GATA family transcriptional factors: emerging suspects in hematologic disorders

Previous research indicated students’ difficulties in acquiring academic reading and writing literacies. Achieving language proficiency expected in higher education often requires hard work from students. Their problems with reading and writing academic texts also presents a challenge for university teachers, who are expected to support students in their academic language development. Our research project aims at exploring how text-based conversations can be used to develop students' understanding of the conventions in academic texts, as well as students’ ability to examine these texts critically.Students’ need for continuous support, related to the educational content, has been discussed before (e.g. Lea & Street, 1998; Monroe, 2003). University teachers, regardless of their subjects or disciplines, can support students’ reading and writing development in a variety of ways (e.g. Lillis & Scott, 2007; Wingate, 2011). Our point of departure is in socio-culturally oriented research on academic writing (e.g. Lea & Street, 1998; Blåsjö, 2004). For this investigation of text-based conversations, however, we also use more text-oriented and genre-based approaches (e.g. Hyland, 2004; Bazerman, Bonini & Figueiredo, 2009).Our project is based on a qualitative study of students' conversations on a scientific text included in their course. The text-based conversations were conducted during a three-hour session, in which the first part included a joint teacher-led discussion between the students and the teacher. This discussion was based on issues focusing some fundamental aspects of a text and its context: what is the problem and purpose of the study, what methods are used and for whom is this article written. The second half of the session was devoted to group discussions, where the task was to examine critically the qualities of the text based on a number of typical features in scientific texts, such as clarity, transparency, independency of context, text structure, and validity claims. The purpose of the assignment was for students to engage in a close reading of the text. These text-based conversations were recorded in several student groups. The recorded material was subsequently transcribed and analysed.We identified three themes relevant to the students’ comprehension of the academic text discussed: the text's usability, the text's reliability, and students' attitudes towards the text and the researchers. The results highlight the teacher’s role in supporting students' reading and writing. Furthermore, the study indicates that students need knowledge about researchers’ working conditions and their writing to understand why academic texts look as they do. In this talk, we focus on the critical potential of text-based conversations as a tool for students’ reading and writing development.References:Bazerman, C., Bonini, A. & Figueiredo, D.D.C. (Eds.). (2009). Genre in a changing world. Fort Collins, Colorado: WAC Clearinghouse.Blåsjö, M. (2004). Studenters skrivande i två kunskapsbyggande miljöer. Stockholm: Almqvist och Wiksell International.Hyland, K. (2004). Disciplinary Discourse. Social Interactions in Academic writing. Michigan: The University of Michigan Press.Lea, M. R. & Street, B. V. (1998). Student writing in higher education: An academic literacies approach. Studies in Higher Education, 23(2), 157-172.Lillis T. M. & Scott, M. (2007). Defining academic literacies research. Issues of epistemology, ideology and strategy. Journal of Applied linguistics, 4(1), 5-32.Monroe, J. (2003). Writing in the disciplines. Peer Review, 6(1), 5-32.Wingate, U., Andon, N. & Cogo, A. (2011). Embedding academic writing instruction int

Effects of Brain-Derived Neurotrophic Factor on Local Inflammation in Experimental Stroke of Rat

This study was aimed to investigate whether brain-derived neurotrophic factor (BDNF) can modulate local cerebral inflammation in ischemic stroke. Rats were subjected to ischemia by occluding the right middle cerebral artery (MCAO) for 2 hours. Rats were randomized as control, BDNF, and antibody groups. The local inflammation was evaluated on cellular, cytokine, and transcription factor levels with immunofluorescence, enzyme-linked immunosorbent assay, real-time qPCR, and electrophoretic mobility shift assay, respectively. Exogenous BDNF significantly improved motor-sensory, sensorimotor function, and vestibulomotor function, while BDNF did not decrease the infarct volume. Exogenous BDNF increased the number of both activated and phagocytotic microglia in brain. BDNF upregulated interleukin10 and its mRNA expression, while downregulated tumor necrosis factor α and its mRNA expression. BDNF also increased DNA-binding activity of nuclear factor-kappa B. BDNF antibody, which blocked the activity of endogenous BDNF, showed the opposite effect of exogenous BDNF. Our data indicated that BDNF may modulate local inflammation in ischemic brain tissues on the cellular, cytokine, and transcription factor levels

