Functional characterization and synergic action of fungal xylanase and arabinofuranosidase for production of xylooligosaccharides.

Plant cell wall degrading enzymes are key technological components in biomass bioconversion platforms for lignocellulosic materials transformation. Cost effective production of enzymes and identification of efficient degradation routes are two economic bottlenecks that currently limit the use of renewable feedstocks through an environmental friendly pathway. The present study describes the hypersecretion of an endo-xylanase (GH11) and an arabinofuranosidase (GH54) by a fungal expression system with potential biotechnological application, along with comprehensive characterization of both enzymes, including spectrometric analysis of thermal denaturation, biochemical characterization and mode of action description. The synergistic effect of these enzymes on natural substrates such as sugarcane bagasse, demonstrated the biotechnological potential of using GH11 and GH54 for production of probiotic xylooligosaccharides from plant biomass. Our findings shed light on enzymatic mechanisms for xylooligosaccharide production, as well as provide basis for further studies for the development of novel enzymatic routes for use in biomass-to-bioethanol applications.

Watermelon stomach, hemorrhagic pericarditis, small cell carcinoma of the lung and synchronous squamous cell carcinoma of the tongue base.

Based on a case of gastric antral vascular ectasia (watermelon stomach) that was associated with hemorrhagic pericarditis, small cell lung carcinoma with mediastinal lymph node metastases and a synchronous squamous cell carcinoma of the base of the tongue, the authors made a review of the clinical, endoscopic and histopathological aspects of this type of gastropathy, and its association with other diseases, and of the results of its endoscopic therapy. The causes of hemorrhagic pericarditis are considered, emphasizing the necessity to know if the effusion has a malignant etiology. To the best of our knowledge the association of watermelon stomach to small cell lung carcinoma and squamous cell carcinoma of the base of the tongue has not yet been described. Extensive metastases to mediastal lymph nodes are common to small cell lung carcinoma.

The Iowa Gambling Task and the somatic marker hypothesis: some questions and answers.

A recent study by Maia and McClelland on participants' knowledge in the Iowa Gambling Task suggests a different interpretation for an experiment we reported in 1997. The authors use their results to question the evidence for the somatic marker hypothesis. Here we consider whether the authors' conclusions are justified.

Neural systems behind word and concept retrieval.

Using both the lesion method and functional imaging (positron emission tomography) in large cohorts of subjects investigated with the same experimental tasks, we tested the following hypotheses: (A) that the retrieval of words which denote concrete entities belonging to distinct conceptual categories depends upon partially segregated regions in higher-order cortices of the left temporal lobe; and (B) that the retrieval of conceptual knowledge pertaining to the same concrete entities also depends on partially segregated regions; however, those regions will be different from those postulated in hypothesis A, and located predominantly in the right hemisphere (the second hypothesis tested only with the lesion method). The analyses provide support for hypothesis A in that several regions outside the classical Broca and Wernicke language areas are involved in name retrieval of concrete entities, and that there is a partial segregation in the temporal lobe with respect to the conceptual category to which the entities belong, and partial support for hypothesis B in that retrieval of conceptual knowledge is partially segregated from name retrieval in the lesion study. Those regions identified here are seen as parts of flexible, multi-component systems serving concept and word retrieval for concrete entities belonging to different conceptual categories. By comparing different approaches the article also addresses a number of method issues that have surfaced in recent studies in this field.

Pathological laughter and crying: a link to the cerebellum.

Patients with pathological laughter and crying (PLC) are subject to relatively uncontrollable episodes of laughter, crying or both. The episodes occur either without an apparent triggering stimulus or following a stimulus that would not have led the subject to laugh or cry prior to the onset of the condition. PLC is a disorder of emotional expression rather than a primary disturbance of feelings, and is thus distinct from mood disorders in which laughter and crying are associated with feelings of happiness or sadness. The traditional and currently accepted view is that PLC is due to the damage of pathways that arise in the motor areas of the cerebral cortex and descend to the brainstem to inhibit a putative centre for laughter and crying. In that view, the lesions 'disinhibit' or 'release' the laughter and crying centre. The neuroanatomical findings in a recently studied patient with PLC, along with new knowledge on the neurobiology of emotion and feeling, gave us an opportunity to revisit the traditional view and propose an alternative. Here we suggest that the critical PLC lesions occur in the cerebro-ponto-cerebellar pathways and that, as a consequence, the cerebellar structures that automatically adjust the execution of laughter or crying to the cognitive and situational context of a potential stimulus, operate on the basis of incomplete information about that context, resulting in inadequate and even chaotic behaviour.

A role for left temporal pole in the retrieval of words for unique entities.

