Upregulation of Anti-Angiogenic miR-106b-3p Correlates Negatively with IGF-1 and Vascular Health Parameters in a Model of Subclinical Cardiovascular Disease: Study with Metformin Therapy

\ua9 2024 by the authors.Well-controlled type 1 diabetes mellitus (T1DM) is regarded as a model of subclinical cardiovascular disease (CVD), characterized by inflammation and adverse vascular health. However, the underlying mechanisms are not fully understood. We investigated insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) levels, their correlation to miR-106b-3p expression in a subclinical CVD model, and the cardioprotective effect of metformin. A total of 20 controls and 29 well-controlled T1DM subjects were studied. Plasma IGF-1, IGFBP-3 levels, and miR-106b-3p expression in colony-forming unit-Hills were analyzed and compared with vascular markers. miR-106b-3p was upregulated in T1DM (p < 0.05) and negatively correlated with pro-angiogenic markers CD34+/100-lymphocytes (p < 0.05) and IGF-1 (p < 0.05). IGF-1 was downregulated in T1DM (p < 0.01), which was associated with increased inflammatory markers TNF-α, CRP, and IL-10 and reduced CD34+/100-lymphocytes. IGFBP-3 had no significant results. Metformin had no effect on IGF-1 but significantly reduced miR-106b-3p (p < 0.0001). An Ingenuity Pathway analysis predicted miR-106b-3p to inhibit PDGFA, PIK3CG, GDNF, and ADAMTS13, which activated CVD. Metformin was predicted to be cardioprotective by inhibiting miR-106b-3p. In conclusion: Subclinical CVD is characterized by a cardio-adverse profile of low IGF-1 and upregulated miR-106b-3p. We demonstrated that the cardioprotective effect of metformin may be via downregulation of upregulated miR-106b-3p and its effect on downstream targets

The inflammation, vascular repair and injury responses to exercise in fit males with and without Type 1 diabetes: an observational study.

Type 1 diabetes is associated with raised inflammation, impaired endothelial progenitor cell mobilisation and increased markers of vascular injury. Both acute and chronic exercise is known to influence these markers in non-diabetic controls, but limited data exists in Type 1 diabetes. We assessed inflammation, vascular repair and injury at rest and after exercise in physically-fit males with and without Type 1 diabetes.Ten well-controlled type 1 diabetes (27 ± 2 years; BMI 24 ± 0.7 kg.m(2); HbA1c 53.3 ± 2.4 mmol/mol) and nine non-diabetic control males (27 ± 1 years; BMI 23 ± 0.8 kg.m(2)) matched for age, BMI and fitness completed 45-min of running. Venous blood samples were collected 60-min before and 60-min after exercise, and again on the following morning. Blood samples were processed for TNF-α using ELISA, and circulating endothelial progenitor cells (cEPCs; CD45(dim)CD34(+)VEGFR2(+)) and endothelial cells (cECs; CD45(dim)CD133(-)CD34(+)CD144(+)) counts using flow-cytometry.TNF-α concentrations were 4-fold higher at all-time points in Type 1 diabetes, when compared with control (P 0.05). Within the Type 1 diabetes group, the delta change in cEPCS from rest to the following morning was related to HbA1c (r = -0.65, P = 0.021) and TNF-α (r = -0.766, P = 0.005).Resting cEPCs and cECs in Type 1 diabetes patients with excellent HbA1c and high physical-fitness are comparable to healthy controls, despite eliciting 4-fold greater TNF-α. Furthermore, Type 1 diabetes patients appear to have a blunted post-exercise cEPCs response (vascular repair), whilst a biomarker of vascular injury (cECs) remained comparable to healthy controls

Subarachnoid Hemorrhage Mimicking Leakage of Contrast Media After Coronary Angiography

We report a patient who developed subarachnoid hemorrhage (SAH) just after coronary angiography (CAG) with non-ionic contrast media (CM) and minimal dose of heparin. The 55-year-old man had a history of acute ST elevation myocardial infarction that had been treated with primary percutaneous coronary intervention and was admitted for a follow-up CAG. The CAG was performed by the transradial approach, using 1000 U of unfractionated heparin for the luminal coating and 70 mL of iodixanol. At the end of CAG, he complained of nausea and rapidly became stuporous. Brain CT showed a diffusely increased Hounsfield unit (HU) in the cisternal space, similar to leakage of CM. The maximal HU was 65 in the cisternal space. No vascular malformations were detected on cerebral angiography. The patient partially recovered his mental status and motor weakness after 2 days. Two weeks later, subacute SAH was evident on magnetic resonance imaging. The patient was discharged after 28 days

