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Fumonisin B1 (FB1), a mycotoxin produced by Fusarium verticillioides, is one of the most common pollutants in natural foods and agricultural crops. It can cause chronic and severe health issues in humans and animals. The aim of this study was to evaluate the transgenerational effects of FB1 exposure on the structure and function of the kidneys in offspring. Virgin female Wistar rats were randomly divided into three groups: group one (control) received sterile water, and groups two and three were intragastrically administered low (20 mg/kg) and high (50 mg/kg) doses of FB1, respectively, from day 6 of pregnancy until delivery. Our results showed that exposure to either dose of FB1 caused histopathological changes, such as atrophy, hypercellularity, hemorrhage, calcification, and a decrease in the glomerular diameter, in both the first and second generations. The levels of the antioxidant markers glutathione, glutathione S-transferase, and catalase significantly decreased, while malondialdehyde levels increased. Moreover, autophagy was induced, as immunofluorescence analysis revealed that LC-3 protein expression was significantly increased in both generations after exposure to either dose of FB1. However, a significant decrease in methyltransferase (DNMT3) protein expression was observed in the first generation in both treatment groups (20 mg/kg and 50 mg/kg), indicating a decrease in DNA methylation as a result of early-life exposure to FB1. Interestingly, global hypomethylation was also observed in the second generation in both treatment groups despite the fact that the mothers of these rats were not exposed to FB1. Thus, early-life exposure to FB1 induced nephrotoxicity in offspring of the first and second generations. The mechanisms of action underlying this transgenerational effect may include oxidative stress, autophagy, and DNA hypomethylation.

This work investigated the protective effects of microalga Halamphora sp. extract (HExt), a nutraceutical and pharmacological natural product, on human lead-intoxicated liver and kidney cells in vitro and in vivo in Wistar rats. The human hepatocellular carcinoma cell line HepG2 and the human embryonic kidney cell line HEK293 were used for the in vitro study. The analysis of the fatty acid methyl esters in the extract was performed via GC/MS. The cells were pretreated with HExt at 100 µg mL−1, followed by treatment with different concentrations of lead acetate, ranging from 25 to 200 µM for 24 h. The cultures were incubated (5% CO, 37 °C) for 24 h. Four groups, each containing six rats, were used for the in vivo experiment. The rats were exposed to subchronic treatment with a low dose of lead acetate (5 mg kg−1 b.w. per day). Pretreating HepG2 and HEK293 cells with the extract (100 µg mL−1) significantly (p < 0.05) protected against the cytotoxicity induced by lead exposure. For the in vivo experiment, the biochemical parameters in serum—namely, the level of malondialdehyde (MDA), and the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)—were measured in the organ homogenate supernatants. HExt was found to be rich in fatty acids, mainly palmitic and palmitoleic acids (29.464% and 42.066%, respectively). In both the in vitro and in vivo experiments, cotreatment with HExt protected the liver and kidney cell structures and significantly preserved the normal antioxidant and biochemical parameters in rats. This study discovered the possible protective effect of HExt, which could be beneficial for Pb-intoxicated cells.

Chemistry textbooks are the most popular teaching material in schools. They can contribute significantly to the attainment of scientific educational goals. Internationally, educational reforms in science subjects are adopting newer practices such as Engineering Design Processes (EDP) for addressing real-world requirements. This study, conducted in Saudi Arabia, employed a qualitative and quantitative content analysis method to evaluate the level of the EDP incorporated in the tenth grade chemistry textbook and accompanying student’s experiments’ guidebook. The results found the inclusive mean for EDP was 1.05, which indicated incorporation was found to be at level one. This inclusion EDP in chemistry textbooks has been rated as novice or deficient, which indicates that it does not fulfill the majority of the requirements for inclusion as suggested by NGSS.

