Positive feedback induces switch between distributive and processive phosphorylation of Hog1

Cellular decision making often builds on ultrasensitive MAPK pathways. The phosphorylation mechanism of MAP kinase has so far been described as either distributive or processive, with distributive mechanisms generating ultrasensitivity in theoretical analyses. However, the in vivo mechanism of MAP kinase phosphorylation and its activation dynamics remain unclear. Here, we characterize the regulation of the MAP kinase Hog1 in Saccharomyces cerevisiae via topologically different ODE models, parameterized on multimodal activation data. Interestingly, our best fitting model switches between distributive and processive phosphorylation behavior regulated via a positive feedback loop composed of an affinity and a catalytic component targeting the MAP kinase-kinase Pbs2. Indeed, we show that Hog1 directly phosphorylates Pbs2 on serine 248 (S248), that cells expressing a non-phosphorylatable (S248A) or phosphomimetic (S248E) mutant show behavior that is consistent with simulations of disrupted or constitutively active affinity feedback and that Pbs2-S248E shows significantly increased affinity to Hog1 in vitro. Simulations further suggest that this mixed Hog1 activation mechanism is required for full sensitivity to stimuli and to ensure robustness to different perturbations.© 2023. The Author(s)

Genetically altered AMPA-type glutamate receptor kinetics in interneurons disrupt long-range synchrony of gamma oscillation

Gamma oscillations synchronized between distant neuronal populations may be critical for binding together brain regions devoted to common processing tasks. Network modeling predicts that such synchrony depends in part on the fast time course of excitatory postsynaptic potentials (EPSPs) in interneurons, and that even moderate slowing of this time course will disrupt synchrony. We generated mice with slowed interneuron EPSPs by gene targeting, in which the gene encoding the 67-kDa form of glutamic acid decarboxylase (GAD67) was altered to drive expression of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor subunit GluR-B. GluR-B is a determinant of the relatively slow EPSPs in excitatory neurons and is normally expressed at low levels in γ-aminobutyric acid (GABA)ergic interneurons, but at high levels in the GAD-GluR-B mice. In both wild-type and GAD-GluR-B mice, tetanic stimuli evoked gamma oscillations that were indistinguishable in local field potential recordings. Remarkably, however, oscillation synchrony between spatially separated sites was severely disrupted in the mutant, in association with changes in interneuron firing patterns. The congruence between mouse and model suggests that the rapid time course of AMPA receptor-mediated EPSPs in interneurons might serve to allow gamma oscillations to synchronize over distance

Exclusive Measurements of pd→3Heππpd\to ^3He \pi\pi : the ABCABC Effect Revisited

Exclusive measurements of the reactions $pd\to$ $^3He \pi^+ \pi^-$ and $pd\to$ $^3He \pi^0\pi^0$ have been carried out at $T_p=0.895$ GeV at the CELSIUS storage ring using the WASA detector. The $\pi^+\pi^-$ channel evidences a pronounced enhancement at low invariant $\pi\pi$ masses - as anticipated from previous inclusive measurements of the ABC effect. This enhancement is seen to be even much larger in the isoscalar $\pi^0\pi^0$ channel. The differential distributions prove this enhancement to be of scalar-isoscalar nature. $\Delta\Delta$ calculations give a good description of the data, if a boundstate condition is imposed for the intermediate $\Delta\Delta$ system.Comment: extended version, 8 pages, 7 figures, theoretical model calculations adde

Five decades of terrestrial and freshwater research at Ny-Ålesund, Svalbard

For more than five decades, research has been conducted at Ny-Alesund, in Svalbard, Norway, to understand the structure and functioning of High Arctic ecosystems and the profound impacts on them of environmental change. Terrestrial, freshwater, glacial and marine ecosystems are accessible year-round from Ny-Alesund, providing unique opportunities for interdisciplinary observational and experimental studies along physical, chemical, hydrological and climatic gradients. Here, we synthesize terrestrial and freshwater research at Ny-Alesund and review current knowledge of biodiversity patterns, species population dynamics and interactions, ecosystem processes, biogeochemical cycles and anthropogenic impacts. There is now strong evidence of past and ongoing biotic changes caused by climate change, including negative effects on populations of many taxa and impacts of rain-on-snow events across multiple trophic levels. While species-level characteristics and responses are well understood for macro-organisms, major knowledge gaps exist for microbes, invertebrates and ecosystem-level processes. In order to fill current knowledge gaps, we recommend (1) maintaining monitoring efforts, while establishing a longterm ecosystem-based monitoring programme; (2) gaining a mechanistic understanding of environmental change impacts on processes and linkages in food webs; (3) identifying trophic interactions and cascades across ecosystems; and (4) integrating long-term data on microbial, invertebrate and freshwater communities, along with measurements of carbon and nutrient fluxes among soils, atmosphere, freshwaters and the marine environment. The synthesis here shows that the Ny-Alesund study system has the characteristics needed to fill these gaps in knowledge, thereby enhancing our understanding of High-Arctic ecosystems and their responses to environmental variability and change

