Phasic Contractions Research Articles

Bouncing Cosmology in f(R,G)$f(R,\mathcal {G})$ Gravity with Thermodynamic Analysis

AbstractThe evolution of the universe in a modified gravity theory that includes the terms Ricci scalar () and the Gauss‐Bonnet invariant () is studied. The function is obtained using the e‐folding number and reconstruction technique by assuming an appropriate parameterization of the scale factor . In this model, the various cosmological parameters are analyzed to explicate the bouncing scenario of the universe with the help of the contraction and expansion phases of the universe before and after the bouncing point of the model, respectively. A violation of the null energy condition is found. Additionally, the ghost condensate nature of the model in the neighborhood of the bouncing point () is seen. Furthermore, the deceleration parameter is not defined at the bouncing point, i.e., at and approaches a finite value in later times (). Finally, the evolution of the Hawking temperature and the validity of the second law of thermodynamics in the bouncing scenario of our model are discussed.

Open air X-ray diffractometer for crystallography, compression, contraction, and structural phase transitions with variable temperature capabilities

It is a fact that materials contract or expand by changing their temperature. In a certain temperature range, the distance between atoms changes linearly in some materials whereas it changes non-linearly in other materials. X-ray diffraction (XRD) is one of the popular techniques used for understanding the crystal structure of these materials. However, XRD is mostly carried in open air at room temperature or require very expensive high vacuum set-ups and expensive temperature controllers for low temperature studies. Here we propose a design of a variable temperature X-ray diffractometer that can operate in dual modes: heating and cooling in open air. The proposed diffractometer has been used for studying structural phase transition in chromium nitride thin films. The results demonstrated not only the effectiveness of our proposed setup but also its applicability in advancing our understanding of complex material behaviors.•A new design of a variable temperature X-ray diffractometer has been introduced in this paper, which can be used for acquiring XRD data while heating or cooling samples in open air.•As a proof of concept, the newly designed variable temperature X-ray diffractometer is used for studying structural phase transition in CrN thin films.

Commonality and heterogeneity of pacemaker mechanisms in the male reproductive organs.

During emission, the first phase of ejaculation, smooth muscle in organs of the male reproductive tract (MRT) vigorously contract upon sympathetic nerve excitation to expel semen consisting of sperm and seminal plasma. During inter-ejaculation phases, the epididymis, seminal vesicles and prostate undergo spontaneous phasic contractions (SPCs), this transporting and maintaining the quality of sperm and seminal plasma. Recent studies have revealed platelet-derived growth factor receptor α-expressing (PDGFRα+) subepithelial interstitial cells in seminal vesicles subserve the role of pacemaker cells that electrically drive SPCs in this organ. PDGFRα+ smooth muscle cells in the epididymis also appear to function as pacemaker cells implicating PDGFRα as a potential signature molecule in MRT pacemaking. The dominant mechanism driving pacemaking in these organs is the cytosolic Ca2+ oscillator. This operates through entrainment of the release-refill cycle of Ca2+ stores, the released Ca2+ ions opening Ca2+-activated chloride channels, including in some cases ANO1 (TMEM16A), with the resultant pacemaker potential activating L-type voltage-dependent Ca2+ channels in the smooth muscle causing contraction (viz. SPCs). A second pacemaker mechanism, namely the membrane oscillator also has a role in specific cases. Further investigations into the commonality and heterogeneity of MRT pacemakers will open an avenue for understanding the pathogenesis of male infertility associated with deterioration of seminal plasma.

Involvement of ANO1 currents in pacemaking of PDGFRα-positive specialised smooth muscle cells in rat caudal epididymis.

