Racial, Ethnic, Sex, and Age Differences in COVID-19 Cases, Hospitalizations, and Deaths Among Incarcerated People and Staff in Correctional Facilities in Six Jurisdictions, United States, March-July 2020.

OBJECTIVES: To examine disparities by sex, age group, and race and ethnicity in COVID-19 confirmed cases, hospitalizations, and deaths among incarcerated people and staff in correctional facilities. METHODS: Six U.S. jurisdictions reported data on COVID-19 confirmed cases, hospitalizations, and deaths stratified by sex, age group, and race and ethnicity for incarcerated people and staff in correctional facilities during March 1- July 31, 2020. We calculated incidence rates and rate ratios (RR) and absolute rate differences (RD) by sex, age group, and race and ethnicity, and made comparisons to the U.S. general population. RESULTS: Compared with the U.S. general population, incarcerated people and staff had higher COVID-19 case incidence (RR = 14.1, 95% CI = 13.9-14.3; RD = 6,692.2, CI = 6,598.8-6,785.5; RR = 6.0, CI = 5.7-6.3; RD = 2523.0, CI = 2368.1-2677.9, respectively); incarcerated people also had higher rates of COVID-19-related deaths (RR = 1.6, CI = 1.4-1.9; RD = 23.6, CI = 14.9-32.2). Rates of COVID-19 cases, hospitalizations, and deaths among incarcerated people and corrections staff differed by sex, age group, and race and ethnicity. The COVID-19 hospitalization (RR = 0.9, CI = 0.8-1.0; RD = -48.0, CI = -79.1- -16.8) and death rates (RR = 0.8, CI = 0.6-1.0; RD = -11.8, CI = -23.5- -0.1) for Black incarcerated people were lower than those for Black people in the general population. COVID-19 case incidence, hospitalizations, and deaths were higher among older incarcerated people, but not among staff. CONCLUSIONS: With a few exceptions, living or working in a correctional setting was associated with higher risk of COVID-19 infection and resulted in worse health outcomes compared with the general population; however, Black incarcerated people fared better than their U.S. general population counterparts.

Neuroligin Plays a Role in Ethanol-Induced Disruption of Memory and Corresponding Modulation of Glutamate Receptor Expression.

Exposure to alcohol causes deficits in long-term memory formation across species. Using a long-term habituation memory assay in Caenorhabditis elegans, the effects of ethanol on long-term memory (> 24 h) for habituation were investigated. An impairment in long-term memory was observed when animals were trained in the presence of ethanol. Cues of internal state or training context during testing did not restore memory. Ethanol exposure during training also interfered with the downregulation of AMPA/KA-type glutamate receptor subunit (GLR-1) punctal expression previously associated with long-term memory for habituation in C. elegans. Interestingly, ethanol exposure alone had the opposite effect, increasing GLR-1::GFP punctal expression. Worms with a mutation in the C. elegans ortholog of vertebrate neuroligins (nlg-1) were resistant to the effects of ethanol on memory, as they displayed both GLR-1::GFP downregulation and long-term memory for habituation after training in the presence of ethanol. These findings provide insights into the molecular mechanisms through which alcohol consumption impacts memory.

Association of Two Opposing Responses Results in the Emergence of a Novel Conditioned Response.

Recent studies examining association of opposing responses, contrasting emotional valences, or counter motivational states have begun to elucidate how learning and memory processes can translate to clinical therapies for trauma or addiction. In the current study, association of opposing responses is tested in C. elegans. Due to its relatively simple and well-described nervous system, it was hypothesized that association of two oppositional stimuli presented in a delayed conditioning protocol would strengthen the behavioral response to the first stimulus (alpha conditioning). To test this, C. elegans were exposed to a tone vibration stimulus (to activate a mechanosensory-driven locomotor reversal response) paired with a blue light (to activate a forward locomotor response) at a 2-s delay. After five pairings, behavior was measured following a tone-alone stimulus. Worms that received stimulus pairing did not show an enhanced response to the first presented stimulus (tone vibration) but rather showed a marked increase in time spent in pause (cessation of movement), a new behavioral response (beta conditioning). This increase in pause behavior was accompanied by changes in measures of both backward and forward locomotion. Understanding the dynamics of conditioned behavior resulting from pairing of oppositional responses could provide further insight into how learning processes occur and may be applied.

