resulting iron deprivation of iron, a key micronutrient, then represents an additional aspect of CyaA toxin action involved in the inhibition of differentiation of monocytes into the enlarged bactericidal macrophage cells. This corroborates the newly discovered paradigm of host defense evasion mechanisms employed by bacterial pathogens, where manipulation of cellular cAMP levels blocks monocyte to macrophage transition and replenishment of exhausted phagocytes, thereby contributing to the formation of a safe niche for pathogen proliferation and dissemination.
Marburg virus exploits the Rab11-mediated endocytic pathway in viral-particle production
Authors: Furuyama Wakako , Yamada Kento , Sakaguchi Miako , Marzi Andrea , Nanbo Asuka 
Published: July 2024

ABSTRACT

Filoviruses produce viral particles with characteristic filamentous morphology. The major viral matrix protein, VP40, is trafficked to the plasma membrane and promotes viral particle formation and subsequent viral egress. In the present study, we assessed the role of the small GTPase Rab11-mediated endocytic pathway in Marburg virus (MARV) particle formation and budding. Although Rab11 was predominantly localized in the perinuclear region, it exhibited a more diffuse distribution in the cytoplasm of cells transiently expressing MARV VP40. Rab11 was incorporated into MARV-like particles. Expression of the dominant-negative form of Rab11 and knockdown of Rab11 decreased the amount of VP40 fractions in the cell periphery. Moreover, downregulation of Rab11 moderately reduced the release of MARV-like particles and authentic MARV. We further demonstrated that VP40 induces the distribution of the microtubule network toward the cell periphery, which was partly associated with Rab11. Depolymerization of microtubules reduced the accumulation of VP40 in the cell periphery along with viral particle formation. VP40 physically interacted with α-tubulin, a major component of microtubules, but not with Rab11. Taken together, these results suggested that VP40 partly interacts with microtubules and facilitates their distribution toward the cell periphery, leading to the trafficking of transiently tethering Rab11-positive vesicles toward the cell surface. As we previously demonstrated the role of Rab11 in the formation of Ebola virus particles, the results here suggest that filoviruses in general exploit the vesicle-trafficking machinery for proper virus-particle formation and subsequent egress. These pathways may be a potential target for the development of pan-filovirus therapeutics.

IMPORTANCE
Filoviruses, including Marburg and Ebola viruses, produce distinct filamentous viral particles. Although it is well known that the major viral matrix protein of these viruses, VP40, is trafficked to the cell surface and promotes viral particle production, details regarding the associated molecular mechanisms remain unclear. To address this knowledge gap, we investigated the role of the small GTPase Rab11-mediated endocytic pathway in this process. Our findings revealed that Marburg virus exploits the Rab11-mediated vesicle-trafficking pathway for the release of virus-like particles and authentic virions in a microtubule network-dependent manner. Previous findings demonstrated that Rab11 is also involved in Ebola virus-particle production. Taken together, these data suggest that filoviruses, in general, may hijack the microtubule-dependent vesicle-trafficking machinery for productive replication. Therefore, this pathway presents as a potential target for the development of pan-filovirus therapeutics.
Determinants of microbial community structure in supraglacial pool sediments of monsoonal Tibetan Plateau
Authors: Fair Heather , Hamilton Trinity L. , Smiley Peter C. , Liu Qiao 
Published: July 2024

