HMGB1 mediates anemia of inflammation in murine sepsis survivors

Patients surviving sepsis develop anemia but the molecular mechanism is unknown. Here we observed that mice surviving polymicrobial Gram-negative sepsis develop hypochromic, microcytic anemia with reticulocytosis. The bone marrow of sepsis survivors accumulates polychromatophilic and orthochromatic erythroblasts. Compensatory extramedullary erythropoiesis in the spleen is defective during terminal differentiation. Circulating TNF and IL-6 are elevated for five days after the onset of sepsis, and serum HMGB1 levels are increased from day seven until at least day 28. Administration of recombinant HMGB1 to healthy mice mediates anemia with extramedullary erythropoiesis and significantly elevated reticulocyte counts. Moreover, administration of anti-HMGB1 monoclonal antibodies after sepsis significantly ameliorates the development of anemia (hematocrit 48.5+/-9.0% versus 37.4+/-6.1%,

Antitumor activity from antigen-specific CD8 T cells generated in vivo from genetically engineered human hematopoietic stem cells

The goal of cancer immunotherapy is the generation of an effective, stable, and self-renewing antitumor T-cell population. One such approach involves the use of high-affinity cancer-specific T-cell receptors in gene-therapy protocols. Here, we present the generation of functional tumor-specific human T cells in vivo from genetically modified human hematopoietic stem cells (hHSC) using a human/mouse chimera model. Transduced hHSC expressing an HLA-A*0201–restricted melanoma-specific T-cell receptor were introduced into humanized mice, resulting in the generation of a sizeable melanoma-specific naïve CD8^+ T-cell population. Following tumor challenge, these transgenic CD8^+ T cells, in the absence of additional manipulation, limited and cleared human melanoma tumors in vivo. Furthermore, the genetically enhanced T cells underwent proper thymic selection, because we did not observe any responses against non–HLA-matched tumors, and no killing of any kind occurred in the absence of a human thymus. Finally, the transduced hHSC established long-term bone marrow engraftment. These studies present a potential therapeutic approach and an important tool to understand better and to optimize the human immune response to melanoma and, potentially, to other types of cancer

Children behind bars: the lived experiences of adult children with incarcerated parents

This study aims to magnify the lived experiences of adults who grew up in the absence of their incarcerated parents. The researchers explored the thoughts, emotions, and perceptions of their lived experiences. This lead to the creation of the themes and meanings ascribed to these lived experiences. Parental incarceration is a type of separation that significantly affects the child\u27s behavioral and emotional implications, such as coping strategies. Interpretative Phenomenological analysis (IPA) was used as the analytical framework of this study. The researchers used an interview schedule for the 7 participants 5 are children of parents who committed common crimes while 2 are children of Martial Law detainees. The participants are adult children who are at least 18 years old with an incarcerated parent. The analysis reveals 3 super-ordinate themes namely, separation resulting from incarceration, consequences of the separation to the child and outcomes of the separation to the child. Themes were also created under each super-ordinate theme which results from the children\u27s perspectives, socio-emotional development and thoughts. The study captured 3 main points. First, the adult children are able to thrive and to become resilient when social support is present and when they are able to regulate their emotions. Second, external and internal stigmatization is present during the experience. Lastly, the adult children were able to conceptualize justice and morality when they realized that they were a part of a larger society

The magnitude of germinal center reactions is restricted by a fixed number of preexisting niches

Antibody affinity maturation occurs in the germinal center (GC), a highly dynamic structure that arises upon antigen stimulation and recedes after infection is resolved. While the magnitude of the GC reaction is highly fluctuating and depends on antigens or pathological conditions, it is unclear whether GCs are assembled ad hoc in different locations or in preexisting niches within B cell follicles. We show that follicular dendritic cells (FDCs), the essential cellular components of the GC architecture, form a predetermined number of clusters. The total number of FDC clusters is the same on several different genetic backgrounds and is not altered by immunization or inflammatory conditions. In unimmunized and germ-free mice, a few FDC clusters contain GC B cells; in contrast, immunization or autoimmune milieu significantly increases the frequency of FDC clusters occupied by GC B cells. Excessive occupancy of GC niches by GC B cells after repeated immunizations or in autoimmune conditions suppresses subsequent antibody responses to new antigens. These data indicate that the magnitude of the GC reaction is restricted by a fixed number of permissive GC niches containing preassembled FDC clusters. This finding may help in the future design of vaccination strategies and in the modulation of antibody-mediated autoimmunity

Reproductive quality evaluation of male Indian white prawn Penaeus indicus broodstock-fed diets supplemented with polychaete extracts (Marphysa sp.)

The present study determined the effect of different polychaete extracts, namely, total soluble fraction (TSF), neutral lipid fraction (NLF) and polar lipid fraction (PLF), in the maturation and sperm quality of male Penaeus indicus. Three levels (0.25, 0.50 and 1.00%) of extracts were included using a 3 × 3 factorial design. Groups fed the basal diet (BD) and fresh-frozen diet served as controls. Extracts in varying doses and control groups did not have a significant effect on broodstock survival (67–87%; p = 0.960), maturation rate (42–68%; p = 0.615), inter-spermatophore period (8–10 days; p = 0.505) or sperm viability (97–100%; p = 0.819). However, sperm counts of broodstock fed BD (11.70 × 106 ±1.05 × 106 per spermatophore) and those fed diets supplemented with polychaete extracts were significantly higher compared to that fed with control fresh diet at 0.73 × 106± .09 × 106 (p = 0.001). Spermatophore crude lipid was highest in groups fed 0.25% TSF and 0.25% PLF of broodstock (p =1.0 x10−6 ). Inclusion of TSF (0.25–1.00%) significantly increased the spermatophore crude protein content of broodstock compared to those fed with other diets (p = 1.20 × 10−5). These results demonstrate that NLF and TSF extracts are bioactive components of polychaete which when fed to male P. indicus, can stimulate aspects of sperm production