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Impaired numerosity perception in developmental dyscalculia (low "number acuity") has been interpreted as evidence of reduced representational precision in the neurocognitive system supporting non-symbolic number sense. However, recent studies suggest that poor numerosity judgments might stem from stronger interference from non-numerical visual information, in line with alternative accounts that highlight impairments in executive functions and visuospatial abilities in the etiology of dyscalculia. To resolve this debate, we used a psychophysical method designed to disentangle the contribution of numerical and non-numerical features to explicit numerosity judgments in a dot comparison task and we assessed the relative saliency of numerosity in a spontaneous categorization task. Children with dyscalculia were compared to control children with average mathematical skills matched for age, IQ, and visuospatial memory. In the comparison task, the lower accuracy of dyscalculics compared to controls was linked to weaker encoding of numerosity, but not to the strength of non-numerical biases. Similarly, in the spontaneous categorization task, children with dyscalculia showed a weaker number-based categorization compared to the control group, with no evidence of a stronger influence of non-numerical information on category choice. Simulations with a neurocomputational model of numerosity perception showed that the reduction of representational resources affected the progressive refinement of number acuity, with little effect on non-numerical bias in numerosity judgments. Together, these results suggest that impaired numerosity perception in dyscalculia cannot be explained by increased interference from non-numerical visual cues, thereby supporting the hypothesis of a core number sense deficit.

Abstract Monocytes directly contribute to atherosclerosis development by their recruitment to plaques in which they differentiate into macrophages. In the present study, we ask how modulating monocyte glucose metabolism could affect their homeostasis and their impact on atherosclerosis. Here we investigate how circulating metabolites control monocyte behavior in blood, bone marrow and peripheral tissues of mice. We find that serum glucose concentrations correlate with monocyte numbers. In diet-restricted mice, monocytes fail to metabolically reprogram from glycolysis to fatty acid oxidation, leading to reduced monocyte numbers in the blood. Mechanistically, Glut1-dependent glucose metabolism helps maintain CD115 membrane expression on monocytes and their progenitors, and regulates monocyte migratory capacity by modulating CCR2 expression. Results from genetic models and pharmacological inhibitors further depict the relative contribution of different metabolic pathways to the regulation of CD115 and CCR2 expression. Meanwhile, Glut1 inhibition does not impact atherosclerotic plaque development in mouse models despite dramatically reducing blood monocyte numbers, potentially due to the remaining monocytes having increased migratory capacity. Together, these data emphasize the role of glucose uptake and intracellular glucose metabolism in controlling monocyte homeostasis and functions.

Summary: Brain metastases are the most common brain tumors in patients and are associated with poor prognosis. Investigating the colonization and outgrowth of brain metastases is challenging given the complexity of the organ, tissue sampling difficulty, and limited experimental models. To address this challenge, we employed a strategy to analyze the metastatic niche in established lesions, based on the release of a cell-penetrating mCherry tag from labeled tumor cells to neighboring niche cells, using different brain metastasis mouse models. We found that CD206+ macrophages were the most abundant cells taking up the mCherry label in established metastases. In vitro and in vivo experiments demonstrated that macrophages uptake and retain the canonical form of mCherry, even without the cell-penetrating portion of the tag. These results identify a specific macrophage subset in the brain that retains tumor-supplied fluorescent molecules, thereby complicating the long-term use of niche labeling strategies in established experimental brain metastasis.

This article describes online writing sessions developed for a CPED Community College Leadership education doctorate EdD program at a research-intensive, land-grant university. Sessions were introduced during the summer of 2020 after the existing executive, face-to-face program shifted entirely to online delivery due to the COVID-19 pandemic. The purpose of the writing sessions was to support students in the EdD, who are practitioners, with dissertation writing productivity by offering multiple weekly opportunities for synchronous writing sessions via online video conferencing. Although this program offering is in early implementation, initial feedback suggests the writing sessions supported students' dissertation progression and established a sense of community and social support in an online environment. This model could benefit online, hybrid, and face-to-face EdD programs in supporting writing progression. Design, delivery, and lessons learned are shared for the benefit of EdD programs as we continue to navigate program delivery impacts from the pandemic.

