bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Ibuprofen and Fusion Protein Inhibitor (FPI) on neutrophil extracellular traps (NETs) in the lung tissue of calves experimentally infected with Bovine Respiratory Syncytial Virus (BRSV)
Authors: Mutua Victoria , Gershwin Laurel J 
Published: January 2023

Abstract
Neutrophil extracellular traps is a mode of neutrophil death targeting extracellular pathogens. They are composed of a complex of processed chromatin bound to granular and cytoplasmic proteins expelled from the cell onto pathogens. Although NETs play a role in trapping and killing extracellular pathogens they may be injurious and are considered to play a role in a wide array of inflammatory diseases. The exact contribution of NETs to clearance of pathogens versus inflammatory injury is poorly understood.
Bovine respiratory syncytial virus (BRSV), like RSV, causes severe respiratory disease.
In this study, we quantified NETs in lung tissue of calves experimentally infected with BRSV after treating with the anti-inflammatory drug Ibuprofen and/or an antiviral drug (FPI). Twenty four calves were infected with BRSV, placed into 6 treatment groups and treated with ibuprofen, FPI or both. Calves were euthanized on day 10 post infection and the lungs evaluated for pathological changes that were correlated with the IHC data. Cryosections of lung tissue were stained with primary antibodies [Rabbit anti citrinated histones(citH3), Rabbit anti neutrophil elastase (NE) and counter stained with secondary antibodies conjugated to Alexa 594 or 488. Slides were examined using an EVOS fluorescence microscope with at least 10 fields from each lung section at ×400 magnification evaluated. NETs were analyzed and quantitated using Materials Image Processing and Automated Reconstruction (MIPAR™) with the total NETs score calculated as the average of NETs in the 10 fields.
Results show that a combination of Ibuprofen and FPI treatment from day 3 following experimental infection had a significant reduction in clinical score and average NETs in lung tissue.
Lytic cell death mechanisms in human respiratory syncytial virus-infected macrophages
Authors: Bedient Lori , Pokharel Swechha Mainali , Casimiro Kim Roxana Chiok , Bose Santanu 
Published: January 2023

Abstract
Human respiratory syncytial virus (hRSV) is the most common cause of viral pneumonia in infants and children worldwide and creates significant airway disease in immunocompromised people and the elderly. Inflammation induced by hRSV infection is responsible for its hallmark manifestations of bronchiolitis and pneumonia. The cellular debris created secondary to lytic cell death of infected cells is a potent initiator of this inflammation. Macrophages are known to play a pivotal role in the early innate immune and inflammatory response to viral pathogens. While previous studies have investigated the mechanisms responsible for lytic cell death in Influenza A-infected macrophages and hRSV-infected neutrophils, the lytic cell death mechanisms associated with hRSV infection in macrophages remain unknown. In order to address this knowledge gap, we treated an hRSV-infected human THP-1 macrophage cell line with various inhibitors that block two lytic cell death pathways: pyroptosis and necroptosis. In addition, we used pyroptosis-deficient human macrophages to further clarify the lytic cell death mechanisms occurring during infection. Our studies revealed that hRSV induces lytic cell death in macrophages via both pyroptosis and necroptosis, specifically through caspase-1 and inflammasome-dependent pyroptotic mechanisms and through RIPK1-RIPK3-MLKL necroptotic mechanisms of cell death.
Expression and characterization of a monoclonal IgA isotype antibody against group 1 and group 2 influenza of the HV1-18 QxxV class
Authors: Ende Zachary S , Mishina Margarita , Kauffman Robert , Guo Zhu , Li Zhunan , Cao Weiping , Ray Sean , Kumar Amrita , Bohannon Caitlin D , Ranjan Priya , Sharma Suresh D , Gangappa Shivaprakash , Levine Min Z , Stevens James , Sambhara Suryaprakash 
Published: January 2023

