Synergizing Mouse and Human Studies to Understand the Heterogeneity of Obesity.

Obesity is routinely considered as a single disease state, which drives a "one-size-fits-all" approach to treatment. We recently convened the first annual University of North Carolina Interdisciplinary Nutrition Sciences Symposium to discuss the heterogeneity of obesity and the need for translational science to advance understanding of this heterogeneity. The symposium aimed to advance scientific rigor in translational studies from animal to human models with the goal of identifying underlying mechanisms and treatments.

Single-cell analyses and machine learning define hematopoietic progenitor and HSC-like cells derived from human PSCs.

Hematopoietic stem and progenitor cells (HSPCs) develop in distinct waves at various anatomical sites during embryonic development. The in vitro differentiation of human pluripotent stem cells (hPSCs) recapitulates some of these processes; however, it has proven difficult to generate functional hematopoietic stem cells (HSCs). To define the dynamics and heterogeneity of HSPCs that can be generated in vitro from hPSCs, we explored single-cell RNA sequencing (scRNAseq) in combination with single-cell protein expression analysis.

Analysis of the Spatiotemporal Development of Hematopoietic Stem and Progenitor Cells in the Early Human Embryo.

Definitive hematopoietic stem cells (HSCs) first emerge in the aorta-gonad-mesonephros (AGM) region in both mice and humans. An ex vivo culture approach has enabled recapitulation and analysis of murine HSC development. Knowledge of early human HSC development is hampered by scarcity of tissue: analysis of both CFU-C and HSC development in the human embryo is limited.

The design and implementation of an obstetric triage system for unscheduled pregnancy related attendances: a mixed methods evaluation.

Background: No standardised system of triage exists in Maternity Care and local audit identified this to be problematic. We designed, implemented and evaluated an Obstetric Triage System in a large UK maternity unit. This includes a standard clinical triage assessment by a midwife, within 15 min of attendance, leading to assignment to a category of clinical urgency (on a 4-category scale).

Conference report: the third BIRAX Regenerative Medicine Conference.

The third Britain/Israel Research and Academic Exchange Partnership Regenerative Medicine conference was recently held in Oxford (UK). This conference report summarizes highlights from the scientific program. There is a particular emphasis on internationally collaborative projects funded by this initiative, the young researchers' symposium, and a lively panel session focused on the relationships between industry and academia.

Enforced Expression of HOXB4 in Human Embryonic Stem Cells Enhances the Production of Hematopoietic Progenitors but Has No Effect on the Maturation of Red Blood Cells.

Unlabelled: : We have developed a robust, Good Manufacturing Practice-compatible differentiation protocol capable of producing scalable quantities of red blood cells (RBCs) from human pluripotent stem cells (hPSCs). However, translation of this protocol to the clinic has been compromised because the RBCs produced are not fully mature; thus, they express embryonic and fetal, rather than adult globins, and they do not enucleate efficiently. Based on previous studies, we predicted that activation of exogenous HOXB4 would increase the production of hematopoietic progenitor cells (HPCs) from hPSCs and hypothesized that it might also promote the production of more mature, definitive RBCs.

Concise review: programming human pluripotent stem cells into blood.

Blood disorders are treated with cell therapies including haematopoietic stem cell (HSC) transplantation as well as platelet and red blood cell transfusions. However the source of cells is entirely dependent on donors, procedures are susceptible to transfusion-transmitted infections and serious complications can arise in recipients due to immunological incompatibility. These problems could be alleviated if it was possible to produce haematopoietic cells in vitro from an autologous and renewable cell source.

Treatment with the reactive oxygen species scavenger EUK-207 reduces lung damage and increases survival during 1918 influenza virus infection in mice.

The 1918 influenza pandemic caused over 40 million deaths worldwide, with 675,000 deaths in the United States alone. Studies in several experimental animal models showed that 1918 influenza virus infection resulted in severe lung pathology associated with dysregulated immune and cell death responses. To determine if reactive oxygen species produced by host inflammatory responses play a central role in promoting severity of lung pathology, we treated 1918 influenza virus-infected mice with the catalytic catalase/superoxide dismutase mimetic, salen-manganese complex EUK-207 beginning 3 days postinfection.

Molecular basis for broad neuraminidase immunity: conserved epitopes in seasonal and pandemic H1N1 as well as H5N1 influenza viruses.

Influenza A viruses, including H1N1 and H5N1 subtypes, pose a serious threat to public health. Neuraminidase (NA)-related immunity contributes to protection against influenza virus infection. Antibodies to the N1 subtype provide protection against homologous and heterologous H1N1 as well as H5N1 virus challenge.

Protection against a lethal H5N1 influenza challenge by intranasal immunization with virus-like particles containing 2009 pandemic H1N1 neuraminidase in mice.

Highly pathogenic H5N1 influenza shares the same neuraminidase (NA) subtype with the 2009 pandemic (H1N1pdm09), and cross-reactive NA immunity might protect against or mitigate lethal H5N1 infection. In this study, mice were either infected with a sublethal dose of H1N1pdm09 or were vaccinated and boosted with virus-like particles (VLP) consisting of the NA and matrix proteins, standardized by NA activity and administered intranasally, and were then challenged with a lethal dose of HPAI H5N1 virus. Mice previously infected with H1N1pdm09 survived H5N1 challenge with no detectable virus or respiratory tract pathology on day 4.

