Reduced frequency of CD4(+)CD25(HIGH)FOXP3(+) cells and diminished FOXP3 expression in patients with Common Variable Immunodeficiency: A link to autoimmunity?

Common Variable Immunodeficiency (CVID) is a primary immunodeficiency disease characterized by defective immunoglobulin production and often associated with autoimmunity. We used flow cytometry to analyze CD4(+)CD25(HIGH)FOXP3(+) T regulatory (Treg) cells and ask whether perturbations in their frequency in peripheral blood could underlie the high incidence of autoimmune disorders in CVID patients. In this study, we report for the first time that CVID patients with autoimmune disease have a significantly reduced frequency of CD4(+)CD25(HIGH)FOXP3(+) cells in their peripheral blood accompanied by a decreased intensity of FOXP3 expression. Notably, although CVID patients in whom autoimmunity was not diagnosed had a reduced frequency of CD4(+)CD25(HIGH)FOXP3(+) cells, FOXP3 expression levels did not differ from those in healthy controls. In conclusion, these data suggest compromised homeostasis of CD4(+)CD25(HIGH)FOXP3(+) cells in a subset of CVID patients with autoimmunity, and may implicate Treg cells in pathological mechanisms of CVID. (C) 2009 Elsevier Inc. All rights reserved.

Effects of Cobalt Chloride in Junctional Epithelium and Reduced Enamel Epithelium of the Rat Maxillary First Molar

Cobalt is one of the main components of cast metal alloys broadly used in dentistry. It is the constituent of 45 to 70% of numerous prosthetic works. There are evidences that metal elements cause systemic and local toxicity. The purpose of the present study was to evaluate the effects of cobalt on the junctional epithelium and reduced enamel epithelium of the first superior molar in rats, during lactation. To do this, 1-day old rats were used, whose mothers received 300mg of cobalt chloride per liter of distilled water in the drinker, during lactation. After 21 days, the rat pups were killed with an anesthetic overdose. The heads were separated, fixed in ""alfac"", decalcified and embedded in paraffin. Frontal sections stained with hematoxylin and eosin were employed. Karyometric methods allowed to estimate the following parameters: biggest, smallest and mean diameters, D/d ratio, perimeter, area, volume, volume/area ratio, eccentricity, form coefficient and contour index. Stereologic methods allow to evaluate: cytoplasm/nucleus ratio, cell and cytoplasm volume, cell number density, external surface/basal membrane ratio, thickness of the epithelial layers and surface density. All the collected data were subjected to statistic analysis by the non-parametric Wilcoxon-Mann-Whitney test. The nuclei of the studied tissues showed smaller values after karyometry for: diameters; perimeter, area, volume and volume/area ratio. Stereologically, it was observed, in the junctional epithelium and in the reduced enamel epithelium, smaller cells with scarce cytoplasm, reflected in the greater number of cells per mm3 of tissue. In this study, cobalt caused epithelial atrophy, indicating a direct action on the junctional and enamel epithelium.

COMMUNICATION AND INFORMATION BARRIERS TO HEALTH ASSISTANCE FOR DEAF PATIENTS

IN BRAZIL, recent regulations require changes in private and public health systems to make special services available to deaf patients. in the present article, the researchers analyze the perceptions of 25 sign language using patients regarding this assistance. The researchers found communication difficulties between these patients and health services staff, as well as a culture clash and a harmful inability among the service providers to distinguish among the roles of companions, caretakers, and professional translator/interpreters. Thus, it became common for the patients to experience prejudice in the course of treatment and information exchange, damage to their autonomy, limits on their access to services, and reduced efficacy of therapy. The researchers conclude that many issues must be dealt with if such barriers to health access are to be overcome, in particular the worrying degree of exclusion of deaf patients from health care systems.

Effect of processing on the antioxidant activity of amaranth grain

Effect of processing on the antioxidant activity of amaranth grain. Amaranth has attracted increasing interest over recent decades because of its nutritional, functional and agricultural characteristics. Amaranth grain can be cooked, popped, toasted, extruded or milled for consumption. This study investigated the effect of these processes on the antioxidant activity of amaranth grain. Total phenolic content and in vitro antioxidant activity were determined according to two methods: inhibition, of lipid oxidation using the beta-carotene/linoleic acid system and the antioxidant activity index using the Rancimat (R) apparatus. The processing reduced the mean total phenolics content in amaranth grain from 31.7 to 22.0 mg of gallic acid equivalent/g of dry residue. It was observed that the ethanol extract from toasted grain was the only one that presented a lower antioxidant activity index compared with the raw grain (1.3 versus 1.7). The extrusion, toasting and popping processes did not change the capacity to inhibit amaranth lipid oxidation (55%). However, cooking increased the inhibition of lipid oxidation (79%), perhaps because of the longer time at high temperatures in this process (100 degrees C/10 min). The most common methods for processing amaranth grain caused reductions in the total phenolics content, although the antioxidant activity of popped and extruded grain, evaluated by the two methods, was similar to that of the raw grain. Both raw and processed amaranth grain presents antioxidant potential. Polyphenols, anthocyanins, flavonoids, tocopherols, vitamin C levels and Maillard reaction products may be related to the antioxidant activity of this grain.