Mesenchymal Stromal Cells Regulate Sialylations of N-Glycans, Affecting Cell Migration and Survival.

N-Glycosylations are an important post-translational modification of proteins that can significantly impact cell function. Terminal sialic acid in hybrid or complex N-glycans has been shown to be relevant in various types of cancer, but its role in non-malignant cells remains poorly understood. We have previously shown that the motility of human bone marrow derived mesenchymal stromal cells (MSCs) can be modified by altering N-glycoforms. The goal of this study was to determine the role of sialylated N-glycans in MSCs. Here, we show that IFN-gamma or exposure to culture media low in fetal bovine serum (FBS) increases sialylated N-glycans, while PDGF-BB reduces them. These stimuli alter mRNA levels of sialyltransferases such as ST3Gal1, ST6Gal1, or ST3Gal4, suggesting that sialylation of N-glycans is regulated by transcriptional control of sialyltransferases. We next show that 2,4,7,8,9-pentaacetyl-3Fax-Neu5Ac-CO2Me (3F-Neu5Ac) effectively inhibits sialylations in MSCs. Supplementation with 3F-Neu5Ac increases adhesion and migration of MSCs, as assessed by both videomicroscopy and wound/scratch assays. Interestingly, pre-treatment with 3F-Neu5Ac also increases the survival of MSCs in an in vitro ischemia model. We also show that pre-treatment or continuous treatment with 3F-Neu5Ac inhibits both osteogenic and adipogenic differentiation of MSCs. Finally, secretion of key trophic factors by MSCs is variably affected upon exposure to 3F-Neu5Ac. Altogether, our experiments suggest that sialylation of N-glycans is tightly regulated in response to environmental cues and that glycoengineering MSCs to reduce sialylated N-glycans could be beneficial to increase both cell migration and survival, which may positively impact the therapeutic potential of the cells.

Locally-Induced CaMKII Translocation Requires Nucleotide Binding.

Calcium-calmodulin-dependent protein kinase (CaMKII) is a molecule involved in several cell processes including plasticity related to learning and memory. Activation of NMDA-type glutamate receptors results in translocation of CaMKII to synapses. However, there are at least two distinct mechanisms by which glutamate-dependent CaMKII translocation occurs: one well-studied process resulting from whole-cell glutamate stimulation and one resulting from brief, local glutamate application. Unlike the relatively fast CaMKII translocation seen following whole-cell glutamate delivery (seconds), local application results in CaMKII translocation that occurs gradually within 6-10 min. This locally-induced translocation of CaMKII requires L-type Ca2+ channel co-activation but does not rely on GluN2B receptor subunit expression, unlike translocation following whole-cell application of glutamate. The current study examined if nucleotide binding is necessary for locally-induced CaMKII translocation, similar to CaMKII translocation resulting from whole-cell glutamate application. Three different mechanisms of inhibition were employed: staurosporine (ATP inhibitor), CaMKII(281-302) peptide inhibitor and expression of the K42M mutation. Locally-induced CaMKII translocation was moderately suppressed in the presence of either the broad-spectrum kinase inhibitor staurosporine (100 nm) or the CaMKII(281-302) peptide inhibitor. However, expression of the catalytically dead K42M mutation that prevents ATP-binding to CaMKII, significantly inhibited locally-induced translocation. Thus, CaMKII translocation following brief, local glutamate application requires nucleotide binding, providing support for future research into the molecular mechanisms of this distinct form of CaMKII translocation.

O chamado do inconsciente: trans, assédio sexual: voltando à questão / The call of the unconscious: Trans, sexual harassment - returning to the question / El llamado del inconsciente: trans, acoso sexual - volviendo al tema / L'appel de l'inconscient: Trans, harcélement sexuel - revenant sur la question

A partir de sua experiência anterior com os temas trans e assédio sexual, a autora argumenta que o diálogo com a psicanálise sobre essas questões controversas e complexas de nosso tempo é tão desafiador quanto urgente. O que acontece quando tentamos introduzir o conceito de inconsciente na realidade de nossa vida política? Ou então quando reconhecemos o lugar do inconsciente nas identidades públicas que encorajamos, habitamos e defendemos? Ambas as questões, trans e assédio, nos confrontam com a questão da justiça social. O papel da psicanálise é sempre o de alertar sobre nossos sonhos de um mundo melhor ou talvez ela esteja bem no centro de nossa luta para alcançá-los?

