Emotional processing and Social Cognition in Amyotrophic Lateral Sclerosis

Building on evidence for cognitive-behavioural change in people with Amyotrophic Lateral Sclerosis (ALS), the current study uses a range of neuropsychological measures to delineate the nature and scope of reported deficits in emotional processing and social cognition in people with ALS. Compared to the healthy control group, the ALS group was impaired on composite scores indexing executive function and performance on the emotional processing and social cognition tasks. Single-case analyses revealed that ALS patients showed heterogeneous performance across the cognitive tasks

Deriving a Provisional Tolerable Intake for Intravenous Exposure to Silver Nanoparticles Released from Medical Devices

Silver nanoparticles (AgNP) are incorporated into medical devices for their anti-microbial characteristics. The potential exposure and toxicity of AgNPs is unknown due to varying physicochemical particle properties and lack of toxicological data. The aim of this safety assessment is to derive a provisional tolerable intake (pTI) value for AgNPs released from blood-contacting medical devices. A literature review of in vivo studies investigating critical health effects induced from intravenous (i. v.) exposure to AgNPs was evaluated by the Annapolis Accords principles and Toxicological Data Reliability Assessment Tool (ToxRTool). The point of departure (POD) was based on an i. v. 28-day repeated AgNP (20 nm) dose toxicity study reporting an increase in relative spleen weight in rats with a 5% lower confidence bound of the benchmark dose (BMDL05) of 0.14 mg/kg bw/day. The POD was extrapolated to humans by a modifying factor of 1,000 to account for intraspecies variability, interspecies differences and lack of long-term toxicity data. The pTI for long-term i. v. exposure to 20 nm AgNPs released from blood-contacting medical devices was 0.14 μg/kg bw/day. This pTI may not be appropriate for nanoparticles of other physicochemical properties or routes of administration. The methodology is appropriate for deriving pTIs for nanoparticles in general

Multi-monoubiquitylation controls VASP-mediated actin dynamics Icon for The Forest of Biologists

The actin cytoskeleton performs multiple cellular functions, and as such, actin polymerization must be tightly regulated. We previously demonstrated that reversible, non-degradative ubiquitylation regulates the function of the actin polymerase VASP in developing neurons. However, the underlying mechanism of how ubiquitylation impacts VASP activity was unknown. Here, we show that mimicking multi-monoubiquitylation of VASP at K240 and K286 negatively regulates VASP interactions with actin. Using in vitro biochemical assays, we demonstrate the reduced ability of multi-monoubiquitylated VASP to bind, bundle, and elongate actin filaments. However, multi-monoubiquitylated VASP maintained the ability to bind and protect barbed ends from capping protein. Finally, we demonstrate the electroporation of recombinant multi-monoubiquitylated VASP protein altered cell spreading morphology. Collectively, these results suggest a mechanism in which ubiquitylation controls VASP-mediated actin dynamics

Simulations of imperfect refractive index matching in scanning laser optical tomography and a method for correction

Since additive manufacturing has become increasingly popular in prototyping, printed optics are also beginning to enter the market. Novel characterization methods for printed optics are needed because traditional, destructive methods often do not work on these optics. The scope of investigation is also different for additively manufactured optics. Homogeneity of subtractive manufactured optics such as glass lenses is usually granted but for printed optics the interfaces in-between layers can cause absorption, scattering or refraction. Functionalized optics can also have characteristics such as fluorescence that cannot be tested with traditional methods. The presented work tries to fill the void for this particular challenge by studying two non-destructive methods for optical characterization of such components and expanding their use by clever combination. In Scanning Laser Optical Tomography (SLOT), a needle-like beam is formed and focused into the sample. The sample is scanned to form projection images and rotated to allow for reconstruction, which yields volumetric data about scattering, transmission and fluorescence of sample structures. Simulated SLOT measurements with imperfect Refractive Index (RI) matching of sample and medium are presented. A method to correct distorted measurements is presented and evaluated. The simulations imply that a measurement with a RI mismatch of up to 0.1 can still yield reasonable results. Copyright 2023 Society of Photo-Optical Instrumentation Engineers. One print or electronic copy may be made for personal use only. Systematic reproduction and distribution, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper are prohibited

Circadian Variations in Blood Pressure, Heart Rate, and HR-BP Cross-Correlation Coefficient during Progression of Diabetes Mellitus in Rat

Circadian changes in cardiovascular function during the progression of diabetes mellitus in the diabetes prone rat (BBDP) (n = 8) were studied. Age-matched diabetes-resistant rats (BBDR) served as controls. BP was recorded via telemetry in contiguous 4 hr time periods over 24 hours starting with 12 midnight to 4 am as period zero (P0). Prior to onset of diabetes BP was high at P0, peaked at P2, and then fell again at P3; BP and heart rate (HR) then increased gradually at P4 and leveled off at P5, thereby exhibiting a bipodal rhythm. These patterns changed during long-term diabetes. The cross-correlation coefficient of BP and HR was not significantly different across groups at onset, but it fell significantly at 9 months of duration of diabetes (BBDP: 0.39 ± 0.06; BBDR: 0.65 ± 0.03; P < .05). These results show that changes in circadian cardiovascular rhythms in diabetes mellitus became significant at the late stage of the disease

Loss of the <i>Arabidopsis thaliana</i> P4-ATPases ALA6 and ALA7 impairs pollen fitness and alters the pollen tube plasma membrane