Abstract
Examining cross-reactive influenza-specific human monoclonal antibodies can inform the rational design of universal flu vaccines. The vast majority of monoclonal antibodies studied to-date are of the IgG isotype or cloned into IgG vectors for expression. However, IgA isotype antibodies are also of interest, especially given their increased concentrations in the respiratory tract where the influenza virus replicates. To acquire anti-influenza monoclonal antibodies that are of both IgG and IgA isotypes, we used a fluorescently labeled hemagglutinin (HA) for fluorescence-activated cell sorting on memory B cells 14 days post-influenza vaccination. We then sequenced paired heavy and light chains with the 10× Genomics platform and chose relevant sequences to synthesize for expression and characterization. An IgA1 antibody of the HV1-18 QxxV class demonstrated binding to both group 1 and group 2 HA subtypes in enzyme-linked immunosorbent assays. Although Hemagglutinin inhibition assays were negative, neutralizing activity was positive in a microneutralization activity, at levels comparable to other published stalk-binding and neutralizing monoclonal antibodies, FI6v3 and CR9114. By testing the antibody against a panel of HA mutants, we found that the antibody bound to a region of the HA stalk previously reported for IgG1 antibodies of this class. Studies are on-going, but thus far demonstrate a broadly cross-reactive and neutralizing IgA antibody that recognizes the HA stalk of both group 1 and group 2 influenza viruses.
Pet shop mice are infected with a novel lymphocytic choriomeningitis virus strain that sustains an abundance of stem-like PD-1+ CD8 T cells
Authors: Beura Lalit K , Pierson Mark J , Wijeyesinghe Sathi P , Scott Milcah C , Semler Mathew R , Quarnstrom Clare , Hart Sara Hamilton , O’Connor David , Estes Jacob D , Vezys Vaiva , Masopust David 
Published: January 2023

Abstract
Lymphocytic choriomeningitis virus (LCMV) is a natural mouse pathogen. LCMV Armstrong, an acutely resolved strain, and LCMV Clone13, 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. Here, we describe LCMV Minnesota (LCMV-MN), which was 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 widely disseminated viral replication and viremia that was controlled within 15–30 days; which is of intermediate duration between LCMV Armstrong and Clone13. The magnitude of the LCMV-MN specific CD8+ T cell was maintained at much higher levels than that observed after LCMV Armstrong or Clone13 infections. LCMV-MN responding CD8+ T cells were further associated with significantly biased differentiation towards the recently described PD1+ CXCR5+ Tim-3lo stem-like CD8+ T cell population that was previously shown to be largely responsible for responsiveness to PD-1 inhibitory checkpoint blockade. In contrast to LCMV Clone13-induced responses, this subset persisted after resolution of LCMV-MN viremia, yet transcriptionally, phenotypically and functionally resembled PD1+ TCF1+ stem-like CD8+ T cells maintained by LCMV Clone13 infection. Together with existing models, LCMV-MN may contribute to a better understanding of the breadth of immune response in different chronic infections or tumor settings as well as the regulation of responsiveness to PD-1 blockade.
Virus-based vaccines with unique replication mechanisms differentially infect and activate dendritic cells leading to distinctive CD8+ T cell responses
Authors: Chiale Carolina , Robek Michael 
Published: January 2023

Abstract
The precise mechanism by which many virus-based vectors activate immune responses remains unknown. Dendritic cells (DCs) play key roles in priming T cell responses and controlling virus replication, but their functions in generating protective immunity following vaccination with viral vectors are not well understood. We hypothesized that highly immunogenic viral vectors with unique replication mechanisms but identical cell entry pathways differentially infect and activate DCs and promote antigen presentation that leads to efficient induction of distinctive antigen-specific T cell responses. To evaluate differences in replication mechanisms, we utilized a rhabdovirus vector (VSV) and an alphavirus-rhabdovirus hybrid vector (VLV), which replicates like an alphavirus but enters the cell via the VSV glycoprotein. We found that while virus replication promotes CD8+ T cell activation by VLV, replication is absolutely required for VSV-induced responses. DC subtypes were differentially infected in vitro with VSV and VLV, and displayed differences in activation following infection that were dependent on vector replication. Although bone marrow-derived DCs produced type I IFN when infected with the vectors, the mechanism of DC infection and activation was independent of type I IFN receptor signaling. Additionally, the ability of the alphavirus-based vector to generate CD8+ T cells in the absence of replication relied on cDC1 cells that promote antigen cross-presentation. These results highlight the differential activation of DCs following infection with unique viral vectors, and indicate potentially distinct roles of DC subtypes in activating the immune response following immunization.
A Comparison of Methods for Determination of Potency as Observed on a Group of Horses Immunized against Diphtheria
Authors: Leonard George F. 
Published: January 2023

