Characterization of Zur-dependent genes and direct Zur targets in Yersinia pestis

Background  

The zinc uptake regulator Zur is a Zn²⁺-sensing metalloregulatory protein involved in the maintenance of bacterial zinc homeostasis. Up to now, regulation of zinc homeostasis by Zur is poorly understood in Y. pestis.     

Oxytocin (OT) and arginine-vasopressin (AVP) act on OT receptors and not AVP V1a receptors to enhance social recognition in adult Syrian hamsters (Mesocricetus auratus)

Social recognition is a fundamental requirement for all forms of social relationships. A majority of studies investigating the neural mechanisms underlying social recognition in rodents have investigated relatively neutral social stimuli such as juveniles or ovariectomized females over short time intervals (e.g., 2 h). The present study developed a new testing model to study social recognition among adult males using a potent social stimulus. Flank gland odors are used extensively in social communication in Syrian hamsters and convey important information such as dominance status. We found that the recognition of flank gland odors after a 3 min exposure lasted for at least 24 h, substantially longer than the recognition of other social cues in rats and mice. Intracerebroventricular injections of OT and AVP prolonged the recognition of flank gland odor for up to 48 h. Selective OTR but not V1aR agonists, mimicked these enhancing effects of OT and AVP. Similarly, selective OTR but not V1aR antagonists blocked recognition of the odors after 20 min. In contrast, the recognition of non-social stimuli was not blocked by either the OTR or the V1aR antagonists. Our findings suggest both OT and AVP enhance social recognition via acting on OTRs and not V1aRs and that the recognition enhancing effects of OT and AVP are limited to social stimuli.     

Oxytocin hypersensitivity in pregnant P-LAP deficient mice

AimsOxytocin (OT) is the strongest uterotonic substance and has been used widely to induce labor. The physiological importance of OT in modulating the initiation and progression of labor remains unclear. In this study, we showed the roles of OT with onset of labor and also the arginine vasopressin (AVP) effect on urine volume in vivo using both wild type (WT) and placental leucine aminopeptidase (P-LAP)-deficient (KO) mice.Main methodsOT (1, 2, 2.5 U/day) or recombinant P-LAP (0.01 U/day) was continuously infused from gestation day 15.5 in WT and P-LAP KO mice. Duration until onset of labor was observed. Before and after administration of AVP (1 U/day) in WT and P-LAP KO mice, urine volume was measured.Key findingsA significant shortening of pregnancy term was observed in P-LAP KO mice. Continuous infusion of OT (1 U/day) revealed that P-LAP KO mice resulted in premature delivery (OT hypersensitivity). We could observe a significant decrease of urine volume in P-LAP KO mice by administration of AVP. Administration of recombinant P-LAP in WT mice resulted in the delay of the onset of labor about 1.5 days compared with control mice.SignificanceOur present study shows that the regulation of the onset of labor mainly depends on OT and its degradation by P-LAP and also the possible role of P-LAP in the regulation of urine output. P-LAP might be involved in the increased OT sensitivity just prior to onset of labor and also in the onset of labor by degradation of OT.     

Modeling system states in liver cells: Survival,apoptosis and their modifications in response to viral infection

Background  

The decision pro- or contra apoptosis is complex, involves a number of different inputs, and is central for the homeostasis of an individual cell as well as for the maintenance and regeneration of the complete organism.     

Computational simulation of vasopressin secretion using a rat model of the water and electrolyte homeostasis

Background  

In mammals, vasopressin (AVP) is released from magnocellular neurons of the hypothalamus when osmotic pressure exceeds a fixed set-point. AVP participates to the hydromineral homeostasis (HH) by controlling water excretion at the level of the kidneys. Our current understanding of the HH and AVP secretion is the result of a vast amount of data collected over the five past decades. This experimental data was collected using a number of systems under different conditions, giving a fragmented view of the components involved in HH.     

Renal aquaporins and water balance disorders

Background

Aquaporins (AQPs) are a family of proteins that can act as water channels. Regulation of AQPs is critical to osmoregulation and the maintenance of body water homeostasis. Eight AQPs are expressed in the kidney of which five have been shown to play a role in body water balance; AQP1, AQP2, AQP3, AQP4 and AQP7. AQP2 in particular is regulated by vasopressin.

Scope of review

This review summarizes our current knowledge of the underlying mechanisms of various water balance disorders and their treatment strategies.

