bluuebunny/crossref_metadata_2025_split huggingface dataset:
Significant upregulation of signaling and pro-inflammatory markers indicate adaptation for tolerance in bovine trypanosomosis
Authors: Morenikeji Olanrewaju , Metelski Jessica L , Thomas Bolaji 
Published: January 2023

Abstract
The initial immune response on exposure to trypanosomosis is a significant factor mitigating disease tolerance or susceptibility in cattle. CD14 is a signaling receptor involved in the activation of the TLR signaling pathway, contributing to the production of cytokines, including tumor necrosis factor-α (TNF-α). We had shown that CD14 expression in trypanotolerant cattle is an adaptation footprint, not found in susceptible animals. To further our analysis in delineating the role of TLR-4 and TNF-α genes in disease tolerance or susceptibility, we examined whole transcriptome and interactome of the two genes by elucidating their expression profiles in bovine tissues (liver, lungs, heart and kidney). Our analyses demonstrate a significant (p&lt; 0.05) upregulation of TLR-4 and TNF-α in trypanotolerant cattle but not others. The upregulation of these genes in tolerant animals reflects a complete activation of the innate immune pathway, thereby hampering disease establishment, which is absent in the susceptible animals. This is contrary to reports in human studies, where the expression of these genes lead to disease chronicity, rather than tolerance. This indicates an evolutionary differentiation between cattle and human during speciation. Furthermore, we catalogued microRNA expression between disease groups via network analysis and identified 13 candidate microRNAs targeting CD14, TLR-4 and TNF-α, amongst others, which GO analysis reveal are involved in gene silencing, cellular protein modification process, etc. We conclude that the upregulation of these markers and the significant co-regulatory interactome is indicative of adaptation footprint in tolerant animal, helpful for bovine immune response against trypanosomiasis.
Immune and epigenetic regulation through histone-lysine N-methyltransferase Setdb2 during severe influenza virus infection
Authors: Ito Toshihiro , Imakita Natsuko , Hara Atsushi , Ouji-Sageshima Noriko , Kitabatake Masahiro 
Published: January 2023

Abstract
Influenza virus causes acute respiratory infections that are highly contagious, and leads to significant morbidity and mortality in humans and animals. Especially, the main severe pathogenesis following influenza virus infection are secondary bacterial pneumonia (SBP) and influenza-associated encephalopathy (IAE). Thus, a better understanding of the molecular mechanisms of these diseases is essential.
In our studies, microarray analysis demonstrated that influenza virus infected cells such as epithelial cells and macrophages upregulated SET domain, bifurcated 2 (Setdb2) expression following influenza virus infection via type-I IFN dependent manner. Setdb2 is a histone methyltransferase that methylates Lys-9 of histone H3 (H3K9), correlated with repression of transcription. Setdb2 expression in both influenza virus pneumonia and IAE models was significantly increased compared to control mice. Next, we investigated the role of Setdb2 in both SBP and IAE models. In SBP model, knocking down Setdb2 increased amphiregulin expression, which plays a critical role in tissue homeostasis of lungs and in decreased mortality of coinfection. In IAE model, the expression of Caveolin-1, one of the key proteins that correlate with protection of the blood-brain barrier, was significantly lower in brains from the IAE group compared with the control group. Furthermore, chromatin immunoprecipitation revealed that methylation of histone H3K9 was correlated with repression of the Caveolin-1 promoter region.
These studies support the idea that an understanding of epigenetic change, especially via Setdb2, during influenza virus infection can provide mechanistic approaches for controlling and modifying the immune response in SBP and IAE.
Human rhinovirus and influenza A H1N1 monoinfection and co-infection induce both proinflammatory and anti-inflammatory responses in macrophages THP-1
Authors: Rosas-Taraco Adrian Geovanni , Martinez-Castilla Azalia M , Salado-Gamez Jaudiel H , Flores-Torres Armando S , Flores-Aldaba Kevin A , Torres-Lopez Ernesto , Salinas-Carmona Mario C 
Published: January 2023

