Macrophage memories of early-life injury drive neonatal nociceptive priming.

The developing peripheral nervous and immune systems are functionally distinct from those of adults. These systems are vulnerable to early-life injury, which influences outcomes related to nociception following subsequent injury later in life (i.e., "neonatal nociceptive priming"). The underpinnings of this phenomenon are unclear, although previous work indicates that macrophages are trained by inflammation and injury. Our findings show that macrophages are both necessary and partially sufficient to drive neonatal nociceptive priming, possibly due to a long-lasting remodeling in chromatin structure. The p75 neurotrophic factor receptor is an important effector in regulating neonatal nociceptive priming through modulation of the inflammatory profile of rodent and human macrophages. This "pain memory" is long lasting in females and can be transferred to a naive host to alter sex-specific pain-related behaviors. This study reveals a mechanism by which acute, neonatal post-surgical pain drives a peripheral immune-related predisposition to persistent pain following a subsequent injury.

Resilient anatomy and local plasticity of naive and stress haematopoiesis.

The bone marrow adjusts blood cell production to meet physiological demands in response to insults. The spatial organization of normal and stress responses are unknown owing to the lack of methods to visualize most steps of blood production. Here we develop strategies to image multipotent haematopoiesis, erythropoiesis and lymphopoiesis in mice. We combine these with imaging of myelopoiesis1 to define the anatomy of normal and stress haematopoiesis. In the steady state, across the skeleton, single stem cells and multipotent progenitors distribute through the marrow enriched near megakaryocytes. Lineage-committed progenitors are recruited to blood vessels, where they contribute to lineage-specific microanatomical structures composed of progenitors and immature cells, which function as the production sites for each major blood lineage. This overall anatomy is resilient to insults, as it was maintained after haemorrhage, systemic bacterial infection and granulocyte colony-stimulating factor (G-CSF) treatment, and during ageing. Production sites enable haematopoietic plasticity as they differentially and selectively modulate their numbers and output in response to insults. We found that stress responses are variable across the skeleton: the tibia and the sternum respond in opposite ways to G-CSF, and the skull does not increase erythropoiesis after haemorrhage. Our studies enable in situ analyses of haematopoiesis, define the anatomy of normal and stress responses, identify discrete microanatomical production sites that confer plasticity to haematopoiesis, and uncover unprecedented heterogeneity of stress responses across the skeleton.

Ayahuasca e saúde mental: efeitos do seu uso associado a casos de depressão / Ayahuasca and mental health: effects of its use in association with depresion cases / Ayahuasca y salud mental: efectos de sue uso en asociación con casos de depressión

O aumento de casos de depressão na população mundial leva ao questionamento sobre a eficácia dos tratamentos farmacológicos e fomenta a busca por tratamentos alternativos. Estudos a respeito da ayahuasca e seus efeitos na depressão vêm sendo realizados. Por meio de uma revisão integrativa, a partir da questão norteadora: "Quais são os efeitos da ayahuasca em indivíduos com depressão?", neste estudo buscou-se: (1) identificar potenciais usos terapêuticos do chá de ayahuasca; (2) analisar as características de segurança e riscos à saúde no seu uso; (3) investigar se o contexto do uso influencia seus efeitos. A busca de artigos foi realizada nas bases BVS e PubMed, produzidos entre 2017-2022, resultando em 8 artigos para análise. Os estudos evidenciaram efeitos antidepressivos advindos das interações neuroquímicas e das experiências psicológicas por meio da ayahuasca e apresentaram que a segurança e potencial terapêutico estão atrelados ao contexto de uso e à dosagem ingerida do chá (AU).

The increase in cases of depression in the world's population leads to questioning the effectiveness of pharmacological treatments and encourages the search for alternative treatments. Studies about ayahuasca andyour effectsondepressionhavebeenconducted. Guided by the question: "What are the effects of ayahuasca in individuals with depression?" this study was a integrativereview that aimed to: (1) identify potential therapeutic uses of ayahuasca tea;(2) analyzethesafetycharacteristics andhealthrisks inyour use; (3) investigatewhetherthecontextofuseinfluences your effects.The search for articles was conducted in the BVS and PubMed databases, produced between 2017-2022, resulting in 8 articles for analysis. Thestudies showed antidepressanteffectsresultingfromneurochemical interactions andpsychologicalexperiences as results of the use of ayahuasca and showed that the safety and therapeutic potential are linked to the context of use and the ingested dosage of the tea (AU).