Major conclusions

Dysfunctions of AQPs are involved in disorders associated with disturbed water homeostasis. Hyponatremia with increased AQP levels can be caused by diseases with low effective circulating blood volume, such as congestive heart failure, or osmoregulation disorders such as the syndrome of inappropriate secretion of antidiuretic hormone. Treatment consists of fluid restriction, demeclocycline and vasopressin type-2 receptor antagonists. Decreased AQP levels can lead to diabetes insipidus (DI), characterized by polyuria and polydipsia. In central DI, vasopressin production is impaired, while in gestational DI, levels of the vasopressin-degrading enzyme vasopressinase are abnormally increased. Treatment consists of the vasopressin analogue dDAVP. Nephrogenic DI is caused by the inability of the kidney to respond to vasopressin and can be congenital, but is most commonly acquired, usually due to lithium therapy. Treatment consists of sufficient fluid supply, low-solute diet and diuretics.

General significance

In recent years, our understanding of the underlying mechanisms of water balance disorders has increased enormously, which has opened up several possible new treatment strategies. This article is part of a Special Issue entitled Aquaporins.     

Effects of cholinergic agents on the vasopressin-mediated water transport in the isolated toad bladder

The aim of this work was to study the effect of some pharmacological cholinergic agents on the events that follow the interaction of arginine vasopressin with toad bladder membrane receptors related to synthesis of 3′5′_cAMP. The water flow through the membrane was measured gravimetrically in sac preparations of the membrane. In the absence of arginine vasopressin (AVP), carbachol induced a significant increase in the water flow (37%) related to the basal (Ringer's solution). On the other hand, when carbachol and AVP were associated, a significant decrease of AVP hydrosmotic activity occurred (23%). The inhibitory effect of carbachol on the AVP action was almost completely abolished by the cholinergic antagonists atropine, pirenzepine, 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) and the calcium antagonist lanthanum. Similarly, when carbachol and 3′5′ cyclic adenosine monophosphate (3′5′_cAMP) were associated, a decrease of nucleotide hydrosmotic activity was observed (12.80%). This effect was partially restored by the addition of pirenzepine or 4-DAMP in the bath solution. These results suggest a role for muscarinic receptors of sub-type M₁ and M₃, which are involved in the intracellular calcium release. The increase of calcium concentration in the intracellular medium acts as a negative modulator in the hydrosmotic action of antidiuretic hormone.     

Oxytocin and vasopressin involved in restraint water-immersion stress mediated by oxytocin receptor and vasopressin 1b receptor in rat brain

Aims

Vasopressin (AVP) and oxytocin (OT) are considered to be related to gastric functions and the regulation of stress response. The present study was to study the role of vasopressinergic and oxytocinergic neurons during the restraint water-immersion stress.

Methods

Ten male Wistar rats were divided into two groups, control and RWIS for 1h. The brain sections were treated with a dual immunohistochemistry of Fos and oxytocin (OT) or vasopressin (AVP) or OT receptor or AVP 1b receptor (V_1bR).

Results

(1) Fos-immunoreactive (Fos-IR) neurons dramatically increased in the hypothalamic paraventricular nucleus (PVN), the supraoptic nucleus (SON), the neucleus of solitary tract (NTS) and motor nucleus of the vagus (DMV) in the RWIS rats; (2) OT-immunoreactive (OT-IR) neurons were mainly observed in the medial magnocellular part of the PVN and the dorsal portion of the SON, while AVP-immunoreactive (AVP-IR) neurons mainly distributed in the magnocellular part of the PVN and the ventral portion of the SON. In the RWIS rats, Fos-IR neurons were indentified in 31% of OT-IR neurons and 40% of AVP-IR neurons in the PVN, while in the SON it represented 28%, 53% respectively; (3) V_1bR-IR and OTR-IR neurons occupied all portions of the NTS and DMV. In the RWIS rats, more than 10% of OTR-IR and V_1bR-IR neurons were activated in the DMV, while lower ratio in the NTS.

Conclusion

RWIS activates both oxytocinergic and vasopressinergic neurons in the PVN and SON, which may project to the NTS or DMV mediating the activity of the neurons by OTR and V_1bR.     

Identification and evaluation of the role of the manganese efflux protein in <Emphasis Type="Italic">Deinococcus radiodurans</Emphasis>

Background  

Deinococcus radiodurans accumulates high levels of manganese ions, and this is believed to be correlated with the radiation resistance ability of this microorganism. However, the maintenance of manganese ion homeostasis in D. radiodurans remains to be investigated.     

