bluuebunny/crossref_metadata_2025_split huggingface dataset:
The type II anti-diabetic activity of an Aloe formulation in DIO mice (B80)
Authors: Kim Kyungjae , Kim Kwanghee , Kim Hyunyul , Kwon Jeunghak , Han Shinha , Lee Chong-Kil 
Published: January 2023

Abstract
Aloe is known to have various medical effects. These include healing damaged skin, as well as anti-diabetic, anti-cancer, and anti-arthritis activity. This study evaluated the anti-hyperglycemic effect of an Aloe formulation in DIO (Diet induced obesity) mice. The aloe formulation (AF) reduced body weight gain, fasting blood glucose, plasma triglyceride, the size of fat cells, and the amount of neutral fat deposits in the liver and improved insulin action. The AF treated group showed a reduction in the size of epididymal fat cells compared with the untreated group, and a lower amount of neutral fat deposits in the liver. AF exerted beneficial effects on lipogenesis related genes, such as SREBP1a, FAS, GPAT, and SCD-1 expressions in liver. These results suggest that AF is useful as an anti-diabetic treatment for Type II diabetes patients.
Spontaneous pulmonary hypertension in mice associated with OX40 ligand overexpression (B82)
Authors: Rabieyousefi Moloud , Zhang Ming-Cai , Soroosh Pejman , Ishii Naoto , Sugamura Kazuo , Ono Masao 
Published: January 2023

Abstract
[Background] Ligation of OX40 receptor on T cells provides potent co-stimulatory signals associated with memory T cell generation, Ag-specific T cell migration, and enhanced inflammatory responses. OX40L is expressed on antigen presenting cells and vascular endothelial cells. Previous studies have shown that OX40L transgenic mice (OX40L-Tg) spontaneously developed ulcerative colitis-like disease and undetermined lung disease, which were evident in C57BL/6 (B6) but not BALB/c (BALB) genetic background.
[Objective] The aim of this study is histopathological and genetic characterizations of the lung disease in OX40L-Tg.
[Methods] We generated 351 OX40L-Tg from (BALB x B6) x B6 OX40L-Tg backcrosses. Severity of pulmonary arterial lesion was evaluated with microscopic examinations (0-1-2 grades). Genome-wide scan and other genetic analyses were carried out based on microsatellite polymorphisms.
[Results] Pulmonary arterial lesion characterized by intimal and medial thickening that was observed in B6 but not BALB OX40L-Tg. Pulmonary hypertension (PH) in OX40L-Tg was shown by the elevation of right ventricular systolic pressure. We identified a novel susceptibility locus to the PH with suggestive linkage (P=0.0012, LOD=1.8) on chromosome 5.
[Conclusion] Augmented OX40-OX40L interaction predisposes mice to spontaneous onset of PH under the influence of particular genetic background.
The regulation of parathyroid hormone expression in thymus by Gcm2-dependent and Gcm2-independent pathways (B83)
Authors: Liu Zhijie , Chen Lizhen , Manley Nancy 
Published: January 2023

Abstract
The promiscuous gene expression of tissue-restricted self-antigens (TRA) in medullary thymic epithelial cells (mTEC) is required for the negative selection to establish the central tolerance. The mechanism of the promiscuous gene expression is still not clear. Two models have been proposed: Mosaic model proposed that many different tissue cells within the medulla express corresponding TRAs following the rules of tissue-specific regulation. Permissive model proposed that some mTECs can express TRAs differently compared to the tissue-specific regulation rules.
Parathyroid hormone (Pth) is one of TRAs expressed in thymus. We explored the mechanism of the regulation of thymic Pth expression in mouse. We found the major thymic Pth expression was from some clusters of misplaced parathyroid cells. In Gcm2 null mutants, thymic Pth expression was greatly reduced due to the ablation of these misplaced parathyroid cells, suggesting a Gcm2-dependent pathway functioning in these cells. Using genetic marker technique, we sorted Foxn1-expressing TECs, and demonstrated that TECs were another source of thymic Pth expression. Thymic Pth expression level was similar in the purified TECs from Gcm2−/− and wildtype, suggesting this expression was regulated by a Gcm2-independent pathway. Our results support the permissive model. It will be interesting to know if this mechanism is also used by other TRAs.
Type I interferon regulation of Th cell responses in SLE (B84)
Authors: Mangini Alyson J. , Meyers John A. , Nagai Taro , vanSeventer Gijs , vanSeventer Jean Maguire 
Published: January 2023

