Patches with links: a unified system for processing faces in the macaque temporal lobe

The brain processes objects through a series of regions along the ventral visual pathway, but the circuitry subserving the analysis of specific complex forms remains unknown. One complex form category, faces, selectively activates six patches of cortex in the macaque ventral pathway. To identify the connectivity of these face patches, we used electrical microstimulation combined with simultaneous functional magnetic resonance imaging. Stimulation of each of four targeted face patches produced strong activation, specifically within a subset of the other face patches. Stimulation outside the face patches produced an activation pattern that spared the face patches. These results suggest that the face patches form a strongly and specifically interconnected hierarchical network.     

Depleting neuronal PrP in prion infection prevents disease and reverses spongiosis

The mechanisms involved in prion neurotoxicity are unclear, and therapies preventing accumulation of PrPSc, the disease-associated form of prion protein (PrP), do not significantly prolong survival in mice with central nervous system prion infection. We found that depleting endogenous neuronal PrPc in mice with established neuroinvasive prion infection reversed early spongiform change and prevented neuronal loss and progression to clinical disease. This occurred despite the accumulation of extraneuronal PrPSc to levels seen in terminally ill wild-type animals. Thus, the propagation of nonneuronal PrPSc is not pathogenic, but arresting the continued conversion of PrPc to PrPSc within neurons during scrapie infection prevents prion neurotoxicity.     

Cross-linking cellular prion protein triggers neuronal apoptosis in vivo

Neuronal death is a prominent, but poorly understood, pathological hallmark of prion disease. Notably, in the absence of the cellular prion protein (PrPC), the disease-associated isoform, PrPSc, appears not to be intrinsically neurotoxic, suggesting that PrPC itself may participate directly in the prion neurodegenerative cascade. Here, cross-linking PrPC in vivo with specific monoclonal antibodies was found to trigger rapid and extensive apoptosis in hippocampal and cerebellar neurons. These findings suggest that PrPC functions in the control of neuronal survival and provides a model to explore whether cross-linking of PrPC by oligomeric PrPSc can promote neuronal loss during prion infection.     

Functional links between Aβ toxicity, endocytic trafficking, and Alzheimer's disease risk factors in yeast

Aβ (beta-amyloid peptide) is an important contributor to Alzheimer's disease (AD). We modeled Aβ toxicity in yeast by directing the peptide to the secretory pathway. A genome-wide screen for toxicity modifiers identified the yeast homolog of phosphatidylinositol binding clathrin assembly protein (PICALM) and other endocytic factors connected to AD whose relationship to Aβ was previously unknown. The factors identified in yeast modified Aβ toxicity in glutamatergic neurons of Caenorhabditis elegans and in primary rat cortical neurons. In yeast, Aβ impaired the endocytic trafficking of a plasma membrane receptor, which was ameliorated by endocytic pathway factors identified in the yeast screen. Thus, links between Aβ, endocytosis, and human AD risk factors can be ascertained with yeast as a model system.     

Mutations in U4atac snRNA, a component of the minor spliceosome, in the developmental disorder MOPD I

Small nuclear RNAs (snRNAs) are essential factors in messenger RNA splicing. By means of homozygosity mapping and deep sequencing, we show that a gene encoding U4atac snRNA, a component of the minor U12-dependent spliceosome, is mutated in individuals with microcephalic osteodysplastic primordial dwarfism type I (MOPD I), a severe developmental disorder characterized by extreme intrauterine growth retardation and multiple organ abnormalities. Functional assays showed that mutations (30G>A, 51G>A, 55G>A, and 111G>A) associated with MOPD I cause defective U12-dependent splicing. Endogenous U12-dependent but not U2-dependent introns were found to be poorly spliced in MOPD I patient fibroblast cells. The introduction of wild-type U4atac snRNA into MOPD I cells enhanced U12-dependent splicing. These results illustrate the critical role of minor intron splicing in human development.     

Bioactivity-guided fractionation for the butyrylcholinesterase inhibitory activity of furanocoumarins from Angelica archangelica L. roots and fruits

Isolation and identification of the inhibitors of butyrylcholinesterase (BChE), obtained from the extracts of roots and fruits of Angelica archangelica L., are reported. Our results confirmed the weak inhibitory effect of Angelica roots on acetylcholinesterase activity. BChE inhibition was much more pronounced at a concentration of 100 μg/mL for hexane extracts and attained a higher rate than 50%. The TLC bioautography guided fractionation and spectroscopic analysis led to the isolation and identification of imperatorin from the fruit's hexane extract and of heraclenol-2'-O-angelate from the root's hexane extract. Both compounds showed significant BChE inhibition activity with IC(50) = 14.4 ± 3.2 μM and IC(50) = 7.5 ± 1.8 μM, respectively. Only C8-substituted and C5-unsubstituted furanocoumarins were active, which could supply information about the initial structures of specific BChE inhibitors.     

