421 research outputs found
Muscle ultrastructural changes from exhaustive exercise performed after prolonged restricted activity and retraining in dogs
The effect of exhaustive treadmill exercise on ultrastructural changes in the quadriceps femoris muscle was studied in 7 normal, healthy dogs, before and after restricted activity (RA), and following a subsequent 2 month treadmill exercise retraining period for the 5 mo group. Mean time to exhaustion in the 2 mo group decreased from 177 + or - 22 min before to 90 + or - 32 min after RA. Retraining increased tolerance to 219 + or - 73 min; 24 pct. above the before RA and 143 pct. above the after RA time. After RA exhaustion time in the 5 mo group was 25 and 45 min. Before RA, pre-exercise muscle structure was normal and post exercise there was only slight swelling of mitochondria. After RA, pre-exercise, numerous glycogen granules and lipid droplets appeared in the muscle fibers, mitochondria were smaller, and sarcoplasmic reticulum channels widened; post exercise these changes were accentuated and some areas were devoid of glycogen, and there was fiber degradation. After 5 mo RA pre-exercise there were more pronounced changes; mitochondria were very small and dense, there were many lipid droplets, myofibrils were often separated, and the fibers appeared edematous and degenerating; post exercise the sarcoplasmic reticulum was swollen, no glycogen was present, and there was marked swelling and deformation of mitochondria. After retraining, both pre-exercise and post exercise there was still evidence of fiber degeneration. Thus, susceptibility of active skeletal muscle structures and subcellular elements, e.g., mitochondria, to the action of damaging factors occurring during exhaustive exercise is enhanced considerably by prolonged disuse
Molecular Mechanisms Leading from Periodontal Disease to Cancer
Periodontitis is prevalent in half of the adult population and raises critical health concerns as it has been recently associated with an increased risk of cancer. While information about the topic remains somewhat scarce, a deeper understanding of the underlying mechanistic pathways promoting neoplasia in periodontitis patients is of fundamental importance. This manuscript presents the literature as well as a panel of tables and figures on the molecular mechanisms of Porphyromonas gingivalis and Fusobacterium nucleatum, two main oral pathogens in periodontitis pathology, involved in instigating tumorigenesis. We also present evidence for potential links between the RANKL–RANK signaling axis as well as circulating cytokines/leukocytes and carcinogenesis. Due to the nonconclusive data associating periodontitis and cancer reported in the case and cohort studies, we examine clinical trials relevant to the topic and summarize their outcome
ABCB1 Does Not Require the Side-Chain Hydrogen-Bond Donors Gln347, Gln725, Gln990 to Confer Cellular Resistance to the Anticancer Drug Taxol
The multidrug efflux transporter ABCB1 is clinically important for drug absorption and
distribution and can be a determinant of chemotherapy failure. Recent structure data shows that three
glutamines donate hydrogen bonds to coordinate taxol in the drug binding pocket. This is consistent
with earlier drug structure-activity relationships that implicated the importance of hydrogen bonds
in drug recognition by ABCB1. By replacing the glutamines with alanines we have tested whether
any, or all, of Gln347, Gln725, and Gln990 are important for the transport of three different drug classes.
Flow cytometric transport assays show that Q347A and Q990A act synergistically to reduce transport
of Calcein-AM, BODIPY-verapamil, and OREGON GREEN-taxol bisacetate but the magnitude of
the effect was dependent on the test drug and no combination of mutations completely abrogated
function. Surprisingly, Q725A mutants generally improved transport of Calcein-AM and BODIPYverapamil, suggesting that engagement of the wild-type Gln725 in a hydrogen bond is inhibitory for
the transport mechanism. To test transport of unmodified taxol, stable expression of Q347/725A
and the triple mutant was engineered and shown to confer equivalent resistance to the drug as
the wild-type transporter, further indicating that none of these potential hydrogen bonds between
transporter and transport substrate are critical for the function of ABCB1. The implications of the
data for plasticity of the drug binding pocket are discussed
Tarcza zegarowa z pierwszej połowy XVII wieku z Muzeum Warmii i Mazur w Olsztynie – zagadnienia historyczno-stylistyczne oraz technologiczno-konserwatorskie.