Drawing on her previous engagement with the topics of trans and sexual harassment, Jacqueline Rose will argue in this lecture that the dialogue with psychoanalysis on both of these vexed, complex issues of our time, is as challenging as it continues to be urgent. What happens when we try to insert the concept of the unconscious into the reality of our political lives? Or rather, when we recognise the place of the unconscious in the public identities we foster, inhabit, and fight. Both trans and harassment confront us with the question of social justice. Is it always the role of psychoanalysis to issue a caution in relation to our dreams of a better world, or might it belong right at the heart of our struggle to attain it?

A partir de su anterior experiencia con los temas trans y acoso sexual, Jacqueline Rose argumentará en esta conferencia que el diálogo con el psicoanálisis sobre ambos asuntos controvertidos y complejos de nuestro tiempo, es tan desafiador como urgente. ¿Qué sucede cuando intentamos introducir el concepto de inconsciente en la realidad de nuestra vida política? O, cuando reconocemos el lugar del inconsciente en las identidades públicas nosotros alentamos, habitamos y luchamos. Ambos temas, trans y acoso, nos enfrentan a la cuestión de la justicia social. ¿El papel del psicoanálisis es siempre alertar sobre nuestros sueños de un mundo mejor o, tal vez, esté en el centro de nuestra lucha por alcanzarlos?

À partir de son expérience préalable avec les thèmes trans et d'harcelement sexuel, Jacquelinhe Rose argumentera, dans cette conférence, que le dialogue avec la psychanalyse, concernant ces deux questions controverses et complèxes de notre temps, c'est autant un défi d'importance qu'il est encore urgente. Ce que se passe-t-il lorsque nous essayons d'introduire le concepte de l'inconscient dans la réalité de notre vie politique? Ou encore, lorsque nous reconnaissons la place de l'inconscient dans les idéntités publiques nous encourageons, nous habitons et nous battons. Les deux questions, trans et harcelèment, nous confrontent avec la question de la justice social. Le rôle de la psychanalyse est toujours celui d'avertir à propos de nos rêves d'un monde meilleur ou, peut-être, elle se situe au bon milieu de notre lutte pour les atteindre.

Specific Aims Workshop: Your Grant in a Sound Bite.

Grant writing is an essential component of research. In an increasingly competitive funding environment, writing successful grants has become an important focus of workshops and websites with each grant proposal component requiring detailed attention. The FUN 2017 Workshop session "Specific Aims: Your Grant in a Sound Bite" was dedicated to provide information and guidance in constructing and composing a Specific Aims document. This workshop drew on the presenters' collective combination of grant experience ranging from successful submissions to serving as grant reviewers. The focus of the session was to provide some key points with regards to the purpose of a Specific Aims document, the typical audience who will read the Specific Aims, and how to construct Specific Aims that catch the attention of reviewers and provide a clear and concise overview of the grant with the goal of attracting funding. The following is a brief summary of this workshop and includes links to additional resources to help construct a Specific Aims document that provides clarity and outlines the impact of proposed research.

Demonstrating Connections Between Neuron Signaling and Behavior using C. elegans Learning Assays and Optogenetics in a Laboratory Class.

Due to its well-described neural circuitry and identified connectome, the Caenorhabditis elegans model is well-suited for demonstrating connections between neuron signaling and behavioral outcome. In the 2017 FUN workshop at Dominican University, three behavior-based techniques were introduced for their ease of introduction to students, the flexible data collection options they offer and the inexpensive cost to implement in an education setting. These behavioral assays were adapted to address some of the challenges of performing C. elegans behavior experiments in lab classes and included: an associative chemosensory avoidance task to examine behavior of groups of worms, a mechanosensory task to observe individual worm behavior and an optogenetics assay to directly manipulate neuron signaling and simultaneously observe resultant behavior. Methods for these assays as well as example data collected by undergraduate students in a lab class are provided. FUN Workshop feedback and assessment indicate these assays were well-received and overall seen as valuable for introducing neuroscience and behavior to undergraduates in a lab class.