Molecular and functional analyses of COPT/Ctr-type copper transporter-like gene family in rice

Background  

The copper (Cu) transporter (COPT/Ctr) gene family has an important role in the maintenance of Cu homeostasis in different species. The rice COPT-type gene family consists of seven members (COPT1 to COPT7). However, only two, COPT1 and COPT5, have been characterized for their functions in Cu transport.     

Rhythmic activities of hypothalamic magnocellular neurons: Autocontrol mechanisms

Electrophysiological recordings in lactating rats show that oxytocin (OT) and vasopressin (AVP) neurons exhibit specific patterns of activities in relation to peripheral stimuli: periodic bursting firing for OT neurons during suckling, phasic firing for AVP neurons during hyperosmolarity (systemic injection of hypertonic saline). These activities are autocontrolled by OT and AVP released somato-dentritically within the hypothalamic magnocellular nuclei. In vivo, OT enhances the amplitude and frequency of bursts, an effect accompanied with an increase in basal firing rate. However, the characteristics of firing change as facilitation proceeds: the spike patterns become very irregular with clusters of spikes spaced by long silences; the firing rate is highly variable and clearly oscillates before facilitated bursts. This unstable behaviour dramatically decreases during intense tonic activation which temporarily interrupts bursting, and could therefore be a prerequisite for bursting. In vivo, the effects of AVP depend on the initial firing pattern of AVP neurons: AVP excites weakly active neurons (increasing duration of active periods and decreasing silences), inhibits highly active neurons, and does not affect neurons with intermediate phasic activity. AVP brings the entire population of AVP neurons to discharge with a medium phasic activity characterised by periods of firing and silence lasting 20–40 s, a pattern shown to optimise the release of AVP from the neurohypophysis. Each of the peptides (OT or AVP) induces an increase in intracellular Ca²⁺ concentration, specifically in the neurons containing either OT or AVP respectively. OT evokes the release of Ca²⁺ from IP3-sensitive intracellular stores. AVP induces an influx of Ca²⁺ through voltage-dependent Ca²⁺ channels of T-, L- and N-types. We postulate that the facilitatory autocontrol of OT and AVP neurons could be mediated by Ca²⁺ known to play a key role in the control of the patterns of phasic neurons.     

Carbachol inhibits Na(+)-K(+)-ATPase activity in choroid plexus via stimulation of the NO/cGMP pathway

Secretion of cerebrospinal fluid by the choroid plexus canbe inhibited by its cholinergic innervation. We demonstrated that carbachol inhibits the Na⁺-K⁺-ATPase in bovinechoroid tissue slices and investigated the mechanism. Many of theactions of cholinergic agents are mediated by nitric oxide (NO), whichplays important roles in fluid homeostasis. The inhibition ofNa⁺-K⁺-ATPase was blocked by the NO synthaseinhibitor [N-nitro-L-argininemethyl ester] and was quantitatively mimicked by the NO agonistssodium nitroprusside (SNP) and diethylenetriamine NO. Inhibition by SNPcorrelated with an increase in tissue cGMP and was abolished by1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, an inhibitor of soluble guanylate cyclase. Inhibition was mimicked bythe protein kinase G activator 8-bromo-cGMP and by okadaic acid, aninhibitor of protein phosphatases 1 and 2A. cGMP-dependent proteinkinase inhibitors Rp-8-pCPT-cGMP (0.5-5 µM) and KT-5823 (2.0 µM) did not block the effects of SNP, but higher concentrations ofthe more selective inhibitor (Rp-8-pCPT-cGMP) had a pharmacological inhibitory effect on Na⁺-K⁺-ATPase. The datasuggest that cholinergic regulation of theNa⁺-K⁺-ATPase is mediated by NO and involvesactivation of guanylate cyclase and elevation of cGMP.

     

Kbus/Idr,a mutant mouse strain with skeletal abnormalities and hypophosphatemia: Identification as an allele of 'Hyp'

Background  

The endopeptidase encoded by Phex (phosphate-regulating gene with homologies to endopeptidases linked to the X chromosome) is critical for regulation of bone matrix mineralization and phosphate homeostasis. PHEX has been identified from analyses of human X-linked hypophosphatemic rickets and Hyp mutant mouse models. We here demonstrated a newly established dwarfism-like Kbus/Idr mouse line to be a novel Hyp model.     

