An updated LSU database and pipeline for environmental DNA identification of arbuscular mycorrhizal fungi.

Recent work established a backbone reference tree and phylogenetic placement pipeline for identification of arbuscular mycorrhizal fungal (AMF) large subunit (LSU) rDNA environmental sequences. Our previously published pipeline allowed any environmental sequence to be identified as putative AMF or within one of the major families. Despite this contribution, difficulties in implementation of the pipeline remain. Here, we present an updated database and pipeline with (1) an expanded backbone tree to include four newly described genera and (2) several changes to improve ease and consistency of implementation. In particular, packages required for the pipeline are now installed as a single folder (conda environment) and the pipeline has been tested across three university computing clusters. This updated backbone tree and pipeline will enable broadened adoption by the community, advancing our understanding of these ubiquitous and ecologically important fungi.

Elongasome core proteins and class A PBP1a display zonal, processive movement at the midcell of Streptococcus pneumoniae.

Ovoid-shaped bacteria, such as Streptococcus pneumoniae (pneumococcus), have two spatially separated peptidoglycan (PG) synthase nanomachines that locate zonally to the midcell of dividing cells. The septal PG synthase bPBP2x:FtsW closes the septum of dividing pneumococcal cells, whereas the elongasome located on the outer edge of the septal annulus synthesizes peripheral PG outward. We showed previously by sm-TIRFm that the septal PG synthase moves circumferentially at midcell, driven by PG synthesis and not by FtsZ treadmilling. The pneumococcal elongasome consists of the PG synthase bPBP2b:RodA, regulators MreC, MreD, and RodZ, but not MreB, and genetically associated proteins Class A aPBP1a and muramidase MpgA. Given its zonal location separate from FtsZ, it was of considerable interest to determine the dynamics of proteins in the pneumococcal elongasome. We found that bPBP2b, RodA, and MreC move circumferentially with the same velocities and durations at midcell, driven by PG synthesis. However, outside of the midcell zone, the majority of these elongasome proteins move diffusively over the entire surface of cells. Depletion of MreC resulted in loss of circumferential movement of bPBP2b, and bPBP2b and RodA require each other for localization and circumferential movement. Notably, a fraction of aPBP1a molecules also moved circumferentially at midcell with velocities similar to those of components of the core elongasome, but for shorter durations. Other aPBP1a molecules were static at midcell or diffusing over cell bodies. Last, MpgA displayed nonprocessive, subdiffusive motion that was largely confined to the midcell region and less frequently detected over the cell body.

Protein Design Using Structure-Prediction Networks: AlphaFold and RoseTTAFold as Protein Structure Foundation Models.

Designing proteins with tailored structures and functions is a long-standing goal in bioengineering. Recently, deep learning advances have enabled protein structure prediction at near-experimental accuracy, which has catalyzed progress in protein design as well. We review recent studies that use structure-prediction neural networks to design proteins, via approaches such as activation maximization, inpainting, or denoising diffusion. These methods have led to major improvements over previous methods in wet-lab success rates for designing protein binders, metalloproteins, enzymes, and oligomeric assemblies. These results show that structure-prediction models are a powerful foundation for developing protein-design tools and suggest that continued improvement of their accuracy and generality will be key to unlocking the full potential of protein design.

Elongasome core proteins and class A PBP1a display zonal, processive movement at the midcell of Streptococcus pneumoniae.

