Petrology, Mineral and Isotope Geochemistry of the External Liguride Peridotites (Northern Apennines, Italy)

Mantle peridotites of the External Liguride (EL) units (Northern Apennines) represent slices of subcontinental lithospheric mantle emplaced at the surface during early stages of rifting of the Jurassic Ligurian Piemontese basin. Petrological, ion probe and isotopic investigations have been used to unravel the nature of their mantle protolith and to constrain the timing and mechanisms of their evolution. EL peridotites are dominantly fertile spinel Iherzolites partly recrystallizfd in the plagiodase Iherzplite stability field Clinopyroxenes stable in the spinel-facies assemblage have nearly fiat REE patterns (CeN/SmN=0·6-0·8) at (10-16)×C1 and high Na, Sr, Ti and Zr contents. Kaersutitic-Ti-pargasitic amphiboles also occur in the spinel-facies assemblage. Their LREE-depleted REE spectra and very low Sr, Zr and Ba contents indicate that they crystallized from hydrous fluids with low concentrations of incompatible elements. Thermometric estimates on the spinelfacies parageneses yield lithospheric equilibrium temperatures in the range 1000-1100°C, in agreement with the stability of amphibole, which implies T<1100°C. Sr and Nd isotopic compositions, determined on carefully handpicked clinopyroxene separates, plot within the depleted end of the MORB field (87Sr/86Sr=0·70222-0·70263; 143Nd/144Nd=0·513047-0·513205) similar to many subcontinental orogenic spinel Iherzolites from the western Mediterranean area (e.g. Ivrea Zpne and Lanzfl N). The interpretation of the EL Iherzolites as subcontinental lithospheric mantle is reinforced by the occurrence of one extremely depleted isotopic composition (87Sr/86Sr=0·701736; 143Nd/144Nd=0·513543). Sr and Nd model ages, calculated assuming both CHUR and DM mantle sources, range between 2·4 Ga and 780 Ma. In particular, the 1·2-Ga Sr age and the 780-Ma Nd age can be regarded as minimum ages of differentiation. The transition from spinel-to plagioclase-facies assemblage, accompanied by progressive deformation (from granular to tectonite-mylonite textures), indicate that the EL Iherzolites experienced a later, subsolidus decompressional evolution, starting from subcontinental lithospheric levels. Sm/Nd isochrons on plagioclase-clinopyroxene pairs furnish ages of ∽165 Ma. This early Jurassic subsolidus decompressional history is consistent with uplift by means of denudation in response to passive and asymmetric lithospheric extension. This is considered to be the most suitable geodynamic mechanism to account for the exposure of huge bodies of subcontinental lithospheric mantle during early stages of opening of an oceanic basi

RIPK3-Dependent Recruitment of Low-Inflammatory Myeloid Cells Does Not Protect from Systemic Salmonella Infection

ABSTRACT Regulated macrophage death has emerged as an important mechanism to defend against intracellular pathogens. However, the importance and consequences of macrophage death during bacterial infection are poorly resolved. This is especially true for the recently described RIPK3-dependent lytic cell death, termed necroptosis. Salmonella enterica serovar Typhimurium is an intracellular pathogen that precisely regulates virulence expression within macrophages to evade and manipulate immune responses, which is a key factor in its ability to cause severe systemic infections. We combined genetic and pharmacological approaches to examine the importance of RIPK3 for S. Typhimurium-induced macrophage death using conditions that recapitulate bacterial gene expression during systemic infection in vivo. Our findings indicate that noninvasive S. Typhimurium does not naturally induce macrophage necroptosis but does so in the presence of pan-caspase inhibition. Moreover, our data suggest that RIPK3 induction (following caspase inhibition) does not impact host survival following S. Typhimurium infection, which differs from previous findings based on inert lipopolysaccharide (LPS) injections. Finally, although necroptosis is typically characterized as highly inflammatory, our data suggest that RIPK3 skews the peritoneal myeloid population away from an inflammatory profile to that of a classically noninflammatory profile. Collectively, these data improve our understanding of S. Typhimurium-macrophage interactions, highlight the possibility that purified bacterial components may not accurately recapitulate the complexity of host-pathogen interactions, and reveal a potential and unexpected role for RIPK3 in resolving inflammation. IMPORTANCE Macrophages employ multiple strategies to limit pathogen infection. For example, macrophages may undergo regulated cell death, including RIPK3-dependent necroptosis, as a means of combatting intracellular bacterial pathogens. However, bacteria have evolved mechanisms to evade or exploit immune responses. Salmonella is an intracellular pathogen that avoids and manipulates immune detection within macrophages. We examined the contribution of RIPK3 to Salmonella-induced macrophage death. Our findings indicate that noninvasive Salmonella does not naturally induce necroptosis, but it does so when caspases are inhibited. Moreover, RIPK3 induction (following caspase inhibition) does not impact host survival following Salmonella systemic infection. Finally, our data show that RIPK3 induction results in recruitment of low-inflammatory myeloid cells, which was unexpected, as necroptosis is typically described as highly inflammatory. Collectively, these data improve our understanding of pathogen-macrophage interactions, including outcomes of regulated cell death during infection in vivo, and reveal a potential new role for RIPK3 in resolving inflammation

