Cryptococcus gattii in the United States: clinical aspects of infection with an emerging pathogen.

BACKGROUND: Cryptococcus gattii (Cg) has caused increasing infections in the US Pacific Northwest (PNW) since 2004. We describe this outbreak and compare clinical aspects of infection in the United States among patients infected with different Cg genotypes. METHODS: Beginning in 2005, PNW state health departments conducted retrospective and prospective passive surveillance for Cg infections, including patient interviews and chart reviews; clinical isolates were genotyped at the US Centers for Disease Control and Prevention (CDC). We examined symptom frequency and underlying conditions in US patients with Cg infection and modeled factors associated with death. RESULTS: From 1 December 2004 to July 2011, 96 Cg infections were reported to the CDC. Eighty-three were in patients in or travelers to the PNW, 78 of which were genotypes VGIIa, VGIIb, or VGIIc (outbreak strains). Eighteen patients in and outside the PNW had other molecular type Cg infections (nonoutbreak strains). Patients with outbreak strain infections were more likely than those with nonoutbreak-strain infections to have preexisting conditions (86% vs 31%, respectively; P < .0001) and respiratory symptoms (75% vs 36%, respectively; P = .03) and less likely to have central nervous system (CNS) symptoms (37% vs 90%, respectively; P = .008). Preexisting conditions were associated with increased pneumonia risk and decreased risk of meningitis and CNS symptoms. Nineteen (33%) of 57 patients died. Past-year oral steroid use increased odds of death in multivariate analysis (P = .05). CONCLUSIONS: Clinical differences may exist between outbreak-strain (VGIIa, VGIIb, and VGIIc) and nonoutbreak-strain Cg infections in the United States. Clinicians should have a low threshold for testing for Cg, particularly among patients with recent travel to the PNW.

Giant enhancement of the second harmonic generation efficiency in poled multilayered silica glass structures.

Multilayered thin-film doped silica structures are experimentally demonstrated as an effective tool to enhance the second-order nonlinear properties induced in thermally poled glass devices. A 204-fold improvement is obtained in the second harmonic generated (SHG) in a poled structure with a 3 µm-thick multilayered stack consisting of sub- 100 nm-thick alternating germanium-doped and undoped silica layers compared to poled bulk silica glass. The induced nonlinearity is localized within the layered region, indicating that the multilayered design can be used to precisely control the thickness and the location of the nonlinearity. Such artificial nonlinear structures can be used to overcome the main limitations of existing poled glass devices, therefore opening the door to practical implementations of efficient active devices in silica glass.

A quantitative analysis of parvalbumin neurons in rabbit auditory neocortex.

Parvalbumin (PV) is a calcium-binding protein present in GABAergic cells in the cerebral cortex and in thalamic relay neurons. In the present study, parvalbumin immunocytochemistry (PVi) and stereological methods were used to obtain estimates of cortical volume, total neuron number, laminar density, and the percentage of PV-immunoreactive neurons in auditory neocortex. PVi clearly delineated the primary auditory cortex (AI), which was characterized by two PV+ bands: dense terminal-like labeling within lamina III/IV and PV+ somata in lamina VIa. Stereological analysis of Nissl-stained sections revealed that the total number of neurons in rabbit AI was 1.48 x 10(6) with a mean neuronal density of 55 x 10(3)/mm3. Based on a mean cortical thickness of 1.92 mm, there are approximately 106,000 neurons in a 1 mm2 column of auditory cortex. PVi yields an extraordinary Golgi-like staining of nonpyramidal cells in all cortical layers. PV+ nonpyramidal cells constitute approximately 7.0% of the neurons in AI. There were significant differences in the morphology and density of PV+ neurons across layers. Although only 5% of cells in lamina I were PV+, three nonpyramidal cell types were present. Lamina II had the highest numerical density within AI but the lowest percentage of PV+ neurons (3.3%). Lamina II, however, contained the greatest diversity of PV+ nonpyramidal cell types, which included small multipolar cells, bipolar cells, and, less frequently, large cells of the bitufted, bipolar, and stellate varieties. Lamina IV had one of the highest numerical densities (67.6 x 10(3) neurons/mm3) and contributed nearly 27% of the total neuron number in AI. The numerical density of PV+ nonpyramidal cells was also greatest within lamina IV (7.1 x 10(3)/mm3) where they formed 10.4% of the neuronal population. PV+ nonpyramidal cells in lamina IV and lamina III were predominantly large basket-type cells with bitufted dendritic domains and tangentially oriented local axonal plexuses. The terminal-like label within lamina III/IV derived in part from the basket-cell axons, which formed pericellular arrays around unstained somata. Cell-sparse lamina V contained the largest PV+ nonpyramidal cells in AI. These cells, which formed 11% of the neuron population in lamina V, were notable for their tangentially oriented dendritic fields and local axonal arbors. PVi partitioned lamina VI into VIa and VIb. Large multipolar nonpyramidal cells were distributed throughout lamina VI and made up approximately 6% of the total population. Lamina VIa contained a band of lightly labeled PV+ pyramidal neurons that formed 15% of the neuronal population.(ABSTRACT TRUNCATED AT 400 WORDS)