Ovoid-shaped bacteria, such as Streptococcus pneumoniae (pneumococcus), have two spatially separated peptidoglycan (PG) synthase nanomachines that locate zonally to the midcell of dividing cells. The septal PG synthase bPBP2x:FtsW closes the septum of dividing pneumococcal cells, whereas the elongasome located on the outer edge of the septal annulus synthesizes peripheral PG outward. We showed previously by sm-TIRFm that the septal PG synthase moves circumferentially at midcell, driven by PG synthesis and not by FtsZ treadmilling. The pneumococcal elongasome consists of the PG synthase bPBP2b:RodA, regulators MreC, MreD, and RodZ, but not MreB, and genetically associated proteins Class A aPBP1a and muramidase MpgA. Given its zonal location separate from FtsZ, it was of considerable interest to determine the dynamics of proteins in the pneumococcal elongasome. We found that bPBP2b, RodA, and MreC move circumferentially with the same velocities and durations at midcell, driven by PG synthesis. However, outside of the midcell zone, the majority of these elongasome proteins move diffusively over the entire surface of cells. Depletion of MreC resulted in loss of circumferential movement of bPBP2b, and bPBP2b and RodA require each other for localization and circumferential movement. Notably, a fraction of aPBP1a molecules also moved circumferentially at midcell with velocities similar to those of components of the core elongasome, but for shorter durations. Other aPBP1a molecules were static at midcell or diffusing over cell bodies. Last, MpgA displayed non-processive, subdiffusive motion that was largely confined to the midcell region and less frequently detected over the cell body.

Effects of a diet low in excitotoxins on PTSD symptoms and related biomarkers.

Post-traumatic stress disorder (PTSD) develops after trauma exposure and involves symptoms of avoidance, intrusive re-experiencing, mood and cognitive dysfunction, and hypervigilance. PTSD is often comorbid with Gulf War Illness (GWI), a neurological condition involving widespread pain, cognitive dysfunction, digestive problems, and other symptoms, in Gulf War veterans. PTSD tends to be more severe when comorbid with GWI. Low cortisol and elevated homocysteine levels have been found in PTSD, making them potential PTSD biomarkers. The low-glutamate diet, which aims to reduce excitotoxicity by eliminating the consumption of free glutamate and aspartate, has been shown to significantly reduce GWI and PTSD symptoms. This study examined whether changes in serum cortisol and homocysteine are associated with reduced PTSD severity in veterans with GWI after one month on the low-glutamate diet, and whether reducing the consumption of dietary excitotoxins was associated changes in PTSD and serum biomarkers. Data were analyzed for 33 veterans. No serum biomarkers significantly changed post-diet; however, cortisol increased as dietary excitotoxin consumption decreased, which held in a multivariable linear regression after adjustment for sex. Reduced dietary excitotoxin consumption was also associated with reduced hyperarousal symptoms, which held in a multivariable linear regression after adjustment for sex. Cortisol increase was associated with reduced avoidance symptoms after adjustment for change in BMI, and was marginally associated with overall PTSD reduction. Change in homocysteine was not significantly related to dietary adherence nor change in PTSD. Results suggest that reducing the consumption of dietary excitotoxins may normalize cortisol levels, which has been associated with alleviating PTSD.

Lanthanide-dependent isolation of phyllosphere methylotrophs selects for a phylogenetically conserved but metabolically diverse community.

The influence of lanthanide biochemistry during methylotrophy demands a reassessment of how the composition and metabolic potential of methylotrophic phyllosphere communities are affected by the presence of these metals. To investigate this, methylotrophs were isolated from soybean leaves by selecting for bacteria capable of methanol oxidation with lanthanide cofactors. Of the 344 pink-pigmented facultative methylotroph isolates, none were obligately lanthanide-dependent. Phylogenetic analyses revealed that all strains were nearly identical to each other and to model strains from the extorquens clade of Methylobacterium, with rpoB providing higher resolution than 16s rRNA for strain-specific identification. Despite the low species diversity, the metabolic capabilities of the community diverged greatly. Strains encoding identical PQQ-dependent alcohol dehydrogenases displayed significantly different growth from each other on alcohols in the presence and absence of lanthanides. Several strains also lacked well-characterized lanthanide-associated genes thought to be important for phyllosphere colonization. Additionally, 3% of our isolates were capable of growth on sugars and 23% were capable of growth on aromatic acids, substantially expanding the range of multicarbon substrates utilized by members of the extorquens clade in the phyllosphere. Whole genome sequences of eleven novel strains are reported. Our findings suggest that the expansion of metabolic capabilities, as well as differential usage of lanthanides and their influence on metabolism among closely related strains, point to evolution of niche partitioning strategies to promote colonization of the phyllosphere.