El artículo presenta un análisis de la recepción de la obra de Federico García Lorca en Italia durante las dos primeras décadas después de su muerte. A pesar de la dificultad histórica y bibliográfica de la época, varios hispanistas e hispanófilos italianos, incluyendo traductores, críticos y escritores, jugaron un papel importante en la introducción de la obra de Lorca en Italia. En el estudio se mencionan los primeros comentarios y reseñas de las obras lorquianas en la prensa italiana, así como entrevistas que se centraron tanto en su trabajo como director teatral como en su personalidad (de entre los primeros receptores, cabe destacar la labor de Levi y Marconi). Estas páginas, publicadas en revistas y diarios, ofrecen una visión temprana de la recepción de Lorca en Italia, pese a la hostilidad del gobierno italiano de la época. En una época en la que las traducciones predominaron sobre la interpretación crítica, se presta atención sobre todo a las figuras de tres hispanistas y comparatistas: Carlo Bo, Vittorio Bodini y Oreste Macrí. Los tres traducen y editan parte sustancial de la obra del poeta granadino, haciéndola accesible al público lector italiano a partir de la década de los cuarenta. Más allá de su labor traductográfica, los tres maestros hispanistas son los principales promotores también de la interpretación de la poesía, el teatro y la prosa de Lorca en Italia, convirtiéndose el autor español en uno de los escritores españoles contemporáneos más leídos y publicados en el país transalpino.

This paper charts the reflective inquiry of a small group of practitioners into their identity and experience whilst undertaking a professional doctorate. The authors met at the 2016 international conference on professional doctorates, held on 24th March, in London, whilst taking part in a conference panel discussion on the Graduate Learning Experience. This paper is the result of our correspondence and particularly, the three reflective vignettes that were produced by three of the group. The analysis of the findings of a narrative inquiry indicate a desire or belief in wanting to contribute to society in some way as an outcome or consequence of their gaining the award and doctoral title and that this title included a notion of responsibility to others.

One of the most urgent challenges for European academic and cultural institutions is to promote an intelligent use of materials and resources available on the web, by implementing best practices of web archiving, and building scientifically valid databases which can have a positive social impact. This paper will present the theoretical and methodological framework of Eredità Culturali, an ongoing project that aims at answering this challenge by focusing on the Florentine cultural heritage. The first stage of Eredità Culturali consisted in surveying similar initiatives within the European research landscape and examining national and international cataloguing models and standards to build a data entry prototype that interacts with other systems. Hence, a flexible and open-access web platform has been designed to validate, preserve and consult cultural information from disparate data sets into a single archive. A geo-referenced information system has also been developed, in which four databases designed by the Department's research groups of Geography, Archaeology, Performing Arts and History of the Book will converge and make sound data available for both non-academic and professional audiences. The analytical investigation is integrated with original ways of dissemination that will facilitate historical connections between different cultural heritages and legacies.

Environmental and climatic factors, as well as host demographics and behaviour, significantly influence the exposure of herbivorous mammalian hosts to pathogens such as Bacillus anthracis, the causative agent of anthrax. Until the early 1990s in Kruger National Park (KNP), kudu (Tragelaphus strepsiceros) was the host species most affected by anthrax, with outbreaks occurring predominantly in the dry season, particularly during drought cycles. However, the most affected host species has shifted to impala (Aepyceros melampus), with more frequent anthrax outbreaks during the wet season. This study investigates the roles of environmental variation and other host species in this shift. Temporal trends in environmental variables such as precipitation, soil moisture, temperature, and normalised difference vegetation index (NDVI) were analyzed in relation to anthrax occurrence (presence/ absence and counts). Additionally, correlations between host species' densities and anthrax mortalities over time were examined. Anthrax cases in 1990 were concentrated in the central and northern regions of KNP(excluding Pafuri), primarily affected kudus; while subsequent mortalities affected mostly impala and were restricted to the far north, in Pafuri. Significant correlations were found between kudu anthrax mortality and a decrease in NDVI, average temperature, SPI-6 and SPI-12 (Standardised Precipitation Index in various time intervals. Conversely, anthrax occurrence in impalas was associated with a decline in SPI-3, and temperature rise, with increased mortality during the rainy season. Elephant density correlated negatively with kudu mortality, but a positive correlation with both impala mortality and impala density. The study concludes that environmental variables and species' densities may alter the diversity and frequency of hosts exposed to B. anthracis. Climate extremes and alterations therein may exacerbate anthrax severity by modifying species susceptibility and their probability of exposure over time.