Both lesion and functional imaging studies have implicated sectors of high-order association cortices of the left temporal lobe in the retrieval of words for objects belonging to varied conceptual categories. In particular, the cortices located in the left temporal pole have been associated with naming unique persons from faces. Because this neuroanatomical-behavioral association might be related to either the specificity of the task (retrieving a name at unique level) or to the possible preferential processing of faces by anterior temporal cortices, we performed a PET imaging experiment to test the hypothesis that the effect is related to the specificity of the word retrieval task. Normal subjects were asked to name at unique level entities from two conceptual categories: famous landmarks and famous faces. In support of the hypothesis, naming entities in both categories was associated with increases in activity in the left temporal pole. No main effect of category (faces vs. landmarks/buildings) or interaction of task and category was found in the left temporal pole. Retrieving names for unique persons and for names for unique landmarks activate the same brain region. These findings are consistent with the notion that activity in the left temporal pole is linked to the level of specificity of word retrieval rather than the conceptual class to which the stimulus belongs.

Neural correlates of naming actions and of naming spatial relations.

Ina [(15)O] water PET experiment, 10 normal subjects retrieved words denoting actions (performed with or without an implement), and another 10 normal subjects retrieved words denoting the spatial relations between objects. Our objective was to test the following hypothesis: that the salient neural activity associated with naming actions and spatial relations occurs in left frontal operculum and left parietal association cortices, but not in the left inferotemporal cortices (IT) or in the right parietal association cortices. There were two control tasks, one requiring a decision on the orientation of unknown faces (a standard control task in our laboratory) and another requiring the retrieval of words denoting the concrete entities used in the action and spatial relations tasks. In accordance with the hypothesis, both naming actions and spatial relations (using the face orientation task as control activated the left frontal operculum; naming actions also activated the left parietal lobe. However, sectors of the left posterior IT were also engaged in both naming actions and spatial relations. When the naming of concrete entities was subtracted from the naming of actions performed with such entities, area MT in the posterior temporo-occipital region was activated bilaterally. On the other hand, when naming of the concrete entities was subtracted from the naming of spatial relations, left parietal activation was found, and when two tasks of naming spatial relations were contrasted to each other bilateral parietal activation was seen, right when abstract stimuli were used and left when concrete objects were used. The activity in posterior IT is thought to be related to object processing and possibly name retrieval at a subconscious level.

The selective vulnerability of brainstem nuclei to Alzheimer's disease.

In a study of thioflavin S-stained serial sections from the entire brainstem, we found that the inferior and superior colliculi and the autonomic, monoaminergic, cholinergic, and classical reticular nuclei were affected with varying degrees of severity and frequencies in 32 patients with Alzheimer's disease, whereas no changes were seen in the brainstems of 26 control subjects. The majority of the affected nuclei in patients with Alzheimer's disease exhibit either neurofibrillary tangles or senile plaques, and only a few display both. However, when sections were immunostained with the antibodies 10D5 and AT8 or ALZ50, both beta-amyloid and hyperphosphorylated epitopes of tau protein were found to be present in various concentrations in all the affected nuclei. Our findings suggest that each brainstem nucleus has a distinct vulnerability to Alzheimer's disease-related pathological changes. Given that each nucleus has idiosyncratic neuroanatomical connections and prevailing neurochemical characteristics, the heterogeneous collection of brainstem nuclei can be considered a suitable anatomical ground for further investigation of selective vulnerability in Alzheimer's disease. The finding of severe pathological changes in some brainstem nuclei also raises the possibility that the dysfunction of these nuclei may contribute to the cognitive defects and increased rates of morbidity and mortality in patients with Alzheimer's disease.

Consciousness and the brainstem.

In the first part of this article we summarize a theoretical framework and a set of hypotheses aimed at accounting for consciousness in neurobiological terms. The basic form of consciousness, core consciousness is placed in the context of life regulation; it is seen as yet another level of biological processing aimed at ensuring the homeostatic balance of a living organism; and the representation of the current organism state within somato-sensing structures is seen as critical to its development. Core consciousness is conceived as the imaged relationship of the interaction between an object and the changed organism state it causes. In the second part of the article we discuss the functional neuroanatomy of nuclei in the brainstem reticular formation because they constitute the basic set of somato-sensing structures necessary for core consciousness and its core self to emerge. The close relationship between the mechanisms underlying cortical activation and the bioregulatory mechanisms outlined here is entirely compatible with the classical idea that the reticular formation modulates the electrophysiological activity of the cerebral cortex. However, in the perspective presented here, that modulation is placed in the setting of the organism's homeostatic regulation.

Single-neuron responses to emotional visual stimuli recorded in human ventral prefrontal cortex.

Both lesion and functional imaging studies in humans, as well as neurophysiological studies in nonhuman primates, demonstrate the importance of the prefrontal cortex in representing the emotional value of sensory stimuli. Here we investigated single-neuron responses to emotional stimuli in an awake person with normal intellect. Recording from neurons within healthy tissue in ventral sites of the right prefrontal cortex, we found short-latency (120-160 ms) responses selective for aversive visual stimuli.

A neural basis for the retrieval of words for actions.

