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Herein we describe the reproductive biology of a population of the Amazon Lava Lizard (Tropidurus torquatus (Wied-Neuwied, 1820)) from Corrientes, northeastern Argentina (Wet Chaco). We describe the male and female reproductive cycles, minimum body size for adults, reproductive output, mean relative clutch mass, fat body cycles, and sexual dimorphism. Our results were compared with data on the reproductive biology of Brazilian populations of T. torquatus and congeneric species. In Corrientes, males of T. torquatus exhibited a continuous reproductive cycle, but with annual variation of testicular parameters associated with spermatogenic activity. In contrast, females were reproductive only from winter to summer (July- February), laying at least two clutches each of six eggs, on average, per reproductive season. The relative clutch mass and egg size values in Corrientes were the highest reported for the species. The annual cycle of energy storage (as fat bodies) was inversely correlated with reproductive activity in both sexes. Males differed from females in snout-vent length, head size, interlimb length, and tail length. We observed interpopulational differences in relative clutch mass, egg volume and mass, incubation period and hatching time, and the minimum body size for sexual maturity probably as a result of phenotypic plasticity or adaptation to local environmental conditions and likely both. Key words: reproductive cycle, Squamata, tropidurid, lizard, Tropidurus torquatus. Nous decrivons la biologie de la reproduction d'une population de lezards Tropidurus torquatus (Wied-Neuwied, 1820) de Corrientes, dans le nord-est de l'Argentine (Chaco humide). Nous decrivons les cycles de reproduction des males et des femelles, la taille minimum du corps des adultes, l'efficacite de la reproduction, la masse moyenne relative des pontes, les cycles des corps adipeux et le dimorphisme sexuel. Nos resultats sont compares a des donnees relatives a la biologie de la reproduction de populations bresiliennes de T. torquatus et d'especes congeneres. A Corrientes, les males de T. torquatus presentent un cycle de reproduction continu, mais des variations annuelles des parametres testiculaires associes a la spermatogenese. En revanche, les femelles ne sont reproductives que de l'hiver a l'ete (de juillet a fevrier), produisant aux moins deux pontes de six oeufs chacune en moyenne chaque saison de reproduction. Les valeurs de la masse relative des pontes et de la taille des oeufs a Corrientes etaient les plus importantes signalees pour l'espece. Le cycle annuel de stockage d'energie (sous forme de corps adipeux) etait inversement correle a l'activite de reproduction pour les deux sexes. Les males se distinguaient des femelles sur le plan de la longueur museau-cloaque, de la taille de la tete, de la longueur entre les membres et de la longueur de la queue. Nous avons observe des differences entre populations en ce qui concerne la masse relative des pontes, le volume et la masse des oeufs, la periode d'incubation et le moment de l'eclosion, ainsi que la taille minimum du corps a maturite sexuelle, ces differences etant probablement dues a la plasticite phenotypique, a l'adaptation a des conditions ambiantes locales ou, vraisemblablement, a une combinaison de ces deux phenomenes. [Traduit par la Redaction] Mots-cles : cycle de reproduction, squamates, tropidurides, lezard, Tropidurus torquatus., Introduction The timing of the reproductive cycles and the determination of the biotic and abiotic factors that affect them is critical in reproductive ecology (James and Shine 1985; Brown and [...]

Loss or dysregulation of the normally precise control of heart rate via the autonomic nervous system plays a critical role during the development and progression of cardiovascular disease-including ischemic heart disease, heart failure, and arrhythmias. While the clinical significance of regulating changes in heart rate, known as the chronotropic effect, is undeniable, the mechanisms controlling these changes remain not fully understood. Heart rate acceleration and deceleration are mediated by increasing or decreasing the spontaneous firing rate of pacemaker cells in the sinoatrial node. During the transition from rest to activity, sympathetic neurons stimulate these cells by activating β-adrenergic receptors and increasing intracellular cyclic adenosine monophosphate. The same signal transduction pathway is targeted by positive chronotropic drugs such as norepinephrine and dobutamine, which are used in the treatment of cardiogenic shock and severe heart failure. The cyclic adenosine monophosphate-sensitive hyperpolarization-activated current (I f ) in pacemaker cells is passed by hyperpolarization-activated cyclic nucleotide-gated cation channels and is critical for generating the autonomous heartbeat. In addition, this current has been suggested to play a central role in the chronotropic effect. Recent studies demonstrate that cyclic adenosine monophosphate-dependent regulation of HCN4 (hyperpolarization-activated cyclic nucleotide-gated cation channel isoform 4) acts to stabilize the heart rate, particularly during rapid rate transitions induced by the autonomic nervous system. The mechanism is based on creating a balance between firing and recently discovered nonfiring pacemaker cells in the sinoatrial node. In this way, hyperpolarization-activated cyclic nucleotide-gated cation channels may protect the heart from sinoatrial node dysfunction, secondary arrhythmia of the atria, and potentially fatal tachyarrhythmia of the ventricles. Here, we review the latest findings on sinoatrial node automaticity and discuss the physiological and pathophysiological role of HCN pacemaker channels in the chronotropic response and beyond., Competing Interests: Disclosures None.

