Blimp-1-dependent and -independent natural antibody production by B-1 and B-1-derived plasma cells.

Natural antibodies contribute to tissue homeostasis and protect against infections. They are secreted constitutively without external antigenic stimulation. The differentiation state and regulatory pathways that enable continuous natural antibody production by B-1 cells, the main cellular source in mice, remain incompletely understood. Here we demonstrate that natural IgM-secreting B-1 cells in the spleen and bone marrow are heterogeneous, consisting of (a) terminally differentiated B-1-derived plasma cells expressing the transcriptional regulator of differentiation, Blimp-1, (b) Blimp-1+, and (c) Blimp-1neg phenotypic B-1 cells. Blimp-1neg IgM-secreting B-1 cells are not simply intermediates of cellular differentiation. Instead, they secrete similar amounts of IgM in wild-type and Blimp-1-deficient (PRDM-1ΔEx1A) mice. Blimp-1neg B-1 cells are also a major source of IgG3. Consequently, deletion of Blimp-1 changes neither serum IgG3 levels nor the amount of IgG3 secreted per cell. Thus, the pool of natural antibody-secreting B-1 cells is heterogeneous and contains a distinct subset of cells that do not use Blimp-1 for initiation or maximal antibody secretion

Knowledge and experience of raw food in animal hospital staff

Råfoder är en form av utfodring till både hund och katt som under senare år märkbart har ökat i trend. Utfodringsformen innebär att innehållet varken tillagas eller värme-behandlas innan det utfodras till djuren. Ämnet råfoder skapar diskussioner då både fördelar och nackdelar som uttrycks kring råfoder kan ha bristfällig evidens och vara av mer anekdotisk karaktär. Förespråkarna anser att råfoder är det mest naturliga fo-der en hund eller katt kan få och ett återkommande argument är hundens och vargens nära släktskap även om det finns studier som påvisar att deras respektive matsmältningssystem numera skiljer sig åt. Syftet med detta arbete var att undersöka vilka självupplevda kunskaper och erfarenheter som finns kring råfoder hos personal på två olika djursjukhus i Sverige ef-tersom nutrition är en viktig del av patienternas hälsa och därmed en stor del av djursjukvården. Kunskapsläget kan med fördel utredas då det är viktigt att personal på djursjukhus är uppdaterade kring olika utfodringsrutiner. Detta för att personalen enigt ska kunna ge professionella och evidensbaserade rekommendationer. Vidare undersöktes även skillnader mellan de olika yrkeskategorierna. Studien bestod av en enkätundersökning som skickades ut till de två djursjukhusen. En litteraturöversikt skrevs som komplement till studien. De vetenskapligt dokumenterade fördelar som finns kring råfoder är bland annat förbättrad munstatus samt potentiellt förändrad immunstatus. De vetenskapligt dokumenterade nackdelar som finns kring råfoder är bland annat innehåll av zoonotiska patogener, obalans i näringsämnen samt risk för främmande kroppar i gastrointestinalkanalen. För att kunna besvara enkäten behövde respondenterna känna till råfoder. Totalt analyserades 52 enkätsvar. Den största skillnaden mellan yrkesrollerna som kunde ses i enkätstudien var att de legitimerade veterinärerna, de legitimerade djursjukskö-tarna och övrig personal såg mer negativt på råfoder medan djurvårdarna var mer positivt inställda till råfoder. Djurvårdarna var den enda yrkesgrupp som var villiga att ge sina egna djur råfoder samt rekommendera råfoder till djurägarna. Alla yrkes-roller var överens om att de största riskerna med råfoder var kontamination med E. coli., Salmonella spp. etc. Resultat från enkäten visade att alla yrkesgrupperna ansåg att de har för lite kunskaper om råfoder, med undantag för gruppen övrig personal där sammansättningen var mer kluven. Hälften av den övriga personalen ansåg att de har tillräckliga kun-skaper kring råfoder, medan den andra hälften ansåg att de har otillräckliga kun-skaper. Erfarenheten var varierande, där majoriteten av djurvårdarna var mer positivt inställda till råfoder och resterande yrkesgrupper var mer kritiskt inställda.Raw food is a form of nutrition for both dogs and cats, a trend which has increased significantly in recent years. This type of feed means that the contents are neither cooked nor heat treated before being fed to the animals. The subject of raw food creates discussions as both the advantages and disadvantages expressed about raw food can have inadequate evidence and be of a more anecdotal nature. The advocates believe that raw food is the most natural feed a dog or cat can get and a recurring argument is that dog's and wolf's have a close kinship, even though there are studies that show that their respective digestive systems actually differ. The purpose of this study was to investigate the self-perceived knowledge and ex-periences that exist around raw food with staff at two different animal hospitals in Sweden, as nutrition is an important and large part of animal health care. The state of knowledge can advantageously be investigated as it is important that staff in animal hospitals are updated about different feeding routines as they should be able to pro-vide professional and evidence-based recommendations. Furthermore, experience and knowledge between staff from different professions were also examined. The study consisted of a questionnaire that was sent out to the two animal hospitals. A literature review was written as a supplement to this study. The scientifically docu-mented benefits of raw food include improved oral status as well as potentially im-proved immune status. The scientifically documented disadvantages that exist around raw food include contamination with zoonotic pathogens, an imbalance in nutrients and the risk of foreign bodies in the gastrointestinal tract. In order to be able to answer the questionnaire, there was a requirement question to ensure that the respondents were knowledgeable in the area of raw food. In total, 52 responses were analysed. The biggest difference between professions in the ques-tionnaire study was that the veterinarians, the legitimate animal nurses and other staff looked more negatively on raw food, while the animal care providers were more pos-itive towards raw food. The animal care providers were the only professional group who were willing to give their own animals’ raw food and recommend raw food to the animal owners. All professions agreed on that the biggest risks with raw food were possible contamination with E. coli, Salmonella spp. etc. The results of the survey showed that all the professional groups felt that they had too little knowledge about raw food, with the exception of other staff where the com-position of the group was more heterogeneous. Half of the other staff felt that they had sufficient knowledge, while the other half felt that they had insufficient knowledge of raw food. The experience varied, with the majority of the animal care providers being more positive about raw food, and the remaining professions were more critical

