Molecular Identification of Brucella Abortus Bv5 and Strain 19 in Water Buffaloes (Bubalus Bubalis) in Northeast Argentina

Buffalo (Bubalus bubalis) populations are spread across northern Argentina, and they share their habitat with bovines. Both species are susceptible to brucellosis, and they are under a National Plan of Control and Eradication. To characterize the Brucella spp. that infects buffaloes, the blood of 35 animals that tested positive to brucellosis by a complement fixation test was collected. DNA was obtained and analyzed by polymerase chain reaction using different molecular markers. The genera, species, and biovars of Brucella were established by analyzing specific regions of the genes omp31, eri, alkB, and omp2ab. Brucella spp. was identified in 15 of 35 tested buffaloes. The product of the omp31 gene identified the genera. The detection of two fragments of 297 bp and/or 1000 bp from the eri gene confirmed the presence of B. abortus S19 and wild-type B. abortus. The amplification of the alkB gene allowed the identification of B. abortus biovars characterized by fragments of 498 bp (bv1, bv2, or bv4). The simultaneous amplification of 498 bp (alkB) and 1000 bp (eri) products suggested the presence of B. abortus bv1, which is highly prevalent in the cattle of Argentina. Fragments of 827 bp and 857 bp were amplified from the omp2ab gene, and their sequences showed 100% identity with B. melitensis and B. abortus bv5 (GenBank). However, the 721 bp product (alkB) specific for B. melitensis could not be amplified. This is the first report indicating the presence of B. abortus bv5 in Latin America.Fil: Martinez, Diana. Universidad Nacional del Nordeste; ArgentinaFil: Thompson, Carolina. Instituto Nacional de Tecnologia Agropecuaria. Centro Regional Santa Fe. Estacion Experimental Agropecuaria Rafaela; ArgentinaFil: Russo, Ana Maria. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro de Investigaciones y Transferencia de Formosa; ArgentinaFil: Jacobo, Roberto. Universidad Nacional del Nordeste; ArgentinaFil: Torioni de Echaide, Susana. Instituto Nacional de Tecnologia Agropecuaria. Centro Regional Santa Fe. Estacion Experimental Agropecuaria Rafaela; Argentin

Detection of Mycobacterium bovis-Infected Dairy Herds Using PCR in Bultk Tank Milk Samples

Bovine tuberculosis (bTB) is a chronic and zoonotic disease due to Mycobacterium bovis. The tuberculosis eradication campaign carried out in Argentina has considerably improved the health situation of the herds. Here we evaluated a strategy to detect M. bovis-infected herds by Touch-Down IS6110 polymerase chain reaction (PCR) in bulk tank raw milk from dairy farms. We evaluated 177 samples from herds with the official tuberculosis free certificate (TFC) and 80 from herds without the certificate, non-tuberculosis-free certificate (NTFC), from 10 departments of Santa Fe province, Argentina. To avoid the effect of Taq polymerase inhibitors, a dilution of DNA template was performed. Positive PCR results were obtained in 102 (40%) of the samples, whereas negative ones were obtained in 155 (60%) of the samples. Importantly, 44% of NTFC and 38% of TFC samples were positive. All samples were subjected to culture in Löwenstein Jensen and Stonebrink media with no positive isolation. The negative predictive value (NPV) of PCR in the TFC group was 95%, while the positive predictive value (PPV) of PCR in the NTFC group was 51%. Based on these results, this work proposes a method that should be applied regularly to detect M. bovis--infected dairy herds, complementary to the official test of tuberculin, or purifed protein derivative (PPD), to control dairy herds, especially those free of tuberculosis.Fil: Zumárraga, Martín José. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Soutullo, Adriana Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Garcia, Maria Ines. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Litoral; ArgentinaFil: Marini, Rocío. Universidad Nacional del Litoral; ArgentinaFil: Abdala, Alejandro Ariel. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Santa Fe. Estación Experimental Agropecuaria Rafaela; ArgentinaFil: Tarabla, Héctor. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Santa Fe. Estación Experimental Agropecuaria Rafaela; ArgentinaFil: Echaide, Susana. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Santa Fe. Estación Experimental Agropecuaria Rafaela; ArgentinaFil: López, Marcela. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; ArgentinaFil: Zerbini, Elsa Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; ArgentinaFil: Canal, Ana. Universidad Nacional del Litoral; ArgentinaFil: Cataldi, Ángel Adrián. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Current Indications and Future Landscape of Bispecific Antibodies for the Treatment of Lung Cancer

Bispecific antibodies are a promising type of therapy for the treatment of cancer due to their ability to simultaneously inhibit different proteins playing a role in cancer progression. The development in lung cancer has been singularly intense because of the increasingly vast knowledge of the underlying molecular routes, in particular, in oncogene-driven tumors. In this review, we present the current landscape of bispecific antibodies for the treatment of lung cancer and discuss potential scenarios where the role of these therapeutics might expand in the near future

Detection of Mycobacterium bovis–infected dairy herds using PCR in bulk tank milk samples