Abstract
Macrophages play an important role in the innate immune response against several pathogens. Viral co-infections have been reported in humans; being human rhinovirus (hRV) and influenza A H1N1 virus (IAV) the most frequent co-infections. hRV and IAV monoinfection and co-infection models were developed in THP-1 macrophages. Viral detection and load were determined by QRT-PCR. Macrophage polarizations were performed using intracellular cytokines staining and flow cytometry; and ELISA was used to determine the cytokines levels. In monoinfection models, higher viral loads were found at 24h compared with 48h. On the other hand, viral load of IAV co-infection was lower compared with monoinfection when macrophages were infected first with hRV. The monoinfection with IAV at 48h and co-infection models induced higher percentages of TNF-a + macrophages when compared to the control (P&lt;0.05). The percentages of IL-4+ macrophages were similar in all study groups (P&gt;0.05). IL-10+ macrophages were significantly increased in hRV monoinfection model at 48h and in the co-infection models compared with control (P&lt;0.05). A high percentage of macrophages that co-expressed IL-4+ and IL-10+ were detected in the IAV monoinfection at 48h and co-infection models compared with control group (P&lt;0.05). Monoinfection models induced high levels of TNF-a at 24h compared with control (P&lt;0.05). IL-4 levels were similar in all study groups (P&gt;0.05). IL-10 levels were elevated in monoinfection models, as well as in hRV/IAV co-infection when compared to control (P&lt;0.05). Our results suggest the presence of proinflammatory and anti-inflammatory responses during monoinfection and co-infection models of hRV and IAV.
LAG-3 marks effector to regulatory evolution of Th1 immunity in influenza
Authors: Dutta Avijit , Hung Chen-Yiu , Hsieh Yu-Chia , Chang Chia-Shiang , Chen Ting-An , Huang Yu-Lin , Lin Yung-Chang , Chen Tse-Ching , Lin Chun-Yen , Huang Ching-Tai 
Published: January 2023

Abstract
Naïve CD4+ T cells respond in influenza with T-bet expression, a transcription factor up-regulated with Th1 commitment. We report concomitant LAG-3 expression on these Th1 committed cells with evolution into regulatory T cells. LAG-3 expression increases with activation as revealed by CFSE cell division study. Cells with moderate LAG-3 expression produce IFN-γ and contribute to inflammation and disease. They no longer produce IFN-γ with higher LAG-3 expression upon further activation. High LAG-3 cells suppress and decouple effector function from the preserved proliferation of CD8+ T cells. They restrain inflammation with facilitated viral clearance and ameliorate the disease of severe influenza. Foxp-3+CD4+ T cells suppress both effector and proliferative responses with impaired viral clearance and they are less potent in disease amelioration. Principal component analysis of genome-wide expression further confirmed the stepwise evolution from effector to regulatory T cells. Regulatory genes are up-regulated progressively from LAG-3Neg to LAG-3Med and to LAG-3High cells.
Mechanism of T cell mediated hemorrhagic disease during LCMV infection
Authors: Luna Evelyn , McAfee Megan , Carmen Joshua , Canter Hannah , Ahmed Rafi , Greenberg Philip D , Blattman Joseph N 
Published: January 2023

Abstract
T cells are essential in controlling and clearing viral pathogens, but they also have the potential to induce immunopathology. We have previously shown that this balance between protection and pathology is dependent on the number of virus-specific T cells. Specifically, intermediate numbers of CD8 T cells result in lethal hemorrhagic disease, while lower doses result in exhaustion, and higher doses in viral clearance. Increasing the number of virus-specific CD4 T cells also leads to lethal hemorrhagic disease, however the mechanism by which T cells mediate this pathology remains unclear. Using lymphocytic choriomeningitis virus (LCMV) and an in vivo adoptive transfer mouse model, we found that lethal pathology induced by CD8 T cells is dependent on tumor necrosis factor (TNF). The absence of TNF signaling abrogates pathology without impeding viral clearance. Interestingly, CD4 T cell induced pathology, while dependent on CD8 T cells, still occurs in the absence of TNF. Furthermore, IL-2 produced by CD4 T cells modulates CD8 T cell responses to generate hemorrhagic disease that is TNF-dependent. Our findings show that TNF plays a significant role in T cell mediated hemorrhagic disease, and further implies that CD4 T cells modulate CD8 T cells to follow a different mechanism of pathology in the absence of this potent pro-inflammatory cytokine.
Memory-like NK responses to Zika virus infection
Authors: Kujur Weshely , Murillo Oscar , Mulik Sachin 
Published: January 2023