S100A8/S100A9 is a proinflammatory mediator released by myeloid cells during many acute and chronic inflammatory disorders. However, the precise mechanism of its release from the cytosolic compartment of neutrophils is unclear. Here, we show that E-selectin-induced rapid S100A8/S100A9 release during inflammation occurs in an NLRP3 inflammasome-dependent fashion. Mechanistically, E-selectin engagement triggers Bruton's tyrosine kinase-dependent tyrosine phosphorylation of NLRP3. Concomitant potassium efflux via the voltage-gated potassium channel K V 1.3 mediates ASC oligomerization. This is followed by caspase 1 cleavage and downstream activation of pore-forming gasdermin D, enabling cytosolic release of S100A8/S100A9. Strikingly, E-selectin-mediated gasdermin D pore formation does not result in cell death but is a transient process involving activation of the ESCRT III membrane repair machinery. These data clarify molecular mechanisms of controlled S100A8/S100A9 release from neutrophils and identify the NLRP3/gasdermin D axis as a rapid and reversible activation system in neutrophils during inflammation., (© 2023. The Author(s).)

Aims: Nfix is a transcription factor belonging to the Nuclear Factor I (NFI) family comprising four members (Nfia, b, c, x). Nfix plays important roles in the development and function of several organs. In muscle development, Nfix controls the switch from embryonic to fetal myogenesis by promoting fast twitching fibres. In the adult muscle, following injury, lack of Nfix impairs regeneration, inducing higher content of slow-twitching fibres. Nfix is expressed also in the heart, but its function has been never investigated before. We studied Nfix role in this organ., Methods: Using Nfix-null and wild type (WT) mice we analyzed: (1) the expression pattern of Nfix during development by qPCR and (2) the functional alterations caused by its absence, by in vivo telemetry and in vitro patch clamp analysis., Results and Conclusions: Nfix expression start in the heart from E12.5. Adult hearts of Nfix-null mice show a hearts morphology and sarcomeric proteins expression similar to WT. However, Nfix-null animals show tachycardia that derives form an intrinsic higher beating rate of the sinus node (SAN). Molecular and functional analysis revealed that sinoatrial cells of Nfix-null mice express a significantly larger L-type calcium current (Cacna1d + Cacna1c). Interestingly, downregulation of Nfix by sh-RNA in primary cultures of neonatal rat ventricular cardiomyocytes induced a similar increase in their spontaneous beating rate and in I CaL current. In conclusion, our data provide the first demonstration of a role of Nfix that, increasing the L-type calcium current, modulates heart rate., (© 2023 The Authors. Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.)

Tongmai Yangxin (TMYX) is a complex compound of the Traditional Chinese Medicine (TCM) used to treat several cardiac rhythm disorders; however, no information regarding its mechanism of action is available. In this study we provide a detailed characterization of the effects of TMYX on the electrical activity of pacemaker cells and unravel its mechanism of action. Single-cell electrophysiology revealed that TMYX elicits a reversible and dose-dependent (2/6 mg/ml) slowing of spontaneous action potentials rate (-20.8/-50.2%) by a selective reduction of the diastolic phase (-50.1/-76.0%). This action is mediated by a negative shift of the I f activation curve (-6.7/-11.9 mV) and is caused by a reduction of the cyclic adenosine monophosphate (cAMP)-induced stimulation of pacemaker channels. We provide evidence that TMYX acts by directly antagonizing the cAMP-induced allosteric modulation of the pacemaker channels. Noticeably, this mechanism functionally resembles the pharmacological actions of muscarinic stimulation or β-blockers, but it does not require generalized changes in cytoplasmic cAMP levels thus ensuring a selective action on rate. In agreement with a competitive inhibition mechanism, TMYX exerts its maximal antagonistic action at submaximal cAMP concentrations and then progressively becomes less effective thus ensuring a full contribution of I f to pacemaker rate during high metabolic demand and sympathetic stimulation., Competing Interests: CP, MP, DM, SL, GB, HJ, YW, YW, YW, AB No competing interests declared, DD DiFrancesco Dario was supported with a grant the research study on the Chinese medicine drug TMYX by Tianjin Zhongxin Pharmaceutical Group Co., Ltd. Le Ren Tang Pharmaceutical Factory who had absolutely no part in the study plan, data collection and analysis, and manuscript writing. The money was given to the University of Milan and no Honorarium was ever paid to DiFrancesco Dario. The author has no other competing interests to declare, AB was supported with a grant the research study on the Chinese medicine drug TMYX by Tianjin Zhongxin Pharmaceutical Group Co., Ltd. Le Ren Tang Pharmaceutical Factory who had absolutely no part in the study plan, data collection and analysis, and manuscript writing. The money was given to the University of Milan and no Honorarium was ever paid to Annalisa Bucchi. The author has no other competing interests to declare, MB was supported with a grant the research study on the Chinese medicine drug TMYX by Tianjin Zhongxin Pharmaceutical Group Co., Ltd. Le Ren Tang Pharmaceutical Factory who had absolutely no part in the study plan, data collection and analysis, and manuscript writing. The money was given to the University of Milan and no Honorarium was ever paid to Mirko Baruscotti. The author has no other competing interests to declare, (© 2022, Piantoni et al.)