For the advancement of current and future economic and overall well-being to occur, STEM professionals are highly needed. STEM education is an approach that integrates science, technology, engineering and mathematics curricula into one interdisciplinary curriculum. In the context of STEM education, learners acquire deep and critical thinking abilities, which help them become creative and analytic thinkers, and hence innovators in their careers. For this to happen, the teacher must be trained to successfully design and effectively teach an integrated STEM curriculum. The purpose of this study was to analyze Saudi Arabian science and mathematics teachers' attitudes toward integrating Science, Technology, Engineering and Mathematics (STEM) in teaching before and after they participated in a short professional development program focused on STEM integration in a specific middle school science and mathematics content. The participants were 48 Saudi Arabian science and mathematics teachers, who participated in a 6-day program held in Riyadh, Saudi Arabia. The research methodology was a pretest-posttest one group (pre-experimental) design. The primary data source was the Instrument for Teachers' Attitudes Toward Teaching Integrated STEM. The results indicate that Saudi Arabian science and mathematics teachers' perceptions of difficulties decreased due to their participation in the professional development program on integrated STEM. Meanwhile, the teachers' self-efficacy improved following their participation in the STEM professional development (PD) program. However, no perceived effect was found for the teachers' perceptions of the relevance of or their anxiety about or enjoyment of Integrated STEM teaching due to their participation in the 6-day PD program. We argue that Engaging teachers in integrated STEM professional development may improve their attitudes toward and increase their interest in teaching this approach. To improve teachers' attitudes toward, it is suggested that future PD programs should be long and continuous, and focus on training science and mathematics teachers to teach integrated STEM subjects.

Background: The annual prevalence of gestational diabetes mellitus—characterized by an increase in blood glucose in pregnant women—has been increasing worldwide. The goal of this study was to evaluate the expression of glucose transporter 1 (GLUT1) and glucose transporter 3 (GLUT3) in the placenta of women with gestational diabetes mellitus. Methods: Sixty-five placentas from women admitted to the King Saud University Medical City, Riyadh, Saudi Arabia, were analyzed; 34 and 31 placentas were from healthy pregnant women and women with gestational diabetes, respectively. The expressions of GLUT1 and GLUT3 were assessed using RT-PCR, Western blotting, and immunohistochemical methods. The degree of apoptosis in the placental villi was estimated via a TUNEL assay. Results: The results of the protein expression assays and immunohistochemical staining showed that the levels of GLUT1 and GLUT3 were significantly higher in the placentas of pregnant women with gestational diabetes than those in the placentas of healthy pregnant women. In addition, the findings showed an increase in apoptosis in the placenta of pregnant women with gestational diabetes compared to that in the placenta of healthy pregnant women. However, the results of gene expression assays showed no significant difference between the two groups. Conclusions: Based on these results, we conclude that gestational diabetes mellitus leads to an increased incidence of apoptosis in the placental villi and alters the level of GLUT1 and GLUT3 protein expressions in the placenta of women with gestational diabetes. Understanding the conditions in which the fetus develops in the womb of a pregnant woman with gestational diabetes may help researchers understand the underlying causes of the development of chronic diseases later in life.

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Problem Statement: Teacher professional development is a prominent feature in the educational landscapes of both developed and developing countries. Teacher development can be conceptualised as a mechanism for driving change in educational systems and/or as a strategy for empowering teachers to improve their professional knowledge and pedagogy. To ensure effective teacher professional development, Science teachers need to be more in control of their own PD. More studies of teacher professional needs have been carried out in Western societies rather than Arab societies. In addition, supervisors' voices in regard to the PD of teachers have not been emphasised by international or national studies. Changing the research contexts might introduce a new understanding of the priority of professional needs. Purpose of the Study: This study aimed to identify and explore science teachers' needs for both pedagogical and content knowledge as a first step toward making decisions and recommendations about the elements of CPD programme(s) required for science teachers. The purpose of the study was to determine the professional development needs perceived by science teachers and their supervisors in Saudi Arabia. Methods: The main instrument used was a questionnaire. The validity and reliability of the instrument were systematically established through relevant test procedures. The questionnaire seeks feedback on the main aspects of science teachers' needs, including generic pedagogical knowledge and skills, knowledge and skills in science subjects, managing and delivering science instruction, diagnosing students' needs, evaluating students' work, planning science instruction, administering the use of facilities and equipment, integrating multimedia technology, and informal science learning. Additionally, the questionnaire covers the key science subject domains in which science teachers might need professional development (PD). Findings and Results: This study argues that science teachers' voices concerning their PD needs are the key guide for their CPD. While science teachers may share a number of perceived needs with science supervisors, teachers have distinct pedagogical and content knowledge needs that may differ according to individual interests. Suggestions and Recommendations: Attention should be given to ensure that individual teachers' differing needs are met because providing the same programme for all teachers may not meet the needs of them all. Science teachers, supervisors, policy makers, and in-service and pre-service training planners need to work together to consider the recommendations that have been identified in the teachers' PD research.

