Reliable measurement of blood pressure in conscious mice is essential in cardiovascular research. Telemetry, the "gold-standard" technique, is invasive and expensive and therefore tail-cuff, a ...noninvasive alternative, is widely used. However, tail-cuff requires handling and restraint during measurement, which may cause stress affecting blood pressure and undermining reliability of the results.
C57Bl/6J mice were implanted with radio-telemetry probes to investigate the effects of the steps of the tail-cuff technique on central blood pressure, heart rate, and temperature. This included comparison of handling techniques, operator's sex, habituation, and influence of hypertension induced by angiotensin II. Direct comparison of measurements obtained by telemetry and tail-cuff were made in the same mouse. The results revealed significant increases in central blood pressure, heart rate, and core body temperature from baseline following handling interventions without significant difference among the different handling technique, habituation, or sex of the investigator. Restraint induced the largest and sustained increase in cardiovascular parameters and temperature. The tail-cuff readings significantly underestimated those from simultaneous telemetry recordings; however, "nonsimultaneous" telemetry, obtained in undisturbed mice, were similar to tail-cuff readings obtained in undisturbed mice on the same day.
This study reveals that the tail-cuff technique underestimates the core blood pressure changes that occur simultaneously during the restraint and measurement phases. However, the measurements between the 2 techniques are similar when tail-cuff readings are compared with telemetry readings in the nondisturbed mice. The differences between the simultaneous recordings by the 2 techniques should be recognized by researchers.
ABSTRACT
Transient receptor potential vanilloid 1 (TRPV1) is involved in sensory nerve nociceptive signaling. Recently, it has been discovered that TRPV1 receptors also regulate basal body ...temperature in multiple species from mice to humans. In the present study, we investigated whether TRPV1 modulates basal sympathetic nervous system (SNS) activity. C57BL6/J wild‐type (WT) mice and TRPV1 knockout (KO) mice were implanted with radiotelemetry probes for measurement of core body temperature. AMG 9810∗∗∗ (50 mg/kg) or vehicle (2% DMSO/5% Tween 80/10 ml/kg saline) was injected intraperitoneally. Adrenoceptor antagonists or vehicle (5 ml/kg saline) was injected subcutaneously. In WT mice, the TRPV1 antagonist, AMG9810, caused significant hyperthermia, associated with increased noradrenaline concentrations in brown adipose tissue. The hyperthermia was significantly attenuated by the β‐adrenoceptor antagonist propranolol, the mixed α‐/β‐adrenoceptor antagonist labetalol, and the α1‐adrenoceptor antagonist prazosin. TRPV1 KO mice have a normal basal body temperature, indicative of developmental compensation. D‐Amphetamine (potent sympathomimetic) caused hyperthermia in WT mice, which was reduced in TRPV1 KO mice, suggesting a decreased sympathetic drive in KOs. This study provides new evidence that TRPV1 controls thermoregulation upstream of the SNS, providing a potential therapeutic target for sympathetic hyperactivity thermoregulatory disorders.—Alawi, K. M., Aubdool, A. A., Liang, L., Wilde, E., Vepa, A., Psefteli, M.‐P., Brain, S. D., Keeble, J. E. The sympathetic nervous system is controlled by transient receptor potential vanilloid 1 in the regulation of body temperature. FASEB J. 29, 4285‐4298 (2015). www.fasebj.org
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
BACKGROUND:Research into the therapeutic potential of α-calcitonin gene–related peptide (α-CGRP) has been limited because of its peptide nature and short half-life. Here, we evaluate whether a novel ...potent and long-lasting (t½ ≥7 hours) acylated α-CGRP analogue (αAnalogue) could alleviate and reverse cardiovascular disease in 2 distinct murine models of hypertension and heart failure in vivo.
METHODS:The ability of the αAnalogue to act selectively via the CGRP pathway was shown in skin by using a CGRP receptor antagonist. The effect of the αAnalogue on angiotensin II–induced hypertension was investigated over 14 days. Blood pressure was measured by radiotelemetry. The ability of the αAnalogue to modulate heart failure was studied in an abdominal aortic constriction model of murine cardiac hypertrophy and heart failure over 5 weeks. Extensive ex vivo analysis was performed via RNA analysis, Western blot, and histology.