ABSTRACT

Supraglacial pools are prevalent on debris-covered mountain glaciers, yet only limited information is available on the microbial communities within these habitats. Our research questions for this preliminary study were: (1) What microbes occur in supraglacial pool sediments of monsoonal Tibet?; (2) Which abiotic and biotic habitat variables have the most influence on the microbial community structure?; and (3) Does microbial composition of supraglacial pool sediments differ from that of glacial-melt stream pool sediments? We collected microbial samples for 16S rRNA sequencing and invertebrates for enumeration and identification and measured 14 abiotic variables from 46 supraglacial pools and nine glacial-melt stream pools in 2018 and 2019. Generalized linear model analyses, small sample Akaike information criterion, and variable importance scores were used to identify the best predictor variables of microbial community structure. Multi-response permutation procedure (MRPP) was used to compare taxa composition between supraglacial pools and stream pools. The most abundant phyla in supraglacial pool sediments were Proteobacteria, Actinobacteria, Bacteroidota, Chloroflexi, and Cyanobacteria. Genera richness, indicator genera richness, and
Polaromonas
relative abundance were best predicted by Chironomidae larvae abundance.
Angustibacter
and
Oryzihumus
relative abundance were best predicted by pH,
Acidiphilium
relative abundance was best predicted by turbidity, and
Sphingomonas
relative abundance was best predicted by glacier zone. Taxa composition was similar between supraglacial and stream pools at the class, genus, and ASV taxonomic levels. Our results indicate that Chironomidae larvae may play a keystone species role in shaping bacterial communities of supraglacial pools on debris-covered glaciers.

IMPORTANCE

Glacier meltwater habitats (cryoconite holes, supraglacial pools, supraglacial ponds and lakes, glacial streams) and their biota have not been well-studied, especially on debris-covered glaciers in temperate monsoonal regions. Our study is the first to document the microbial community-habitat relationships in supraglacial pools on a debris-covered glacier in Tibet. Microbial genera richness, indicator genera richness, and
Polaromonas
relative abundance declined with increasing larval Chironomidae abundance, which is a novel finding that highlights the importance of larval insects in structuring microbial communities in supraglacial pools.
Balancing the oceanic Zn isotope budget: The key role of deep-sea pelagic sediments
Authors: Zhang Ganglan , Zhu Yangtao , Deng Yinan , Cao Jun , Wang Pengcong , Yang Ao , He Gaowen , Zhao Bin , Zhao Mingyu 
Published: July 2024

Abstract
Oxygenated deep-sea pelagic sediments with Fe-Mn–oxide particles represent a key oceanic oxic sink for transition metals in the modern ocean. However, the isotopic composition of authigenic Zn in the pelagic zone remains poorly constrained, which hampers our understanding of the global budget of Zn isotopes. Here, we analyzed the Zn isotopic compositions of two deep-sea pelagic sediment columns collected from the Pacific Ocean. The results show that authigenic Zn in deep-sea sediments is primarily hosted by the Fe-Mn (oxyhydr)oxides. The light Zn isotopic signatures (δ66Zn: −0.02‰ to 0.34‰, n = 42; computed as the per mille deviation of the 66Zn/64Zn ratio from the JMC-Lyon standard) observed in deep-sea sediments are completely different from the previously assumed values of ~1.0‰ based on the Zn isotopic compositions of Fe-Mn crusts and nodules. Based on this observation (Zn flux of deep-sea sediments = 5.3 × 108 mol yr–1), we propose a new, balanced global budget for Zn isotopes.
СО2 and СН4 Fluxes in Wetland Ecosystems of the Mezquital Valley, Central Mexico
Authors: García-Calderón N. E. , Fuentes-Romero E. , Ikkonen E. , Sidorova V. 
Published: July 2024

