5,644 research outputs found
Re-structuring lentiviral vectors to express genomic RNA via cap-dependent translation
Lentiviral (LV) vectors based on human immunodeficiency virus type I (HIV-1) package two copies of their single-stranded RNA into vector particles. Normally, this RNA genome is reverse transcribed into a double-stranded DNA provirus that integrates into the cell genome, providing permanent gene transfer and long-term expression. Integration-deficient LV vectors have been developed to reduce the frequency of genomic integration and thereby limit their persistence in dividing cells. Here, we describe optimization of a reverse-transcriptase-deficient LV vector, which enables direct translation of LV RNA genomes upon cell entry, for transient expression of vector payloads as mRNA without a DNA intermediate. We have engineered a novel LV genome arrangement in which HIV-1 sequences are removed from the 5′ end, to enable ribosomal entry from the 5′ 7-methylguanylate cap for efficient translation of the vector payload. We have shown that this LV-mediated mRNA delivery platform provides transient transgene expression in vitro and in vivo. This has a potential application in gene and cell therapy scenarios requiring temporary payload expression in cells and tissues that can be targeted with pseudotyped LV vectors
Characteristics of C-4 photosynthesis in stems and petioles of C-3 flowering plants
Most plants are known as C-3 plants because the first product of photosynthetic CO2 fixation is a three-carbon compound. C-4 plants, which use an alternative pathway in which the first product is a four-carbon compound, have evolved independently many times and are found in at least 18 families. In addition to differences in their biochemistry, photosynthetic organs of C-4 plants show alterations in their anatomy and ultrastructure. Little is known about whether the biochemical or anatomical characteristics of C-4 photosynthesis evolved first. Here we report that tobacco, a typical C-3 plant, shows characteristics of C-4 photosynthesis in cells of stems and petioles that surround the xylem and phloem, and that these cells are supplied with carbon for photosynthesis from the vascular system and not from stomata. These photosynthetic cells possess high activities of enzymes characteristic of C-4 photosynthesis, which allow the decarboxylation of four-carbon organic acids from the xylem and phloem, thus releasing CO2 for photosynthesis. These biochemical characteristics of C-4 photosynthesis in cells around the vascular bundles of stems of C-3 plants might explain why C-4 photosynthesis has evolved independently many times
Who bullies whom at a garden feeder? Interspecific agonistic interactions of small passerines during a cold winter
Interspecific agonistic interactions are important
selective factors for maintaining ecological niches of
different species, but their outcome is difficult to predict
a priori. Here, we examined the direction and intensity of
interspecific interactions in an assemblage of small passerines
at a garden feeder, focussing on three finch species
of various body sizes. We found that large and mediumsized
birds usually initiated and won agonistic interactions
with smaller species. Also, the frequency of fights increased
with decreasing differences in body size between
the participants. Finally, the probability of engaging in a
fight increased with the number of birds at the feeder
The Omega Deformation, Branes, Integrability, and Liouville Theory
We reformulate the Omega-deformation of four-dimensional gauge theory in a
way that is valid away from fixed points of the associated group action. We use
this reformulation together with the theory of coisotropic A-branes to explain
recent results linking the Omega-deformation to integrable Hamiltonian systems
in one direction and Liouville theory of two-dimensional conformal field theory
in another direction.Comment: 96 p
Modeling Slope Instability as Shear Rupture Propagation in a Saturated Porous Medium
