The spinal cord supports of vertebrae in the crown‐group salamanders (Caudata,Urodela)

The development of spinal cord supports (bony thickenings which extend into the vertebral canal of vertebrae) in primitive (Salamandrella keyserlingii) and derived (Lissotriton vulgaris) salamanders were described. The spinal cord supports develop as the protuberances of periostal bone of the neural arches in the anteroproximal part of the septal collagenous fibers which connect a transverse myoseptum with the notochord and spinal cord, in the septal bundle inside the vertebral canal. Spinal cord supports were also found in some teleostean (Salmo salar, Oncorhynchus mykiss) and dipnoan (Protopterus sp.) fishes. The absence of the spinal cord supports in vertebrates with cartilaginous vertebrae (lampreys, chondrichthyan, and chondrostean fishes) corresponds to the fact that the spinal cord supports are bone structures. The absence of the spinal cord supports in frogs correlates with the lack of the well developed septal bundles inside the vertebral canal. The spinal cord supports are, presumably, a synapomorphic character for salamanders which originated independently of those observed in teleostean and dipnoan fishes. J. Morphol. 2012. © 2012 Wiley Periodicals, Inc.     

Identification of Tumor Antigens in the HLA Peptidome of Patient-derived Xenograft Tumors in Mouse

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Highlights

• •Sufficient tumor tissues are often unavailable large HLA peptidome discovery.
• •Using patient derived xenograft (PDX) tumors can overcome this limitation.
• •The large PDX HLA peptidomes expand significantly those of the original biopsies.
• •The HLA peptidomes of the PDX tumors included many tumor antigens.

     

Importance of hydrogen-bonding interactions involving the side chain of Asp158 in the catalytic mechanism of papain

In a previous study, it was shown that replacing Asp158 in papain by Asn had little effect on activity and that the negatively charged carboxylate of Asp158 does not significantly stabilize the active site thiolate-imidazolium ion pair of papain (Ménard et al., 1990). In this paper, we report the kinetic characterization of three more mutants at this position: Asp158Gly, Asp158Ala, and Asp158Glu. From the pH-activity profiles of these and other mutants of papain, it has been possible to develop a model that enables us to dissect out the contribution of the various mutations toward (i) intrinsic activity, (ii) ion pair stability, and (iii) the electrostatic potential at the active site. Results obtained with mutants that place either Gly or Ala at position 158 indicate that the hydrogen bonds involving the side chain of Asp158 in wild-type papain are indirectly important for enzyme activity. When CBZ-Phe-Arg-MCA is used as a substrate, the (kcat/KM)obs values at pH 6.5 are 3650 and 494 M-1 s-1 for Asp158Gly and Asp158Ala, respectively, as compared to 119,000 M-1 s-1 for papain. Results with the Asp158Glu mutant suggest that the side chain of Glu moves closer to the active site and cannot form hydrogen bonds similar to those involving Asp158 in papain. From the four mutations introduced at position 158 in papain, we can conclude that it is not the charge but the hydrogen-bonding interactions involving the side chain of Asp158 that contribute the most to the stabilization of the thiolate-imidazolium ion pair in papain. However, the charge and the hydrogen bonds of Asp158 both contribute to the intrinsic activity of the enzyme.     

Translating Cancer Molecular Variability into Personalized Information Using Bulk and Single Cell Approaches

Cancer research is striving toward new frontiers of assigning the correct personalized drug(s) to a given patient. However, extensive tumor heterogeneity poses a major obstacle. Tumors of the same type often respond differently to therapy, due to patient‐specific molecular aberrations and/or untargeted tumor subpopulations. It is frequently not possible to determine a priori which patients will respond to a certain therapy or how an efficient patient‐specific combined therapy should be designed. Large‐scale datasets have been growing at an accelerated pace and various technologies and analytical tools for single cell and bulk level analyses are being developed to extract significant individualized signals from such heterogeneous data. However, personalized therapies that dramatically alter the course of the disease remain scarce, and most tumors still respond poorly to medical care. In this review, the basic concepts of bulk and single cell approaches are discussed, as well as their emerging role in individualized designs of drug therapies, including the advantages and limitations of their applications in personalized medicine.     

Diagnosis,Burden and Mortality of Pneumocystis jirovecii Pneumonia in Venezuela

Current Fungal Infection Reports - The aim of this work is to contribute to the knowledge of diagnosis, burden, and mortality of pneumocystosis or Pneumocystis jirovecii pneumonia (PCP) in...     

Post-Glacial Climate–Fire Interactions Control Tree Composition of Mesic Temperate Forests in Eastern North America

Stand-scale gap-phase dynamics is generally viewed as the main driver of development in mesic deciduous forests of the temperate biome. Soil charcoal of temperate forests in eastern North America are unnoticed in most surveys, thus explaining why fire is undervalued as a driver of forest succession. The extent to which gap-phase, fire, or other processes are responsible for the regeneration and maintenance of mesic deciduous forests is unknown because paleoecological evidence is lacking. We tested the fire-driven succession hypothesis on the development of this major forest type. Based on charcoal ¹⁴C dates of two sites, 44 and 55 fires occurred since early Holocene, with a mean interval of 170 to 215 years. The vegetation of both sites followed comparable post-glacial trajectories consisting of three distinct periods. Conifers dominated the two first periods during 5200–6000 years and were replaced by hardwoods–conifers over the last 3500 years. The first period was represented by boreal conifers, whereas the second period, dominated by white pine (Pinus strobus) forests, persisted during 3000–4300 years. The third period marked the development of hardwood (sugar maple, Acer saccharum) forests. Fires occurred continuously on the sites since early Holocene likely under dry conditions during the conifer periods and cooler and moister conditions during the hardwood–conifer period. Recurrent fires appear with climate as key drivers of the long-term dynamics of several temperate forests in eastern North America. Similar studies on other temperate forests should be pursued to test the hypothesis of climate–fire interactions influencing tree composition change.

     

In pursuit of negative Fukui functions: examples where the highest occupied molecular orbital fails to dominate the chemical reactivity

In our quest to explore molecules with chemically significant regions where the Fukui function is negative, we explored reactions where the frontier orbital that indicates the sites for electrophilic attack is not the highest occupied molecular orbital. The highest occupied molecular orbital (HOMO) controls the location of the regions where the Fukui function is negative, supporting the postulate that negative values of the Fukui function are associated with orbital relaxation effects and nodal surfaces of the frontier orbitals. Significant negative values for the condensed Fukui function, however, were not observed.