Engineered gene-drive techniques for population modification and/or suppression have the potential for tackling complex challenges, including reducing the spread of diseases and invasive species. ...Gene-drive systems with low threshold frequencies for invasion, such as homing-based gene drive, require initially few transgenic individuals to spread and are therefore easy to introduce. The self-propelled behavior of such drives presents a double-edged sword, however, as the low threshold can allow transgenic elements to expand beyond a target population. By contrast, systems where a high threshold frequency must be reached before alleles can spread-above a fitness valley-are less susceptible to spillover but require introduction at a high frequency. We model a proposed drive system, called "daisy quorum drive," that transitions over time from a low-threshold daisy-chain system (involving homing-based gene drive such as CRISPR-Cas9) to a high-threshold fitness-valley system (requiring a high frequency-a "quorum"-to spread). The daisy-chain construct temporarily lowers the high thresholds required for spread of the fitness-valley construct, facilitating use in a wide variety of species that are challenging to breed and release in large numbers. Because elements in the daisy chain only drive subsequent elements in the chain and not themselves and also carry deleterious alleles ("drive load"), the daisy chain is expected to exhaust itself, removing all CRISPR elements and leaving only the high-threshold fitness-valley construct, whose spread is more spatially restricted. Developing and analyzing both discrete patch and continuous space models, we explore how various attributes of daisy quorum drive affect the chance of modifying local population characteristics and the risk that transgenic elements expand beyond a target area. We also briefly explore daisy quorum drive when population suppression is the goal. We find that daisy quorum drive can provide a promising bridge between gene-drive and fitness-valley constructs, allowing spread from a low frequency in the short term and better containment in the long term, without requiring repeated introductions or persistence of CRISPR elements.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
2.
CoQ10 and Aging Barcelos, Isabella Peixoto de; Haas, Richard H
Biology,
05/2019, Letnik:
8, Številka:
2
Journal Article
Recenzirano
Odprti dostop
The aging process includes impairment in mitochondrial function, a reduction in anti-oxidant activity, and an increase in oxidative stress, marked by an increase in reactive oxygen species (ROS) ...production. Oxidative damage to macromolecules including DNA and electron transport proteins likely increases ROS production resulting in further damage. This oxidative theory of cell aging is supported by the fact that diseases associated with the aging process are marked by increased oxidative stress. Coenzyme Q10 (CoQ
) levels fall with aging in the human but this is not seen in all species or all tissues. It is unknown whether lower CoQ
levels have a part to play in aging and disease or whether it is an inconsequential cellular response to aging. Despite the current lay public interest in supplementing with CoQ
, there is currently not enough evidence to recommend CoQ
supplementation as an anti-aging anti-oxidant therapy.
Objective
The Mental Health Self‐Direction Scale (MHSD) measures the extent to which clients are able to resolve mental problems by themselves. Because this scale had not yet been evaluated, the aims ...of this paper were (a) to evaluate and improve the MHSD and (b) to explore the sensitivity to change of the improved scale.
Method
The MHSD was evaluated and improved by means of confirmatory factor analyses of data from one longitudinal and two cross‐sectional outpatient sample. Inconsistent items were removed in a stepwise fashion. Subsequently, the scale's sensitivity to change was explored in the longitudinal sample by using latent growth curve models.
Results
The original 31‐item scale was reduced to a more stable version with 19 items that yielded four factors named: actorship, demoralization, commitment, and understanding. Throughout clients’ treatment, actorship and understanding tended to increase; demoralization tended to decrease; and commitment remained consistently high.
Conclusions
The abridged MHSD scale is stable and sensitive to change. It measures the extent to which clients experience and develop self‐direction throughout their treatment. With the use of the new MHSD scale, new views on mental health that emphasize clients’ ability to actively engage and cope with health‐challenges can be incorporated into clinical treatment.
