Background:The contribution of B lymphocytes to the bone loss caused by estrogen deficiency is unclear. Results: Deletion of the cytokine receptor activator of NFB ligand from B lymphocytes, but not T lymphocytes, blunted bone loss in ovariectomized mice. Conclusion: Cytokine production by B lymphocytes contributes to ovariectomy-induced bone loss. Significance: This mechanism may be relevant to the mechanisms responsible for postmenopausal osteoporosis.

Interferon-producing killer dendritic cells (IKDCs) have only recently been described and they share some properties with plasmacytoid dendritic cells (pDCs). We now show that they can arise from some of the same progenitors. However, IKDCs expressed little or no RAG-1, Spi-B, or TLR9, but responded to the TLR9 agonist CpG ODN by production of IFN␥. The RAG-1 ؊ pDC2 subset was more similar to IKDCs than RAG-1 ؉ pDC1s with respect to IFN␥ production. The Id-2 transcriptional inhibitor was essential for production of IKDCs and natural killer (NK) cells, but not pDCs. IKDCs developed from lymphoid progenitors in culture but, unlike pDCs, were not affected by Notch receptor ligation. While IKDCs could be made from estrogen-sensitive progenitors, they may have a slow turnover because their numbers did not rapidly decline in hormonetreated mice. Four categories of progenitors were compared for IKDC-producing ability in transplantation assays. Of these, Lin ؊ Sca- IntroductionFunctionally specialized cells in the innate and adaptive immune systems are still being discovered, 1-3 and each needs to be fully understood in terms of developmental history. Replacement of immune effector cells from hematopoietic stem cells (HSCs) is an ordered process where multiple lineage potentials are gradually lost coincident with gain of specialized functions, and within the context of patterns of transcriptional activity and surface marker expression. [4][5][6][7][8][9] The focus of the present study was on recently identified interferon-producing killer dendritic cells (IKDCs). IKDCs exhibit "hybrid" phenotypic and functional characteristics of dendritic and natural killer (NK) cells. 2,3 Shared properties include expression of B220, CD11c, CD122, and NK1.1, as well as production of interferons, capability of antigen presentation, and strong cytotoxic or antitumor activities. Thus, IKDCs are unique, multifunctional cells that merit study with respect to development.HSCs and several categories of primitive progenitors reside in the lineage marker-negative Sca1 ϩ c-kit hi (LSK) fraction of BM. Up-regulation of Flk-2 and corresponding loss of erythroid/ megakaryocytic potential is an early event that sets the stage for lymphopoiesis. 10,11 LSKs include 2 overlapping subsets of lymphopoietic cells identified as Flk-2 ϩ/Ϫ Thy1.1 Ϫ L-selectin ϩ progenitors (LSPs) and RAG-1 ϩ Flk-2 ϩ CD27 ϩ early lymphoid progenitors (ELPs). [12][13][14] Although clearly B-and T-lymphoid specified, LSPs and ELPs retain some potential for myeloid, NK, and dendritic cell (DC) lineages. Firm commitment in these pathways and repression of alternative fates involve expression of key transcription factors, such as Pax5, Notch-1, and Spi-B, as well as environmental cues. 15 All lymphoid progenitors in BM are rapidly and preferentially depleted in estrogen-treated mice. 16,17 Progenitors that can more quickly give rise to lymphocytes reside in a Lin Ϫ Flk-2 ϩ c-Kit Lo prolymphocyte (Pro-L) fraction that includes Lin Ϫ c-Kit Lo Sca-1 ϩ IL-7R␣ ϩ common lymphoid proge...

Porcine circovirus 2 (PCV2) can cause porcine circovirus diseases and porcine circovirus-associated diseases (PCVD/PCVAD), which are widely presented in swine-producing countries. Since the discovery of this virus, considerable efforts have been devoted to understanding this pathogen and its interactions with its host. Here, we review the current state of knowledge on interactions between host cell factors and PCV2 with respect to viral proliferation, virus-induced cell apoptosis and autophagy, and host antiviral defenses during PCV2 infection. We also review mouse model systems for PCV2 infection.