Parvalbumin is expressed in a reciprocal circuit linking the medial geniculate body and auditory neocortex in the rabbit.

Recent studies of the rabbit auditory forebrain have shown that antibodies directed against the calcium-binding protein parvalbumin (PV) specifically demarcate auditory neocortex and the ventral division of the medial geniculate body (MGV). The auditory cortex is characterized by two PV- immunoreactive bands: dense terminal-like labeling within layer III/IV and a prominent band of PV+ somata in the upper half of layer VI. In some cases, there are distinct patches of PV immunoreactivity within layers III/IV of auditory cortex that appear similar to the patchy termination of thalamocortical axons labeled by the injection of anterograde tracers into MGV. The presence of PV+ patches in III/IV, PV+ somata in layer VI, and the high density of PV+ neurons and terminals in the MGV suggest the existence of a reciprocal PV+ circuit linking primary auditory cortex (AI) and the MGV. In the present study, double-labeling experiments in adult rabbits were carried out to provide evidence for this circuit. Focal injections of the tracers biocytin or biotinylated dextran amine (BDA) into the MGV labeled thalamocortical afferent patches within layer III/IV and retrogradely labeled corticothalamic neurons in layer VIa of the ipsilateral auditory cortex. Adjacent sections stained with antibodies against PV revealed terminal-like PV-immunoreactive patches in III/IV and PV+ somata in VIa that were in register with those labeled by BDA injections into the MGV. Serial section reconstruction of BDA-labeled corticothalamic neurons in VIa revealed pyramidal cells with tangentially oriented basal dendrites and sparsely branched apical dendrites that ascended to layer I. Fluorescent double-labeling studies demonstrated that a subpopulation of corticothalamic neurons also express PV. PV-negative corticothalamic neurons were also found. Discrete injections of BDA into auditory cortex labeled bands of neurons in the ipsilateral MGV, whose orientation paralleled the fibrodendritic laminae characteristic of this subdivision. Retrograde double-labeling experiments showed that most MGV relay neurons also express PV. Small numbers of PV-negative relay neurons were also found. These studies provide evidence for the existence of multiple, chemically coded pathways linking primary auditory cortex and the MGV.

Complementary expression of parvalbumin and calbindin D-28k delineates subdivisions of the rabbit medial geniculate body.