Discovered some 40 years ago, the I f current has since been known as the "pacemaker" current due to its role in the initiation and modulation of the heartbeat and of neuronal excitability. But this is not all, the funny current keeps entertaining the researchers; indeed, several data discovering novel and uncanonical roles of f/HCN channel are quickly accumulating. In the present review, we provide an overview of the expression and cellular functions of HCN/f channels in a variety of systems/organs, and particularly in sour taste transduction, hormones secretion, activation of astrocytes and microglia, inhibition of osteoclastogenesis, renal ammonium excretion, and peristalsis in the gastrointestinal and urine systems. We also analyzed the role of HCN channels in sustaining cellular respiration in mitochondria and their participation to mitophagy under specific conditions. The relevance of HCN currents in undifferentiated cells, and specifically in the control of stem cell cycle and in bioelectrical signals driving left/right asymmetry during zygote development, is also considered. Finally, we present novel data concerning the expression of HCN mRNA in human leukocytes. We can thus conclude that the emerging evidence presented in this review clearly points to an increasing interest and importance of the "funny" current that goes beyond its role in cardiac sinoatrial and neuronal excitability regulation., Competing Interests: Declaration of competing interest None., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The sinoatrial node (SAN) is the primary pacemaker of the heart and is responsible for generating the intrinsic heartbeat. Within the SAN, spontaneously active pacemaker cells initiate the electrical activity that causes the contraction of all cardiomyocytes. The firing rate of pacemaker cells depends on the slow diastolic depolarization (SDD) and determines the intrinsic heart rate (HR). To adapt cardiac output to varying physical demands, HR is regulated by the autonomic nervous system (ANS). The sympathetic and parasympathetic branches of the ANS innervate the SAN and regulate the firing rate of pacemaker cells by accelerating or decelerating SDD-a process well-known as the chronotropic effect. Although this process is of fundamental physiological relevance, it is still incompletely understood how it is mediated at the subcellular level. Over the past 20 years, most of the work to resolve the underlying cellular mechanisms has made use of genetically engineered mouse models. In this review, we focus on the findings from these mouse studies regarding the cellular mechanisms involved in the generation and regulation of the heartbeat, with particular focus on the highly debated role of the hyperpolarization-activated cyclic nucleotide-gated cation channel HCN4 in mediating the chronotropic effect. By focusing on experimental data obtained in mice and humans, but not in other species, we outline how findings obtained in mice relate to human physiology and pathophysiology and provide specific information on how dysfunction or loss of HCN4 channels leads to human SAN disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hennis, Rötzer, Piantoni, Biel, Wahl-Schott and Fenske.)

