Project description:Vampire bats and snakes have taken thermosensation to the extreme by developing specialized systems for detecting infrared radiation. As such, these creatures provide a window into the molecular and genetic mechanisms underlying evolutionary tuning of thermoreceptors in a species or cell type specific manner. In each case, robust thermal sensitivity likely reflects specialized anatomical features of infrared sensing pit organs, as well as intrinsic heat sensitivity of trigeminal nerve fibers that innervate these structures. Here we show that vampire bats use a molecular strategy involving alternative splicing of the TRPV1 gene to generate a channel specifically within trigeminal ganglia that has a reduced thermal activation threshold. Selective expression of splicing factors in trigeminal, but not dorsal root ganglia, together with unique organization of the vampire bat TRPV1 gene underlies this mechanism of sensory adaptation. Comparative genomic analysis of the TRPV1 locus supports phylogenetic relationships within the proposed Pegasoferae clade of mammals. Gene expression measurements implicate a TRPV1 splice isoform as the heat-sensitive channel in vampire bats
Project description:A study of cardiac troponin I evolution in mammals with high heart rates, including shrews, moles, and bats. With genomic, mRNA and protein level analyses we showed repeated loss of the N-terminal extension. Here, liquid chromatography with tandem mass spectrometry was used to verify cardiac troponin I (TNNI3) protein identity in ∼22 kDa bands from Pyrenean desman (Galemys pyrenaicus) and northern short-tailed shrew (Blarina brevicauda) hearts.
Project description:Hearing mediates many behaviors critical for survival in echolocating bats, including foraging and navigation. Although most mammals are susceptible to progressive age-related hearing loss, the evolution of biosonar, which requires the ability to hear low-intensity echoes from outgoing sonar signals, may have selected against the development of hearing deficits in bats. Many echolocating bats exhibit exceptional longevity and rely on acoustic behaviors for survival to old age; however relatively little is known about the aging bat auditory system. In this study, we used DNA methylation to estimate the ages of wild-caught big brown bats (Eptesicus fuscus) and measured hearing sensitivity in young and aging bats using auditory brainstem responses (ABRs) and distortion product otoacoustic emissions (DPOAEs). We found no evidence for hearing deficits in bats up to 12.5 years of age, demonstrated by comparable thresholds and similar ABR and DPOAE amplitudes across age groups. We additionally found no significant histological evidence for cochlear aging, with similar hair cell counts, afferent, and efferent innervation patterns in young and aging bats. Here we demonstrate that big brown bats show minimal evidence for age-related hearing loss and therefore represent informative models for investigating mechanisms that may preserve hearing function over a long lifetime.
Project description:Bats harbour various viruses without severe symptoms and act as natural reservoirs. This tolerance of bats toward viral infections is assumed to be originated from the uniqueness of their immune system. However, how the innate immune response varies between primates and bats remains unclear. To illuminate differences in innate immune responses among animal species, we performed a comparative single-cell RNA-sequencing analysis on peripheral blood mononuclear cells (PBMCs) from four species including Egyptian fruit bats inoculated with various infectious stimuli.
Project description:As the only truly flying mammals, bats use their unique wing formed from elongated digits connected by membranes to power their flight. The forelimb of bats consists of four elongated digits (digits II-V) and one shorter digit (digit I) that is morphologically similar to the hindlimb digits. Elongation of bat forelimb digits is thought to results from changes in the temporal and spatial expression of a number of developmental genes. As a result, comparing gene expression profiles between short and elongated digit morphologies of the fore- and hindlimbs may elucidate the molecular mechanisms underlying digit elongation in bats. Here, we performed a large-scale analysis of gene expression of forelimb digit I, forelimb digits II-V, and all five hindlimb digits in Myotis ricketti using digital gene expression tag profiling approach. Results of this study not only implicate several developmental genes as robust candidates underlying digit elongation in bats, but also provide a better understanding of the genes involved in autopodial development in general. A large-scale analysis of gene expression of 3 different parts of autopods in Myotis ricketti using digital gene expression tag profiling approach.
