Aging entails a progressive decline in protein homeostasis, which often leads to age-related diseases. The endoplasmic reticulum (ER) is the site of protein synthesis and maturation for secreted and ...membrane proteins. Correct folding of ER proteins requires covalent attachment of N-linked glycan oligosaccharides. Here, we report that increased synthesis of N-glycan precursors in the hexosamine pathway improves ER protein homeostasis and extends lifespan in C. elegans. Addition of the N-glycan precursor N-acetylglucosamine to the growth medium slows aging in wild-type animals and alleviates pathology of distinct neurotoxic disease models. Our data suggest that reduced aggregation of metastable proteins and lifespan extension depend on enhanced ER-associated protein degradation, proteasomal activity, and autophagy. Evidently, hexosamine pathway activation or N-acetylglucosamine supplementation induces distinct protein quality control mechanisms, which may allow therapeutic intervention against age-related and proteotoxic diseases.
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•Hexosamine pathway activation leads to ER stress resistance and longevity•Supplementation with N-glycan precursor GlcNAc extends wild-type lifespan•Increased HP activity elevates ERAD, proteasome activity, and autophagy•GlcNAc treatment suppresses proteotoxicity of different metastable proteins
Increasing the levels of N-glycan precursors such as GlcNAc activates the hexosamine pathway, which, in turn, leads to improved cellular proteostasis and enhanced longevity.
Predation risk has long been known to exert a strong influence on behavior, but no study to date has determined whether predators influence offspring antipredator behavior via maternal effects. Here, ...we provide a unique example of a transgenerational maternal effect in antipredator behavior that takes the form of a “warning” about predators that female fall field cricketsGryllus pennsylvanicustransmit to their offspring. Specifically, the offspring of gravid crickets exposed to a wolf spiderHogna helluoexhibit greater antipredator immobility in response toHognachemical cues than do offspring of nonexposed females. These “forewarned” crickets exhibit greater survival in the presence ofHognathan do those not forewarned. Accordingly, gravid crickets from areas with significantHognapopulations produce offspring that are more responsive toHognacues than do those from nearbyHogna‐free areas. Such transgenerational maternal effects may be more common than currently realized.
We report experiments and modeling of translocation of double-strand DNA through a siliconoxide nanopore. Long DNA molecules with different lengths ranging from 6500 to 97000 base pairs have been ...electrophoretically driven through a 10 nm pore. We observe a power-law scaling of the translocation time with the length, with an exponent of 1.27. This nonlinear scaling is strikingly different from the well-studied linear behavior observed in similar experiments performed on protein pores. We present a theoretical model where hydrodynamic drag on the section of the polymer outside the pore is the dominant force counteracting the electrical driving force. We show that this applies to our experiments, and we derive a power-law scaling with an exponent of 1.22, in good agreement with the data.
Summary
The realistic representation of material degradation at a fully evolved crack is still one of the main challenges of the phase‐field method for fracture. An approach with realistic ...degradation behavior is only available for isotropic elasticity in the small deformation framework. In this paper, a variational framework is presented for the standard phase‐field formulation, which allows to derive the kinematically consistent material degradation. For this purpose, the concept of representative crack elements (RCE) is introduced to analyze the fully degraded material state. The realistic material degradation is further tested using the self‐consistency condition, where the behavior of the phase‐field model is compared to a discrete crack model. The framework is applied to isotropic elasticity, anisotropic elasticity and thermo‐elasticity, but not restricted to these constitutive formulations.
In cases of sexual assault, the interpretation of biological traces on clothing, and particularly undergarments, may be complex. This is especially so when the complainant and defendant interact ...socially, for instance as (ex-)partners or by co-habitation. Here we present the results from a study where latent male DNA on female worn undergarments is recovered in four groups with different levels of male-female social interaction. The results conform to prior expectation, in that less interaction tend to result in less male DNA on undergarments. We explore the use of these experimental data for evaluative reporting given activity level propositions in a mock case scenario. We show how the selection of different populations to represent the social interaction between complainant and defendant may affect the strength of the evidence. We further show how datasets of limited size can be used for robust activity level evaluative reporting.