This paper describes the redesign of a community college executive leadership doctoral program that seeks to develop senior-level leaders. The paper provides how the redesign was intentionally aligned with the CPED principles and specifically the sixth principle. The paper sought data from students, faculty and other documents to gain an insight into the impact of aligning the program with principles and design concepts. The paper suggests that it is important for this program to integrate examples from practice and practitioners, include job shadowing experiences for students and faculty, and ensure there are active learning activities that are relevant to the students. The paper includes an overview of the program redesign as well as reflection on the first iteration of the new coursework through student's voice, faculty feedback, and a discussion of lessons learned.

One alternative to make biofuels and replace petroleum-based fuels is to convert non-food ingredients from Ulva reticulata seaweed into bioethanol. Seventy percent of the earth's surface is covered by microalgae and seaweeds that can be converted into bioethanol. Ulva seaweed contains 50.3% carbohydrates in the form of heteropolysaccharides such as glucose, arabinose, rhamnose and xylose. Optimization of the seaweed hydrolysis catalyzed by HNO3 using Microwave irradiation was done by varying acid concentration (1, 3, 5, 7%), hydrolysis time (30, 40, 50, and 60 minutes), and hydrolysis temperature (75, 100, 125, 150°C). Fermentation was carried out by varying inoculum concentrations (6, 8, and 10% (v/v)) for 5, 6 and 7 days at a temperature of 30°C and a pH of 4.5. Analysis of the surface texture of the sample was carried out by Scanning Electron Microscopy (SEM). The analysis of reducing sugars concentration was carried out using the dinitrosalicylate (DNS) method. Ethanol analysis was carried out by Gas Chromatography (GC). The results of SEM analysis showed that prior to hydrolysis, the surface morphology of the powder was still compact and intact. Whereas after being hydrolyzed with HNO3 it was seen that the surface texture of the powder suffered significant damage. The hydrolysis results showed that the optimum conditions during the pretreatment of U. reticulata powder was at acid concentration of 7%, reaction time of 50 minutes, reaction temperature of 150°C and 250 watts of power which gave hydrolysate with reducing sugar concentration of 86.5 g/L. Fermentation of the hydrolysate using yeast Saccharomyces cerevisiae produced bioethanol with concentration of 37.2% as analyzed using a gas chromatograph.

BackgroundImmune cell expression profiling from patient samples is critical for the successful development of immuno-oncology agents and is useful to understand mechanism-of-action, to identify exploratory biomarkers predictive of response, and to guide treatment selection and combination therapy strategies. LAG-3 is an inhibitory immune checkpoint that can suppress antitumor T-cell responses and targeting LAG-3, in combination with PD-1, is a rational approach to enhance antitumor immunity that has recently demonstrated clinical success. Here, we sought to identify human immune cell subsets that express LAG-3 and its ligands, to characterize the marker expression profile of these subsets, and to investigate the potential relationship between LAG-3 expressing subsets and clinical outcomes to immuno-oncology therapies.MethodsComprehensive high-parameter immunophenotyping was performed using mass and flow cytometry of tumor-infiltrating lymphocytes (TILs) and peripheral blood mononuclear cells (PBMCs) from two independent cohorts of samples from patients with various solid tumor types. Profiling of circulating immune cells by single cell RNA-seq was conducted on samples from a clinical trial cohort of melanoma patients treated with immunotherapy.ResultsLAG-3 was most highly expressed by subsets of tumor-infiltrating CD8 T central memory (TCM) and effector memory (TEM) cells and was frequently co-expressed with PD-1. We determined that these PD-1+ LAG-3+ CD8 memory T cells exhibited a unique marker profile, with greater expression of activation (CD69, HLA-DR), inhibitory (TIM-3, TIGIT, CTLA-4) and stimulatory (4-1BB, ICOS) markers compared to cells that expressed only PD-1 or LAG-3, or that were negative for both checkpoints. In contrast to tumors, LAG-3 expression was more limited in circulating immune cells from healthy donors and solid tumor patients. Additionally, we found abundant expression of the LAG-3 ligands MHC-II and galectin-3 in diverse immune cell types, whereas FGL1 and LSECtin were minimally expressed by immune cells in the tumor microenvironment (TME). Lastly, we found an inverse relationship between baseline and on-treatment levels of circulating LAG3 transcript-expressing CD8 memory T cells and response to combination PD-1 and CTLA-4 blockade in a clinical trial cohort of melanoma patients profiled by scRNAseq.ConclusionsThese results provide insights into the nature of LAG-3- and ligand-expressing immune cells within the TME, and suggest a biological basis for informing mechanistic hypotheses, treatment selection strategies, and combination immunotherapy approaches to support continued development of dual PD-1 and LAG-3 blockade.

