Diversification within the Mexican vole ( Microtus mexicanus ) and the role of post-Pleistocene climate change

Normal 0 false false false MicrosoftInternetExplorer4 st1\:*{behavior:url(#ieooui) } /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman"; mso-ansi-language:#0400; mso-fareast-language:#0400; mso-bidi-language:#0400;} To examine the partitioning of genetic variation within the Mexican vole ( Microtus mexicanus ), we analyzed variation within the cytochrome b (cyt b, ca. 953 bp) from 44 samples of the Mexican vole from the mountains of the southwestern United States and Mexico. Phylogeographic analyses demonstrated strong support for a western clade and an eastern clade, corresponding to the Sierra Madre Occidental and mountains of the southwestern United States (western clade) and the Sierra Madre Oriental and the Sierra Madre del Sur (eastern clade). Levels of genetic distinctiveness among vole populations in Mexico and the southwestern United States support recognition of the Mogollon vole ( Microtus mogollonensis ). Estimates of lineage divergence suggested an older divergence for populations in Mexico and a more recent divergence for the presumptive M. mogollonensis. Ecological analyses demonstrated a distinct climate niche between vole lineages in the Southwest and Mexico, which indicated the possible role of environmental variation in diversification of the Mexican vole. A similar pattern of climatic separation was also demonstrated between clades of the codistributed taxa Sigmodon hispidus, Neotoma mexicana, and Peromyscus truei, suggesting a broader role for climatic variation in the origin and maintenance of the region’s biodiversity. Para examinar la distribución de la variación genética en el metorito mexicano, analizamos la variación en el citocromo b (cyt b, c. 953 pb ) en 44 muestras del metorito mexicano de las montañas de México y del suroeste de Estados Unidos. Los análisis filogeográficos demostraron fuerte apoyo para un clado occidental y un clado oriental, correspondientes a la Sierra Madre Occidental y las montañas del suroeste de Estados Unidos (oeste) y la Sierra Madre Oriental y la Sierra Madre del Sur (este). Los niveles de diferencia genética entre las poblaciones de metoritos en México y las del sur de Estados Unidos apoyan el reconocimiento del metorito Mogollon ( Microtus mogollonensis ) como especie. Las estimaciones de divergencia entre linajes indican una divergencia más remota para las poblaciones en México y una más reciente para el presunto M. mogollonensis. Los análisis ecológicos demuestran nichos climáticos distintos entre los linajes de metorito en el suroeste de Estados Unidos y en México, lo cual indica el posible papel de la variación ambiental en la diversificación del metorito mexicano. Un patrón similar de separación climática fue también demostrado entre clados de los taxones codistribuidos: Sigmodon hispidus, Neotoma mexicana y Peromysus truei, sugiriendo que la variación climática tiene un mayor papel en el origen y el mantenimiento de la biodiversidad de la región.     

Slip rate variations on normal faults during glacial-interglacial changes in surface loads

Geologic and palaeoseismological data document a marked increase in the slip rates of the Wasatch fault and three adjacent normal faults in the Basin and Range Province during the Late Pleistocene/Early Holocene epochs. The cause of this synchronous acceleration of fault slip and the subsequent clustering of earthquakes during the Holocene has remained enigmatic, although it has been suggested that the coincidence between the acceleration of slip and the shrinkage of Lake Bonneville after the Last Glacial Maximum may indicate a causal relationship. Here we use finite-element models of a discrete normal fault within a rheologically layered lithosphere to evaluate the relative importance of two competing processes that affect fault slip: postglacial unloading (the removal of mass), which decreases the slip rate, and lithospheric rebound, which promotes faster slip. We show that lithospheric rebound caused by regression of Lake Bonneville and deglaciation of adjacent mountain ranges provides a feasible mechanism for the high Holocene rates of faulting in the Wasatch region. Our analysis implies that climate-controlled changes in loads applied to Earth's surface may exert a fundamental control on the slip history of individual normal faults.     

EphrinB2 is the entry receptor for Nipah virus, an emergent deadly paramyxovirus

Nipah virus (NiV) is an emergent paramyxovirus that causes fatal encephalitis in up to 70 percent of infected patients, and there is evidence of human-to-human transmission. Endothelial syncytia, comprised of multinucleated giant-endothelial cells, are frequently found in NiV infections, and are mediated by the fusion (F) and attachment (G) envelope glycoproteins. Identification of the receptor for this virus will shed light on the pathobiology of NiV infection, and spur the rational development of effective therapeutics. Here we report that ephrinB2, the membrane-bound ligand for the EphB class of receptor tyrosine kinases (RTKs), specifically binds to the attachment (G) glycoprotein of NiV. Soluble Fc-fusion proteins of ephrinB2, but not ephrinB1, effectively block NiV fusion and entry into permissive cell types. Moreover, transfection of ephrinB2 into non-permissive cells renders them permissive for NiV fusion and entry. EphrinB2 is expressed on endothelial cells and neurons, which is consistent with the known cellular tropism for NiV. Significantly, we find that NiV-envelope-mediated infection of microvascular endothelial cells and primary cortical rat neurons is inhibited by soluble ephrinB2, but not by the related ephrinB1 protein. Cumulatively, our data show that ephrinB2 is a functional receptor for NiV.     

