Suppression of Sleep Spindle Rhythmogenesis in Mice with Deletion of CaV3.2 and CaV3.3 T-type Ca(2+) Channels.

STUDY OBJECTIVES: Low-threshold voltage-gated T-type Ca(2+) channels (T-channels or CaV3 channels) sustain oscillatory discharges of thalamocortical (TC) and nucleus Reticularis thalami (nRt) cells. The CaV3.3 subtype dominates nRt rhythmic bursting and mediates a substantial fraction of spindle power in the NREM sleep EEG. CaV3.2 channels are also found in nRt, but whether these contribute to nRt-dependent spindle generation is unexplored. We investigated thalamic rhythmogenesis in mice lacking this subtype in isolation (CaV3.2KO mice) or in concomitance with CaV3.3 deletion (CaV3.double-knockout (DKO) mice). METHODS: We examined discharge characteristics of thalamic cells and intrathalamic evoked synaptic transmission in brain slices from wild-type, CaV3.2KO and CaV3.DKO mice through patch-clamp recordings. The sleep profile of freely behaving CaV3.2KO and CaV3.DKO mice was assessed by polysomnographic recordings. RESULTS: CaV3.2 channel deficiency left nRt discharge properties largely unaltered, but additional deletion of CaV3.3 channels fully abolished low-threshold whole-cell Ca(2+) currents and bursting, and suppressed burst-mediated inhibitory responses in TC cells. CaV3.DKO mice had more fragmented sleep, with shorter NREM sleep episodes and more frequent microarousals. The NREM sleep EEG power spectrum displayed a relative suppression of the σ frequency band (10-15 Hz), which was accompanied by an increase in the δ band (1-4 Hz). CONCLUSIONS: Consistent with previous findings, CaV3.3 channels dominate nRt rhythmogenesis, but the lack of CaV3.2 channels further aggravates neuronal, synaptic, and EEG deficits. Therefore, CaV3.2 channels can boost intrathalamic synaptic transmission, and might play a modulatory role adjusting the relative presence of NREM sleep EEG rhythms

Phasic, nonsynaptic GABA-A receptor-mediated inhibition entrains thalamocortical oscillations.

GABA-A receptors (GABA-ARs) are typically expressed at synaptic or nonsynaptic sites mediating phasic and tonic inhibition, respectively. These two forms of inhibition conjointly control various network oscillations. To disentangle their roles in thalamocortical rhythms, we focally deleted synaptic, γ2 subunit-containing GABA-ARs in the thalamus using viral intervention in mice. After successful removal of γ2 subunit clusters, spontaneous and evoked GABAergic synaptic currents disappeared in thalamocortical cells when the presynaptic, reticular thalamic (nRT) neurons fired in tonic mode. However, when nRT cells fired in burst mode, slow phasic GABA-AR-mediated events persisted, indicating a dynamic, burst-specific recruitment of nonsynaptic GABA-ARs. In vivo, removal of synaptic GABA-ARs reduced the firing of individual thalamocortical cells but did not abolish slow oscillations or sleep spindles. We conclude that nonsynaptic GABA-ARs are recruited in a phasic manner specifically during burst firing of nRT cells and provide sufficient GABA-AR activation to control major thalamocortical oscillations

Reconstructing Bioinvasion Dynamics Through Micropaleontologic Analysis Highlights the Role of Temperature Change as a Driver of Alien Foraminifera Invasion

Invasive alien species threaten biodiversity and ecosystem structure and functioning, but incomplete assessments of their origins and temporal trends impair our ability to understand the relative importance of different factors driving invasion success. Continuous time-series are needed to assess invasion dynamics, but such data are usually difficult to obtain, especially in the case of small-sized taxa that may remain undetected for several decades. In this study, we show how micropaleontologic analysis of sedimentary cores coupled with radiometric dating can be used to date the first arrival and to reconstruct temporal trends of foraminiferal species, focusing on the alien Amphistegina lobifera and its cryptogenic congener A. lessonii in the Maltese Islands. Our results show that the two species had reached the Central Mediterranean Sea several decades earlier than reported in the literature, with considerable implications for all previous hypotheses of their spreading patterns and rates. By relating the population dynamics of the two foraminifera with trends in sea surface temperature, we document a strong relationship between sea warming and population outbreaks of both species. We conclude that the micropaleontologic approach is a reliable procedure for reconstructing the bioinvasion dynamics of taxa having mineralized remains, and can be added to the toolkit for studying invasions