Summary
The potencies of antidiphtheritic sera obtained on trial bleedings during the course of immunization of a group of 20 horses were obtained by three different methods: The official test of the Hygienic Laboratory, based on prolongation of life of guinea pigs when injected subcutaneously with the trial serum along with an L + dose of standardized toxin. The so-called intracutaneous method, based upon the production of erythema at the site of intradermal injection into a guinea pig of a mixture of trial serum and standardized toxin. Flocculation in vitro when the trial serum is mixed with standardized toxin. The intracutaneous test yields results in closer agreement with those obtained by the official test than does the flocculation test. The last gives consistently lower values. The substantial accuracy of the intracutaneous test, as well as its economy of time and materials, makes it probably the method of choice for estimation of antidiphtheritic potency on trial bleedings.
Agglutinin Production in Suprarenalectomized Rats
Authors: Khorazo Devorah 
Published: January 2023

Abstract
Recent work of Jaffe and Marine (1) indicated that suprarenalectomized rats immunized with typhoid vaccine, within three weeks after operation, showed agglutinins against B. typhosus of a titer two to three times greater than that of normal rats similarly treated. On the other hand, Steinbach (2) found a lowering of resistance to tuberculosis in suprarenalectomized rats. This would seem to indicate that in spite of the fact Jaffe and Marine obtained an increase in antibody formation in suprarenalectomized rats, nevertheless the resistance of these animals to infection had been impaired by this operation. Therefore, because of the possible relationship which may exist between the suprarenal and antibody formation and of the discrepancy which seems to exist between antibody formation and resistance to disease, we have undertaken a series of experiments to repeat the work of Jaffe and Marine.
The present investigation was carried out in a manner similar to that described by these investigators.
Studies of the Properties of Bouillon Filtrates of the Meningococcus: Production of a Soluble Toxin
Authors: Ferry N. S. , Norton J. F. , Steele A. H. 
Published: January 2023

Abstract
No conclusive evidence has been found in the literature to prove that an extracellular or soluble toxin has been obtained from the meningococcus. The concensus of opinion is that the toxic reaction of this organism is due entirely to a substance or to substances intracellular or endotoxic in nature, and while the term “toxin” has been used rather loosely in the literature to identify the poisonous elements of this organism, it has referred specifically to products endoplasmic in character and not to those commonly classified as soluble toxins.
Zinsser (1) in his Textbook of Bacteriology states, “No soluble exotoxin has ever been conclusively isolated from the meningococcus” and he accounts for the so-called toxin on the ground that “A number of investigators have found that cultures that have been kept in broth long enough for a certain amount of extraction or autolysis to occur, yield toxic products which are in general identical in their action to that of whole meningococci injected in analogous quantities.”
Flocculation of Vaccinial Virus-Tissue Suspensions by Specific Antisera
Authors: Thompson Richard , Buchbinder Leon 
Published: January 2023