The discovery of gasdermin D (GSDMD) as the terminal executioner of pyroptosis provided a large piece of the cell death puzzle, whilst simultaneously and firmly putting the gasdermin family into the limelight. In its purest form, GSDMD provides a connection between the innate alarm systems to an explosive, inflammatory form of cell death to jolt the local environment into immunological action. However, the gasdermin field has moved rapidly and significantly since the original seminal work and novel functions and mechanisms have been recently uncovered, particularly in response to infection. Gasdermins regulate and are regulated by mechanisms such as autophagy, metabolism and NETosis in fighting pathogen and protecting host. Importantly, activators and interactors of the other gasdermins, not just GSDMD, have been recently elucidated and have opened new avenues for gasdermin-based discovery. Key to this is the development of potent and specific tool molecules, so far a challenge for the field. Here we will cover some of these recently discovered areas in relation to bacterial infection before providing an overview of the pharmacological landscape and the challenges associated with targeting gasdermins.

Environmental and climatic factors, as well as host demographics and behaviour, significantly influence the exposure of herbivorous mammalian hosts to pathogens such as Bacillus anthracis, the causative agent of anthrax. Until the early 1990s in Kruger National Park (KNP), kudu (Tragelaphus strepsiceros) was the host species most affected by anthrax, with outbreaks occurring predominantly in the dry season, particularly during drought cycles. However, the most affected host species has shifted to impala (Aepyceros melampus), with more frequent anthrax outbreaks during the wet season. This study investigates the roles of environmental variation and other host species in this shift. Temporal trends in environmental variables such as precipitation, soil moisture, temperature, and normalised difference vegetation index (NDVI) were analyzed in relation to anthrax occurrence (presence/ absence and counts). Additionally, correlations between host species' densities and anthrax mortalities over time were examined. Anthrax cases in 1990 were concentrated in the central and northern regions of KNP(excluding Pafuri), primarily affected kudus; while subsequent mortalities affected mostly impala and were restricted to the far north, in Pafuri. Significant correlations were found between kudu anthrax mortality and a decrease in NDVI, average temperature, SPI-6 and SPI-12 (Standardised Precipitation Index in various time intervals. Conversely, anthrax occurrence in impalas was associated with a decline in SPI-3, and temperature rise, with increased mortality during the rainy season. Elephant density correlated negatively with kudu mortality, but a positive correlation with both impala mortality and impala density. The study concludes that environmental variables and species' densities may alter the diversity and frequency of hosts exposed to B. anthracis. Climate extremes and alterations therein may exacerbate anthrax severity by modifying species susceptibility and their probability of exposure over time. [ABSTRACT FROM AUTHOR]

