Mutations in dynein link motor neuron degeneration to defects in retrograde transport

Degenerative disorders of motor neurons include a range of progressive fatal diseases such as amyotrophic lateral sclerosis (ALS), spinal-bulbar muscular atrophy (SBMA), and spinal muscular atrophy (SMA). Although the causative genetic alterations are known for some cases, the molecular basis of many SMA and SBMA-like syndromes and most ALS cases is unknown. Here we show that missense point mutations in the cytoplasmic dynein heavy chain result in progressive motor neuron degeneration in heterozygous mice, and in homozygotes this is accompanied by the formation of Lewy-like inclusion bodies, thus resembling key features of human pathology. These mutations exclusively perturb neuron-specific functions of dynein.     

The V-antigen of Yersinia forms a distinct structure at the tip of injectisome needles

Many pathogenic bacteria use injectisomes to deliver effector proteins into host cells through type III secretion. Injectisomes consist of a basal body embedded in the bacterial membranes and a needle. In Yersinia, translocation of effectors requires the YopB and YopD proteins, which form a pore in the target cell membrane, and the LcrV protein, which assists the assembly of the pore. Here we report that LcrV forms a distinct structure at the tip of the needle, the tip complex. This unique localization of LcrV may explain its crucial role in the translocation process and its efficacy as the main protective antigen against plague.     

The contribution of single synapses to sensory representation in vivo

The extent to which synaptic activity can signal a sensory stimulus limits the information available to a neuron. We determined the contribution of individual synapses to sensory representation by recording excitatory postsynaptic currents (EPSCs) in cerebellar granule cells during a time-varying, quantifiable vestibular stimulus. Vestibular-sensitive synapses faithfully reported direction and velocity, rather than position or acceleration of whole-body motion, via bidirectional modulation of EPSC frequency. The lack of short-term synaptic dynamics ensured a highly linear relationship between velocity and charge transfer, and as few as 100 synapses provided resolution approaching psychophysical limits. This indicates that highly accurate stimulus representation can be achieved by small networks and even within single neurons.     

Dynamic visualization of thrombopoiesis within bone marrow

Platelets are generated from megakaryocytes (MKs) in mammalian bone marrow (BM) by mechanisms that remain poorly understood. Here we describe the use of multiphoton intravital microscopy in intact BM to visualize platelet generation in mice. MKs were observed as sessile cells that extended dynamic proplatelet-like protrusions into microvessels. These intravascular extensions appeared to be sheared from their transendothelial stems by flowing blood, resulting in the appearance of proplatelets in peripheral blood. In vitro, proplatelet production from differentiating MKs was enhanced by fluid shear. These results confirm the concept of proplatelet formation in vivo and are consistent with the possibility that blood flow-induced hydrodynamic shear stress is a biophysical determinant of thrombopoiesis.     

Stakeholder participation in agricultural research projects: a conceptual framework for reflection and decision-making

Recent discourse in the field of participatory agricultural research has focused on how to blend various forms and intensities of stakeholder participation with quality agricultural science, moving beyond the simple “farmer-first” ideology of the 1980s and early 1990s. Yet, most existing frameworks of participation in agricultural research still adhere to a linear typology of participatory research with an inherent claim of “the more participation, the better.” In this article, we propose a new framework that looks at participatory research elements along different dimensions and attributes and thus takes into account the diversity and dynamics of agricultural research projects. The framework provides a basis for agricultural researchers engaged in participatory processes with local stakeholders to decide for which issues and in which phases certain participatory elements could be used in a specific research context. Rather than aiming at maximizing the adoption of participatory methods, it can thus become a tool for optimizing the use of participatory approaches in agricultural research. We conclude that this framework can be a starting point for a more thoughtful integration of participatory elements in agricultural research projects that does justice to the multidimensional and dynamic nature of stakeholder participation in varying contexts.     

Detection of near-atmospheric concentrations of CO2 by an olfactory subsystem in the mouse

Carbon dioxide (CO2) is an important environmental cue for many organisms but is odorless to humans. It remains unclear whether the mammalian olfactory system can detect CO2 at concentrations around the average atmospheric level (0.038%). We demonstrated the expression of carbonic anhydrase type II (CAII), an enzyme that catabolizes CO2, in a subset of mouse olfactory neurons that express guanylyl cyclase D (GC-D+ neurons) and project axons to necklace glomeruli in the olfactory bulb. Exposure to CO2 activated these GC-D+ neurons, and exposure of a mouse to CO2 activated bulbar neurons associated with necklace glomeruli. Behavioral tests revealed CO2 detection thresholds of approximately 0.066%, and this sensitive CO2 detection required CAII activity. We conclude that mice detect CO2 at near-atmospheric concentrations through the olfactory subsystem of GC-D+ neurons.     

Rise of the Andes

The surface uplift of mountain belts is generally assumed to reflect progressive shortening and crustal thickening, leading to their gradual rise. Recent studies of the Andes indicate that their elevation remained relatively stable for long periods (tens of millions of years), separated by rapid (1 to 4 million years) changes of 1.5 kilometers or more. Periodic punctuated surface uplift of mountain belts probably reflects the rapid removal of unstable, dense lower lithosphere after long-term thickening of the crust and lithospheric mantle.     

Ice flow direction change in interior West Antarctica

Upstream of Byrd Station (West Antarctica), ice-penetrating radar data reveal a distinctive fold structure within the ice, in which isochronous layers are unusually deep. The fold has an axis more than 50 kilometers long, which is aligned up to 45 degrees to the ice flow direction. Although explanations for the fold's formation under the present flow are problematic, it can be explained if flow was parallel to the fold axis approximately 1500 years ago. This flow change may be associated with ice stream alterations nearer the margin. If this is true, central West Antarctica may respond to future alterations more than previously thought.