Although much has been learned in recent years about the neural basis for retrieving words denoting concrete entities, the neural basis for retrieving words denoting actions remains poorly understood. We addressed this issue by testing two specific anatomical hypotheses. (1) Naming of actions depends not only on the classical implementation structures of the left frontal operculum, but also on mediational structures located in left premotor/prefrontal areas. (2) The neural systems subserving naming of actions and naming of concrete entities are segregated. The study used the lesion method and involved 75 subjects with focal, stable lesions in the left or right hemispheres, whose magnetic resonance data were analysed with a three-dimensional reconstruction method. The experimental tasks were standardised procedures for measuring action and object naming. The findings offered partial support for the hypotheses, in that: (1) lesions related to impaired action naming overlapped maximally in the left frontal operculum and in the underlying white matter and anterior insula; and (2) lesions of the left anterior temporal and inferotemporal regions, which produce impairments in naming of concrete entities, did not cause action naming deficits. A follow-up analysis indicated that action naming impairments, especially when they were disproportionate relative to concrete entity naming impairments, were not only associated with premotor/prefrontal lesions, but also with lesions of the left mesial occipital cortex and of the paraventricular white matter underneath the supramarginal and posterior temporal regions.

Subcortical and cortical brain activity during the feeling of self-generated emotions.

In a series of [15O]PET experiments aimed at investigating the neural basis of emotion and feeling, 41 normal subjects recalled and re-experienced personal life episodes marked by sadness, happiness, anger or fear. We tested the hypothesis that the process of feeling emotions requires the participation of brain regions, such as the somatosensory cortices and the upper brainstem nuclei, that are involved in the mapping and/or regulation of internal organism states. Such areas were indeed engaged, underscoring the close relationship between emotion and homeostasis. The findings also lend support to the idea that the subjective process of feeling emotions is partly grounded in dynamic neural maps, which represent several aspects of the organism's continuously changing internal state.

Selective pathological changes of the periaqueductal gray matter in Alzheimer's disease.

The periaqueductal gray matter (PAG) is a major neuroanatomical component of the brainstem and has pivotal roles in autonomic functions, behavior, and cognition, most notably in the processing of emotions and feelings. In a study of 32 brains obtained from patients with Alzheimer's disease (AD), thioflavin S-stained sections from the PAG contained major pathological changes in 81% of cases. These changes were absent in all 26 control brains (13 from normal subjects and 13 from non-AD patients). In the AD cases, both sides of the PAG were affected symmetrically; in 72%, there were only senile plaques, but there were both senile plaques and neurofibrillary tangles in 9%. Using immunohistochemical methods with 10D5, ALZ-50, and AT8 antibodies, we also established the presence of beta-amyloid peptide and abnormally phosphorylated tau protein in the PAG. Furthermore, we found that the type and density of pathological changes were expressed differently in different PAG regions and correlated with gender and the duration of dementia. These findings constitute a first step in documenting the selective changes of PAG in AD. The compartmentalized pattern of AD changes in PAG also reveals for the first time the columnar organization of PAG in human subjects.

A role for somatosensory cortices in the visual recognition of emotion as revealed by three-dimensional lesion mapping.

Although lesion and functional imaging studies have broadly implicated the right hemisphere in the recognition of emotion, neither the underlying processes nor the precise anatomical correlates are well understood. We addressed these two issues in a quantitative study of 108 subjects with focal brain lesions, using three different tasks that assessed the recognition and naming of six basic emotions from facial expressions. Lesions were analyzed as a function of task performance by coregistration in a common brain space, and statistical analyses of their joint volumetric density revealed specific regions in which damage was significantly associated with impairment. We show that recognizing emotions from visually presented facial expressions requires right somatosensory-related cortices. The findings are consistent with the idea that we recognize another individual's emotional state by internally generating somatosensory representations that simulate how the other individual would feel when displaying a certain facial expression. Follow-up experiments revealed that conceptual knowledge and knowledge of the name of the emotion draw on neuroanatomically separable systems. Right somatosensory-related cortices thus constitute an additional critical component that functions together with structures such as the amygdala and right visual cortices in retrieving socially relevant information from faces.

Emotion, decision making and the orbitofrontal cortex.

The somatic marker hypothesis provides a systems-level neuroanatomical and cognitive framework for decision making and the influence on it by emotion. The key idea of this hypothesis is that decision making is a process that is influenced by marker signals that arise in bioregulatory processes, including those that express themselves in emotions and feelings. This influence can occur at multiple levels of operation, some of which occur consciously and some of which occur non-consciously. Here we review studies that confirm various predictions from the hypothesis. The orbitofrontal cortex represents one critical structure in a neural system subserving decision making. Decision making is not mediated by the orbitofrontal cortex alone, but arises from large-scale systems that include other cortical and subcortical components. Such structures include the amygdala, the somatosensory/insular cortices and the peripheral nervous system. Here we focus only on the role of the orbitofrontal cortex in decision making and emotional processing, and the relationship between emotion, decision making and other cognitive functions of the frontal lobe, namely working memory.