Brain mechanisms associated with top-down processes in perception.

Perception arises through an interaction between sensory input and prior knowledge. We propose that at least two brain areas are required for such an interaction: the ''site'' where analysis of afferent signals occurs and the ''source'' which applies the relevant prior knowledge. In the human brain, functional imaging studies have demonstrated that selective attention modifies activity in early visual processing areas specific to the attended feature. Early processing areas are also modified when prior knowledge permits a percept to emerge from an otherwise meaningless stimulus. Sources of this modification have been identified in parietal cortex and in prefrontal cortex. Modification of early processing areas also occurs on the basis of prior knowledge about the predicted sensory effects of the subject''s own actions. Activity associated with mental imagery resembles that associated with response preparation (for motor imagery) and selective attention (for sensory imagery) suggesting that mental imagery reflects the effects of prior knowledge on sensory processing areas in the absence of sensory input. Damage to sensory processing areas can lead to a form of sensory hallucination which seems to arise from the interaction of prior knowledge with random sensory activity. In contrast, hallucinations associated with schizophrenia may arise from a failure of prior knowledge about motor intentions to modify activity in relevant sensory areas. When functioning normally, this mechanism permits us to distinguish our own actions from those of independent agents in the outside world. Failure to make this distinction correctly may account for the strong association between hallucinations and paranoid delusions in schizophrenia; the patient not only hears voices, but attributes (usually hostile) intentions to these voices.     

Hemispheric specialization for global and local processing: the effect of stimulus category.

Neuropsychological evidence indicates that the global aspect of complex visual scenes is preferentially processed by the right hemisphere, and local aspects are preferentially processed by the left hemisphere. Using letter-based hierarchical stimuli (Navon figures), we recently demonstrated, in a directed-attention task, lateralized neural activity (assessed by positron emission tomography) in the left prestriate cortex during local processing, and in the right prestriate cortex during global processing. Furthermore, temporal-parietal cortex was critically activated bilaterally in a divided-attention task that involved varying the number of target switches between local and global levels of letter-based hierarchical stimuli. Little is known about whether such stimulus categories influence such hemispheric lateralization. We now present data on brain activity, derived from positron emission tomography, in normal subjects scanned during either local or global processing of object-based hierarchical stimuli. We again observe attentional modulation of neural activity in prestriate cortex. There is now greater right-sided activation for local processing and greater left-sided activation for global processing, which is the opposite of that seen with letter-based stimuli. The results suggest that the relative differential hemispheric activations in the prestriate areas during global and local processing are modified by stimulus category.     

Proteolytic enzymes in green wheat leaves I. Isolation on DEAE-cellulose of several proteinases with acid pH optima

Several peptide hydrolases have been isolated in a partiallypurified form from green wheat leaves by a combination of gelchromatography and chromatography on DEAE-cellulose. These hydrolasesall degrade haemoglobin and other substrates tested at an acidpH. Three of the enzymes have been identified as proteinasesby measurement of the total N: -amino N ratio of the degradationproducts. These three enzymes have a similar optimum assay pHof about 4.5 with haemoglobin as substrate, but differ markedlyin their stability at high temperatures. ¹ Nomenclature in this paper follows the recommendation of theCommission on Biochemical Nomenclature (1972). (Received November 30, 1977; )     

Investigating a network model of word generation with positron emission tomography.

By using positron emission tomography (PET) we examined the biological validity of a network model describing changes in cerebral activity associated with intrinsic and extrinsic word generation. The production of words not specified by an extrinsic stimulus constitutes willed or intrinsic generation. Perceiving a heard word is an example of extrinsic generation. The model incorporates three neuronal systems: a pool that stores word representations in a distributed fashion, an afferent system conveying sensory input to the pool and a modulating system that alters the responsivity of neurons in the pool. Simulations based on the model suggested that intrinsic generation would be associated with low activity in the pool, consequent on reduced modulation, and extrinsic generation with high activity. We measured cerebral activity with PET during intrinsic (verbal fluency) and extrinsic (responding to heard words) word generation and found this pattern of changes in the left superior temporal region. We were able to designate this region the site of the distributed word store and implicate the left dorsolateral prefrontal cortex (DLPFC) as the source of modulation. The relation between the superior temporal gyrus and DLPFC was shown by examining the correlation between the two regions in terms of cerebral activity. We conclude that the left DLPFC is responsible for modulating the responsivity of a neural system in the superior temporal gyrus and is the probable mediator of changes in attentional and intentional states that underlies the intrinsic generation of words.     