Complex rearrangements in patients with duplications of MECP2 can occur by fork stalling and template switching

Duplication at the Xq28 band including the MECP2 gene is one of the most common genomic rearrangements identified in neurodevelopmentally delayed males. Such duplications are non-recurrent and can be generated by a non-homologous end joining (NHEJ) mechanism. We investigated the potential mechanisms for MECP2 duplication and examined whether genomic architectural features may play a role in their origin using a custom designed 4-Mb tiling-path oligonucleotide array CGH assay. Each of the 30 patients analyzed showed a unique duplication varying in size from similar to 250 kb to similar to 2.6 Mb. Interestingly, in 77% of these non-recurrent duplications, the distal breakpoints grouped within a 215 kb genomic interval, located 47 kb telomeric to the MECP2 gene. The genomic architecture of this region contains both direct and inverted low-copy repeat (LCR) sequences; this same region undergoes polymorphic structural variation in the general population. Array CGH revealed complex rearrangements in eight patients; in six patients the duplication contained an embedded triplicated segment, and in the other two, stretches of non-duplicated sequences occurred within the duplicated region. Breakpoint junction sequencing was achieved in four duplications and identified an inversion in one patient, demonstrating further complexity. We propose that the presence of LCRs in the vicinity of the MECP2 gene may generate an unstable DNA structure that can induce DNA strand lesions, such as a collapsed fork, and facilitate a Fork Stalling and Template Switching event producing the complex rearrangements involving MECP2.

Contributions to the taxonomy of the Normanellidae (Copepoda, Harpacticoida): description of a new genus from the Brazilian continental shelf and re-assignment of Pseudocletodes vararensis Scott & Scott, 1893 (ex Nannopodidae)

A new genus and species of Normanellidae (Copepoda, Harpacticoida), Paranaiara inajae gen. et sp. nov., is described from the continental shelf off the northern coast of Sao Paulo State, Brazil. The new genus differs from the type genus Normanella Brady, 1880 and Sagamiella Lee & Huys, 1999 in its presence of lamelliform caudal rami, a maxillulary endopod represented by 2 setae, an unarmed maxillipedal syncoxa, and reduced setation on P2 enp-2 (without outer spine) and P3 enp-2 (with only 2 inner setae). All these apomorphic character states are shared with the genus Pseudocletodes Scott & Scott, 1893, formerly placed in the family Nannopodidae (ex Huntemanniidae) and here assigned to the Normanellidae. Pseudocletodes can be differentiated from Paranaiara by the loss of the P1 endopod and of the inner seta on P2-P4 enp-1, the presence of only 2 inner setae on P2 enp-2 (instead of 3) and only 1 inner seta on P4 exp-3 (instead of 2), the presence of a second inner seta on P4 enp-2 (instead of 1), the morphology of the fifth pair of legs which are not medially fused and have only 3 endopodal elements (instead of 4) in the male, and the well developed caudal ramus seta V (instead of rudimentary). It is postulated that prehensility of the P1 endopod was secondarily lost in the common ancestor of Paranaiara and Pseudocletodes. An updated family diagnosis of the Normanellidae and a dichotomous identification key to the 22 currently valid species are presented.

UPR-mediated TRIB3 expression correlates with reduced AKT phosphorylation and inability of interleukin 6 to overcome palmitate-induced apoptosis in RINm5F cells