RESULTS:The angiotensin II–induced hypertension was attenuated by cotreatment with the αAnalogue (50 nmol·kg·d, SC, at a dose selected for lack of long-term hypotensive effects at baseline). The αAnalogue protected against vascular, renal, and cardiac dysfunction, characterized by reduced hypertrophy and biomarkers of fibrosis, remodeling, inflammation, and oxidative stress. In a separate study, the αAnalogue reversed angiotensin II–induced hypertension and associated vascular and cardiac damage. The αAnalogue was effective over 5 weeks in a murine model of cardiac hypertrophy and heart failure. It preserved heart function, assessed by echocardiography, while protecting against adverse cardiac remodeling and apoptosis. Moreover, treatment with the αAnalogue was well tolerated with neither signs of desensitization nor behavioral changes.
CONCLUSIONS:These findings, in 2 distinct models, provide the first evidence for the therapeutic potential of a stabilized αAnalogue, by mediating (1) antihypertensive effects, (2) attenuating cardiac remodeling, and (3) increasing angiogenesis and cell survival to protect against and limit damage associated with the progression of cardiovascular diseases. This indicates the therapeutic potential of the CGRP pathway and the possibility that this injectable CGRP analogue may be effective in cardiac disease.
Few studies focus on the modes of knowledge transmission (or concealment), or the trends of continuity or change from the Ancient to the Late Antique worlds. In Antiquity, knowledge was cherished as ...a scarce good, cultivated through the close teacher-student relationship and often preserved in the closed circle of the initated. From Assyrian and Babylonian cuneiform texts to a Shi'ite Islamic tradition, this volume explores how and why knowledge was shared or concealed by diverse communities in a range of Ancient and Late Antique cultural contexts. From caves by the Dead Sea to Alexandria, both normative and heterodox approaches to knowledge in Jewish, Christian and Muslim communities are explored. Biblical and qur'anic passages, as well as gnostic, rabbinic and esoteric Islamic approaches are discussed. In this volume, a range of scholars from Assyrian studies to Jewish, Christian and Islamic studies examine diverse approaches to, and modes of, knowledge transmission and concealment, shedding new light on both the interconnectedness, as well as the unique aspects, of the monotheistic faiths, and their relationship to the ancient civilisations of the Fertile Crescent.
Transient receptor potential vanilloid 1 (TRPV1) is involved in pain and neurogenic inflammation. It has recently been found that TRPV1 anatgonism causes hyperthermia in multiple species from mice to ...humans. In the present study, we investigated whether TRPV1 regulates basal sympathetic nervous system (SNS) activity. C57BL6/J wild-type (WT) mice and TRPV1 knockout (KO) mice were implanted with radio-telemetry probes for measurement of core body temperature. AMG9810 (50 mg/kg) or vehicle (2% DMSO/5% Tween 80/10 ml/kg saline) was injected via the peritoneal route. Adrenoceptor antagonists or vehicle (5 ml/kg saline) was injected s.c. In WT mice, theTRPVl antagonist, AMG9810, caused a significantincrease in body temperature, along with increased noradrenaline concentrations in brown adipose tissue. The hyperthermia was significantly attenuated by the (^-adrenoceptor antagonist propranolol, the mixed a-/p-adrenoceptor antagonist labetalol, and the al-adrenoceptor antagonist prazosin. TRPV1 KO mice have a normal basal body temperature, indicative of developmental compensatory events. Amphetamine (potent sympathomimetic) caused hyperthermia in WT mice, which was reduced in TRPV1 KO mice, suggesting a decreased sympathetic drive in KOs. This study provides new evidence thatTRPVl regulates thermoregulatory pathways, upstream of the SNS.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK, ZRSKP
Explores nuances of xenophobia and Islamophobia in liberal, secular and Christian environments where Christians and Muslims have interacted and depicted one another, focusing on those aspects that ...might be particular to immigrant societies whose populations have significant percentages of European extraction. Highlights the importance of historical, sociological and theological awareness for successful incorporation of Muslims in (historically) Christian-majority societies, especially in Europe and European settlements. Source: National Library of New Zealand Te Puna Matauranga o Aotearoa, licensed by the Department of Internal Affairs for re-use under the Creative Commons Attribution 3.0 New Zealand Licence.