Blastomitogenic agents in leguminosae and other families

Résumé Des agents blastomitogéniques furent décelés non seulement dans les extraits de 4 genres propres à la famille des Légumineuses, mais aussi dans les graines d'espèces déterminées appartenant aux familles des Solanacées, Composées, Ephédracées et Clusiacées. Ces 4 dernières sources, non mentionnées au préalable, témoignent de la répartition variée de ces agents dans la nature et donnent lieu à des conjectures aux points de vue de leur affinité chimique, du mécanisme de leur action blastomitogénique, de leur rôle dans la physiologie végétale et de leur importance dans l'évolution.     

Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer

A main limitation of therapies that selectively target kinase signalling pathways is the emergence of secondary drug resistance. Cetuximab, a monoclonal antibody that binds the extracellular domain of epidermal growth factor receptor (EGFR), is effective in a subset of KRAS wild-type metastatic colorectal cancers. After an initial response, secondary resistance invariably ensues, thereby limiting the clinical benefit of this drug. The molecular bases of secondary resistance to cetuximab in colorectal cancer are poorly understood. Here we show that molecular alterations (in most instances point mutations) of KRAS are causally associated with the onset of acquired resistance to anti-EGFR treatment in colorectal cancers. Expression of mutant KRAS under the control of its endogenous gene promoter was sufficient to confer cetuximab resistance, but resistant cells remained sensitive to combinatorial inhibition of EGFR and mitogen-activated protein-kinase kinase (MEK). Analysis of metastases from patients who developed resistance to cetuximab or panitumumab showed the emergence of KRAS amplification in one sample and acquisition of secondary KRAS mutations in 60% (6 out of 10) of the cases. KRAS mutant alleles were detectable in the blood of cetuximab-treated patients as early as 10 months before radiographic documentation of disease progression. In summary, the results identify KRAS mutations as frequent drivers of acquired resistance to cetuximab in colorectal cancers, indicate that the emergence of KRAS mutant clones can be detected non-invasively months before radiographic progression and suggest early initiation of a MEK inhibitor as a rational strategy for delaying or reversing drug resistance.     

Modulation of intracortical synaptic potentials by presynaptic somatic membrane potential

Traditionally, neuronal operations in the cerebral cortex have been viewed as occurring through the interaction of synaptic potentials in the dendrite and soma, followed by the initiation of an action potential, typically in the axon. Propagation of this action potential to the synaptic terminals is widely believed to be the only form of rapid communication of information between the soma and axonal synapses, and hence to postsynaptic neurons. Here we show that the voltage fluctuations associated with dendrosomatic synaptic activity propagate significant distances along the axon, and that modest changes in the somatic membrane potential of the presynaptic neuron modulate the amplitude and duration of axonal action potentials and, through a Ca2+-dependent mechanism, the average amplitude of the postsynaptic potential evoked by these spikes. These results indicate that synaptic activity in the dendrite and soma controls not only the pattern of action potentials generated, but also the amplitude of the synaptic potentials that these action potentials initiate in local cortical circuits, resulting in synaptic transmission that is a mixture of triggered and graded (analogue) signals.     

Positive and negative effects of widespread badger culling on tuberculosis in cattle

Human and livestock diseases can be difficult to control where infection persists in wildlife populations. For three decades, European badgers (Meles meles) have been culled by the British government in a series of attempts to limit the spread of Mycobacterium bovis, the causative agent of bovine tuberculosis (TB), to cattle. Despite these efforts, the incidence of TB in cattle has risen consistently, re-emerging as a primary concern for Britain's cattle industry. Recently, badger culling has attracted controversy because experimental studies have reached contrasting conclusions (albeit using different protocols), with culled areas showing either markedly reduced or increased incidence of TB in cattle. This has confused attempts to develop a science-based management policy. Here we use data from a large-scale, randomized field experiment to help resolve these apparent differences. We show that, as carried out in this experiment, culling reduces cattle TB incidence in the areas that are culled, but increases incidence in adjoining areas. These findings are biologically consistent with previous studies but will present challenges for policy development.