Search

Persistent activity of protein kinase M (PKM), the truncated form of protein kinase C (PKC), can maintain long-term changes in synaptic strength in many systems, including the hermaphrodite marine mollusk, Aplysia californica Moreover, different types of long-term facilitation (LTF) in cultured Aplysia sensorimotor synapses rely on the activities of different PKM isoforms in the presynaptic sensory neuron and postsynaptic motor neuron. When the atypical PKM isoform is required, the kidney and brain expressed adaptor protein (KIBRA) is also required. Here, we explore how this isoform specificity is established. We find that PKM overexpression in the motor neuron, but not the sensory neuron, is sufficient to increase synaptic strength and that this activity is not isoform-specific. KIBRA is not the rate-limiting step in facilitation since overexpression of KIBRA is neither sufficient to increase synaptic strength, nor to prolong a form of PKM-dependent intermediate synaptic facilitation. However, the isoform specificity of dominant-negative-PKMs to erase LTF is correlated with isoform-specific competition for stabilization by KIBRA. We identify a new conserved region of KIBRA. Different splice isoforms in this region stabilize different PKMs based on the isoform-specific sequence of an α-helix "handle" in the PKMs. Thus, specific stabilization of distinct PKMs by different isoforms of KIBRA can explain the isoform specificity of PKMs during LTF in Aplysia SIGNIFICANCE STATEMENT Long-lasting changes in synaptic plasticity associated with memory formation are maintained by persistent protein kinases. We have previously shown in the Aplysia sensorimotor model that distinct isoforms of persistently active protein kinase Cs (PKMs) maintain distinct forms of long-lasting synaptic changes, even when both forms are expressed in the same motor neuron. Here, we show that, while the effects of overexpression of PKMs are not isoform-specific, isoform specificity is defined by a "handle" helix in PKMs that confers stabilization by distinct splice forms in a previously undefined domain of the adaptor protein KIBRA. Thus, we define new regions in both KIBRA and PKMs that define the isoform specificity for maintaining synaptic strength in distinct facilitation paradigms.

Based on previous research and theory, six hypotheses were tested concerning relations of geek culture engagement to grandiose narcissism and self-esteem. A sample of 203 undergraduates completed a questionnaire assessing narcissism with the NARQ (Back et al. Journal of Personality and Social Psychology, 105, 1013-1037, 2013 (See CR1)), self-esteem with the Rosenberg Self-Esteem Scale (Rosenberg 1965 (See CR24)), and status and inclusion with the scales of Mahadevan et al. (Journal of Personality and Social Psychology, 116, 444-466, 2019 (See CR14)). Measures of geek identity, geek activity, and video gaming also were included. In the main analyses, without or with statistical control for age, gender, and international student status, correlation and sequential multiple regression showed that higher narcissism was associated with greater geek identity, geek activity, video gaming, and their composite. Self-esteem, status, and inclusion showed no relation to the four geek measures with or without demographic statistical control. Consequently, H1 of the present study that higher narcissism is associated with greater attraction to geek culture was strongly supported. H2 that higher self-esteem is associated with attraction to geek culture gained no support. Expected relations of status and inclusion to narcissism and self-esteem were not found, offering no support for H3 or H4. H5 and H6 that status and inclusion can account for some variance in the geek criteria accounted for by narcissism and self-esteem were not supported. Results bolster support for the Great Fantasy Migration hypothesis which holds that when faced with the perception of dire economic circumstances and prospects, narcissists tend to turn to the realms of fantasy and virtual reality in attempting to satisfy their desires for social status and recognition., Author(s): Tyler W. Andrews [sup.1] , Stewart J. H. McCann [sup.1] Author Affiliations: (1) grid.253649.f, 0000 0001 2151 8595, Department of Psychology, Cape Breton University, , 1250 Grand Lake Road, [...]

This study examines whether changes in classroom quality predict within-child changes in achievement and behavioral problems in elementary school (ages spanning approximately 6-11 years old). Drawing on data from a longitudinal study of children in predominantly low-income, nonurban communities (n = 1,078), we relied on child fixed effects modeling, which controlled for stable factors that could bias the effects of classroom quality. In general, we found that changes in classroom quality had small and statistically nonsignificant effects on achievement and behavior. However, we found that moving into a high-quality classroom, particularly those rated as high in Classroom Organization, had positive effects on achievement and behavior for children with significant exposure to poverty in early life.