Voicing narratives of structural violence in interpersonal firearm violence research and prevention in the United States

Violence is defined as “the intentional use of physical force or power, threatened or actual, against oneself, another person, or against a group or community, that either results in or has a high likelihood of resulting in injury, death, psychological harm, maldevelopment, or deprivation.” Encompassed in this definition are multiple, interrelated forms of violence, including interpersonal firearm death and injury, but also the systems, policies, and practices enacted by those with power to advantage some groups while depriving others of meaningful opportunities for meeting their basic needs—known as “structural violence”. Yet dominant violence prevention narratives too often ignore or deemphasize the deeply intertwined threads of structural violence with other forms of violence, leading to policies and practices that are frequently insufficient, and often harmful, for reducing interpersonal firearm violence and building community safety, particularly in minoritized and structurally marginalized communities. We highlight ways in which limited scrutiny of structural violence, the omission of its defining characteristics—power and deprivation—from functional characterizations and frameworks of interpersonal firearm violence, and the inadequate distribution of power and resources to those most impacted by violence to self-determine narratives of and solutions to interpersonal firearm violence grossly impacts how interpersonal firearm violence is collectively conceived, discussed, and addressed. Expanding dominant narratives of interpersonal firearm violence, guided by the wisdom and determination of those most impacted, such that the goal of prevention and intervention efforts is not merely the absence of violence but rather the creation of a community safety and health ecosystem is essential to meet this critical moment in firearm violence research and prevention

High-Fat Diet: Bacteria Interactions Promote Intestinal Inflammation Which Precedes and Correlates with Obesity and Insulin Resistance in Mouse

