N-Acetylcysteine Alters Disease Progression and Increases Janus Kinase Mutation Frequency in a Mouse Model of Precursor B-Cell Acute Lymphoblastic Leukemia.

B-cell acute lymphoblastic leukemia (B-ALL) is the most prevalent type of cancer in young children and is associated with high levels of reactive oxygen species (ROS). The antioxidant N-acetylcysteine (NAC) was tested for its ability to alter disease progression in a mouse model of B-ALL. Mb1-CreΔPB mice have deletions in genes encoding PU.

IKZF3/Aiolos H195Y mutation identified in a mouse model of B cell leukemia results in altered DNA binding and altered STAT5-dependent gene expression.

Precursor B cell acute lymphoblastic leukemia (Pre-B-ALL) arises from developing B cells and frequently involves mutations in genes encoding transcription factors. In this study, we investigated the function of mutations in the transcription factor IKZF3 (Aiolos), R137* and H195Y, discovered in a mouse model of pre-B-ALL. R137* IKZF3 mutation resulted in a truncated protein, while electrophoretic mobility shift assay showed that H195Y IKZF3 mutation resulted in a protein with altered DNA binding.

Spi-C and PU.1 Counterregulate Rag1 and Igκ Transcription to Effect Vκ-Jκ Recombination in Small Pre-B Cells.

B cell development requires the ordered rearrangement of Ig genes encoding H and L chain proteins that assemble into BCRs or Abs capable of recognizing specific Ags. Igκ rearrangement is promoted by chromatin accessibility and by relative abundance of RAG1/2 proteins. Expression of the E26 transformation-specific transcription factor Spi-C is activated in response to dsDNA double-stranded breaks in small pre-B cells to negatively regulate pre-BCR signaling and Igκ rearrangement.

The E26 Transformation-Specific Family Transcription Factor Spi-C Is Dynamically Regulated by External Signals in B Cells.

Spi-C is an E26 transformation-specific transcription factor closely related to PU.1 and Spi-B. Spi-C has lineage-instructive functions important in B cell development, Ab-generating responses, and red pulp macrophage generation.

ETV6-RUNX1 interacts with a region in SPIB intron 1 to regulate gene expression in pre-B-cell acute lymphoblastic leukemia.

The most frequently occurring genetic abnormality in pediatric B-lymphocyte-lineage acute lymphoblastic leukemia is the t(12;21) chromosomal translocation that results in a ETV6-RUNX1 (also known as TEL-AML1) fusion gene. Expression of ETV6-RUNX1 induces a preleukemic condition leading to acquisition of secondary driver mutations, but the mechanism is poorly understood. SPI-B (encoded by SPIB) is an important transcriptional activator of B-cell development and differentiation.

Driver mutations in Janus kinases in a mouse model of B-cell leukemia induced by deletion of PU.1 and Spi-B.

Precursor B-cell acute lymphoblastic leukemia (B-ALL) is associated with recurrent mutations that occur in cancer-initiating cells. There is a need to understand how driver mutations influence clonal evolution of leukemia. The E26-transformation-specific (ETS) transcription factors PU.

[Spatial change of the grain-size of aeolian sediments in Qira oasis-desert ecotone, Northwest China].

In order to understand the environmental influence of oasis-desert ecotone to oasis ecological system, we comparatively analyzed the grain size characteristics of various aeolian sediments, including the sediments in oasis-desert ecotone, shelterbelt and the inside oasis and in Qira River valley. The results showed that the grain size characteristics (including grain-size distribution curve, grain size parameters, and content of different size classes) of sediments in the oasis-desert ecotone were consistent along the prevailing wind direction with a grain-size range of 0.3-200 μm and modal size of 67 μm.

PU.1 Regulates Ig Light Chain Transcription and Rearrangement in Pre-B Cells during B Cell Development.

B cell development and Ig rearrangement are governed by cell type- and developmental stage-specific transcription factors. PU.1 and Spi-B are E26-transformation-specific transcription factors that are critical for B cell differentiation.

Pre-Expanded Submental Island Flap for Resurfacing Middle and Lower Facial Defect.

Resurfacing large facial defect is a continuing challenge for plastic surgeons. Skin graft or free flap is hard to obtain satisfactory results or is beyond the skill of most surgeons. The authors performed 13 expended submental island flaps to resurface middle and lower facial defects and achieved satisfactory results.

Utilization of Health Services Among Adults With Recurrent Clostridium difficile Infection: A 12-Year Population-Based Study.

BACKGROUND Considerable efforts have been dedicated to developing strategies to prevent and treat recurrent Clostridium difficile infection (rCDI); however, evidence of the impact of rCDI on patient healthcare utilization and outcomes is limited. OBJECTIVE To compare healthcare utilization and 1-year mortality among adults who had rCDI, nonrecurrent CDI, or no CDI. METHODS We performed a nested case-control study among adult Kaiser Foundation Health Plan members from September 1, 2001, through December 31, 2013.

Correction: Relative Importance and Additive Effects of Maternal and Infant Risk Factors on Childhood Asthma.

[This corrects the article DOI: 10.1371/journal.pone.

Respiratory syncytial virus immunoprophylaxis in high-risk infants and development of childhood asthma.

Background: Respiratory syncytial virus (RSV) lower respiratory tract infection is implicated in asthma development. RSV immunoprophylaxis during infancy is efficacious in preventing RSV-related hospitalizations and has been associated with decreased wheezing in the first years of life.

Objective: We investigated whether greater adherence to immunoprophylaxis in infants at high risk for severe RSV would be associated with decreased childhood asthma.

