Co-localization of molecules involved in antigen processing and presentation in an early endocytic compartment

The pathways of intracellular traffic involved in antigen processing and presentation have been defined by immunoelectron microscopy. The export pathway for class II histocompatibility molecules and the antigen import pathway meet in a peripheral endocytic compartment having all the molecular machinery believed to be required for antigen processing and presentation, including internalized surface immunoglobulins, proteolytic enzymes and invariant chains. This compartment defines a site where peptides from endocytosed antigen can bind class II molecules en route to the cell surface for presentation to T cells.     

Genetic and developmental basis of evolutionary pelvic reduction in threespine sticklebacks

Hindlimb loss has evolved repeatedly in many different animals by means of molecular mechanisms that are still unknown. To determine the number and type of genetic changes underlying pelvic reduction in natural populations, we carried out genetic crosses between threespine stickleback fish with complete or missing pelvic structures. Genome-wide linkage mapping shows that pelvic reduction is controlled by one major and four minor chromosome regions. Pitx1 maps to the major chromosome region controlling most of the variation in pelvic size. Pelvic-reduced fish show the same left-right asymmetry seen in Pitx1 knockout mice, but do not show changes in Pitx1 protein sequence. Instead, pelvic-reduced sticklebacks show site-specific regulatory changes in Pitx1 expression, with reduced or absent expression in pelvic and caudal fin precursors. Regulatory mutations in major developmental control genes may provide a mechanism for generating rapid skeletal changes in natural populations, while preserving the essential roles of these genes in other processes.     

Exercise conditioning decreases downstream movement of pond-reared razorback suckers released into a stream environment

Despite augmentation stocking efforts, wild populations of razorback suckers ( Xyrauchen texanus ) continue to decline. Endangered razorback suckers are commonly raised in off-channel ponds until maturity (approximately 300 mm TL) and then stocked into the Colorado River or its tributaries. After fish are stocked, they commonly move large distances downstream. We conducted an experiment to determine if downstream dispersal could be reduced through exercise conditioning. Two groups of razorback suckers, exercised and nonexercised, were released into Fossil Creek, Arizona. Prior to release, a subsample from each treatment group was tested in a laboratory flow chamber. Razorback suckers that had been exercise conditioned were able to maintain a position in the flow chamber 2 times longer and at velocities 25 cm · s –1 higher than nonexercised fish. Although the intended method of field data collection via passive-integrated-transponder (PIT) antennas and a remote communication station failed because river otters ( Lontra canadensis ) preyed upon the released razorback suckers, implanted PIT tags were retained in otter scat. Recovered PIT tags enabled distributional analysis, which indicated that exercised razorback suckers did not move as far downstream from the point of release as nonexercised razorbacks. Exercise conditioning may increase overall fitness of pond-reared razorback suckers, and, consequently, increase the effectiveness of augmentation stocking. A pesar de los esfuerzos de repoblación, las poblaciones silvestres del matalote jorobado ( Xyrauchen texanus ) siguen en declive. Los matalotes jorobados, que están en peligro de extinción, se crían en estanques fuera del cauce hasta la etapa adulta (~300 mm) y después son liberados en el Río Colorado o uno de sus afluentes. Los peces suelen desplazarse largas distancias río abajo después de su introducción al río. Llevamos a cabo un experimento para determinar si la dispersión río abajo se podía reducir mediante el acondicionamiento por ejercicio. Dos grupos de matalotes fueron liberados en Fossil Creek, Arizona, uno que había sido acondicionado y otro que no. Antes de liberarlos, examinamos una submuestra de cada grupo en una cámara de flujo en el laboratorio. Los matalotes que habían sido acondicionados por ejercicio pudieron mantener sus posición en la cámara de flujo dos veces más tiempo y a velocidades de 25 cm · s –1 más altas que los peces no acondicionados. Aunque falló el método de colecta de datos mediante antenas de sistema PIT (passive integrated transponder) y una estación remota de comunicación, los matalotes liberados fueron depredados por nutrias de río ( Lontra canadensis ) y las marcas PIT implantadas se quedaron en las heces de las nutrias. La recuperación de estas etiquetas PIT permitió un análisis de distribución que indicó que los matalotes acondicionados no se desplazaron río abajo tan lejos del punto de liberación como los matalotes no acondicionados. El acondicionamiento por ejercicio podría mejorar la condición física de los matalotes jorobados criados en cautiverio y así aumentar la eficacia de la reintroducción.     

Multiscale gigapixel photography

Pixel count is the ratio of the solid angle within a camera's field of view to the solid angle covered by a single detector element. Because the size of the smallest resolvable pixel is proportional to aperture diameter and the maximum field of view is scale independent, the diffraction-limited pixel count is proportional to aperture area. At present, digital cameras operate near the fundamental limit of 1-10 megapixels for millimetre-scale apertures, but few approach the corresponding limits of 1-100 gigapixels for centimetre-scale apertures. Barriers to high-pixel-count imaging include scale-dependent geometric aberrations, the cost and complexity of gigapixel sensor arrays, and the computational and communications challenge of gigapixel image management. Here we describe the AWARE-2 camera, which uses a 16-mm entrance aperture to capture snapshot, one-gigapixel images at three frames per minute. AWARE-2 uses a parallel array of microcameras to reduce the problems of gigapixel imaging to those of megapixel imaging, which are more tractable. In cameras of conventional design, lens speed and field of view decrease as lens scale increases, but with the experimental system described here we confirm previous theoretical results suggesting that lens speed and field of view can be scale independent in microcamera-based imagers resolving up to 50 gigapixels. Ubiquitous gigapixel cameras may transform the central challenge of photography from the question of where to point the camera to that of how to mine the data.     

Cell-specific ATP7A transport sustains copper-dependent tyrosinase activity in melanosomes

Copper is a cofactor for many cellular enzymes and transporters. It can be loaded onto secreted and endomembrane cuproproteins by translocation from the cytosol into membrane-bound organelles by ATP7A or ATP7B transporters, the genes for which are mutated in the copper imbalance syndromes Menkes disease and Wilson disease, respectively. Endomembrane cuproproteins are thought to incorporate copper stably on transit through the trans-Golgi network, in which ATP7A accumulates by dynamic cycling through early endocytic compartments. Here we show that the pigment-cell-specific cuproenzyme tyrosinase acquires copper only transiently and inefficiently within the trans-Golgi network of mouse melanocytes. To catalyse melanin synthesis, tyrosinase is subsequently reloaded with copper within specialized organelles called melanosomes. Copper is supplied to melanosomes by ATP7A, a cohort of which localizes to melanosomes in a biogenesis of lysosome-related organelles complex-1 (BLOC-1)-dependent manner. These results indicate that cell-type-specific localization of a metal transporter is required to sustain metallation of an endomembrane cuproenzyme, providing a mechanism for exquisite spatial control of metalloenzyme activity. Moreover, because BLOC-1 subunits are mutated in subtypes of the genetic disease Hermansky-Pudlak syndrome, these results also show that defects in copper transporter localization contribute to hypopigmentation, and hence perhaps other systemic defects, in Hermansky-Pudlak syndrome.