The aim of this work was to study the ecotoxicological effects of an endocrine disruptor triclosan on the clam Ruditapes decussatus. The bivalves were exposed to three concentrations of this biocide (C1 = 100 ng/L, C2 = 200 ng/L and C3 = 500 ng/L) for three and seven days. The impact was assessed at the gills and digestive glands, through activities of an antioxidant defense biomarker (Gluthatione S-Transferase, GST), a damage biomarker (Malondialdehyde, MDA), and a neurotoxicity biomarker (Acetylcholinesterase, AChE). Furthermore, histological traits were approached in different organs to evaluate any possible alteration induced by triclosan. It appears from this study that both gills and digestive glands responded discernibly to triclosan and effects were concentration-dependent. The stressed clams showed a significant increase in their GST and MDA activities in gills and digestive glands compared to controls for both time slots considered. In turn, the AChE activity was clearly inhibited in both organs in a time dependent way. The histological study made it possible to observe several structural pathologies caused by triclosan in the gills and the digestive gland. These alterations consisted mainly of inflammatory reactions, malformations of the lamellae and fusion of the gill filaments, degeneration of the connective tissue, and the erosion of the gill cilia with the appearance of certain severe alterations (cell necrosis and apoptosis), which can thus cause a malfunction of the gills and eventually lead to a reduction in oxygen consumption and a disruption of the osmoregulation for bivalves. Alterations in the digestive gland have also been detected, mainly by epithelial alterations, thinning of the tubules, and alteration of the basal cell membrane which can impair the ability of clams to absorb food. At germinal cells, several damages were observed in the oocytes which probably disturbed the reproductive function and the fertility of the clams. The damages observed in female gonads were caused by the cytolysis of a large number of oocytes through autophagy and necrosis at 200 ng triclosan/L. Moreover, at 500 ng triclosan/L, hemocytic infiltration was observed in acini and apoptotic bodies reflected in the fragmentation of more than 90% of oocytes.

BackgroundThere is growing evidence of the need to consider cultural factors in the design and implementation of digital health interventions. However, there is still inadequate knowledge pertaining to the aspects of the Saudi Arabian culture that need to be considered in the design and implementation of digital health programs, especially in the context of home health care services for patients who are chronically and terminally ill. ObjectiveThis study aims to explore the specific cultural factors related to patients and their caregivers from the perspective of physicians, nurses, and trainers that have influenced the pilot implementation of Remotely Accessible Healthcare At Home, a connected health program in the Home Health Care department at King Saud University Medical City, Riyadh, Saudi Arabia. MethodsA qualitative study design was adopted to conduct a focus group discussion in July 2019 using a semistructured interview guide with 3 female and 4 male participants working as nurses, family physicians, and information technologists. Qualitative data obtained were analyzed using a thematic framework analysis. ResultsA total of 2 categories emerged from the focus group discussion that influenced the experiences of digital health program intervention: first, culture-related factors including language and communication, cultural views on using cameras during consultation, nonadherence to web-based consultations, and family role and commitment and second, caregiver characteristics in telemedicine that includes their skills and education and electronic literacy. Participants of this study revealed that indirect contact with patients and their family members may work as a barrier to proper communication through the Remotely Accessible Healthcare At Home program. ConclusionsWe recommend exploring the use of interpreters in digital health, creating awareness among the local population regarding privacy in digital health, and actively involving direct family members with the health care providers.