Summary
The flocculation of vaccinial virus-skin suspensions by homologous antiserum noted by Gordon (5) and utilized by Burgess et al. (4) in the diagnosis of variola has been readily confirmed. The same antigens were also flocculated by immune sera against vaccinial brain and testicle tissues but not by sera from rabbits immunized against normal skin, normal brain, normal testicle, or streptococcal skin tissue. The sera from rabbits recovered from extensive vaccinial skin infections did not flocculate the virus-skin suspensions. Control antigens of normal skin and streptococcal skin suspensions were not flocculated by sera which caused marked flocculation of the virus-skin suspensions. Calf lymph and crusts from skin lesions of a small pox case were flocculated readily by antisera against the rabbit viruses. Brain and testicle virus suspensions, although they produced potent flocculating sera, were found to be unsuitable antigens for demonstrating the specific flocculation. There is a well marked correlation between the flocculating and neutralizing titers of the various antisera, although occasionally the neutralizing titer may be quite high in the absence of any flocculating power. The flocculating antibodies are specifically absorbed by the virus-skin suspensions and it is indicated, but by no means proved, that they are also absorbed by the non-flocculable virus brain and virus testicle antigens.
Studies on the Serological Reactions of the Flagella of B. Typhosus
Authors: Craigie James 
Published: January 2023

Summary
A complement-fixation technique applicable to suspensions of the flagella of B. typhosus has shown that such suspensions deviate complement specifically in the presence of (a) somatic agglutinating sera, (b) pure flagellar agglutinating sera. The “antigen” which reacts with (a) is heat stable while that which reacts with (b) is not completely inactivated by exposure to 100°C. for one hour.
If the labilotropic agglutinin of Felix is identical with flagellar agglutinin then the double receptor hypothesis is of doubtful validity. The possibility that the complement-fixation technique adopted by this author is unsuited for the demonstration of fixation in which the labilotropic antibody is involved is discussed.
It is probable that flagella are much more sensitive to the action of agglutinating sera than are somata and, if so, the antibody content of flagellar and somatic sera cannot legitimately be compared on the basis of agglutinin titres. If the H titre of a serum gives an exaggerated impression of the amount of H antibody present the main arguments in favour of the double receptor hypothesis require reconsideration.
The author desires to record his indebteness to Professor W. J. Tulloch for the facilities which he has afforded for the work described in these papers, for his constant interest and for his advice and criticism.
Parenteral Denaturization of Foreign Proteins
Authors: Sox Harold C. , Manwaring W. H. 
Published: January 2023

Summary
Horse serum incubated in a mixture with 10 to 1000 volumes of normal canine serum, shows a fairly rapid and consistent destruction (or total denaturization) of proteins of full horse protein specificity, accompanied by an initial increase and subsequent gradual decrease in proteins intermediary in specificity between horse and dog.
These intermediary test tube products are apparently identical with the metaphorical “hybrid” specificities demonstrable in the canine circulation after intravenous injection with horse proteins.
Electric Charge of Bacterial Antigens
Authors: Olitzki Leo 
Published: January 2023

Abstract
A number of investigators have studied the nature of the electric charge of bacteria. Bechhold (1904) was the first to record the fact that bacterial cells carry a negative charge. Cernovodeanu and Henri (1906) studied a larger series of bacteria and reported that all species, except B. dysenteriae (Flexner), carried a negative charge; but the claim that the dysentery bacillus is electropositive has been contradicted by Szent-Gyorgi (1921). Since then a number of investigators have reported that bacteria migrate to the anode (Szent-Gyorgi (1921); Putter (1921); Winslow, Falk, and Caulfield (1923); Govaerts (1923)).
Winslow and his co-workers (1923, 1924) used the microscopic cell devised by Northrop (1922) to study the electrophoretic migration of a large number of microörganisms under a wide range of pH values. This method enabled the authors to determine the migration velocities of various microörganisms and particles in substrates having various pH values.
Bacterial Endotoxin
Authors: Hanks John H. , Rettger Leo F. 
Published: January 2023

Abstract
Since Pfeiffer (1894) first used the word “endotoxin” to describe the toxic substances which he derived from the cholera vibrio and the typhoid bacillus, numerous efforts have been made to demonstrate similar substances in various pathogenic organisms. A review of the voluminous literature which has accumulated on the subject of toxin production by members of the colon-typhoid group of bacteria reveals that the organisms employed in such investigations were grown under cultural conditions which are widely different from those of the animal body, and that, with few exceptions, the toxins thus obtained were studied in animals other than the natural host.
It would appear that the more nearly the conditions of the animal body are approximated in artificial culture the greater will be the possibility of the in vivo and in vitro metabolism of the parasite being similar or identical.
This consideration seems important in any study of the rôle of bacterial toxins in disease.
Purification of Concentrated Antitoxins
Authors: Gerlough Tillman D. , White Woodford 
Published: January 2023

