Etude biostratigraphique du cretace inferieur (Barremien Superieur-Albien) du haut atlas occidental (Maroc)

The lower Cretaceous (mainly Upper Barremian and Albian) of the Westem High Atlas of Morocco displays a diversified fauna constitued by Ammonite, Ostracoda, and foraminifera. The analysis of the microfauna, especially the planctonic foraminifera, allowed the characterization of various lithologic units, and their subdivision and datation. We have identified different biozona with planctonic foraminifera typical of the Tethysian realm characterising the Upper Barremian to the Albian. These biozona are described and their limits are discussed.Les affleurements du Crétacé inférieur, et principalement le Barrémien supérieur- Albien du Haut Atlas occidental marocain, ont fourni une faune diversifiée constituée par des ammonites, des ostracodes et des foraminifkres. L'analyse détaillée de la microfaune et principalement les foraminifkres planctoniques a permis de caractériser diverses unités lithologiques, de les subdiviser et de les dater. Nous avons identifié différentes biozones a foraminifkres planctoniques reconnues a l'échelle de la Téthys et caracténsant le Barrémien supérieur-Albien. Ces différentes biozones ont été décrites et leurs limites ont été discutées

Angular Diameters of the G Subdwarf μ\mu Cassiopeiae A and the K Dwarfs σ\sigma Draconis and HR 511 from Interferometric Measurements with the CHARA Array

Using the longest baselines of the CHARA Array, we have measured the angular diameter of the G5 V subdwarf $\mu$ Cas A, the first such determination for a halo population star. We compare this result to new diameters for the higher metallicity K0 V stars, $\sigma$ Dra and HR 511, and find that the metal-poor star, $\mu$ Cas A, has an effective temperature ($T_{\rm eff}=5297\pm32$ K), radius ($R=0.791\pm0.008 R_{\rm \odot}$), and absolute luminosity ($L=0.442\pm0.014 L_{\rm \odot}$) comparable to the other two stars with later spectral types. We show that stellar models show a discrepancy in the predicted temperature and radius for $\mu$ Cas A, and we discuss these results and how they provide a key to understanding the fundamental relationships for stars with low metallicity.Comment: Accepted for publication in The Astrophysical Journa

COVID-19 vaccination coverage for half a million non-EU migrants and refugees in England

Despite evidence suggesting that some migrants are at risk of under-immunization and have experienced severe health inequities during the pandemic, data are limited on migrants’ COVID-19 vaccine coverage globally. Here we linked data from non-European Union migrants and resettled refugees to the national COVID-19 vaccination dataset in England. We estimated patterns in second and third dose delays and overdue doses between 12 December 2020 and 20 April 2022 by age, visa type and ethnicity. Of the 465,470 linked records, 91.8% (427,073/465,470) of migrants received a second dose and 51.3% (238,721/465,470) received a third. Refugees had the highest risk of delayed second (adjusted odds ratio 1.66; 95% confidence interval 1.55–1.79) and third dose (1.55; 1.43–1.69). Black migrants were twice as likely to have a second dose delayed (2.37; 2.23–2.54) than white migrants, but this trend reversed for the third dose. Older migrants (>65 years) were four times less likely to have received their second or third dose compared with the general population in England aged >65 or older. Policymakers, researchers and practitioners should work to understand and address personal and structural barriers to vaccination for diverse migrant populations

Analysis of KLF transcription factor family gene variants in type 2 diabetes

<p>Abstract</p> <p>Background</p> <p>The Krüppel-like factor (<it>KLF</it>) family consists of transcription factors that can activate or repress different genes implicated in processes such as differentiation, development, and cell cycle progression. Moreover, several of these proteins have been implicated in glucose homeostasis, making them candidate genes for involvement in type 2 diabetes (T2D).</p> <p>Methods</p> <p>Variants of nine <it>KLF </it>genes were genotyped in T2D cases and controls and analysed in a two-stage study. The first case-control set included 365 T2D patients with a strong family history of T2D and 363 normoglycemic individuals and the second set, 750 T2D patients and 741 normoglycemic individuals, all of French origin. The SNPs of six <it>KLF </it>genes were genotyped by Taqman^®SNP Genotyping Assays. The other three <it>KLF </it>genes (KLF2, -15 and -16) were screened and the identified frequent variants of these genes were analysed in the case-control studies.</p> <p>Results</p> <p>Three of the 28 SNPs showed a trend to be associated with T2D in our first case-control set (P < 0.10). These SNPs, located in the <it>KLF2, KLF4 </it>and <it>KLF5 </it>gene were then analysed in our second replication set, but analysis of this set and the combined analysis of the three variants in all 2,219 individuals did not show an association with T2D in this French population. As the <it>KLF2</it>, -15 and -16 variants were representative for the genetic variability in these genes, we conclude they do not contribute to genetic susceptibility for T2D.</p> <p>Conclusion</p> <p>It is unlikely that variants in different members of the <it>KLF </it>gene family play a major role in T2D in the French population.</p