NLR family, apoptosis inhibitory proteins (NAIPs) detect bacterial flagellin and structurally related components of bacterial type III secretion systems (T3SS), and recruit NLR family CARD domain containing protein 4 (NLRC4) and caspase-1 into an inflammasome complex that induces pyroptosis. NAIP/NLRC4 inflammasome assembly is initiated by the binding of a single NAIP to its cognate ligand, but a subset of bacterial flagellins or T3SS structural proteins are thought to evade NAIP/NLRC4 inflammasome sensing by not binding to their cognate NAIPs. Unlike other inflammasome components such as NLRP3, AIM2, or some NAIPs, NLRC4 is constitutively present in resting macrophages and not known to be induced by inflammatory signals. Here, we demonstrate that Toll-like receptor (TLR)-dependent p38 mitogen-activated protein kinase signaling up-regulates NLRC4 transcription and protein expression in murine macrophages, which licenses NAIP detection of evasive ligands. In contrast, TLR priming in human macrophages did not up-regulate NLRC4 expression, and human macrophages remained unable to detect NAIP-evasive ligands even following priming. Critically, ectopic expression of either murine or human NLRC4 was sufficient to induce pyroptosis in response to immunoevasive NAIP ligands, indicating that increased levels of NLRC4 enable the NAIP/NLRC4 inflammasome to detect these normally evasive ligands. Altogether, our data reveal that TLR priming tunes the threshold for the murine NAIP/NLRC4 inflammasome to enable inflammasome responses against immunoevasive or suboptimal NAIP ligands. These findings provide insight into species-specific TLR regulation of NAIP/NLRC4 inflammasome activation. [ABSTRACT FROM AUTHOR]

Impaired numerosity perception in developmental dyscalculia (low "number acuity") has been interpreted as evidence of reduced representational precision in the neurocognitive system supporting non‐symbolic number sense. However, recent studies suggest that poor numerosity judgments might stem from stronger interference from non‐numerical visual information, in line with alternative accounts that highlight impairments in executive functions and visuospatial abilities in the etiology of dyscalculia. To resolve this debate, we used a psychophysical method designed to disentangle the contribution of numerical and non‐numerical features to explicit numerosity judgments in a dot comparison task and we assessed the relative saliency of numerosity in a spontaneous categorization task. Children with dyscalculia were compared to control children with average mathematical skills matched for age, IQ, and visuospatial memory. In the comparison task, the lower accuracy of dyscalculics compared to controls was linked to weaker encoding of numerosity, but not to the strength of non‐numerical biases. Similarly, in the spontaneous categorization task, children with dyscalculia showed a weaker number‐based categorization compared to the control group, with no evidence of a stronger influence of non‐numerical information on category choice. Simulations with a neurocomputational model of numerosity perception showed that the reduction of representational resources affected the progressive refinement of number acuity, with little effect on non‐numerical bias in numerosity judgments. Together, these results suggest that impaired numerosity perception in dyscalculia cannot be explained by increased interference from non‐numerical visual cues, thereby supporting the hypothesis of a core number sense deficit. Research Highlights: A strongly debated issue is whether impaired numerosity perception in dyscalculia stems from a deficit in number sense or from poor executive and visuospatial functions.Dyscalculic children show reduced precision in visual numerosity judgments and weaker number‐based spontaneous categorization, but no increasing reliance on continuous visual properties.Simulations with deep neural networks demonstrate that reduced neural/computational resources affect the developmental trajectory of number acuity and account for impaired numerosity judgments.Our findings show that weaker number acuity in developmental dyscalculia is not necessarily related to increased interference from non‐numerical visual cues. [ABSTRACT FROM AUTHOR]

Introduction: Deciphering the biological and physical requirements for the outset of multicellularity is limited to few experimental models. The early embryonic development of annual killifish represents an almost unique opportunity to investigate de novo cellular aggregation in a vertebrate model. As an adaptation to seasonal drought, annual killifish employs a unique developmental pattern in which embryogenesis occurs only after undifferentiated embryonic cells have completed epiboly and dispersed in low density on the egg surface. Therefore, the first stage of embryogenesis requires the congregation of embryonic cells at one pole of the egg to form a single aggregate that later gives rise to the embryo proper. This unique process presents an opportunity to dissect the self-organizing principles involved in early organization of embryonic stem cells. Indeed, the physical and biological processes required to form the aggregate of embryonic cells are currently unknown.Methods: Here, we developed an in silico, agent-based biophysical model that allows testing how cell-specific and environmental properties could determine the aggregation dynamics of early Killifish embryogenesis. In a forward engineering approach, we then proceeded to test two hypotheses for cell aggregation (cell-autonomous and a simple taxis model) as a proof of concept of modeling feasibility. In a first approach (cell autonomous system), we considered how intrinsic biophysical properties of the cells such as motility, polarity, density, and the interplay between cell adhesion and contact inhibition of locomotion drive cell aggregation into self-organized clusters. Second, we included guidance of cell migration through a simple taxis mechanism to resemble the activity of an organizing center found in several developmental models.Results: Our numerical simulations showed that random migration combined with low cell-cell adhesion is sufficient to maintain cells in dispersion and that aggregation can indeed arise spontaneously under a limited set of conditions, but, without environmental guidance, the dynamics and resulting structures do not recapitulate in vivo observations.Discussion: Thus, an environmental guidance cue seems to be required for correct execution of early aggregation in early killifish development. However, the nature of this cue (e.g., chemical or mechanical) can only be determined experimentally. Our model provides a predictive tool that could be used to better characterize the process and, importantly, to design informed experimental strategies.

