The major renal Na+/phosphate cotransporter, NaPi-IIa, is regulated by a number of factors including parathyroid hormone (PTH), dopamine, and dietary phosphate intake. PTH induces the acute ...internalization of NaPi-IIa from the brush border membrane (BBM) and its routing to and subsequent degradation in lysosomes. Previous work indicated that megalin, part of the apical receptor-mediated endocytic apparatus, may play a role in the PTH-induced removal of NaPi-IIa. Here we examined in rats the time-dependent internalization route of NaPi-IIa after acute PTH application using immunohistochemistry and markers of several endocytic compartments. NaPi-IIa removal from the BBM was detectable as early as 5 min after PTH injection. After 10–15 min, NaPi-IIa was localized in subapical compartments positive for clathrin. Shortly thereafter, NaPi-IIa appeared in endosomes stained for EEA1 (early endosomal antigen 1). After 45–60 min, NaPi-IIa was found in late endosomes/lysosomes marked with lgp120. In contrast, no change in the subcellular localization of megalin and the Na+/H+ exchanger NHE3 was detected up to 60 min after PTH injection. To further characterize the internalization route, insulin, as a marker for receptor-mediated endocytosis, and horseradish peroxidase (HRP) and fluorescein isothiocyanate (FITC)-dextran (10 kDa), as markers for fluid-phase mediated endocytosis, were used. NaPi-IIa colocalized with insulin 5–30 min after PTH injection but did not overlap with HRP or FITC-dextran. These results demonstrate a distinct internalization route of NaPi-IIa in response to acute PTH application that may involve the receptor-mediated endocytic pathway including clathrin-coated vesicles and EEA1-positive early endosomes, and routes NaPi-IIa to lysosomes for degradation.
One of the main diagnostic features of individuals with autism spectrum disorders is nonverbal behaviour difficulties during naturalistic social interactions. The 'Interactional Heterogeneity ...Hypothesis' of ASD proposes that the degree to which individuals share a common ground substantially influences their ability to achieve smooth social interactions.
To test this hypothesis, we filmed 29 autistic and 29 matched typically developed adults engaged in several conversational tasks. Windowed cross-lagged correlations were computed using the time series of motion energy of both individuals in a dyad. These coefficients were then compared across the three dyad types that were homo- or heterogenous with respect to diagnosis: pairs of two autistic individuals, two typically developed individuals or pairs of one autistic and one typically developed person.
We found that all dyad types achieved above-chance interpersonal synchrony, but that synchrony was more expressed in typical dyads compared to both autistic and mixed dyads.
The method presented here provides only one, albeit objective and robust, approach to explore synchrony. The methodological choices as well as the lack of consideration for other communication modalities may limit our interpretation of the findings. Moreover, the sample size is small with respect to exploring associations between synchrony and various outcome and social skill measures.
The present results do not provide support for the Interactional Heterogeneity Hypothesis given that autistic individuals do not coordinate better when interacting with another autistic individual, compared to when interacting with a typical individual.
Abstract Large Igneous Provinces (LIPs) are associated with global warming and carbon cycle perturbations during Oceanic Anoxic Event 2 (OAE2, ~94 Ma) and the Mid-Cenomanian Event (MCE, ~96.5 Ma). ...However, there is still no consensus on the role volcanism played as a trigger, or its source – previously ascribed to the Caribbean LIP or High Arctic LIP. Here, we use Mentelle Basin sedimentary mercury (Hg) concentrations to determine the timing of volcanism, and neodymium (Nd) and strontium (Sr) isotopes for sedimentary provenance. High Hg concentrations compared to Northern Hemisphere records, and a shift to radiogenic Nd isotopes, indicates Kerguelen LIP volcanic activity and plateau uplift occurred in the lead up to and within OAE2. Whilst we find limited evidence that a volcanic event caused the MCE, pulsed Hg spikes before and during OAE2 imply volcanic emissions were key in driving climate and carbon cycle changes and triggering OAE2.
Polyphosphate Is a Primordial Chaperone Gray, Michael J.; Wholey, Wei-Yun; Wagner, Nico O. ...
