Diversidad y morfometría de tardígrados de una ciudad mediana de la región Neotropical: Santa Rosa (La Pampa, Argentina)

Tardigrade diversity was studied in a medium–sized city in the Neotropical Region: Santa Rosa (La Pampa, Argentina). Samples were collected between February 1999 and January 2000 from lichens and mosses growing on sidewalk trees of the urban and periurban area. Five species of tardigrades were found, i.e., Echiniscus rufoviridis du Bois–Reymond Marcus, 1944, Macrobiotus areolatus Murray, 1907, Ramazzottius oberhaeuseri (Doyère, 1840), Milnesium cf. tardigradum and a non–described species of Macrobiotus. Only one species, M. cf. tardigradum, was found in areas with high levels of vehicle traffic. Results are compared with those from cities in the Nearctic and Palearctic regions. Measurements and pt index values (percentage ratios between the length of the structure considered and the buccal tube length) are provided for M. areolatus, R. oberhaeuseri and M. cf. tardigradum. Amongst the characters considered, the pt index for the stylet support insertion shows the least intraspecific variation. This character is also independent from body length and buccal–tube length. Key words: Tardigrades, Neotropical fauna, Urban environment, Biotic homogenization, Morphometric analysis, Medium–size cities.Se estudió la diversidad de tardígrados en una ciudad mediana de la Región Neotropical: Santa Rosa (La Pampa, Argentina). Las muestras se recolectaron entre febrero de 1999 y enero de 2000 de líquenes y musgos que crecían sobre árboles de vereda de áreas urbanas y periurbanas. Se encontraron cinco especies de tardígrados: Echiniscus rufoviridis du Bois–Reymond Marcus, 1944, Macrobiotus areolatus Murray, 1907, Ramazzottius oberhaeuseri (Doyère, 1840), Milnesium cf. tardigradum y una especie no descrita de Macrobiotus. M. cf. tardigradum fue la única especie encontrada en áreas con alto tránsito vehicular. Los resultados se comparan con los de ciudades de las Regiones Neártica y Paleártica. Se brindan medidas y valores del índice pt (relación porcentual entre la longitud de la estructura considerada y la longitud del tubo bucal) para M. areolatus, R. oberhaeuseri y M. cf. tardigradum. Entre los caracteres considerados, el índice pt correspondiente a la inserción del soporte de los estiletes es el que muestra la menor variabilidad intraespecífica. Además, este carácter es independiente del largo total del cuerpo y del largo del tubo bucal. Palabras clave: Tardígrados, Fauna neotropical, Ambiente urbano, Homogenización biótica, Análisis morfométrico, Ciudades medianas

Species diversity and morphometrics of tardigrades from a medium-size city in the Neotropical Region: Santa Rosa (La Pampa, Argentina)

Tardigrade diversity was studied in a medium-sized city in the Neotropical Region: Santa Rosa (La Pampa, Argentina). Samples were collected between February 1999 and January 2000 from lichens and mosses growing on sidewalk trees of the urban and periurban area. Five species of tardigrades were found, i.e., Echiniscus rufoviridis du Bois-Reymond Marcus, 1944, Macrobiotus areolatus Murray, 1907, Ramazzottius oberhaeuseri (Doyère, 1840), Milnesium cf. tardigradum and a non-described species of Macrobiotus. Only one species, M. cf. tardigradum, was found in areas with high levels of vehicle traffic. Results are compared with those from cities in the Nearctic and Palearctic regions. Measurements and pt index values (percentage ratios between the length of the structure considered and the buccal tube length) are provided for M. areolatus, R. oberhaeuseri and M. cf. tardigradum. Amongst the characters considered, the pt index for the stylet support insertion shows the least intraspecific variation. This character is also independent from body length and buccal-tube length

Identification and relative quantification of tyrosine nitration in a model peptide using two-dimensional infrared spectroscopy

Nitration of tyrosine in proteins and peptides is a post-translational modification that occurs under conditions of oxidative stress. It is implicated in a variety of medical conditions, including neurodegenerative and cardiovascular diseases. However, monitoring tyrosine nitration and understanding its role in modifying biological function remains a major challenge. In this work, we investigate the use of electron-vibration-vibration (EVV) two-dimensional infrared (2DIR) spectroscopy for the study of tyrosine nitration in model peptides. We demonstrate the ability of EVV 2DIR spectroscopy to differentiate between the neutral and deprotonated states of 3-nitrotyrosine, and we characterize their spectral signatures using information obtained from quantum chemistry calculations and simulated EVV 2DIR spectra. To test the sensitivity of the technique, we use mixed-peptide samples containing various levels of tyrosine nitration, and we use mass spectrometry to independently verify the level of nitration. We conclude that EVV 2DIR spectroscopy is able to provide detailed spectroscopic information on peptide side-chain modifications and to detect nitration levels down to 1%. We further propose that lower nitration levels could be detected by introducing a resonant Raman probe step to increase the detection sensitivity of EVV 2DIR spectroscopy. (Graph Presented)