Molecular mechanisms controlling synaptic recruitment of GluA4 subunit-containing AMPAreceptors

Synaptic recruitment of AMPA receptors (AMPARs) represents a key postsynaptic mechanism driving functional development and maturation of glutamatergic synapses. At immature hippocampal synapses, PKA-driven synaptic insertion of GluA4 is the predominant mechanism for synaptic reinforcement. However, the physiological significance and molecular determinants of this developmentally restricted form of plasticity are not known. Here we show that PKA activation leads to insertion of GluA4 to synaptic sites with initially weak or silent AMPAR-mediated transmission. This effect depends on a novel mechanism involving the extreme C-terminal end of GluA4, which interacts with the membrane proximal region of the C-terminal domain to control GluA4 trafficking. In the absence of GluA4, strengthening of AMPAR-mediated transmission during postnatal development was significantly delayed. These data suggest that the GluA4-mediated activation of silent synapses is a critical mechanism facilitating the functional maturation of glutamatergic circuitry during the critical period of experience-dependent fine-tuning

Five decades of terrestrial and freshwater research at Ny-Ålesund, Svalbard

For more than five decades, research has been conducted at Ny-Ålesund, in Svalbard, Norway, to understand the structure and functioning of High-Arctic ecosystems and the profound impacts on them of environmental change. Terrestrial, freshwater, glacial and marine ecosystems are accessible year-round from Ny-Ålesund, providing unique opportunities for interdisciplinary observational and experimental studies along physical, chemical, hydrological and climatic gradients. Here, we synthesize terrestrial and freshwater research at Ny-Ålesund and review current knowledge of biodiversity patterns, species population dynamics and interactions, ecosystem processes, biogeochemical cycles and anthropogenic impacts. There is now strong evidence of past and ongoing biotic changes caused by climate change, including negative effects on populations of many taxa and impacts of rain-on-snow events across multiple trophic levels. While species-level characteristics and responses are well understood for macro-organisms, major knowledge gaps exist for microbes, invertebrates and ecosystem-level processes. In order to fill current knowledge gaps, we recommend (1) maintaining monitoring efforts, while establishing a long-term ecosystem-based monitoring programme; (2) gaining a mechanistic understanding of environmental change impacts on processes and linkages in food webs; (3) identifying trophic interactions and cascades across ecosystems; and (4) integrating long-term data on microbial, invertebrate and freshwater communities, along with measurements of carbon and nutrient fluxes among soils, atmosphere, freshwaters and the marine environment. The synthesis here shows that the Ny-Ålesund study system has the characteristics needed to fill these gaps in knowledge, thereby enhancing our understanding of High-Arctic ecosystems and their responses to environmental variability and change

Location of studies and evidence of effects of herbivory on Arctic vegetation : a systematic map

Background: Herbivores modify the structure and function of tundra ecosystems. Understanding their impacts is necessary to assess the responses of these ecosystems to ongoing environmental changes. However, the effects of herbivores on plants and ecosystem structure and function vary across the Arctic. Strong spatial variation in herbivore effects implies that the results of individual studies on herbivory depend on local conditions, i.e., their ecological context. An important first step in assessing whether generalizable conclusions can be produced is to identify the existing studies and assess how well they cover the underlying environmental conditions across the Arctic. This systematic map aims to identify the ecological contexts in which herbivore impacts on vegetation have been studied in the Arctic. Specifically, the primary question of the systematic map was: "What evidence exists on the effects of herbivores on Arctic vegetation?". Methods: We used a published systematic map protocol to identify studies addressing the effects of herbivores on Arctic vegetation. We conducted searches for relevant literature in online databases, search engines and specialist websites. Literature was screened to identify eligible studies, defined as reporting primary data on herbivore impacts on Arctic plants and plant communities. We extracted information on variables that describe the ecological context of the studies, from the studies themselves and from geospatial data. We synthesized the findings narratively and created a Shiny App where the coded data are searchable and variables can be visually explored. Review findings We identified 309 relevant articles with 662 studies (representing different ecological contexts or datasets within the same article). These studies addressed vertebrate herbivory seven times more often than invertebrate herbivory. Geographically, the largest cluster of studies was in Northern Fennoscandia. Warmer and wetter parts of the Arctic had the largest representation, as did coastal areas and areas where the increase in temperature has been moderate. In contrast, studies spanned the full range of ecological context variables describing Arctic vertebrate herbivore diversity and human population density and impact. Conclusions: The current evidence base might not be sufficient to understand the effects of herbivores on Arctic vegetation throughout the region, as we identified clear biases in the distribution of herbivore studies in the Arctic and a limited evidence base on invertebrate herbivory. In particular, the overrepresentation of studies in areas with moderate increases in temperature prevents robust generalizations about the effects of herbivores under different climatic scenarios.Peer reviewe