Chronic social defeat induces long-term behavioral depression of aggressive motivation in an invertebrate model system.

Losing a fight against a conspecific male (social defeat) induces a period of suppressed aggressiveness and general behaviour, often with symptoms common to human psychiatric disorders. Agonistic experience is also discussed as a potential cause of consistent, behavioral differences between individuals (animal "personality"). In non-mammals, however, the impact of single agonistic encounters typically last only hours, but then again studies of repeated intermittent defeat (chronic social defeat) are seldom. We report the effect of chronic social defeat in adult male crickets (Gryllus bimaculatus), for which all known behavioral effects of defeat last only 3 h. Firstly, after 48 h social isolation, crickets that experienced 5 defeats at 24 h intervals against the same, weight-matched opponent exhibited suppressed aggressiveness lasting >24 h, which was still evident when the animals were matched against an unfamiliar opponent at the last trial. Secondly, this longer-term depression of aggression also occurred in 48 h isolated crickets that lost 6 fights at 1 h intervals against unfamiliar opponents at each trial. Thirdly, crickets isolated as larvae until adult maturity (>16 days) were significantly more aggressive, and less variable in their aggressiveness at their very first fight than 48 h isolates, and also significantly more resilient to the effects of chronic social defeat. We conclude that losing an aggressive encounter in crickets has a residual effect, lasting at least 24 h, that accumulates when repeated defeats are experienced, and leads to a prolonged depression of aggressive motivation in subordinates. Furthermore, our data indicate that social interactions between young adults and possibly larvae can have even longer, possibly lifelong influences on subsequent behavior. Social subjugation is thus likely to be a prime determinant of inter-individual behavioral differences in crickets. Our work also opens new avenues for investigating proximate mechanisms underlying depression-like phenomena.

Parental and larval exposure to nicotine modulate spontaneous activity as well as cholinergic and GABA receptor expression in adult C. elegans.

Early nicotine exposure has been associated with many long-term consequences that include neuroanatomical alterations, as well as behavioral and cognitive deficits. To describe the effects of early nicotine exposure in Caenorhabditis elegans, the current study observed spontaneous locomotor activity (i.e., reversals) either in the presence or absence of nicotine. Expression of acr-16 (a nicotinic receptor subunit) and a ß-like GABA(A) receptor subunit, gab-1, were also examined with RT-PCR. Worms were exposed to nicotine (30 µM) throughout "zygote formation" (period that includes oocyte maturation, ovulation and fertilization), from hatching to adulthood ("larval development") or across both zygote and larval development. Adult larval-exposed worms only showed an increase in spontaneous behavior when tested on nicotine (p<0.001) but levels of activity similar to controls when tested on plain plates (p>0.30). Larval-exposed worms also showed control levels of acr-16 nicotinic receptor expression (p>0.10) but increased gab-1 expression relative to controls (p<0.01). In contrast, zygote-exposed and zygote- plus larval-exposed worms showed a similar increase in spontaneous behavior on plain plates (p<0.001 and p=0.001, respectively) but control levels of responding when tested on nicotine (p>0.90 for each). However, expression of acr-16 and gab-1 was downregulated in zygote-exposed (p<0.01 and p<0.05, respectively) and significantly upregulated in the zygote- plus larval-exposed worms (p<0.000 for each); most surprising was the over five-fold increase in gab-1 expression. These results suggest that spontaneous motor behavior and receptor expression are differentially modulated by nicotine exposure during larval development and/or zygote formation. As well, these findings demonstrate that C. elegans, as a model system, is also sensitive to nicotine exposure during early development and provides the basis for future research to uncover specific mechanisms by which early nicotine exposure modifies neuronal signaling and alters behavior.

The FMRFamide-related neuropeptide FLP-20 is required in the mechanosensory neurons during memory for massed training in C. elegans.