Summary
A study has been made of the application of the isoelectric method for further purification of concentrated antitoxins of varying age and previous treatment dialyzed to different specific conductances. The effectiveness of this method for removal of objectionable impurities was compared with that of fractional precipitation by salting out. The potency and amount of protein found in the isoelectric precipitates varied not only with age and previous treatment of the antitoxin, but also with the conductivity of the dialyzed solution. The specific conductance of the diluted antitoxin solutions which afforded optimum practical separations was found to be between 125 and 85 × 10-6. In the concentration of antitoxins, heating of the plasma renders subsequent isoelectric purification of the concentrates more effective for the removal of phosphorus bearing materials. After the removal of isoelectric protein from tetanus and diphtheria antitoxins and especially after electrodialysis the potencies of the fractions precipitated at lower concentrations of ammonium sulphate were increased. In the case of electrodialyzed tetanus the fractions precipitating between 34 and 43 per cent of saturation with ammonium sulphate, representing the bulk of the active protein, were of uniform potency. Data are submitted which show quantitatively the superiority of the isoelectric method over salt fractionation for removing euglobulin, fat and phospholipins from concentrated antitoxin.
Immunological Studies in Tuberculosis
Authors: Petroff S. A. , Steenken, W. , Winn W. A. 
Published: January 2023

Discussion and Summary
The prevalence of avian tuberculosis has been pointed out in the preceding pages. What rôle this type of disease and avian tubercle bacilli play in the epidemiology of human infection and disease is not yet clear.
Human tuberculosis, as we see it today, is unquestionably due in most cases to human tubercle bacilli. The occasional isolation of types of bacilli from sputum or lesions of tuberculous patients which do not fit into the standard pattern of human, bovine and avian strains, suggest the possibility of a mutation. At present we have no definite proof that the avian organism may change into the human or bovine type. The only evidence we have is that it has apparently been isolated from human beings by Lowenstein, Urbach, Joannovich, Deutsch and others and that of L'Esperance finding it in Hodgkin's disease. Although the avian tubercle bacillus is found very rarely in human beings, we must take into consideration that this organism is a possible epidemiological factor when we map out our campaign against tuberculosis in man. The infection may enter the body either through eggs (raw or partially cooked) which contain the bacilli or through partially cooked chickens.
The eradication of avian tuberculosis must be advised not only for epidemiological reasons, but also as an actual practical economic factor.
In the past ten years attempts have been made to eliminate fowls reacting to tuberculin. This method has been moderately successful. We must hope also to direct our efforts to building up resistance to avian tuberculosis by some method of vaccination.
In this paper we have presented experimental studies using heat-killed and living avirulent organisms to produce sensitization. Chickens sensitized with various types of dissociated avian tubercle bacilli may be thus made tuberculin hypersensitive. Those sensitized with heat-killed “R” developed a greater sensitiveness; those sensitized with heat-killed “S” reacted to a lesser degree. The heat-killed undissociated culture and the living “R” inoculated into fowls were allergic only for a short period and showed a lower intensity (see tables 1, 2, 3 and 4). So far as this experiment can be taken as an indication, a greater degree of protection was demonstrated in chickens vaccinated with heat-killed “S” organisms. In this group 28 out of 48 fowls were free from tuberculosis. Unfortunately, 8 out of 42 controls were free from tuberculosis. We cannot explain at present these negative results in the controls. Possibly the first attempt to give them an enteric infection gave them a resistance against the intravenous infection. It will be noted histological examination revealed greater calcification and healing in the vaccinated fowls and especially those vaccinated with heat-killed “S” organisms.