Abstract
The formation of memory is a hallmark feature of adaptive immune cells such as T and B lymphocytes. Natural killer cells (NK), though part of the innate immunity, have also been shown to undergo memory program to haptens, cytomegalovirus and other pathogens. We investigated NK response after Zika virus infection in mice. The activation of NK cells was evident early after infection, with increased frequencies of CD27+KLRG1+ NK cells producing higher amount of IFN-γ and perforin. These responses were normalized a month post infection. However, investigating CD27+ NK cells a month post Zika infection led to identification of memory like phenotype in these cells. The CD27+ NK subset (day 37 post infection) demonstrated greater therapeutic potential than CD27− NK subset or naive CD27+ NK cells when adoptively transferred to Zika infected interferon receptor deficient mice. The cell trace violet labeled CD27+ NK cells (day 37 post infection) when transferred to recipient mice robustly proliferated after Zika challenge. Moreover, the response of these memory-like CD27+ NK cells were antigen specific as these cells failed to proliferate in the recipient mice after bacterial challenge. Memory-like CD27+ NK cells persisted, had lesser reactive oxygen species, healthy mitochondria and lesser apoptotic features. This study reveals memory-like NK responses to Zika virus infection. It remains to be seen if specific NK receptor or cytokines are involved in generation of memory-like NK responses to Zika infection.
Studies of the Flocculation-Reaction Time in the Course of Immunization and the Quantitative and Qualitative Changes of the Proteins
Authors: Berthelsen Knud C. 
Published: January 2023

Summary
A consistent increase in the flocculation-reaction time has been found during the immunization period of horses used for diphtheria antitoxin production. It is suggested that the speed of reaction is an expression of the interfacial state of the antitoxic-protein-molecule complex.
A study was made of various quantitative and qualitative characteristics of antitoxic sera as related to the flocculation reaction.
Nine horses were immunized with infusion-free toxin, by both a slow and a rapid immunization technic. Three horses were immunized with purified infusion-free toxin and three horses with a routine toxin containing meat infusion. During the immunization period the horses were followed for any biochemical changes in order to determine, if possible, the existence of any relationship between the flocculation-reaction time and quantitative differences of one or more of the physicochemical constants of sera.
A technic was developed for determination of the surface tension of plasma in order to exclude the errors present when serum is used.
The Distribution of Electrolytes in Serum During Immunization
Authors: Berthelsen Knud C. , Murdick Philip P. 
Published: January 2023

Summary
At progressive stages of immunization before and after toxin injection the diffusible calcium, non-diffusible calcium, and total base have been estimated.
At weekly intervals during the course of immunization the diffusible and non-diffusible phosphorus has been determined.
The ultrafiltration technic has been employed in order to separate the diffusible from the non-diffusible constituents.
Random Mating and Blood Groups
Authors: Jenkins R. L. 
Published: January 2023

Summary
A criterion on internal consistency of blood groups is here presented for application to large bodies of data in the study of blood groups from an anthropological standpoint. The failure of data to meet this criterion is to be interpreted as evidence either of selective mating with regard to blood groups or of errors in the technique of grouping and indicates that the data is unsuitable for the application of the technique of Snyder for calculating p, q, and r, the absolute frequencies of the triple allelomorph gens among the population.
On Immune Isoagglutinins in Rabbits
Authors: Levine Philip , Landsteiner K. 
Published: January 2023

Abstract
In this paper several additional observations are recorded on the production and properties of immune isoagglutinins in rabbits.
Contributions to this subject not covered in our first article (1) and in the papers by Fischer and Klinkhardt (2) are the following. Ascoli (3) describes in two among numerous cases the formation of isolysins and isoagglutinins after injection of rabbits with their own blood hemolyzed by water (cf. Hulot and Ramond (4)). These results could not be duplicated by Kraus and Ludwig (5). Robertson and Rous (6) observed the development of isoagglutinins and autoagglutinins as the result of transfusing rabbits with the blood of other rabbits. A report of normal isohemagglutinins in rabbits was recently made by Gara (7).
An extensive study on isoagglutinins in rabbits was made by Fischer and Klinkhardt. Their experiments, made mostly after serological selection of donors and recipients, resulted in the demonstration of two sorts of agglutinins, determining two agglutinable properties.
Studies in Anaphylaxis in the Rabbit
Authors: Grove Ella F. 
Published: January 2023