A Catalog of Compact Groups of Galaxies in the SDSS Commissioning Data

Compact groups (CGs) of galaxies -- relatively poor groups of galaxies in which the typical separations between members is of the order of a galaxy diameter -- offer an exceptional laboratory for the study of dense galaxian environments with short (<1Gyr) dynamical time-scales. In this paper, we present an objectively defined catalog of CGs in 153 sq deg of the Sloan Digital Sky Survey Early Data Release (SDSS EDR). To identify CGs, we applied a modified version of Hickson's (1982) criteria aimed at finding the highest density CGs and thus reducing the number of chance alignments. Our catalog contains 175 CGs down to a limiting galaxy magnitude of r* = 21. The resulting catalog has a median depth of approximately z = 0.13, substantially deeper than previous CG catalogs. Since the SDSS will eventually image up to one quarter of the celestial sphere, we expect our final catalog, based upon the completed SDSS, will contain on the order of 5,000 - 10,000 CGs. This catalog will be useful for conducting studies of the general characteristics of CGs, their environments, and their component galaxies.Comment: 61 pages, 15 figures (Figs. 13, 14, 15 are jpegs). Atlas of compact groups (Fig. 16) is available at http://home.fnal.gov/~sallam/LeeCG/ . Accepted for publication by the Astronomical Journa

Robust Off- and Online Separation of Intracellularly Recorded Up and Down Cortical States

BACKGROUND: The neuronal cortical network generates slow (<1 Hz) spontaneous rhythmic activity that emerges from the recurrent connectivity. This activity occurs during slow wave sleep or anesthesia and also in cortical slices, consisting of alternating up (active, depolarized) and down (silent, hyperpolarized) states. The search for the underlying mechanisms and the possibility of analyzing network dynamics in vitro has been subject of numerous studies. This exposes the need for a detailed quantitative analysis of the membrane fluctuating behavior and computerized tools to automatically characterize the occurrence of up and down states. METHODOLOGY/PRINCIPAL FINDINGS: Intracellular recordings from different areas of the cerebral cortex were obtained from both in vitro and in vivo preparations during slow oscillations. A method that separates up and down states recorded intracellularly is defined and analyzed here. The method exploits the crossover of moving averages, such that transitions between up and down membrane regimes can be anticipated based on recent and past voltage dynamics. We demonstrate experimentally the utility and performance of this method both offline and online, the online use allowing to trigger stimulation or other events in the desired period of the rhythm. This technique is compared with a histogram-based approach that separates the states by establishing one or two discriminating membrane potential levels. The robustness of the method presented here is tested on data that departs from highly regular alternating up and down states. CONCLUSIONS/SIGNIFICANCE: We define a simple method to detect cortical states that can be applied in real time for offline processing of large amounts of recorded data on conventional computers. Also, the online detection of up and down states will facilitate the study of cortical dynamics. An open-source MATLAB toolbox, and Spike 2-compatible version are made freely available

The synthetic peptide P111-136 derived from the C-terminal domain of heparin affin regulatory peptide inhibits tumour growth of prostate cancer PC-3 cells

<p>Abstract</p> <p>Background</p> <p>Heparin affin regulatory peptide (HARP), also called pleiotrophin, is a heparin-binding, secreted factor that is overexpressed in several tumours and associated to tumour growth, angiogenesis and metastasis. The C-terminus part of HARP composed of amino acids 111 to 136 is particularly involved in its biological activities and we previously established that a synthetic peptide composed of the same amino acids (P111-136) was capable of inhibiting the biological activities of HARP. Here we evaluate the ability of P111-136 to inhibit <it>in vitro </it>and <it>in vivo </it>the growth of a human tumour cell line PC-3 which possess an HARP autocrine loop.</p> <p>Methods</p> <p>A total lysate of PC-3 cells was incubated with biotinylated P111-136 and pulled down for the presence of the HARP receptors in Western blot. <it>In vitro</it>, the P111-136 effect on HARP autocrine loop in PC-3 cells was determined by colony formation in soft agar. <it>In vivo</it>, PC-3 cells were inoculated in the flank of athymic nude mice. Animals were treated with P111-136 (5 mg/kg/day) for 25 days. Tumour volume was evaluated during the treatment. After the animal sacrifice, the tumour apoptosis and associated angiogenesis were evaluated by immunohistochemistry. <it>In vivo </it>anti-angiogenic effect was confirmed using a mouse Matrigel™ plug assay.</p> <p>Results</p> <p>Using pull down experiments, we identified the HARP receptors RPTPβ/ζ, ALK and nucleolin as P111-136 binding proteins. <it>In vitro</it>, P111-136 inhibits dose-dependently PC-3 cell colony formation. Treatment with P111-136 inhibits significantly the PC-3 tumour growth in the xenograft model as well as tumour angiogenesis. The angiostatic effect of P111-136 on HARP was also confirmed using an <it>in vivo </it>Matrigel™ plug assay in mice</p> <p>Conclusions</p> <p>Our results demonstrate that P111-136 strongly inhibits the mitogenic effect of HARP on <it>in vitro </it>and <it>in vivo </it>growth of PC-3 cells. This inhibition could be linked to a direct or indirect binding of this peptide to the HARP receptors (ALK, RPTPβ/ζ, nucleolin). <it>In vivo</it>, the P111-136 treatment significantly inhibits both the PC-3 tumour growth and the associated angiogenesis. Thus, P111-136 may be considered as an interesting pharmacological tool to interfere with tumour growth that has now to be evaluated in other cancer types.</p