Abstract
Type I interferons (IFNs) can have contrasting effects on adaptive Th1 responses. IFN-α/β are well recognized anti-viral agents that promote anti-viral Th1 immune responses. In contrast, IFN-β therapy provides a beneficial effect in multiple sclerosis patients, in part, by suppressing Th1 type autoimmune responses. In systemic lupus erythematosus (SLE), autoimmune complex-induced, plasmacytoid dendritic cell (pDC)-derived IFN-α is thought to be a major disease effector. To investigate how type I IFNs regulate Th cell autoimmune inflammatory responses in SLE, we established a model of human peripheral blood mononuclear cell (PBMC) stimulation. In this model, the effects of continuous type I IFN exposure are mimicked by pretreating PBMC with either recombinant type I IFN or the pDC-TLR9 agonist, CpG-A, and stimulation of autoreactive Th cells is mimicked by stimulation with the superantigen, SEA. Type I IFN neutralization with B18R, a vaccinia virus-derived soluble type I IFN receptor, is used to specifically identify effects of CpG-A-induced type I IFN. Our results indicate that pretreatment with rIFN-α, rIFN-β, or CpG-A-induced type I IFN inhibits SEA-stimulated IFN-γ secretion by healthy donor PBMC. Preliminary experiments demonstrate that, when compared to serum from control individuals, some SLE patient sera similarly inhibit IFN-γ secretion by normal PBMC. In addition, co-pretreatment of PBMC with B18R and serum from several SLE patients reveals a type I IFN-mediated inhibitory effect on IFN-γ secretion. Our findings suggest that in SLE circulating type I IFNs may suppress Th cell-mediated tissue injury by inhibiting inflammatory cytokine-secreting autoreactive Th cells
Genetically controlled preferential loss of myelin-associated glycoprotein (MAG) coincides with severity and relapsing course of experimental autoimmune encephalomyelitis in H-2b/s mice (B85)
Authors: Skndric Dusanka , Zhou Weili , Dai Rujuan 
Published: January 2023

Abstract
Multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) are demyelinating diseases of central nervous system (CNS). Four types of demyelinating lesions and associated distinct immunopathogenetic mechanisms reflect heterogeneity of clinical MS. It is unknown if demyelinating patterns in EAE recapitulate those found in MS. We investigated patterns of demyelination in genetically related H-2band H-2b/s mice following immunization with H-2b restricted immunodominant epitope of myelin oligodendrocyte protein (MOG35–55). We measured loss of myelin proteins specifically, MOG, myelin associated glycoprotein (MAG), myelin basic protein (MBP), and levels of neurofilament (NF160), and DNA-binding apoptosis regulatory protein (PARPp80) in demyelinating lesions of EAE mice. While loss of MOG was apparent in both strains during acute disease, it was significantly higher in H-2b/s compared to H-2b mice. Conversely, profound depletion of MAG, accompanied with decreased NF160, and elevated PARPp80 levels were exclusively found in severely relapsing H-2b/s mice. Levels of MBP remained relatively unchanged in both strains. Our data show that preferential loss of MAG, which is suggestive of distal oligodendrogliopathy, associates with reduction of axonal neurofilament, signs of apoptosis, and severe relapsing disease in H-2b/s mice. We propose that pattern of demyelination in H-2b/s mice resembles the type III MS lesion.
Human cardiac myosin (HCM) activates Toll-like receptors 2, 7 and 8 (B87)
Authors: Zhang Ping , Alvarez Kathy M. , Heuser Janet S. , Cunningham Madeleine W. 
Published: January 2023