Molecular hydrogen (H2) has antioxidant, anti-inflammatory, and anti-fibrotic effects. In a rat model simulating pulmonary fibrotic changes induced by monocrotaline-induced pulmonary hypertension (MPH), we had previously explored the impact of inhaled H2 on lung inflammation and blood pressure. In this study, we further focused the biological effects of H2 on mast cells (MCs) and the parameters of the fibrotic phenotype of the local tissue microenvironment. MPH resulted in a significantly increased number of MCs in both the pneumatic and respiratory parts of the lungs, an increased number of tryptase-positive MCs with increased expression of TGF-β, activated interaction with immunocompetent cells (macrophages and plasma cells) and fibroblasts, and increased MC colocalization with a fibrous component of the extracellular matrix of connective tissue. The alteration in the properties of the MC population occurred together with intensified collagen fibrillogenesis and an increase in the integral volume of collagen and elastic fibers of the extracellular matrix of the pulmonary connective tissue. The exposure of H2 together with monocrotaline (MCT), despite individual differences between animals, tended to decrease the intrapulmonary MC population and the severity of the fibrotic phenotype of the local tissue microenvironment compared to changes in animals exposed to the MCT effect alone. In addition, the activity of collagen fibrillogenesis associated with MCs and the expression of TGF-β and tryptase in MCs decreased, accompanied by a reduction in the absolute and relative content of reticular and elastic fibers in the lung stroma. Thus, with MCT exposure, inhaled H2 has antifibrotic effects involving MCs in the lungs of rats. This reveals the unknown development mechanisms of the biological effects of H2 on the remodeling features of the extracellular matrix under inflammatory background conditions of the tissue microenvironment. [ABSTRACT FROM AUTHOR]

The world is confronting numerous challenges, including global warming, health epidemics, and population growth, each presenting significant threats to the stability and sustainability of our planet's ecosystems. Such issues have collectively contributed to a reduction in agricultural productivity, corresponding with an increase in demand and costs of essential commodities. This critical situation requires more sustainable environmental, social, and technological solutions. Molecular hydrogen (H2) has been suggested as a "green" solution for our energy needs and many health, agricultural, and food applications. H2 supplementation in agriculture may represent a novel and lowcarbon biotechnological strategy applicable to the abundant production of crops, vegetables, and fruits in agri-food chains. H2 is a potential green alternative to conventional chemical fertilizers. The use of a hydrogen-rich water irrigation system may also provide other health-related advantages, i.e., decreasing the heavy metal accumulation in crops. By adopting a H2 strategy, crop producers, food processors, and decision-makers can contribute to sustainable solutions in the face of global challenges such as climate change, communicable disease epidemics, and a growing population. The versatile applications of H2 in agriculture and the wider food industry position it as a uniquely suitable approach to address today's significant challenges, potentially fostering better crop production and positively impacting the agri-food chain. The present review is timely in combining the latest knowledge about the potential applications of H2 in the agriculture and food industry, from farm to fork. [ABSTRACT FROM AUTHOR]

Background: Blood product component-only resuscitation (CORe) has been the standard of practice in both military and civilian trauma care with a 1:1:1 ratio used in attempt to recreate whole blood (WB) until recent data demonstrated WB to confer a survival advantage, leading to the emergence of WB as the contemporary resuscitation strategy of choice. Little is known about the cost and waste reduction associated with WB vs CORe. Methods: This study is a retrospective single-center review of adult trauma patients admitted to a community trauma center who received WB or CORe as part of their massive transfusion protocol (MTP) resuscitation from 2017 to 2021. The WB group received a minimum of one unit WB while CORe received no WB. Univariate and multivariate analyses were completed. Statistical analysis was conducted using a 95% confidence level. Non-normally distributed, continuous data were analyzed using the Wilcoxon rank sum test. Results: 576 patients were included (201 in WB and 375 in CORe). Whole blood conveyed a survival benefit vs CORe (OR 1.49 P <.05, 1.02-2.17). Whole blood use resulted in an overall reduction in products prepared (25.8%), volumes transfused (16.5%), product waste (38.7%), and MTP activation (56.3%). Cost savings were $849 923 annually and $3 399 693 over the study period. Discussion: Despite increased patient volumes over the study period (43.7%), the utilization of WB as compared to CORe resulted in an overall $3.39 million cost savings while improving mortality. As such, we propose WB should be utilized in all resuscitation strategies for the exsanguinating trauma patient. [ABSTRACT FROM AUTHOR]

In an effort to promote best practices regarding mathematics teaching and learning at the preschool level, national advisory panels and organizations have emphasized the importance of children's emergent counting and related competencies, such as the ability to verbally count, maintain one-to-one correspondence, count with cardinality, subitize, and count forward or backward from a given number. However, little research has investigated whether the kind of mathematical knowledge promoted by the various standards documents actually predict later mathematics achievement. The present study uses longitudinal data from a primarily low-income and minority sample of children to examine the extent to which preschool mathematical competencies, specifically basic and advanced counting, predict fifth grade mathematics achievement. Using regression analyses, we find early numeracy abilities to be the strongest predictors of later mathematics achievement, with advanced counting competencies more predictive than basic counting competencies. Our results highlight the significance of preschool mathematics knowledge for future academic achievement.

Prior research shows that short-term effects from preschool may disappear, but little research has considered which environmental conditions might sustain academic advantages from preschool into elementary school. Using secondary data from two preschool experiments, we investigate whether features of elementary schools, particularly advanced content and high-quality instruction in kindergarten and first grade, as well as professional supports to coordinate curricular instruction, reduce fadeout. Across both studies, our measures of instruction did not moderate fadeout. However, results indicated that targeted teacher professional supports substantially mitigated fadeout between kindergarten and first grade but that this was not mediated through classroom quality. Future research should investigate the specific mechanisms through which aligned preschool-elementary school curricular approaches can sustain the benefits of preschool programs for low-income children.