Background: Small supernumerary marker chromosomes (sSMC) are a heterogeneous group of structurally abnormal chromosomes, with an incidence of 0,044% in newborns that increases up to almost 7 times in developmentally retarded patients. sSMC from all 24 chromosome have been described, most of them originate from the group of the acrocentric, with around half deriving from the chromosome 15. Non-acrocentric sSMC are less common and, in the 30 percent of the cases, are associated with phenotypic effect. Complex sSMC consist of chromosomal material derived from more than one chromosome. Genotype-phenotype correlations in patients with sSMC are difficult to assess. Clinical features depend on factors such as its size, genetic content, the involvement of imprinted genes which may be influenced by uniparental disomy and the level of mosaicism. Trisomy of the short arm of chromosome 18 (18p) is an infrequent finding and does not appear to be associated with a specific syndrome. However, mild intellectual disability with or without other anomalies is reported in almost one-third of the patients., Case Presentation: Here we present clinical and molecular characterization of a new case of de novo complex sSMC consisting of the entire short arm of chromosome 18p associated with a centromere of either chromosome 13 or 21, evidenced in a 5-year-old boy during diagnostic workup for moderate intellectual disability and dysmorphisms. To date, only seven cases of isolated trisomy 18p due to a sSMC have been reported, three of which have been characterized by array CGH. In two of them the breakpoints and the size of the duplication have been described. In the manuscript we also reviewed cases reported in the DECIPHER database carrying similar duplication and also considered smaller duplications within the region of interest, in order to evaluate the presence of critical regions implicated in the pathological phenotype., Conclusions: Our case provides additional information about phenotypic effects of pure trisomy 18p, confirms chromosomal microarray analysis as gold standard to characterize complex sSMC, and supplies additional elements for genetic counselling.

Studies on ectothermic vertebrates generally lead to average indicators of thermal preferences measured in the laboratory, which do not say about responses to natural environmental change and may not inform about individual variation and its triggering mechanisms. We studied whether and how changes in costs of thermoregulation influence the preferred temperature (T p ) of individual lizards and their energetic investment in thermoregulation by exposing specimens to three treatments of increasing costs, recording body temperature (T b ) and distance walked (energetic investment). Moderate costs induced an investment trade-off between energy-investment in thermoregulation and T b , and highlighted individual variation that decreased with higher costs. Lower average T p 's were observed in the high costs trials as a result of the decreased values of the lower and upper voluntary T b 's. As costs increased, lizards walked a shorter overall distance and accepted lower T b 's, but lizards still engaged in costly thermoregulation. Individual variation resulted in two main thermoregulatory patterns that in certain ecological contexts may have an important role in decision-making and adjusting to temperatures that are far from optimal temperatures for performance and physiological processes., (Copyright © 2019 Elsevier B.V. All rights reserved.)

While the link between thermoregulation and aging is generally accepted, much further research, reflection, and debate is required to elucidate the physiological and molecular pathways that generate the observed thermal-induced changes in lifespan. Our aim in this review is to present, discuss, and scrutinize the thermoregulatory mechanisms that are implicated in the aging process in endotherms and ectotherms. Our analysis demonstrates that low body temperature benefits lifespan in both endothermic and ectothermic organisms. Research in endotherms has delved deeper into the physiological and molecular mechanisms linking body temperature and longevity. While research in ectotherms has been steadily increasing during the past decades, further mechanistic work is required in order to fully elucidate the underlying phenomena. What is abundantly clear is that both endotherms and ectotherms have a specific temperature zone at which they function optimally. This zone is defended through both physiological and behavioral means and plays a major role on organismal senescence. That low body temperature may be beneficial for lifespan is contrary to conventional medical theory where reduced body temperature is usually considered as a sign of underlying pathology. Regardless, this phenomenon has been targeted by scientists with the expectation that advancements may compress morbidity, as well as lower disease and mortality risk. The available evidence suggests that lowered body temperature may prolong life span, yet finding the key to temperature regulation remains the problem. While we are still far from a complete understanding of the mechanisms linking body temperature and longevity, we are getting closer.

The Caribbean barrier reef near Carrie Bow Cay, Belize, has been a focus of Smithsonian Institution (Washington) reef and mangrove investigations since the early 1970s. Systematics and biology of sponges (Porifera) were addressed by several researchers but none of the studies dealt with cryptic habitats, such as the shaded undersides of coral rubble, reef crevices, and caves, although a high species diversity was recognized and samples were taken for future reference and study. This paper is the result of processing samples taken between 1972 and 2012. In all, 122 species were identified, 14 of them new (including one new genus). The new species are Tetralophophora (new genus) mesoamericana, Geodia cribrata, Placospongia caribica, Prosuberites carriebowensis, Timea diplasterina, Timea oxyasterina, Rhaphidhistia belizensis, Wigginsia curlewensis, Phorbas aurantiacus, Myrmekioderma laminatum, Niphates arenata, Siphonodictyon occultum, Xestospongia purpurea, and Aplysina sciophila. We determined that about 75 of the 122 cryptic sponge species studied (61%) are exclusive members of the sciophilic community, 47 (39 %) occur in both, light-exposed and shaded or dark habitats. Since we estimate the previously known sponge population of Carrie Bow reefs and mangroves at about 200 species, the cryptic fauna makes up 38 % of total diversity.