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Adrenomedullin: multiple functions in human pregnancy.

Adrenomedullin is a 52 amino acid peptide originally isolated from human phaeochromocytoma in 1993. It was initially demonstrated to have profound effects on the vasculature including vasodilatation and subsequently promotion of angiogenesis. Since then it has become apparent that it has a wide range of other biological actions including regulation of cell growth and differentiation. Successful pregnancy outcome relies on establishing and maintaining throughout gestation an efficient blood supply to the fetus. This allows the exchange of nutrients, oxygenation of fetal blood and removal of cytotoxins from the fetus, such as carbon dioxide. One of the most important local adaptations to pregnancy is the change in maternal blood flow to the implantation site. Evidence now points towards a vital role for adrenomedullin in the regulation of placentation. It appears that adrenomedullin may play important roles in the regulation of fetal perfusion both in normal and in compromised pregnancies. However, most studies have focused on measuring adrenomedullin levels and studying its expression as well as that of its receptors. More functional studies are now required to elucidate the underlying mechanisms involved.

Adrenomedullin↗

Development and Characterization of Microsatellite Markers for the Euryhaline Polychaete Laeonereis acuta (Annelida: Nereididae) in the Southwestern Brazilian Coast.

Laeonereis acuta is a polychaete species typically found at high abundance in estuarine and coastal lagoon environments. Due to its association with polluted habitats, it is commonly used in ecotoxicological studies. Moreover, its occurrence in spatially discontinuous environments with high environmental variability makes it a suitable model for evolutionary studies of local adaptation, genetic landscape, and early stages of speciation. This study aimed to develop primers and characterize microsatellite markers for L. acuta sampled from three coastal lagoons in southwestern Brazil. A total of 10 loci were characterized based on the genotyping of 40 individuals. The number of alleles per locus ranged from 2 to 19. Evidence of null alleles was detected at five loci, although their frequency decreased when coastal lagoons were analyzed separately. When considering all individuals as a single population, five loci showed positive and significant FIS values, and seven loci deviated from Hardy-Weinberg equilibrium. Maricá and Guarapina exhibited heterozygote excess at several loci, whereas Jaconé showed evidence of population genetic isolation. The 10 microsatellite loci were polymorphic and suitable for population genetic analysis in L. acuta, although these patterns may not necessarily be representative of other geographic regions. These markers may contribute to ecotoxicological studies by clarifying whether physiological responses to pollutants are associated with genetic differentiation among populations. Furthermore, they provide valuable tools for investigating genetic structure and connectivity in discontinuous environments.

Animals↗

Hybrid disadvantage in the larval foraging behaviour of the two neotropical species of Drosophila pavani and Drosophila gaucha.

Flies from two populations of the Chilean endemic neotropical species Drosophila pavani and two populations of its sibling species Drosophila gaucha were crossed reciprocally to obtain intra- and interspecific hybrids. The developmental pathways of locomotor activity and feeding rate were analysed for eleven of twelve possible genotype groups. The hybrids showed reduced fitness indicated by a decrease in the measured traits. Hybrid disadvantage was strongest in interspecific hybrids, especially with respect to feeding behaviour. This evidence supports the contention that D. pavani and D. gaucha have evolved different coadapted gene pools controlling the developmental pathways for behavioural traits expressed during larval foraging; but genetic divergence affecting these behaviours has also taken place between locally adapted populations within each species.

Animals↗

Detecting natural selection on cis-regulatory DNA.

Changes in transcriptional regulation play an important role in the genetic basis for evolutionary change. Here I review a growing body of literature that seeks to determine the forces governing the non-coding regulatory sequences underlying these changes. I address the challenges present in studying natural selection without the familiar structure and regularity of protein-coding sequences, but show that most tests of neutrality that have been used for coding regions are applicable to non-coding regions, albeit with some caveats. While some experimental investment is necessary to identify heritable regulatory variation, the most basic inferences about selection require very little functional information. A growing body of research on cis-regulatory variation has uncovered all the forms of selection common to coding regions, in addition to novel forms of selection. An emerging pattern seems to be the ubiquity of local adaptation and balancing selection, possibly due to the greater freedom organisms have to fine-tune gene expression without changing protein function. It is clear from multiple single locus and whole genome studies of non-coding regulatory DNA that the effects of natural selection reach far beyond the start and stop codons.

