bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cross-Talk between HLA Class I and TLR4 Mediates P-Selectin Surface Expression and Monocyte Capture to Human Endothelial Cells
Authors: Jin Yi-Ping , Nevarez-Mejia Jessica , Terry Allyson Q , Sosa Rebecca A , Heidt Sebastiaan , Valenzuela Nicole M , Rozengurt Enrique , Reed Elaine F 
Published: October 2022

Abstract
Donor-specific HLA Abs contribute to Ab-mediated rejection (AMR) by binding to HLA molecules on endothelial cells (ECs) and triggering intracellular signaling, leading to EC activation and leukocyte recruitment. The molecular mechanisms involving donor-specific HLA Ab–mediated EC activation and leukocyte recruitment remain incompletely understood. In this study, we determined whether TLRs act as coreceptors for HLA class I (HLA I) in ECs. We found that human aortic ECs express TLR3, TLR4, TLR6, and TLR10, but only TLR4 was detected on the EC surface. Consequently, we performed coimmunoprecipitation experiments to examine complex formation between HLA I and TLR4. Stimulation of human ECs with HLA Ab increased the amount of complex formation between HLA I and TLR4. Reciprocal coimmunoprecipitation with a TLR4 Ab confirmed that the crosslinking of HLA I increased complex formation between TLR4 and HLA I. Knockdown of TLR4 or MyD88 with small interfering RNAs inhibited HLA I Ab–stimulated P-selectin expression, von Willebrand factor release, and monocyte recruitment on ECs. Our results show that TLR4 is a novel coreceptor for HLA I to stimulate monocyte recruitment on activated ECs. Taken together with our previous published results, we propose that HLA I molecules form two separate signaling complexes at the EC surface, that is, with TLR4 to upregulate P-selectin surface expression and capture of monocytes to human ECs and integrin β4 to induce mTOR-dependent firm monocyte adhesion via ICAM-1 clustering on ECs, two processes implicated in Ab-mediated rejection.
Unique Cell Subpopulations and Disease Progression Markers in Canines with Atopic Dermatitis
Authors: Sparling Brandi A , Moss Nicholas , Kaur Gagandeep , Clark David , Hawkins R David , Drechsler Yvonne 
Published: October 2022

Abstract
Atopic dermatitis (AD) is a common pruritic inflammatory skin disease with unclear molecular and cellular contributions behind the complex etiology. To unravel these differences between healthy control and AD skin we employed single-cell transcriptomics, utilizing the canine AD model for its resemblance to human clinical and molecular phenotypes. In this study, we show that there are overall increases in keratinocytes and T cells and decreases in fibroblast populations in AD dogs. Within immune cell types, we identified an enriched γδ T cell population in AD, which may contribute to cutaneous inflammation. A prominent IL26-positive fibroblast subpopulation in AD was detected, which may activate neighboring cells in the dermal–epidermal niche. Lastly, by comparing dogs with different disease severities, we found genes that follow disease progression and may serve as potential biomarkers. In this study, we characterized key AD cell types and cellular processes that can be further leveraged in diagnosis and treatment.
Modification of the HLA-A*24:02 Peptide Binding Pocket Enhances Cognate Peptide-Binding Capacity and Antigen-Specific T Cell Activation
Authors: Murata Kenji , Ly Dalam , Saijo Hiroshi , Matsunaga Yukiko , Sugata Kenji , Ihara Fumie , Oryoji Daisuke , Ohashi Yota , Saso Kayoko , Wang Chung-Hsi , Zheng Evey Y F , Burt Brian D , Butler Marcus O , Hirano Naoto 
Published: October 2022

Abstract
The immunogenicity of a T cell Ag is correlated with the ability of its antigenic epitope to bind HLA and be stably presented to T cells. This presents a challenge for the development of effective cancer immunotherapies, as many self-derived tumor-associated epitopes elicit weak T cell responses, in part due to weak binding affinity to HLA. Traditional methods to increase peptide–HLA binding affinity involve modifying the peptide to reflect HLA allele binding preferences. Using a different approach, we sought to analyze whether the immunogenicity of wild-type peptides could be altered through modification of the HLA binding pocket. After analyzing HLA class I peptide binding pocket alignments, we identified an alanine 81 to leucine (A81L) modification within the F binding pocket of HLA-A*24:02 that was found to heighten the ability of artificial APCs to retain and present HLA-A*24:02–restricted peptides, resulting in increased T cell responses while retaining Ag specificity. This modification led to increased peptide exchange efficiencies for enhanced detection of low-avidity T cells and, when expressed on artificial APCs, resulted in greater expansion of Ag-specific T cells from melanoma-derived tumor-infiltrating lymphocytes. Our study provides an example of how modifications to the HLA binding pocket can enhance wild-type cognate peptide presentation to heighten T cell activation.
Novel Lymphocytic Choriomeningitis Virus Strain Sustains Abundant Exhausted Progenitor CD8 T Cells without Systemic Viremia
Authors: Beura Lalit K , Scott Milcah C , Pierson Mark J , Joag Vineet , Wijeyesinghe Sathi , Semler Matthew R , Quarnstrom Clare F , Busman-Sahay Kathleen , Estes Jacob D , Hamilton Sara E , Vezys Vaiva , O’Connor David H , Masopust David 
Published: October 2022

