A Light Challenge: First Graders Engineer an Obstacle Course with Flashlights

In this class, we wanted to support students’ knowledge of light and the ways in which it interacts with other materials through a series of connected learning experiences. These experiences are related to NGSS standard 1-PS4-3 Waves and Their Applications in Technologies for Information Transfer. Plan and conduct investigations to determine the effect of placing objects made with different materials in the path of a beam of light. We aimed for children to discover that light tends to move in a straight line unless something gets in the way, materials can affect the beam of light, and the way light moves can be impacted by moving the objects. The connected activities described here were guided by the 5E learning cycle. The students watched the video to spark their curiosity about the path in which something might travel, worked in teams to design and test ideas while exploring the properties of the light, and documented and communicated their observations

Clinicopathological features of Bu Gu Zhi-induced liver injury, a long-term follow-up cohort study

Background & Aims Bu Gu Zhi (BGZ) is a Chinese herb consumed mainly for osteoporosis treatment. Only small case series of BGZ-induced liver injury (BGZILI) have been reported. We describe the clinicopathological features and clinical course of BGZILI. Methods Patients diagnosed with drug-induced liver injury (DILI) at Beijing Friendship Hospital from 2005 to 2017 were reviewed. Clinical and follow-up data were analysed. Results Of the 547 DILI patients, 40 cases (7.3%) were attributed to BGZILI. About 34/40 (85.0%) patients were females with a median age of 63 (range, 54-70) years. The median latency period was 45 (range, 29-90) days. Patients commonly presented with loss of appetite (57.5%), dark urine (57.5%) and fatigue (55.0%). The median level of alanine aminotransferase and aspartate aminotransferase at BGZILI onset was 673.5 and 423.0 U/L respectively. Total bilirubin (TB) and direct bilirubin (DB) were 59.0 and 39.4 mu mol/L respectively. The biochemical liver injury pattern was hepatocellular (92.5%), cholestatic (5.0%) and mixed (2.5%). They were categorized into 'mild' (N = 23, 57.5%), 'moderate' (6, 15.0%) or 'severe' (11, 27.5%) according to severity assessment by DILI network. The main histological injury pattern in 9/40 patients with liver biopsy was acute hepatitis with/without cholestasis. Median duration of follow-up was 26.3 months with recovery in 37 patients within 6 months. No patients died or required transplantation. Conclusions BGZ-induced liver injury manifested more often as a hepatocellular injury pattern with mild to moderate hepatocellular damage. Most patients recovered after cessation of BGZ within 6 months, and none developed end-stage liver disease or died

A High Serum Level of Taurocholic Acid is Correlated with the Severity and Resolution of Drug-induced Liver Injury

Background & Aims Alterations in the serum levels of bile acids are associated with drug-induced liver injury (DILI). We investigated the association between serum levels of bile acids and the severity and outcome of DILI, along with the potential role of variants in the ATP binding cassette subfamily B member 11 ( ABCB11) gene and expression of its product, ABCB11 (also called BSEP). Methods We performed this prospective study of 95 patients (median age, 53 years; 73.7% female) with DILI from August 2018 through August 2019. Patients were matched for age, gender, and body mass index with healthy individuals (n=100; healthy controls) and patients with chronic hepatitis B (n=105; CHB controls). We collected demographic and biochemical data at baseline and 1 week, 1 month, 3 months, and 6 months after DILI onset and at the time of biochemical recovery, liver failure or liver transplantation. Serum levels of bile acids were measured using high-performance liquid-chromatography tandem mass-spectrometry. All 27 exons of ABCB11 were sequenced and expression of BSEP were analyzed by immunohistochemistry in liver biopsy specimens. Results Levels of 30 of the 37 bile acids analyzed differed significantly between patients with DILI and healthy controls. Changes in levels of taurocholic acid (TCA), glycocholic acid, taurochenodeoxycholate, and glycochenodeoxycholate associated with the increased levels of bilirubin and greater severity of DILI, and were also associated with CHB. Cox regression analysis showed that only change in the levels of TCA independently associated with biochemical resolution of DILI. Combination of TCA level (≥ 1955.41 nmol/L), patient age, and DILI severity was associated with abnormal blood biochemistry at 6 months after DILI onset (area under the curve, 0.81; 95% confidence interval, 0.71–0.88; sensitivity, 0.69; specificity, 0.81). ABCB11 missense variants were not associated with differences in the serum bile acid profiles, DILI severity, or clinical resolution. However, lower levels of BSEP in bile canaliculi in liver biopsies were associated with altered serum levels of bile acids. Conclusions In this prospective study performed in Chinese patients, we found that the serum levels of TCA were associated with the severity and clinical resolution of DILI. Reduced protein expression of BSEP in liver tissue, rather than variants of the ABCB11 gene were associated with altered serum levels of bile acids