Targeting surface nucleolin with a multivalent pseudopeptide delays development of spontaneous melanoma in RET transgenic mice

<p>Abstract</p> <p>Background</p> <p>The importance of cell-surface nucleolin in cancer biology was recently highlighted by studies showing that ligands of nucleolin play critical role in tumorigenesis and angiogenesis. By using a specific antagonist that binds the C-terminal tail of nucleolin, the HB-19 pseudopeptide, we recently reported that HB-19 treatment markedly suppressed the progression of established human breast tumor cell xenografts in the athymic nude mice without apparent toxicity.</p> <p>Methods</p> <p>The <it>in vivo </it>antitumoral action of HB-19 treatment was assessed on the spontaneous development of melanoma in the RET transgenic mouse model. Ten days old RET mice were treated with HB-19 in a prophylactic setting that extended 300 days. In parallel, the molecular basis for the action of HB-19 was investigated on a melanoma cell line (called TIII) derived from a cutaneous nodule of a RET mouse.</p> <p>Results</p> <p>HB-19 treatment of RET mice caused a significant delay in the onset of cutaneous tumors, several-months delay in the incidence of large tumors, a lower frequency of cutaneous nodules, and a reduction of visceral metastatic nodules while displaying no toxicity to normal tissue. Moreover, microvessel density was significantly reduced in tumors recovered from HB-19 treated mice compared to corresponding controls. Studies on the melanoma-derived tumor cells demonstrated that HB-19 treatment of TIII cells could restore contact inhibition, impair anchorage-independent growth, and reduce their tumorigenic potential in mice. Moreover, HB-19 treatment caused selective down regulation of transcripts coding matrix metalloproteinase 2 and 9, and tumor necrosis factor-α in the TIII cells and in melanoma tumors of RET mice.</p> <p>Conclusions</p> <p>Although HB-19 treatment failed to prevent the development of spontaneous melanoma in the RET mice, it delayed for several months the onset and frequency of cutaneous tumors, and exerted a significant inhibitory effect on visceral metastasis. Consequently, HB-19 could provide a novel therapeutic agent by itself or as an adjuvant therapy in association with current therapeutic interventions on a virulent cancer like melanoma.</p

Molecular Components and Functions of the Endocannabinoid System in Mouse Prefrontal Cortex

Background. Cannabinoids have deleterious effects on prefrontal cortex (PFC)-mediated functions and multiple evidences link the endogenous cannabinoid (endocannabinoid) system, cannabis use and schizophrenia, a disease in which PFC functions are altered. Nonetheless, the molecular composition and the physiological functions of the endocannabinoid system in the PFC are unknown. Methodology/Principal Findings. Here, using electron microscopy we found that key proteins involved in endocannabinoid signaling are expressed in layers V/VI of the mouse prelimbic area of the PFC: presynaptic cannabinoid CB1 receptors (CB1R) faced postsynaptic mGluR5 while diacylglycerol lipase alpha (DGL-alpha), the enzyme generating the endocannabinoid 2-arachidonoyl-glycerol (2-AG) was expressed in the same dendritic processes as mGluR5. Activation of presynaptic CB1R strongly inhibited evoked excitatory post-synaptic currents. Prolonged synaptic stimulation at 10Hz induced a profound long-term depression (LTD) of layers V/VI excitatory inputs. The endocannabinoid -LTD was presynaptically expressed and depended on the activation of postsynaptic mGluR5, phospholipase C and a rise in postsynaptic Ca2+ as predicted from the localization of the different components of the endocannabinoid system. Blocking the degradation of 2-AG (with URB 602) but not of anandamide (with URB 597) converted subthreshold tetanus to LTD-inducing ones. Moreover, inhibiting the synthesis of 2-AG with Tetrahydrolipstatin, blocked endocannabinoid-mediated LTD. All together, our data show that 2-AG mediates LTD at these synapses. Conclusions/Significance. Our data show that the endocannabinoid -retrograde signaling plays a prominent role in long-term synaptic plasticity at the excitatory synapses of the PFC. Alterations of endocannabinoid -mediated synaptic plasticity may participate to the etiology of PFC-related pathologies