The aim of the current study was to assess the multifaceted effects of the polycylic aromatic hydrocarbon phenanthrene, mainly used in the colouring, explosive, and pharmaceutical industries, on the physiology of two bivalve species with economic value as seafood, namely, the Mediterranean mussel Mytilus galloprovincyalis and the European clam Ruditapes decussatus. The current study assessed how the phenanthrene affected several biomarkers and biometric endpoints in both bivalves, based on an in vivo experiment in silico approach. The bivalves were exposed during four time slots (i.e., 7, 15, 21, and 28 days) to two concentrations of phenanthrene in water (50 µg/L and 100 µg/L). For the clam R. decussatus, an additional contamination of sediment was applied due their typical benthic lifestyle (50 µg/kg and 100 µg/kg). The phenanthrene significantly reduced the ability of bivalves to tolerate desiccation and their Median Lethal Time, and also inhibited the activity of the enzyme acetylcholinesterase in a time-dependent manner. The activity of catalase indicated that bivalves also experienced oxidative stress during the first 21 days of the experiment. The significant decline in catalase activity observed during the last week of the experiment for the mussel M. galloprovincyalis supported a depletion of enzymes caused by the phenanthrene. The phenanthrene has also toxicokinetic and toxicodynamic properties, as assessed by the in silico approach. Overall, the results obtained suggest that the bivalves Ruditapes decussatus and M. galloprovincyalis can be used as a sentinel species in monitoring studies to assess the environmental impact of phenanthene in marine ecosystems. The significance of our findings is based on the fact that in ecotoxicology, little is known about the chronic effects, the simultaneous use of multiple species as bioindicators, and the interactions molecular modelling.

Introduction: Osteoporosis is a systemic age-related disease characterized by reduced bone mass and microstructure deterioration, leading to increased risk of bone fragility fractures. Osteoporosis is a worldwide major health care problem and there is a need for preventive approaches. Methods and Results: Apigenin and Rutaecarpine are plant-derived antioxidants identified through functional screen of a natural product library (143 compounds) as enhancers of osteoblastic differentiation of human bone marrow stromal stem cells (hBMSCs). Global gene expression profiling and Western blot analysis revealed activation of several intra-cellular signaling pathways including focal adhesion kinase (FAK) and TGFb. Pharmacological inhibition of FAK using PF-573228 (5 mM) and TGFb using SB505124 (1mM), diminished Apigenin- and Rutaecarpine-induced osteoblast differentiation. In vitro treatment with Apigenin and Rutaecarpine, of primary hBMSCs obtained from elderly female patients enhanced osteoblast differentiation compared with primary hBMSCs obtained from young female donors. Ex-vivo treatment with Apigenin and Rutaecarpine of organotypic embryonic chick-femur culture significantly increased bone volume and cortical thickness compared to control as estimated by mCT-scanning. Discussion: Our data revealed that Apigenin and Rutaecarpine enhance osteoblastic differentiation, bone formation, and reduce the age-related effects of hBMSCs. Therefore, Apigenin and Rutaecarpine cellular treatment represent a potential strategy for maintaining hBMSCs health during aging and osteoporosis. [ABSTRACT FROM AUTHOR]

Abstract Background Recent developments in connected health technology provide an opportunity to remotely monitor and provide health care to the patient needing long-term medical care. However, information about how any connected health interventions should be implemented for remote patient monitoring, and how patients should be educated and enabled for active participation in treatment is still not available to a sufficient degree. Discussion In this paper, we discussed what the components of a connected health intervention, entitled Remotely Accessible Health Care at Home (RAHAH), are, and how this intervention has been implemented in Saudi Arabia and Pakistan. The aim of this intervention is to remotely monitor, treat and educate patients needing long-term medical care. The description of the intervention is presented based on the Template for Intervention Description and Replication (TIDieR) checklist for the transparent, comprehensive and explicit reporting. Conclusion We believe, successful implementation of RAHAH would be crucial to monitor and manage growing chronic care populations more effectively and efficiently in Saudi Arabia and Pakistan.