Environmental variables and machine learning models to predict cetacean abundance in the Central-eastern Mediterranean Sea

: Although the Mediterranean Sea is a crucial hotspot in marine biodiversity, it has been threatened by numerous anthropogenic pressures. As flagship species, Cetaceans are exposed to those anthropogenic impacts and global changes. Assessing their conservation status becomes strategic to set effective management plans. The aim of this paper is to understand the habitat requirements of cetaceans, exploiting the advantages of a machine-learning framework. To this end, 28 physical and biogeochemical variables were identified as environmental predictors related to the abundance of three odontocete species in the Northern Ionian Sea (Central-eastern Mediterranean Sea). In fact, habitat models were built using sighting data collected for striped dolphins Stenella coeruleoalba, common bottlenose dolphins Tursiops truncatus, and Risso's dolphins Grampus griseus between July 2009 and October 2021. Random Forest was a suitable machine learning algorithm for the cetacean abundance estimation. Nitrate, phytoplankton carbon biomass, temperature, and salinity were the most common influential predictors, followed by latitude, 3D-chlorophyll and density. The habitat models proposed here were validated using sighting data acquired during 2022 in the study area, confirming the good performance of the strategy. This study provides valuable information to support management decisions and conservation measures in the EU marine spatial planning context

Constitutive basal and stimulated human small bowel contractility is enhanced in obesity

Small bowel contractility may be more prominent in obese subjects, such that there is enhanced nutrient absorption and hunger stimulation. However, there is little evidence to support this. This study examined in vitro small bowel contractility in obese patients versus non-obese patients

Observational Evidence of the Basin-Wide Gyre Reversal in the Gulf of Taranto

The paper shows for the first time the observational evidence of basin-wide gyre reversal in the Gulf of Taranto (north-western Ionian Sea in the eastern Mediterranean Sea) by means of two specifically designed in situ oceanographic campaigns (based on CTD and ADCP measurements). The analysis of the in situ data shows a change in circulation from anticyclonic in October 2014 to cyclonic in June\u2013July 2016. Furthermore, long-term (1993\u20132018) analysis using gridded satellite altimetry data in the Gulf of Taranto shows that the cyclonic gyres are more frequent than anticyclonic gyres. The latter occur only for 2 to 3 years at a time in some decades

Bladder inflammatory transcriptome in response to tachykinins: Neurokinin 1 receptor-dependent genes and transcription regulatory elements

Background Tachykinins (TK), such as substance P, and their neurokinin receptors which are ubiquitously expressed in the human urinary tract, represent an endogenous system regulating bladder inflammatory, immune responses, and visceral hypersensitivity. Increasing evidence correlates alterations in the TK system with urinary tract diseases such as neurogenic bladders, outflow obstruction, idiopathic detrusor instability, and interstitial cystitis. However, despite promising effects in animal models, there seems to be no published clinical study showing that NK-receptor antagonists are an effective treatment of pain in general or urinary tract disorders, such as detrusor overactivity. In order to search for therapeutic targets that could block the tachykinin system, we set forth to determine the regulatory network downstream of NK1 receptor activation. First, NK1R-dependent transcripts were determined and used to query known databases for their respective transcription regulatory elements (TREs). Methods: An expression analysis was performed using urinary bladders isolated from sensitized wild type (WT) and NK1R-/- mice that were stimulated with saline, LPS, or antigen to provoke inflammation. Based on cDNA array results, NK1R-dependent genes were selected. PAINT software was used to query TRANSFAC database and to retrieve upstream TREs that were confirmed by electrophoretic mobility shift assays. Results: The regulatory network of TREs driving NK1R-dependent genes presented cRel in a central position driving 22% of all genes, followed by AP-1, NF-kappaB, v-Myb, CRE-BP1/c-Jun, USF, Pax-6, Efr-1, Egr-3, and AREB6. A comparison between NK1R-dependent and NK1R-independent genes revealed Nkx-2.5 as a unique discriminator. In the presence of NK1R, Nkx2-5 _01 was significantly correlated with 36 transcripts which included several candidates for mediating bladder development (FGF) and inflammation (PAR-3, IL-1R, IL-6, α-NGF, TSP2). In the absence of NK1R, the matrix Nkx2-5_02 had a predominant participation driving 8 transcripts, which includes those involved in cancer (EYA1, Trail, HSF1, and ELK-1), smooth-to-skeletal muscle trans-differentiation, and Z01, a tight-junction protein, expression. Electrophoretic mobility shift assays confirmed that, in the mouse urinary bladder, activation of NK1R by substance P (SP) induces both NKx-2.5 and NF-kappaB translocations. Conclusion: This is the first report describing a role for Nkx2.5 in the urinary tract. As Nkx2.5 is the unique discriminator of NK1R-modulated inflammation, it can be imagined that in the near future, new based therapies selective for controlling Nkx2.5 activity in the urinary tract may be used in the treatment in a number of bladder disorders

