252 research outputs found
dATF4 regulation of mitochondrial folate-mediated one-carbon metabolism is neuroprotective.
Neurons rely on mitochondria as their preferred source of energy. Mutations in PINK1 and PARKIN cause neuronal death in early-onset Parkinson's disease (PD), thought to be due to mitochondrial dysfunction. In Drosophila pink1 and parkin mutants, mitochondrial defects lead to the compensatory upregulation of the mitochondrial one-carbon cycle metabolism genes by an unknown mechanism. Here we uncover that this branch is triggered by the activating transcription factor 4 (ATF4). We show that ATF4 regulates the expression of one-carbon metabolism genes SHMT2 and NMDMC as a protective response to mitochondrial toxicity. Suppressing Shmt2 or Nmdmc caused motor impairment and mitochondrial defects in flies. Epistatic analyses showed that suppressing the upregulation of Shmt2 or Nmdmc deteriorates the phenotype of pink1 or parkin mutants. Conversely, the genetic enhancement of these one-carbon metabolism genes in pink1 or parkin mutants was neuroprotective. We conclude that mitochondrial dysfunction caused by mutations in the Pink1/Parkin pathway engages ATF4-dependent activation of one-carbon metabolism as a protective response. Our findings show a central contribution of ATF4 signalling to PD that may represent a new therapeutic strategy. A video abstract for this article is available at https://youtu.be/cFJJm2YZKKM
Fatigue and microgap behaviour of a three-unit implant-fixed dental prosthesis combining conventional and dynamic abutments
This is an in vitro study composed by a fatigue test followed by an optical microscopy analysis. Dynamic abutments concept, recently introduced on screw-retained implant dental prosthesis, consists on the screw channel customisation according to the individual needs of each rehabilitation. Geometry and tightening torque differences advise the assessment of their mechanical performance. Clarify whether the combination of dynamic and conventional abutments in a three-unit implant-fixed prosthesis has detrimental effects either on the mechanical performance under cyclic loading or on the implant-abutment microgap dimensions. The fatigue test was performed in agreement with the ISO standard 14801. Then on the samples that resisted 5 million
cycles, the implant-abutment microgap was measured on dynamic and conventional abutments using optical microscopy. Two unloaded samples were used as control group. The samples supported a load of 1050 N. The implant-abutment microgap measurement did not show statistically significant differences (p=.086) between loaded and unloaded groups, but the loaded conventional abutments showed a significant lower implant-abutment microgap (p=.05) than the loaded dynamic abutments. The combination of conventional and dynamic
abutments do not seem to produce a decrease in fatigue resistance to a level below the mastication forces or an increase in the joint dimensions.The study was supported in part by SciTech - Science and Technology for
Competitive and Sustainable Industries, and the R&D project was cofinanced by the
North Portugal Regional Operational Program ("NORTE2020") and the European
Regional Development Fund (FEDER)
Clonal diversity and conservation genetics of the medicinal plant Carapichea ipecacuanha (Rubiaceae)
The roots of the understorey shrub Carapichea ipecacuanha (ipecac) have medicinal properties, and the uprooting of wild plants has supplied most of the world demand for this species. Although under severe population decline, C. ipecacuanha lacks legal protection. In the wild, the aerial stems of ipecac clump together to form clusters with well-defined borders. Cluster size may range from several to hundreds of aerial stems. To investigate the extent of clonality among aerial stems in ipecac clusters, we sampled 50 wild clusters (a total of 291 aerial stems) and screened them with 89 inter-simple sequence repeat (ISSR) markers. The 291 aerial stems were grouped into 42 putative clones. The clonal groups generally consisted of aerial stems from the same cluster, and there was little or no genetic differentiation among aerial stems at the cluster level. These findings suggest that strategies designed to conserve ipecac in situ should not rely upon census data, which are based on the number of aerial stems per cluster and the number of clusters per population, because such data greatly underestimate the species effective population size and genetic diversity. Our results also indicate that this species needs protection at a federal level