Overlapping Localization of MAP65-2, -6, and -7 in Arabidopsis Hypocotyl Cells.

Microtubules are essential components of eukaryotic cells. Myriad proteins associate with microtubules to facilitate the organization and operation of microtubule arrays. Various M icrotubule A ssociated P roteins (MAPs) assist the assembly and function of mitotic spindles and interphase arrays. Nine MAP65 genes exist in the genome of the acentrosomal model plant, Arabidopsis thaliana, and the function of majority of these proteins is unclear. To address this knowledge gap, we demonstrate the localization of A. thaliana MAP65-6 and MAP65-7 fusion proteins expressed from native promoters in interphase cells of developing A. thaliana seedlings. Analyses of these fusion proteins co-expressed with alpha-tubulin 6 reporters indicate that MAP65-6 and MAP65-7 bind a subset of interphase microtubules. Co-expression of GFP: MAP65-6 with mCherry: MAP65-2 from native promoters in A. thaliana showed overlapping localization patterns on interphase microtubule bundles. Collectively, these data suggested that MAP65-2 , -6, and -7 bind cortical microtubule bundles in plant interphase microtubule arrays.

Building Evidence for Principles to Guide the Development of Products for Adults with Intellectual and Developmental Disabilities and Extreme Low Literacy-A Product Development Tool.

This article presented a new product development tool for adults with intellectual and developmental disabilities (IDD) developed by the Centers for Disease Control and Prevention (CDC). People with IDD who also have extreme low literacy (ELL) have unique communication needs; public health communicators often face challenges developing effective communication materials for this audience. To support CDC communication specialists with the development of communication products for adults with IDD/ELL, CDC, with its partners RTI International and CommunicateHealth, created a product development tool for this audience through literature review, expert input, and interviews with adults with IDD/ELL and caregivers of adults with IDD/ELL. To build evidence around the principles described in the tool, RTI conducted interviewer-administered surveys with 100 caregivers who support people with IDD/ELL. During the interviews, we presented caregivers with stimuli (portions of a communication product) that either did or did not apply a single principle and asked which would be easier for the person they support to understand. Across all 14 principles tested, the caregiver respondents indicated that the principle-based version would be easier for the person they support to understand compared with the non-principle-based version(s). These findings provide additional evidence to support the principles included in CDC's Tool for Developing Products for People with IDD/ELL.

A pilot study of experiencing racial microaggressions, obsessive-compulsive symptoms, and the role of psychological flexibility.

BACKGROUND: Experiencing racial microaggressions has clear effects on physical and psychological health, including obsessive-compulsive disorder symptoms (OCS). More research is needed to examine this link. Psychological flexibility is an important process to examine in this work. AIMS: This study aimed to examine if, while controlling for depression and anxiety, experiences of microaggressions and psychological flexibility helped explain OCD symptoms within a university-affiliated sample (undergraduate, graduate and law students). This was a pilot exploration of the relationships across themes. METHOD: Initial baseline data from a longitudinal study of psychological flexibility, OCD symptoms, depression, anxiety and experience of microaggressions was utilized. Correlations and regressions were utilized to examine which OCD symptom dimensions were associated with experiencing racial microaggressions in addition to anxiety and depression, and the added role of psychological flexibility was examined. RESULTS: OCD symptoms, experiences of microaggressions and psychological flexibility were correlated. Experiences of racial microaggressions explained responsibility for harm and contamination OCD symptoms above and beyond psychological distress. Exploratory results support the relevance of psychological flexibility. CONCLUSION: Results support other work that experiences of racial microaggressions help explain OCS and they add some support for psychological flexibility as a relevant risk or protective factor for mental health in marginalized populations. These topics should be studied longitudinally with continued consideration of all OCD themes, larger sample sizes, intersecting identities, clinical samples, and continued exploration of psychological flexibility and mindfulness and values-based treatments.

Sex Hormones, Neurosteroids, and Glutamatergic Neurotransmission: A Review of the Literature.