Lasting memories are likely to result from a lasting change in neurotransmission. In the nematode Caenorhabditis elegans, spaced training with a tap stimulus induces habituation to the tap that lasts for >24 h and is dependent on glutamate transmission, postsynaptic AMPA receptors, and CREB. Here we describe a distinct, presynaptic mechanism for a shorter lasting memory for tap habituation induced by massed training. We report that a FMRFamide-related peptide (FMRF = Phe-Met-Arg-Phe-NH(2)), FLP-20, is critical for memory lasting 12 h following massed training, but is not required for other forms of memory. Massed training correlated with a flp-20-dependent increase in synaptobrevin tagged with green fluorescent protein in the presynaptic terminals of the PLM mechanosensory neurons that followed the timeline of the memory trace. We also demonstrated that flp-20 is required specifically in the mechanosensory neurons for memory 12 h after massed training. These findings show that within the same species and form of learning, memory is induced by distinct mechanisms to create a lasting alteration in neurotransmission that is dependent upon the temporal pattern of training: memory of spaced training results from postsynaptic changes in the interneurons of the neural circuit, whereas memory of massed training results from presynaptic changes in the mechanosensory neurons of the neural circuit.

Differential stimulus-dependent synaptic recruitment of CaMKIIα by intracellular determinants of GluN2B.

The calcium-calmodulin activated kinase CaMKII mediates many forms of learning and memory. Activity-regulated translocation of CaMKII to synapses is important for its functions in synaptic plasticity. Here, we tested the role of the NMDA receptor subunit GluN2B in recruiting CaMKIIα to synapses with different paradigms: global bath stimulation of NMDA receptors, a chemical long term potentiation (cLTP) protocol that selectively activates synaptic NMDA receptors, or local stimulation of NMDA receptors at a contiguous set of ~10-30 synapses that triggers a propagating synaptic accumulation of CaMKII. Global or cLTP-induced synaptic accumulation of CaMKIIα occurred in wild-type but not sister GluN2B -/- cultured mouse hippocampal neurons. Expression of YFP-GluN2B, but not a similar level of YFP-GluN2A, rescued global and cLTP-induced CaMKIIα translocation. Using chimeric constructs, the pore-forming extracellular and membrane domains of GluN2A combined with the cytoplasmic tail of GluN2B were sufficient to rescue CaMKIIα translocation, whereas the reverse chimera was ineffective. Furthermore, the dual point mutation R1300Q,S1303D in GluN2B that blocks interaction of this high affinity site with CaMKII abolished rescue. Thus, CaMKII binding to GluN2B is required for global and cLTP-induced synaptic accumulation of CaMKIIα. However, surprisingly, locally induced propagating synaptic accumulation of CaMKIIα occurred normally in GluN2B -/- neurons, indistinguishably from wild-type. Thus, synaptic trapping of CaMKII during locally induced propagating translocation occurs by different mechanisms and molecular partners compared with global stimulation and cLTP paradigms. These findings underscore the complex regulatory properties and molecular interactions of CaMKIIα, a key player in synaptic plasticity.

Heterosynaptic molecular dynamics: locally induced propagating synaptic accumulation of CaM kinase II.

Calcium-calmodulin-dependent protein kinase II (CaMKII) is a key mediator of synaptic plasticity and learning. Global pyramidal cell glutamate stimulation induces translocation of CaMKII from dendritic shafts to spines. Here we show that local dendritic stimulation by puffing glutamate onto a region containing 7-32 synapses induces translocation of CaMKII to synapses initially at the puff site but that translocation subsequently spreads within dendrites to the distal dendrite arbor, resulting in a persistent, widespread synaptic accumulation. This locally induced propagating synaptic (L-IPS) accumulation of CaMKII requires activation of NMDA receptors and L-type Ca(2+) channels and is preceded by a Ca(2+) spike. L-IPS translocation of CaMKII alters biochemical signaling and is associated with an increase in AMPA receptor GluR1 at both stimulated and nonstimulated synapses and thus provides a molecular mechanism for heterosynaptic plasticity.

Essential role of SBP-1 activation in oxygen deprivation induced lipid accumulation and increase in body width/length ratio in Caenorhabditis elegans.