Proliferative Hypothalamic Neurospheres Express NPY, AGRP, POMC, CART and Orexin-A and Differentiate to Functional Neurons
Some pathological conditions with feeding pattern alterations, including obesity and Huntington disease (HD) are associated with hypothalamic dysfunction and neuronal cell death. Additionally, the hypothalamus is a neurogenic region with the constitutive capacity to generate new cells of neuronal lineage, in adult rodents
An analysis of Methylenetetrahydrofolate reductase and Glutathione S-transferase omega-1 genes as modifiers of the cerebral response to ischemia
<p>Abstract</p> <p>Background</p> <p>Cerebral ischemia involves a series of reactions which ultimately influence the final volume of a brain infarction. We hypothesize that polymorphisms in genes encoding proteins involved in these reactions could act as modifiers of the cerebral response to ischemia and impact the resultant stroke volume. The final volume of a cerebral infarct is important as it correlates with the morbidity and mortality associated with non-lacunar ischemic strokes.</p> <p>Methods</p> <p>The proteins encoded by the methylenetetrahydrofolate reductase (<it>MTHFR</it>) and glutathione S-transferase omega-1 (<it>GSTO-1</it>) genes are, through oxidative mechanisms, key participants in the cerebral response to ischemia. On the basis of these biological activities, they were selected as candidate genes for further investigation. We analyzed the C677T polymorphism in the <it>MTHFR </it>gene and the C419A polymorphism in the <it>GSTO-1 </it>gene in 128 patients with non-lacunar ischemic strokes.</p> <p>Results</p> <p>We found no significant association of either the <it>MTHFR </it>(p = 0.72) or <it>GSTO-1 </it>(p = 0.58) polymorphisms with cerebral infarct volume.</p> <p>Conclusion</p> <p>Our study shows no major gene effect of either the <it>MTHFR </it>or <it>GSTO-1 </it>genes as a modifier of ischemic stroke volume. However, given the relatively small sample size, a minor gene effect is not excluded by this investigation.</p
Productive restructuring and the reallocation of work and employment: a survey of the ânewâ forms of social inequality
O propĂłsito do presente artigo consiste
em questionar a inevitabilidade dos processos de
segmentação e precarização das relaçÔes de trabalho
e emprego, responsåveis pela inscrição de
ânovasâ formas de desigualdade social que alicerçam
o actual modelo de desenvolvimento das economias
e sociedades. Visa-se criticar os limites da
lĂłgica econĂŽmica e financeira, de contornos globais,
que configuram um ânovo espĂrito do capitalismoâ,
ou seja, uma espécie de divinização da
ordem natural das coisas. ImpÔe-se fazer, por isso,
um pĂ©riplo analĂtico pelas transformaçÔes em curso
no mercado de trabalho, acompanhado pela vigilĂąncia
epistemolĂłgica que permita enquadrar e
relativizar as (di)visÔes neoliberais e teses tecnodeterministas
dominantes. A perspectivação de cenårios
sobre o futuro do trabalho encerrarĂĄ este
périplo, permitindo-nos alertar para os condicionalismos
histĂłrico-temporais, para a urgĂȘncia de
se desocultar o que de ideolĂłgico e polĂtico existe
nas actuais lógicas de racionalização e para os
processos de ressimbolização do trabalho e emprego
enquanto âexperiĂȘncia social centralâ na
contemporaneidade.The scope of this paper is to question
the inevitability of the processes of segmentation
and increased precariousness of the relations
of labor and employment, which are responsible
for the introduction of ânewâ forms of
social inequality that underpin the current model
of development of economies and societies. It
seeks to criticize the limits of global financial and
economic logic, which constitute a ânew spirit of
capitalism,â namely a kind of reverence for the
natural order of things. It is therefore necessary
to conduct an analytical survey of the ongoing
changes in the labor market, accompanied by epistemological
vigilance which makes it possible to
see neoliberal (di)visions and dominant technodeterministic
theses in context. The enunciation
of scenarios on the future of work will conclude
this survey and will make it possible to draw attention
to both the historical and temporal constraints
and to the urgent need to unveil what is
ideological and political in the prevailing logic of
rationalization and processes to reinstate work
and employment as a âcentral social experienceâ
in contemporary times
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