This study examines Saudi Arabian middle school science textbooks' coverage of the essential features of scientific inquiry. All activities in the middle school science textbooks and workbooks were analyzed by using the scientific inquiry "essential features" rubric. The results indicated that the essential features are included in about 59% of the analyzed science activities. However, feature 2, "making learner give priority to evidence in responding to questions" and feature 3, "allowing learner to formulate explanations from evidence" appeared more frequently than the other three features (feature 1: engaging learner in scientifically oriented questions, feature 4: helping learner connect explanations to scientific knowledge, and feature 5: helping learner communicate and justify explanations to others), whether in the activities as a whole, or in the activities included in each of the four science domains (physical science, Earth science, life science and chemistry). These features are represented in almost all activities. This means that almost all activities in the middle school science textbooks and the workbooks include features 2 and 3. Meanwhile, the mean level of inclusion of the five essential features of scientific inquiry found in the middle school science textbooks and workbooks as a whole is 2.55. However, results found for features 1, 4, 5 and for in-level inclusion of the inquiry features in each of the science domains indicate that the inclusion of the essential inquiry features is teacher-centred. As a result, neither science textbooks nor workbooks provide students with the opportunity or encouragement to develop their inquiry skills. Consequently, the results suggest important directions for educational administrators and policy-makers in the preparation and use of science educational content.

This study analyzes the content of 12th-grade mathematics textbooks and workbooks, based on their inclusion of mathematical discourse components. The mathematics textbooks and workbooks were used in a Saudi Arabian school, where students are transitioning from secondary education to university. The results revealed that Saudi Arabian school textbooks and workbooks did not appropriately include discourse components or discourse skills to help facilitate mathematical learning among students. Furthermore, these textbooks did not exceed level two of the four levels of inclusion. As a result, the inclusion was insufficient in helping students meaningfully understand mathematical concepts, become active students, and develop successful community leadership. This implies that mathematics textbooks and workbooks should be revised to include mathematical discourse so that this inclusion is more student directed than teacher directed.

Developments in Outcome-based education (OBE) and innovative shifts in its pedagogical approaches have reshaped the learning environment of curricula at medical schools. This instructional design has gained popularity due to its authenticity and systematic approach. However, this needs organized supervision and faculty training in order to achieve the desired goals for the program. Aim: This article examines the evaluation of OBE at a private medical school in Saudi Arabia. It describes the curriculum review process and the characteristics of the curriculum reviewers involved. It evaluates the curriculum using Harden's OBE implementation inventory. OBE reviewers' satisfaction about OBE implementation was evaluated using the OBE inventory. Results: This analysis shows our institutional profile to be similar to the 'transition to beavers' symbol in Harden's representation. At the program level, the study identifies gaps and suggests suitable recommendations to enhance the enactment of OBE. Conclusion: We strongly encourage medical educators to apply the nine components of the OBE implementation inventory to evaluate their level of implementation of OBE. To further build up this model, the authors propose a mnemonic "ADAPTIVE Species" as an instructional prompt to develop these qualities in medical faculty. "ADAPTIVE Species" stands for Assertive, Developer, Assessors, Prime-movers, Transparent, Innovators, Vigilant, Evaluators, and Selectors.

Breast cancer (BC) is the foremost cause of cancer-related deaths in women. BC patients are oftentimes presented with lymph node metastasis (LNM), which increases their risk of recurrence. Compelling data have recently implicated microRNAs in promoting BC metastasis. Therefore, the identification of microRNA (miRNA)-based molecular signature associated with LNM could provide an opportunity for a more personalized treatment for BC patients with high risk of LNM. In current study, we performed comprehensive miRNA profiling in matched primary breast and LNM and identified 40 miRNAs, which were differentially expressed in LNM compared to primary tumors. The expression of 14 miRNAs (Up: hsa-miR-155-5p, hsa-miR-150-5p, hsa-miR-146a-5p, hsa-miR-142-5p and down: hsa-miR-200a-3p, hsa-miR-200b-3p, hsa-miR-200c-3p, hsa-miR-205-5p, hsa-miR-210-3p, hsa-miR-214-3p, hsa-miR-141-3p, hsa-miR-127-3p, hsa-miR-125a-5p, and hsa-let-7c-5p) was subsequently validated in a second cohort of 32 breast and 32 matched LNM tumor tissues. Mechanistically, forced expression of hsa-miR-205-5p, or hsa-miR-214-3p epigenetically inhibited MDA-MB-231 cell proliferation, colony formation, and cell migration. Global gene expression profiling on MDA-MB-231 cells overexpressing hsa-miR-205-5p, or hsa-miR-214-3p in combination with in silico target prediction and ingenuity pathway analyses identified multiple bona fide targets for hsa-miR-205-5p, hsa-miR-214-3p affecting cellular proliferation and migration. Interestingly, interrogation of the expression levels of hsa-miR-205 and hsa-miR-214 in the METABRIC breast cancer dataset revealed significantly poor overall survival in patients with downregulated expression of miR-205 [HR = 0.75 (0.61–0.91)], p = 0.003 and hsa-miR-214 [HR = 0.74 (0.59–0.93) p = 0.008]. Our data unraveled the miRNA-transcriptional landscape associated with LNM and provide novel insight on the role of several miRNAs in promoting BC LNM, and suggest their potential utilization in the clinical management of BC patients.