Abstract
We measured dark CO2 fluxes and CH4 emissions from two naturally vegetated ecosystems of the Mezquital Valley irrigated with wastewater from Mexico City. The ecosystems were characterized by high groundwater levels; the vegetation was represented mainly by saltgrass in the first plot and chairmaker’s bulrush in the second. A dark chamber technique was used for the study from August 2008 to June 2009. For the two studied plots, mean values (mean ± SE) for dark ecosystem CO2 fluxes (Rtot), soil CO2 emission (Rsoil), and heterotrophic respiration (Rhet) were 26 ± 5, 14 ± 3 and 12 ± 3 mg C m–2 h–1, respectively, The annual cumulative fluxes Rtot, Rsoil and Rhet equal to 234, 127 and 103 g C m–2 y–1, respectively. The contribution of Rsoil to Rtot, and Rhet to Rsoil varied significantly over the study period, with no clear relationship to seasonal dynamics. The observed low CO2 fluxes may be due to soil salinization resulting from wastewater flooding. The fluxes of CH4 were observed in the flooded plot, with peaks up to 370 µg C m–2 h–1. The fluxes of CH4 were significantly higher when plants were present in the measurement chamber than when there were no plants, confirming the important role of plant cover in CH4 transport. Unlike CH4 fluxes, CO2 fluxes show seasonal dynamics, mainly due to their strong dependence on temperature. The observed results may be useful for properly estimating the global C budget and the contribution of saline soils to C fluxes.
Case 327: Exogenous Lipoid Pneumonia
Authors: Decavèle Maxens , Pichon Jérémie , Fajac Anne , Milon Audrey , Antoine Martine , Gibelin Aude , Parrot Antoine , Fartoukh Muriel 
Published: July 2024

History A 58-year-old male patient with an active smoking status was admitted twice to the intensive care unit (ICU) of a tertiary referral thoracic center for severe hypercapnic acute respiratory failure and persistent bilateral chest radiograph opacities that were unchanged over the course of the two ICU admissions within a 3-month period. The patient had obesity (body mass index, 36), stage 3 vascular chronic renal insufficiency, and hebephrenic schizophrenia treated with haloperidol, carbamazepine, and cyamemazine. He reported chronic dyspnea on exertion, which worsened for 6 months. At the second ICU admission, the patient was afebrile, with a blood pressure of 160/72 mm Hg and pulse oximetry of 93% on 6 L/min oxygen therapy through a nonrebreathing mask. Physical examination showed signs of respiratory failure with wheezing and active abdominal expiration, and bilateral pulmonary crackles without chest pain, hemoptysis, clubbing, or signs of cardiac failure. The patient had no peripheral lymphadenopathy and no enlarged spleen. Blood gases (on 6 L/min oxygen) showed respiratory acidosis (pH, 7.15 [normal range, 7.38–7.42]; PaO2 level, 67 mm Hg [normal range, 80–100 mm Hg]; PaCO2 level, 102 mm Hg [normal range, 38–42 mm Hg]; bicarbonate [HCO3−], 29 mmol/L [normal range, 22–27 mmol/L]). Noninvasive ventilation was initiated. Imaging performed during the second ICU hospitalization included CT and MRI of the chest without contrast enhancement, and fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT.
Case 331
Authors: Umer Muhammad , Sagheer Usman , Furtado Wilfred , Shotwell Matthew , Joshi Jonathan , Shetty Mrinali , Kalra Dinesh K. 
Published: July 2024

History A 43-year-old male patient with no known past medical history presented to the emergency department with new-onset bitemporal headache, dizziness, and bilateral lower extremity weakness for 1 day. The patient denied chest pain, shortness of breath, cough, or recent exposure to sick individuals. He was not on any medications and denied alcohol or illicit drug use. Vital signs were unremarkable. Physical examination was notable for a left-sided pronator drift and bilateral dysmetria that was more pronounced on the left. Results of routine laboratory workup, including complete blood count, metabolic panel, and high-sensitivity troponin level, were normal. An electrocardiogram revealed sinus tachycardia with a heart rate of 102 beats per minute, T-wave inversions in the inferior leads, left axis deviation, incomplete right bundle branch block, and frequent premature ventricular contractions. A radiograph of the chest was unremarkable. CT of the head without contrast enhancement demonstrated no acute intracranial abnormities. MRI of the brain without contrast enhancement revealed multiple acute infarcts involving left posterior inferior cerebellar artery distribution, right cerebellar hemisphere, right mesial temporal lobe, and right posterior limb of the internal capsule. CT angiography of the head and neck showed an occlusion of the right posterior cerebral artery near its origin, with a trace of distal flow. Given that these findings were concerning for a cardioembolic etiology of acute ischemic stroke, transesophageal echocardiography was performed. This showed mild left ventricular systolic dysfunction with an ejection fraction of 40%, mild global hypokinesis, and an additional finding also seen at subsequent cardiac CT and MRI that will be disclosed in part 2 of the case. The patient was started on systemic anticoagulation and guideline-directed medical therapy for heart failure with reduced ejection fraction. CT of the chest showed no evidence of lymphadenopathy or abnormalities in the lung parenchyma or interstitium. Coronary CT angiography was performed ( Fig 1 ), followed by cardiac MRI ( Fig 2 ).
cUMP elicits interendothelial gap formation during Pseudomonas aeruginosa infection
Authors: deWeever Althea , Paudel Sunita S. , Zhou Chun , Francis C. Michael , Tambe Dhananjay T. , Frank Dara W. , Balczon Ron , Stevens Troy 
Published: July 2024

