bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of NK and NKT cells in the immunopathogenesis of HCV-induced hepatitis
Authors: Ahmad Ali , Alvarez Fernando 
Published: June 2004

AbstractNatural killer (NK) cells constitute the first line of host defense against invading pathogens. They usually become activated in an early phase of a viral infection. Liver is particularly enriched in NK cells, which are activated by hepatotropic viruses such as hepatitis C virus (HCV). The activated NK cells play an essential role in recruiting virus-specific T cells and in inducing antiviral immunity in liver. They also eliminate virus-infected hepatocytes directly by cytolytic mechanisms and indirectly by secreting cytokines, which induce an antiviral state in host cells. Therefore, optimally activated NK cells are important in limiting viral replication in this organ. This notion is supported by the observations that interferon treatment is effective in HCV-infected persons in whom it increases NK cell activity. Not surprisingly, HCV has evolved multiple strategies to counter host's NK cell response. Compromised NK cell functions have been reported in chronic HCV-infected individuals. It is ironic that activated NK cells may also contribute toward liver injury. Further studies are needed to understand the role of these cells in host defense and in liver pathology in HCV infections. Recent advances in understanding NK cell biology have opened new avenues for boosting innate and adaptive antiviral immune responses in HCV-infected individuals.
Eosinophils function as antigen-presenting cells
Authors: Shi Huan-Zhong 
Published: June 2004

AbstractEosinophils release lipid mediators, including leukotriene C4, platelet-activating factor, and liposins, and contain four distinct granule cationic proteins, major basic protein, eosinophil peroxidase, eosinophil cationic protein, and eosinophil-derived neurotoxin, which may cause dysfunction and destruction of other cells. Eosinophils are primarily thought of as terminal effectors of allergic responses and of parasite elimination. Eosinophils are characteristically present within the airway lumina of asthmatics, and these airway eosinophils have been induced in vivo to express major histocompatibility complex II (MHC-II) complexes and costimulatory molecules, which are required for T lymphocytes to be functionally activated. In in vitro experiments, eosinophils can process antigen and express the costimulatory molecules, and after cytokine-elicited induction of MHC-II, expression can function as antigen-presenting cells in stimulating T lymphocyte responses. Airway luminal eosinophils can migrate into draining paratracheal lymph nodes, localized to T cell-rich paracortical areas, and stimulate antigen-specific T cell proliferation in vivo within paratracheal lymph nodes, which was CD80- and CD86-dependent and limited to CD4+ T cells. Furthermore, eosinophils within the lumina of airways promote expansion of T helpr cell type 2 (Th2) by presenting antigen, suggesting that eosinophils actively modulate immune responses by amplifying Th2 cell responses.
HIV-1 compartmentalization in diverse leukocyte populations during antiretroviral therapy
Authors: Potter Simon J , Lemey Philippe , Achaz Guillaume , Chew Choo Beng , Vandamme Anne-Mieke , Dwyer Dominic E , Saksena Nitin K 
Published: June 2004

AbstractCD4+ T lymphocytes are the primary target of human immunodeficiency virus type 1 (HIV-1), but there is increasing evidence that other immune cells in the blood, including CD8+ T lymphocytes and monocytes, are also productively infected. The extent to which these additional cellular reservoirs contribute to ongoing immunodeficiency and viral persistence during therapy remains unclear. In this study, we conducted a detailed investigation of HIV-1 diversity and genetic structure in CD4+ T cells, CD8+ T cells, and monocytes of 13 patients receiving highly active antiretroviral therapy (HAART). Analysis of molecular variance and nonparametric tests performed on HIV-1 envelope sequences provided statistically significant evidence of viral compartmentalization in different leukocyte populations. Signature pattern analysis and predictions of coreceptor use provided no evidence that selection arising from viral tropism was responsible for the genetic structure observed. Analysis of viral genetic variation in different leukocyte populations demonstrated the action of founder effects as well as significant variation in the extent of genetic differentiation between subpopulations among patients. In the absence of evidence for leukocyte-specific selection, these features were supportive of a metapopulation model of HIV-1 replication as described previously among HIV-1 populations in the spleen. Compartmentalization of the virus in different leukocytes may have significant implications for current models of HIV-1 population genetics and contribute to the highly variable way in which drug resistance evolves in different individuals during HAART.
Functional plasticity of macrophages: reversible adaptation to changing microenvironments
Authors: Stout Robert D , Suttles Jill 
Published: June 2004