H2AX Deficiency is Associated with Erythroid Dysplasia and Compromised Haematopoietic Stem Cell Function

Myelodysplastic syndromes (MDS) are clonal disorders of haematopoiesis characterised by dysplastic changes of major myeloid cell lines. However, the mechanisms underlying these dysplastic changes are poorly understood. Here, we used a genetically modified mouse model and human patient data to examine the physiological roles of H2AX in haematopoiesis and how the loss of H2AX contributes to dyserythropoiesis in MDS. H2AX knockout mice showed cell-autonomous anaemia and erythroid dysplasia, mimicking dyserythropoiesis in MDS. Also, dyserythropoiesis was increased in MDS patients with the deletion of chromosome 11q23, where H2AX is located. Although loss of H2AX did not affect the early stage of terminal erythropoiesis, enucleation was decreased. H2AX deficiency also led to the loss of quiescence of hematopoietic stem and progenitor cells, which dramatically compromised their bone marrow engraftment. These results reveal important roles of H2AX in late-stage terminal erythropoiesis and hematopoietic stem cell function

Clinical effects of unilateral biportal endoscopic decompression for lumbar posterior apophyseal ring separation

ObjectiveThe purpose of the study was to investigate the feasibility and effects of unilateral biportal endoscopic decompression for lumbar posterior apophyseal ring separation (PARS).MethodsPatients with lumbar PARS who received unilateral biportal endoscopic decompression from June 2020 to September 2021 were analyzed, including 11 females and 15 males. The clinical symptoms were consistent with the imaging findings. Operation time, length of postoperative hospital stay and complications were recorded, and the clinical efficacy was evaluated by Visual Analogue Scale (VAS), Oswestry Disability Index (ODI) and modified Macnab scale at preoperative, postoperative 1, 3, 6 months and the last follow-up.ResultsPreoperative VAS scores of low back pain were (5.04 ± 1.37) and respectively decreased to (2.81 ± 0.75), (2.35 ± 0.98), (1.65 ± 0.69) and (1.15 ± 0.68) at postoperative 1, 3, 6 months and at the last follow-up, and the difference was statistically significant (F = 127.317, P = 0.000). Preoperative VAS scores of lower limb pain were (6.92 ± 1.38) and respectively decreased to (2.88 ± 1.07), (2.54 ± 1.03), (1.81 ± 0.80) and (1.00 ± 0.69) at postoperative 1, 3, 6 months and at the last follow-up, and the difference was statistically significant (F = 285.289, P = 0.000). Preoperative ODI scores were (60.47 ± 8.89) and respectively decreased to (34.72 ± 4.13), (25.80 ± 3.65), (17.71 ± 3.41) and (5.65 ± 2.22) at postoperative 1, 3, 6 months and at the last follow-up, and the difference was statistically significant (F = 725.255, P = 0.000). According to the modified Macnab criteria, the final outcome was excellent in 22 cases, good in 3 cases, fair in 1 cases. 26 patients could return to work or normal activities within 3 weeks.ConclusionsUnilateral biportal endoscopic decompression has the advantages of clear and wide field of vision, large operating space, relatively simple need of surgical instrument and convenient and flexible operation procedure. It can achieve excellent clinical results with favorable efficacy and safety and may become a new minimally invasive endoscopic treatment for lumbar PARS

KRAS mutation in secondary malignant histiocytosis arising from low grade follicular lymphoma