Glutamatergic dysfunction has been implicated in the pathophysiology of multiple conditions including epilepsy, chronic pain, post-traumatic stress disorder (PTSD), and premenstrual dysphoric disorder (PMDD), raising interest in potential ways of modifying glutamate in the nervous system. Emerging research has suggested an interactive effect between sex hormones and glutamatergic neurotransmission. The objective of this paper was to review existing literature on the mechanism of interaction between sex hormones and glutamatergic neurotransmission, as well as to explore what is known about these interactions in various neurological and psychiatric conditions. This paper summarizes knowledge regarding mechanisms for these effects, and glutamatergic response to direct modulation of sex hormones. Research articles were identified via scholarly databases including PubMed, Google Scholar, and ProQuest. Articles were included if they were original research from peer-reviewed academic journals that dealt with glutamate, estrogen, progesterone, testosterone, neurosteroids, glutamate and sex hormone interactions, or the potential impact of glutamate and sex hormone interactions in the following conditions: chronic pain, epilepsy, PTSD, and PMDD. Current evidence suggests that sex hormones can directly modulate glutamatergic neurotransmission, with specific protective effects against excitotoxicity noted for estrogens. An effect of monosodium glutamate consumption on sex hormone levels has also been demonstrated, suggesting a possible bidirectional effect. Overall, there is a good deal of evidence suggesting a role for sex hormones, and specifically for estrogens, in the modulation of glutamatergic neurotransmission.

WAVE-DAMPENED2-LIKE4 modulates the hyper-elongation of light-grown hypocotyl cells.

Light, temperature, water, and nutrient availability influence how plants grow to maximize access to resources. Axial growth, the linear extension of tissues by coordinated axial cell expansion, plays a central role in these adaptive morphological responses. Using Arabidopsis (Arabidopsis thaliana) hypocotyl cells to explore axial growth control mechanisms, we investigated WAVE-DAMPENED2-LIKE4 (WDL4), an auxin-induced, microtubule-associated protein and member of the larger WDL gene family shown to modulate hypocotyl growth under changing environmental conditions. Loss-of-function wdl4 seedlings exhibited a hyper-elongation phenotype under light conditions, continuing to elongate when wild-type Col-0 hypocotyls arrested and reaching 150% to 200% of wild-type length before shoot emergence. wdl4 seedling hypocotyls showed dramatic hyper-elongation (500%) in response to temperature elevation, indicating an important role in morphological adaptation to environmental cues. WDL4 was associated with microtubules under both light and dark growth conditions, and no evidence was found for altered microtubule array patterning in loss-of-function wdl4 mutants under various conditions. Examination of hormone responses showed altered sensitivity to ethylene and evidence for changes in the spatial distribution of an auxin-dependent transcriptional reporter. Our data provide evidence that WDL4 regulates hypocotyl cell elongation without substantial changes to microtubule array patterning, suggesting an unconventional role in axial growth control.

Intersectionality Policymaking Toolkit: Key Principles for an Intersectionality-Informed Policymaking Process to Serve Diverse Women, Children, and Families.

Health and economic inequities among U.S. racial/ethnic minority women and children are staggering. These inequities underscore a dire need for intersectionality-informed, social-justice-oriented maternal and child (MCH) policies and programs for U.S. women and children. In response, we developed the "Intersectionality Policymaking Toolkit: Key Principles for an Intersectionality Informed Policymaking Process to Serve Diverse Women, Children and Families" to assist U.S. policymakers/aides, practitioners, and other stakeholders in developing more equitable MCH policies/programs. This article describes the Toolkit development process and initial assessments of acceptability and feasibility for use in MCH policymaking. Between 2018 and 2021, we utilized the process that the World Health Organization (WHO) used to develop its WHO Surgical Safety Checklist to develop the content (e.g., case studies) and format (i.e., structure), make strategic decisions (e.g., core items, primary audiences, timing of utilization), test concepts, and receive feedback. We convened a 2-day planning meeting with experts (n = 8) in intersectionality, policymaking, and MCH to draft the Toolkit. Next, we convened half-day workshops with policymaking and program leadership and staff in Washington, DC, New Orleans, LA, and Santa Fe, NM, to refine the Toolkit (n = 37). Then we conducted an initial assessment of the Toolkits' acceptability and feasibility using surveys (n = 21), followed by focus groups (n = 7). The resulting Toolkit distills Critical Race Theory's and intersectionality's most critical elements into a user-friendly modality to promote and enhance equitable MCH policies and programs for diverse U.S. women and families.

