Gut Microbiota and Bipolar Disorder: An Overview on a Novel Biomarker for Diagnosis and Treatment

The gut microbiota is the set of microorganisms that colonize the gastrointestinal tract of living creatures, establishing a bidirectional symbiotic relationship that is essential for maintaining homeostasis, for their growth and digestive processes. Growing evidence supports its involvement in the intercommunication system between the gut and the brain, so that it is called the gut–brain–microbiota axis. It is involved in the regulation of the functions of the Central Nervous System (CNS), behavior, mood and anxiety and, therefore, its implication in the pathogenesis of neuropsychiatric disorders. In this paper, we focused on the possible correlations between the gut microbiota and Bipolar Disorder (BD), in order to determine its role in the pathogenesis and in the clinical management of BD. Current literature supports a possible relationship between the compositional alterations of the intestinal microbiota and BD. Moreover, due to its impact on psychopharmacological treatment absorption, by acting on the composition of the microbiota beneficial effects can be obtained on BD symptoms. Finally, we discussed the potential of correcting gut microbiota alteration as a novel augmentation strategy in BD. Future studies are necessary to better clarify the relevance of gut microbiota alterations as state and disease biomarkers of BD.     

Quantitative analysis for linear hybrid cellular automata and LFSR as built-in self-test generators for sequential faults

This paper presents a combinatorial method of evaluating the effectiveness of linear hybrid cellular automata (LHCA) and linear feedback shift registers (LFSR) as generators for stimulating faults requiring a pair of vectors. We provide a theoretical analysis and empirical comparisons to see why the LHCA are better than the LFSRs as generators for sequential-type faults in a built-in self-test environment. Based on the concept of a partner set, the method derives the number of distinctk-cell substate vectors which have 2^2k , 1k[n/2], transition capability for ann-cell LHCA and ann-cell LFSR with maximum length cycles. Simulation studies of the ISCAS85 benchmark circuits provide evidence of the effectiveness of the theoretrical metric.This work was supported in part by Reserach Grants No. 5711 and No. 39409 and a Strategic Grant from the Natural Sciences and Engineering Research Council of Canada and by an equipments loan from the Canadian Microelectronics Corporation.A preliminary version of this paper is partially presented at theIEEE ISCAS'94, May 1994.     

Biocompatible glass–ceramic materials for bone substitution

A new bioactive glass composition (CEL2) in the SiO₂–P₂O₅–CaO–MgO–K₂O–Na₂O system was tailored to control pH variations due to ion leaching phenomena when the glass is in contact with physiological fluids. CEL2 was prepared by a traditional melting-quenching process obtaining slices that were heat-treated to obtain a glass-ceramic material (CEL2GC) that was characterized thorough SEM analysis. Pre-treatment of CEL2GC with SBF was found to enhance its biocompatibility, as assessed by in vitro tests. CEL2 powder was then used to synthesize macroporous glass–ceramic scaffolds. To this end, CEL2 powders were mixed with polyethylene particles within the 300–600 μm size-range and then pressed to obtain crack-free compacted powders (green). This was heat-treated to remove the organic phase and to sinter the inorganic phase, leaving a porous structure. The biomaterial thus obtained was characterized by X-ray diffraction, SEM equipped with EDS, density measurement, image analysis, mechanical testing and in vitro evaluation, and found to be a glass–ceramic macroporous scaffold with uniformly distributed and highly interconnected porosity. The extent and size-range of the porosity can be tailored by varying the amount and size of the polyethylene particles.     

Effects of lesions in the medial pallium on instrumental learning in the toad (Bufo arenarum)

Lesions of the medial pallium in toads significantly retarded extinction of a water-reinforced instrumental response in a runway training situation, relative to sham-operated and intact controls. The lesion had no effect on acquisition or in the amount of water uptake during acquisition. The results suggest that the medial pallium of toads plays a role in response inhibition. This possibility is discussed in relation to the results of analogous experiments with hippocampectomized rats.     

Constrained parity testing

A generalized testing technique called constrained parity testing is presented for detecting multiple stuck-at faults in any single-output irredundant combinational network by verifying the subparities of the network. Implementation independent testability conditions are established for single- and multiple-input stuck-at faults. A spanning parity signature (SPS) is introduced to detect vacuous faults, which include all the input stuck-at faults and a majority of all other multiple stuck-at faults. The SPS is considered for testing all stuck-at faults in networks with small numbers of fanout lines, and a method of deriving tests for nonvacuous faults is proposed. For networks with large fanouts, a hybrid scheme by combining with syndrome testing is suggested to eliminate or reduce the need for expensive fault simulation. The proposed technique is a theoretical generalization of many existing methods and offers advantages such as versatility, flexibility, low test volume, low test time, high fault coverage, and reduced fault simulation and test generation costs.     