The complementary pattern of immunohistochemical staining for the calcium-binding proteins parvalbumin (PV) and calbindin D-28k (CB) was used to delineate four major subdivisions of the rabbit medial geniculate body (MGB). PV immunoreactivity predominates in the ventral and medial divisions, whereas CB-immunoreactive cells characterize the dorsal and internal divisions. The ventral nucleus is strongly PV+ due to dense neuropil labeling and moderately labeled somata. The medial nucleus contains both medium-sized and large PV+ somata, as well as thick PV+ axons and terminals. The wedge-shaped internal nucleus composed of densely labeled CB+ cells, separates the dorsal and ventral nuclei rostrally, and expands caudally to encapsulate the posterior MGV. Large multipolar CB+ neurons with radiate dendrites characterize the dorsal nucleus. The differential expression of PV and CB also distinguishes the deep dorsal and superficial dorsal subnuclei in the dorsal division and a ventrolateral component in the ventral division. A comparison with studies of MGB connectivity in a variety of species suggests that PV immunoreactivity is highest in subdivisions that receive a substantial input from the central nucleus of the inferior colliculus and that project to primary auditory cortex. In contrast, CB immunoreactivity characterizes nuclei that receive input primarily from other sources, such as the paracentral nuclei of the inferior colliculus, the lateral tegmentum, and the spinal cord, and that project to secondary auditory areas. The ability of calcium-binding protein immunohistochemistry to delineate neuronal compartments across indistinct cytoarchitectonic borders makes it a powerful tool for guiding future connectional and physiological studies of the MGB.

Parvalbumin expression reveals a vibrissa-related pattern in rabbit SI cortex.

The expression of parvalbumin-like immunoreactivity (PV-LIR) was examined in the mystacial representation within the primary somatosensory cortex (SI) of postnatal day 21 and adult rabbits. PV-LIR was expressed in a prominent vibrissa-like array of patches in layer IV despite the fact that barrels were indistinct in the cytoarchitecture. Each patch consisted of dense terminal-like PV-LIR and a preferential concentration of intensely labeled stellate neurons. Layer V contained scattered small and large intensely labeled basket cells. Layer Vb had a distinct layer of lightly labeled large pyramidal cells that received labeled basket cell terminations. Upper layer VI also contained patches of terminal-like PV-LIR that were in register with the overlying vibrissae pattern. These patches also contained a preferential distribution of labeled non-pyramidal cells as well as modified pyramidal cells. These results suggest that PV-LIR in rabbits delineates cortical modules composed of thalamocortical afferents and inhibitory local circuits in the absence of a distinct barrel cytoarchitecture. In contrast, prior studies of rat SI cortex have revealed a distinct barrel cytoarchitecture but a uniform distribution of PV-LIR. The differences in PV-LIR between rodents and lagomorphs within the vibrissae representation in SI may be related to species differences in thalamic and local cortical circuits devoted to the whisker sense.

Generation of pure two-beam interference grating structures in an optical fiber with a femtosecond infrared source and a phase mask.

Fiber Bragg gratings were fabricated in all-silica core fiber by focusing 125-fs 800-nm pulses with an 80-mm lens through a phase mask with 4.28-microm pitch onto a fiber sample. When the phase-mask-fiber separation was 5 mm the observed structure was clearly the result of two-beam interference between the +/- 1 orders. The elimination of the remaining 9 orders is a consequence of the walk-off experienced by the mask orders and the short duration of the femtosecond pulse. This effect is unique to the fabrication of Bragg gratings with femtosecond sources and would not be observed with a longer pulse duration or incoherent UV sources.

Hydration-state-responsive proteins link cold and drought stress in spinach.

Spinach (Spinacia oleracea L.) seedlings exposed to low nonfreezing temperatures (0-10° C) that promote cold acclimation, synthesize a variety cold-acclimation proteins and at the same time acquire a greater ability to withstand cellular dehydration imposed by the freezing of tissue water. Two of these proteins (160 and 85 kDa) become more abundant over time at low temperature. In addition, a small decline in tissue water status from a maximally hydrated state also appears to be associated with an initiation of the accumulation of these proteins at a noninductive temperature. Imposing a severe water stress on young seedlings grown at 25° C by withholding water leads to substantial accumulation of the 160- and 85-kDa proteins, and maximal induction of freezing tolerance. This evidence implies that responses to cold acclimation and water stress involve common mechanisms, and further establishes the linkage of these two proteins with stresses having an osmotic component.