El aumento de los casos de depresión en la población mundial lleva a cuestionar la eficacia de los tratamientos farmacológicos y fomenta la búsqueda de tratamientos alternativos. Se han realizado estudios sobre la ayahuasca y sus efectos sobre la depresión. Por medio de la cuestión: "¿Cuáles son los efectos de la ayahuasca en personas con depresión?", este estudio de revisión integrativabuscó: (1) identificar los usos terapéuticos potenciales del té de ayahuasca; (2) analizar las características de seguridad y los riesgos para la salud en su uso; (3) investigar si el contexto de uso influye en sus efectos. La búsqueda de artículos se realizó en las bases de datos BVS y PubMed, producidas entre 2017-2022, resultando 8 artículos para análisis. Fueron observados en los estudios efectos antidepresivos advenidos de la ayahuasca y que la seguridad y potencial terapéutico están vinculados al contexto de uso y la dosis ingerida del té (AU).

A new dracunculus species (Nematoda: Dracunculoidea) in neotropical otters (Lontra longicaudis) from Argentina: morphological and molecular characterization.

A new species of Dracunculus is described in wild neotropical otters, Lontra longicaudis, occurring in Corrientes, Argentina, based on morphological and molecular characteristics. Worms were located in the subcutaneous tissue from two of five investigated otters. Dracunculus jaguape n. sp. is differentiated from the 14 species of Dracunculus described from mammals and reptiles by the prominent dorsal and ventral papillae on the head; deirids posterior to nerve ring; male with long needlelike spicules and presence of gubernaculum; and long first stage larva. Phylogenetic analysis using the 18S rRNA positioned Dracunculus jaguape n. sp. in an anterior position to the rest of Dracunculus sequences available and COI positioned it in a separated clade sister to Dracunculus lutrae sequences. This is the first report on the presence of this nematode in Lontra longicaudis in Argentina.

The amygdala is not necessary for the familiarity aspect of recognition memory.

Dual-process accounts of item recognition posit two memory processes: slow but detailed recollection, and quick but vague familiarity. It has been proposed, based on prior rodent work, that the amygdala is critical for the familiarity aspect of item recognition. Here, we evaluated this proposal in male rhesus monkeys (Macaca mulatta) with selective bilateral excitotoxic amygdala damage. We used four established visual memory tests designed to assess different aspects of familiarity, all administered on touchscreen computers. Specifically, we assessed monkeys' tendencies to make low-latency false alarms, to make false alarms to recently seen lures, to produce curvilinear ROC curves, and to discriminate stimuli based on repetition across days. Three of the four tests showed no familiarity impairment and the fourth was explained by a deficit in reward processing. Consistent with this, amygdala damage did produce an anticipated deficit in reward processing in a three-arm-bandit gambling task, verifying the effectiveness of the lesions. Together, these results contradict prior rodent work and suggest that the amygdala is not critical for the familiarity aspect of item recognition.

Experimental and Theoretical Investigation of the Reaction of NH2 with NO at Very Low Temperatures.

The first experimental study of the low-temperature kinetics of the gas-phase reaction between NH2 and NO has been performed. A pulsed laser photolysis-laser-induced fluorescence technique was used to create and monitor the temporal decay of NH2 in the presence of NO. Measurements were carried out over the temperature range of 24-106 K, with the low temperatures achieved using a pulsed Laval nozzle expansion. The negative temperature dependence of the reaction rate coefficient observed at higher temperatures in the literature continues at these lower temperatures, with the rate coefficient reaching 3.5 × 10-10 cm3 molecule-1 s-1 at T = 26 K. Ab initio calculations of the potential energy surface were combined with rate theory calculations using the MESMER software package in order to calculate and predict rate coefficients and branching ratios over a wide range of temperatures, which are largely consistent with experimentally determined literature values. These theoretical calculations indicate that at the low temperatures investigated for this reaction, only one product channel producing N2 + H2O is important. The rate coefficients determined in this study were used in a gas-phase astrochemical model. Models were run over a range of physical conditions appropriate for cold to warm molecular clouds (10 to 30 K; 104 to 106 cm-3), resulting in only minor changes (<1%) to the abundances of NH2 and NO at steady state. Hence, despite the observed increase in the rate at low temperatures, this mechanism is not a dominant loss mechanism for either NH2 or NO under dark cloud conditions.