AbstractThere has been substantial research activity in the past decade directed at phenotyping macrophage lineages and defining macrophage functional subsets or patterns of activity. The emphasis over the past 2–3 years has been to divide macrophage functional patterns into type 1 (Th1-driven) or type 2 (Th2-driven) functions. However, a huge array of environmental factors (including cytokines, chemokines, pattern recognition receptors, hormones) differentially regulates macrophage response patterns, resulting in the display of numerous distinct, functional phenotypes. Upon stimulation, a macrophage does not display just a single set of functions but rather displays a progression of functional changes in response to the progressive changes in its microenvironment. The remarkable ability of monocytes and tissue macrophages to adapt to changes in their microenvironment challenges the thesis that macrophages displaying unique tissue-specific or response-specific, functional patterns represent distinct lineages. With the exception of mature osteoclasts and mature dendritic cells, evidence supporting stable differentiation as the basis for macrophage functionl heterogeneity is equivocal. The concept of whether macrophages develop into functional subsets as opposed to continuously adapting their functional pattern in response to the changing environment of a progressive inflammatory response is important to resolve from the perspectives of therapeutic targeting and understanding the role of macrophages in disease pathogenesis.
Role of endogenous IL-10 in LPS-induced STAT3 activation and IL-1 receptor antagonist gene expression
Authors: Carl Virginia S , Gautam Jitendra K , Comeau Laurey D , Smith Michael F 
Published: June 2004

AbstractThe regulation of secretory interleukin (IL)-1 receptor antagonist (sIL-1Ra) in response to IL-10 is unique. In contrast to most cytokines, the lipopolysaccharide (LPS)-induced expression of the sIL-1Ra gene is enhanced by concomitant treatment with IL-10. Cotreatment of RAW 264.7 cells with IL-10 + LPS resulted in at least a twofold increase in sIL-1Ra promoter activity and mRNA expression compared with LPS alone; IL-10 alone had no effect on promoter activity or mRNA expression. Examination of sIL-1Ra mRNA expression in bone marrow-derived macrophages (BMDM) resulted in identical results. Transfection of RAW 264.7 cells with the sIL-1Ra/luc reporter and a dominant-negative signal transducer and activator of transcripton (STAT)3 (Y705A) expression plasmid inhibited the enhanced response induced by exogenous IL-10 in the presence of LPS. The presence of a functional STAT3-bininding site within the proximal sIL-1Ra promoter was demonstrated. As IL-10 is produced by LPS-stimulated macrophages, a role for endogenously produced IL-10 in the response of the sIL-1Ra gene to LPS was suggested. This was confirmed in IL-10-deficient BMDM, which when compared with normal BMDM, had significantly decreased LPS-induced sIL-1Ra mRNA levels that could be restored by exogenously provided IL-10, which induced a fivefold increase of LPS-induced IL-1Ra mRNA in cells from IL-10−/− BMDM. Western blot analysis of phosphorylated STAT3 from wild-type and IL-10−/− BMDM and IL-10 neutralization experiments demonstrated a role for endogenously produced IL-10 in the LPS-induced STAT3 activity. Together, these results demonstrate that endogenously produced IL-10 plays a significant role in LPS-induced sIL-1Ra gene expression via the activation of STAT3.
Structural Characterization of Three Novel Rat OKL38 Transcripts, Their Tissue Distributions, and Their Regulation by Human Chorionic Gonadotropin
Authors: Ong Choon Kiat , Ng Chuan Young , Leong Caine , Ng Chee Pang , Ong Chye Sun , Nguyen Thi Thanh Tuyen , Huynh Hung 
Published: June 2004