Measurement of the Inclusive Charm Cross Section at 4.03 GeV and 4.14 GeV

The cross section for charmed meson production at $\sqrt{s} = 4.03$ and 4.14 GeV has been measured with the Beijing Spectrometer. The measurement was made using 22.3 $pb^{-1}$ of $e^+e^-$ data collected at 4.03 GeV and 1.5 $pb^{-1}$ of $e^+e^-$ data collected at 4.14 GeV. Inclusive observed cross sections for the production of charged and neutral D mesons and momentum spectra are presented. Observed cross sections were radiatively corrected to obtain tree level cross sections. Measurements of the total hadronic cross section are obtained from the charmed meson cross section and an extrapolation of results from below the charm threshold.Comment: 11 pages, 13 figures. The top level tex file is paper.tex. It builds the paper from other tex files in this .tar and the .eps file

Measurement of ψ(2S)\psi(2S) decays to baryon pairs

A sample of 3.95M $\psi(2S)$ decays registered in the BES detector are used to study final states containing pairs of octet and decuplet baryons. We report branching fractions for $\psi(2S)\to p\bar{p}$, $\Lambda\bar{\Lambda}$, $\Sigma^0\bar{\Sigma}{}^0$, $\Xi^-\bar{\Xi}{}^+$, $\Delta^{++}\bar{\Delta}{}^{--}$, $\Sigma^+(1385)\bar{\Sigma}{}^-(1385)$, $\Xi^0(1530)\bar{\Xi}{}^0(1530)$, and $\Omega^-\bar{\Omega}{}^+$. These results are compared to expectations based on the SU(3)-flavor symmetry, factorization, and perturbative QCD.Comment: 22 pages, 21 figures, 4 table

Type 1 IP3 receptors activate BKCa channels via local molecular coupling in arterial smooth muscle cells

Plasma membrane large-conductance Ca2+-activated K+ (BKCa) channels and sarcoplasmic reticulum inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) are expressed in a wide variety of cell types, including arterial smooth muscle cells. Here, we studied BKCa channel regulation by IP3 and IP3Rs in rat and mouse cerebral artery smooth muscle cells. IP3 activated BKCa channels both in intact cells and in excised inside-out membrane patches. IP3 caused concentration-dependent BKCa channel activation with an apparent dissociation constant (Kd) of ∼4 µM at physiological voltage (−40 mV) and intracellular Ca2+ concentration ([Ca2+]i; 10 µM). IP3 also caused a leftward-shift in BKCa channel apparent Ca2+ sensitivity and reduced the Kd for free [Ca2+]i from ∼20 to 12 µM, but did not alter the slope or maximal Po. BAPTA, a fast Ca2+ buffer, or an elevation in extracellular Ca2+ concentration did not alter IP3-induced BKCa channel activation. Heparin, an IP3R inhibitor, and a monoclonal type 1 IP3R (IP3R1) antibody blocked IP3-induced BKCa channel activation. Adenophostin A, an IP3R agonist, also activated BKCa channels. IP3 activated BKCa channels in inside-out patches from wild-type (IP3R1+/+) mouse arterial smooth muscle cells, but had no effect on BKCa channels of IP3R1-deficient (IP3R1−/−) mice. Immunofluorescence resonance energy transfer microscopy indicated that IP3R1 is located in close spatial proximity to BKCa α subunits. The IP3R1 monoclonal antibody coimmunoprecipitated IP3R1 and BKCa channel α and β1 subunits from cerebral arteries. In summary, data indicate that IP3R1 activation elevates BKCa channel apparent Ca2+ sensitivity through local molecular coupling in arterial smooth muscle cells

Synthetic light-cone catalogues of modern redshift and weak lensing surveys waith abacussummit