Obesity induced by high fat (HF) diet is associated with inflammation which contributes to development of insulin resistance. Most prior studies have focused on adipose tissue as the source of obesity-associated inflammation. Increasing evidence links intestinal bacteria to development of diet-induced obesity (DIO). This study tested the hypothesis that HF western diet and gut bacteria interact to promote intestinal inflammation, which contributes to the progression of obesity and insulin resistance.Conventionally raised specific-pathogen free (CONV) and germ-free (GF) mice were given HF or low fat (LF) diet for 2-16 weeks. Body weight and adiposity were measured. Intestinal inflammation was assessed by evaluation of TNF-alpha mRNA and activation of a NF-kappaB(EGFP) reporter gene. In CONV but not GF mice, HF diet induced increases in body weight and adiposity. HF diet induced ileal TNF-alpha mRNA in CONV but not GF mice and this increase preceded obesity and strongly and significantly correlated with diet induced weight gain, adiposity, plasma insulin and glucose. In CONV mice HF diet also resulted in activation of NF-kappaB(EGFP) in epithelial cells, immune cells and endothelial cells of small intestine. Further experiments demonstrated that fecal slurries from CONV mice fed HF diet are sufficient to activate NF-kappaB(EGFP) in GF NF-kappaB(EGFP) mice.Bacteria and HF diet interact to promote proinflammatory changes in the small intestine, which precede weight gain and obesity and show strong and significant associations with progression of obesity and development of insulin resistance. To our knowledge, this is the first evidence that intestinal inflammation is an early consequence of HF diet which may contribute to obesity and associated insulin resistance. Interventions which limit intestinal inflammation induced by HF diet and bacteria may protect against obesity and insulin resistance

Molecular robots guided by prescriptive landscapes

Traditional robots rely for their function on computing, to store internal representations of their goals and environment and to coordinate sensing and any actuation of components required in response. Moving robotics to the single-molecule level is possible in principle, but requires facing the limited ability of individual molecules to store complex information and programs. One strategy to overcome this problem is to use systems that can obtain complex behaviour from the interaction of simple robots with their environment. A first step in this direction was the development of DNA walkers, which have developed from being non-autonomous, to being capable of directed but brief motion on one-dimensional tracks. Here we demonstrate that previously developed random walkers—so-called molecular spiders that comprise a streptavidin molecule as an inert ‘body’ and three deoxyribozymes as catalytic ‘legs’—show elementary robotic behaviour when interacting with a precisely defined environment. Single-molecule microscopy observations confirm that such walkers achieve directional movement by sensing and modifying tracks of substrate molecules laid out on a two-dimensional DNA origami landscape. When using appropriately designed DNA origami, the molecular spiders autonomously carry out sequences of actions such as ‘start’, ‘follow’, ‘turn’ and ‘stop’. We anticipate that this strategy will result in more complex robotic behaviour at the molecular level if additional control mechanisms are incorporated. One example might be interactions between multiple molecular robots leading to collective behaviour; another might be the ability to read and transform secondary cues on the DNA origami landscape as a means of implementing Turing-universal algorithmic behaviour

A global experiment on motivating social distancing during the COVID-19 pandemic

Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e., a controlling message) compared with no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared with the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing. Controlled motivation was associated with more defiance and less long-term behavioral intention to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges

Humanized zebrafish enhance human hematopoietic stem cell survival and promote acute myeloid leukemia clonal diversity

Xenograft models are invaluable tools in establishing the current paradigms of hematopoiesis and leukemogenesis. The zebrafish has emerged as a robust alternative xenograft model but, like mice, lack specific cytokines that mimic the microenvironment found in human patients. To address this critical gap, we generated the first humanized zebrafish that express human hematopoietic-specific cytokines (GM-CSF, SCF, and SDF1α). Termed GSS fish, these zebrafish promote survival, self-renewal and multilineage differentiation of human hematopoietic stem and progenitor cells and result in enhanced proliferation and hematopoietic niche-specific homing of primary human leukemia cells. Using error-corrected RNA sequencing, we determined that patient-derived leukemias transplanted into GSS zebrafish exhibit broader clonal representation compared to transplants into control hosts. GSS zebrafish incorporating error-corrected RNA sequencing establish a new standard for zebrafish xenotransplantation that more accurately recapitulates the human context, providing a more representative cost-effective preclinical model system for evaluating personalized response-based treatment in leukemia and therapies to expand human hematopoietic stem and progenitor cells in the transplant setting

Biochromoendoscopy: molecular imaging with capsule endoscopy for detection of adenomas of the GI tract

Current capsule endoscopy (CE) provides minimally invasive technology for gastrointestinal imaging, but has limited ability to discriminate different polyp types. Near Infrared Fluorescent (NIRF) probes activated by biomarkers upregulated in adenomas (e.g., cathepsin B) are potentially powerful tools to distinguish premalignant or malignant lesions from benign or inflammatory lesions