Screen-detected colorectal cancers show improved cancer-specific survival when compared with cancers diagnosed via the 2-week suspected colorectal cancer referral guidelines.

Aim: Biennial screening for colorectal cancer using faecal occult blood testing has been shown to reduce the relative risk of mortality from colorectal cancer. The Norwich screening centre commenced screening in July 2006 and so far has diagnosed over 350 patients with colorectal cancer. We compared the stage at diagnosis and cancer-specific mortality and survival in patients diagnosed through screening with a cohort of symptomatic patients with colorectal cancer within the same age range.

Cigarette smoke extract (CSE) delays NOD2 expression and affects NOD2/RIPK2 interactions in intestinal epithelial cells.

Background: Genetic and environmental factors influence susceptibility to Crohn's disease (CD): NOD2 is the strongest individual genetic determinant and smoking the best-characterised environmental factor. Carriage of NOD2 mutations predispose to small-intestinal, stricturing CD, a phenotype also associated with smoking. We hypothesised that cigarette smoke extract (CSE) altered NOD2 expression and function in intestinal epithelial cells.

Immunization with 1976 swine H1N1- or 2009 pandemic H1N1-inactivated vaccines protects mice from a lethal 1918 influenza infection.

Background: Zoonotic infections with H1N1 influenza viruses that evolved initially from the 1918 virus (1918) and adapted to swine threatened a pandemic in 1976 (1976 swH1N1) and a novel reassortant H1N1 virus caused a pandemic in 2009-2010 (2009 pH1N1). Epidemiological and laboratory animal studies show that protection from severe 2009 pH1N1 infection is conferred by vaccination or prior infection with 1976 swH1N1 or 1918.

Objectives: Our aim was to demonstrate cross-protection by immunization with 2009 pH1N1 or 1976 swH1N1 vaccines following a lethal challenge with 1918.

Estrogen and progesterone affect responses to malaria infection in female C57BL/6 mice.

Background: Previous data from our laboratory suggest that gonadally intact C57BL/6 male mice are more likely than their female counterparts to die from Plasmodium chabaudi infection, to recover more slowly from weight loss and hematocrit loss, and to have reduced interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) responses. Removal of the ovaries, and hence, the primary production of sex steroids in females, reverses these differences.

Objective: We hypothesized that sex differences in response to P chabaudi may be mediated by differential synthesis of IFN-gamma and IL-10 that is influenced by estrogen, progesterone, or both.

Seoul virus enhances regulatory and reduces proinflammatory responses in male Norway rats.

Zoonotic pathogens, including hantaviruses, are maintained in the environment by causing persistent infection in the absence of disease in their reservoir hosts. Spillover of hantaviruses to humans can cause severe disease that is mediated by excessive proinflammatory responses. The mechanisms mediating hantaviral persistence in rodent reservoirs remain largely unknown.

A survey of rodent-borne pathogens carried by wild-caught Norway rats: a potential threat to laboratory rodent colonies.

Unintentional infection of laboratory rodents can compromise scientific research as well as the health of the animals and animal handlers. The source of contamination often is unknown, but may be introduced by wild rats from surrounding environments. To determine whether rats in Baltimore, Maryland, USA carry infectious agents commonly found in laboratory rodent colonies, we live-trapped 162 rats during 2005 to 2006 and screened them for a panel of viruses, bacteria and parasites.

Regulatory T cells enhance persistence of the zoonotic pathogen Seoul virus in its reservoir host.

Hantaviruses are zoonotic pathogens that maintain a persistent infection in their reservoir hosts, yet the mechanisms mediating persistence remain unknown. Regulatory T cell responses cause persistent infection by suppressing proinflammatory and effector T cell activity; hantaviruses may exploit these responses to cause persistence. To test this hypothesis, male Norway rats were inoculated with Seoul virus and regulatory T cells were monitored during infection.

A survey of zoonotic pathogens carried by Norway rats in Baltimore, Maryland, USA.

Norway rats (Rattus norvegicus) carry several zoonotic pathogens and because rats and humans live in close proximity in urban environments, there exists potential for transmission. To identify zoonotic agents carried by rats in Baltimore, Maryland, USA, we live-trapped 201 rats during 2005-2006 and screened them for a panel of viruses, bacteria, and parasites. Antibodies against Seoul virus (57.

Magnetic resonance imaging evaluation of patellofemoral malalignment.

Purpose: The purpose of this study was to determine the relationship between anterior knee pain secondary to suspected patellofemoral malalignment and tibial tubercle lateralization, patellar tilt, and patellar lateralization on magnetic resonance imaging.

Methods: We compared the bony relationships of the knee in patients with anterior knee pain and patients with nonspecific internal derangements of the knee. We measured the lateral deviation of the tibial tubercle and the patella from the trochlea, patellar tilt, and patellar and patellar tendon length.