Abstract Background Better understanding of the signaling pathways that regulate human bone marrow stromal stem cell (hBMSC) differentiation into bone-forming osteoblasts is crucial for their clinical use in regenerative medicine. Chemical biology approaches using small molecules targeting specific signaling pathways are increasingly employed to manipulate stem cell differentiation fate. Methods We employed alkaline phosphatase activity and staining assays to assess osteoblast differentiation and Alizarin R staining to assess mineralized matrix formation of cultured hBMSCs. Changes in gene expression were assessed using an Agilent microarray platform, and data normalization and bioinformatics were performed using GeneSpring software. For in vivo ectopic bone formation experiments, hMSCs were mixed with hydroxyapatite–tricalcium phosphate granules and implanted subcutaneously into the dorsal surface of 8-week-old female nude mice. Hematoxylin and eosin staining and Sirius Red staining were used to detect bone formation in vivo. Results We identified several compounds which inhibited osteoblastic differentiation of hMSCs. In particular, we identified ruxolitinib (INCB018424) (3 μM), an inhibitor of JAK-STAT signaling that inhibited osteoblastic differentiation and matrix mineralization of hMSCs in vitro and reduced ectopic bone formation in vivo. Global gene expression profiling of ruxolitinib-treated cells identified 847 upregulated and 822 downregulated mRNA transcripts, compared to vehicle-treated control cells. Bioinformatic analysis revealed differential regulation of multiple genetic pathways, including TGFβ and insulin signaling, endochondral ossification, and focal adhesion. Conclusions We identified ruxolitinib as an important regulator of osteoblast differentiation of hMSCs. It is plausible that inhibition of osteoblast differentiation by ruxolitinib may represent a novel therapeutic strategy for the treatment of pathological conditions caused by accelerated osteoblast differentiation and mineralization.

Background: Clinical use of stromal stem cells in regenerative medicine is increasingly recognized as a promising treatment modality for age-related degenerative diseases based on the promising initial results of clinical trials. However, the magnitude of positive effects observed in these trials has been variable which can be explained by the lack of standardization of the stem cell products “cell product.” Bone marrow-derived stromal (also known mesenchymal) stem cells (BM-hMSC) and adipose tissue-hMSC (AD-hMSC) have been used interchangeably in clinical trials employing stromal stem cells as they were thought to be functionally identical. Methods: In the present study, we performed an extensive side-by-side comparison of BM-hMSC and AD-hMSC for their CD marker expression using FACS analysis, molecular phenotype using global mRNA gene expression analysis, and functional studies for their in vitro differentiation capacity to osteoblasts and adipocytes. Results: We observed both stromal cell populations were CD44+ CD13+ CD90+ CD29+ CD105+ CD14− HLDR−. We also observed that they express common genetic signature consisting of 13,667 genes with enrichment in a number of pathways relevant to stem cell biology, for example, focal adhesion, insulin signaling, and mitogen-activated protein kinase signaling. On the other hand, we observed significant differences in their molecular phenotype with 3282 and 1409 genes differentially expression in BM-hMSC and AD-hMSC, respectively. Further analysis revealed higher expression of genes associated with osteoblast differentiation in BM-hMSC and those of adipocyte differentiation in AD-hMSC which correlated with their differential capacity for osteoblast versus adipocyte differentiation, respectively. Conclusion: Our data suggest that the clinical use of MSC in therapy depend on MSC site of origin, and thus, BM-hMSC are better suited for clinical trials aiming at enhancing bone regeneration. We suggest that molecular phenotype of stem cells is relevant approach for stem cell screening before their clinical transplantation.