Abstract
Lymphocytic choriomeningitis virus (LCMV) is the prototypic arenavirus and a natural mouse pathogen. LCMV-Armstrong, an acutely resolved strain, and LCMV-clone 13, a mutant that establishes chronic infection, have provided contrasting infection models that continue to inform the fundamental biology of T cell differentiation, regulation of exhaustion, and response to checkpoint blockade. In this study, we report the isolation and characterization of LCMV-Minnesota (LCMV-MN), which was naturally transmitted to laboratory mice upon cohousing with pet shop mice and shares 80–95% amino acid homology with previously characterized LCMV strains. Infection of laboratory mice with purified LCMV-MN resulted in viral persistence that was intermediate between LCMV-Armstrong and -clone 13, with widely disseminated viral replication and viremia that was controlled within 15–30 d, unless CD4 T cells were depleted prior to infection. LCMV-MN–responding CD8+ T cells biased differentiation toward the recently described programmed death-1 (PD-1)+CXCR5+Tim-3lo stemlike CD8+ T cell population (also referred to as progenitor exhausted T cells) that effectuates responses to PD-1 blockade checkpoint inhibition, a therapy that rejuvenates responses against chronic infections and cancer. This subset resembled previously characterized PD-1+TCF1+ stemlike CD8+ T cells by transcriptional, phenotypic, and functional assays, yet was atypically abundant. LCMV-MN may provide a tool to better understand the breadth of immune responses in different settings of chronic Ag stimulation as well as the ontogeny of progenitor exhausted T cells and the regulation of responsiveness to PD-1 blockade.
Complement Is Required for Microbe-Driven Induction of Th17 and Periodontitis
Authors: Wang Hui , Ideguchi Hidetaka , Kajikawa Tetsuhiro , Mastellos Dimitrios C , Lambris John D , Hajishengallis George 
Published: October 2022

Abstract
In both mice and humans, complement and Th17 cells have been implicated in periodontitis, an oral microbiota-driven inflammatory disease associated with systemic disorders. A recent clinical trial showed that a complement C3 inhibitor (AMY-101) causes sustainable resolution of periodontal inflammation, the main effector of tissue destruction in this oral disease. Although both complement and Th17 are required for periodontitis, it is uncertain how these immune components cooperate in disease development. In this study, we dissected the complement–Th17 relationship in the setting of ligature-induced periodontitis (LIP), a model that previously established that microbial dysbiosis drives Th17 cell expansion and periodontal bone loss. Complement was readily activated in the periodontal tissue of LIP-subjected mice but not when the mice were placed on broad-spectrum antibiotics. Microbiota-induced complement activation generated critical cytokines, IL-6 and IL-23, which are required for Th17 cell expansion. These cytokines as well as Th17 accumulation and IL-17 expression were significantly suppressed in LIP-subjected C3-deficient mice relative to wild-type controls. As IL-23 has been extensively studied in periodontitis, we focused on IL-6 and showed that LIP-induced IL-17 and bone loss required intact IL-6 receptor signaling in the periodontium. LIP-induced IL-6 was predominantly produced by gingival epithelial cells that upregulated C3a receptor upon LIP challenge. Experiments in human gingival epithelial cells showed that C3a upregulated IL-6 production in cooperation with microbial stimuli that upregulated C3a receptor expression in ERK1/2- and JNK-dependent manner. In conclusion, complement links the periodontal microbiota challenge to Th17 cell accumulation and thus integrates complement- and Th17-driven immunopathology in periodontitis.
Progressive Loss of Donor-Reactive CD4+ Effector Memory T Cells due to Apoptosis Underlies Donor-Specific Hyporesponsiveness in Stable Renal Transplant Recipients
Authors: van der List Amy C J , Litjens Nicolle H R , Klepper Mariska , Prevoo Fréderique , Betjes Michiel G H 
Published: October 2022