Importin α/ß promote Kif18B microtubule association and enhance microtubule destabilization activity.

Tight regulation of microtubule (MT) dynamics is necessary for proper spindle assembly and chromosome segregation. The MT destabilizing Kinesin-8, Kif18B, controls astral MT dynamics and spindle positioning. Kif18B interacts with importin α/ß as well as with the plus-tip tracking protein EB1, but how these associations modulate Kif18B is not known. We mapped the key binding sites on Kif18B, made residue-specific mutations, and assessed their impact on Kif18B function. Blocking EB1 interaction disrupted Kif18B MT plus-end accumulation and inhibited its ability to control MT length on monopolar spindles in cells. Blocking importin α/ß interaction disrupted Kif18B localization without affecting aster size. In vitro, importin α/ß increased Kif18B MT association by increasing the on-rate and decreasing the off-rate from MTs, which stimulated MT destabilization. In contrast, EB1 promoted MT destabilization without increasing lattice binding in vitro, which suggests that EB1 and importin α/ß have distinct roles in the regulation of Kif18B-mediated MT destabilization. We propose that importin α/ß spatially modulate Kif18B association with MTs to facilitate its MT destabilization activity. Our results suggest that Ran regulation is important not only to control molecular motor function near chromatin but also to provide a spatial control mechanism to modulate MT binding of nuclear localization signal-containing spindle assembly factors.

Composition and seasonal variation of the arbuscular mycorrhizal fungi spore community in litter, root mat, and soil from a subtropical rain forest.

Community composition and seasonal variation of sporulation of arbuscular mycorrhizal fungi (AMF) have been studied in soils from many ecosystems including subtropical forest. Yet, AMF community composition has been surveyed only from the mineral soil but not from the litter layer and the root mat, and long-term variation in sporulation is not fully understood. We sampled a 75-m2 plot from a subtropical forest to determine AMF community composition in the following habitats: the litter layer, the root mat, and the mineral soil. Moreover, samples were taken in fall, winter, spring, and summer over a 2-year period to follow the seasonal variation of AMF sporulation. We detected 47 AMF species belonging to six families and 14 genera, Glomeraceae and Acaulosporaceae being the most represented families. Sixteen species were common to all three habitats, five species were shared between two habitats, and 26 species were recovered exclusively from single habitats. While species richness was not significantly different among habitats, AMF total spore numbers were significantly higher in the litter and root mat compared to the soil. PERMANOVA did not detect a significant effect of habitats on community composition when species presence/absence was considered, but significant differences between litter versus soil and root mat versus soil were detected when spore abundance was considered. A seasonal pattern of spore abundance for species was not observed over the 2-year sampling period regardless of habitat. This study revealed that (i) different AMF species sporulate in the different habitats; thus, field surveys considering only the mineral soil might underestimate species richness and (ii) AMF species sporulate asynchronously in subtropical forest.

Effect on intrinsic peroxidase activity of substituting coevolved residues from Ω-loop C of human cytochrome c into yeast iso-1-cytochrome c.

