Neural Substrates of Attentive Listening Assessed with a Novel Auditory Stroop Task

A common explanation for the interference effect in the classic visual Stroop test is that reading a word (the more automatic semantic response) must be suppressed in favor of naming the text color (the slower sensory response). Neuroimaging studies also consistently report anterior cingulate/medial frontal, lateral prefrontal, and anterior insular structures as key components of a network for Stroop-conflict processing. It remains unclear, however, whether automatic processing of semantic information can explain the interference effect in other variants of the Stroop test. It also is not known if these frontal regions serve a specific role in visual Stroop conflict, or instead play a more universal role as components of a more generalized, supramodal executive-control network for conflict processing. To address these questions, we developed a novel auditory Stroop test in which the relative dominance of semantic and sensory feature processing is reversed. Listeners were asked to focus either on voice gender (a more automatic sensory discrimination task) or on the gender meaning of the word (a less automatic semantic task) while ignoring the conflicting stimulus feature. An auditory Stroop effect was observed when voice features replaced semantic content as the “to-be-ignored” component of the incongruent stimulus. Also, in sharp contrast to previous Stroop studies, neural responses to incongruent stimuli studied with functional magnetic resonance imaging revealed greater recruitment of conflict loci when selective attention was focused on gender meaning (semantic task) over voice gender (sensory task). Furthermore, in contrast to earlier Stroop studies that implicated dorsomedial cortex in visual conflict processing, interference-related activation in both of our auditory tasks was localized ventrally in medial frontal areas, suggesting a dorsal-to-ventral separation of function in medial frontal cortex that is sensitive to stimulus context

RECAST: Extending the Impact of Existing Analyses

Searches for new physics by experimental collaborations represent a significant investment in time and resources. Often these searches are sensitive to a broader class of models than they were originally designed to test. We aim to extend the impact of existing searches through a technique we call 'recasting'. After considering several examples, which illustrate the issues and subtleties involved, we present RECAST, a framework designed to facilitate the usage of this technique.Comment: 13 pages, 4 figure

Frontotemporal lobar dementia mutant tau impairs axonal transport through a protein phosphatase 1γ-dependent mechanism

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Combs, B., Christensen, K. R., Richards, C., Kneynsberg, A., Mueller, R. L., Morris, S. L., Morfini, G., Brady, S. T., & Kanaan, N. M. Frontotemporal lobar dementia mutant tau impairs axonal transport through a protein phosphatase 1γ-dependent mechanism. Journal of Neuroscience, 41(45), (2021): 9431-9451, https://doi.org/10.1523/JNEUROSCI.1914-20.2021.Pathologic tau modifications are characteristic of Alzheimer's disease and related dementias, but mechanisms of tau toxicity continue to be debated. Inherited mutations in tau cause early onset frontotemporal lobar dementias (FTLD-tau) and are commonly used to model mechanisms of tau toxicity in tauopathies. Previous work in the isolated squid axoplasm model demonstrated that several pathogenic forms of tau inhibit axonal transport through a mechanism involving activation of protein phosphatase 1 (PP1). Here, we determined that P301L and R5L FTLD mutant tau proteins elicit a toxic effect on axonal transport as monomeric proteins. We evaluated interactions of wild-type or mutant tau with specific PP1 isoforms (α, β, and γ) to examine how the interaction contributes to this toxic effect using primary rat hippocampal neurons from both sexes. Pull-down and bioluminescence resonance energy transfer experiments revealed selective interactions of wild-type tau with PP1α and PP1γ isoforms, but not PP1β, which were significantly increased by the P301L tau mutation. The results from proximity ligation assays confirmed the interaction in primary hippocampal neurons. Moreover, expression of FTLD-linked mutant tau in these neurons enhanced levels of active PP1, also increasing the pausing frequency of fluorescently labeled vesicles in both anterograde and retrograde directions. Knockdown of PP1γ, but not PP1α, rescued the cargo-pausing effects of P301L and R5L tau, a result replicated by deleting a phosphatase-activating domain in the amino terminus of P301L tau. These findings support a model of tau toxicity involving aberrant activation of a specific PP1γ-dependent pathway that disrupts axonal transport in neurons.This work was supported by National Institutes of Health (NIH) Grants R01 NS082730 (N.M.K. and S.T.B.), R01 AG044372 (N.M.K.), and R01 AG067762 (N.M.K.); NIH/National Institute on Aging, Michigan Alzheimer's Disease Research Center Grant 5P30AG053760 (B.C.); Office of the Assistant Secretary of Defense for Health Affairs through the Peer Reviewed Alzheimer's Research Program Award W81XWH-20-1-0174 (B.C.); Alzheimer's Association Research Grants 20-682085 (B.C.), R01 NS118177 (G.A.M.), and R21NS120126 (G.A.M.); Zenith Award from the Alzheimer's Association (S.T.B.); Tau Consortium/Rainwater Foundation (S.T.B.); Neurodegenerative Research (G.A.M.); and the Secchia Family Foundation (N.M.K.)