Category: Diabetes; Midfoot/Forefoot Introduction/Purpose: Diabetic foot infections (DFI) are complications of poorly controlled diabetes and are the proximate cause of lower extremity amputations. Wounds lead to bacterial colonization, the development of a biofilm and antibiotic resistance. Management requires aggressive debridement, maximizing vascularity and preserving viable soft tissues. Large dorsal and plantar incisions may be necessary for adequate debridement. The purpose of this paper is to discuss a technique that allows both dorsal and plantar approaches, using smaller incisions, for the management of diabetic foot infections and to evaluate complications and outcomes with this technique. Methods: From January 2015 through January 2022, diabetic patients with osteomyelitis or abscesses were identified. Exclusion criteria were osteomyelitis or abscesses of the tibia, ankle, fibula, talus, calcaneus, or navicular; gangrene; or patients who underwent an amputation of their toe(s) or foot as primary treatment. Inclusion criteria were patients with abscesses or osteomyelitis of the mid- or forefoot who underwent a pull-though technique. This Technique uses dorsal and plantar incisions, sterile betadine scrub (soap) and RAY-TEC sponges (Johnson and Johnson, Dublin, Ohio, U.S.A). After plantar wound debridement, a small dorsal incision is made over the plantar wound. The betadine soaked sponges are then individually passed, one time, from dorsal to plantar (pull-through), mimicking the face of a clock (12-1-2, 3, etc.), followed by formal irrigation solutions. Demographics and complications were recorded. Results: 155 patients were diagnosed with osteomyelitis or abscess of the foot or ankle. 82 patients had excluded areas of infection. 29 patients underwent a primary amputation as index procedure. 34 patients only had debridements leaving 10 patients, with 18 procedures, utilizing the pull-through technique. All pull-though patients presented with plantar wounds in the forefoot or midfoot. The 7 males, 3 females averaged 62.8 years (29-81). BMI averaged 34.1(25-48.8), with an A1C of 8.1 (6.3-12.9). Plantar wound duration was 11.4 months (3-36) and only one patient accurately detected a 5.07 monofilament. One patient had a positive smoking history, 6 patients had peripheral arterial disease. No skin or wound problems occurred as a result of the pull-through technique and no patient required an amputation. Of the 18 procedures (n=36, incisions plus plantar wounds) only one plantar wound (3%) failed to completely heal. Conclusion: DFI leads to production of biofilms and bacterial tissue adherence by various organisms. Surgical debridement is a key part of the treatment. Plantar wounds need larger incisions for acceptable debridement but may not adequately reach dorsal areas of involvement. The addition of a pull-through technique allows for the placement of small dorsal incisions to augment the plantar debridement, providing more debridement of the involved DFI. This technique did not produce any skin necrosis or additional wound problems, with 97% of wounds plus incisions completely healing. The authors feel this is an adequate adjunct for the management of mid-and forefoot DFI.

Adipose tissue is composed of a number of adipocytes and a number of other cells including immune cells. Here the authors use single-cell sequencing of murine brown adipose tissue immune cells and describe multiple macrophage and monocyte subsets and show that monocytes contribute to brown adipose tissue expansion.