Evolutionary conflict between the sexes can induce arms races in which males evolve traits that are detrimental to the fitness of their female partners, and vice versa. This interlocus sexual ...conflict (IRSC) has been proposed as a cause of perpetual intersexual antagonistic coevolution with wide-ranging evolutionary consequences. However, theory suggests that the scope for perpetual coevolution is limited, if traits involved in IRSC are subject to pleiotropic constraints. Here, we consider a biologically plausible form of pleiotropy that has hitherto been ignored in treatments of IRSC and arrive at drastically different conclusions. Our analysis is based on a quantitative genetic model of sexual conflict, in which genes controlling IRSC traits have side effects in the other sex, due to incompletely sex-limited gene expression. As a result, the genes are exposed to intralocus sexual conflict (IASC), a tug-of-war between opposing male- and female-specific selection pressures. We find that the interaction between the two forms of sexual conflict has contrasting effects on antagonistic coevolution: Pleiotropic constraints stabilize the dynamics of arms races if the mating traits are close to evolutionary equilibrium but can prevent populations from ever reaching such a state. Instead, the sexes are drawn into a continuous cycle of arms races, causing the buildup of IASC, alternated by phases of IASC resolution that trigger the next arms race. These results encourage an integrative perspective on the biology of sexual conflict and generally caution against relying exclusively on equilibrium stability analysis.
Although Morocco has evolved into one of the world’s leading emigration countries, the systematic study of the developmental impact of migration in migrant-sending regions in Morocco and the Maghreb ...has been relatively neglected after a temporary surge of pessimistic studies in the 1970s. Empirical work from this region has therefore been largely absent from the lively theoretical debate on migration and development. This study attempts to re-establish this link through qualitative research and a survey among 507 non-migrant, internal and international migrant households in the Moroccan Todgha oasis. The study shows that international migration and remittances have significantly contributed to economic development, improved standards of living and enabled the partial emancipation of subaltern ethnic groups. International migrant households invest more than others in housing, agriculture and other enterprises. Risk spreading and income stabilisation rather than increasing incomes seem to be the prime rationale behind internal migration, although internal migration tends to facilitate the education and international migration of younger household members. Remittance expenditure and investments have stimulated the diversifying and urbanising regional economy and have triggered a counter-flow of “reverse” internal migration. However, several structural constraints prevent the high development potential of migration from being fully realised.
In western Europe, Pectobacterium carotovorum subsp. brasiliense is emerging as a causal agent of blackleg disease. In field experiments in the Netherlands, the virulence of this pathogen was ...compared with strains of other Dickeya and Pectobacterium species. In 2013 and 2014, seed potato tubers were vacuum infiltrated with high densities of bacteria (106 CFU mL−1) and planted in clay soil. Inoculation with P. carotovorum subsp. brasiliense and P. atrosepticum resulted in high disease incidences (75–95%), inoculation with D. solani and P. wasabiae led to incidences between 5% and 25%, but no significant disease development was observed in treatments with P. carotovorum subsp. carotovorum, D. dianthicola or the water control. Co‐inoculations of seed potatoes with P. carotovorum subsp. brasiliense and D. solani gave a similar disease incidence to inoculation with only P. carotovorum subsp. brasiliense. However, co‐inoculation of P. carotovorum subsp. brasiliense with P. wasabiae resulted in a decrease in disease incidence compared to inoculation with only P. carotovorum subsp. brasiliense. In 2015, seed potatoes were inoculated with increasing densities of P. carotovorum subsp. brasiliense, D. solani or P. atrosepticum (103–106 CFU mL−1). After vacuum infiltration, even a low inoculum density resulted in high disease incidence. However, immersion without vacuum caused disease only at high bacterial densities. Specific TaqMan assays were evaluated and developed for detection of P. carotovorum subsp. brasiliense, P. wasabiae and P. atrosepticum and confirmed the presence of these pathogens in progeny tubers of plants derived from vacuum‐infiltrated seed tubers.
•Histaminergic (HA) neurons of the caudal hypothalamus fire at maximum during active wakefulness supporting cortical arousal.•Substance P increases the firing rate of HA neurons.•Tachykinins permit ...long lasting enhancement of firing by capsaicin.•Pharmacology and single cell RT-PCR support involvement of all 3 neurokinin receptor types.