Functional connectivity of the default mode network predicts subsequent polysomnographically measured sleep in people with symptoms of insomnia.

Insomnia is often accompanied by excessive pre-sleep rumination. Such ruminative thinking is also associated with increased connectivity of the default mode network (DMN). It is likely that DMN connectivity and associated rumination contribute to the pathogenesis of insomnia. We hypothesized that resting state functional connectivity (rsFC) between the DMN and other brain regions prior to bedtime would predict objectively measured sleep among individuals with insomnia. Twenty participants (12 female; M age = 26.9, SD = 6.6 years) with symptoms of insomnia underwent an rsFC scan in the early evening followed by a night of polysomographically (PSG) measured sleep. Connectivity of the DMN with other brain regions was regressed against several PSG sleep metrics, including time in wake, N1, N2, N3, REM, total sleep time (TST), and sleep efficiency (SE) at a cluster corrected false discovery rate (FDR) correction P < 0.05. The connectivity between DMN and cortical regions was negatively correlated with PSG indices of poorer sleep including time in wake (right angular gyrus) and N1 (precuneus) but positively correlated with time in REM (orbitofrontal cortex), TST (insula, orbitofrontal cortex, superior frontal gyrus, paracingulate gyrus), SE (orbitofrontal cortex). Connectivity between DMN and the pons was negatively correlated with SE. Among individuals with symptoms of insomnia, better sleep was predicted by rsFC between the DMN and cortical regions involved in executive functioning, consciousness, and complex cognition. Findings raise the possibility that future interventions aimed at suppressing pre-sleep DMN activation may weaken synergy between pre-sleep ruminative worry and complex cognitions, potentially ameliorating problems falling asleep.

Ab Initio and Statistical Rate Theory Exploration of the CH (X2Π) + OCS Gas-Phase Reaction.

The first theoretical results regarding the gas-phase reaction mechanism and kinetics of the CH (X2Π) + OCS reaction are presented here. This reaction has a proposed importance in the removal of OCS in regions of the interstellar medium (ISM) and has the potential to form the recently observed HCS/HSC isomers, with both constitutional isomers having recently been observed in the L483 molecular cloud in a 40:1 ratio. Statistical rate theory simulations were performed on stationary points along the reaction potential energy surface (PES) obtained from ab initio calculations at the RO-CCSD(T)/aug-cc-pV(Q+d)Z//M06-2X-D3/aug-cc-pV(Q+d)Z level of theory over the temperature and total density range of 150-3000 K and 1011-1024 cm-3, respectively, using a Master Equation analysis. Exploration of the reaction potential energy surface revealed that all three pathways identified to create CS + HCO products required surmounting barriers of 16.5 kJ mol-1 or larger when CH approached the oxygen side of OCS, rendering this product formation negligible below 1000 K, and certainly under low-temperature ISM conditions. In contrast, when CH approaches the sulfur side of OCS, only submerged barriers are found along the reaction potential energy surface to create HCCO + S or CO + HCS, both of which are formed via a strongly bound OCC(H)S intermediate (-358.9 kJ mol-1). Conversion from HCS to HSC is possible via a barrier of 77.8 kJ mol-1, which is still -34.1 kJ mol-1 below the CH + OCS entrance channel. No direct route from CH + OCS to H + CO + CS was found from our ab initio calculations. Rate theory simulations suggest that the reaction has a strong negative temperature dependence, in accordance with the barrierless addition of CH to the sulfur side of OCS. Product branching fractions were also determined from MESMER simulations over the same temperature and total density range. The product branching fraction of CO + HCS reduces from 79% at 150 K to 0.0% at 800 K, while that of HCS dissociation to H + CS + CO increases from 22% at 150 K to 100% at 800 K. The finding of CO + HCS as the major product at the low temperatures relevant to the ISM, instead of H + CS + CO, is in opposition to the current supposition used in the KIDA database and should be adapted in astrochemical models as another source of the HCS isomer.