Abstract Over the last decade, the African turquoise killifish, Nothobranchius furzeri, has emerged as an important model system for the study of vertebrate biology and ageing. Propagation of laboratory inbred strains of Nothobranchius furzeri, such as GRZ, however, can pose challenges due to the short window of fertility, the efforts and space requirements involved in continuous strain maintenance, and the risks of further inbreeding. The current method for long term strain preservation relies on arrest of embryos in diapause. To create an alternative for long term maintenance, we developed a robust protocol to cryopreserve and revive sperm for in vitro fertilization (IVF). We tested a variety of extender and activator buffers for sperm IVF, as well as cryoprotectants to achieve practical long-term storage and fertilization conditions tailored to this species. Our protocol enabled sperm to be preserved in a cryogenic condition for months and to be revived with an average of 40% viability upon thawing. Thawed sperm were able to fertilize nearly the same number of eggs as natural fertilization, with an average of ~ 25% and peaks of ~ 55% fertilization. This technical advance will greatly facilitate the use of N. furzeri as a model organism.

This essay describes an online writing group introduced to a CPED EdD program at a research-intensive, land-grant university during the summer of 2020 when the existing face-to-face program shifted to fully online delivery. The purpose of the writing sessions was to support EdD student practitioners with dissertation writing productivity by offering multiple weekly opportunities for synchronous writing sessions via Zoom online video conferencing. Although this new program is still in development, initial student feedback suggests that the writing sessions not only supported students’ dissertation progression, but it also established a sense of community and social support in an online environment. Lessons learned are shared, and we argue that this could be an ideal time to offer online writing sessions, especially since the pandemic will continue into the coming months.

Stress exposure has been shown to modulate innate and adaptive immune responses. Indeed, stress favors myelopoiesis and monocyte generation and contributes to cardiovascular disease development. As sex hormones regulate innate and adaptive immune responses, we decided to investigate whether stress exposure leads to a different immune response in female and male mice. Our data demonstrated that psychosocial stressinduced neutrophilia in male, but not female mice. Importantly, we identified that B‐cell numbers were reduced in female, but not male mice upon exposure to stress. Thus, our study revealed that the stress‐induced immune alterations are sex‐dependent, and this is an important feature to consider for future investigations. [ABSTRACT FROM AUTHOR]

Summary: Despite the ubiquitous function of macrophages across the body, the diversity, origin, and function of adrenal gland macrophages remain largely unknown. We define the heterogeneity of adrenal gland immune cells using single-cell RNA sequencing and use genetic models to explore the developmental mechanisms yielding macrophage diversity. We define populations of monocyte-derived and embryonically seeded adrenal gland macrophages and identify a female-specific subset with low major histocompatibility complex (MHC) class II expression. In adulthood, monocyte recruitment dominates adrenal gland macrophage maintenance in female mice. Adrenal gland macrophage sub-tissular distribution follows a sex-dimorphic pattern, with MHC class IIlow macrophages located at the cortico-medullary junction. Macrophage sex dimorphism depends on the presence of the cortical X-zone. Adrenal gland macrophage depletion results in altered tissue homeostasis, modulated lipid metabolism, and decreased local aldosterone production during stress exposure. Overall, these data reveal the heterogeneity of adrenal gland macrophages and point toward sex-restricted distribution and functions of these cells.

Abstract Numerosity perception is thought to be foundational to mathematical learning, but its computational bases are strongly debated. Some investigators argue that humans are endowed with a specialized system supporting numerical representations; others argue that visual numerosity is estimated using continuous magnitudes, such as density or area, which usually co-vary with number. Here we reconcile these contrasting perspectives by testing deep neural networks on the same numerosity comparison task that was administered to human participants, using a stimulus space that allows the precise measurement of the contribution of non-numerical features. Our model accurately simulates the psychophysics of numerosity perception and the associated developmental changes: discrimination is driven by numerosity, but non-numerical features also have a significant impact, especially early during development. Representational similarity analysis further highlights that both numerosity and continuous magnitudes are spontaneously encoded in deep networks even when no task has to be carried out, suggesting that numerosity is a major, salient property of our visual environment.