The epididymal duct exhibits spontaneous phasic contractions (SPCs) to store and transport sperm. Here, we explored molecular identification of pacemaker cells driving SPCs in the caudal epididymal duct and also investigated properties of pacemaker currents underlying SPCs focusing on ANO1 Ca2+-activated Cl- channels (CaCCs). Immunohistochemistry was performed to visualise the distribution of platelet-derived growth factor receptor α (PDGFRα)- or ANO1-positive cells in the rat caudal epididymal duct. Perforated whole-cell patch clamp technique was applied to enzymatically isolated epididymal cells, while SPCs were recorded with video edge-tracking technique. Immunohistochemistry revealed the distribution of α-smooth muscle actin (α-SMA)-positive cells co-expressing both PDGFRα and ANO1 in the innermost smooth muscle layer. Approximately one-third of isolated epididymis cells exhibited spontaneous transient inward currents (STICs) at the holding potential -60 mV. The reversal potential for STICs was close to the calculated chloride equivalent potential depending on intracellular Cl- concentrations. Ani9 (3 µM), the ANO1 specific inhibitor, decreased both amplitude and frequency of STICs, while cyclopiazonic acid (CPA, 30 µM), a sarco-/endoplasmic reticulum Ca2+-ATPase (SERCA) inhibitor, abolished STICs. Ani9 (3 or 10 µM) reduced the frequency of SPCs without changing their amplitude. Thus, PDGFRα+, ANO1+ specialised smooth muscle cells (SMCs) appear to function as pacemaker cells to electrically drive epididymal SPCs by generating ANO1-dependnet STICs. STICs arising from spontaneous Ca2+ release from intracellular Ca2+ store and subsequent opening of ANO1 result in depolarisations that spread into adjacent SMCs where L-type voltage-dependent Ca2+ channels are activated to develop SPCs.

Cretaceous extensional and contractional stages in the Colombian Andes unraveled by a source-to-sink geochronological and thermochronological study in the Upper Magdalena Basin

Extensional and flexural basins can evolve through multiple stages under the same plate tectonic regime over tens of millions of years. The Cretaceous tectonic evolution of the Colombian Andes is characterized by shifts between contractional and extensional tectonics. The upper plate response to these changes is recorded in the Cretaceous sedimentary rocks along the Western, Central, and Eastern cordilleras, and their adjacent basins, including the Upper Magdalena hinterland basin. We integrated field observations, petrography, geochronology, and thermochronology in the Cretaceous sedimentary units in the southern Upper Magdalena Basin and in the adjacent crystalline basement to decipher the provenance of these units and the exhumation patterns of the source areas. These results suggest that the source areas were exhumed between the Late Jurassic to Early Cretaceous, which may have resulted from the combination of Jurassic contraction and the Early Cretaceous extension. Between ∼120 and 100 Ma, a major stage of crustal extension is recorded in the Caballos Formation. Subsequently, between ∼100 and 80 Ma, sedimentation in the Villeta Group marks the end of the extension and the onset of contraction. This contractional phase was characterized by minor rock uplift within the basin. Basin modification continued between 80 and 65 Ma, involving two successive contractional stages that changed the sedimentary patterns, leading to the burial of a previously exhumed horst block and the appearance of new source areas. These major changes in source areas and sedimentary systems are the result of deformation episodes during prolonged extensional and contractional phases. This geologic evolution highlights the stages that characterize extensional to contractional settings.

Disentangling responses of aquatic and terrestrial invertebrates to drying in saline streams and shallow lakes

In inland aquatic ecosystems, drying and salinity can co-occur as natural stressors, affecting aquatic invertebrate communities. Despite recent appreciation of the importance of temporary waterbodies for terrestrial invertebrates, knowledge about the effects of drying on dynamics of aquatic and terrestrial invertebrate communities is scarce, especially in saline ecosystems. This study analyzed structural and compositional responses of both communities to the coupled effects of drying and salinity in two streams and two shallow lakes in Spain, during three hydrological phases: wet, contraction, and dry. In the two studied saline streams, the contraction phase presented the highest aquatic and terrestrial abundance and richness, and the main compositional changes were mainly due, to an increase in aquatic lentic taxa (e.g., Coleoptera), and Araneae and Formicidae as terrestrial taxa. In shallow lakes, which presented highly variable salinity conditions, the highest abundance and diversity values were found at the wet phase for aquatic invertebrates and at the dry phase for terrestrial invertebrates. Compositional invertebrate community changes were due to a decrease in Rotifera and Anostraca (aquatic taxa) in the contraction phase for aquatic communities, and to an increase of Araneae, Coleoptera, and Formicidae (terrestrial taxa) at the dry phase for the terrestrial. Our study evidences the significant effect of drying on both aquatic and terrestrial invertebrates communities in natural inland saline waters and the need to integrate aquatic and terrestrial perspectives to study temporary inland waters.