hElp3 Directly Modulates the Expression of HSP70 Gene in HeLa Cells via HAT Activity

Human Elongator complex, which plays a key role in transcript elongation in vitro assay, is incredibly similar in either components or function to its yeast counterpart. However, there are only a few studies focusing on its target gene characterization in vivo. We studied the effect of down-regulation of the human elongation protein 3 (hELP3) on the expression of HSP70 through antisense strategy. Transfecting antisense plasmid p1107 into HeLa cells highly suppressed hELP3 expression, and substantially reduced expression of HSP70 mRNA and protein. Furthermore, chromatin immunoprecipitation assay (ChIP Assay) revealed that hElp3 participates in the transcription elongation of HSPA1A in HeLa cells. Finally, complementation and ChIP Assay in yeast showed that hElp3 can not only complement the growth and slow activation of HSP70 (SSA3) gene transcription, but also directly regulates the transcription of SSA3. On the contrary, these functions are lost when the HAT domain is deleted from hElp3. These data suggest that hElp3 can regulate the transcription of HSP70 gene, and the HAT domain of hElp3 is essential for this function. These findings now provide novel insights and evidence of the functions of hELP3 in human cells

Self-Renewal of Acute Lymphocytic Leukemia Cells Is Limited by the Hedgehog Pathway Inhibitors Cyclopamine and IPI-926

Conserved embryonic signaling pathways such as Hedgehog (Hh), Wingless and Notch have been implicated in the pathogenesis of several malignancies. Recent data suggests that Hh signaling plays a role in normal B-cell development, and we hypothesized that Hh signaling may be important in precursor B-cell acute lymphocytic leukemia (B-ALL). We found that the expression of Hh pathway components was common in human B-ALL cell lines and clinical samples. Moreover, pathway activity could be modulated by Hh ligand or several pathway inhibitors including cyclopamine and the novel SMOOTHENED (SMO) inhibitor IPI-926. The inhibition of pathway activity primarily impacted highly clonogenic B-ALL cells expressing aldehyde dehydrogenase (ALDH) by limiting their self-renewal potential both in vitro and in vivo. These data demonstrate that Hh pathway activation is common in B-ALL and represents a novel therapeutic target regulating self-renewal and persistence of the malignant clone

The Impact of an Integrated STEM Collaborative Approach on Preservice Teachers’ Pedagogical Content Knowledge and Curricular Role Identity for Teaching Science

The current study investigated the impact of an integrated STEM collaborative approach embedded in a science methods course on early childhood and elementary preservice teachers’ pedagogical content knowledge (PCK) and curricular role identity for teaching science, as well as the potential relationship between these two constructs. Participants were recruited from a group of preservice early childhood and elementary teacher candidates (N = 65) completing an undergraduate teacher education program at a university in the southeastern United States. Using a mixed-methods design, the preservice teachers’ pedagogical content knowledge and curricular role identity were assessed using concept maps and a curricular role identity for teaching science survey (Forbes & Davis, 2008) at the beginning and end of the semester. Semi-structured interviews were conducted after the semester to collect qualitative data to clarify and explain the quantitative results. Findings suggested that the integrated STEM collaborative approach led to a significant increase in preservice teachers’ PCK and curricular role identity for teaching science over the semester. The significant increase was found in both early childhood and elementary education preservice teachers, with little to no departmental difference. There was no statistically significant relationship between the preservice teachers’ PCK and curricular role identity. Preservice teachers in this study found that examining science standards, unit planning, microteaching, and connecting with other teachers were beneficial for their development of PCK and curricular role identity for teaching science. This study affirms the collaboration among university faculty and preservice and in-service teachers. Implications and suggestions for future research are included