A Compact Cold-Atom Interferometer with a High Data-Rate Grating Magneto-Optical Trap and a Photonic-Integrated-Circuit-Compatible Laser System

The extreme miniaturization of a cold-atom interferometer accelerometer requires the development of novel technologies and architectures for the interferometer subsystems. Here we describe several component technologies and a laser system architecture to enable a path to such miniaturization. We developed a custom, compact titanium vacuum package containing a microfabricated grating chip for a tetrahedral grating magneto-optical trap (GMOT) using a single cooling beam. In addition, we designed a multi-channel photonic-integrated-circuit-compatible laser system implemented with a single seed laser and single sideband modulators in a time-multiplexed manner, reducing the number of optical channels connected to the sensor head. In a compact sensor head containing the vacuum package, sub-Doppler cooling in the GMOT produces 15 uK temperatures, and the GMOT can operate at a 20 Hz data rate. We validated the atomic coherence with Ramsey interferometry using microwave spectroscopy, then demonstrated a light-pulse atom interferometer in a gravimeter configuration for a 10 Hz measurement data rate and T = 0 - 4.5 ms interrogation time, resulting in $\Delta$ g / g = 2.0e-6. This work represents a significant step towards deployable cold-atom inertial sensors under large amplitude motional dynamics.Comment: 21 pages, 10 figure

A new portable vibrator for plaster pouring: effect on the marginal fit at cylinder-abutment

OBJECTIVE: The aim of this study was to test a new portable vibrator for plaster pouring (developed for this purpose), comparing the effect of its use on the accuracy of working cast of implant-supported restorations to the conventional vibrator. MATERIAL AND METHODS: From a master cast with 2 implants, 30 transfer moldings were made randomly and divided into three groups: Group I (GI): pouring performed in an outsourced dental laboratory with conventional plaster vibrator (10 casts), Group II (GII): pouring performed in the laboratory of the Federal University of Santa Catarina (UFSC) with conventional plaster vibrator (10 casts) and Group III (GIII): pouring performed with the portable vibrator fabricated for this study (10 casts). The position of the analogue and marginal adaptation of the infrastructure were verified by testing the single screw on the master model and on the working model. The measurement of misfit was blindly performed with a precision microscope and analyzing unit, Quadra-Check 200. The data were statistically analyzed by analysis of variance (ANOVA) and the Holm-Sidak test (α=0.05). RESULTS: Means±standard deviations were as follows: GI: 19.19±4.73 µm; GII: 21.72±5.41 µm; GIII: 13.5±2.39 µm (P<0.05), with GIII significantly lower as compared to the other groups. CONCLUSION: Within the limitations of this study, it was concluded that a greater accuracy of working cast was achieved when a portable vibrator was used for casting molds