Relative Importance and Additive Effects of Maternal and Infant Risk Factors on Childhood Asthma.

Background: Environmental exposures that occur in utero and during early life may contribute to the development of childhood asthma through alteration of the human microbiome. The objectives of this study were to estimate the cumulative effect and relative importance of environmental exposures on the risk of childhood asthma.

Methods: We conducted a population-based birth cohort study of mother-child dyads who were born between 1995 and 2003 and were continuously enrolled in the PRIMA (Prevention of RSV: Impact on Morbidity and Asthma) cohort.

Incidence of Dravet Syndrome in a US Population.

Objective: De novo mutations of the gene sodium channel 1α (SCN1A) are the major cause of Dravet syndrome, an infantile epileptic encephalopathy. US incidence of DS has been estimated at 1 in 40 000, but no US epidemiologic studies have been performed since the advent of genetic testing.

Methods: In a retrospective, population-based cohort of all infants born at Kaiser Permanente Northern California during 2007-2010, we electronically identified patients who received ≥2 seizure diagnoses before age 12 months and who were also prescribed anticonvulsants at 24 months.

Genome-wide comparison of PU.1 and Spi-B binding sites in a mouse B lymphoma cell line.

Background: Spi-B and PU.1 are highly related members of the E26-transformation-specific (ETS) family of transcription factors that have similar, but not identical, roles in B cell development. PU.

PU.1 opposes IL-7-dependent proliferation of developing B cells with involvement of the direct target gene bruton tyrosine kinase.

Deletion of genes encoding the E26 transformation-specific transcription factors PU.1 and Spi-B in B cells (CD19-CreΔPB mice) leads to impaired B cell development, followed by B cell acute lymphoblastic leukemia at 100% incidence and with a median survival of 21 wk. However, little is known about the target genes that explain leukemogenesis in these mice.

Adherence to Immunoprophylaxis Regimens for Respiratory Syncytial Virus Infection in Insured and Medicaid Populations.

Background: Immunoprophylaxis is the only pharmaceutical intervention for mitigating respiratory syncytial virus (RSV) infection. Patient level data on adherence to American Academy of Pediatrics (AAP) immunoprophylaxis recommendations are limited. This study characterizes adherence to AAP guidelines in privately insured and Medicaid populations.

Regulation of B cell linker protein transcription by PU.1 and Spi-B in murine B cell acute lymphoblastic leukemia.

B cell acute lymphoblastic leukemia (B-ALL) is frequently associated with mutations or chromosomal translocations of genes encoding transcription factors. Conditional deletion of genes encoding the E26-transformation-specific transcription factors, PU.1 and Spi-B, in B cells (ΔPB mice) leads to B-ALL in mice at 100% incidence rate and with a median survival of 21 wk.

Frequency, duration and predictors of bronchiolitis episodes of care among infants ≥32 weeks gestation in a large integrated healthcare system: a retrospective cohort study.

Background: Bronchiolitis is common in the first two years of life and is the most frequent cause of hospitalization in this age group. No previous studies have used an episode-of-care analysis to describe the frequency, duration, and predictors of bronchiolitis episodes of care during the first two years.

Methods: We conducted a retrospective cohort study of 123,264 infants ≥32 weeks gestation born at 6 Northern California Kaiser Permanente hospitals between 1996 and 2002.

In vitro and in vivo characterization of silk fibroin/gelatin composite scaffolds for liver tissue engineering.

Objective: To investigate the cytotoxicity of silk fibroin/gelatin (SF/G) composite scaffolds in vitro as well as their biocompatibility and degradation in vivo.

Methods: The proliferation and relative growth rate of human hepatic QZG cells grown on different blends of two-dimensional (2-D) SF/G scaffolds were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Flow cytometry was used to evaluate apoptotic rate of QZG cells on different blends of 2-D SF/G scaffolds.

Human HERC5 restricts an early stage of HIV-1 assembly by a mechanism correlating with the ISGylation of Gag.

Background: The identification and characterization of several interferon (IFN)-induced cellular HIV-1 restriction factors, defined as host cellular proteins or factors that restrict or inhibit the HIV-1 life cycle, have provided insight into the IFN response towards HIV-1 infection and identified new therapeutic targets for HIV-1 infection. To further characterize the mechanism underlying restriction of the late stages of HIV-1 replication, we assessed the ability of IFNbeta-induced genes to restrict HIV-1 Gag particle production and have identified a potentially novel host factor called HECT domain and RCC1-like domain-containing protein 5 (HERC5) that blocks a unique late stage of the HIV-1 life cycle.

Results: HERC5 inhibited the replication of HIV-1 over multiple rounds of infection and was found to target a late stage of HIV-1 particle production.

Regulation of follicular B cell differentiation by the related E26 transformation-specific transcription factors PU.1, Spi-B, and Spi-C.

Splenic B-2 cells can be divided into two major subsets: follicular (FO) and marginal zone (MZ) B cells. FO and MZ B cells are generated from immature transitional B cells. Few transcription factors have been identified that regulate FO B cell differentiation.

Recurrent wheezing in the third year of life among children born at 32 weeks' gestation or later: relationship to laboratory-confirmed, medically attended infection with respiratory syncytial virus during the first year of life.

Objective: To quantify the relationship between recurrent wheezing (RW) in the third year of life and respiratory syncytial virus (RSV) infection, prematurity, and neonatal oxygen exposure.

Design: Retrospective cohort study linking inpatient, outpatient, and laboratory databases for cohort assembly and logistic regression analysis.

Setting: Integrated health care delivery system in Northern California.