Microbial iron management mechanisms in extremely acidic environments: comparative genomics evidence for diversity and versatility

Background  

Iron is an essential nutrient but can be toxic at high intracellular concentrations and organisms have evolved tightly regulated mechanisms for iron uptake and homeostasis. Information on iron management mechanisms is available for organisms living at circumneutral pH. However, very little is known about how acidophilic bacteria, especially those used for industrial copper bioleaching, cope with environmental iron loads that can be 10¹⁸ times the concentration found in pH neutral environments. This study was motivated by the need to fill this lacuna in knowledge. An understanding of how microorganisms thrive in acidic ecosystems with high iron loads requires a comprehensive investigation of the strategies to acquire iron and to coordinate this acquisition with utilization, storage and oxidation of iron through metal responsive regulation. In silico prediction of iron management genes and Fur regulation was carried out for three Acidithiobacilli: Acidithiobacillus ferrooxidans (iron and sulfur oxidizer) A. thiooxidans and A. caldus (sulfur oxidizers) that can live between pH 1 and pH 5 and for three strict iron oxidizers of the Leptospirillum genus that live at pH 1 or below.     

Central effects of angiotensin II in conscious hamsters: drinking,pressor response,and release of vasopressin

Summary The effects of intracerebroventricular (icv) injections of angiotensin II (ANG II) on water intake, blood pressure, heart rate, and plasma arginine-vasopressin (AVP) concentration were studied in chronically instrumented adult male Syrian golden hamsters (Mesocricetus auratus). Furthermore, the effects of pharmacological ganglionic blockade, and of vascular AVP receptor blockade, on central ANG II-induced cardiovascular responses were investigated. ANG II (1, 10, and 100 ng, icv) elicited dose-dependent increases in water intake and arterial blood pressure. Heart rate showed a biphasic response with a short initial non dose-dependent tachycardic and a subsequent longer lasting bradycardic phase. Plasma AVP concentration was increased two and a half fold with 100 ng ANG II icv. Both ganglionic blockade and vascular AVP receptor blockade significantly attenuated the central ANG II-induced pressor response. The tachycardic phase of the heart rate response was abolished by ganglionic blockade and the bradycardic phase was significantly diminished by AVP receptor blockade. The results support the hypothesis that brain ANG II may participate in the central control of body fluid volume and in central cardiovascular regulation in conscious hamsters.     

Salivary vasopressin increases following intranasal oxytocin administration

Extant research has documented the effects of intranasal administration of oxytocin (OT), and to a lesser degree Arginine Vasopressin (AVP) – two structurally-related neuropeptides – on brain and behaviour, yet the effects of exogenous manipulation of one on circulating levels of the other remain unknown. Studies have shown that OT administration impacts the peripheral levels of numerous hormones; however, whether OT administration also increases AVP concentrations has not been explored. Utilizing a double-blind placebo-controlled within-subject design, ten male and female subjects provided ten saliva samples over four consecutive hours: at baseline and nine times following OT administration. Results indicate that salivary AVP increased in the first hour following OT manipulation (OT condition: mean AVP = 2.17 pg/ml, SE = 28, placebo condition: mean AVP = 1.42 pg/ml, SE = .18) but returned to baseline levels at the next assessment (80 min) and remained low for the remaining period. Similar to OT, AVP showed high degree of individual stability and baseline levels of AVP correlated with AVP concentrations at the first and second post-administration hours regardless of drug condition (Pearson r = .85–.93). Validity of salivary AVP ELISA measurement was verified by demonstrating individual stability of salivary AVP over a six-month period (r = .70, p < .000) as well correlation with plasma levels over the same period (r = .32, p = .037) in a sample of 45 young adults who did not participate in the current study. Overall, findings suggest a potential crosstalk between OT and AVP and indicate that baseline levels of the two neuropeptides may shape the degree to which these systems respond to exogenous manipulation.     

<Emphasis Type="Italic">Drosophila</Emphasis>EGFR pathway coordinates stem cell proliferation and gut remodeling following infection

Background  

Gut homeostasis is central to whole organism health, and its disruption is associated with a broad range of pathologies. Following damage, complex physiological events are required in the gut to maintain proper homeostasis. Previously, we demonstrated that ingestion of a nonlethal pathogen, Erwinia carotovora carotovora 15, induces a massive increase in stem cell proliferation in the gut of Drosophila. However, the precise cellular events that occur following infection have not been quantitatively described, nor do we understand the interaction between multiple pathways that have been implicated in epithelium renewal.