Statistical Modeling of the Partitioning of Nonylphenol in Soil

Partition coefficients K _P of nonylphenol (NP) in soil were determined for 193 soil samples which differed widely in content of soil organic carbon (SOC), hydrogen activity, clay content, and in the content of dissolved organic carbon (DOC). By means of multiple linear regression analysis (MLR), pedotransfer functions were derived to predict partition coefficients from soil data. SOC and pH affected the sorption, though the latter was in a range significantly below the pK_a of NP. Quality of soil organic matter presumably plays an important but yet not quantified role in sorption of NP. For soil samples with SOC values less than 3 g kg^?1, model prediction became uncertain with this linear approach. We suggest that using only SOC and pH data results in good prediction of NP sorption in soils with SOC higher than 3 g kg^?1. Considering the varying validity of the linear model for different ranges of the most sensitive parameter SOC, a more flexible, nonlinear approach was tested. The application of an artificial neuronal network (ANN) to predict sorption of NP in soils showed a sigmoidal relation between K _P and SOC. The nonlinear ANN approach provided good results compared to the MLR approach and represents an alternative tool for prediction of NP partitioning coefficients.     

Shoot-tip culture and subsequent regeneration in cowpea

Shoot tips of cowpea (Vigna ungulata) were successfully cultured in Murashige and Skoog's medium supplemented with IAA and 2iP. The factors responsible for organogenesis are discussed.     

Spatial variability in the mineralisation of the phenylurea herbicide linuron within a Danish agricultural field: multivariate correlation to simple soil parameters

The spatial variability in the mineralisation rate of linuron [N-(3,4-dichlorophenyl)-N'-methoxy-N'-methylurea] was studied within a previously treated Danish agricultural field by sampling soils from eleven different plots randomly distributed across an area of 20 x 20 m. The soils were characterised with respect to different abiotic and biotic properties including moisture content, organic matter content, pH, nutrient content, bacterial biomass, potential for mineralisation of MCPA [(4-chloro-2-methylphenoxy)acetic acid] and linuron. Five soils had a potential for mineralisation of linuron, with 5-15% of the added [ring-U-14C]linuron metabolised to 14CO2 within 60 days at 10 degrees C, while no extensive mineralisation of linuron was observed in the six remaining soils within this period. A TLC analysis of the methanol-extractable residues showed no development of 14C-labelled metabolites from linuron in any of the samples. Multivariate analysis was conducted to elucidate relationships between the intrinsic properties of single soil samples and initial rate of linuron mineralisation. The analysis indicated that important soil parameters in determining the spatial heterogeneity included the C(total)/N(total) ratio, pH and the water-extractable potassium contents, with the first of these highly negatively correlated and the last two highly positively correlated to the initial linuron mineralisation rate. This study shows that enhanced biodegradation of linuron may develop with successive field treatments, but that considerable in-field spatial heterogeneity in the degradation rate still exists. Combined with a parallel enrichment study focused on the underlying microbial processes, the present results suggest that intrinsic soil properties affect the linuron-metabolising bacterial population and thereby determine the spatial variability in the linuron mineralisation activity.     

Funisitis associated with leptospiral abortion in an equine placenta

Funisitis, inflammation of the umbilical cord, is well recognized in human placentas. This report describes a case of funisitis associated with leptospiral infection in the placenta of a Thoroughbred foal born prematurely. The umbilical cord had diffuse superficial yellow discoloration along its entire length. Microscopic evaluation showed an exudate of neutrophils admixed with fibrin on the surface. Warthin-Starry staining showed spirochetes in the Wharton's jelly of the umbilical cord. A locally extensive, severe placentitis not involving the star and allantoic cystic hyperplasia were the other lesions observed in the allantochorion. Leptospira funisitis is similar to the funisitis of congenital syphilis in humans, although there are some major microscopic differences. In Leptospira funisitis, lesions were limited to the cord surface, whereas in lesions in human umbilical cords with Treponema pallidum infection, the changes are observed mostly around the vessels and in the Wharton's jelly.