Methamphetamine-associated dysregulation of the hypothalamic–pituitary–thyroid axis

Methamphetamine and HIV impair thyroid function, but few studies have investigated their combined effects on thyroid dysregulation. This study examined the associations of methamphetamine use alone and in combination with HIV on thyroid function among men in South Florida. Measures of thyroid function in methamphetamine-using, HIV-infected (METH+HIV+; n?=?127) and HIV-negative (METH+HIV?; n?=?46) men who have sex with men (MSM) were compared to non-methamphetamine-using, HIV-negative men (METH?HIV?; n?=?136). Thyroid function was dysregulated in methamphetamine-using MSM, irrespective of HIV status. Both meth-using groups had greater odds of abnormal thyroid stimulating hormone levels and significantly higher mean free triiodothyronine (T3) levels. Elevated free T3 was associated with greater depressive symptoms. Overall, outcomes have important implications for assessment of thyroid function in methamphetamine users, particularly among those presenting with depression.     

Emergence and evolution of the renin–angiotensin–aldosterone system

The renin-angiotensin-aldosterone system (RAAS) is not the sole, but perhaps the most important volume regulator in vertebrates. To gain insights into the function and evolution of its components, we conducted a phylogenetic analysis of its main related genes. We found that important parts of the system began to appear with primitive chordates and tunicates and that all major components were present at the divergence of bony fish, with the exception of the Mas receptor. The Mas receptor first appears after the bony-fish/tetrapod divergence. This phase of evolutionary innovation happened about 400 million years ago. We found solid evidence that angiotensinogen made its appearance in cartilage fish. The presence of several RAAS genes in organisms that lack all the components shows that these genes have had other ancestral functions outside of their current role. Our analysis underscores the utility of sequence comparisons in the study of evolution. Such analyses may provide new hypotheses as to how and why in today's population an increased activity of the RAAS frequently leads to faulty salt and volume regulation, hypertension, and cardiovascular diseases, opening up new and clinically important research areas for evolutionary medicine.     

The Effects of Lesions to the Striatum on the Function of the Hypothalamo–Hypophyseal–Adrenal System in Adrenalectomized Rats

Experiments on white rats were performed to study the effects of bilateral lesioning of the striatum on activation of the hypothalamo-hypophyseal-adrenal system (HHAS) after unilateral adrenalectomy. These studies showed that increases in the weight of the surviving adrenal gland were smaller in striatectomized rats than in controls. There was a significant decrease in corticosteroid production by the intact gland. These changes were most marked after destruction of the dorsal parts of the nucleus. These data provide evidence for involvement of the striatum in controlling HHAS activity via a feedback mechanism.     

Wave intensity analysis and the development of the reservoir–wave approach

The parameters of wave intensity analysis are calculated from incremental changes in pressure and velocity. While it is clear that forward- and backward-traveling waves induce incremental changes in pressure, not all incremental changes in pressure are due to waves; changes in pressure may also be due to changes in the volume of a compliant structure. When the left ventricular ejects blood rapidly into the aorta, aortic pressure increases, in part, because of the increase in aortic volume: aortic inflow is momentarily greater than aortic outflow. Therefore, to properly quantify the effects of forward or backward waves on arterial pressure and velocity (flow), the component of the incremental change in arterial pressure that is due only to this increase in arterial volume—and not, fundamentally, due to waves—first must be excluded. This component is the pressure generated by the filling and emptying of the reservoir, Otto Frank’s Windkessel.     

Understanding immune–microbiota interactions in the intestine

The past two decades have seen an explosion in research that aims to understand how the dynamic interplay with the gut microbiota impacts host health and disease, establishing a role for the gut microbiota in a plethora of pathologies. Understanding how health-promoting microbiota are established and how beneficial host–microbiota interactions are maintained is of immense biomedical importance. Despite the enormous progress that has been made, our knowledge of the specific microbiota members that mediate these effects and the mechanisms underlying these interactions is rudimentary. The dearth of information regarding the nature of advantageous host–microbiota interactions, and the factors that cause these relationships to go awry, has hampered our ability to realize the therapeutic potential of the microbiota. Here we discuss key issues that limit current knowledge and describe a path forwards to improving our understanding of the contributions of the microbiota to host health.     