Animals↗

Hybridization and the colonization of novel habitats by annual sunflowers.

Although invasive plant species often have a hybrid ancestry, unambiguous evidence that hybridization has stimulated the evolution of invasive behaviors has been difficult to come by. Here, we briefly review how hybridization might contribute to the colonization of novel habitats, range expansions, and invasiveness and then describe work on hybrid sunflowers that forges a direct link between hybridization and ecological divergence. We first discuss the invasion of Texas by the common sunflower and show that the introgression of chromosomal segments from a locally adapted species may have facilitated range expansion. We then present evidence that the colonization of sand dune, desert floor, and salt marsh habitats by three hybrid sunflower species was made possible by selection on extreme or "transgressive" phenotypes generated by hybridization. This body of work corroborates earlier claims regarding the role of hybridization in adaptive evolution and provides an experimental and conceptual framework for ongoing studies in this area.

Biological Evolution↗

Response to host volatiles by native and introduced populations of Dendroctonus valens (Coleoptera: Curculionidae, Scolytinae) in North America and China.

Bark beetles (Coleoptera: Curculionidae, Scolytinae) have specialized feeding habits, and commonly colonize only one or a few closely related host genera in their geographical ranges. The red turpentine beetle, Dendroctonus valens LeConte, has a broad geographic distribution in North America and exploits volatile cues from a wide variety of pines in selecting hosts. Semiochemicals have been investigated for D. valens in North America and in its introduced range in China, yielding apparent regional differences in response to various host volatiles. Testing volatiles as attractants for D. valens in its native and introduced ranges provides an opportunity to determine whether geographic separation promotes local adaptation to host compounds and to explore potential behavioral divergence in native and introduced regions. Furthermore, understanding the chemical ecology of host selection facilitates development of semiochemicals for monitoring and controlling bark beetles, especially during the process of expansion into new geographic ranges. We investigated the responses of D. valens to various monoterpenes across a wide range of sites across North America and one site in China, and used the resulting information to develop an optimal lure for monitoring populations of D. valens throughout its Holarctic range. Semiochemicals were selected based on previous work with D. valens: (R)-(+)-alpha-pinene, (S)-(-)-alpha-pinene, (S)-(-)-beta-pinene, (S)-(+)-3-carene, a commercially available lure [1:1:1 ratio of (R)-(+)-alpha-pinene:(S)-(-)-beta-pinene:(S)-(+)-3-carene], and a blank control. At the release rates used, (+)-3-carene was the most attractive monoterpene tested throughout the native range in North America and introduced range in China, confirming results from Chinese studies. In addition to reporting a more effective lure for D. valens, we present a straightforward statistical procedure for analysis of insect trap count data yielding cells with zero counts, an outcome that is common but makes the estimation of the variance with a Generalized Linear Model unreliable because of the variability/mean count dependency.

Animals↗

Repeated and chronic morphine administration causes differential long-lasting changes in dopaminergic neurotransmission in rat striatum without changing its delta- and kappa-opioid receptor regulation.

Repeated, once daily morphine treatment (14 days) as well as chronic morphine administration (6 days) caused a rebound reduction in the electrically evoked release of [3H]dopamine from superfused rat striatal slices 1 day after the last subcutaneous injection. Interestingly, whereas [3H]dopamine release remained significantly reduced for at least 3 weeks following morphine withdrawal in chronically treated (tolerant/dependent) rats, neurotransmitter release from dopaminergic nerve terminals gradually increased above control values following cessation of repeated morphine administration. Postsynaptically, dopamine D1 receptor-stimulated adenylate cyclase appeared to be sensitized 1-3 days but was unchanged 3 weeks after chronic morphine treatment. In contrast, such an enhanced postsynaptic dopamine D1 receptor efficacy did not occur 1-3 days following repeated morphine administration, but appeared to develop slowly resulting in a profound increase of dopamine-sensitive adenylate cyclase 3 weeks after the last injection. The inhibitory effect of dynorphin A-(1-13) on [3H]dopamine release, as well as that of [Met5]enkephalin on dopamine D1 receptor-stimulated adenylate cyclase appeared to be unchanged subsequent to repeated or chronic morphine treatment. These data indicate that, long after cessation of drug treatment, chronic morphine treatment causes a reduction whereas repeated morphine administration gradually induces an enhancement of opioid receptor-regulated dopaminergic neurotransmission due to local adaptive changes within the rat striatum. Such distinct long-lasting alterations of dopaminergic neurotransmission induced by different temporal patterns of morphine administration in projection areas of mesencephalic dopaminergic neurons may be related to the enduring effects of drug abuse such as behavioural sensitization and drug craving.