Ecological factors shaping the ectoparasite community assembly of the Azara's Grass Mouse, Akodon azarae (Rodentia: Cricetidae).

Parasites are integral members of the global biodiversity. They are useful indicators of environmental stress, food web structure and diversity. Ectoparasites have the potential to transmit vector-borne diseases of public health and veterinary importance and to play an important role in the regulation and evolution of host populations. The interlinkages between hosts, parasites and the environment are complex and challenging to study, leading to controversial results. Most previous studies have been focused on one or two parasite groups, while hosts are often co-infected by different taxa. The present study aims to assess the influence of environmental and host traits on the entire ectoparasite community composition of the rodent Akodon azarae. A total of 278 rodents were examined and mites (Mesostigmata), lice (Phthiraptera), ticks (Ixodida) and fleas (Siphonaptera) were determined. A multi-correspondence analysis was performed in order to analyze interactions within the ectoparasite community and the influence of environmental and host variables on this assembly. We found that environmental variables have a stronger influence on the composition of the ectoparasite community of A. azarae than the host variables analyzed. Minimum temperature was the most influential variable among the studied. In addition, we found evidence of agonistic and antagonistic interactions between ticks and mites, lice and fleas. The present study supports the hypothesis that minimum temperature plays a major role in the dynamics that shape the ectoparasite community of A. azarae, probably through both direct and indirect processes. This finding becomes particularly relevant in a climate change scenario.

Defects in placental syncytiotrophoblast cells are a common cause of developmental heart disease.

Placental abnormalities have been sporadically implicated as a source of developmental heart defects. Yet it remains unknown how often the placenta is at the root of congenital heart defects (CHDs), and what the cellular mechanisms are that underpin this connection. Here, we selected three mouse mutant lines, Atp11a, Smg9 and Ssr2, that presented with placental and heart defects in a recent phenotyping screen, resulting in embryonic lethality. To dissect phenotype causality, we generated embryo- and trophoblast-specific conditional knockouts for each of these lines. This was facilitated by the establishment of a new transgenic mouse, Sox2-Flp, that enables the efficient generation of trophoblast-specific conditional knockouts. We demonstrate a strictly trophoblast-driven cause of the CHD and embryonic lethality in one of the three lines (Atp11a) and a significant contribution of the placenta to the embryonic phenotypes in another line (Smg9). Importantly, our data reveal defects in the maternal blood-facing syncytiotrophoblast layer as a shared pathology in placentally induced CHD models. This study highlights the placenta as a significant source of developmental heart disorders, insights that will transform our understanding of the vast number of unexplained congenital heart defects.

Condições de trabalho, adoecimento e enfrentamento da enfermagem na pandemia de covid-19 em uma capital brasileira / Working conditions, illness and nursing coping in the covid-19 pandemic in a brazilian capital / Condiciones de trabajo, enfermedades y enfermería enfrentando la pandemia del covid-19 en una capital brasileña

Objetivo: Descrever as condições de trabalho, adoecimento e o enfrentamento da enfermagem na pandemia de COVID-19 em uma capital brasileira. Métodos: Trata-se de um estudo descritivo, transversal, com abordagem quantitativa. Os dados foram coletados entre agosto e setembro de 2021, de forma on-line. A análise foi realizada por meio do BioEstat 5.0, com técnicas de estatística descritiva e analítica a partir do teste Qui-quadrado de Pearson e do Exato de Fisher, sendo calculado o Odds Ratio nas variáveis em que houve associação significativa. Resultados: Dos 121 participantes do estudo, 106 eram do sexo feminino e mais de 50% possuíam dois vínculos de trabalho. 102 profissionais referiram receber baixos salários pela complexidade do trabalho desenvolvido e 46 apontaram condições precárias para o exercício profissional. Foi encontrada associação estatística na variável referente às orientações de como inspecionar as máscaras N95/PFF2 ou equivalente (p=0.017; OR=0.31; IC 95%=0.13-0.77) e na variável acerca dos profissionais que já apresentaram sintomas de COVID-19 e/ou tiveram diagnóstico confirmado (p=0.047; OR=0.43; IC 95%=0.20-0.93). Conclusão: O presente estudo aponta a necessidade de melhor organização e condições de trabalho nos serviços de saúde de forma que os profissionais de enfermagem possam prestar uma assistência de qualidade. (AU)