Abstract
Toll-like receptor (TLR) activation has been implicated as a link between innate immunity and adaptive immunity in autoimmune diseases including myocarditis. Human cardiac myosin (HCM) has long been known as an autoantigen in myocarditis. The role of HCM on innate immunity has not been studied. To test the hypothesis that HCM activates TLRs, HEK 293 cells transfected with human (h) TLR2, 3, 4, 5, 7, 8, and 9 were treated with HCM or a cryptic HCM peptide S2-16 for 72h. IL-8 levels in supernatants were measured by ELISA. HCM or S2-16 treatment resulted in 2–4 times more IL-8 from hTLR2, 7 and 8 transfected cell lines compared with media. HEK control cells treated with HCM or S2-16 showed same level of IL-8 as media. In addition, skeletal muscle myosin treated hTLR transfected cell lines showed no difference in IL-8 levels from media. To confirm this observation, human monocytes were isolated and treated with HCM and S2-16. Supernatant was harvested 24 h later and IL-8 was measured by ELISA. Both HCM and S2-16 treatment resulted in a dose-dependent increase of IL-8. Similar increase in IL-8 in human monocytic THP-1 cell line was also observed. The finding that HCM activates innate immunity through TLR 2, 7, and 8 is novel, and links innate and adaptive immunity in autoimmune myocarditis. Exposure of HCM during viral infection or after apoptosis or necrosis in the heart may lead to chronic stimulation of TLRs and autoimmune heart disease.
A role for mast cells in EAE: W/Wv, Wsh, and CD34−/− mice are fully susceptible to disease induction using standard protocols (B92)
Authors: Bennett Jami L , Blanchet Marie Renee , Kubes Paul , McNagny Kelly 
Published: January 2023

Abstract
EAE is a murine model of multiple sclerosis involving destruction of myelin by the immune system. Mast cells, known for a role in asthma and allergy, are reportedly required for EAE induction in mice. Our lab has reported that mature mast cells express the surface marker CD34. To further understand the role of mast cells in EAE, we utilized CD34−/− mice which have functional mast cells in the tissues, but are defective in their mobilization. We asked whether mast cells seeded in development were sufficient for EAE induction. Previous studies of mast cells in EAE used W/Wv mice, where reconstitution with WT-mast cells restored susceptibility to EAE. It was possible that CD34−/− mice were protected from EAE due to the decreased peripheral mobility of mast cells, or, seeding of CNS- or vascular-localized mast cells during development could be sufficient for their function. Here we compare clinical disease in WT, CD34−/−, W/Wv, and Wsh mice. We find CD34−/− mice are susceptible to induction of EAE, consistent with suggestions that mast cells act remotely in this model. Surprisingly, however, we also find both W/Wv and Wsh mice susceptible to disease in our hands. This result was confirmed by other laboratories. Interestingly, analysis of infiltrating leukocytes in the CD34−/− CNS shows increased mast cells vs. WT. We are now investigating whether inflammatory factors have bypassed the requirement for cKit on mast cells in EAE.
‘Type B’ T cells escape T cell tolerance in HLA-DRB5 transgenic mice (B93)
Authors: Forsthuber Thomas G. , Murphey Cathi , Kawamura Kazuyuki 
Published: January 2023

Abstract
Multiple sclerosis (MS) is associated with the MHC class II genes HLA-DR2 and HLA-DRB5. The role of these MHC II molecules in the pathogenesis of MS has remained unresolved, but it is conceivable that these molecules fail to induce T cell tolerance. We have investigated T cell tolerance to MBP in HLA-DR2, -DRB5, and –DR4 transgenic mice. Our results showed profound T cell tolerance to MBP in all three tg mouse lines. However, ‘type B’ T cells recognizing MBP85-99 in an altered conformation escaped tolerance in HLA-DRB5 tg mice. These T cells responded only to the MBP85-99 peptide, but not to the native MBP protein. Importantly, these T cells induced severe EAE upon adoptive transfer into naïve recipients. Thus, the data suggest that ‘type B’ T cells could escape T cell tolerance in MS patients with the HLA-DR2 haplotype and contribute to the disease.
Expression of Leukotrienes is Increased in Human MS and in a Mouse Adoptive Transfer Model of MS (B98)
Authors: Mendoza Lisa M. , King Beverly , Rosser Mary , Almond Cosima , Hidalgo ToniRose , Schaefer Caralee , Mahmoudi Mithra , Harvey Susan , Kirkland Thomas , Guilford William , Vogel David , Lassmann Hans , Reder Anthony , Parkinson John , Halks-Miller Meridith 
Published: January 2023