During pneumonia, bacteria utilize a virulence arsenal to communicate with host cells. The Pseudomonas aeruginosa T3SS directly introduces virulence molecules into the host cell cytoplasm. These molecules are enzymes that trigger interkingdom communication. One of the exoenzymes is a nucleotidyl cyclase that produces noncanonical cyclic nucleotides like cUMP. Little is known about how cUMP acts in the cell. Here we found that cUMP instigates pulmonary edema during Pseudomonas aeruginosa infection of the lung.
TGFβ1, SNAIL2, and PAPP‐A Expression in Placenta of Gestational Diabetes Mellitus Patients
Authors: He Yujing , Yang Xiyao , Wu Na 
Published: July 2024

Background: Gestational diabetes mellitus (GDM) is a pregnancy‐related diabetic condition that may cause serious complications. However, its pathogenesis remains unclear. Placental damage due to GDM may lead to several health issues that cannot be ignored. Thus, we aimed to identify the mechanisms underlying GDM by screening differentially expressed genes (DEGs) related to vascular endothelial cells in the GDM databases and verify the expression of these DEGs in the placentas of women afflicted by GDM.Methods: We used GDM microarray datasets integrated from the Gene Expression Omnibus (GEO) database. Functional annotation and protein–protein interaction (PPI) analyses were used to screen DEGs. Placental tissues from 20 pregnant women with GDM and 20 healthy pregnant women were collected, and differential gene expression in the placental tissues was verified via qRT‐PCR, western blotting, and immunofluorescence.Results: Bioinformatics analysis revealed three significant DEGs: SNAIL2, PAPP-A, and TGFβ1. These genes were all predicted to be underexpressed in patients with GDM. The results of qRT‐PCR, western blot, and immunofluorescence analyses indicated that SNAIL2 and PAPP‐A in the placenta tissue of patients with GDM were significantly underexpressed. However, TGFβ1 in the placenta tissues of GDM was significantly overexpressed.Conclusion: SNAIL2, TGFβ1, and PAPP‐A may affect the placentas of pregnant women with GDM, warranting further investigation.
Cervical Cancer Evades the Host Immune System through the Inhibition of Type I Interferon and CXCL9 by LIF
Authors: Bonfill-Teixidor Ester , Neva-Alejo Almudena , Arias Alexandra , Cuartas Isabel , Iurlaro Raffaella , Planas-Rigol Ester , Solé Laura , Pecharromán Irene , Cabrera Silvia , García Ángel , Garcia-Illescas David , Espinosa Lluís , Gil-Moreno Antonio , Oaknin Ana , Seoane Joan 
Published: July 2024

Abstract

Purpose:
Cervical cancer is a viral-associated tumor caused by the infection with the human papilloma virus. Cervical cancer is an immunogenic cancer that expresses viral antigens. Despite being immunogenic, cervical cancer does not fully respond to immune checkpoint inhibitors (ICI). LIF is a crucial cytokine in embryo implantation, involved in maternal tolerance that acts as an immunomodulatory factor in cancer. LIF is expressed in cervical cancer and high levels of LIF is associated with poor prognosis in cervical cancer.