Abstract
Following kidney transplantation, donor-specific hyporesponsiveness (DSH) may develop, defined as a lowered response of alloreactive T cells, specifically directed to donor Ag. This study aimed to characterize the nature of DSH through multiparameter flow cytometric assays measuring changes in phenotype and function of donor-reactive T cells after transplantation. This study characterized donor-reactive T cells, identified by CD137 expression, from the peripheral blood of stable human kidney transplant recipients (n = 47) before, at 3–5 y after, and &gt;5 y after transplantation. The phenotype (T cell subset, differentiation status, and transcription factor expression) and function (proinflammatory cytokine production) of CD4+ and CD8+ donor-reactive CD137+ T cells was evaluated by both supervised and unsupervised analyses. Results demonstrated a decline in CD4+ donor-reactive T cells within the first 3–5 y after transplantation. Predominantly, the population of effector memory T cells capable of producing two or more proinflammatory cytokines was affected. This decline was strongly correlated with reduced proliferation of CD4+ T cells to donor Ag. The donor-reactive CD8+ T cells declined substantially only after &gt;10 y. The frequency of T cells reactive to unrelated alloantigens did not alter significantly after transplantation, excluding an aspecific effect of immunosuppressive medication. After transplantation, an increase in donor Ag-induced apoptosis was found, specifically within the donor-reactive CD4+ memory T cell subsets. In conclusion, a significant decrease in donor-reactive polyfunctional effector memory CD4+ T cells underlies the development of DSH in kidney transplant recipients, which is likely mediated by specific activation-induced cell death.
Uterine NK Cells Ace an “A” in Education: NKG2A Sets Up Crucial Functions at the Maternal–Fetal Interface
Authors: Colucci Francesco 
Published: October 2022

Abstract
I argue in this review that reproduction was a driving force in the evolution of NK cell education, which is set by interactions between inhibitory receptors and self-MHC. Maternal lymphocytes also interact with allogeneic MHC on fetal trophoblast cells. How the maternal immune system tolerate the semiallogeneic fetus is a fascinating question. But it may be the wrong question. Tissue lymphocytes, like uterine NK cells, do not attack the mismatched fetus and its placenta. Instead, they help the local vasculature to tolerate changes necessary to nourish the fetus. Education of uterine NK cells, driven by the ancient CD94:NKG2A inhibitory receptor and self-MHC, sets them up to deliver these key functions at the maternal–fetal interface.
IL-4-Induced Quiescence of Resting Naive B Cells Is Disrupted in Systemic Lupus Erythematosus
Authors: Gao Min , Liu Shanrun , Chatham W Winn , Mountz John D , Hsu Hui-Chen 
Published: October 2022

Abstract
Activated naive (aNAV) B cells have been shown to be the precursor of the CD11c+T-bet+ IgD−CD27− double-negative (DN)2 or atypical memory (aMEM) B cells in systemic lupus erythematosus (SLE). To determine factors that maintain resting naive (rNAV) B cells, the transcriptomic program in naive (IGHD+IGHM+) B cells in human healthy control subjects (HC) and subjects with SLE was analyzed by single-cell RNA-sequencing analysis. In HC, naive B cells expressed IL-4 pathway genes, whereas in SLE, naive B cells expressed type I IFN-stimulated genes (ISGs). In HC, aNAV B cells exhibited upregulation of the gene signature of germinal center and classical memory (cMEM) B cells. In contrast, in SLE, aNAV B cells expressed signature genes of aMEM. In vitro exposure of SLE B cells to IL-4 promoted B cell development into CD27+CD38+ plasmablasts/plasma and IgD−CD27+ cMEM B cells. The same treatment blocked the development of CD11c+Tbet+ aNAV and DN2 B cells and preserved DN B cells as CD11c−Tbet− DN1 B cells. Lower expression of IL-4R and increased intracellular IFN-β in naive B cells was correlated with the accumulation of CD21−IgD− B cells and the development of anti-Smith and anti-DNA autoantibodies in patients with SLE (n = 47). Our results show that IL-4R and type I IFN signaling in naive B cells induce the development of distinct lineages of cMEM versus aMEM B cells, respectively. Furthermore, diminished IL-4R signaling shifted activated B cell development from the DN1 to the DN2 trajectory in patients with SLE. Therapies that enhance IL-4R signaling may be beneficial for ISGhi SLE patients.
Neutrophilic Pleuritis Is a Severe Complication of Klebsiella pneumoniae Pneumonia in Old Mice
Authors: Hollwedel Femke D , Maus Regina , Stolper Jennifer , Jonigk Danny , Hildebrand Christina B , Welte Tobias , Brandenberger Christina , Maus Ulrich A 
Published: October 2022