A 19 to 17 Ma amagmatic extension event at the Mid-Atlantic Ridge: Ultramafic mylonites from the Vema Lithospheric Section

A >300 km long lithospheric section (Vema Lithospheric Section or VLS) is exposed south of the Vema transform at 11°N in the Atlantic. It is oriented along a seafloor spreading flow line and represents ∼26 Ma of accretion at a single 80 km long segment (EMAR) of the Mid-Atlantic Ridge. The basal part of the VLS exposes a mantle unit made mostly of relatively undeformed coarse-grained/porphyroclastic peridotites that were sampled at close intervals. Strongly deformed mylonitic peridotites were found at 14 contiguous sites within a ∼80 km stretch (∼4.7 Ma interval); they are dominant in a time interval of 1.4 Ma, from crustal ages of 16.8 to 18.2 Ma (mylonitic stretch). Some of the mylonites are "dry," showing anhydrous high-T deformation, but most contain amphibole. The mylonitic peridotites tend to be less depleted than the porphyroclastic peridotites on the basis of mineral major and trace elements composition, suggesting that the mylonites parent was a subridge mantle that underwent a relatively low degree of melting. The Sr, Nd, and O isotopic composition of the amphiboles is MORB-like and suggests either that seawater did not contribute to their isotopic signature or that their isotopic ratios re-equilibrated during fluid circulation in the upper mantle. Four 40Ar/39Ar ages, on three amphiboles separated from the peridotites, are close to crustal ages predicted from magnetic anomalies, confirming that the amphiboles formed close to ridge axis. We propose that crustal accretion at the EMAR segment has been mostly symmetrical for the 26 Ma of its recorded history, except for the ∼1.4 Ma interval of prevalent ultramafic mylonites (mylonitic stretch) that may record a period of quasi-amagmatic asymmetric accretion of oceanic lithosphere close to the ridge–Vema transform intersection, possibly with development of detachment faults. This interval may correspond to a thermal minimum of the subridge upwelling mantle, marking the transition from a period of decreasing to one of increasing mantle melting below the EMAR segment

Is Shifting to a Progestin Worthwhile When Estrogen-Progestins Are Inefficacious for Endometriosis-Associated Pain?

The purpose of this study was to assess the proportion of patients satisfied with their treatment after a change from a low-dose oral contraceptive (OC) to norethisterone acetate (NETA) because of inefficacy of OC on pain symptoms. To this end, prospective, self-controlled study was conducted on 153 women using OC as a treatment for endometriosis and with persistence of one or more moderate or severe pain symptoms. At baseline and during 12 months after a shift from OC to oral NETA, 2.5 mg/d, pelvic pain was measured by means of a 0- to 10-point numerical rating scale and a multidimensional categorical rating scale. Variations in health-related quality of life, psychological status, and sexual function were also evaluated with validated scales. At the end of the study period, participants indicated the degree of satisfaction with their treatment according to a 5-degree scale from very satisfied to very dissatisfied. A total of 28 women dropped out of the study, the main reason was intolerable side effects (n = 15). At 12-month assessment, 70% of participants were very satisfied or satisfied with NETA treatment (intention-to-treat analysis). Statistically significant improvements were observed in health-related quality of life, psychological status, and sexual function. At per-protocol analysis, almost half of the patients (58/125) reported suboptimal drug tolerability. However, complaints were not severe enough to cause dissatisfaction, drug discontinuation, or request for surgery. These encouraging results could be used to counsel women with symptomatic endometriosis not responding to OC and to inform their decisions on modifications of disease management

Randomized controlled trials in pediatric complementary and alternative medicine: Where can they be found?