Abstract
We previously identified a novel pregnancy-induced growth inhibitory gene, OKL38. To develop a rat model for further characterization of OKL38’s role in the initiation and progression of breast and ovarian cancer, we now report the cloning and characterization of three novel rat OKL38 cDNAs that are derived through alternative splicing and differential promoter usage. These three transcripts differ in their 5′ untranslated regions but share a common open reading frame that encoded for a 52-kDa protein. OKL38 is mapped to chromosome 19, spanning a region of approximately 15 kb, and contains eight exons. Differential expression of these three rat OKL38 transcripts was observed in liver, kidney, ovary, mammary gland, and uterus. In situ hybridization localized the rat OKL38 transcripts to the luminal epithelial cells of the rat mammary gland and to the granulosa cells in the rat ovary. In vivo studies showed that the RtOKL38-2.0 transcript and protein were regulated by human chorionic gonadotropin in the rat mammary gland and ovary. Importantly, overexpression of RtOKL38-enhanced green florescence protein fusion protein in Buffalo rat liver cells resulted in growth inhibition and cell death. Our present findings suggest that OKL38 may function as an effector for human chorionic gonadotropin protection against mammary carcinogenesis, and the availability of the three rat OKL38 cDNAs may help to elucidate the possible role of OKL38 in cellular growth, differentiation, and carcinogenesis.
Editorial: Consulting, Research, and Consulting Research
Authors: Shugan Steven M. 
Published: June 2004

Consulting and scholarly research often have very different objectives with respect to advancements in practice, theory, and observation (e.g., data collections). For example, consulting often emphasizes immediate benefits, specialized applications, and a focus on only the key variables. Scholarly research often emphasizes replicability, generalizability, and introducing previously uninvestigated variables. However, these activities complement each other, and each activity is important for the advancement of the other. Benefiting from that complementarity requires the literature to bridge knowledge gained from each activity. It is unnecessary for every researcher to try to bridge theory and practice by working on the interface between academics and practice. However, it is critical that some researchers do so. This issue of Marketing Science examines several excellent applications of Marketing Science that provide detailed microexaminations of the fundamental marketing practices that we seek to understand and improve. Beyond demonstrating how to solve specific problems in practice, in my opinion, the articles and commentaries in this issue also illustrate at least the following ideas: Short-term tactics can produce significant short-term advantages. Existing models in the literature can be useful with proper implementation. State-of-the-art research is most useful for infrequent decisions. Finally, knowing the decision-making context is essential for determining which variables to include in the analysis.
Brain- and Heart-Type Fatty Acid-Binding Proteins in the Brain: Tissue Distribution and Clinical Utility
Authors: Pelsers Maurice M A L , Hanhoff Thorsten , Van der Voort Daniëlle , Arts Baer , Peters Maarten , Ponds Rudolf , Honig Adriaan , Rudzinski Wojtek , Spener Friedrich , de Kruijk Jelle R , Twijnstra Albert , Hermens Wim T , Menheere Paul P C A , Glatz Jan F C 
Published: June 2004

AbstractBackground: Detection of brain injury by serum markers is not a standard procedure in clinical practice, although several proteins, such as S100B, neuron-specific enolase (NSE), myelin basic protein, and glial fibrillary acidic protein, show promising results. We investigated the tissue distribution of brain- and heart-type fatty acid-binding proteins (B-FABP and H-FABP) in segments of the human brain and the potential of either protein to serve as plasma marker for diagnosis of brain injury.Methods: B-FABP and H-FABP were measured immunochemically in autopsy samples of the brain (n = 6) and in serum samples from (a) patients with mild traumatic brain injury (MTBI; n = 130) and (b) depressed patients undergoing bilateral electroconvulsive therapy (ECT; n = 14). The protein markers S100B and NSE were measured for comparison. Reference values of B-FABP and H-FABP were established in healthy individuals (n = 92).Results: The frontal, temporal, and occipital lobes, the striatum, the pons, and the cerebellum had different tissue concentrations of B-FABP and of H-FABP. B-FABP ranged from 0.8 μg/g wet weight in striatum tissue to 3.1 μg/g in frontal lobe. H-FABP was markedly higher, ranging from 16.2 μg/g wet weight in cerebellum tissue to 39.5 μg/g in pons. No B-FABP was detected in serum from healthy donors. H-FABP serum reference value was 6 μg/L. In the MTBI study, serum B-FABP was increased in 68% and H-FABP in 70% of patients compared with S100B (increased in 45%) and NSE (increased in 51% of patients). In ECT, serum B-FABP was increased in 6% of all samples (2 of 14 patients), whereas H-FABP was above its upper reference limit (6 μg/L) in 17% of all samples (8 of 14 patients), and S100B was above its upper reference limit (0.3 μg/L) in 0.4% of all samples.Conclusions: B-FABP and H-FABP patterns differ among brain tissues, with the highest concentrations in the frontal lobe and pons, respectively. However, in each part of the brain, the H-FABP concentration was at least 10 times higher than that of B-FABP. Patient studies indicate that B-FABP and H-FABP are more sensitive markers for minor brain injury than the currently used markers S100B and NSE.
Identification of Transthyretin Variants by Sequential Proteomic and Genomic Analysis
Authors: Bergen H Robert , Zeldenrust Steven R , Butz Malinda L , Snow Denise S , Dyck Peter J , Dyck P James B , Klein Christopher J , O’Brien John F , Thibodeau Stephen N , Muddiman David C 
Published: June 2004