Abstract Background Transformation of follicular lymphoma most typically occurs as diffuse large B-cell lymphoma, however other forms of transformation such as classic Hodgkin lymphoma and lymphoblastic transformation can occur. Secondary malignant histiocytosis also represents a rare form of transformation, which is thought to occur due to a process of transdifferentiation whereby the lymphoma cells exhibit lineage plasticity and lose all evidence of B-cell phenotype and instead acquire the phenotype of a histiocytic neoplasm. Little is known about the underlying genetic alterations that occur during this unusual process. Comparative genetic analysis of pre- and post-transformation/transdifferentiation would be one tool by which we could better understand how this phenomenon occurs. Case presentation Here we report the clinical, immunophenotypic and genetic features of a rare case of secondary malignant histiocytosis, Langerhans cell-type (Langerhans cell sarcoma) arising from a previous low grade follicular lymphoma. FISH analysis confirmed the presence of IgH/BCL2 rearrangement in both the low grade follicular lymphoma (FL) and transformed Langerhans cells sarcoma (LCS) samples, demonstrating a clonal relationship. Comparative whole exome sequencing was then performed, which identified a KRAS p.G13D mutation in the LCS that was not present in the FL. Conclusions This report highlights genetic alterations, in particular an acquired somatic KRAS mutation, that may occur during transdifferentiation, with additional significance of KRAS mutation as a possible therapeutic target in cases which otherwise would have limited treatment options.https://deepblue.lib.umich.edu/bitstream/2027.42/145736/1/13000_2018_Article_758.pd

Blood glucose level affects prognosis of patients who received intravenous thrombolysis after acute ischemic stroke? A meta-analysis

Background and objectivesIntravenous recombinant tissue plasminogen activator (rtPA) thrombolysis is an effective treatment for acute ischemic stroke. Hyperglycemia is a major risk factor for the occurrence, development, and prognosis of ischemic stroke. This meta-analysis purposefully estimates the association between hyperglycemia and poor prognosis in acute ischemic stroke patients receiving intravenous rtPA thrombolytic therapy.Materials and methodsAccording to the predefined inclusion criteria, we searched PubMed, Web of Science, and Cochrane Library databases. The association of high blood glucose(>140mg/dl) with symptomatic intracranial hemorrhage (sICH), poor clinical outcome and mortality at 90 days post-rtPA thrombolysis was studied using both a common effects model and a random effects model. Odds ratios (ORs) were plotted on forest plots.ResultsOf a total cohort of 2565 patients who received intravenous thrombolytic therapy, 721 had higher blood glucose. High glucose level significantly increased the odds of sICH (OR 1.80; 95% confidence interval(95%CI): 1.30- 2.50) and poor clinical outcome at 90 days (OR 1.82; 95%CI: 1.52-2.19), and all-cause mortality at 90 days (OR 2.51; 95%CI:1.65-3.82).ConclusionsIn our meta-analysis, high blood glucose was significantly associated with sICH, poor clinical outcome and higher mortality at 90 days

Down-regulation of pancreatic and duodenal homeobox-1 by somatostatin receptor subtype 5: a novel mechanism for inhibition of cellular proliferation and insulin secretion by somatostatin

Somatostatin (SST) is a regulatory peptide and acts as an endogenous inhibitory regulator of the secretory and proliferative responses of target cells. SST's actions are mediated by a family of seven transmembrane domain G protein-coupled receptors that comprise five distinct subtypes (SSTR1-5). SSTR5 is one of the major SSTRs in the islets of Langerhans. Homeodomain-containing transcription factor pancreatic and duodenal homeobox-1 (PDX-1) is essential for pancreatic development, β cell differentiation, maintenance of normal β cell functions in adults and tumorigenesis. Recent studies show that SSTR5 acts as a negative regulator for PDX-1 expression and that SSTR5 mediates somatostatin's inhibitory effect on cell proliferation and insulin expression/excretion through down-regulating PDX-1 expression. SSTR5 exerts its inhibitory effect on PDX-1 expression at both the transcriptional level by down-regulating PDX-1 mRNA and the post-translational level by enhancing PDX-1 ubiquitination. Identification of PDX-1 as a transcriptional target for SSTR5 may help in guiding the choice of therapeutic cancer treatments