Pathogenic MAST3 Variants in the STK Domain Are Associated with Epilepsy

Objective: The MAST family of microtubule-associated serine–threonine kinases (STKs) have distinct expression patterns in the developing and mature human and mouse brain. To date, only MAST1 has been conclusively associated with neurological disease, with de novo variants in individuals with a neurodevelopmental disorder, including a mega corpus callosum. Methods: Using exome sequencing, we identify MAST3 missense variants in individuals with epilepsy. We also assess the effect of these variants on the ability of MAST3 to phosphorylate the target gene product ARPP-16 in HEK293T cells. Results: We identify de novo missense variants in the STK domain in 11 individuals, including 2 recurrent variants p.G510S (n = 5) and p.G515S (n = 3). All 11 individuals had developmental and epileptic encephalopathy, with 8 having normal development prior to seizure onset at \u3c2 years of age. All patients developed multiple seizure types, 9 of 11 patients had seizures triggered by fever and 9 of 11 patients had drug-resistant seizures. In vitro analysis of HEK293T cells transfected with MAST3 cDNA carrying a subset of these patient-specific missense variants demonstrated variable but generally lower expression, with concomitant increased phosphorylation of the MAST3 target, ARPP-16, compared to wild-type. These findings suggest the patient-specific variants may confer MAST3 gain-of-function. Moreover, single-nuclei RNA sequencing and immunohistochemistry shows that MAST3 expression is restricted to excitatory neurons in the cortex late in prenatal development and postnatally. Interpretation: In summary, we describe MAST3 as a novel epilepsy-associated gene with a potential gain-of-function pathogenic mechanism that may be primarily restricted to excitatory neurons in the cortex. ANN NEUROL 2021;90:274–284

Earlier snowmelt may lead to late season declines in plant productivity and carbon sequestration in Arctic tundra ecosystems

Arctic warming is affecting snow cover and soil hydrology, with consequences for carbon sequestration in tundra ecosystems. The scarcity of observations in the Arctic has limited our understanding of the impact of covarying environmental drivers on the carbon balance of tundra ecosystems. In this study, we address some of these uncertainties through a novel record of 119 site-years of summer data from eddy covariance towers representing dominant tundra vegetation types located on continuous permafrost in the Arctic. Here we found that earlier snowmelt was associated with more tundra net CO2 sequestration and higher gross primary productivity (GPP) only in June and July, but with lower net carbon sequestration and lower GPP in August. Although higher evapotranspiration (ET) can result in soil drying with the progression of the summer, we did not find significantly lower soil moisture with earlier snowmelt, nor evidence that water stress affected GPP in the late growing season. Our results suggest that the expected increased CO2 sequestration arising from Arctic warming and the associated increase in growing season length may not materialize if tundra ecosystems are not able to continue sequestering CO2 later in the season

Earlier snowmelt may lead to late season declines in plant productivity and carbon sequestration in Arctic tundra ecosystems

Arctic warming is affecting snow cover and soil hydrology, with consequences for carbon sequestration in tundra ecosystems. The scarcity of observations in the Arctic has limited our understanding of the impact of covarying environmental drivers on the carbon balance of tundra ecosystems. In this study, we address some of these uncertainties through a novel record of 119 site-years of summer data from eddy covariance towers representing dominant tundra vegetation types located on continuous permafrost in the Arctic. Here we found that earlier snowmelt was associated with more tundra net CO2 sequestration and higher gross primary productivity (GPP) only in June and July, but with lower net carbon sequestration and lower GPP in August. Although higher evapotranspiration (ET) can result in soil drying with the progression of the summer, we did not find significantly lower soil moisture with earlier snowmelt, nor evidence that water stress affected GPP in the late growing season. Our results suggest that the expected increased CO2 sequestration arising from Arctic warming and the associated increase in growing season length may not materialize if tundra ecosystems are not able to continue sequestering CO2 later in the season.Peer reviewe