Albumin synthesis and catabolism following partial hepatectomy in the rat. The effects of amino acids and adrenocortical steroids on albumin synthesis after partial hepatectomy.

Plasma albumin levels were measured in partially hepatectomized, sham operated and control rats. The levels fell in both the partially hepatectomized and sham operated groups; while the latter group returned to normal within a few days, the low plasma albumin in the partially hepatectomized animals was sustained. Albumin synthesis rates in the isolated perfused rat liver were measured in the three groups of animals at varying intervals after partial hepatectomy. There was a significant depression of albumin synthesis rate in terms of both liver and whole animal weights when compared to the sham operated and control animals. This depression was almost completely reversed by the addition of arginine, asparagine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, threonine, tryptophan and valine added together to 10 times their normal plasma concentrations. The addition of hydrocortisone had no effect on the albumin synthesis rate after partial hepatectomy. Studies in vivo in the three groups of animals (partially hepatectomized, sham operated and control animals) revealed a fall in the albumin catabolic rate after partial hepatectomy coinciding with the fall in the albumin synthesis rate. An hypothesis whereby the amino acids may have their stimulatory effect is proposed.     

TBC1D14 regulates autophagy via the TRAPP complex and ATG9 traffic

Macroautophagy requires membrane trafficking and remodelling to form the autophagosome and deliver its contents to lysosomes for degradation. We have previously identified the TBC domain‐containing protein, TBC1D14, as a negative regulator of autophagy that controls delivery of membranes from RAB11‐positive recycling endosomes to forming autophagosomes. In this study, we identify the TRAPP complex, a multi‐subunit tethering complex and GEF for RAB1, as an interactor of TBC1D14. TBC1D14 binds to the TRAPP complex via an N‐terminal 103 amino acid region, and overexpression of this region inhibits both autophagy and secretory traffic. TRAPPC8, the mammalian orthologue of a yeast autophagy‐specific TRAPP subunit, forms part of a mammalian TRAPPIII‐like complex and both this complex and TBC1D14 are needed for RAB1 activation. TRAPPC8 modulates autophagy and secretory trafficking and is required for TBC1D14 to bind TRAPPIII. Importantly, TBC1D14 and TRAPPIII regulate ATG9 trafficking independently of ULK1. We propose a model whereby TBC1D14 and TRAPPIII regulate a constitutive trafficking step from peripheral recycling endosomes to the early Golgi, maintaining the cycling pool of ATG9 required for initiation of autophagy.     

Multimodal spatial representations engaged in human parietal cortex during both saccadic and manual spatial orienting

BACKGROUND: Recent neuroimaging studies have found that several areas of the human brain, including parietal regions, can respond multimodally. But given single-cell evidence that responses in primate parietal cortex can be motor-related, some of the human multimodal activations might reflect convergent activation of potentially motor-related areas, rather than multimodal representations of space independent of motor factors. Here we crossed sensory stimulation of different modalities (vision or touch, in left or right hemifield) with spatially directed responses to such stimulation by different effector-systems (saccadic or manual). RESULTS: The fMRI results revealed representations of contralateral space in both the posterior part of the superior parietal gyrus and the anterior intraparietal sulcus that activated independently of both sensory modality and motor response. Multimodal saccade-related or manual-related activations were found, by contrast, in different regions of parietal cortex. CONCLUSIONS: Whereas some parietal regions have specific motor functions, others are engaged during the execution of movements to the contralateral hemifield irrespective of both input modality and the type of motor effector.     

A ubiquitous and conserved signal for RNA localization in chordates

During oogenesis in Xenopus laevis, several RNAs that localize to the vegetal cortex via one of three temporally defined pathways have been identified. Although individual mRNAs utilize only one pathway, there is functional overlap and apparent continuity between them, suggesting that common cis-acting sequences may exist. Because previous work with the Vg1 mRNA revealed that short nontandem repeats are important for localization, we developed a new computer program, called REPFIND, to expedite the identification of repeated motifs in other localized RNAs. Here we show that clusters of short CAC-containing motifs characterize the localization elements (LEs) of virtually all mRNAs localized to the vegetal cortex of Xenopus oocytes. A search for this signal in GenBank [9] resulted in the identification of new localized mRNAs, demonstrating the applicability of REPFIND to predict localized RNAs. CAC-rich LEs are also found in ascidians and other vertebrates, indicating that these cis regulatory elements are conserved in chordates. Interestingly, biochemical evidence shows that distinct CAC-containing motifs have different functions in the localization process. Thus, clusters of CAC-containing motifs are a ubiquitous signal for RNA localization and can signal localization in a variety of pathways through slight variations in sequence composition.