When a region of intense shear in a slope is much thinner than other relevant geometric lengths, this shear failure may be approximated as localized slip, as in faulting, with strength determined by frictional properties of the sediment and effective stress normal to the failure surface. Peak and residual frictional strengths of submarine sediments indicate critical slope angles well above those of most submarine slopes—in contradiction to abundant failures. Because deformation of sediments is governed by effective stress, processes affecting pore pressures are a means of strength reduction. However, common methods of exami ning slope stability neglect dynamically variable pore pressure during failure. We examine elastic-plastic models of the capped Drucker-Prager type and derive approximate equations governing pore pressure about a slip surface when the adjacent material may deform plastically. In the process we identify an elastic-plastic hydraulic diffusivity with an evolving permeability and plastic storage term analogous to the elastic term of traditional poroelasticity. We also examine their application to a dynamically propagating subsurface rupture and find indications of downslope directivity.Earth and Planetary SciencesEngineering and Applied Science
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Output from VIP cells of the mammalian central clock regulates daily physiological rhythms
The suprachiasmatic nucleus (SCN) circadian clock is critical for optimising daily cycles in mammalian physiology and behaviour. The roles of the various SCN cell types in communicating timing information to downstream physiological systems remain incompletely understood, however. In particular, while vasoactive intestinal polypeptide (VIP) signalling is essential for SCN function and whole animal circadian rhythmicity, the specific contributions of VIP cell output to physiological control remains uncertain. Here we reveal a key role for SCN VIP cells in central clock output. Using multielectrode recording and optogenetic manipulations, we show that VIP neurons provide coordinated daily waves of GABAergic input to target cells across the paraventricular hypothalamus and ventral thalamus, supressing their activity during the mid to late day. Using chemogenetic manipulation, we further demonstrate specific roles for this circuitry in the daily control of heart rate and corticosterone secretion, collectively establishing SCN VIP cells as influential regulators of physiological timing
Cosmological phase transitions in warped space: gravitational waves and collider signatures
We study the electroweak phase transition within a 5D warped model including
a scalar potential with an exponential behavior, and strong back-reaction over the metric,
in the infrared. By means of a novel treatment of the superpotential formalism, we explore
parameter regions that were previously inaccessible. We nd that for large enough values
of the t'Hooft parameter (e.g. N = 25) the holographic phase transition occurs, and it
can force the Higgs to undergo a rst order electroweak phase transition, suitable for
electroweak baryogenesis. The model exhibits gravitational waves and colliders signatures.
It typically predicts a stochastic gravitational wave background observable both at the
Laser Interferometer Space Antenna and at the Einstein Telescope. Moreover the radion
tends to be heavy enough such that it evades current constraints, but may show up in
future LHC runs.The work of EM is supported by the Spanish MINEICO under
Grant FPA2015-64041-C2-1-P and FIS2017-85053-C2-1-P, by the Junta de Andaluc a under
Grant FQM-225, by the Basque Government under Grant IT979-16, and by the Spanish
Consolider Ingenio 2010 Programme CPAN (CSD2007-00042). The research of EM is also
supported by the Ram on y Cajal Program of the Spanish MINEICO, and by the Universidad
del Pa s Vasco UPV/EHU, Bilbao, Spain, as a Visiting Professor. GN is supported
by the Swiss National Science Foundation (SNF) under grant 200020-168988. The work
of MQ is partly supported by Spanish MINEICO under Grant CICYT-FEDER-FPA2014-
55613-P and FPA2017-88915-P, by the Severo Ochoa Excellence Program of MINEICO
under Grant SEV-2016-0588, and by CNPq PVE fellowship project 405559/2013-5
Sexual Abuse-Current Medico-legal, Forensic and Psychiatric Aspects
Abstract
Violence against women and minors is a worldwide problem that has not yet been sufficiently acknowledged. There are many obstacles especially when sexual abuses have to be evaluated. These problems are present both when victims of sexual abuse are evaluated and when sex offenders are dealt with, especially when the offenders are juvenile sex offenders (JSO).
These issues give cause for great concern about prognosis, and the resulting psychosocial implications, and call for a special effort from the scientific community in identifying appropriate prevention and treatment methods.
This chapter is divided into two parts. The first part deals with the forensic and psychiatric features, such as diagnostic and therapeutic/rehabilitative strategies for JSO, while the second part analyzes the legal–medicine aspects related to rape/sexual assault in a European context
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