Members of the P4 subfamily of P-type ATPases are thought to create and maintain lipid asymmetry in biological membranes by flipping specific lipids between membrane leaflets. In Arabidopsis, 7 of the 12 Aminophospholipid ATPase (ALA) family members are expressed in pollen. Here we show that double knockout of ALA6 and ALA7 (ala6/7) results in siliques with a ~2-fold reduction in seed set with a high frequency of empty seed positions near the bottom. Seed set was reduced to near zero when plants were grown under a hot/cold temperature stress. Reciprocal crosses indicate that the ala6/7 reproductive deficiencies are due to a defect related to pollen transmission. In-vitro growth assays provide evidence that that ala6/7 pollen tubes are short and slow, with ~2-fold reductions in both maximal growth rate and overall length relative to wild-type. Outcrosses show that when ala6/7 pollen are in competition with wild-type pollen, they have a near 0% success rate in fertilizing ovules near the bottom of the pistil, consistent with ala6/7 pollen having short and slow growth defects. The ala6/7 phenotypes were rescued by the expression of either an ALA6-YFP or GFP-ALA6 fusion protein, which showed localization to both the plasma membrane and highly-mobile endomembrane structures. A mass spectrometry analysis of mature pollen grains revealed significant differences between ala6/7 and wild-type, both in the relative abundance of lipid classes and in the average number of double bonds present in acyl side chains. A change in the properties of the ala6/7 plasma membrane was also indicated by a ~10-fold reduction of labeling by lipophilic FM-dyes relative to wild-type. Together, these results indicate that ALA6 and ALA7 provide redundant activities that function to directly or indirectly change the distribution and abundance lipids in pollen, and support a model in which ALA6 and ALA7 are critical for pollen fitness under normal and temperature-stress conditions

Tomographic Separation of Composite Spectra. VIII. The Physical Properties of the Massive Compact Binary in the Triple Star System HD 36486 (delta Orionis A)

Double-lined spectroscopic orbital elements have recently been found for the central binary in the massive triple, delta Orionis A based on radial velocities from cross-correlation techniques applied to IUE high dispersion spectra and He I 6678 spectra obtained at Kitt Peak. The primary and secondary velocity amplitudes were found to be 94.9 +/- 0.6 km/s and 186 +/- 9 km/s respectively. Tomographic reconstructions of the primary and secondary stars' spectra confirm the O9.5 II classification of the primary and indicate a B0.5 III type for the secondary. The widths of the UV cross-correlation functions are used to estimate the projected rotational velocities, Vsin i = 157 +/- 6 km/s and 138 +/- 16 km/s for the primary and secondary, respectively implying that both stars rotate faster than their orbital motion. We used the spectroscopic results to make a constrained fit of the Hipparcos light curve of this eclipsing binary, and the model fits limit the inclination to the range between 67 and 77 degrees. The i = 67 degrees solution, which corresponds to a near Roche-filling configuration, results in a primary mass of 11.2 solar masses and a secondary mass of 5.6 solar masses, both of which are substantially below the expected masses for stars of their luminosity. This binary may have experienced a mass ratio reversal caused by Case A Roche lobe overflow, or the system may have suffered extensive mass loss through a binary interaction, perhaps during a common envelope phase, in which most of the primary's mass was lost from the system rather than transferred to the secondary.Comment: 27 pages, 15 figures in press, the Astrophysical Journal, February 1, 200

Reporting to parents on children’s exposures to asthma triggers in low-income and public housing, an interview-based case study of ethics, environmental literacy, individual action, and public health benefits

Background Emerging evidence about the effects of endocrine disruptors on asthma symptoms suggests new opportunities to reduce asthma by changing personal environments. Right-to-know ethics supports returning personal results for these chemicals to participants, so they can make decisions to reduce exposures. Yet researchers and institutional review boards have been reluctant to approve results reports in low-income communities, which are disproportionately affected by asthma. Concerns include limited literacy, lack of resources to reduce exposures, co-occurring stressors, and lack of models for effective reporting. To better understand the ethical and public health implications of returning personal results in low-income communities, we investigated parents’ experiences of learning their children’s environmental chemical and biomonitoring results in the Green Housing Study of asthma. Methods The Green Housing Study measured indoor chemical exposures, allergens, and children’s asthma symptoms in “green”-renovated public housing and control sites in metro-Boston and Cincinnati in 2011–2013. We developed reports for parents of children in the study, including results for their child and community. We observed community meetings where results were reported, and metro-Boston residents participated in semi-structured interviews in 2015 about their report-back experience. Interviews were systematically coded and analyzed. Results Report-back was positively received, contributed to greater understanding, built trust between researchers and participants, and facilitated action to improve health. Sampling visits and community meetings also contributed to creating a positive study experience for participants. Participants were able to make changes in their homes, such as altering product use and habits that may reduce asthma symptoms, though some faced roadblocks from family members. Participants also gained access to medical resources, though some felt that clinicians were not responsive. Participants wanted larger scale change from government or industry and wanted researchers to leverage study results to achieve change. Conclusions Report-back on environmental chemical exposures in low-income communities can enhance research benefits by engaging residents with personally relevant information that informs and motivates actions to reduce exposure to asthma triggers. Ethical practices in research should support deliberative report-back in vulnerable communities