Adenylyl Cyclases↗

Global factors generate the McCollough effect.

It has recently been demonstrated that certain globally orthogonal pattern pairs derived from Hoffman's Lie Transformation Group Model of Neuropsychology (LTG/NP) are sufficient to generate McCollough effects (pattern-contingent colour aftereffects: PCCAES). We now provide evidence that the global factors postulated to generate these particular PCCAEs are also necessary. In Experiment 1 observers made controlled eye movements over the induction patterns and subsequently showed PCCAEs which were as strong as those obtained under central fixation. The induction process therefore did not depend on selectively adapting local oriented and colour-specific edge detectors. The global structure of the inducing patterns appears to be a necessary component of the generation of such aftereffects. In Experiment 2, a number of pattern pairs having various degrees of global organization were used as induction patterns, but in every case there was an equal degree of local orthogonality. Local orthogonality was shown not to be sufficient to induce PCCAEs, but global orthogonality was. These results lend strong support to the notion that McCollough-type PCCAEs are generated in a structure of the visual system somewhat above the level of strictly local operations, whether defined as edge and bar detectors or, equivalently, as units selectively tuned to different spatial frequencies and orientations. The global nature of the effects, and the particular pattern structures involved, lead us to suggest that Hoffman's LTG/NP provides a sound basis for explaining our findings.

Adolescent↗

Dynamic noise backgrounds facilitate target fading.

With strict fixation, a small uniform target of medium contrast, placed at 10 deg eccentricity, faded much faster when presented on a dynamic random noise background than on either a static random noise background or a uniform background of the same luminance. Time to first disappearance was between 10 and 16 sec when the background was dynamic, 26 sec when it was static, and 57 sec when it was uniform. Times were shortest for temporal noise frequencies of the background between 3.5 and 15 Hz. These findings are unexpected: the frequent change of pixel contrast at the edge of the target should perceptually enhance the border, make it less susceptible to local adaptation, and prevent fading. Instead, dynamic random noise facilitates, rather than suppresses fading. Three potential mechanisms are discussed: edge perturbation, jerk effect and surround induction.

Adaptation, Ocular↗

Effect of exercise on human arterial and regional venous plasma concentrations of prostaglandin E.

Healthy male volunteers underwent catheterization of a brachial artery and subclavian, hepatic, renal, and femoral veins. Blood was sampled simultaneously from all catheters, at rest as well as during supine leg exercise at 130 W. Plasma PGE were extracted and purified, using silicic acid chromatography, and subsequently quantified, using RIA. At rest no release or uptake of PGE was observed in the arm, the splanchnic region, or the leg, but in the kidney an uptake was noted. During exercise a significant release of PGE developed in the arm and in the leg. The data support the hypothesis that vascular PGs play a role in the local adaptation of the circulatory system to exercise.

Adult↗

Effects of photic stimulation on heart rate of infant rats.

We present the results of three experiments which characterize the heart rate (HR) response of infant rats at a number of different ages to the onset, or the offset, of a bright light. Experiment 1 demonstrated that at ages 5, 8, 11, 14, 17 and 21 days, a sudden increase in ambient illumination caused a HR deceleration, whereas a sudden decrease in ambient illumination caused a HR acceleration. At each age, the HR acceleration did not habituate over 60 stimulus presentations, whereas at all ages beginning at 8 days, the HR deceleration did habituate. By varying the intensity of either the visual or thermal component of the stimulus at ages 8 and 17 days, Experiment 2 revealed that the directional effects were a result of the visual and not the thermal component of the stimulus, thereby ruling out any account of the findings in terms of local adaptational reflexes. Finally, Experiment 3 varied the rate of stimulation, tested for spontaneous recovery, and demonstrated that the decrement in response magnitude observed across trials conformed to several of the accepted parametric characteristics of habituation, and could not be accounted for by changes in baseline HR across trials. These results are discussed in terms of traditional interpretations of HR changes as orienting and defensive reactions.