Physico-chemical constraints associated with hypogene hydrothermal alteration and supergene oxidation at the Farallón Negro intermediate-sulfidation epithermal Au-Ag deposit, NW Argentina

The Farallón Negro deposit is located in the Farallón Negro Volcanic Complex (FNVC; ∼9.40 to 4.88 Ma) in NW Argentina and includes intermediate-sulfidation, epithermal Au-Ag mineralization in the Alto de la Blenda deposit. Detailed mineralogical and geochemical investigations of the Esperanza-Esperanza Sureste, Cecilia veins, both hosted in the Alto de la Blenda monzonite, and the Laboreo vein, hosted in the volcaniclastic Morada Central andesitic breccia, reveal four hypogene vein stages. Each of these four stages are comprised of a texturally early quartz, followed by a sulfide-sulfosalt and a late Mn-carbonate sub-stage. Stage 1 is characterized by a quartz, base metal and Mn-carbonate sub-stage showing high δ18OVSMOW (δ18OQuartz = 13.7 ± 0.4‰ and δ18OMn-Calcite = 11.6 ± 0.2‰) and low δ13CVPDB values (δ13CMn-Calcite = –4.7 ± 0.2‰). Stage 2 includes most gold and silver minerals in a tennantite-tetrahedrite-sphalerite-pyrite-galena±electrum sub-stage. Fluid inclusions trapped in vein-anhydrite, only associated with stage 2, record the highest temperatures (TEntrapment = 327–335°C) and highest salinity (3.8NaCleq.wt.%) when compared to all other stages. Stage 2 quartz (δ18OQuartz = 9.9 to 11.9‰) and carbonate display lower δ18OVSMOW (δ18OMn-Calcite = 7.9 to 10.3‰), as well as lower δ13CVPDB values (δ13CMn-Calcite = -5.2 to 4.7‰) than all other stages. Stages 3 and 4 consist of barren quartz and carbonate sub-stages that show lower temperatures (TEntrapment = 187–262°C) and higher δ18OVSMOW (δ18OQuartz = 13.4 to 13.9‰ and δ18OMn-Calcite = 10.7 to 11.8‰) and δ13CVPDB values (δ13CMn-Calcite = –3.5 to −3.9‰) when compared to earlier stages.Petrographic, sulfide mineral chemistry, microthermometric, and stable isotope data combined with distinct alteration mineral assemblages allow the reconstruction of a model for the Alto de la Blenda deposit. During the hypogene hydrothermal fluid flow stage, around 7.16 Ma, at ∼2.2 km depth (PHYDROSTATIC = 220 bars), the high temperature alteration mineralogy, low fluid salinities and 18O and 13C isotope compositions indicate cooling of ascending magmatic-hydrothermal fluids. These fluids were derived from a contracted magmatic vapor phase that exchanged with unexposed sedimentary rocks of the Sierras Pampeanas. Hypogene quartz-R3 illite/smectite-chlorite-calcite-pyrite alteration in the andesitic-breccia and quartz-illite-R3 illite/smectite-chlorite-calcite-pyrite alteration in the monzonite are temporally and spatially to the hydrothermal vein minerals deposited between 187 and 335°C. During the post-hydrothermal supergene weathering event, around 2.70 Ma, sulfuric acids generated by meteoric fluids and supergene oxidation of hypogene sulfides, particularly pyrite, descended along normal fault zones and related vein and fracture networks to at least 450 m depth below the surface level, forming the supergene alteration assemblage of dioctahedral smectite-kaolinite-Mn-/Fe-oxides/-hydroxides-gypsum±interstratified chlorite/smectite±interstratified R1 illite/smectite in both wall rock types at temperatures <50°C.The dominant hypogene alteration assemblage, present in the monzonite and volcaniclastic andesitic breccia, may be indicative of deeper-seated, transitional magmatic-hydrothermal systems (>1 km depth), generally controlled by fluid cooling, as is the case at Farallón Negro. Pervasive supergene alteration can conceal these systems but the identified supergene alteration assemblage of dioctahedral smectite-kaolinite-interstratified chlorite/smectite-interstratified R1 illite/smectite that replaces the hypogene alteration assemblage along the permeable fault, vein and fracture zone network may present a useful vectoring tool towards concealed, deeper-seated, epithermal Au-Ag mineralization in arid climates.