Abstract
Background: Transthyretin-associated hereditary amyloidosis (ATTR) is an inherited disease in which variants in the primary structure of transthyretin (TTR; prealbumin) lead to the extracellular polymerization of insoluble protein fibrils, causing organ failure and ultimately death when major organs are involved. We have developed an integrated approach to molecular diagnosis with initial analysis of intact plasma TTR by electrospray ionization mass spectrometry (MS) and referral of positive samples for DNA sequence analysis and real-time PCR to confirm the common Gly6Ser polymorphism.
Methods: Samples from 6 patients previously diagnosed with ATTR and from 25 controls with (n = 15) or without (n = 10) polyneuropathy were analyzed in a blinded fashion for the presence of variant TTR. TTR protein was extracted with an immunoaffinity resin from 20 μL of archived plasma samples. The purified TTR was reduced with tris(2-carboxyethyl)phosphine and analyzed by MS. The appearance of two peaks (or a single peak shifted in mass indicative of a homozygous variant), including the wild-type mass of 13 761 Da, was indicative of the presence of a variant, and the individual was referred for DNA sequence analysis.
Results: MS analysis of intact reduced TTR correctly identified each of six samples known to contain variant TTR. These results were corroborated by subsequent DNA sequence analysis. Additionally, all Gly6Ser polymorphisms were correctly called based on the +30 mass shift and an equal relative abundance of the +30 polymorphism relative to wild-type TTR. No false-positive results were seen.
Conclusions: This referral method eliminates the necessity of sequencing most samples and allows screening for the familial forms of amyloidosis in a broad patient population in a timely fashion. This method correctly identified all previously known variants and also identified a novel variant, Val94Ala.
Elastic critical local buckling load and behavior of local buckling for cold‐formed lipped channel steel member under compression
Authors: Mitsui Kazuya , Ikarashi Kikuo 
Published: February 2024

AbstractThe objective of this study was to analyze the elastic critical local buckling of cold‐formed lipped channel sections using the energy method. A mechanical model and unique displacement functions simulating the local buckling behavior were proposed to consider the plate element interaction. Using the proposed mechanical mode, an analytical formula for local buckling that directly reflects the parameters of the channel member was proposed. Based on the proposed formula, the relationship between the cross‐sectional geometry and local buckling behavior was investigated. In addition, a simplified design equation was proposed. The reliability and effectiveness of the proposed equations were presented by comparing with the results of eigenvalue analysis based on the finite element method.
Progress in Anode Stability Improvement for Seawater Electrolysis to Produce Hydrogen
Authors: Zhang Sixie , Xu Wenwen , Chen Haocheng , Yang Qihao , Liu Hua , Bao Shanjun , Tian Ziqi , Slavcheva Evelina , Lu Zhiyi 
Published: February 2024