Molecular cell,
03/2014, Letnik:
53, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Composed of up to 1,000 phospho-anhydride bond-linked phosphate monomers, inorganic polyphosphate (polyP) is one of the most ancient, conserved, and enigmatic molecules in biology. Here we ...demonstrate that polyP functions as a hitherto unrecognized chaperone. We show that polyP stabilizes proteins in vivo, diminishes the need for other chaperone systems to survive proteotoxic stress conditions, and protects a wide variety of proteins against stress-induced unfolding and aggregation. In vitro studies reveal that polyP has protein-like chaperone qualities, binds to unfolding proteins with high affinity in an ATP-independent manner, and supports their productive refolding once nonstress conditions are restored. Our results uncover a universally important function for polyP and suggest that these long chains of inorganic phosphate may have served as one of nature’s first chaperones, a role that continues to the present day.
Display omitted
•Polyphosphate protects against proteotoxic oxidative stress conditions•Polyphosphate is a prebiotic and universally conserved molecular chaperone•Different-length polyphosphates differ in their chaperone efficacies•Polyphosphate accumulation is mediated by the redox-regulated enzyme PPX
Studies of bacterial resistance to proteotoxic stress reveal that inorganic polyphosphate functions as a chaperone, stabilizing unfolding proteins and preventing aggregation. Here, Gray et al. help uncover polyphosphate’s long known but largely unexplained role in protecting organisms against stress, and suggest that polyP may have served as one of nature’s first chaperones.
Summary
Nicotinamide adenine dinucleotide (NAD+) is an essential coenzyme required for all living organisms. In eukaryotic cells, the final step of NAD+ biosynthesis is exclusively cytosolic. Hence, ...NAD+ must be imported into organelles to support their metabolic functions. Three NAD+ transporters belonging to the mitochondrial carrier family (MCF) have been biochemically characterized in plants. AtNDT1 (At2g47490), focus of the current study, AtNDT2 (At1g25380), targeted to the inner mitochondrial membrane, and AtPXN (At2g39970), located in the peroxisomal membrane. Although AtNDT1 was presumed to reside in the chloroplast membrane, subcellular localization experiments with green fluorescent protein (GFP) fusions revealed that AtNDT1 locates exclusively in the mitochondrial membrane in stably transformed Arabidopsis plants. To understand the biological function of AtNDT1 in Arabidopsis, three transgenic lines containing an antisense construct of AtNDT1 under the control of the 35S promoter alongside a T‐DNA insertional line were evaluated. Plants with reduced AtNDT1 expression displayed lower pollen viability, silique length, and higher rate of seed abortion. Furthermore, these plants also exhibited an increased leaf number and leaf area concomitant with higher photosynthetic rates and higher levels of sucrose and starch. Therefore, lower expression of AtNDT1 was associated with enhanced vegetative growth but severe impairment of the reproductive stage. These results are discussed in the context of the mitochondrial localization of AtNDT1 and its important role in the cellular NAD+ homeostasis for both metabolic and developmental processes in plants.
Significance Statement
The mitochondrial NAD+ carrier (NDT1) plays an important role in cellular NAD+ homeostasis in leaves. Impaired NDT1 function results in reduced pollen grain viability, tube growth and seed filling, seed germination and seedling establishment.
The fate of insects in the Anthropocene has been widely discussed in the scientific literature, the popular media, and in policy circles. This recent attention is justified because reductions in ...insect abundance and diversity have the potential to undermine the stability of terrestrial ecosystems. Reports of insect declines have also been accompanied by skepticism that is healthy and to be expected in scientific discussion. However, we are concerned about a prevalent misconception that equates reports from monitored natural areas with the global status of insects. In the vast majority of cases, areas monitored for arthropods are undeveloped and thus do not record or even necessarily reflect the masses of insects that are continuously being impacted by habitat loss to urban, suburban and agricultural expansion. We address this misconception and discuss ways in which conservation and policy can be enhanced by correctly locating results from insect monitoring programs within our broader knowledge of biodiversity loss.