Abstract
Leukotrienes are well established as mediators of inflammation, however little is known regarding their role in the pathogenesis of multiple sclerosis (MS). In humans, elevated LTA4-h levels were reported in acute inflammatory lesions of a single primary progressive (PP) patient, while increased mRNA and protein levels of 5-lipoxygenase were seen in both PP-MS and relapsing remitting (RR) patients. LTB4 levels were higher in the cerebrospinal fluid of patients with active MS compared to controls, while levels of cysteinyl leukotrienes LTC4, LTD4, and LTE4 were not different. Beyond these preliminary disease association data, little is known about role of leukotrienes in MS. BLT1, the high affinity receptor for LTB4, has recently been reported to be expressed on both human and mouse antigen-experienced T lymphocytes. We show here that encephalitogenic T cells specific for a myelin antigen express functional BLT1. When transferred into naïve recipients these T cells are sufficient to induce disease. In addition, peripheral blood T cells from RR-MS patients express altered levels of the BLT1 receptor as compared to normal healthy controls. In the CNS, we show that demyelinating plaques in human MS brain tissues have up-regulated levels of LTA4-h and BLT1 by immunohistochemistry suggesting involvement of this pathway in the pathogenesis of MS and highlighting potential new targets for therapeutic intervention.
Distinct roles of STAT4α and STAT4β in the pathogenesis of experimental allergic encephalomyelitis (B99)
Authors: Mo Caiqing , Chearwae Wanida , O’Malley John T , Kaplan Mark H , Bright John J 
Published: January 2023

Abstract
Experimental allergic encephalomyelitis (EAE) is a T cell-mediated autoimmune disease model of multiple sclerosis (MS). Interleukin 12 (IL-12) and IL-23 are heterodimeric cytokines, which share common IL-12p40/IL-12Rb2 subunits and play distinct roles in the pathogenesis of EAE. Signaling through JAK-STAT pathway, IL-12 induces Th1 cell development, while IL-23 enhances ThIL17 cell differentiation. We and other have shown earlier that therapeutic intervention or targeted disruption of STAT4 was effective in ameliorating EAE. Recent studies have identified the expression of a full-length STAT4α and a truncated STAT4β, which lacks 44 amino acids at the C-terminus. In this study we show that the STAT4β transgenic mice, induced to develop EAE by immunization with MOGp35-55 peptide, develop an exacerbated EAE than the wild type littermates. However, the STAT4α transgenic mice remain resistant to EAE, as seen in STAT4 knockout mice. Further analyses, by real-time PCR, ELISA and Western blot, show that STAT4β transgenic mice express higher levels of IFNγ, IL-17, IL-12, IL-23 and IL-27 in the brain and spleen than STAT4α transgenic mice, which correlates with the clinical outcome of EAE. Although the distinct roles played by STAT4α and STAT4β in IL-12 and IL-23 signaling in EAE is not known, this study validates the use of STAT4β as a novel therapeutic target in the treatment of MS and other autoimmune diseases.
Incidence of Blood Groups among the Maya Indians of Yucatan
Authors: Goodner Kenneth 
Published: January 2023

Summary
Two hundred and twenty-three pure Mayas and 202 people of mixed Maya and Spanish blood were grouped. A high percentage incidence of Group O was found, in the case of the Mayas amounting to 97.7 per cent. This points to the racial purity and antiquity of the Maya stock.
Hypersensitiveness to Diphtheria Bacterial Products
Authors: Neill James M. , Fleming William L. , Sugg John Y. , Avery Roy C. , Richardson Lurline V. , Kane Bernard E. 
Published: January 2023

Summary
The hypersensitive man (individual C) previously reported reactive with toxin-containing and non-reactive with non-toxin-containing test materials, was studied further by a comparison of the hypersensitive reactivity or non-reactivity of the filtrates of highly and of weakly toxicogenic strains of diphtheria bacilli. With a constant test dose (3.0 × 10−4 cc.) of filtrate, each of the 18 highly toxicogenic strains produced a moderate to strong immediate skin reaction; in contrast, none of the 14 weakly toxicogenic strains gave any reaction at all. This sharp demarcation was acceptable proof that the agent of this man's hypersensitive reaction was consistently present in higher concentration in the filtrates of highly toxicogenic than in the filtrates of weakly toxicogenic strains.
When dealing with complex mixtures like bacterial filtrates, it is difficult to assign hypersensitive reactions to any one particular constituent. However, in the present instance, significance must be attached to the regular association between toxin and the agent of C's hypersensitiveness, particularly because of the biological assays of the filtrates for their contents of two other diphtheria constituents (the agent of the delayed “pseudo” reaction and the agent of the immediate reaction on individual A). The fact that some of the weakly toxicogenic strains non-reactive with C were just as potent as any of the highly toxicogenic strains in respect to other diphtheria bacterial substances was important because it showed that the consistent association between the toxin content and content of the agent of C's reaction was not due simply to a greater concentration of bacterial substance in the toxicogenic filtrates by virtue of more luxuriant growth or of consistently greater autolysis on the part of the toxicogenic strains.
While the evidence is of indirect nature, it strongly suggests that diphtheria toxin is the substance involved in the described hypersensitive immediate skin reaction.
The Toxicity of Human Serum for the Guinea Pig. Serum in Various Clinical Conditions
Authors: Ramsdell Susan G. , Davidsohn I. 
Published: January 2023

