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Objective: To report an outbreak of follicular conjunctivitis in a group of sheep diagnosed with Anaplasma spp., without any other co‐infection. Animals Studied: In all, 18 animals from a sheep head, males and females, from eight months to four years of age, were assessed for follicular conjunctivitis. Procedures: The procedures performed included general physical and ophthalmological examinations; PCR evaluation for infectious agents; analysis of hematological parameters, microbiological tests of ocular swabs, coproparasitological examination, histopathological examination of conjunctival biopsy. Results: All 18 animals had uni‐ or bilateral follicular conjunctivitis, and one animal also had unilateral uveitis. The results of microbiological analyzes were negative for Moraxella spp., Staphylococcus spp., and Pseudomonas spp., and PCR analysis results were negative for Chlamydia spp., Mycoplasma spp., and Toxoplasma gondii. Anemia, thrombocytopenia, lymphocytosis, and an inclusion body in some erythrocytes, compatible with Anaplasma and PCR analysis for Anaplasma spp. were positive. Conclusion: Anaplasmosis may be associated with follicular conjunctivitis in sheep and should be included in the differential diagnosis list and investigated in cases of conjunctivitis in herds. [ABSTRACT FROM AUTHOR]

It is projected that higher doses of KT-333 will achieve the predicted degradation profile in tumors that may translate into clinical benefit in patients with STAT3-dependent T cell malignancies. B Background: b KT-333 is a first-in-class, potent, highly selective, heterobifunctional small molecule degrader of the signal transducer and activator of transcription 3 (STAT3) protein. Phase 1 trial of KT-333, a STAT3 degrader, in patients with relapsed or refractory lymphomas, large granular lymphocytic leukemia and solid tumors. [Extracted from the article]

Contents To support conservation strategies in wild species, simple but highly reproducible procedures of sperm cryopreservation are required for an application under field conditions. We used epididymal sperm of the domestic cat to optimize a sperm freezing procedure for felid species, particularly questioning the demand for sperm cooling to 4°C. We equilibrated sperm during slow cooling to only 15 or 10°C in a Tes-Tris-fructose extender with final concentrations of 4.7% (v/v) glycerol and 10% (v/v) of the water-soluble fraction of hen's egg yolk (low-density lipoproteins). Subsequently, sperm were frozen over liquid nitrogen. Total and progressive motility (mean ± SD) after thawing was 60.7 ± 8.6% and 53.9 ± 9.6% in samples cooled to 15°C or 61.6 ± 9.5% and 55.3 ± 9.9% in samples cooled to 10°C. Therefore, a one-step addition of glycerol to sperm at room temperature together with the freezing extender, the use of cryovials (loaded with diluted sperm aliquots of 300 μl), an equilibration period of 40 min comprising slow cooling to 15°C at a rate of approximately −0.14 K/min before rapid freezing over liquid nitrogen, yielded satisfying results. Cooling, freezing and thawing rates were exactly characterized as a prerequisite for further optimization and to provide a repeatable protocol to other practitioners. [ABSTRACT FROM AUTHOR]

Background IgE-mediated allergy is a common disease characterized by a harmful immune response towards otherwise harmless environmental antigens. Induction of specific immunological non-responsiveness towards allergens would be a desirable goal. Blockade of costimulatory pathways is a promising strategy to modulate the immune response in an antigen-specific manner. Recently, OX40 ( CD134) was identified as a costimulatory receptor important in Th2-mediated immune responses. Moreover, synergy between OX40 blockade and 'conventional' costimulation blockade (anti- CD40L, CTLA4Ig) was observed in models of alloimmunity. Objective We investigated the potential of interfering with OX40 alone or in combination with CD40/ CD28 signals to influence the allergic immune response. Methods The OX40 pathway was investigated in an established murine model of IgE-mediated allergy where BALB/c mice are repeatedly immunized with the clinically relevant grass pollen allergen Phl p 5. Groups were treated with combinations of anti- OX40L, CTLA4Ig and anti- CD40L. In selected mice, Tregs were depleted with anti- CD25. Results Blockade of OX40L alone at the time of first or second immunization did not modulate the allergic response on the humoral or effector cell levels but slightly on T cell responses. Administration of a combination of anti- CD40L/ CTLA4Ig delayed the allergic immune response, but antibody production could not be inhibited after repeated immunization even though the allergen-specific T cell response was suppressed in the long run. Notably, additional blockade of OX40L had no detectable supplementary effect. Immunomodulation partly involved regulatory T cells as depletion of CD25+ cells led to restored T cell proliferation. Conclusions and Clinical Relevance Collectively, our data provide evidence that the allergic immune response towards Phl p 5 is independent of OX40L, although reduction on T cell responses and slightly on the asthmatic phenotype was detectable. Besides, no relevant synergistic effect of OX40L blockade in addition to CD40L/ CD28 blockade could be detected. Thus, the therapeutic potential of OX40L blockade for IgE-mediated allergy appears to be ineffective in this setting. [ABSTRACT FROM AUTHOR]