Objective: To describe the working conditions, illness and nursing coping in the COVID-19 pandemic in a Brazilian capital. Methods: This is a descriptive, cross-sectional study with a quantitative approach. Data were collected between August and September 2021, online. The analysis was performed using BioEstat 5.0, with descriptive and analytical statistical techniques from Pearson's chi-square test and Fisher's exact test, with the Odds Ratio being adequate for the variables in which there was a linked association. Results: Of the 121 study participants, 106 were female and more than 50% had two jobs. 102 professionals reported salaries earned due to the complexity of the work performed and 46 indicated precarious conditions for professional practice. A statistical association was found regarding the guidelines on how to inspect with masks N95 / PFF2 or equivalent (p = 0.017; OR = 0.31; 95% CI = 0.13-0.77) and the relative variable of professionals who are already associated students of COVID-19 and/or had a confirmed diagnosis (p = 0.047; OR = 0.43; 95% CI = 0.20-0.93). Conclusion: This study points to the need for better organization and working conditions in health services so that nursing professionals must provide quality care. (AU)

Objetivo: Describir las condiciones de trabajo, enfermedad y afrontamiento de enfermería en la pandemia de COVID-19 en una capital brasileña. Métodos: Se trata de un estudio descriptivo, transversal con enfoque cuantitativo. Los datos se recopilaron entre agosto y septiembre de 2021, en línea. El análisis se realizó mediante BioEstat 5.0, con técnicas estadísticas descriptivas y analíticas de la prueba chi-cuadrado de Pearson y la prueba exacta de Fisher, siendo la Odds Ratio adecuada para las variables en las que existía asociación ligada. Resultados: De los 121 participantes del estudio, 106 eran mujeres y más del 50% tenían dos trabajos. 102 profesionales reportaron sueldos percibidos por la complejidad del trabajo realizado y 46 señalaron condiciones precarias para el ejercicio profesional. Se encontró asociación estadística con respecto a las guías sobre cómo inspeccionar con mascarilla N95 / PFF2 o equivalente (p = 0.017; OR = 0.31; IC 95% = 0.13-0.77) y la variable relativa de profesionales que ya son estudiantes asociados de COVID- 19 y / o tenían un diagnóstico confirmado (p = 0,047; OR = 0,43; IC 95% = 0,20-0,93). Conclusión: Este estudio apunta a la necesidad de una mejor organización y condiciones de trabajo en los servicios de salud para que los profesionales de enfermería deban brindar una atención de calidad. (AU)

Outcomes of Open Bankart Repair Plus Inferior Capsular Shift Compared with Latarjet Procedure in Contact Athletes with Recurrent Anterior Shoulder Instability.