Summary and Conclusions
When normal horse serum was used in large amounts as an antigen in the human, the phenomenon of a toxicity of the serum of such treated persons for the guinea pig was found to occur more regularly and to continue for a longer period of time than had been shown to be the case in our former experiments with sera of persons treated with various immune sera. This increase is attributed to the relatively large amounts of serum with which the patients were treated.
Certain cases were found where the serum taken at a pretreatment bleeding contained the factor for toxicity. This was usually, but not always, accompanied with a higher-than-normal (heterophilic) agglutinin titer for sheep red cells. Such sera tended to become more toxic subsequent to treatment of the patient along with an increase of the agglutinin and hemolysin titers. When the sera of a group of seriously ill patients were tested, the phenomenon of toxicity was found with considerable frequency, especially in those suffering from syphilis and acute infectious processes. Of the sera of the last, the toxicity was correlated with the presence in the serum of heterophilic antibody (sheep cell agglutinin in a titer above that normally found) in 50 per cent of the cases.
It is evident that the toxicity of human serum for the guinea pig must be ascribed to two or more different factors in the serum: one of these its content in heterophilic antibody, the other as yet undetermined.
The role of Akt in NF-kappaB mediated lymphocyte gene regulation in activated T cells (35.11)
Authors: Cheng Jing , Kane Lawrence P 
Published: January 2023

Abstract
Akt is a serine/threonine kinase that is activated by growth factor and antigen receptors. Although NF-kappaB is one of several downstream targets for Akt, it is not known what role NF-kappaB plays in Akt-dependent biological process. The NF-kappaB-dependent gene expression during T cell activation is analyzed and a subset of genes requires Akt for upregulation is established in this study. Duplicate samples of D10 T cells are left unstimulated, stimulated with antibodies to T cell receptor (TCR) and CD28 for 2h, 6h or 12h, with or without Akt inhibitor (or SiRNA against Akt). RNAs are made and hybridized to NF-kappaB-enriched microarray which contains oligonucleotides corresponding to 113 genes that are known targets and regulators of NF-kappaB signaling. We show that of the many genes that are upregulated after T cell activation only a subset is affected by Akt inhibition. Further studies are underway to analyze these genes for transcription factor binding sites with the goal of ascertaining which transcription factors are affected among TCR/CD28-responsive genes that require Akt. Our results may be useful for identifying new targets for therapy of tumors with constitutive Akt and/or NF-kappaB activity.
Apoptotic alkalinization induced by loss of a growth signal is mediated by phosphorylation of the Na+/H+ Exchanger isoform 1 at Ser726 and Ser729 (35.12)
Authors: Khaled Annette R , Zhang Ge , Ruppert Shannon , Boohaker Rebecca , Khaled Amr S 
Published: January 2023

Abstract
Apoptosis is a complex process essential for cellular homeostasis. Early physiological changes that initiate cell death remain poorly understood. Previously, we observed that lymphocytes, undergoing apoptosis in response to loss of a growth factor experienced a rapid rise in cytosolic pH. We found that the protein responsible was the Na+/H+ Exchanger isoform 1 (NHE1), and that its activity was impeded by inhibition of p38 MAP kinase (MAPK). In the current study, we examined how NHE1 is activated during apoptosis. We identified the phosphorylation sites on NHE1 that regulate its alkalinizing activity in response to a death stimulus. Performing targeted mutagenesis, we observed that substitution of Ser726 and Ser729 for alanines produced a mutant form of NHE1 that did not alkalinize in response to apoptosis, and expression of which protected cells from serum-withdrawal induced death. In contrast, substitution of Ser726 and Ser729 for glutamic acids raised the basal pH and induced susceptibility to death. Serine phosphorylation of NHE1 during apoptosis decreased upon mutation of S726 and S729. Our findings thus confirm a necessary function for NHE1 during apoptosis and reveal the critical regulatory sites that when phosphorylated mediate the alkalinizing activity of NHE1 in the early stages of cell death.