Measurement of the Lifetime Difference Between B_s Mass Eigenstates

We present measurements of the lifetimes and polarization amplitudes for B_s --> J/psi phi and B_d --> J/psi K*0 decays. Lifetimes of the heavy (H) and light (L) mass eigenstates in the B_s system are separately measured for the first time by determining the relative contributions of amplitudes with definite CP as a function of the decay time. Using 203 +/- 15 B_s decays, we obtain tau_L = (1.05 +{0.16}/-{0.13} +/- 0.02) ps and tau_H = (2.07 +{0.58}/-{0.46} +/- 0.03) ps. Expressed in terms of the difference DeltaGamma_s and average Gamma_s, of the decay rates of the two eigenstates, the results are DeltaGamma_s/Gamma_s = (65 +{25}/-{33} +/- 1)%, and DeltaGamma_s = (0.47 +{0.19}/-{0.24} +/- 0.01) inverse ps.Comment: 8 pages, 3 figures, 2 tables; as published in Physical Review Letters on 16 March 2005; revisions are for length and typesetting only, no changes in results or conclusion

N-acetylcysteine treatment ameliorates the skeletal phenotype of a mouse model of diastrophic dysplasia.

Diastrophic dysplasia (DTD) is a recessive chondrodysplasia caused by mutations in SLC26A2, a cell membrane sulfate-chloride antiporter. Sulfate uptake impairment results in low cytosolic sulfate, leading to cartilage proteoglycan (PG) undersulfation. In this work, we used the dtd mouse model to study the role of N-acetyl-l-cysteine (NAC), a well-known drug with antioxidant properties, as an intracellular sulfate source for macromolecular sulfation. Because of the important pre-natal phase of skeletal development and growth, we administered 30 g/l NAC in the drinking water to pregnant mice to explore a possible transplacental effect on the fetuses. When cartilage PG sulfation was evaluated by high-performance liquid chromatography disaccharide analysis in dtd newborn mice, a marked increase in PG sulfation was observed in newborns from NAC-treated pregnancies when compared with the placebo group. Morphometric studies of the femur, tibia and ilium after skeletal staining with alcian blue and alizarin red indicated a partial rescue of abnormal bone morphology in dtd newborns from treated females, compared with pups from untreated females. The beneficial effect of increased macromolecular sulfation was confirmed by chondrocyte proliferation studies in cryosections of the tibial epiphysis by proliferating cell nuclear antigen immunohistochemistry: the percentage of proliferating cells, significantly reduced in the placebo group, reached normal values in dtd newborns from NAC-treated females. In conclusion, NAC is a useful source of sulfate for macromolecular sulfation in vivo when extracellular sulfate supply is reduced, confirming the potential of therapeutic approaches with thiol compounds to improve skeletal deformity and short stature in human DTD and related disorders

Measurement of WγW\gamma and ZγZ\gamma Production in ppˉp\bar{p} Collisions at s\sqrt{s} = 1.96 TeV

The Standard Model predictions for $W\gamma$ and $Z\gamma$ production are tested using an integrated luminosity of 200 pb$^{-1}$ of \ppbar collision data collected at the Collider Detector at Fermilab. The cross sections are measured selecting leptonic decays of the $W$ and $Z$ bosons, and photons with transverse energy $E_T>7$ GeV that are well separated from leptons. The production cross sections and kinematic distributions for the $W\gamma$ and $Z\gamma$ are compared to SM predictions.Comment: 7 pages, 4 figures, submitted to PR