Abstract
The pathomechanisms underlying the frequently observed fatal outcome of Klebsiella pneumoniae pneumonia in elderly patients are understudied. In this study, we examined the early antibacterial immune response in young mice (age 2–3 mo) as compared with old mice (age 18–19 mo) postinfection with K. pneumoniae. Old mice exhibited significantly higher bacterial loads in lungs and bacteremia as early as 24 h postinfection compared with young mice, with neutrophilic pleuritis nearly exclusively developing in old but not young mice. Moreover, we observed heavily increased cytokine responses in lungs and pleural spaces along with increased mortality in old mice. Mechanistically, Nlrp3 inflammasome activation and caspase-1–dependent IL-1β secretion contributed to the observed hyperinflammation, which decreased upon caspase-1 inhibitor treatment of K. pneumoniae–infected old mice. Irradiated old mice transplanted with the bone marrow of young mice did not show hyperinflammation or early bacteremia in response to K. pneumoniae. Collectively, the accentuated lung pathology observed in K. pneumoniae–infected old mice appears to be due to regulatory defects of the bone marrow but not the lung, while involving dysregulated activation of the Nlrp3/caspase-1/IL-1β axis.
Altered-Self MHC Class I Sensing via Functionally Disparate Paired NK Cell Receptors Counters Murine Cytomegalovirus gp34–Mediated Immune Evasion
Authors: Cronk John M , Dziewulska Karolina H , Puchalski Patryk , Crittenden Rowena B , Hammarskjöld Marie-Louise , Brown Michael G 
Published: October 2022

Abstract
The murine CMV (MCMV) immunoevasin m04/gp34 escorts MHC class I (MHC I) molecules to the surface of infected cells where these complexes bind Ly49 inhibitory receptors (IRs) and prevent NK cell attack. Nonetheless, certain self–MHC I–binding Ly49 activating and inhibitory receptors are able to promote robust NK cell expansion and antiviral immunity during MCMV infection. A basis for MHC I-dependent NK cell sensing of MCMV-infected targets and control of MCMV infection however remains unclear. In this study, we discovered that the Ly49R activation receptor is selectively triggered during MCMV infection on antiviral NK cells licensed by the Ly49G2 IR. Ly49R activating receptor recognition of MCMV-infected targets is dependent on MHC I Dk and MCMV gp34 expression. Remarkably, although Ly49R is critical for Ly49G2-dependent antiviral immunity, blockade of the activation receptor in Ly49G2-deficient mice has no impact on virus control, suggesting that paired Ly49G2 MCMV sensing might enable Ly49R+ NK cells to better engage viral targets. Indeed, MCMV gp34 facilitates Ly49G2 binding to infected cells, and the IR is required to counter gp34-mediated immune evasion. A specific requirement for Ly49G2 in antiviral immunity is further explained by its capacity to license cytokine receptor signaling pathways and enhance Ly49R+ NK cell proliferation during infection. These findings advance our understanding of the molecular basis for functionally disparate self-receptor enhancement of antiviral NK cell immunity.
Assessment of motor function by development of a new program in community-dwelling elderly
Authors: Muragod Anil R. , Kanabur Vijayalaxmi 
Published: October 2022

OBJECTIVES:
The present study intended to identify community elderly at risk for Motor dysfunction by developing a new programme.

METHODOLOGY:
Twenty-one Individuals aged ≥60 years were assessed using Five minutes sit to stand test (FTSTST) for lower limb strength, mobility; The Functional Gait Index (FGI) assessed Balance, Gait; Older people's Quality of Life Scale-Brief (OPQL-Brief) assessed Quality of Life.

RESULTS:
One way ANOVA (P < 0.05) was used for Comparison of gender specific scores of FTSTST, FGI, OPQL-Brief the first two had no significant change but the third one showed significantly higher difference in males (P = 0.0004). Correlation analysis between age and all three outcome measures was significantly positive for FTSTST, significantly negative for FGI; OPQL-Brief scale showed non-significant negative correlation.