Navigating the structure–function–evolutionary relationship of CsaA chaperone in archaea

CsaA is a protein involved in the post-translational translocation of proteins across the cytoplasmic membrane. It is considered to be a functional homolog of SecB which participates in the Sec-dependent translocation pathway in an analogous manner. CsaA has also been reported to act as a molecular chaperone, preventing aggregation of unfolded proteins. It is essentially a prokaryotic protein which is absent in eukaryotes, but found extensively in bacteria and earlier thought to be widely present in archaea. The study of phylogenetic distribution of CsaA among prokaryotes suggests that it is present only in few archaeal organisms, mainly species of Thermoplasmatales and Halobacteriales. Interestingly, the CsaA protein from these two archaeal orders cluster separately on the phylogenetic tree with CsaA from Gram-positive and Gram-negative bacteria. It, thus, appears that this protein might have been acquired in these archaeal organisms through independent horizontal gene transfer (HGT) events from different bacteria. In this review, we summarize the earlier biochemical, structural, and functional characterization studies of CsaA. We draw new insights into the evolutionary history of this protein through phylogenetic and structural comparison of bacterial CsaA with modelled archaeal CsaA from Picrophilus torridus and Natrialba magadii.     

Experimental investigation of the stent–artery interaction

Abstract

It is well acknowledged that stent implantation causes abnormal stretch and strains on the arterial wall, which contribute to the formation and progression of restenosis. However, the experimental characterization of the strain field on the stented vessel is scant. In this work, the balloon-expandable stent implantation inside an artery analogue was captured through two high-speed CCD cameras. The surface strain maps on the stented tube were quantified with a 3-D digital image correlation technique. The strain history at one specific reference point illustrated three stenting phases, including balloon inflation, pressurization and deflation. The surface strain distributions along one axial path were obtained at various time points to demonstrate the stent–vessel interactions. The radial wall thickness reduction history was used to evaluate the pressure–diameter relationship for the balloon. Results indicated that the expansion process of the balloon was significantly altered by the external loadings from both the stent and artery analogue. In addition, the repeatability of the stenting experiments was demonstrated through two tests with a change of 5% in the stent-induced maximum first principal strain. Moreover, a computational model of the stenting procedure was developed to recapture the stenting experiments. Comparison between experiments and simulation showed a difference of 7.17% in the first principal strain averaged over the high strain area. This indicated the validation of the computational framework, which can be used to investigate the strain or stress field throughout the computational domain, a feature that is not affected by experimental techniques.     

Nano-surgery at the leukocyte–endothelial docking site

The endothelium has an important role in controlling the extravasation of leukocytes from blood to tissues. Endothelial permeability for leukocytes is influenced by transmembrane proteins that control inter-endothelial adhesion, as well as steps of the leukocyte transmigration process. In a cascade consisting of leukocyte rolling, adhesion, firm adhesion, and diapedesis, a new step was recently introduced, the formation of a docking structure or “transmigratory cup.” Both terms describe a structure formed by endothelial pseudopods embracing the leukocyte. It has been found associated with both para- and transcellular diapedesis. The aim of this study was to characterize the leukocyte–endothelial contact area in terms of morphology and cell mechanics to investigate how the endothelial cytoskeleton reorganizes to engulf the leukocyte. We used atomic force microscopy (AFM) to selectively remove the leukocyte and then analyze the underlying cell at this specific spot. Firmly attached leukocytes could be removed by AFM nanomanipulation. In few cases, this exposed 8–12 μm wide and 1 μm deep footprints, representing the cup-like docking structure. Some of them were located near endothelial cell junctions. The interaction area did not exhibit significant alterations neither morphologically nor mechanically as compared to the surrounding cell surface. In conclusion, the endothelial invagination is formed without a net depolymerization of f-actin, as endothelial softening at the site of adhesion does not seem to be involved. Moreover, there were no cases of phagocytotic engulfment, but instead the formation of a transmigratory channel could be observed.     

Highlights on the EAACI–WAO Congress 2013

European Academy of Allergy and Clinical Immunology and World Allergy Organization. World Allergy and Asthma Congress.

Milano, Italy, 22–26 June 2013

The European Academy of Allergy and Clinical Immunology and World Allergy Organization congress provided a meeting for researchers and clinicians interested in allergy and clinical immunology from all over the world and a unique opportunity to exchange experience with other professionals in this fields.     

