Myosin-Vb functions as a dynamic tether for peripheral endocytic compartments during transferrin trafficking

<p>Abstract</p> <p>Background</p> <p>Myosin-Vb has been shown to be involved in the recycling of diverse proteins in multiple cell types. Studies on transferrin trafficking in HeLa cells using a dominant-negative myosin-Vb tail fragment suggested that myosin-Vb was required for recycling from perinuclear compartments to the plasma membrane. However, chemical-genetic, dominant-negative experiments, in which myosin-Vb was specifically induced to bind to actin, suggested that the initial hypothesis was incorrect both in its site and mode of myosin-Vb action. Instead, the chemical-genetic data suggested that myosin-Vb functions in the actin-rich periphery as a dynamic tether on peripheral endosomes, retarding transferrin transport to perinuclear compartments.</p> <p>Results</p> <p>In this study, we employed both approaches, with the addition of overexpression of full-length wild-type myosin-Vb and switching the order of myosin-Vb inhibition and transferrin loading, to distinguish between these hypotheses. Overexpression of full-length myosin-Vb produced large peripheral endosomes. Chemical-genetic inhibition of myosin-Vb after loading with transferrin did not prevent movement of transferrin from perinuclear compartments; however, virtually all myosin-Vb-decorated particles, including those moving on microtubules, were halted by the inhibition. Overexpression of the myosin-Vb tail caused a less-peripheral distribution of early endosome antigen-1 (EEA1).</p> <p>Conclusion</p> <p>All results favored the peripheral dynamic tethering hypothesis.</p

Structure and deformation of the Kermadec forearc in response to subduction of the Pacific oceanic plate

The Tonga-Kermadec forearc is deforming in response to on-going subduction of the Pacific Plate beneath the Indo-Australian Plate. Previous research has focussed on the structural development of the forearc where large bathymetric features such as the Hikurangi Plateau and Louisville Ridge seamount chain are being subducted. Consequently, knowledge of the ‘background’ forearc in regions of normal plate convergence is limited. We report on an ∼250-km-long multichannel seismic reflection profile that was shot perpendicular to the Tonga-Kermadec trench at ∼28°S to determine the lateral and temporal variations in the structure, stratigraphy and deformation of the Kermadec forearc resulting solely from Pacific Plate subduction. Interpretation of the seismic profile, in conjunction with regional swath bathymetry data, shows that the Pacific Plate exhibits horst and graben structures that accommodate bending-induced extensional stresses, generated as the trenchward dip of the crust increases. Trench infill is also much thicker than expected at 1 km which, we propose, results from increased sediment flux into and along the trench. Pervasive normal faulting of the mid-trench slope most likely accommodates the majority of the observed forearc extension in response to basal subduction erosion, and a structural high is located between the mid- and upper-trench slopes. We interpret this high as representing a dense and most likely structurally robust region of crust lying beneath this region. Sediment of the upper-trench slope documents depositional hiatuses and on-going uplift of the arc. Strong along-arc currents appear to erode the Kermadec volcanic arc and distribute this sediment to the surrounding basins, while currents over the forearc redistribute deposits as sediment waves. Minor uplift of the transitional Kermadec forearc, observed just to the north of the profile, appears to relate to an underlying structural trend as well as subduction of the Louisville Ridge seamount chain 250 km to the north. Relative uplift of the Kermadec arc is observed from changes in the tilt of upper-trench slope deposits and extensional faulting of the basement immediately surrounding the Louisville Ridge

Synergistic Effect of Multi-Walled Carbon Nanotubes and Ladder-Type Conjugated Polymers on the Performance of N-Type Organic Electrochemical Transistors

Organic electrochemical transistors (OECTs) have the potential to revolutionize the field of organic bioelectronics. To date, most of the reported OECTs include p-type (semi-)conducting polymers as the channel material, while n-type OECTs are yet at an early stage of development, with the best performing electron-transporting materials still suffering from low transconductance, low electron mobility, and slow response time. Here, the high electrical conductivity of multi-walled carbon nanotubes (MWCNTs) and the large volumetric capacitance of the ladder-type π-conjugated redox polymer poly(benzimidazobenzophenanthroline) (BBL) are leveraged to develop n-type OECTs with record-high performance. It is demonstrated that the use of MWCNTs enhances the electron mobility by more than one order of magnitude, yielding fast transistor transient response (down to 15\ua0ms) and high μC* (electron mobility 7 volumetric capacitance) of about 1 F cm−1\ua0V−1 s−1. This enables the development of complementary inverters with a voltage gain of &gt;16 and a large worst-case noise margin at a supply voltage of &lt;0.6\ua0V, while consuming less than 1 \ub5W of power

The psychological science accelerator’s COVID-19 rapid-response dataset

In response to the COVID-19 pandemic, the Psychological Science Accelerator coordinated three large-scale psychological studies to examine the effects of loss-gain framing, cognitive reappraisals, and autonomy framing manipulations on behavioral intentions and affective measures. The data collected (April to October 2020) included specific measures for each experimental study, a general questionnaire examining health prevention behaviors and COVID-19 experience, geographical and cultural context characterization, and demographic information for each participant. Each participant started the study with the same general questions and then was randomized to complete either one longer experiment or two shorter experiments. Data were provided by 73,223 participants with varying completion rates. Participants completed the survey from 111 geopolitical regions in 44 unique languages/dialects. The anonymized dataset described here is provided in both raw and processed formats to facilitate re-use and further analyses. The dataset offers secondary analytic opportunities to explore coping, framing, and self-determination across a diverse, global sample obtained at the onset of the COVID-19 pandemic, which can be merged with other time-sampled or geographic data.info:eu-repo/semantics/publishedVersio

Are Small Effects the Indispensable Foundation for a Cumulative Psychological Science? A Reply to Götz et al. (2022).