CONCLUSION:
This study provides evidence that the new programme developed is effective in assessing motor dysfunction in community elderly.
Literatur Review Pengaruh Discharge Planning Dengan Kualitas Hidup Pasien Stroke
Authors: Sitompul Osrika , Ida Faridah  , Yati Afiyanti  
Published: October 2022

Stroke adalah penyebab tertinggi kematian dan menimbulkan kelemahan anggota gerak yang menyebabkan keterbatasan gerak dan beraktifitas. Tujuan dari kajian literatur adalah untuk mengetahui pengaruh Discharge Planning dengan Kualitas Hidup Pasien Stroke di Fasilitas Kesehatan. Metode Penelitian: Penelitian yang dilakukan dengan metode kajian literature. Penelusuran literature didapatkan dari data base online Google Schollar, PubMed, dan Elsiver, dari tahun 2016-2020 untuk artikel jurnal, dengan menggunakan kata kunci: Discharge planning, Kualitas hidup dan Pasien stroke. Setelah dilakukan search didapatkan 245 artikel terdiri dari 245 artikel pada Google Schollar, PUBMED, dan Elsiver, yang sesuai dengan kriteria inklusi dan eksliusi ditemukan 10 artikel. Hasil: Setelah dilakukan pembahasan pada ke-10 artikel tersebut didapatkan bahwa pengaruh discharge planning sangat baik, serta dukungan keluarga akan menimbulkan dampak yaitu memperbaiki kualitas hidup pasien stroke yaitu dapat meningkatkan aktifitas, pencegahan komplikasi penyakit dan kepatuhan pasien dalam mengkonsumsi obat dan rutin menjalankan kontrol penyakitnya.
Influence of Self-Care Awareness on the Physical Well-Being of African Religious Women in Karen, Nairobi, Kenya: A Psycho - Educational Intervention
Authors: Uche Anthonia Odilile 
Published: October 2022

Purpose: This study explored how self-care awareness practice influences the physical well-being of African religious Women of the Catholic Church in Karen, Nairobi-Kenya.
Methodology: Qualitative paradigm and phenomenological design were used. Target was all African religious women living in Karen. Maximum variation sampling technique was used to select four religious women’s congregations that participated in the study. Criterion sampling technique was used to select 10 participants for the study, comprising of 4 religious women, 2 religious brothers, 2 priests and 2 lay persons.
Methodology: Findings revealed that, religious women in Karen-Nairobi were prevented from adequate self-caring due to overwork, negligence, wrong concept of religious life, poor remuneration, poverty, influence of entrenched gender role, inability to integrate prayer life, the apostolate and community life as well as a misunderstanding of the meaning of self-care.
Unique Contribution to Theory, Policy and Practice: This study concluded that the lack of self-care awareness among African Catholic Religious Women in Karen affected their physical well-being. Suggested remedial interventions included awareness creation, greater access to education, designing and use of a self-care curriculum, regular supervision of self-care practice by superiors, the replacement of life-diminishing structures in the religious life and the Church, revision of life and establishing economic sustainability.
ĐÁNH GIÁ HIỆN TRẠNG SỬ DỤNG ĐẤT NĂM 2021 THỊ TRẤN BẰNG LŨNG – HUYỆN CHỢ ĐỒN – TỈNH BẮC KẠN
Authors: Nguyễn Thị Hồng 
Published: October 2022

Nghiên cứu đánh giá hiện trạng và biến động diện tích các lọai hình sử dụng đất thị trấn Bằng Lũng, huyện Chợ Đồn, tỉnh Bắc Kạn năm 2021. Trong nghiên cứu, tác giả sử dụng phương pháp thu thập và tổng hợp số liệu; từ đó xử lý, phân tích và so sánh kết quả; kết hợp với điều tra để khoanh vẽ, chỉnh lý trên bản đồ bằng phần mềm Microstation. Kết quả cho thấy tổng diện tích đất tự nhiên toàn thị trấn là 2,496.39 ha, trong đó, diện tích đất nông nghiệp là 2,069.46 ha, chiếm 82.90%; diện tích đất phi nông nghiệp là 250.57 ha, chiếm 10.04%; diện tích đất chưa sử dụng là 174.69 ha, chiếm 7.06%. Thị trấn Bằng Lũng có biến động diện tích đất theo chiều hướng: giảm diện tích đất nông nghiệp so với năm 2014 do chuyển mục đích sang đất phi nông nghiệp, chủ yếu là xây dựng cơ sở hạ tầng; diện tích nhóm đất phi nông nghiệp tăng so với năm 2014 do đất nông nghiệp và đất chưa sử dụng chuyển sang. Trên cơ sở đánh giá hiện trạng sử dụng đất, nghiên cứu đề xuất các giải pháp tăng cường về quản lý nâng cao hiệu quả sử dụng đất.