The role of the renin–angiotensin system in the pathogenesis of preeclampsia – New insights into the renin–angiotensin system in preeclampsia

The renin–angiotensin system (RAS) plays an important role in the pathogenesis of hypertension. However, the role of RAS in preeclampsia is largely unknown, because the plasma concentration of renin and angiotensin (AII) is lower in preeclampsia than in normal pregnancy, whereas its cardinal sign is hypertension. A pressor response to AII infusions can predict the onset of preeclampsia, resulting in involvement of RAS in the pathogenesis of preeclampsia. It has been reported that patients with preeclampsia exhibit angiotensin type I receptor agonistic autoantibody (AT1-AA), suggesting the involvement of RAS in the pathogenesis of this condition. The physiological action of AT1-AA can explain the various clinical symptoms of preeclampsia. However, the significance of circulatory RAS, including AT1-AA, in the pathogenesis of preeclampsia remains obscure. Since many reports state that circulating RAS is thought to be suppressed in preeclampsia it is difficult to explain the onset of hypertension in preeclampsia by circulating RAS. Therefore, I propose new insights into the role of RAS in preeclampsia to resolve the contradiction as above-mentioned. The recent discovery of tissue RAS, on which prorenin and its receptor act, suggests a promising new direction in understanding the role of RAS in the pathogenesis of preeclampsia.     

Correlates of child–father and child–mother attachment in the preschool years

The increase in fathers’ involvement in childrearing, particularly beyond infancy, warrants research exploring factors influencing the quality of child–father attachment relationships, and the impact of these relationships on children’s social development. The current investigation explored various correlates of preschoolers’ child–father attachment security to both parents, including contextual factors (i.e., socioeconomic status, child temperament, parenting stress), parental play sensitivity, and child social adaptation. Participants included 107 preschool-aged children (59 girls; M = 46.67 months, SD = 8.57) and their fathers and mothers. Results revealed that both mothers’ and fathers’ play sensitivity were associated with child attachment security after controlling for different contextual factors. Furthermore, the magnitude of the association between child conduct problems and child–father attachment insecurity was stronger than the corresponding association with child–mother attachment insecurity. Findings provide important information on caregiving factors associated with child–father attachment security in the preschool years and the importance of this bond to children’s social adaptation.     

Arm–trunk coordination in the absence of proprioception

During trunk-assisted reaching to targets placed within arms length, the influence of trunk motion on the hand trajectory is compensated for by changes in the arm configuration. The role of proprioception in this compensation was investigated by analyzing the movements of 2 deafferented and 12 healthy subjects. Subjects reached to remembered targets (placed ~80° ipsilateral or ~45° contralateral to the sagittal midline) with an active forward movement of the trunk produced by hip flexion. In 40% of randomly selected trials, trunk motion was mechanically blocked. No visual feedback was provided during the experiment. The hand trajectory and velocity profiles of healthy subjects remained invariant whether or not the trunk was blocked. The invariance was achieved by changes in arm interjoint coordination that, for reaches toward the ipsilateral target, started as early as 50 ms after the perturbation. Both deafferented subjects exhibited considerable, though incomplete, compensation for the effects of the perturbation. Compensation was more successful for reaches to the ipsilateral target. Both deafferented subjects showed invariance between conditions (unobstructed or blocked trunk motion) in their hand paths to the ipsilateral target, and one did to the contralateral target. For the other deafferented subject, hand paths in the two types of trials began to deviate after about 50% into the movement, because of excessive elbow extension. In movements to the ipsilateral target, when deafferented subjects compensated successfully, the changes in arm joint angles were initiated as early as 50 ms after the trunk perturbation, similar to healthy subjects. Although the deafferented subjects showed less than ideal compensatory control, they compensated to a remarkably large extent given their complete loss of proprioception. The presence of partial compensation in the absence of vision and proprioception points to the likelihood that not only proprioception but also vestibulospinal pathways help mediate this compensation.Due to an error in the citation line, this revised PDF (published in December 2003) deviates from the printed version, and is the correct and authoritative version of the paper.     

Dendritic cell–epithelial cell crosstalk in the gut

Intestinal epithelial cells are fundamental to maintain barrier integrity and to participate in food degradation and absorption, but they can also decipher signals coming from the outside world and ‘educate’ the immune system accordingly. In particular, they interact with dendritic cells (DCs) and other intraepithelial immune cells to drive tolerogenic responses under steady state, but they can also release immune mediators to recruit inflammatory cells and to elicit immunity to infectious agents. When these interactions are deregulated, immune disorders can develop. In this review, we discuss some important features of epithelial cells and DCs and their fruitful interactions.