Background Development of antigen-specific preventive strategies is a challenging goal in IgE-mediated allergy. We have recently shown in proof-of-concept experiments that allergy can be successfully prevented by induction of durable tolerance via molecular chimerism. Transplantation of syngeneic hematopoietic stem cells genetically modified to express the clinically relevant grass pollen allergen Phl p 5 into myeloablated recipients led to high levels of chimerism (i.e. macrochimerism) and completely abrogated Phl p 5-specific immunity despite repeated immunizations with Phl p 5. Objective It was unclear, however, whether microchimerism (drastically lower levels of chimerism) would be sufficient as well which would allow development of minimally toxic tolerance protocols. Methods Bone marrow cells were transduced with recombinant viruses integrating Phl p 5 to be expressed in a membrane-anchored fashion. The syngeneic modified cells were transplanted into non-myeloablated recipients that were subsequently immunized repeatedly with Phl p 5 and Bet v 1 (control). Molecular chimerism was monitored using flow cytometry and PCR. T cell, B-cell and effector-cell tolerance were assessed by allergen-specific proliferation assays, isotype levels in sera and RBL assays. Results Here we demonstrate that transplantation of Phl p 5-expressing bone marrow cells into recipients having received non-myeloablative irradiation resulted in chimerism persisting for the length of follow-up. Chimerism levels, however, declined from transient macrochimerism levels to persistent levels of microchimerism (followed for 11 months). Notably, these chimerism levels were sufficient to induce B-cell tolerance as no Phl p 5-specific IgE and other high affinity isotypes were detectable in sera of chimeric mice. Furthermore, T-cell and effector-cell tolerance were achieved. Conclusions and Clinical Relevance Low levels of persistent molecular chimerism are sufficient to induce long-term tolerance in IgE-mediated allergy. These results suggest that it will be possible to develop minimally toxic conditioning regimens sufficient for low level engraftment of genetically modified bone marrow. [ABSTRACT FROM AUTHOR]

Habitat selection in ungulates should ensure access to abundant forage of sufficiently high quality. Species living in rugged mountain areas have to face nutritional bottlenecks regularly and should show particularly sophisticated habitat selection behaviour. However, patterns and mechanisms of such adaptations remain little studied. We analysed habitat selection and its seasonal variability of 10 GPS-collared red deer Cervus elaphus living in a topographically challenging landscape of the Swiss Alps. We hypothesised that resource selection by red deer was scale-dependent and predicted that scale-dependence would vary among seasons in relation to seasonal changes of available forage biomass and quality, which we sampled across the entire study area of 250 km2. The studied population of Alpine red deer undertook altitudinal migrations and showed scale-dependent habitat selection that was strongest in winter and declined through spring and summer. Selection occurred mostly at the larger (landscape/home-range location) scale and less so at the smaller (within home-range) scale. Topographic parameters were selected mainly at the landscape scale and mostly in winter. About 70% of all instances of preference for habitat parameters were associated with above-average forage characteristics, represented mostly by higher crude protein content, in a few cases also by higher biomass or both. The overall pattern of space use by red deer characterised by migration and seasonal habitat selection was therefore closely linked to the quality of food resources, although some trade-offs with avoiding human disturbance may also have been involved. [ABSTRACT FROM AUTHOR]