Epidemiological evidence suggests a link between chronic oxygen starvation and fat accumulation/obesity, however the underlying mechanism remains unclear. Using Caenorhabditis elegans we found extended oxygen deprivation resulted in activation of SBP-1, the worm homologue of SREBP1, a transcription factor important in maintaining lipid homeostasis. SBP-1 knockdown prevented hypoxia-induced fat accumulation and the associated increase in worm width/length ratio, demonstrating that SBP-1/SREBP1 plays an essential role in hypoxia-induced lipid accumulation and body shape alteration. This study provides the first evidence suggesting that activation of SREBP1 may be a critical pathogenic factor contributing to chronic hypoxia associated excessive fat accumulation/obesity in humans.

Blocking memory reconsolidation reverses memory-associated changes in glutamate receptor expression.

It has been reported that consolidated memories can return to a labile state when reactivated and undergo a process of re-storage, termed reconsolidation, required for later recall. We investigated memory for a nonassociative learning task (habituation) and found that memory for this task also undergoes reconsolidation after recall. To investigate reconsolidation, we first demonstrated that adult Caenorhabditis elegans are capable of reliable memory 48 h after habituation training (p < 0.05). When heat shock was administered immediately after a reminder, response magnitudes of trained animals matched response levels of untrained animals: the inhibitory effects of heat shock on protein synthesis disrupted memory reconsolidation. Pharmacological blockade of non-NMDA-type glutamate receptors during reminder also eliminated 48 h retention. When expression levels of a specific glutamate receptor subunit (GLR-1) (40% homology to mammalian AMPA-type glutamate receptors) (Hart et al., 1995; Maricq et al., 1995) were measured 48 h after training, there was a significant decrease in trained compared with untrained controls. If trained worms were given a reminder followed immediately by heat shock, the effect of training on GLR-1 levels was reversed. From these studies, we conclude that both the behavioral expression of long-term memory for habituation and a cellular correlate of that memory (the alteration in expression levels of GLR-1) in C. elegans can be altered after retrieval. Furthermore, conditions that impair memory consolidation similarly disrupt memory reconsolidation, suggesting that similar mechanisms are involved.

Decreased sensory stimulation reduces behavioral responding, retards development, and alters neuronal connectivity in Caenorhabditis elegans.

Activity-dependent plasticity is a critical component of nervous systems. We show that in Caenorhabditis elegans, worms raised in isolation made smaller responses to mechanosensory stimulation and were smaller and slower to begin laying eggs than age-matched group-raised worms. The glutamate receptor gene GLR-1 was critical for the observed alterations in behavior but not in size, whereas the cGMP-dependent protein kinase gene EGL-4 was critical for the observed changes in size but not the changes in behavior. Mechanosensory stimulation during development reversed the effects of isolation on behavior and began to reduce the effects of isolation on size. In C. elegans, the six mechanosensory touch neurons synapse onto the four pair of command interneurons for forward and backward movement. Touch (mechanosensory) neurons of worms raised in isolation expressed lower levels of green fluorescent protein (GFP)-tagged synaptobrevin than touch neurons of worms raised in colonies. Command interneurons of worms raised in isolation expressed lower levels of GFP-tagged glutamate receptors than command interneurons of worms raised in groups. Brief mechanical stimulation during larval development rescued the expression of GFP-tagged glutamate receptors but not GFP-tagged synaptobrevin. Together, these results indicate that the level of stimulation experienced by C. elegans during development profoundly affects the development of neuronal connectivity and has widespread cellular and behavioral consequences.

GLR-1, a non-NMDA glutamate receptor homolog, is critical for long-term memory in Caenorhabditis elegans.

Long-term memory for habituation to tap in Caenorhabditis elegans depends on glr-1, a homolog of mammalian non-NMDA glutamate receptors; mutations in glr-1 blocked long-term memory formation. Green fluorescent protein (GFP) constructs were used to visualize glr-1 expression in the interneurons of the mechanosensory circuit and synaptobrevin in the tap sensory neurons of trained and untrained worms. Trained animals had less GLR-1::GFP expression than untrained animals; there was no difference in the vesicle marker synaptobrevin. Heat shock during training blocked both the behavioral expression of long-term memory and the change in GLR-1::GFP expression. Thus, long-term memory in C. elegans is dependent on glr-1 and likely involves changes in the expression or localization of glutamate receptors.