Naturally-occurring variants of human cytochrome c (Cytc) that induce thrombocytopenia IV occur within Ω-loop C (residues 40-57). These variants enhance the peroxidase activity of human Cytc apparently by facilitating access to the heme by destabilizing Ω-loops C and D (residues 70-85). Given the importance of peroxidase activity in the early stages of apoptosis, we identified three sites with the EVmutation algorithm in or near Ω-loop C that coevolve and differ between yeast iso-1-Cytc and human Cytc. We prepared iso-1-Cytc variants with all possible combinations of the S40T, V57I and N63T substitutions to determine if these residues decrease the peroxidase activity of iso-1-Cytc to that of human Cytc producing an effective off state for a peroxidase signaling switch. At pH 6 and above, all variants significantly decreased peroxidase activity. However, the correlation of peroxidase activity with local and global stability, expected if cooperative unfolding of Ω-loops C and D is required for peroxidase activity, was generally poor. The m-values derived from the guanidine hydrochloride dependence of the kinetics of imidazole binding to horse Cytc, which is well-characterized by native-state hydrogen exchange methods, and K72A/K73A/K79A iso-1-Cytc show that local structural fluctuations and not subglobal cooperative unfolding of Ω-loops C and D are sufficient to permit binding of a small molecule like peroxide to the heme. A 2.46 Å structure of N63T iso-1-Cytc identifies a change to a hydrogen bond network linking Ω-loops C and D that could modulate the local fluctuations needed for the intrinsic peroxidase activity of Cytc.

Environmental identification of arbuscular mycorrhizal fungi using the LSU rDNA gene region: an expanded database and improved pipeline.

Arbuscular mycorrhizal fungi (AMF; Glomeromycota) are difficult to culture; therefore, establishing a robust amplicon-based approach to taxa identification is imperative to describe AMF diversity. Further, due to low and biased sampling of AMF taxa, molecular databases do not represent the breadth of AMF diversity, making database matching approaches suboptimal. Therefore, a full description of AMF diversity requires a tool to determine sequence-based placement in the Glomeromycota clade. Nonetheless, commonly used gene regions, including the SSU and ITS, do not enable reliable phylogenetic placement. Here, we present an improved database and pipeline for the phylogenetic determination of AMF using amplicons from the large subunit (LSU) rRNA gene. We improve our database and backbone tree by including additional outgroup sequences. We also improve an existing bioinformatics pipeline by aligning forward and reverse reads separately, using a universal alignment for all tree building, and implementing a BLAST screening prior to tree building to remove non-homologous sequences. Finally, we present a script to extract AMF belonging to 11 major families as well as an amplicon sequencing variant (ASV) version of our pipeline. We test the utility of the pipeline by testing the placement of known AMF, known non-AMF, and Acaulospora sp. spore sequences. This work represents the most comprehensive database and pipeline for phylogenetic placement of AMF LSU amplicon sequences within the Glomeromycota clade.

Imaging Chambers for Arabidopsis Seedlings for Mitotic Studies.

Flowering plants evolved away from creating centrosomes or conventional microtubule organizing centers. Therein, plants have posed a long-standing challenge to many of the conventional ideas for mitotic spindle construction and the process of chromosome segregation. The Arabidopsis seedling has emerged as a leading model for plant cell biological studies of the cytoskeleton and vesicle trafficking. Here we describe methods for creating a reusable chamber for mitotic studies in both seedling root and shoot cells with instruction for best practices with conventional microscopic techniques.

Perennial, but not annual legumes synergistically benefit from infection with arbuscular mycorrhizal fungi and rhizobia: a meta-analysis.

Many plant species simultaneously interact with multiple symbionts, which can, but do not always, generate synergistic benefits for their host. We ask if plant life history (i.e. annual vs perennial) can play an important role in the outcomes of the tripartite symbiosis of legumes, arbuscular mycorrhizal fungi (AMF), and rhizobia. We performed a meta-analysis of 88 studies examining outcomes of legume-AMF-rhizobia interactions on plant and microbial growth. Perennial legumes associating with AMF and rhizobia grew larger than expected based on their response to either symbiont alone (i.e. their response to co-inoculation was synergistic). By contrast, annual legume growth with co-inoculation did not differ from additive expectations. AMF and rhizobia differentially increased phosphorus (P) and nitrogen (N) tissue concentration. Rhizobium nodulation increased with mycorrhizal fungi inoculation, but mycorrhizal fungi colonization did not increase with rhizobium inoculation. Microbial responses to co-infection were significantly correlated with synergisms in plant growth. Our work supports a balanced plant stoichiometry mechanism for synergistic benefits. We find that synergisms are in part driven by reinvestment in complementary symbionts, and that time-lags in realizing benefits of reinvestment may limit synergisms in annuals. Optimization of microbiome composition to maximize synergisms may be critical to productivity, particularly for perennial legumes.