Retinoids are known to have potent effects on hemopoietic stem cell integrity, and our objective was to learn whether they influence cells destined to replenish the immune system. Total CD19+ B lineage cells increased substantially in the marrow and spleens of all-trans retinoic acid (ATRA)-treated C57BL6 mice, while lymphoid progenitors were reduced. All B lymphoid progenitors were targets of ATRA in culture and overall cell yields declined without reductions in proliferation. Remarkably, ATRA shortened the time required for primitive progenitors to generate CD19+ cells. PCR analysis and a panel of retinoid acid receptor (RAR)/retinoid X receptor agonist treatments suggested that RARα mediates these responses. The transcription factors EBF1 and Pax-5 were elevated during treatment and ATRA had similar effects on human B cell differentiation. That is, it inhibited the expansion of human progenitor cells and accelerated their differentiation to B lineage cells. There may be previously unsuspected side effects of ATRA therapy, and the new findings suggest retinoids can normally contribute to the lymphopoietic environment in bone marrow.

Classical swine fever (CSF) caused by classical swine fever virus (CSFV) is one of the most detrimental diseases, and leads to significant economic losses in the swine industry. Despite efforts by many government authorities to stamp out the disease from national pig populations, the disease remains widespread. Here, antiviral small hairpin RNAs (shRNAs) were selected and then inserted at the porcine Rosa26 (pRosa26) locus via a CRISPR/Cas9-mediated knock-in strategy. Finally, anti-CSFV transgenic (TG) pigs were produced by somatic nuclear transfer (SCNT). Notably, in vitro and in vivo viral challenge assays further demonstrated that these TG pigs could effectively limit the replication of CSFV and reduce CSFV-associated clinical signs and mortality, and disease resistance could be stably transmitted to the F1-generation. Altogether, our work demonstrated that RNA interference (RNAi) technology combining CRISPR/Cas9 technology offered the possibility to produce TG animal with improved resistance to viral infection. The use of these TG pigs can reduce CSF-related economic losses and this antiviral strategy may be useful for future antiviral research.

In order to recapitulate the best available evidence of milk consumption and multiple health-related outcomes, we performed an umbrella review of meta-analyses and systematic reviews in humans. Totally, 41 meta-analyses with 45 unique health outcomes were included. Milk consumption was more often related to benefits than harm to a sequence of health-related outcomes. Dose–response analyses indicated that an increment of 200 ml (approximately 1 cup) milk intake per day was associated with a lower risk of cardiovascular disease, stroke, hypertension, colorectal cancer, metabolic syndrome, obesity and osteoporosis. Beneficial associations were also found for type 2 diabetes mellitus and Alzheimer's disease. Conversely, milk intake might be associated with higher risk of prostate cancer, Parkinson’s disease, acne and Fe-deficiency anaemia in infancy. Potential allergy or lactose intolerance need for caution. Milk consumption does more good than harm for human health in this umbrella review. Our results support milk consumption as part of a healthy diet. More well-designed randomized controlled trials are warranted.

The well-defined photoresponsive polymethacrylate containing azo chromophore, poly{1‘-octyloxy-4‘-(6-methacryloxy)hexyloxy-5‘-phenylmethaneone-(2-phenyl)azobenzene (AHMA)} (PAHMA), was prepared via reversible addition−fragmentation chain transfer (RAFT) polymerization in anisole solution using 2-cyanoprop-2-yl 1-dithionaphthalate (CPDN) as the RAFT agent and 2,2‘-azobis(isobutyronitrile) (AIBN) as an initiator. The kinetic plots of polymerization were first-order and the molecular weights (M n(GPC)s) of the homopolymer (PAHMA) with relatively low polydispersity index values (PDIs ≤ 1.37) increased with monomer conversions throughout the polymerization processes. Furthermore, the kinetic plots of chain extension with both methyl methacrylate (MMA) and styrene (St) using the obtained PAHMA as a macro-RAFT agent were also first-order. The M n(GPC)s of the diblock copolymers, PAHMA-b-PMMA and PAHMA-b-PS, increased with the respective monomer conversions. These results indicated that most of the PAHMA chains were still “living”. The structure and properties of the polymers were characterized by 1H NMR, GPC, and UV−vis spectra. The photoisomerization of the polymer was examined. On irradiation with a linearly polarized Kr+ laser beam, the birefringence was induced in the polymer films to the level of 0.075. With illumination of linearly polarized Kr+ laser beam at modest intensities (120 mW/cm2), significant surface relief gratings (SRGs) formed on the polymer films were observed.

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