A red-letter day for RBC research: The study of primary human red blood cell (huRBC) disorders such as sickle cell disease (SCD) and infectious diseases such as malaria has been hampered by a lack of in vivo models of human erythropoiesis. Song et al. transferred human fetal liver cells into MISTRG mice, which are immunodeficient and are genetically engineered with several human genes involved in hematopoiesis. This approach was unsuccessful because mature huRBCs are rapidly destroyed in the mouse liver. They then used CRISPR-Cas9 to mutate these mice into a fumarylacetoacetate hydrolase–deficient strain, allowing them to replace the mouse liver with engrafted human hepatocytes. These mice exhibited enhanced human erythropoiesis and circulating huRBC survival and could recapitulate SCD pathology when reconstituted with SCD-derived HSCs. Science , this issue p. 1019

Antigen-specific human NKT cells from tuberculosis patients produce IL-21 to help B cells for the production of immunoglobulins

Progesterone (Pg) is an essential steroid hormone during mammary gland development and tumorigenesis, including the maintenance of epithelial stem/progenitor cells. Pg functions through interaction with the progesterone receptors (PR) and Pg-PR signaling is thought to be mediated by key transcription factors, which are largely unidentified. In this study, we have identified the ATBF1 transcription factor as a transcriptional target of Pg-PR signaling in mammary epithelial cells. Pg treatment dramatically increased ATBF1 expression at both mRNA and protein levels in cultured cells and mammary tissues. As expected, the induction of ATBF1 was PR-dependent, as it only occurred in PR-positive but not in PR-negative cells, and pretreatment with the Pg antagonist RU-486 or RNAi-mediated knockdown of PR abolished the upregulation of ATBF1 by Pg. Promoter-reporter and ChIP assays further showed that Pg-activated PR directly binds to the ATBF1 promoter to induce its transcription. Prevention of ATBF1 induction inhibited the function of Pg in promoting progenitor cell transition, as indicated by colony formation in a Matrigel culture assay and expression of stem cell markers CD49f and CD44. These findings suggest that ATBF1 plays a crucial role in the Pg-PR signaling pathway in mammary epithelial cells.

Senescence-accelerated mouse-prone (SAMP1; SAMP1@Umz) is an animal model of senile amyloidosis with apolipoprotein A-II (apoA-II) amyloid fibril (AApoAII) deposits. This study was undertaken to investigate the effects of dietary fats on AApoAII deposits in SAMP1 mice when purified diets containing 4% fat as butter, safflower oil, or fish oil were fed to male mice for 26 weeks. The serum HDL cholesterol was significantly lower (P < 0.01) in mice on the diet containing fish oil (7.4 ± 3.0 mg/dl) than in mice on the butter diet (38.7 ± 12.5 mg/dl), which in turn had significantly lower (P < 0.01) HDL levels than mice on the safflower oil diet (51.9 ± 5.6 mg/dl). ApoA-II was also significantly lower (P < 0.01) in mice on the fish oil diet (7.6 ± 2.7 mg/dl) than on the butter (26.9 ± 7.3 mg/dl) or safflower oil (21.6 ± 3.7 mg/dl) diets. The mice fed fish oil had a significantly greater ratio (P < 0.01) of apoA-I to apoA-II, and a smaller HDL particle size than those fed butter and safflower oil. Severe AApoAII deposits in the spleen, heart, skin, liver, and stomach were shown in the fish oil group compared with those in the butter and safflower oil groups (fish oil > butter > safflower oil group, P < 0.05).

DOA estimation algorithm based on adaptive filtering divided the received signal into desired signal and auxiliary signal, and solved the weight parameters through adaptive structure iteration, making the weighted auxiliary signal approach to the desired signal, so as to form the spatial spectrum peak in the direction of signal arrival. Traditional fixed-step-size LMS algorithm is used to solve the weight parameters, but it is difficult to choose a suitable step size. The variable-step-size LMS algorithm can adjust the step size according to SNR, but it is still a biased estimation of the weight parameters in principle. In this paper, an unbiased variable-step-size LMS algorithm is proposed to compensate the bias on the loss function so as to realize the unbiased estimation of the weight parameters, and further improve the performance of DOA estimation. The feasibility of the algorithm is verified through simulation experiments, and the performance of the proposed algorithm is compared with that of the traditional algorithm.