Specjalistyczne badania, przeprowadzone na XVII-wiecznej, dwustronnej tarczy zegarowej, ze zbiorów Muzeum Warmii i Mazur w Olsztynie, pozwoliły nie tylko na identyfikację pigmentów zastosowanych to wykonania oryginalnej polichromii oraz materiałów warstw wtórnych, ale także na rozpoznanie typów i określenie zakresu występowania produktów chemicznej degradacji warstw barwnych. Dzięki analizie historycznej i stylistycznej, możliwe było również ulokowanie badanego obiektu w kontekście dziejów sztuki zegarmistrzowskiej, a także odtworzenie jego losów od poł. XX wieku to czasów obecnych. Zgromadzony materiał stał się podstawą do stworzenia szczegółowej dokumentacji na temat stanu zachowania obiektu, a także odegrał kluczową rolę w trakcie podejmowania kolejnych decyzji w trakcie prowadzonych prac konserwatorskich
Differential Expression of Ovine Innate Immune Genes by Preterm and Neonatal Lung Epithelia Infected with Respiratory Syncytial Virus
Preterm infants have increased susceptibility to severe manifestations of respiratory syncytial virus (RSV) infection. The cause(s) for this age-dependent vulnerability is/are not well-defined, but alterations in innate immune products have been implicated. In sheep, RSV disease severity has similar age-dependent characteristics and sheep have several related innate molecules for study during pulmonary infection including surfactant protein A (SP-A), surfactant protein D (SP-D), sheep beta defensin 1 (SBD1), monocyte chemotactic protein 1 (MCP1), and Toll-like receptor 4 (TLR4). However, the in vivo cellular gene expression as a response to RSV infection is poorly understood. In this study, the effect of RSV infection on expression of these innate immune genes was determined for bovine RSV-infected (bRSV+ fluorescence) epithelial cells, adjacent cells lacking bRSV antigen (adjoining cells lacking fluorescence), and control cells from non-infected lung using laser capture microdissection (LCM) and real-time RT-PCR. Control lambs had increased expression of innate immune molecules in full term (term) compared to preterm epithelia with statistical significance in SBD1, SP-D, and TLR4 mRNA. Infected cells (bRSV+ fluorescent cells) had consistently higher mRNA levels of SP-A (preterm and term), MCP1 (preterm and term), and SP-D (preterm). Interestingly, bRSV- cells of infected term lambs had significantly reduced SP-D mRNA expression compared to bRSV+ and control epithelia, suggesting that RSV infected cells may regulate the adjacent epithelial SP-D expression. This study defines specific innate immune components (e.g., SBD1, SP-D, and TLR4) that have differential age-dependent expression in the airway epithelia. Furthermore, cellular bRSV infection enhanced certain innate immune components while suppressing adjacent cellular SP-D expression in term animals. These in vivo gene expression results provide a framework for future studies on age-dependent susceptibility to RSV and RSV pathogenesis
A review and comparison of ontology-based approaches to robot autonomy
Within the next decades, robots will need to be able to execute a large variety of tasks autonomously in a large variety of environments. To relax the resulting programming effort, a knowledge-enabled approach to robot programming can be adopted to organize information in re-usable knowledge pieces. However, for the ease of reuse, there needs to be an agreement on the meaning of terms. A common approach is to represent these terms using ontology languages that conceptualize the respective domain. In this work, we will review projects that use ontologies to support robot autonomy. We will systematically search for projects that fulfill a set of inclusion criteria and compare them with each other with respect to the scope of their ontology, what types of cognitive capabilities are supported by the use of ontologies, and which is their application domain.Peer ReviewedPostprint (author's final draft
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