New insights into the characterization of the mechanism of action of hyoscine butylbromide in the human colon ex vivo

IntroductionHyoscine butylbromide (HBB) is one of the most used antispasmodics in clinical practice. Recent translational consensus has demonstrated a similarity between human colonic motor patterns studied ex vivo and in vivo, suggesting ex vivo can predict in vivo results. It is unclear whether the mechanism of action of antispasmodics can predict different use in clinical practice. The aim of the present study is to bridge this gap dissecting HBB's role in excitatory and inhibitory neural pathways. Methods: 309 colon samples from 48 patients were studied in muscle bath experiments. HBB was tested on: 1-spontaneous phasic contractions (SPCs); 2-carbachol-induced contractility; electrical field stimulation (EFS)-induced selective stimulation of 3-excitatory and 4-inhibitory pathways and 5- SPCs and EFS-induced contractions enhanced by neostigmine. Atropine, AF-DX116 (M2 blocker) and DAU-5884 (M3 blocker) were used as comparators. ResultsIn the presence of tetrodotoxin (TTX), HBB and atropine 1 μM reduced SPCs. HBB and atropine concentration-dependently reduced carbachol- and EFS-induced contractions. Inhibitory effects of DAU-5884 on EFS-induced contractions were more potent than of AF-DX116. HBB did not affect the off-response associated to neural inhibitory responses. Neostigmine enhanced both SPCs and EFS-induced contractions. In the presence of TTX and ω-conotoxin (GVIA), neostigmine still enhanced SPCs. Addition of HBB and atropine reduced these responses. ConclusionsThis study demonstrates that HBB inhibits neural cholinergic contractions associated to muscarinic (mainly M3) receptors. HBB has a potential role in reducing colonic spasm induced by the release of acetylcholine from enteric motor neurons and from an atypical source including a potential non-neuronal origin.

Evolutionary pattern and influencing factors of the aquaculture development in the Guangdong-Hong Kong-Macao Greater Bay area during 1986–2020

The rapid expansion of aquaculture ponds at the end of the last century raised concerns about their environmental and ecological impacts in the Guangdong-Hong Kong-Macao Greater Bay Area (GBA). This study aims to comprehensively investigate the spatiotemporal evolutionary characteristics and explore the influencing factors of aquaculture development in the GBA. An automated approach was established to extract the aquaculture pond areas on the Google Earth Engine (GEE) platform using Landsat images and showed high accuracy. The aquaculture development in the GBA underwent three phases of rapid expansion (1986–1996), constant transformation (1996–2010), and drastic contraction (2010–2020), and was closely related to the important aquaculture policies in China and Guangdong Province. The local aquaculture ponds showed three evolutionary patterns of continuous shrinkage, earlier shrinkage, and later shrinkage, which were mainly influenced by the economic development level and urbanization in each city. Rapid urbanization created great demands for aquaculture products and intense land use competition, which drove the conversion of aquaculture ponds into impervious land and migration from the central GBA towards the surrounding coast and upstream areas. Government policies promoted the initial rapid increase and regulated the aquaculture ponds to develop towards a more environment-friendly and intensive mode, which led to a steady increase of aquaculture products despite the drastic decrease in aquaculture pond areas in the past decade. These evolutionary features are of significance for policymakers and farmers to maintain the sustainable development of aquaculture in the GBA and Guangdong Province.

Pacemaking in the lymphatic system.

Lymphatic collecting vessels exhibit spontaneous phasic contractions that are critical for lymph propulsion and tissue fluid homeostasis. This rhythmic activity is driven by action potentials conducted across the lymphatic muscle cell (LMC) layer to produce entrained contractions. The contraction frequency of a lymphatic collecting vessel displays exquisite mechanosensitivity, with a dynamic range from <1 to >20 contractions per minute. A myogenic pacemaker mechanism intrinsic to the LMCs was initially postulated to account for pressure-dependent chronotropy. Further interrogation into the cellular constituents of the lymphatic vessel wall identified non-muscle cell populations that shared some characteristics with interstitial cells of Cajal, which have pacemaker functions in the gastrointestinal and lower urinary tracts, thus raising the possibility of a non-muscle cell pacemaker. However, recent genetic knockout studies in mice support LMCs and a myogenic origin of the pacemaker activity. LMCs exhibit stochastic, but pressure-sensitive, sarcoplasmic reticulum calcium release (puffs and waves) from IP3R1 receptors, which couple to the calcium-activated chloride channel Anoctamin 1, causing depolarisation. The resulting electrical activity integrates across the highly coupled lymphatic muscle electrical syncytia through connexin 45 to modulate diastolic depolarisation. However, multiple other cation channels may also contribute to the ionic pacemaking cycle. Upon reaching threshold, a voltage-gated calcium channel-dependent action potential fires, resulting in a nearly synchronous calcium global calcium flash within the LMC layer to drive an entrained contraction. This review summarizes the key ion channels potentially responsible for the pressure-dependent chronotropy of lymphatic collecting vessels and various mechanisms of IP3R1 regulation that could contribute to frequency tuning.