Problem. Normative Islamic tradition has come to understand the Qur'an as the inimitable and uncreated word of God. And, unlike Moses' Tawrat or Jesus' Injil, which were corrupted by later ...generations of Jews and Christians, the message that Muhammad received is believed to have been preserved, in the form in which he received it, in the Uthmanic codex of the Arabic Qur'an (literally, 'recitation'). This dissertation explores the various ways in which Arabophone Christians who came to live in Muslim-ruled territories employed the Qur'an in their apologetic agendas. Did the Qur'an shape Christian theology? And, might contemporary students of the Qur'an mine early Christian Arabic discussions thereof in order the better to understand the history of the reception, if not the transmission, of the Qur'an? Method. Three Christian Arabic texts that date to the Abbasid caliphate were examined for their use of qur'anic passages, which were divided into four categories and compared with Islamic exegetical tradition thereon: passages that Islamic tradition and the Christian authors understand as referencing Christians and/or Christianity; passages that the Christian authors, but not Islamic tradition, understand as containing Christian themes; passages that Islamic tradition and the Christian authors read as referencing Jews and/or Judaism; passages that neither the Christian authors nor Islamic tradition read as referencing Judeo-Christian themes. Results. Both because this investigation did not entail an exhaustive examination of the entire manuscript tradition of each of the texts (except for that of the unique manuscript, Sinai Ar. 434), and as the authors did not claim verbatim qur'anic quotation, this research sheds light more on the history of Christian-Muslim interactions and approaches to the Qur'an, rather than the qur'anic text. Christian preservation of qur'anic passages are, generally, not so much a reliable indicator of the contents of the Qur'an, as Christian theological (or socio-political) (re)readings thereof. Conclusion. Christian interpretation of passages from the first three categories are helpful in understanding trends within the Christian communities, including certain Muslim-Christian dynamics; Christian Arab usage and preservation of passages in the last category may have a place in historical and/or form criticism of the text of the Qur'an.
Ever since the first case was reported at the end of 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the associated coronavirus disease 2019 (COVID-19) has become a serious ...threat to public health globally in short time. At this point in time, there is no proven effective therapy. The interactions with concomitant disease are largely unknown, and that may be particularly pertinent to inherited arrhythmia syndrome. An arrhythmogenic effect of COVID-19 can be expected, potentially contributing to disease outcome. This may be of importance for patients with an increased risk of cardiac arrhythmias, either secondary to acquired conditions or comorbidities or consequent to inherited syndromes. Management of patients with inherited arrhythmia syndromes such as long QT syndrome, Brugada syndrome, short QT syndrome, and catecholaminergic polymorphic ventricular tachycardia in the setting of the COVID-19 pandemic may prove particularly challenging. Depending on the inherited defect involved, these patients may be susceptible to proarrhythmic effects of COVID-19-related issues such as fever, stress, electrolyte disturbances, and use of antiviral drugs. Here, we describe the potential COVID-19-associated risks and therapeutic considerations for patients with distinct inherited arrhythmia syndromes and provide recommendations, pending local possibilities, for their monitoring and management during this pandemic.
Cullin RING-type E3 ubiquitin ligases SCF
and their AUX/IAA targets perceive the phytohormone auxin. The F-box protein TIR1 binds a surface-exposed degron in AUX/IAAs promoting their ubiquitylation ...and rapid auxin-regulated proteasomal degradation. Here, by adopting biochemical, structural proteomics and in vivo approaches we unveil how flexibility in AUX/IAAs and regions in TIR1 affect their conformational ensemble allowing surface accessibility of degrons. We resolve TIR1·auxin·IAA7 and TIR1·auxin·IAA12 complex topology, and show that flexible intrinsically disordered regions (IDRs) in the degron's vicinity, cooperatively position AUX/IAAs on TIR1. We identify essential residues at the TIR1 N- and C-termini, which provide non-native interaction interfaces with IDRs and the folded PB1 domain of AUX/IAAs. We thereby establish a role for IDRs in modulating auxin receptor assemblies. By securing AUX/IAAs on two opposite surfaces of TIR1, IDR diversity supports locally tailored positioning for targeted ubiquitylation, and might provide conformational flexibility for a multiplicity of functional states.
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