AbstractSeawater electrolysis for hydrogen production is a sustainable and economical approach that can mitigate the energy crisis and global warming issues. Although various catalysts/electrodes with excellent activities have been developed for high‐efficiency seawater electrolysis, their unsatisfactory durability, especially for anodes, severely impedes their industrial applications. In this review, attention is paid to the factors that affect the stability of anodes and the corresponding strategies for designing catalytic materials to prolong the anode's lifetime. In addition, two important aspects—electrolyte optimization and electrolyzer design—with respect to anode stability improvement are summarized. Furthermore, several methods for rapid stability assessment are proposed for the fast screening of both highly active and stable catalysts/electrodes. Finally, perspectives on future investigations aimed at improving the stability of seawater electrolysis systems are outlined.
Fenofibrate Recognition and Gq Protein Coupling Mechanisms of the Human Cannabinoid Receptor CB1
Authors: Wang Tianxin , Tang Wenqin , Zhao Ziyi , Zhao Ran , Lv Zhenyu , Guo Xuzhen , Gu Quanchang , Liu Boxiang , Lv Haoyu , Chen Jiayan , Zhang Kaiquan , Li Fahui , Wang Jiangyun 
Published: February 2024

AbstractThe G‐protein‐coupled human cannabinoid receptor 1 (CB1) is a promising therapeutic target for pain management, inflammation, obesity, and substance abuse disorders. The structures of CB1‐Gi complexes in synthetic agonist‐bound forms have been resolved to date. However, the commercial drug recognition and Gq coupling mechanisms of CB1 remain elusive. Herein, the cryo‐electron microscopy (cryo‐EM) structure of CB1‐Gq complex, in fenofibrate‐bound form, at near‐atomic resolution, is reported. The structure elucidates the delicate mechanisms of the precise fenofibrate recognition and Gq protein coupling by CB1 and will facilitate future drug discovery and design.
Supramolecular phthalocyanine assemblies‐enhanced synergistic photodynamic and photothermal therapy guided by photoacoustic imaging
Authors: Zhao Yuan‐Yuan , Zhang Xiaojun , Chen Zixuan , Xu Yihui , Kim Heejeong , Jeong Hyunsun , Lee You Rim , Lee Jiah , Li Xingshu , Yoon Juyoung 
Published: February 2024

AbstractPhototherapeutic nanoplatforms that combine photodynamic therapy (PDT) and photothermal therapy (PTT) with the guidance of photoacoustic (PA) imaging are an effective strategy for the treatment of tumors, but establishing a universal method for this strategy has been challenging. In this study, we present a supramolecular assembly strategy based on Förster resonance energy transfer to construct a supramolecular nanostructured phototherapeutic agent (PcDA) via the anion and cation supramolecular interaction between two water‐soluble phthalocyanine ramifications, PcD and PcA. This approach promotes the absorption of energy, thus enhancing the generation of reactive oxygen species (ROS) and heat by PcDA, improving its therapeutic efficacy, and overcoming the low photon utilization efficiency of conventional PSs. Notably, after the intravenous injection of PcDA, neoplastic sites could be clearly visualized using PA imaging, with a PA signal‐to‐liver ratio as high as 11.9. Due to these unique features, PcDA exhibits excellent antitumor efficacy in a preclinical model at a low dose of light irradiation. This study thus offers a general approach for the development of efficient phototherapeutic agents based on the simultaneous effect of PDT and PTT against tumors with the assistance of PA imaging.
Lipid droplet‐targeted NIR AIE photosensitizer evoking concurrent ferroptosis and apoptosis
Authors: Jia Jia , Ma Zhedong , Zhuang Jiabao , Huo Lantian , Zhou Chunli , Li Nan , Zhao Na 
Published: February 2024

AbstractLipid droplets (LDs), which are the hubs of lipid metabolism, play a critical role in maintaining cellular energy homeostasis. The construction of advanced photosensitizers (PSs) capable of manipulating LD‐mediated cell fate regulation is highly desirable though rarely reported. In this study, a near‐infrared emissive PS (DPCMP) with LDs specificity was synthesized and successfully applied to induce ferroptosis and apoptosis. DPCMP exhibited typical aggregation‐induced emission characteristics owing to its twisted molecular conformation. Excellent biocompatibility and suitable lipophilicity allowed DPCMP to specifically stain the LDs in living cells. Under white light illumination, the DPCMP displayed potent reactive oxygen species (ROS) generation capacity through both type I and II photochemistry. The massive accumulation of lethal ROS generated by DPCMP‐mediated photosensitization initiated lipid peroxidation, impaired cellular redox homeostasis, and led to endoplasmic reticulum oxidative stress, ultimately inhibiting cellular proliferation via concurrent ferroptosis and apoptosis in both living cancer cells and multicellular tumor spheroids.