Summary
Of 20 rabbits that received two injections of fowl corpuscles at an interval of five days, all were found to be maximally sensitive upon the intravenous test injection seven days after the second sensitizing injection. All of the sera of these sensitized rabbits agglutinated the corpuscles used for injection and the agglutinins were only slightly reduced by mixing the serum with relatively large quantities of the water-soluble corpuscular substances. Rabbits sensitized with two injections of whole fowl corpuscles are not necessarily sensitive to the water-soluble corpuscular substances, and are not desensitized by large quantities of the latter to the subsequent injection of whole corpuscles. Antisera prepared against goose corpuscles (which are said to lack the Forssman antigen) are toxic for normal guinea pigs; this toxicity can be removed by absorption with guinea pig kidney. Anti-goose corpuscle serum rendered non-toxic by absorption with guinea pig kidney tissue and injected intravenously into normal guinea pigs renders these animals hypersusceptible to the injection of whole goose corpuscles one hour later. The subcutaneous reinjection of fowl corpuscles almost always results in the development of the Arthus necrosis.
Natural Resistance to Disease in the Chicken
Authors: Lambert W. V. 
Published: January 2023

Summary
Extensive bacteriological examination of the organs of 61 breeding birds, all survivors of a fowl typhoid infection, showed 21.3 per cent of them to be carriers of S. gallinarum. The ovary was the most frequent seat of localization of the bacterium in the females. Only 1 of 7 males examined proved to be a carrier. Chicks hatching from the carrier hens proved slightly, but not significantly, less resistant than those from non-carrier hens. The mortality among 129 chicks from carrier hens was 44.2 per cent and among 366 chicks from non-carrier hens 40.2 per cent. The non-carrier hens were those from which the organism was not isolated.
Data secured from bacteriologic examination of a small number of chicks killed at various intervals after infection suggest that chicks from the selected population are more refractory to the fowl typhoid organism than are chicks from an unselected population. Agglutination tests on the blood serum of these chicks indicate that the young chick lacks the ability to develop agglutinins of high titer, if at all.
Studies in the Variability of Tubercle Bacilli
Authors: Rice Christine E. , Reed G. B. 
Published: January 2023

Summary
The S type of various strains of acid-fast bacteria, Mycob. leprae and human, bovine and avian tubercle bacilli have been found to contain antigenic substances not present in the R type of the same strain, dissociation apparently being accompanied by a considerable loss in antigenic complexity.
Immune sera prepared against such S organisms contain certain antibodies reacting with extracts of the homologous S organisms but not with the homologous R type, other antibodies reacting with both S and R of the same species and a third type of antibody detected by antigens prepared from the other species of acid-fast bacteria, that is a group antibody.
Antisera prepared against R organisms on the other hand appear to lack the S-specific antibody which is found in S antiserum but contain a much higher proportion of antibodies reacting with extracts prepared from other acid-fast species. The possible chemical nature of the various antigenic substances has been briefly discussed.
Inheritance As a Factor in Resistance to an Infectious Disease
Authors: Irwin M. R. 
Published: January 2023

Abstract
Reference has been made in the preceding article (1) to the error in using the mean percentage mortality as typifying the underlying probability for an event, such as death, in a population, unless the deviation of the mortalities by an authentic subdivision lies within the errors of random sampling of that of a binomial, or Bernouillan, distribution.
In the experiments heretofore reported, if heredity has played a major part in determining the resistance of an animal, it follows that the behavior to an infection of the offspring from any mating will be determined in the main by the interaction of the factors received from the respective parents. Under such conditions, the litters constitute the logical subsets into which the population should be divided for an analysis of the type of distribution.
A method for such an analysis has been previously described by the author (2, 3). A much more complete exposition has been presented by Snedecor (4).
Chemical and Immunological Studies of the Pneumococcus
Authors: Wadsworth Augustus , Brown Rachel 
Published: January 2023