Monitoring of Cropland Abandonment and Land Reclamation in the Farming–Pastoral Zone of Northern China

The farming–pastoral zone in northern China is one of the most ecologically sensitive areas globally, having experienced extensive cropland abandonment and land reclamation over decades, primarily influenced by policy adjustment and global warming. However, the spatiotemporal patterns and suitability of long-term cropland change remain poorly understood. Using the annual China land cover dataset (CLCD), we provide a cropland abandonment and land reclamation mapping approach based on actual land use processes (rather than land cover conditions) to investigate spatiotemporal features of abandonment and reclamation and evaluate the rationality. Our findings show that: (1) Returning farmland to forest and grassland has been a clear trend in the study area over the past 30 years. Specifically, cropland use has undergone three phases of change, i.e., cropland contraction and expansion alternately (before 2000), followed by substantial abandonment (after 2000), and low-intensity reclamation (after 2010). (2) In the last decade, the intensity of the abandonment of cropland with high and moderate suitability is low. The rate of abandonment decreased, while the intensity of land reclamation was relatively high. The rate of the reclamation increased, and the spatial distribution of cropland tended to be reasonable. Our study emphasizes the importance of monitoring actual cropland changes based on land use processes, and this method can be effectively extended to regional or global long-term cropland monitoring.

Strain partitioning in the Patagonian Broken Foreland: influence of structural inheritance of early Andean deformation

In the context of Andean-type oblique convergence, strain partitioning between thrust and strike-slip tectonics is well documented in the arc region. However, the impact of this configuration in the retroarc remains poorly understood, especially in broken foreland systems where basement structures compartmentalize the retroarc into small intermontane sedimentary basins. The spatiotemporal analysis of tectonic evolution and the role of inherited weaknesses in this area are often debated. This study addresses these uncertainties by integrating geometric and kinematic analyses of tectonic structures within the Sañicó Massif in the North Patagonian foreland. Results reveal two deformational episodes. The initial Late Cretaceous to Paleocene episode represents a contractional deformation phase, with NW–SE shortening direction causing the tectonic inversion of pre-Andean rift depocentres. The second episode records a Neogene transpressional regime with both contractional and strike-slip deformation, with east–west to NE–SW shortening direction, which progressed under reactivation of pre-existing structures and generated new faults. This work demonstrates the Neogene propagation of the strike-slip regime towards the retroarc, defining strain partitioning at various scales and highlighting its interaction with pre-existing structures. These results enhance our understanding of the complex tectonic history in oblique subduction settings, providing significant evidence of the structural inheritance in retroarc systems.

Structural and Geochemistry of Air Piau Gold Mineralisation in Kelantan, North-East Peninsular Malaysia

The formation of the Air Piau Gold Deposit in North-East Peninsular Malaysia due to Permo–Triassic subduction and collision between Sibumasu and East Malaya blocks and resulted in several phases of deformation, contraction, and metamorphism. Kinematic and petrography study of quartz veins in Air Piau area observed whether following the foliation of metamorphic rock or crosscut the foliation. Early generation of veining system in Air Piau follow the host rock foliation (V1). Meanwhile the later formation of the hydrothermal vein has a cross-cutting relationship with foliation (V2). Some veins observed were sheared and brecciated (V3). Positive correlation between Au and As concentration that can be characterized these deposit formed at mesozonal zone. V3 vein type showed the brecciated texture of vein indicates the brittle structure deformation. The conceptual model of orogenic gold, this type of V3 vein can be classified as epizonal zone. Regionally, the Air Piau gold deposit shares geologically similarities (in term of tectonic setting, geological structures controlled, host rock, ore gechemistry) with many other sediment/metasediment- hosted, orogenic gold deposits in Peninsular Malaysia such as Tersang, Selinsing and Penjom. Furthermore, Air Piau gold deposit characteristics as discussed before supported the theory related with orogenic/mesothermal gold from various researchers However, a number of inferences on classified Air Piau gold deposit model as orogenic gold deposit remains speculative in the absence importance data like ore geochemistry data (Hg, Sb and Te element concentrations) and fluid inclusion data.