Experimental Design:
We evaluated the impact of LIF on the immune response to ICI using primary plasmocytoid dendritic cells (pDC) and macrophage cultures, syngeneic animals and patient-derived models that recapitulate the human tumor microenvironment.

Results:
We found that the viral proteins E6 and E7 induce the expression of LIF via the NFκB pathway. The secreted LIF can then repress type I interferon expressed in pDCs and CXCL9 expressed in tumor-associated macrophages. Blockade of LIF promotes the induction of type I interferon and CXCL9 inducing the tumor infiltration of CD8 T cells. This results in the sensitization of the tumor to ICI. Importantly, we observed that patients with cervical cancer expressing high levels of LIF tend to be resistant to ICI.

Conclusions:
Our data show that the HPV virus induces the expression of LIF to provide a selective advantage to the tumor cell by generating local immunosuppression via the repression of type I interferon and CXCL9. Combinatory treatment with blocking antibodies against LIF and ICI could be effective against cervical cancer expressing high levels of LIF.
Pharmacogenomic Score Effectively Personalizes Treatment of Acute Myeloid Leukemia
Authors: Marrero Richard J. , Wu Huiyun , Cao Xueyuan , Parcha Phani Krishna , Elsayed Abdelrahman H. , Inaba Hiroto , Kuo Dennis John , Degar Barbara A. , Heym Kenneth , Taub Jeffrey W. , Lacayo Norman , Pui Ching-Hon , Ribeiro Raul C. , Rubnitz Jeffrey E. , Pounds Stanley B. , Lamba Jatinder K. 
Published: July 2024

Abstract

Purpose:
Cytarabine (also known as ara-C) has been the backbone of acute myeloid leukemia (AML) chemotherapy for more than five decades. Recent pharmacogenomics-based 10-SNP ara-C (ACS10) scores showed low ACS10 (≤0) to be associated with poor outcomes in patients with AML treated with standard chemotherapy. Here, we evaluated the ACS10 score in the context of three different induction I regimens in patients with pediatric AML.

Experimental Design:
ACS10 score groups (low, ≤0, or high, &gt;0) were evaluated for association with event-free survival (EFS) and overall survival (OS) by three randomized treatment arms in patients treated on the AML02 (NCT00136084) and AML08 (NCT00703820) clinical trials: AML02 low-dose ara-C (LDAC arm, n = 91), AML02 + AML08 high-dose ara-C (HDAC arm, n = 194), and AML08 clofarabine + ara-C (Clo/ara-C arm, n = 105) induction I regimens.

Results:
Within the low-ACS10 score (≤0) group, significantly improved EFS and OS were observed among patients treated with Clo/ara-C as compared with LDAC (EFS, HR = 0.45; 95% CI, 0.23–0.88; P = 0.020; OS, HR = 0.44; 95% CI, 0.19–0.99; P = 0.048). In contrast, within the high-ACS10 score group (score &gt;0), augmentation with Clo/ara-C was not favorable as compared with LDAC (Clo/ara-C vs. LDAC, EFS, HR = 1.95; 95% CI, 1.05–3.63; P = 0.035; OS, HR = 2.10; 95% CI, 0.96–4.59; P = 0.063). Personalization models predicted 9% improvement in the outcome in ACS10 score–based tailored induction (Clo/ara-C for low and LDAC for high-ACS10 score groups) as compared with nonpersonalized approaches (P &lt; 0.002).

Conclusions:
Our findings suggest that tailoring induction regimens using ACS10 scores can significantly improve outcomes in patients with AML. Given the SNPs are germline, preemptive genotyping can accelerate matching the most effective remission induction regimen.