Craters on Ceres, such as Haulani, Kupalo, Ikapati, and Occator show postimpact modification by the deposition of extended plains material with pits, multiple lobate flows, and widely dispersed ...deposits that form a diffuse veneer on the preexisting surface. Bright material units in these features have a negative spectral slope in the visible range, making it appear bluish with respect to the grey‐toned overall surface of Ceres. We calculate the drop height‐to‐runout length ratio of several flow features and obtain a coefficient of friction of < 0.1: The results imply higher flow efficiency for flow features on Ceres than for similar features on other planetary bodies with similar gravity, suggesting low‐viscosity material. The special association of flow features with impact craters could either point to an impact melt origin or to an exogenic triggering of cryovolcanic processes.
Key Points
We analyzed the geomorphology several flows of craters to prove if they were formed by impact melt or cryovolcanic processes
The low coefficient of friction implies higher flow efficiency for flows on Ceres than for similar features on other planetary bodies
The formation of the flows could be due to the mobility of crustal subsurface reservoirs enriched with hydrated salts by impacts
Geographical parthenogenesis describes the enigmatic phenomenon that asexual organisms have larger distribution areas than their sexual relatives, especially in previously glaciated areas. Classical ...models suggest temporary advantages to asexuality in colonization scenarios because of uniparental reproduction and clonality. We analyzed population genetic structure and self-fertility of the plant species Ranunculus kuepferi on 59 populations from the whole distribution area (European Alps, Apennines and Corsica). Amplified fragment length polymorphisms (AFLPs) and five microsatellite loci revealed individual genotypes for all populations and mostly insignificant differences between diploid sexuals and tetraploid apomicts in all measures of genetic diversity. Low frequencies of private AFLP fragments/simple sequence repeat alleles, and character incompatibility analyses suggest that facultative recombination explains best the unexpectedly high genotypic diversity of apomicts. STRUCTURE analyses using AFLPs revealed a higher number of partitions and a stronger geographical subdivision for diploids than for tetraploids, which contradicts expectations of standard gene flow models, but indicates a reduction of genetic structure in asexuals. Apomictic populations exhibited high admixture near the sexual area, but appeared rather uniform in remote areas. Bagging experiments and analyses of pollen tube growth confirmed self-fertility for pollen-dependent apomicts, but self-sterility for diploid sexuals. Facultative apomixis combines advantages of both modes of reproduction: uniparental reproduction allows for rapid colonization of remote areas, whereas facultative sexuality and polyploidy maintains genetic diversity within apomictic populations. The density dependence of outcrossing limits range expansions of sexual populations.
The therapeutic benefits of dopamine (DA) agonists after traumatic brain injury (TBI) imply a role for DA systems in mediating functional deficits post‐TBI. We investigated how experimental TBI ...affects striatal dopamine systems using fast scan cyclic voltammetry (FSCV), western blot, and d‐amphetamine‐induced rotational behavior. Adult male Sprague–Dawley rats were injured by a controlled cortical impact (CCI) delivered unilaterally to the parietal cortex, or were naïve controls. Amphetamine‐induced rotational behavior was assessed 10 days post‐CCI. Fourteen days post‐CCI, animals were anesthetized and underwent FSCV with bilateral striatal carbon fiber microelectrode placement and stimulating electrode placement in the medial forebrain bundle (MFB). Evoked DA overflow was assessed in the striatum as the MFB was electrically stimulated at 60 Hz for 10 s. In 23% of injured animals, but no naïve animals, rotation was observed with amphetamine administration. Compared with naïves, striatal evoked DA overflow was lower for injured animals in the striatum ipsilateral to injury (p < 0.05). Injured animals exhibited a decrease in Vmax (52% of naïve, p < 0.05) for DA clearance in the hemisphere ipsilateral to injury compared with naïves. Dopamine transporter (DAT) expression was proportionally decreased in the striatum ipsilateral to injury compared with naïve animals (60% of naïve, p < 0.05), despite no injury‐related changes in vesicular monoamine transporter or D2 receptor expression (DRD2) in this region. Collectively, these data appear to confirm that the clinical efficacy of dopamine agonists in the treatment of TBI may be related to disruptions in the activity of subcortical dopamine systems.
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