Substance P (SP), a product of the tachykinin 1 (Tac1) gene, is expressed in many hypothalamic neurons. Its wake-promoting potential could be mediated through histaminergic (HA) neurons of the tuberomamillary nucleus (TMN), where functional expression of neurokinin receptors (NKRs) waits to be characterized. As in the process of nociception in the peripheral nervous system (PNS) capsaicin-receptor (transient potential vanilloid 1: TRPV1) signalling is amplified by local release of histamine and SP, we tested the involvement of tachykinins in the capsaicin-induced long-lasting enhancement (LLEcaps) of HA neurons firing by investigating selective neurokinin receptor ligands in the hypothalamic mouse brain slice preparation using patch-clamp recordings in cell-attached mode combined with single-cell RT-PCR. We report that the majority of HA neurons respond to SP (EC50 3 nM), express the SP precursor tachykinin 1 (Tac1) gene and at least one of the neurokinin receptors. Responses to selective agonists of three known neurokinin receptors were sensitive to corresponding antagonists. LLEcaps was significantly impaired by the neurokinin receptor antagonists, indicating that in hypothalamus, as in the PNS, release of tachykinins downstream to TRPV1 activation is able to boost the release of histamine. The excitatory action of SP on histaminergic neurons adds another pathway to the noradrenergic and orexinergic ones to synergistically enhance cortical arousal. We show NK1R to play a prominent role on HA neurons and thus the control of wakefulness.
Long-term (⩽1-year) records obtained by seabed observatories (BOBO) and repeated (24-h) CTD casts show the presence of a highly energetic environment in and around two cold-water carbonate-mound ...provinces, on the Southwest and Southeast Rockall Trough (SW and SE RT) margin. Carbonate mounds, covered with a thriving coral cover, are embedded mainly in the Eastern North Atlantic Water (ENAW) and are observed in a confined bathymetric zone between 600 and 1000
m water depth. Cold-water corals seem to be restricted in their growth by temperature and food availability. The presence of living corals on top of the carbonate mounds appears linked to the presence of internal waves and tidal currents in the water column, and consequently carbonate mound structures are shaped by the local hydrodynamic regime. Mound clusters have an elongated shape perpendicular to the regional contours and corresponding to the direction of the highest current speeds. On the SW RT margin temperature, salinity and current speed reflect a diurnal tidal pattern, causing maximum temperature variations at 900
m depth of more than 3
°C. Current speeds up to 45
cm
s
−1 occur, and a residual current of 10
cm
s
−1 is directed along the slope to the southwest. At the SE RT margin the temperature of the bottom water fluctuates more than 1
°C with a semi-diurnal tidal cyclicity. Amplitudes of average and peak current speeds here are comparable with those measured on the southwest margin, but the residual current in this area is directed to the northeast. Tidal currents and internal waves at both margins force the formation of intermediate and bottom nepheloid layers and bring fresh food particles with increased velocity to the mounds. The distribution of corals in both mound areas is considered directly related to the presence of enhanced turbidity. An increase in temperature can be directly related to an increase in the amount of particles in the water column. Current velocity increases when a transition occurs from cold to warm waters. High current velocities prevent local sedimentation but provide sufficient food particles to the corals, so that the corals thrive at the mound summits.
Issue Title: Carbonate Mounds on the NW European Margin: A window into Earth History Cold-water coral carbonate mounds, owing their presence mainly to the framework building coral Lophelia pertusa ...and the activity of associated organisms, are common along the European margin with their spatial distribution allowing them to be divided into a number of mound provinces. Variation in mound attributes are explored via a series of case studies on mound provinces that have been the most intensely investigated: Belgica, Hovland, Pelagia, Logachev and Norwegian Mounds. Morphological variation between mound provinces is discussed under the premise that mound morphology is an expression of the environmental conditions under which mounds are initiated and grow. Cold-water coral carbonate mounds can be divided into those exhibiting "inherited" morphologies (where mound morphology reflects the morphology of the colonised features) and "developed" morphology (where the mounds assume their own gross morphology mainly reflecting dominant hydrodynamic controls). Finer-scale, surface morphological features mainly reflecting biological growth forms are also discussed.PUBLICATION ABSTRACT
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