Cardiac natriuretic peptide deficiency sensitizes the heart to stress-induced ventricular arrhythmias via impaired CREB signalling.

AIMS: The cardiac natriuretic peptides [atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP)] are important regulators of cardiovascular physiology, with reduced natriuretic peptide (NP) activity linked to multiple human cardiovascular diseases. We hypothesized that deficiency of either ANP or BNP would lead to similar changes in left ventricular structure and function given their shared receptor affinities. METHODS AND RESULTS: We directly compared murine models deficient of ANP or BNP in the same genetic backgrounds (C57BL6/J) and environments. We evaluated control, ANP-deficient (Nppa-/-) or BNP-deficient (Nppb-/-) mice under unstressed conditions and multiple forms of pathological myocardial stress. Survival, myocardial structure, function and electrophysiology, tissue histology, and biochemical analyses were evaluated in the groups. In vitro validation of our findings was performed using human-derived induced pluripotent stem cell cardiomyocytes (iPS-CMs). In the unstressed state, both ANP- and BNP-deficient mice displayed mild ventricular hypertrophy which did not increase up to 1 year of life. NP-deficient mice exposed to acute myocardial stress secondary to thoracic aortic constriction (TAC) had similar pathological myocardial remodelling but a significant increase in sudden death. We discovered that the NP-deficient mice are more susceptible to stress-induced ventricular arrhythmias using both in vivo and ex vivo models. Mechanistically, deficiency of either ANP or BNP led to reduced myocardial cGMP levels and reduced phosphorylation of the cAMP response element-binding protein (CREBS133) transcriptional regulator. Selective CREB inhibition sensitized wild-type hearts to stress-induced ventricular arrhythmias. ANP and BNP regulate cardiomyocyte CREBS133 phosphorylation through a cGMP-dependent protein kinase 1 (PKG1) and p38 mitogen-activated protein kinase (p38 MAPK) signalling cascade. CONCLUSIONS: Our data show that ANP and BNP act in a non-redundant fashion to maintain myocardial cGMP levels to regulate cardiomyocyte p38 MAPK and CREB activity. Cardiac natriuretic peptide deficiency leads to a reduction in CREB signalling which sensitizes the heart to stress-induced ventricular arrhythmias.

Beyond "heartfelt condolences": A critical take on mainstream psychology's responses to anti-Black police brutality.

Anti-Black police brutality in the United States is not a new problem, but at least a 400-year old one. Mainstream psychology has responded to this critical racial and social justice issue by conceptualizing it primarily as an outcome of police officers' social cognition (e.g., threat perceptions) or implicit racial biases. Such individualistic and cognitive perspectives, however, ignore the fundamental role of anti-Black structural racism in facilitating the ability of law enforcement to terrorize, brutalize, and kill Black people with impunity. As with the media and public attention, mainstream psychology has also tended to frame acts of anti-Black police brutality as outliers, or occasional lethal and spectacular events, rather than as a broad spectrum of routine acts that structure policing and police brutality as a world for Black people in the United States. Informed by critical psychology, and the critical theoretical frameworks of critical race theory, intersectionality, and Afro-Pessimism, the goal of this article is to critically engage with the topic of anti-Black police brutality. By critically engage, we mean expose and challenge the economic, social, and material power relations that disproportionately expose Black people to police brutality; and conceptualize police brutality not as a series of aberrant incidents, but as a structure that in essence constructs and reifies Blackness and Whiteness. We also introduce the Anti-Black Police Brutality Continuum, a conceptual framework of police brutality as a broad spectrum of routine manifestations of anti-Black structural racism, and criticize mainstream psychology's deferral of a critical and transformative response to anti-Black police brutality. (PsycInfo Database Record (c) 2022 APA, all rights reserved).