We replicated and extended Shoda, Mischel, and Peake's (1990) famous marshmallow study, which showed strong bivariate correlations between a child's ability to delay gratification just before entering school and both adolescent achievement and socioemotional behaviors. Concentrating on children whose mothers had not completed college, we found that an additional minute waited at age 4 predicted a gain of approximately one tenth of a standard deviation in achievement at age 15. But this bivariate correlation was only half the size of those reported in the original studies and was reduced by two thirds in the presence of controls for family background, early cognitive ability, and the home environment. Most of the variation in adolescent achievement came from being able to wait at least 20 s. Associations between delay time and measures of behavioral outcomes at age 15 were much smaller and rarely statistically significant.

The current study estimated the causal links between preschool mathematics learning and late elementary school mathematics achievement using variation in treatment assignment to an early mathematics intervention as an instrument for preschool mathematics change. Estimates indicate (n = 410) that a standard deviation of intervention-produced change at age 4 is associated with a 0.24-SD gain in achievement in late elementary school. This impact is approximately half the size of the association produced by correlational models relating later achievement to preschool math change, and is approximately 35% smaller than the effect reported by highly controlled ordinary least squares (OLS) regression models (Claessens et al., 2009; Watts et al., ) using national data sets. Implications for developmental theory and practice are discussed.

Gross primary production (GPP)-the uptake of carbon dioxide (CO2) by leaves, and its conversion to sugars by photosynthesis-is the basis for life on land. Earth System Models (ESMs) incorporating the interactions of land ecosystems and climate are used to predict the future of the terrestrial sink for anthropogenic CO21 . ESMs require accurate representation of GPP. However, current ESMs disagree on how GPP responds to environmental variations 1,2 , suggesting a need for a more robust theoretical framework for modelling 3,4 . Here, we focus on a key quantity for GPP, the ratio of leaf internal to external CO2 (χ). χ is tightly regulated and depends on environmental conditions, but is represented empirically and incompletely in today's models. We show that a simple evolutionary optimality hypothesis 5,6 predicts specific quantitative dependencies of χ on temperature, vapour pressure deficit and elevation; and that these same dependencies emerge from an independent analysis of empirical χ values, derived from a worldwide dataset of >3,500 leaf stable carbon isotope measurements. A single global equation embodying these relationships then unifies the empirical light-use efficiency model 7 with the standard model of C3 photosynthesis 8 , and successfully predicts GPP measured at eddy-covariance flux sites. This success is notable given the equation's simplicity and broad applicability across biomes and plant functional types. It provides a theoretical underpinning for the analysis of plant functional coordination across species and emergent properties of ecosystems, and a potential basis for the reformulation of the controls of GPP in next-generation ESMs.

The chromatin remodeling gene CHD8 represents a central node in neurodevelopmental gene networks implicated in autism. We examined the impact of germline heterozygous frameshift Chd8 mutation on neurodevelopment in mice. Chd8+/del5 mice displayed normal social interactions with no repetitive behaviors but exhibited cognitive impairment correlated with increased regional brain volume, validating that phenotypes of Chd8+/del5 mice overlap pathology reported in humans with CHD8 mutations. We applied network analysis to characterize neurodevelopmental gene expression, revealing widespread transcriptional changes in Chd8+/del5 mice across pathways disrupted in neurodevelopmental disorders, including neurogenesis, synaptic processes and neuroimmune signaling. We identified a co-expression module with peak expression in early brain development featuring dysregulation of RNA processing, chromatin remodeling and cell-cycle genes enriched for promoter binding by Chd8, and we validated increased neuronal proliferation and developmental splicing perturbation in Chd8+/del5 mice. This integrative analysis offers an initial picture of the consequences of Chd8 haploinsufficiency for brain development.

The processes that define mammalian physiology evolved millions of years ago in response to ancient signaling molecules, most of which were acquired by ingestion and digestion. In this way, evolution inextricably linked diet to all major physiological systems including the nervous system. The importance of diet in neurological development is well documented, although the mechanisms by which diet-derived signaling molecules (DSMs) affect cognition are poorly understood. Studies on the positive impact of nutritive and non-nutritive bioactive molecules on brain function are encouraging but lack the statistical power needed to demonstrate strong positive associations. Establishing associations between DSMs and cognitive functions like mood, memory and learning are made even more difficult by the lack of robust phenotypic markers that can be used to accurately and reproducibly measure the effects of DSMs. Lastly, it is now apparent that processes like neurogenesis and neuroplasticity are embedded within layers of interlocked signaling pathways and gene regulatory networks. Within these interdependent pathways and networks, the various transducers of DSMs are used combinatorially to produce those emergent adaptive gene expression responses needed for stimulus-induced neurogenesis and neuroplasticity. Taken together, it appears that cognition is encoded genomically and modified by epigenetics and epitranscriptomics to produce complex transcriptional programs that are exquisitely sensitive to signaling molecules from the environment. Models for how DSMs mediate the interplay between the environment and various neuronal processes are discussed in the context of the food-brain axis.