Age Factors↗

Evaluation of mastic, a crude drug obtained from Pistacia lentiscus for gastric and duodenal anti-ulcer activity.

The effect of mastic, a concrete resinous exudate obtained from the stem of the tree Pistacia lentiscus, has been studied on experimentally-induced gastric and duodenal ulcers in rats. Mastic at an oral dose of 500 mg/kg produced a significant reduction in the intensity of gastric mucosal damage induced by pyloric ligation, aspirin, phenylbutazone, reserpine and restraint + cold stress. It produced a significant decrease of free acidity in 6-h pylorus-ligated rats and a marked cytoprotective effect against 50% ethanol in rats which could be reversed by prior treatment with indomethacin. The protective effect was not seen when it was given intraperitoneally in phenylbutazone and restraint + cold stress models. The reduction in the intensity of ulceration in cysteamine-induced duodenal ulcers was not found to be statistically significant in mastic-pretreated rats. The results suggest that mild antisecretory and a localized adaptive cytoprotectant action may be responsible for its anti-ulcer activity. These observations support the results of an earlier study on the clinical effectiveness of mastic in the therapy of duodenal ulcer.

Animals↗

Generation of atrial natriuretic peptide (ANP) in perfused lungs of spontaneously hypertensive rats (SHR). Comparison to Wistar-Kyoto (WKY) and Wistar (W) rat strains.

1. Lungs can take up from the vasculature, circulating forms of atrial natriuretic peptide (Turrin and Gillis, 1986, 1987) and also to synthesize ANP. 2. The lung peptide directly delivered by lungs into the lung vasculature could play a role in the local water/electrolytic balance. 3. Using Spontaneously Hypertensive Rats (SHR), isogenic normotensive controls, the Wistar-Kyoto strain (WKY), and the regular Wistar strain as second control (W), and using a highly sensitive RIA, we measured the immunoreactive IR-ANP content of extracted plasma, lung homogenate and lung perfusate, since there are references of altered ANP levels in this kind of hypertension. 4. The IR-ANP measured in the lung vasculature effluent collected throughout 32 min of Krebs perfusion, was significantly different in all of the three analyzed strains (SHR > WKY > W). 5. The results support the idea of a local function for the peptide hormone directly delivered into the lung vasculature of SHR, which could represent a local adaptation to haemodynamics SHR characteristics besides a genetic characteristic distinguishing WKY from W strains.

Animals↗

Identification of telomerase activity in gametocytes of Plasmodium falciparum.

Telomerase, a specialized cellular reverse transcriptase, compensates the chromosome shortening during the replication of most eukaryotic cells and contributes to cellular immortalization in cell culture (in vitro) and cancerous cell (in vivo). In the present study, the telomerase activity in the gametocytes of Plasmodium falciparum was investigated. Here, we report for the first time, the presence of telomerase activity in the gametocytes of P. falciparum using P. falciparum telomere repeat amplification protocol (Pf-TRAP) assay and Southern blot hybridization. Telomerase inhibitors such as 7-deaza-dGTP and AZT-TP, when used with the cytoplasmic extract of gametocytes in the Pf-TRAP assay, efficiently inhibit the product, which confirms the presence of telomerase in the gametocytes. The presence of telomerase activity in the laboratory adapted local (eastern India) isolates of P. falciparum indicates that telomerase might be the major player in chromosomal end protection during replication. The finding suggests that telomerase can be a potent target for the transmission blocking vaccine and drugs for combating malaria caused by P. falciparum.

Animals↗

Honeybees foraging response in genetically diversified opium poppy.