Location of studies and evidence of effects of herbivory on Arctic vegetation: a systematic map

Herbivores modify the structure and function of tundra ecosystems. Understanding their impacts is necessary to assess the responses of these ecosystems to ongoing environmental changes. However, the effects of herbivores on plants and ecosystem structure and function vary across the Arctic. Strong spatial variation in herbivore effects implies that the results of individual studies on herbivory depend on local conditions, i.e., their ecological context. An important first step in assessing whether generalizable conclusions can be produced is to identify the existing studies and assess how well they cover the underlying environmental conditions across the Arctic. This systematic map aims to identify the ecological contexts in which herbivore impacts on vegetation have been studied in the Arctic. Specifically, the primary question of the systematic map was: “What evidence exists on the effects of herbivores on Arctic vegetation?”

Gastrin-Releasing Peptide Signaling Plays a Limited and Subtle Role in Amygdala Physiology and Aversive Memory

Links between synaptic plasticity in the lateral amygdala (LA) and Pavlovian fear learning are well established. Neuropeptides including gastrin-releasing peptide (GRP) can modulate LA function. GRP increases inhibition in the LA and mice lacking the GRP receptor (GRPR KO) show more pronounced and persistent fear after single-trial associative learning. Here, we confirmed these initial findings and examined whether they extrapolate to more aspects of amygdala physiology and to other forms of aversive associative learning. GRP application in brain slices from wildtype but not GRPR KO mice increased spontaneous inhibitory activity in LA pyramidal neurons. In amygdala slices from GRPR KO mice, GRP did not increase inhibitory activity. In comparison to wildtype, short- but not long-term plasticity was increased in the cortico-lateral amygdala (LA) pathway of GRPR KO amygdala slices, whereas no changes were detected in the thalamo-LA pathway. In addition, GRPR KO mice showed enhanced fear evoked by single-trial conditioning and reduced spontaneous firing of neurons in the central nucleus of the amygdala (CeA). Altogether, these results are consistent with a potentially important modulatory role of GRP/GRPR signaling in the amygdala. However, administration of GRP or the GRPR antagonist (D-Phe6, Leu-NHEt13, des-Met14)-Bombesin (6–14) did not affect amygdala LTP in brain slices, nor did they affect the expression of conditioned fear following intra-amygdala administration. GRPR KO mice also failed to show differences in fear expression and extinction after multiple-trial fear conditioning, and there were no differences in conditioned taste aversion or gustatory neophobia. Collectively, our data indicate that GRP/GRPR signaling modulates amygdala physiology in a paradigm-specific fashion that likely is insufficient to generate therapeutic effects across amygdala-dependent disorders

Data from an International Multi-Centre Study of Statistics and Mathematics Anxieties and Related Variables in University Students (the SMARVUS Dataset)

This large, international dataset contains survey responses from N = 12,570 students from 100 universities in 35 countries, collected in 21 languages. We measured anxieties (statistics, mathematics, test, trait, social interaction, performance, creativity, intolerance of uncertainty, and fear of negative evaluation), self-efficacy, persistence, and the cognitive reflection test, and collected demographics, previous mathematics grades, self-reported and official statistics grades, and statistics module details. Data reuse potential is broad, including testing links between anxieties and statistics/mathematics education factors, and examining instruments’ psychometric properties across different languages and contexts. Data and metadata are stored on the Open Science Framework website [https://osf.io/mhg94/]