BACKGROUND: The safety and effectiveness of CAM interventions are of great relevance to pediatric health care providers. The objective of this study is to identify sources of reported randomized controlled trials (RCTs) in the field of pediatric complementary and alternative medicine (CAM). METHODS: Reports of RCTs were identified by searching Medline and 12 additional bibliographic databases and by reviewing the reference lists of previously identified pediatric CAM systematic reviews. RESULTS: We identified 908 reports of RCTs that included children under 18 and investigated a CAM therapy. Since 1965, there has been a steady growth in the number of these trials that are being published. The four journals that published the most reported RCTs are The American Journal of Clinical Nutrition, Pediatrics, Journal of Pediatrics, and Lancet. Medline, CAB Health, and Embase were the best database sources for identifying these studies; they indexed 93.2%, 58.4% and 42.2 % respectively of the journals publishing reports of pediatric CAM RCTs. CONCLUSIONS: Those working or interested in the field of pediatric CAM should routinely search Medline, CAB Health and Embase for literature in the field. The four core journals identified above should be included in their collection

Disrupted endothelial cell heterogeneity and network organization impair vascular function in prediabetic obesity

Background: Obesity is a major risk factor for diabetes and cardiovascular diseases such as hypertension, heart failure, and stroke. Impaired endothelial function occurs in the earliest stages of obesity and underlies vascular alterations that give rise to cardiovascular disease. However, the mechanisms that link weight gain to endothelial dysfunction are ill-defined. Increasing evidence suggests that endothelial cells are not a population of uniform cells but are highly heterogeneous and are organized as a communicating multicellular network that controls vascular function. Purpose: To investigate the hypothesis that disrupted endothelial heterogeneity and network-level organization contribute to impaired vascular reactivity in obesity. Methods and Results: To study obesity-related vascular function without complications associated with diabetes, a state of prediabetic obesity was induced in rats. Small artery diameter recordings confirmed nitric-oxide mediated vasodilator responses were dependent on increases in endothelial calcium levels and were impaired in obese animals. Single-photon imaging revealed a linear relationship between blood vessel relaxation and population-wide calcium responses. Obesity did not alter the slope of this relationship, but impaired calcium responses in the endothelial cell network. The network comprised structural and functional components. The structural architecture, a hexagonal lattice network of connected cells, was unchanged in obesity. The functional network contained sub-populations of clustered specialized agonist-sensing cells from which signals were communicated through the network. In obesity there were fewer but larger clusters of sensory cells and communication path lengths between clusters increased. Communication between neighboring cells was unaltered in obesity. Altered network organization resulted in impaired, population-level calcium signaling and deficient endothelial control of vascular tone. Conclusions: The distribution of cells in the endothelial network is critical in determining overall vascular response. Altered cell heterogeneity and arrangement in obesity decreases endothelial function and provides a novel framework for understanding compromised endothelial function in cardiovascular disease

Transmission of Avian Influenza A Viruses among Species in an Artificial Barnyard

Waterfowl and shorebirds harbor and shed all hemagglutinin and neuraminidase subtypes of influenza A viruses and interact in nature with a broad range of other avian and mammalian species to which they might transmit such viruses. Estimating the efficiency and importance of such cross-species transmission using epidemiological approaches is difficult. We therefore addressed this question by studying transmission of low pathogenic H5 and H7 viruses from infected ducks to other common animals in a quasi-natural laboratory environment designed to mimic a common barnyard. Mallards (Anas platyrhynchos) recently infected with H5N2 or H7N3 viruses were introduced into a room housing other mallards plus chickens, blackbirds, rats and pigeons, and transmission was assessed by monitoring virus shedding (ducks) or seroconversion (other species) over the following 4 weeks. Additional animals of each species were directly inoculated with virus to characterize the effect of a known exposure. In both barnyard experiments, virus accumulated to high titers in the shared water pool. The H5N2 virus was transmitted from infected ducks to other ducks and chickens in the room either directly or through environmental contamination, but not to rats or blackbirds. Ducks infected with the H7N2 virus transmitted directly or indirectly to all other species present. Chickens and blackbirds directly inoculated with these viruses shed significant amounts of virus and seroconverted; rats and pigeons developed antiviral antibodies, but, except for one pigeon, failed to shed virus