Studies were carried out on honeybees foraging on plant flowers. Results showed significantly higher foraging response of honeybees (Apis mellifera) in genetically divergent narcotic plant opium poppy (Papaver somniferum). Of the 18 mutants and two locally adapted cultivars of diverse genotypes screened, eight revealed significantly greater foraging response manifesting honeybee's preference towards specific plant morphotypes. The number of flower bloom did not correspond to number of foraging bees in both mutant and cultivar plant types of opium poppy. The genotype specific foraging response of honeybees could be attributed to physico-chemical properties of opium poppy flowers. This could have implications for the development of opium alkaloid fortified honeys for novel pharmaceuticals and isolation of natural spray compounds to attract honeybee pollinators for promoting crossing and sustainable hybridity in crops.

Animals↗

ERP measures of auditory word repetition and translation priming in bilinguals.

Motivated by the demonstration of similarly localized adaptation of the hemodynamic response in a first (L1) and second (L2) language, this study examined event-related brain potentials (ERPs) to spoken words in L1 and L2 in 15 English-French bilinguals. We examined whether the temporal pattern of N400 adaptation due to within-language repetitions (i.e., repetition priming) was similar in L1 and L2 and whether the release from adaptation elicited by a within-language word change was similar. Furthermore, using word changes across language, we examined the phonological mismatch negativity (PMN) and N400 components to determine the kind of information activated during translation priming. In contrast to within-language repetition, we expected between-language repetition (i.e., translations) to be characterized by conceptual rather than lexical/phonological word form priming. Overall, the pattern of adaptation and release from adaptation was similar in L1 and L2, with evidence of delayed semantic analysis in L2 in the form of a later N400 effect. A change in language (L1 to L2) elicited a similar pattern of PMN and N400 activity compared to a within-language change in meaning in L1, suggesting that neither word form nor conceptual information was available on-line for the forward translation. In contrast, the presence of strong PMN but minimal N400 effects for L2-to-L1 translations suggests that conceptual but not phonological information is available on-line for backwards translation. L2 proficiency influenced the extent to which conceptual representations were activated by translations. These data are discussed in light of current models of bilingual word processing and suggest modality differences in the pattern of activation of lexical and conceptual information.

Acoustic Stimulation↗

Localized PD-1 CAR T therapy reprograms neuroinflammation.

B cell-depleting therapies are effective in multiple sclerosis (MS), yet some patients relapse, underscoring the need for more precise interventions. To identify new therapeutic targets, we generated a single-cell RNA sequencing (scRNA-seq) atlas of cerebrospinal fluid (CSF), brain, and blood from non-inflammatory controls and patients with MS or other neuroinflammatory diseases. We found disease-associated enrichment of class-switched immunoglobulin G+ (IgG+) B cells and plasma cells in MS CSF. Unbiased analysis identified a rare disease-enriched subset of activated, T cell receptor (TCR)-restricted, PD-1+ T follicular helper-like cells with B cell-recruiting features. To target this population, we developed PD-1-directed chimeric antigen receptor (CAR) T cells that selectively depleted pathogenic PD-1+ CD4 T cells and locally released IL-10. This strategy attenuated central nervous system (CNS) inflammation, reprogrammed the local immune milieu, and improved clinical outcomes across murine neuroinflammation models. These findings define a CNS-localized adaptive immune circuit in MS and nominate programmable PD-1 CAR T cells as a strategy to disrupt it.

Animals↗

Positive selection on a human-specific transcription factor binding site regulating IL4 expression.

A single nucleotide polymorphism in the promoter of the multifunctional cytokine Interleukin 4 (IL4) affects the binding of NFAT, a key transcriptional activator of IL4 in T cells. This regulatory polymorphism influences the balance of cytokine signaling in the immune system, with important consequences-positive and negative-for human health. We determined that the NFAT binding site is unique to humans; it arose by point mutation along the lineage separating humans from other great apes. We show that its frequency distribution among human subpopulations has been shaped by the balance of selective forces on IL4's diverse roles. New statistical approaches, based on parametric and nonparametric comparisons to neutral variants typed in the same individuals, indicate that differentiation among subpopulations at the IL4 promoter polymorphism is too great to be attributed to neutral drift. The allele frequencies of this binding site represent local adaptation to diverse pathogenic challenges; disease states associated with the common derived allele are side-effects of positive selection on other IL4 functions.

Animals↗