•Prevalence of male DNA on female worn brassieres and underpants was studied.•Four different living situations of female volunteers are compared.•As expected more male DNA is found in closer female-male interaction•Individual female behaviours affect prevalent male DNA more strongly than living conditions.•Small datasets on DNA TPPR can be used to support robust conclusions in activity level evaluative reports.
The phase-field formulation for fracture based on the framework of representative crack elements is extended to transient thermo-mechanics. The finite element formulation is derived starting from the ...variational principle of total virtual power. The intention of this manuscript is to demonstrate the potential of the framework for multi-physical fracture models and complex processes inside the crack. The present model at hand allows to predict realistic deformation kinematics and heat fluxes at cracks. At the application of fully coupled, transient thermo-elasticity to a pre-cracked plate, the opened crack yields thermal isolation between both parts of the plate. Inhomogeneous thermal strains result in a curved crack surface, inhomogeneous recontact and finally heat flow through the crack regions in contact. The novel phase-field framework further allows to study processes inside the crack, which is demonstrated by heat radiation between opened crack surfaces. Finally, numerically calculated crack paths at a disc subjected to thermal shock load are compared to experimental results from literature and a curved crack in a three-dimensional application are presented.
The pseudo-ductile material behavior of fiber reinforced high performance concrete is mainly characterized by the fiber pullout process. Thereby, complex fiber–concrete interactions, i.e. interface ...debonding, concrete micro cracks, slippage, adhesion and further unknown processes, are commonly investigated in single-fiber pullout tests. The study in this contribution is based on the experimental results of Gebuhr etal., (2019) and compares three different numerical models applied to the fiber pullout test. An accurate and efficient model for fiber pullout behavior forms the basis for the prediction of the overall behavior by means of composite models or multi-scale approaches in subsequent studies.
•Three different numerical models applied to fiber pullout test are compared.•The study is based on the experimental results of Gebuhr etal., (2019).•Simulations methods are phase-field fracture, cohesive interface and a super-element.
Direct imaging of impressed dc currents inside the head can provide valuable conductivity information, possibly improving electro-magnetic neuroimaging. Ultra-low field magnetic resonance imaging ...(ULF MRI) at μT Larmor fields can be utilized for current density imaging (CDI). Here, a measurable impact of the magnetic field BJ, generated by the impressed current density J, on the MR signal is probed using specialized sequences. In contrast to high-field MRI, the full tensor of BJ can be derived without rotation of the subject in the scanner, due to a larger flexibility in the sequence design.
We present an ULF MRI setup based on a superconducting quantum interference device (SQUID), which is operating at a noise level of 380 aT Hz−1/2 and capable of switching all imaging fields within a pulse sequence. Thereby, the system enables zero-field encoding, where the full tensor of BJ is probed in the absence of other magnetic fields. 3D CDI is demonstrated on phantoms with different geometries carrying currents of approximately 2 mA corresponding to current densities between 0.45 and 8 A/m2. By comparison to an in vivo acquired head image, we provide insights to necessary improvements in signal-to-noise ratio.
Chronic wasting disease (CWD) is a fatal neurodegenerative disease caused by infectious prions (PrP
) affecting cervids. Circulating PrP
in blood may pose a risk for indirect transmission by way of ...hematophagous ectoparasites acting as mechanical vectors. Cervids can carry high tick infestations and exhibit allogrooming, a common tick defense strategy between conspecifics. Ingestion of ticks during allogrooming may expose naïve animals to CWD, if ticks harbor PrP
. This study investigates whether ticks can harbor transmission-relevant quantities of PrP
by combining experimental tick feeding trials and evaluation of ticks from free-ranging white-tailed deer (Odocoileus virginianus). Using the real-time quaking-induced conversion (RT-QuIC) assay, we show that black-legged ticks (Ixodes scapularis) fed PrP
-spiked blood using artificial membranes ingest and excrete PrP
. Combining results of RT-QuIC and protein misfolding cyclic amplification, we detected seeding activity from 6 of 15 (40%) pooled tick samples collected from wild CWD-infected white-tailed deer. Seeding activities in ticks were analogous to 10-1000 ng of CWD-positive retropharyngeal lymph node collected from deer upon which they were feeding. Estimates revealed a median infectious dose range of 0.3-42.4 per tick, suggesting that ticks can take up transmission-relevant amounts of PrP
and may pose a CWD risk to cervids.
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