Summary
From the bacterial cells of types I, II, III and of an atypical variant of type I pneumococci, substances of carbohydrate nature have been prepared. They all contained phosphorus and nitrogen. They differed in their precipitative activity. The fractions from the virulent organisms of the three types reacted in high dilution with the homologous antisera only, while that from the atypical type I pneumococci reacted with type I antiserum in a very low dilution and with types II and III in high dilution. They gave rise to skin reactions in immunized but not in normal rabbits. The response was not highly specific. They induced purpura in mice. This activity of the type I cellular carbohydrate, which further distinguished it from the soluble specific substance, was not destroyed when the cellular substance was heated in n/100 sodium hydroxide or hydrochloric acid, at 100°C. for thirty minutes or was autoclaved in n/100 sodium hydroxide, at 120°C. for twenty minutes. It was inhibited by type I antipneumococcus rabbit serum and intensified by immune horse serum. The type I material could be separated by acid precipitation into two fractions which differed in their precipitative activity and in their ability to induce purpura in mice. The type I cellular carbohydrate precipitated from two to three times as much nitrogen from immune serum as did the soluble specific substance. When injected through the trachea into the rabbit lung, the type I cellular carbohydrate gave rise to a marked diffuse inflammatory reaction. The cellular carbohydrates of all three types induced specific anaphylactic shock in sensitized guinea pigs. The cellular carbohydrate from the type I attenuated strain did not induce this phenomenon in guinea pigs sensitized with any one of the three types of antisera.
A Note on the Fractionation of Antimeningococcus Serum
Authors: Murdick Philip P. , Cohen Sophia M. 
Published: January 2023

Abstract
Experiments were undertaken to determine the protein fraction or fractions of antimeningococcus serum with which are associated the agglutinative and precipitative activities and also the neutralizing activity for the toxic substance of the meningococcus which induces the phenomenon of local skin reactivity.
In the method for the concentration of antimeningococcus serum described in a paper by Neal and others (1) concentration of the agglutinative activity was obtained by separation of a water-insoluble globulin after partial removal of euglobulin by saturation of the serum with sodium chloride. Similar results have been obtained in this laboratory with Banzhaf's method (1). It was noted, however, with certain sera, that a lower degree of concentration of potency for group II strains was obtained than for strains of groups I and III. With one serum particularly, potency for group II strains, as determined by the precipitation reaction, was adversely affected by concentration.
Tissue Culture Studies on the Relation of the Tuberculin Reaction to Anaphylaxis and the Arthus Phenomenon
Authors: Aronson Joseph D. 
Published: January 2023

Summary
The growth and migration of cells in explants from the spleen and bone marrow of tuberculous guinea pigs are inhibited by the addition of tuberculin; those explanted from non-tuberculous guinea pigs sensitized by a single injection of horse serum are not inhibited by horse serum.
Migration and growth in similar explants from tuberculous guinea pigs sensitized to horse serum are not inhibited by the addition of horse serum; it was found that they are, on the other hand, inhibited by tuberculin.
When the Arthus phenomenon was elicited by injections of horse serum into normal and tuberculous guinea pigs the tissue cultures were unaffected by the addition of the serum.
These tissue-culture experiments suggest that the mechanism underlying the tuberculin reaction is different from the mechanisms of anaphylaxis and the Arthus phenomenon.
Blood Grouping Among the “Blackfeet” and “Blood” Tribes of American Indians
Authors: Matson G. A. , Schrader H. F. 
Published: January 2023

Summary
Although various tribes of American Indians have consistently been reported as belonging primarily to group O, the Blackfeet and Blood tribes appear to be an exception, showing as high a percentage of group A as other tribes show of group O. This may be seen by comparing tables 2 and 3, with 1 and 4.
These results suggest the necessity for reconsidering the origin of the American Indian.
Complement Fixation Test in Carcinoma
Authors: Saphir William , Hirschberg Nell 
Published: January 2023

Summary and Conclusions
The complement fixation test in carcinoma has been studied in 27 sera of cancer patients and 82 control sera. The tests were positive in 77.7 per cent of the 27 sera from the cancer patients, and of the 82 control sera only one, from a patient with lobar pneumonia, gave a positive reaction. The authors are of the opinion that the reaction is of a physical-chemical nature due to the influence of the antigen upon the serum globulins rather than a specific antigen-antibody reaction. The clinical value of the reaction awaits further observation after refinement and a better understanding of the nature and the limitations of the test.