Project description:Chemotherapy resistance is a relevant clinical issue in the tumor treatment, in particular in biliary tract carcinoma (BTC), for which there are no effective therapies, neither in the first nor in the second line. The development of chemoresistant cell lines as experimental models to investigate the mechanisms of resistance and identify alternative druggable pathways is mandatory. In BTC, in which genetics and biological behavior depend on the etiology, ethnicity and anatomical site of origin, the creation of models that better recapitulate these characteristics is even more crucial. Here we have established and characterized an intrahepatic cholangiocarcinoma (iCCA) cell line derived from an Italian patient, called 82.3. Cells were isolated from a patient-derived xenograft and, after establishment, immunophenotypic, biological, genetic, molecular characteristics and tumorigenicity in vivo in NOD/SCID mice were investigated. 82.3 cells exhibited epithelial morphology and cell markers (EPCAM, CK7 and 19); they also expressed different cancer stem markers (CD44, CD133, CD49b, CD24, Stro1, PAX6, FOXA2, OCT3 / 4) and under anchorage-independent and serum-free conditions were capable of originating cholangiospheres. The population doubling time was approximately 53 hours. In vitro they demonstrated a poor ability to migrate, but in vivo, 82.3 cells retained their tumorigenicity, with a long latency period (16 weeks). Genetic identity using DNA fingerprinting analysis revealed 16 different loci and the cell line was characterized by a complex hyperdiploid karyotype. Furthermore, 82.3 cells showed cross-resistance to gemcitabine, 5-fluorouracil, carboplatin and oxaliplatin; in fact their genetic profile showed that in a panel of genes (n = 168), specific for drug resistance and related to the epithelial-mesenchymal transition, 60% of them were deregulated in 82.3 cells compared to a control iCCA cell line sensitive to chemotherapeutics. In conclusion, we have created new iCCA cell line of Caucasian origin that could be exploited as a preclinical model to study drug resistance mechanisms and to identify alternative therapies to improve the prognosis of this tumor type.
Project description:As the only truly flying mammals, bats use their unique wing formed from elongated digits connected by membranes to power their flight. The forelimb of bats consists of four elongated digits (digits II-V) and one shorter digit (digit I) that is morphologically similar to the hindlimb digits. Elongation of bat forelimb digits is thought to results from changes in the temporal and spatial expression of a number of developmental genes. As a result, comparing gene expression profiles between short and elongated digit morphologies of the fore- and hindlimbs may elucidate the molecular mechanisms underlying digit elongation in bats. Here, we performed a large-scale analysis of gene expression of forelimb digit I, forelimb digits II-V, and all five hindlimb digits in Myotis ricketti using digital gene expression tag profiling approach. Results of this study not only implicate several developmental genes as robust candidates underlying digit elongation in bats, but also provide a better understanding of the genes involved in autopodial development in general.
Project description:A combined transcriptomic and miRNA-based analysis of the molecular mechanism of collection preference in Italian honey bees was conducted, mainly selecting the long-range sensor tentacles and the proximal sensor mouthparts.
Project description:Vampire bats and snakes have taken thermosensation to the extreme by developing specialized systems for detecting infrared radiation. As such, these creatures provide a window into the molecular and genetic mechanisms underlying evolutionary tuning of thermoreceptors in a species or cell type specific manner. In each case, robust thermal sensitivity likely reflects specialized anatomical features of infrared sensing pit organs, as well as intrinsic heat sensitivity of trigeminal nerve fibers that innervate these structures. Here we show that vampire bats use a molecular strategy involving alternative splicing of the TRPV1 gene to generate a channel specifically within trigeminal ganglia that has a reduced thermal activation threshold. Selective expression of splicing factors in trigeminal, but not dorsal root ganglia, together with unique organization of the vampire bat TRPV1 gene underlies this mechanism of sensory adaptation. Comparative genomic analysis of the TRPV1 locus supports phylogenetic relationships within the proposed Pegasoferae clade of mammals.