Bovine tuberculosis (bTB) is a chronic and zoonotic disease due to Mycobacterium bovis. The tuberculosis eradication campaign carried out in Argentina has considerably improved the health situation of the herds. Here we evaluated a strategy to detect M. bovis–infected herds by Touch-Down IS6110 polymerase chain reaction (PCR) in bulk tank raw milk from dairy farms. We evaluated 177 samples from herds with the official tuberculosis free certificate (TFC) and 80 from herds without the certificate, non-tuberculosis-free certificate (NTFC), from 10 departments of Santa Fe province, Argentina. To avoid the effect of Taq polymerase inhibitors, a dilution of DNA template was performed. Positive PCR results were obtained in 102 (40%) of the samples, whereas negative ones were obtained in 155 (60%) of the samples. Importantly, 44% of NTFC and 38% of TFC samples were positive. All samples were subjected to culture in Löwenstein Jensen and Stonebrink media with no positive isolation. The negative predictive value (NPV) of PCR in the TFC group was 95%, while the positive predictive value (PPV) of PCR in the NTFC group was 51%. Based on these results, this work proposes a method that should be applied regularly to detect M. bovis--infected dairy herds, complementary to the official test of tuberculin, or purifed protein derivative (PPD), to control dairy herds, especially those free of tuberculosis.Instituto de BiotecnologíaFil: Zumarraga, Martin Jose. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; ArgentinaFil: Soutullo, Adriana. Ministerio de la Producción. Dirección General de Sanidad Animal. Laboratorio de Diagnóstico e Investigaciones Agropecuarias; ArgentinaFil: Garcia, Maria Ines. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Cátedra de Inmunología Básica; ArgentinaFil: Marini, M. Rocío. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Cátedra de Patología Básica; ArgentinaFil: Abdala, Alejandro Ariel. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Rafaela; ArgentinaFil: Tarabla, Hector Dante. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Rafaela; ArgentinaFil: Echaide, Susana T. de. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Rafaela; ArgentinaFil: Lopez, Marcela. Administración Nacional de Laboratorios e Institutos de Salud Dr. Carlos Malbrán (ANLIS). Instituto Nacional de Enfermedades Respiratorias Dr. Emilio Coni; ArgentinaFil: Zervini, Elsa. Administración Nacional de Laboratorios e Institutos de Salud Dr. Carlos Malbrán (ANLIS). Instituto Nacional de Enfermedades Respiratorias Dr. Emilio Coni; ArgentinaFil: Canal, Ana María. Ministerio de la Producción. Dirección General de Sanidad Animal. Laboratorio de Diagnóstico e Investigaciones Agropecuarias; Argentina. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Cátedra de Patología Básica; ArgentinaFil: Cataldi, Angel Adrian. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentin

Immune Profiling Uncovers Memory T-Cell Responses with a Th17 Signature in Cancer Patients with Previous SARS-CoV-2 Infection Followed by mRNA Vaccination

It is unclear whether patients with cancer present inherently impaired responses to COVID-19 and vaccination due to their treatments, neoplastic diseases or both. To address this question, immune profiling was performed in three cohorts of healthy donors and oncologic patients: infected with SARS-CoV-2, BNT162b2-vaccinated, and with previous COVID-19 disease and subsequently vaccinated. Cancer patients showed good antibody responses to vaccination, but poor induction of T-cell responses towards the S protein when compared to infection. Following natural infection, the major targets for T-cells were the SARS-CoV-2 structural proteins M and S, but not the N protein. Similar to antibody titers, the T-cell responses quickly decayed after six months post-vaccination. Significant memory T-cell expansion was observed in vaccinated donors only if previously diagnosed with COVID-19 before undergoing vaccination. Oncologic patients with previous COVID-19 followed by vaccination exhibited potent IL-17+ CD4 and CD8 T-cell responses and elevated numbers of circulating neutrophils in peripheral blood

A Proteomic Atlas of Lineage and Cancer-Polarized Expression Modules in Myeloid Cells Modeling Immunosuppressive Tumor-Infiltrating Subsets

Monocytic and granulocytic myeloid-derived suppressor cells together with tumor-infiltrating macrophages constitute the main tumor-infiltrating immunosuppressive myeloid populations. Due to the phenotypic resemblance to conventional myeloid cells, their identification and purification from within the tumors is technically difficult and makes their study a challenge. We differentiated myeloid cells modeling the three main tumor-infiltrating types together with uncommitted macrophages, using ex vivo differentiation methods resembling the tumor microenvironment. The phenotype and proteome of these cells was compared to identify linage-dependent relationships and cancer-specific interactome expression modules. The relationships between monocytic MDSCs and TAMs, monocytic MDSCs and granulocytic MDSCs, and hierarchical relationships of expression networks and transcription factors due to lineage and cancer polarization were mapped. Highly purified immunosuppressive myeloid cell populations that model tumor-infiltrating counterparts were systematically analyzed by quantitative proteomics. Full functional interactome maps have been generated to characterize at high resolution the relationships between the three main myeloid tumor-infiltrating cell types. Our data highlights the biological processes related to each cell type, and uncover novel shared and differential molecular targets. Moreover, the high numbers and fidelity of ex vivo-generated subsets to their natural tumor-shaped counterparts enable their use for validation of new treatments in high-throughput experiments