The joint analysis of different cosmological probes, such as galaxy clustering and weak lensing, can potentially yield invaluable insights into the nature of the primordial Universe, dark energy, and dark matter. However, the development of high-fidelity theoretical models is a necessary stepping stone. Here, we present public high-resolution weak lensing maps on the light-cone, generated using the N-body simulation suite abacussummit, and accompanying weak lensing mock catalogues, tuned to the Early Data Release small-scale clustering measurements of the Dark Energy Spectroscopic Instrument. Available in this release are maps of the cosmic shear, deflection angle, and convergence fields at source redshifts ranging from z = 0.15 to 2.45 as well as cosmic microwave background convergence maps for each of the 25 base-resolution simulations (and Npart = 69123) as well as for the two huge simulations (and Npart = 86403) at the fiducial abacussummit cosmology. The pixel resolution of each map is 0.21 arcmin, corresponding to a healpix Nside of 16 384. The sky coverage of the base simulations is an octant until z ≈ 0.8 (decreasing to about 1800 deg2 at z ≈ 2.4), whereas the huge simulations offer full-sky coverage until z ≈ 2.2. Mock lensing source catalogues are sampled matching the ensemble properties of the Kilo-Degree Survey, Dark Energy Survey, and Hyper Suprime-Cam data sets. The mock catalogues are validated against theoretical predictions for various clustering and lensing statistics, such as correlation multipoles, galaxy-shear, and shear-shear, showing excellent agreement. All products can be downloaded via a Globus endpoint (see Data Availability section)

Gravitational Waves From Known Pulsars: Results From The Initial Detector Era

We present the results of searches for gravitational waves from a large selection of pulsars using data from the most recent science runs (S6, VSR2 and VSR4) of the initial generation of interferometric gravitational wave detectors LIGO (Laser Interferometric Gravitational-wave Observatory) and Virgo. We do not see evidence for gravitational wave emission from any of the targeted sources but produce upper limits on the emission amplitude. We highlight the results from seven young pulsars with large spin-down luminosities. We reach within a factor of five of the canonical spin-down limit for all seven of these, whilst for the Crab and Vela pulsars we further surpass their spin-down limits. We present new or updated limits for 172 other pulsars (including both young and millisecond pulsars). Now that the detectors are undergoing major upgrades, and, for completeness, we bring together all of the most up-to-date results from all pulsars searched for during the operations of the first-generation LIGO, Virgo and GEO600 detectors. This gives a total of 195 pulsars including the most recent results described in this paper.United States National Science FoundationScience and Technology Facilities Council of the United KingdomMax-Planck-SocietyState of Niedersachsen/GermanyAustralian Research CouncilInternational Science Linkages program of the Commonwealth of AustraliaCouncil of Scientific and Industrial Research of IndiaIstituto Nazionale di Fisica Nucleare of ItalySpanish Ministerio de Economia y CompetitividadConselleria d'Economia Hisenda i Innovacio of the Govern de les Illes BalearsNetherlands Organisation for Scientific ResearchPolish Ministry of Science and Higher EducationFOCUS Programme of Foundation for Polish ScienceRoyal SocietyScottish Funding CouncilScottish Universities Physics AllianceNational Aeronautics and Space AdministrationOTKA of HungaryLyon Institute of Origins (LIO)National Research Foundation of KoreaIndustry CanadaProvince of Ontario through the Ministry of Economic Development and InnovationNational Science and Engineering Research Council CanadaCarnegie TrustLeverhulme TrustDavid and Lucile Packard FoundationResearch CorporationAlfred P. Sloan FoundationAstronom

First narrow-band search for continuous gravitational waves from known pulsars in advanced detector data

Spinning neutron stars asymmetric with respect to their rotation axis are potential sources of continuous gravitational waves for ground-based interferometric detectors. In the case of known pulsars a fully coherent search, based on matched filtering, which uses the position and rotational parameters obtained from electromagnetic observations, can be carried out. Matched filtering maximizes the signalto- noise (SNR) ratio, but a large sensitivity loss is expected in case of even a very small mismatch between the assumed and the true signal parameters. For this reason, narrow-band analysis methods have been developed, allowing a fully coherent search for gravitational waves from known pulsars over a fraction of a hertz and several spin-down values. In this paper we describe a narrow-band search of 11 pulsars using data from Advanced LIGO’s first observing run. Although we have found several initial outliers, further studies show no significant evidence for the presence of a gravitational wave signal. Finally, we have placed upper limits on the signal strain amplitude lower than the spin-down limit for 5 of the 11 targets over the bands searched; in the case of J1813-1749 the spin-down limit has been beaten for the first time. For an additional 3 targets, the median upper limit across the search bands is below the spin-down limit. This is the most sensitive narrow-band search for continuous gravitational waves carried out so far