Götz et al. (2022) argue that small effects are “the indispensable foundation for a cumulative psychological science”. They support their argument by claiming that (i) psychology, like genetics, consists of complex phenomena explained by additive small effects, (ii) psychological research culture rewards large effects, which means small effects are being ignored, and (iii) small effects become meaningful at scale and over time. We rebut these claims with three objections: (i) the analogy between genetics and psychology is misleading, (ii) p-values are the main currency for publication in psychology, meaning that any biases in the literature are (currently) caused by a pressure to publish statistically significant results and not large effects, and (iii) claims regarding small effects as important and consequential must be supported by empirical evidence or, at least, a falsifiable line of reasoning. If accepted uncritically, we believe the arguments of Götz et al. (2022) could be used as a blanket justification for the importance of any and all ‘small’ effects, thereby undermining best practices in effect size interpretation. We end with guidance on evaluating effect sizes in relative, not absolute terms

Walker-Warburg syndrome

Walker-Warburg Syndrome (WWS) is a rare form of autosomal recessive congenital muscular dystrophy associated with brain and eye abnormalities. WWS has a worldwide distribution. The overall incidence is unknown but a survey in North-eastern Italy has reported an incidence rate of 1.2 per 100,000 live births. It is the most severe form of congenital muscular dystrophy with most children dying before the age of three years. WWS presents at birth with generalized hypotonia, muscle weakness, developmental delay with mental retardation and occasional seizures. It is associated with type II cobblestone lissencephaly, hydrocephalus, cerebellar malformations, eye abnormalities and congenital muscular dystrophy characterized by hypoglycosylation of α-dystroglycan. Several genes have been implicated in the etiology of WWS, and others are as yet unknown. Several mutations were found in the Protein O-Mannosyltransferase 1 and 2 (POMT1 and POMT2) genes, and one mutation was found in each of the fukutin and fukutin-related protein (FKRP) genes. Laboratory investigations usually show elevated creatine kinase, myopathic/dystrophic muscle pathology and altered α-dystroglycan. Antenatal diagnosis is possible in families with known mutations. Prenatal ultrasound may be helpful for diagnosis in families where the molecular defect is unknown. No specific treatment is available. Management is only supportive and preventive

The Psychological Science Accelerator's COVID-19 rapid-response dataset

In response to the COVID-19 pandemic, the Psychological Science Accelerator coordinated three large-scale psychological studies to examine the effects of loss-gain framing, cognitive reappraisals, and autonomy framing manipulations on behavioral intentions and affective measures. The data collected (April to October 2020) included specific measures for each experimental study, a general questionnaire examining health prevention behaviors and COVID-19 experience, geographical and cultural context characterization, and demographic information for each participant. Each participant started the study with the same general questions and then was randomized to complete either one longer experiment or two shorter experiments. Data were provided by 73,223 participants with varying completion rates. Participants completed the survey from 111 geopolitical regions in 44 unique languages/dialects. The anonymized dataset described here is provided in both raw and processed formats to facilitate re-use and further analyses. The dataset offers secondary analytic opportunities to explore coping, framing, and self-determination across a diverse, global sample obtained at the onset of the COVID-19 pandemic, which can be merged with other time-sampled or geographic data

The Psychological Science Accelerator: Advancing Psychology Through a Distributed Collaborative Network

Source at https://doi.org/10.1177/2515245918797607.Concerns about the veracity of psychological research have been growing. Many findings in psychological science are based on studies with insufficient statistical power and nonrepresentative samples, or may otherwise be limited to specific, ungeneralizable settings or populations. Crowdsourced research, a type of large-scale collaboration in which one or more research projects are conducted across multiple lab sites, offers a pragmatic solution to these and other current methodological challenges. The Psychological Science Accelerator (PSA) is a distributed network of laboratories designed to enable and support crowdsourced research projects. These projects can focus on novel research questions or replicate prior research in large, diverse samples. The PSA’s mission is to accelerate the accumulation of reliable and generalizable evidence in psychological science. Here, we describe the background, structure, principles, procedures, benefits, and challenges of the PSA. In contrast to other crowdsourced research networks, the PSA is ongoing (as opposed to time limited), efficient (in that structures and principles are reused for different projects), decentralized, diverse (in both subjects and researchers), and inclusive (of proposals, contributions, and other relevant input from anyone inside or outside the network). The PSA and other approaches to crowdsourced psychological science will advance understanding of mental processes and behaviors by enabling rigorous research and systematic examination of its generalizability

The psychological science accelerator’s COVID-19 rapid-response dataset

In response to the COVID-19 pandemic, the Psychological Science Accelerator coordinated three large-scale psychological studies to examine the effects of loss-gain framing, cognitive reappraisals, and autonomy framing manipulations on behavioral intentions and affective measures. The data collected (April to October 2020) included specific measures for each experimental study, a general questionnaire examining health prevention behaviors and COVID-19 experience, geographical and cultural context characterization, and demographic information for each participant. Each participant started the study with the same general questions and then was randomized to complete either one longer experiment or two shorter experiments. Data were provided by 73,223 participants with varying completion rates. Participants completed the survey from 111 geopolitical regions in 44 unique languages/dialects. The anonymized dataset described here is provided in both raw and processed formats to facilitate re-use and further analyses. The dataset offers secondary analytic opportunities to explore coping, framing, and self-determination across a diverse, global sample obtained at the onset of the COVID-19 pandemic, which can be merged with other time-sampled or geographic data