Background: Open Bankart repair plus inferior capsular shift (OBICS) and Latarjet procedure (LA) are considered appropriate treatment alternatives for high-performance athletes. The purpose of this study was to evaluate the functional outcomes and recurrence rate of each surgery. Our hypothesis: there were no differences between the two treatments. Methods: A prospective cohort study was conducted with n=90 contact athletes divided into two groups of 45 patients. One group was treated with OBICS, and the other one with LA. The mean follow-up period was 25 (24-32) months for the OBICS group and 26 (24-31) months for the LA group. Primary functional outcomes of each group were assessed at baseline, six months, one year, and two years after surgery. The functional outcomes were also compared between the groups. The evaluation tools used were the Western Ontario Shoulder Instability score (WOSI) and the American Shoulder and Elbow Surgeons scale (ASES). In addition, recurrent instability and range of motion (ROM) were also evaluated. Results: In each group, significant changes were found in the WOSI score and ASES scale from pre-op to postop. However, there were no significant differences between the functional outcomes of the groups at the final follow-up (P-values 0.73 and 0.19). Three dislocations and one subluxation (8.8%) were reported in the OBICS group, and three subluxations were reported in the LA group (6.6%), revealing no significant differences between the groups (P=0.37). Moreover, there were no significant differences between preoperative and postoperative ROM in each group or in terms of external rotation (ER) and ER in 90º abduction between the groups. Conclusion: No differences were found between OBICS and LA surgery. Both procedures can be indicated according to the surgeon's preference to reduce recurrence rates in contact athletes with recurrent anterior shoulder instability.

Macrophage epigenetic memories of early life injury drive neonatal nociceptive priming.

The developing peripheral nervous and immune systems are functionally distinct from adults. These systems are vulnerable to early life injury, which influences outcomes related to nociception following subsequent injury later in life (neonatal nociceptive priming). The underpinnings of this phenomenon are largely unknown, although previous work indicates that macrophages are epigenetically trained by inflammation and injury. We found that macrophages are both necessary and partially sufficient to drive neonatal nociceptive priming possibly due to a long-lasting epigenetic remodeling. The p75 neurotrophic factor receptor (NTR) was an important effector in regulating neonatal nociceptive priming through modulation of the inflammatory profile of rodent and human macrophages. This pain memory was long lasting in females and could be transferred to a naive host to alter sex-specific pain-related behaviors. This study reveals a novel mechanism by which acute, neonatal post-surgical pain drives a peripheral immune-related predisposition to persistent pain following a subsequent injury.

A new hyperelastic lookup table for RT-DC.

Real-time deformability cytometry (RT-DC) is an established method that quantifies features like size, shape, and stiffness for whole cell populations on a single-cell level in real-time. A lookup table (LUT) disentangles the experimentally derived steady-state cell deformation and the projected area to extract the cell stiffness in the form of the Young's modulus. So far, two lookup tables exist but are limited to simple linear material models and cylindrical channel geometries. Here, we present two new lookup tables for RT-DC based on a neo-Hookean hyperelastic material numerically derived by simulations based on the finite element method in square and cylindrical channel geometries. At the same time, we quantify the influence of the shear-thinning behavior of the surrounding medium on the stationary deformation of cells in RT-DC and discuss the applicability and impact of the proposed LUTs regarding past and future RT-DC data analysis. Additionally, we provide insights about the cell strain and stresses, as well as the influence resulting from the rotational symmetric assumption on the cell deformation and volume estimation. The new lookup tables and the numerical cell shapes are made freely available.

Artificial Intelligence on Diagnostic Aid of Leprosy: A Systematic Literature Review.

Leprosy is a neglected tropical disease that can cause physical injury and mental disability. Diagnosis is primarily clinical, but can be inconclusive due to the absence of initial symptoms and similarity to other dermatological diseases. Artificial intelligence (AI) techniques have been used in dermatology, assisting clinical procedures and diagnostics. In particular, AI-supported solutions have been proposed in the literature to aid in the diagnosis of leprosy, and this Systematic Literature Review (SLR) aims to characterize the state of the art. This SLR followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) framework and was conducted in the following databases: ACM Digital Library, IEEE Digital Library, ISI Web of Science, Scopus, and PubMed. Potentially relevant research articles were retrieved. The researchers applied criteria to select the studies, assess their quality, and perform the data extraction process. Moreover, 1659 studies were retrieved, of which 21 were included in the review after selection. Most of the studies used images of skin lesions, classical machine learning algorithms, and multi-class classification tasks to develop models to diagnose dermatological diseases. Most of the reviewed articles did not target leprosy as the study's primary objective but rather the classification of different skin diseases (among them, leprosy). Although AI-supported leprosy diagnosis is constantly evolving, research in this area is still in its early stage, then studies are required to make AI solutions mature enough to be transformed into clinical practice. Expanding research efforts on leprosy diagnosis, coupled with the advocacy of open science in leveraging AI for diagnostic support, can yield robust and influential outcomes.