Dose-dependent inhibition of cell proliferation induced by lipid peroxidation products in rat hepatoma cells after enrichment with arachidonic acid

Polyunsaturated fatty acids (PUFA) are important constituents of membrane phospholipids, whose levels are decreased in some tumor cells. This deficiency may cause alterations in signal transduction and an interruption of normal cellular events. The enrichment of tumor cells with PUFA may stimulate or inhibit tumor growth, probably depending on the type of PUFA and the cellular concentration of aldehydes derived from restored lipid peroxidation. We examined the effect of several doses of prooxidant on the growth of hepatoma cells with different aldehyde dehydrogenase activities, enriched with arachidonic acid. Two doses of prooxidant were sufficient to reduce growth of hepatoma cells with low aldehyde dehydrogenase activity, whereas three doses were necessary for those with high enzyme activity. In both cases, lipid peroxidation products blocked the cells in the S phase.     

Inhibition of class-3 aldehyde dehydrogenase and cell growth by restored lipid peroxidation in hepatoma cell lines

Hepatoma cells have a below-normal content of polyunsaturated fatty acids; this reduces lipid peroxidation and the production of cytotoxic and cytostatic aldehydes within the cells. In proportion to the degree of deviation, hepatoma cells also show an increase in the activity of Class-3 aldehyde dehydrogenase, an enzyme important in the metabolism of lipid peroxidation products and also in that of several drugs. When hepatoma cells with different degrees of deviation were enriched with arachidonic acid and stimulated to peroxidize by ascorbate/iron sulphate, their growth rate was reduced in proportion to the quantity of aldehydes produced and to the activity of aldehyde dehydrogenase. Therefore, 7777 cells, less deviated and with low Class-3 aldehyde dehydrogenase activity, were more susceptible to lipid peroxidation products than JM2 cells. It is noteworthy that repeated treatments with prooxidant also caused a decrease in mRNA and activity of Class-3 aldehyde dehydrogenase, contributing to the decreased growth and viability. Thus, Class-3 aldehyde dehydrogenase could be considered relevant for the growth of hepatoma cells, since it defends them against cell growth inhibiting aldehydes derived from lipid peroxidation.     

BOD5 estimation for pulp and paper mill effluent using UV absorbance

A novel method based on UV absorbance, is presented for estimating the BOD5 in pulp and paper mill effluent. This method could eventually be incorporated into an on-line sensor for BOD5 that is suitable for process control applications. Two streams, the reactor entrance and the final effluent, from two different mills were studied. One mill employed the Kraft pulping process, while the second mill was a thermo-mechanical one. The absorbance over the range 200-350 nm showed significant differences between the two mills. Because the two mills use very distinct processes, separate correlations were used to relate the absorbance to the BOD5 for both the mills. Results indicate that prediction of reactor entrance BOD5 was reasonable, whereas prediction of final effluent BOD5 was inaccurate, for both mills. Also studied was the effect of aeration on BOD5 results obtained at low BOD5 values for the Kraft mill.     

An induced proximity model for caspase-8 activation

The assembly of the CD-95 (Fas/Apo-1) receptor death-inducing signaling complex occurs in a hierarchical manner; the death domain of CD-95 binds to the corresponding domain in the adapter molecule Fas-associated death domain (FADD) Mort-1, which in turn recruits the zymogen form of the death protease caspase-8 (FLICE/Mach-1) by a homophilic interaction involving the death effector domains. Immediately after recruitment, the single polypeptide FLICE zymogen is proteolytically processed to the active dimeric species composed of large and small catalytic subunits. Since all caspases cleave their substrates after Asp residues and are themselves processed from the single-chain zymogen to the two-chain active enzyme by cleavage at internal Asp residues, it follows that an upstream caspase can process a downstream zymogen. However, since FLICE represents the most apical caspase in the Fas pathway, its mode of activation has been enigmatic. We hypothesized that the FLICE zymogen possesses intrinsic enzymatic activity such that when approximated, it autoprocesses to the active protease. Support for this was provided by (i) the synthesis of chimeric Fpk3FLICE molecules that can be oligomerized in vivo by the synthetic cell-permeable dimerizer FK1012H2. Cells transfected with Fpk3FLICE underwent apoptosis after exposure to FK1012H2; (ii) the creation of a nonprocessable zymogen form of FLICE that retained low but detectable protease activity.