Research advances in primary biliary cholangitis

Primary biliary cholangitis is a chronic intrahepatic cholestatic liver disease and has increasing incidence and prevalence rates, as is reported in the literature. Examination of specific antibodies including serum anti-mitochondrial antibody subtype M2 and liver histopathological examination help to make a definite diagnosis of this disease. Ursodeoxycholic acid (UDCA) is often used for the treatment of this disease, but patients with an unsatisfactory biochemical response to UDCA tend to have rapid disease progression. At present, there are no effective treatment methods for such patients. The addition of budesonide, fenofibrate, bezafibrate, or obeticholic acid may be effective in these patients, but this needs to be verified by further clinical studies

Road Maps and Roadblocks to English Language Learning: Successful DLL Narratives

Four early childhood professionals, who are all English language learners, will tell their stories in this interactive presentation. They will discuss road maps and roadblocks in their journey to learning Standard English to meet academic demands, and provide specific real-life examples to support their thinking so the audience will have a clearer understanding of their perspectives. The presenters will also discuss various ways early childhood practitioners can respect and reinforce the learners\u27 first language at home and in school. These measures are supported by research. The audience will also be engaged by discussing their challenges and strategies when dealing with ELLs/DLLs and their families in small groups and sharing these to the whole group

Involvement of Activation of PKR in HBx-siRNA-Mediated Innate Immune Effects on HBV Inhibition

RNA interference (RNAi) of virus-specific genes offers the possibility of developing a new anti-hepatitis B virus (anti-HBV) therapy. Recent studies have revealed that siRNAs can induce an innate immune response in vitro and in vivo. Here, HBVx (HBx) mRNA expression and HBV replication were significantly inhibited, followed by the enhancement of expression of type I interferons (IFNs), IFN-stimulated genes (ISG15 and ISG56) and proinflammatory cytokines after HepG2.2.15 cells were transfected with chemically synthesized HBx-siRNAs. Transfection with HBx-siRNAs also significantly increased expression of dsRNA-dependent protein kinase R (PKR) in HepG2.2.15 cells, followed by activation of downstream signaling events such as eukaryotic initiation factor 2a (eIF2-a). In PKR-over-expressing HepG2.2.15 cells, HBx-siRNAs exerted more potent inhibitory effects on HBV replication and greater production of type I IFNs. By contrast, the inhibitory effect of HBx-siRNAs on HBV replication was attenuated when PKR was inhibited or silenced, demonstrating that HBx-siRNAs greatly promoted PKR activation, leading to the higher production of type I IFN. Therefore, we concluded that PKR is involved in the innate immune effects mediated by HBx-siRNAs and further contributes to HBV inhibition. The bifunctional siRNAs with both gen

HBx-siRNA inhibits hepatitis B virus (HBV) expression in HepG2.2.15 cells.

<p>(A) Scramble siRNA or HBx-siRNA (siRNA1, siRNA2, siRNA3, siRNA4) (100 nM) was transfected into HepG2.2.15 cells using lipofectamine 2000 (LF). LF-treated group was used as a control. The cells were harvested, and RNA was extracted at 24 h after transfection. Expression of HBx mRNA were detected by real-time PCR (top). The level of each sample is expressed as the percentage of the RNA level in scramble siRNA-treated cells. The levels of HBx protein were detected by western blot at 48 h after transfection (bottom). (B) HepG2.2.15 cells were transfected for 48 h, and then cells were fixed, immunostained for HBcAg and visualized under a microscope. Representative fields from each cell group are shown (original magnification ×100). (C, D) The supernatants were harvested after 48 h, and the dose-dependent reductions in HBsAg (C) and HBeAg (D) were detected with ELISA. Data showing the silencing effect are representative of three independent experiments. Data are expressed as the mean ± SD from at least three separate experiments. *<i>p</i><0.05 versus the LF-treated group.</p