JAK-STAT signaling in inflammatory breast cancer enables chemotherapy-resistant cell states

Inflammatory breast cancer (IBC) is a difficult-to-treat disease with poor clinical outcomes due to high risk of metastasis and resistance to treatment. In breast cancer, CD44+CD24- cells possess stem cell-like features and contribute to disease progression, and we previously described a CD44+CD24-pSTAT3+ breast cancer cell subpopulation that is dependent on JAK2/STAT3 signaling. Here we report that CD44+CD24- cells are the most frequent cell-type in IBC and are commonly pSTAT3+. Combination of JAK2/STAT3 inhibition with paclitaxel decreased IBC xenograft growth more than either agent alone. IBC cell lines resistant to paclitaxel and doxorubicin were developed and characterized to mimic therapeutic resistance in patients. Multi-omic profiling of parental and resistant cells revealed enrichment of genes associated with lineage identity and inflammation in chemotherapy resistant derivatives. Integrated pSTAT3 ChIP-seq and RNA-seq analyses showed pSTAT3 regulates genes related to inflammation and epithelial to mesenchymal transition (EMT) in resistant cells, as well as PDE4A, a cAMP-specific phosphodiesterase. Metabolomic characterization identified elevated cAMP signaling and CREB as a candidate therapeutic target in IBC. Investigation of cellular dynamics and heterogeneity at the single cell level during chemotherapy and acquired resistance by CyTOF and single cell RNA-seq identified mechanisms of resistance including a shift from luminal to basal/mesenchymal cell states through selection for rare pre-existing subpopulations or an acquired change. Lastly, combination treatment with paclitaxel and JAK2/STAT3 inhibition prevented the emergence of the mesenchymal chemo-resistant subpopulation. These results provide mechanistic rational for combination of chemotherapy with inhibition of JAK2/STAT3 signaling as a more effective therapeutic strategy in IBC

Nonviral Approaches for Neuronal Delivery of Nucleic Acids

The delivery of therapeutic nucleic acids to neurons has the potential to treat neurological disease and spinal cord injury. While select viral vectors have shown promise as gene carriers to neurons, their potential as therapeutic agents is limited by their toxicity and immunogenicity, their broad tropism, and the cost of large-scale formulation. Nonviral vectors are an attractive alternative in that they offer improved safety profiles compared to viruses, are less expensive to produce, and can be targeted to specific neuronal subpopulations. However, most nonviral vectors suffer from significantly lower transfection efficiencies than neurotropic viruses, severely limiting their utility in neuron-targeted delivery applications. To realize the potential of nonviral delivery technology in neurons, vectors must be designed to overcome a series of extra- and intracellular barriers. In this article, we describe the challenges preventing successful nonviral delivery of nucleic acids to neurons and review strategies aimed at overcoming these challenges

Response and resistance to BET bromodomain inhibitors in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a heterogeneous and clinically aggressive disease for which there is no targeted therapy. BET bromodomain inhibitors, which have shown efficacy in several models of cancer, have not been evaluated in TNBC. These inhibitors displace BET bromodomain proteins such as BRD4 from chromatin by competing with their acetyl-lysine recognition modules, leading to inhibition of oncogenic transcriptional programs. Here we report the preferential sensitivity of TNBCs to BET bromodomain inhibition in vitro and in vivo, establishing a rationale for clinical investigation and further motivation to understand mechanisms of resistance. In paired cell lines selected for acquired resistance to BET inhibition from previously sensitive TNBCs, we failed to identify gatekeeper mutations, new driver events or drug pump activation. BET-resistant TNBC cells remain dependent on wild-type BRD4, which supports transcription and cell proliferation in a bromodomain-independent manner. Proteomic studies of resistant TNBC identify strong association with MED1 and hyper-phosphorylation of BRD4 attributable to decreased activity of PP2A, identified here as a principal BRD4 serine phosphatase. Together, these studies provide a rationale for BET inhibition in TNBC and present mechanism-based combination strategies to anticipate clinical drug resistance