Evidence for transit-timing variations of the 11 Myr exoplanet TOI-1227 b

TOI-1227 b is an 11 Myr old validated transiting planet in the middle of its contraction phase, with a current radius of 0.85 Rj. It orbits a low-mass pre-main sequence star (0.170 M⊙, 0.56 R⊙) every 27.4 days. The magnetic activity of its young host star induces radial velocity jitter and prevents good measurements of the planetary mass. We gathered additional transit observations of TOI-1227 b with space- and ground-based telescopes, and we detected highly significant transit-timing variations (TTVs). Their amplitude is about 40 min and their dominant timescale is longer than 3.7 yr. Their most probable origin is dynamical interactions with additional planets in the system. We modeled the TTVs with inner and outer perturbers near first and second order resonances; several orbital configurations provide an acceptable fit. More data are needed to determine the actual orbital configuration and eventually measure the planetary masses. These TTVs and an updated transit chromaticity analysis reinforce the evidence that TOI-1227 b is a planet.

MOOD SWINGS AND THE FIRM SIZE PREMIUM

Evidence accumulated in the literature indicates that the size effect is related to corporate and macroeconomic variables and is paid to compensate for bearing risk. We show that the size premium is also driven by daily variations in investors’ moods. We focus on two conditions often cited as possible mechanisms that drive variations in mood: Monday and seasonal affective disorder. The findings are consistent with the evidence that mood deteriorates on Mondays and in the fall and are consistent with the claim that the size effect manifests during economic expansion but weakens in the contraction phase of the economic cycle.

Đo lường chu kỳ tài chính Việt Nam: Ứng dụng phương pháp phân tích quang phổ

The article proposes measuring the financial cycles of Vietnam using the spectral analysis method. This method determines financial cycle dynamics based on the simultaneous fluctuations of financial indicators, allowing its frequency and magnitude to vary over time, as opposed to remaining fixed as in traditional methods. The results indicate that Vietnam’s financial cycles from 2010Q1 to 2023Q3 exhibit significant volatility, with both frequency and amplitude of fluctuations increasing over time. The expansion and contraction phases of financial cycles are closely linked to economic fluctuations. Within the financial cycle components, the credit cycle has a lower frequency compared to the bond and stock market cycles, yet it significantly influences the overall financial cycle’s dynamics

PTHrP attenuates spontaneous contractions in detrusor smooth muscle of the rat bladder by activating spontaneous transient outward potassium currents.

Parathyroid hormone-related protein (PTHrP) released from detrusor smooth muscle (DSM) cells upon bladder distension attenuates spontaneous phasic contractions (SPCs) in DSM and associated afferent firing to facilitate urine storage. Here, we investigate the mechanisms underlying PTHrP-induced inhibition of SPCs, focusing on large-conductance Ca2+-activated K+ channels (BK channels) that play a central role in stabilizing DSM excitability. Perforated patch-clamp techniques were applied to DSM cells of the rat bladder dispersed using collagenase. Isometric tension changes were recorded from DSM strips, while intracellular Ca2+ dynamics were visualized using Cal520AM-loaded DSM bundles. DSM cells developed spontaneous transient outward potassium currents (STOCs) arising from the opening of BK channels. PTHrP (10nM) increased the frequency of STOCs without affecting their amplitude at a holding potential of - 30mV but not - 40mV. PTHrP enlarged depolarization-induced, BK-mediated outward currents at membrane potentials positive to + 20mV in a manner sensitive to iberiotoxin (100nM), the BK channel blocker. The PTHrP-induced increases in BK currents were also prevented by inhibitors of sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) (CPA 10µM), L-type voltage-dependent Ca2+ channel (LVDCC) (nifedipine 3µM) or adenylyl cyclase (SQ22536 100µM). PTHrP had no effect on depolarization-induced LVDCC currents. PTHrP suppressed and slowed SPCs in an iberiotoxin (100nM)-sensitive manner. PTHrP also reduced the number of Ca2+ spikes during each burst of spontaneous Ca2+ transients. In conclusion, PTHrP accelerates STOCs discharge presumably by facilitating SR Ca2+ release which prematurely terminates Ca2+ transient bursts resulting in the attenuation of SPCs.