Depressive disorders are associated with increased peripheral blood cell deformability: a cross-sectional case-control study (Mood-Morph).

Pathophysiological landmarks of depressive disorders are chronic low-grade inflammation and elevated glucocorticoid output. Both can potentially interfere with cytoskeleton organization, cell membrane bending and cell function, suggesting altered cell morpho-rheological properties like cell deformability and other cell mechanical features in depressive disorders. We performed a cross-sectional case-control study using the image-based morpho-rheological characterization of unmanipulated blood samples facilitating real-time deformability cytometry (RT-DC). Sixty-nine pre-screened individuals at high risk for depressive disorders and 70 matched healthy controls were included and clinically evaluated by Composite International Diagnostic Interview leading to lifetime and 12-month diagnoses. Facilitating deep learning on blood cell images, major blood cell types were classified and morpho-rheological parameters such as cell size and cell deformability of every individual cell was quantified. We found peripheral blood cells to be more deformable in patients with depressive disorders compared to controls, while cell size was not affected. Lifetime persistent depressive disorder was associated with increased cell deformability in monocytes and neutrophils, while in 12-month persistent depressive disorder erythrocytes deformed more. Lymphocytes were more deformable in 12-month major depressive disorder, while for lifetime major depressive disorder no differences could be identified. After correction for multiple testing, only associations for lifetime persistent depressive disorder remained significant. This is the first study analyzing morpho-rheological properties of entire blood cells and highlighting depressive disorders and in particular persistent depressive disorders to be associated with increased blood cell deformability. While all major blood cells tend to be more deformable, lymphocytes, monocytes, and neutrophils are mostly affected. This indicates that immune cell mechanical changes occur in depressive disorders, which might be predictive of persistent immune response.

The collagen receptor, discoidin domain receptor 2, functions in Gli1-positive skeletal progenitors and chondrocytes to control bone development.

Discoidin Domain Receptor 2 (DDR2) is a collagen-activated receptor kinase that, together with integrins, is required for cells to respond to the extracellular matrix. Ddr2 loss-of-function mutations in humans and mice cause severe defects in skeletal growth and development. However, the cellular functions of Ddr2 in bone are not understood. Expression and lineage analysis showed selective expression of Ddr2 at early stages of bone formation in the resting zone and proliferating chondrocytes and periosteum. Consistent with these findings, Ddr2+ cells could differentiate into hypertrophic chondrocytes, osteoblasts, and osteocytes and showed a high degree of colocalization with the skeletal progenitor marker, Gli1. A conditional deletion approach showed a requirement for Ddr2 in Gli1-positive skeletal progenitors and chondrocytes but not mature osteoblasts. Furthermore, Ddr2 knockout in limb bud chondroprogenitors or purified marrow-derived skeletal progenitors inhibited chondrogenic or osteogenic differentiation, respectively. This work establishes a cell-autonomous function for Ddr2 in skeletal progenitors and cartilage and emphasizes the critical role of this collagen receptor in bone development.

Anatomy of Hematopoiesis and Local Microenvironments in the Bone Marrow. Where to?

The shape and spatial organization -the anatomy- of a tissue profoundly influences its function. Knowledge of the anatomical relationships between parent and daughter cells is necessary to understand differentiation and how the crosstalk between the different cells in the tissue leads to physiological maintenance and pathological perturbations. Blood cell production takes place in the bone marrow through the progressive differentiation of stem cells and progenitors. These are maintained and regulated by a heterogeneous microenvironment composed of stromal and hematopoietic cells. While hematopoiesis has been studied in extraordinary detail through functional and multiomics approaches, much less is known about the spatial organization of blood production and how local cues from the microenvironment influence this anatomy. Here, we discuss some of the studies that revealed a complex anatomy of hematopoiesis where discrete local microenvironments spatially organize and regulate specific subsets of hematopoietic stem cells and/or progenitors. We focus on the open questions in the field and discuss how new tools and technological advances are poised to transform our understanding of the anatomy of hematopoiesis.