Monosynaptic GABAergic Signaling from Dentate to CA3 with a Pharmacological and Physiological Profile Typical of Mossy Fiber Synapses

AbstractMossy fibers are the sole excitatory projection from dentate gyrus granule cells to the hippocampus, where they release glutamate, dynorphin, and zinc. In addition, mossy fiber terminals show intense immunoreactivity for the inhibitory neurotransmitter GABA. Fast inhibitory transmission at mossy fiber synapses, however, has not previously been reported. Here, we show that electrical or chemical stimuli that recruit dentate granule cells elicit monosynaptic GABAA receptor–mediated synaptic signals in CA3 pyramidal neurons. These inhibitory signals satisfy the criteria that distinguish mossy fiber–CA3 synapses: high sensitivity to metabotropic glutamate receptor agonists, facilitation during repetitive stimulation, and NMDA receptor–independent long-term potentiation. GABAergic transmission from the dentate gyrus to CA3 has major implications not only for information flow into the hippocampus but also for developmental and pathological processes involving the hippocampus

Mitochondrial Ca²⁺ Uniporter haploinsufficiency enhances long-term potentiation at hippocampal mossy fibre synapses

Long-term changes in synaptic strength form the basis of learning and memory. These changes rely upon energy demanding mechanisms which are regulated by local Ca2+ signaling. Mitochondria are optimised for providing energy and buffering Ca2+. However, our understanding of the role of mitochondria in regulating synaptic plasticity is incomplete. Here we have used optical and electrophysiological techniques in cultured hippocampal neurons and ex vivo hippocampal slices from mice with haploinsufficiency of the mitochondrial Ca2+ uniporter (MCU+/-) to address whether reducing mitochondrial Ca2+ uptake alters synaptic transmission and plasticity. We found that cultured MCU+/- hippocampal neurons have impaired Ca2+ clearance, and consequently enhanced synaptic vesicle fusion at presynapses occupied by mitochondria. Furthermore, long-term potentiation (LTP) at mossy fibre (MF) synapses, a process which is dependent on presynaptic Ca2+ accumulation, is enhanced in MCU+/- slices. Our results reveal a previously unrecognized role for mitochondria in regulating presynaptic plasticity of a major excitatory pathway involved in learning and memory

To what extent do fiscal regimes equalize opportunities for income acquisition among citizens?.

This paper employs the theory of equality of opportunity, described in Roemer’s book (Equality of Opportunity, Harvard University Press, 1998), to compute the extent to which tax-and-transfer regimes in 11 countries equalize opportunities among citizens for income acquisition. Roughly speaking, equality of opportunity for incomes has been achieved in a country when it is the case that the distributions of post-fisc income are the same for different types of citizen, where a citizen’s type is defined by the socio-economic status of his parents. Intuitively, a country will have equalized opportunity if the chances of earning high (or low) income are equal for citizens from all family backgrounds. Of course, pre-fisc income distributions, by type, will not be identical, as long as the educational system does not entirely make up for the disadvantage that children, who come from poor families face, but the tax-and-transfer system can play a role in rectifying that inequality. We include, in our computation, two numbers that summarize the extent to which each country’s current fiscal regime achieves equalization of opportunities for income, and the deadweight loss that would be incurred by moving to the regime that does.Fiscal regimes; Equal opportunities; Income acquisition;

Restriction Factors: From Intrinsic Viral Restriction to Shaping Cellular Immunity Against HIV-1

Antiviral restriction factors are host cellular proteins that constitute a first line of defense blocking viral replication and propagation. In addition to interfering at critical steps of the viral replication cycle, some restriction factors also act as innate sensors triggering innate responses against infections. Accumulating evidence suggests an additional role for restriction factors in promoting antiviral cellular immunity to combat viruses. Here, we review the recent progress in our understanding on how restriction factors, particularly APOBEC3G, SAMHD1, Tetherin, and TRIM5α have the cell-autonomous potential to induce cellular resistance against HIV-1 while promoting antiviral innate and adaptive immune responses. Also, we provide an overview of how these restriction factors may connect with protein degradation pathways to modulate anti-HIV-1 cellular immune responses, and we summarize the potential of restriction factors-based therapeutics. This review brings a global perspective on the influence of restrictions factors in intrinsic, innate, and also adaptive antiviral immunity opening up novel research avenues for therapeutic strategies in the fields of drug discovery, gene therapy, and vaccines to control viral infections

Iron as a tracer in galaxy clusters and groups

Available X-ray data are collected and organized concerning the iron and gas content of galaxy clusters and groups, together with the optical luminosity, mass and iron abundance of cluster galaxies. Several astrophysical inferences are then drawn, including the evidence for rich clusters having evolved without much baryon exchange with their surrondings, and having experienced very similar star formation histories. Groups are much gas-poor compared to clusters, and appear instead to have shed a major fraction of their original cosmic share of baryons, which indicates that galaxy clusters cannot have formed by assembling groups similar to the present day ones. It is argued that this favors low-$\Omega$ universes, in which the growth of rich clusters is virtually complete at high redshifts. It is also argued that elemental abundance ratios in clusters are nearly solar, which is consistent with a similar proportion of supernovae of Type Ia and Type II having enriched both the solar neghborhood as well clusters as a whole. Much of the iron in clusters appears to reside in the intracluster medium rather than inside galaxies. It appears that the baryon to star conversion in clusters has been nearly as efficient as currently adopted for the universe as a whole. Yet the metallicity of the clusters is $\sim 5$ times higher than the global metallicity adopted for the nearby universe. It is concluded that the intergalactic medium should have a metallicity $\sim 1/3$ solar if stellar nucleosynthesis has proceeded in stars within field galaxies with the same efficiency as in stars within clusters of galaxies.Comment: AASTex Latex, 29 pages, 6 figure

The Origins of a Rich Absorption Line Complex in a Quasar at Redshift 3.45

We discuss the nature and origin of a rich complex of narrow absorption lines in the quasar J102325.31+514251.0 at redshift 3.447. We measure nine C IV(\lambda1548,1551) absorption line systems with velocities from -1400 to -6200 km/s, and full widths at half minimum ranging from 16 to 350 km/s. We also detect other absorption lines in these systems, including H I, C III, N V, O VI, and Si IV. Lower ionisation lines are not present, indicating a generally high degree of ionisation in all nine systems. The total hydrogen column densities range from <=10^{17.2} to 10^{19.1}cm^{-2}. We examine several diagnostics to estimate more directly the location and origin of each absorber. Four of the systems can be attributed to a quasar-driven outflow based on line profiles that are smooth and broad compared to thermal line widths. Several systems also have other indicators of a quasar outflow origin, including partial covering. Altogether there is direct evidence for 6 of the 9 systems forming in a quasar outflow. Consistent with a near-quasar origin, eight of the systems have metallicity values or lower limits in the range Z >= 1-8 Z_{sun}. The lowest velocity system, which has an ambiguous location, also has the lowest metallicity, Z <= 0.3 Z_{sun}, and might form in a non-outflow environment farther from the quasar. Overall, however, this complex of narrow absorption lines can be identified with a highly structured, multi-component outflow from the quasar. The high metallicities are similar to those derived for other quasars at similar redshifts and luminosities, and are consistent with evolution scenarios wherein quasars appear after the main episodes of star formation and metal enrichment in the host galaxies.Comment: 16 pages, 12 figures, Accepted to MNRAS, July 201