Transparency and Monitoring of Public Procurement Contract Performance

This study analyzes the monitoring of public procurement contracts’ performance in six countries under EU public procurement rules: Finland, Portugal, Slovenia, Italy, Hungary, and Serbia. Through an in-depth comparative analysis, we explore the nexus between perceived corruption in these countries and the contract performance monitoring systems established or in the making. The analysis centers on four key aspects: the organizational framework, the redress system, the IT infrastructure, and the level of data publicity in each country’s procurement landscape. Expert evaluations conducted by national specialists unveil which countries pay less attention to public contract performance monitoring and transparency. Our findings indicate that countries facing higher corruption rates tend to place greater emphasis on transparency and contract performance monitoring. Moreover, countries greatly differ in their organizational setup, objectives, and monitoring tools, including IT adoption. The insights derived from this study can influence policy and reform efforts focused on the contract phase of public procurement, leading to a more accountable and efficient procurement landscape across Europe.

Inhibition of PDE-4 isoenzyme attenuates frequency and overall contractility of agonist-evoked ureteral phasic contractions.

The aim of this study was to investigate the functional role of phosphodiesterase enzymes (PDE) in the isolated porcine ureter. Distal ureteral strips were mounted in organ baths and pre-contracted with 5-HT (100 μM). Upon generation of stable phasic contractions, PDE-4 and PDE-5 inhibitors were added cumulatively to separate tissues. PDE-4 inhibitors, such as rolipram (10 nM and greater) and roflumilast (100 nM and greater), resulted in significant attenuation of ureteral contractile responses, while a higher concentration of piclamilast (1 μM and greater) was required to induce a significant depressant effect. The attenuation effect by rolipram was abolished by SQ22536 (100 μM). PDE-5 inhibitors, such as sildenafil and tadalafil, were not nearly as effective and were only able to suppress the 5-HT-induced contractions at higher concentrations of 1 μM. Rolipram significantly enhanced the depressant effect of forskolin, while sodium nitroprusside-induced attenuation of contractile responses remained unchanged in the presence of tadalafil. In summary, our study demonstrates that PDE-4 inhibitors are effective in attenuating 5-HT-induced contractility in porcine distal ureteral tissues, while PDE-5 inhibitors are less effective. These findings suggest that PDE-4 inhibitors, such as rolipram, may hold promise as potential therapeutic agents for the treatment of ureteral disorders attributable to increased intra-ureteral pressure.

Efficacy of BAY 60-2770, a Soluble Guanylate Cyclase Activator, for Coronary Spasm in Animal Models.

Ischemia with non-obstructive coronary arteries (INOCA), caused by coronary artery spasm, has gained increasing attention owing to the poor quality of life of impacted patients. Therapeutic options to address INOCA remain limited, and developing new therapeutic agents is desirable. Here, we examined whether soluble guanylate cyclase (sGC) activators could be beneficial in preventing coronary spasms. In organ chamber experiments with isolated canine coronary arteries, prostaglandin F2 α -induced, endothelin-1-induced, 5-hydroxytryptamine-induced, and potassium chloride-induced contractions were suppressed by the sGC activator BAY 60-2770 (0.1, 1, and 10 nM). In isolated pig coronary arteries, BAY 60-2770 (0.1, 1, and 10 nM) could prolong the cycle length of phasic contractions induced by 3,4-diaminopyridine, as well as lower the peak and bottom tension of the contraction in a concentration-dependent manner. Additionally, BAY 60-2770 (1 pM-0.1 µM) evoked a concentration-related relaxation to a greater extent in small (first diagonal branch) coronary arteries than in large (left anterior descending) coronary arteries. In vasopressin-induced angina model rats, pretreatment with BAY 60-2770 (3 µg/kg) suppressed electrocardiogram S-wave depression induced by arginine vasopressin without affecting changes in mean blood pressure and heart rate. These findings suggest that BAY 60-2770 could be valuable in preventing both large and small coronary spasms. Therefore, sGC activators could represent a novel and efficacious therapeutic option for INOCA. SIGNIFICANCE STATEMENT: The soluble guanylate cyclase (sGC) activator BAY 60-2770 exerted antispastic effects on the coronary arteries in animal vasospasm models as proof-of-concept studies. These data can help to support potential clinical development with sGC activators, suitable for human use in patients with vasospastic angina.