Unfolded protein response (UPR)-mediated pancreatic beta-cell death has been described as a common mechanism by which palmitate (PA) and pro-inflammatory cytokines contribute to the development of diabetes. There are evidences that interleukin 6 (IL6) has a protective action against beta-cell death induced by proinflammatory cytokines; the effects of IL6 on PA-induced apoptosis have not been investigated yet. In the present study, we have demonstrated that PA selectively disrupts IL6-induced RAC-alpha serine/threonine-protein kinase (AKT) activation without interfering with signal transducer and activator of transcription 3 phosphorylation in RINm5F cells. The inability of IL6 to activate AKT in the presence of PA correlated with an inefficient protection against PA-induced apoptosis. In contrast to PA, IL6 efficiently reduced apoptosis induced by pro-inflammatory cytokines. In addition, we have demonstrated that IL6 is unable to overcome PA-stimulated UPR, as assessed by activating transcription factor 4 (ATF4) andC/EBP homologous protein (CHOP) expression, X-box binding protein-1 gene mRNA splicing, and pancreatic eukaryotic initiation factor-2 alpha kinase phosphorylation, whereas no significant induction of UPR by pro-inflammatory cytokines was detected. This unconditional stimulation of UPR and apoptosis by PA was accompanied by the stimulation of CHOP and tribble3 (TRIB3) expression, irrespective of the presence of IL6. These findings suggest that IL6 is unable to protect pancreatic beta-cells from PA-induced apoptosis because it does not repress UPR activation. In this way, CHOP and ATF4 might mediate PA-induced TRIB3 expression and, by extension, the suppression of IL6 activation of pro-survival kinase AKT. Journal of Endocrinology (2010) 206, 183-193

Switching control of sympathetic activity from forebrain to hindbrain in chronic dehydration

We investigated the mechanisms responsible for increased blood pressure and sympathetic nerve activity (SNA) caused by 2-3 days dehydration (DH) both in vivo and in situ preparations. In euhydrated (EH) rats, systemic application of the AT(1) receptor antagonist Losartan and subsequent pre-collicular transection (to remove the hypothalamus) significantly reduced thoracic (t) SNA. In contrast, in DH rats, Losartan, followed by pre-collicular and pontine transections, failed to reduce tSNA, whereas transection at the medulla-spinal cord junction massively reduced tSNA. In DH but not EH rats, selective inhibition of the commissural nucleus tractus solitarii (cNTS) significantly reduced tSNA. Comparable data were obtained in both in situ and in vivo (anaesthetized/conscious) rats and suggest that following chronic dehydration, the control of tSNA transfers from supra-brainstem structures (e. g. hypothalamus) to the medulla oblongata, particularly the cNTS. As microarray analysis revealed up-regulation of AP1 transcription factor JunD in the dehydrated cNTS, we tested the hypothesis that AP1 transcription factor activity is responsible for dehydration-induced functional plasticity. When AP1 activity was blocked in the cNTS using a viral vector expressing a dominant negative FosB, cNTS inactivation was ineffective. However, tSNA was decreased after pre-collicular transection, a response similar to that seen in EHrats. Thus, the dehydration-induced switch in control of tSNA from hypothalamus to cNTS seems to be mediated via activation of AP1 transcription factors in the cNTS. If AP1 activity is blocked in the cNTS during dehydration, sympathetic activity control reverts back to forebrain regions. This unique reciprocating neural structure-switching plasticity between brain centres emphasizes the multiple mechanisms available for the adaptive response to dehydration.

Transcriptional memory and switching in the Plasmodium falciparum rif gene family

The human malaria parasite Plasmodium falciparum expresses erythrocyte-surface directed variant antigens which are important virulence factors Many are transcribed from multigene families and presumably their mode of expression is strictly controlled to guarantee immune evasion in the human host. In order to elucidate the dynamics of rif transcription and to investigate if rif switching is comparable to var switching we monitored rif variant gene expression in parasites with different cytoadhesive properties as well as after a number of reinvasions. We found identical transcripts in parasite lines with different adhesive phenotypes suggesting that rif genes do not have a critical role in determining the cytoadhesion specificity of infected erythrocytes. We show for the first time that rif genes may show a conserved mode of transcription, maintaining the previously dominant rif transcript in subsequent reinvasions, but also observed rapid switching at rates up to 45% per generation, much higher than for the var gene family. (C) 2009 Elsevier B.V. All rights reserved.

Bubbling transition to spatial mode excitation in an extended dynamical system

We investigated the transition to spatio-temporal chaos in spatially extended nonlinear dynamical systems possessing an invariant subspace with a low-dimensional attractor. When the latter is chaotic and the subspace is transversely stable we have a spatially homogeneous state only. The onset of spatio-temporal chaos, i.e. the excitation of spatially inhomogeneous modes, occur through the loss of transversal stability of some unstable periodic orbit embedded in the chaotic attractor lying in the invariant subspace. This is a bubbling transition, since there is a switching between spatially homogeneous and nonhomogeneous states with statistical properties of on-off intermittency. Hence the onset of spatio-temporal chaos depends critically both on the existence of a chaotic attractor in the invariant subspace and its being transversely stable or unstable. (C) 2008 Elsevier B.V. All rights reserved.

REALIZING PROFINITE REDUCED SPECIAL GROUPS

Special groups are an axiomatization of the algebraic theory of quadratic forms over fields. It is known that any finite reduced special group is the special group of some field. We show that any special group that is the projective limit of a projective system of finite reduced special groups is also the special group of some field.