Adult human bone marrow stromal cells (hBMSC) cultured for cell therapy require evaluation of potency and stability for safe use. Chromosomal aberrations upsetting genomic integrity in such cells have been contrastingly described as “Limited” or “Significant”. Previously reported stepwise acquisition of a spontaneous neoplastic phenotype during three-year continuous culture of telomerized cells (hBMSC-TERT20) didn't alter a diploid karyotype measured by spectral karyotype analysis (SKY). Such screening may not adequately monitor abnormal and potentially tumorigenic hBMSC in clinical scenarios. We here used array comparative genomic hybridization (aCGH) to more stringently compare non-tumorigenic parental hBMSC-TERT strains with their tumorigenic subcloned populations. Confirmation of a known chromosome 9p21 microdeletion at locus CDKN2A/B, showed it also impinged upon the adjacent MTAP gene. Compared to reference diploid human fibroblast genomic DNA, the non-tumorigenic hBMSC-TERT4 cells had a copy number variation (CNV) in at least 14 independent loci. The pre-tumorigenic hBMSC-TERT20 cell strain had further CNV including 1q44 gain enhancing SMYD3 expression and 11q13.1 loss downregulating MUS81 expression. Bioinformatic analysis of gene products reflecting 11p15.5 CNV gain in tumorigenic hBMSC-TERT20 cells highlighted networks implicated in tumorigenic progression involving cell cycle control and mis-match repair. We provide novel biomarkers for prospective risk assessment of expanded stem cell cultures.

This paper explores science teachers' experiences, views, and preferences of what constitutes effective teacher professional development. The research method utilised both quantitative and qualitative analyses. The former was used with responses from closed-ended questions while responses to an open-ended question were analysed qualitatively. The questionnaire was administrated to science teachers in Saudi Arabia of both genders with a variety of teaching experiences, science specialisms and to those teaching in primary, middle and secondary stage schools. The findings indicate that teachers have concerns about continuing professional development (CPD) programmes offered to them. Teachers' description of CPD showed that they were passive recipients of a pre-packed programme paving the way to how they form their professional identity. Teachers reflected on the aspects that can lead to effective CPD. Drawing on the findings, this paper presents a framework for effective CPD for science teachers where teachers are collaborative, proactive as leaders of reform and with positive professional identities in a context of reform.

Understanding the regulatory networks underlying lineage differentiation and fate determination of human bone marrow stromal cells (hBMSC) is a prerequisite for their therapeutic use. The goal of the current study was to unravel the novel role of the low-density lipoprotein receptor-related protein 3 (LRP3) in regulating the osteogenic and adipogenic differentiation of immortalized hBMSCs. Gene expression profiling revealed significantly higher LRP3 levels in the highly osteogenic hBMSC clone imCL1 than in the less osteogenic clone imCL2, as well as a significant upregulation of LRP3 during the osteogenic induction of the imCL1 clone. Data from functional and gene expression assays demonstrated the role of LRP3 as a molecular switch promoting hBMSC lineage differentiation into osteoblasts and inhibiting differentiation into adipocytes. Interestingly, microRNA (miRNA) expression profiling identified miR-4739 as the most under-represented miRNA (−36.11 fold) in imCL1 compared to imCL2. The TargetScan prediction algorithm, combined with functional and biochemical assays, identified LRP3 mRNA as a novel target of miR-4739, with a single potential binding site for miR-4739 located in the LRP3 3′ UTR. Regulation of LRP3 expression by miR-4739 was subsequently confirmed by qRT-PCR, western blotting, and luciferase assays. Over-expression of miR-4739 mimicked the effects of LRP3 knockdown on promoting adipogenic and suppressing osteogenic differentiation of hBMSCs. Hence, we report for the first time a novel biological role for the LRP3/hsa-miR-4739 axis in balancing osteogenic and adipocytic differentiation of hBMSCs. Our data support the potential utilization of miRNA-based therapies in regenerative medicine.