The number of elements in a small set of items is appraised in a fast and exact manner, a phenomenon called subitizing. In contrast, humans provide imprecise responses when comparing larger numerosities, with decreasing precision as the number of elements increases. Estimation is thought to rely on a dedicated system for the approximate representation of numerosity. While previous behavioral and neuroimaging studies associate subitizing to a domain-general system related to object tracking and identification, the nature of small numerosity processing is still debated. We investigated the neural processing of numerosity across subitizing and estimation ranges by examining electrophysiological activity during the memory retention period in a delayed numerical match-to-sample task. We also assessed potential differences in the neural signature of numerical magnitude in a fully non-symbolic or cross-format comparison. In line with behavioral performance, we observed modulation of parietal-occipital neural activity as a function of numerosity that differed in two ranges, with distinctive neural signatures of small numerosities showing clear similarities with those observed in visuospatial working memory tasks. We also found differences in neural activity related to numerical information in anticipation of single vs. cross-format comparison, suggesting a top-down modulation of numerical processing. Finally, behavioral results revealed enhanced performance in the mixed-format conditions and a significant correlation between task performance and symbolic mathematical skills. Overall, we provide evidence for distinct mechanisms related to small and large numerosity and differences in numerical encoding based on task demands.

Category: Diabetes Introduction/Purpose: Calcification of the vessels is a common finding in patients with peripheral arterial disease (PAD) and can indicate a compromised extremity. The incidence of PAD disease has been reported in approximately 29% of diabetics and calcification may also indicate a foot or ankle at risk. The purpose of this study was to evaluate toe pressures (TP) in patients who presented with radiographic calcification of vessels in the foot and ankle and determine if adequate flow existed despite the calcification. Methods: Using a Diabetic Registry from January, 2011 through February, 2021, a retrospective review was used to identify patients who presented with x-ray calcifications of the foot and ankle and was compared to patients who had undergone TP. For the purpose of this study, the findings of Vitti et al., who demonstrated that no surgical failures occurred in patients with TP >68 mm Hg, were used to stratify patients as having adequate (68 mm Hg) or a compromised ( 68 mm Hg with only 2 patients demonstrating compromised TP. Conclusion: Calcification of vessels in the foot and ankle has been stated to suggest vascular compromise and indicate a foot and ankle at risk. These patients are obese, older individuals with poor glycemic control who, for the most part, are neuropathic. However, in this small study group, patients who had calcification of their vessels and had TP, demonstrated that despite the calcifications, adequate blood flow was achieved into the foot. This may indicate that combined with improved glycemic control, patients can undergo elective or semi-elective surgical procedures with adequate healing rates expected.

Cell death plays a critical role in inflammatory responses. During pyroptosis, inflammatory caspases cleave Gasdermin D (GSDMD) to release an N-terminal fragment that generates plasma membrane pores that mediate cell lysis and IL-1 cytokine release. Terminal cell lysis and IL-1β release following caspase activation can be uncoupled in certain cell types or in response to particular stimuli, a state termed hyperactivation. However, the factors and mechanisms that regulate terminal cell lysis downstream of GSDMD cleavage remain poorly understood. In the course of studies to define regulation of pyroptosis during Yersinia infection, we identified a line of Card19-deficient mice (Card19lxcn) whose macrophages were protected from cell lysis and showed reduced apoptosis and pyroptosis, yet had wild-type levels of caspase activation, IL-1 secretion, and GSDMD cleavage. Unexpectedly, CARD19, a mitochondrial CARD-containing protein, was not directly responsible for this, as an independently-generated CRISPR/Cas9 Card19 knockout mouse line (Card19Null) showed no defect in macrophage cell lysis. Notably, Card19 is located on chromosome 13, immediately adjacent to Ninj1, which was recently found to regulate cell lysis downstream of GSDMD activation. RNA-seq and western blotting revealed that Card19lxcn BMDMs have significantly reduced NINJ1 expression, and reconstitution of Ninj1 in Card19lxcn immortalized BMDMs restored their ability to undergo cell lysis in response to caspase-dependent cell death stimuli. Card19lxcn mice exhibited increased susceptibility to Yersinia infection, whereas independently-generated Card19Null mice did not, demonstrating that cell lysis itself plays a key role in protection against bacterial infection, and that the increased infection susceptibility of Card19lxcn mice is attributable to loss of NINJ1. Our findings identify genetic targeting of Card19 being responsible for off-target effects on the adjacent gene Ninj1, disrupting the ability of macrophages to undergo plasma membrane rupture downstream of gasdermin cleavage and impacting host survival and bacterial control during Yersinia infection.