Physical mapping of a powdery mildew resistance related gene Hv-S/TPK by FISH with a TAC clone in wheat

Dissertação de mestrado integrado em Medicina (Hematologia), apresentado á Faculdade de Medicina da Universidade de Coimbra.A Policitemia Vera (PV) é uma doença clonal de etiologia desconhecida, na maior parte dos casos, que envolve a célula estaminal progenitora hematopoiética multipotencial. É uma neoplasia mieloproliferativa crónica (NMP) que se caracteriza pela expansão das três linhas celulares hematopoiéticas: eritróide, granulocítica e megacariocítica, com predomínio da primeira, de modo independente dos mecanismos normais de regulação da eritropoiese. Além disso, as células têm aspecto morfológico normal, a fibrose medular é pouco significativa e os níveis de eritropoietina (Epo) são habitualmente normais a baixos. Além da hipercelularidade medular com sobreprodução de uma ou de todas as linhas celulares, a doença cursa com hematopoiese extramedular, hiperviscosidade, propensão para complicações como trombose ou hemorragia e risco de desenvolvimento de mielofibrose ou transformação em leucemia aguda. A descrição relativamente recente da associação de uma mutação no gene JAK2, localizado no cromosoma 9p24, com as doenças mieloproliferativas clássicas negativas para BCR-ABL, como a PV, veio permitir avanços significativos na compreensão da patofisiologia deste grupo de doenças hematológicas. A mutação provoca uma alteração do aminoácido V (valina) para F (fenilalanina) na posição 617 (JAK2V617F). De acordo com os dados publicados, a frequência da detecção da mutação JAK2V617F em doentes com PV é de cerca de 95%. A proteína JAK2 é uma tirosina cinase citoplasmática, que se encontra associada ao domínio intracelular dos receptores de citocinas (como a Epo e trombopoietina - Tpo), e de factores de crescimento, essenciais para a função destes receptores. A mutação da JAK2 conduz à activação constitutiva dos receptores, independente da ligação à respectiva citocina e/ou hipersensibilidade a factores de crescimento, com consequente activação de múltiplas vias de sinalização intracelulares como a JAK/STAT (Janus Kinase/Signal Transductor and activator of transcription), a PI3K (fosfatidilinositol 3 cinase) e a MAPK (proteína cinase activadora de mitose), envolvidas na transformação e proliferação dos progenitores hematopoiéticos. Por outro lado, as células evidenciam alteração na diferenciação terminal e resistência à apoptose in vitro que poderá estar relacionada com o aumento da expressão da proteína anti-apoptótica Bcl-XL. Além dos avanços no diagnóstico, a detecção da mutação JAK2V617F tem contribuido para melhorar a classificação e a terapêutica dos doentes com PV. Deste modo, o conhecimento dos mecanismos moleculares envolvidos na PV tem levado os investigadores à descoberta de novos fármacos dirigidos ao defeito molecular, permitindo novas abordagem terapêuticas mais eficazes e provavelmente de menor toxicidade. Este trabalho procura fazer uma revisão sobre o actual conhecimento da caracterização molecular e clínica da PV e quais as suas implicações no diagnóstico e abordagem terapêutica desta NMP.Polycythemia Vera (PV) is a clonal disease of unknown etiology, which often involves the pluripotential hematopoietic stem cell. This disease integrates the family of chronic myeloproliferative neoplasm (MPN) and is characterized by the growth of the three hematopoietic celular lineages: granulocytic, megakaryocytic and erythroid, with predominance of the last one and regardless the normal mechanisms of erythropoiesis regulation. Moreover, cells have normal morphological aspect, bone marrow shows slight fibrosis and the levels of erythropoietin (Epo) usually vary from normal to low. Besides marrow hypercellularity with overproduction of one or all the celular lineages, the disease courses with extramedullary hematopoiesis, hyperviscosity, leading to complications such as thrombosis or bleeding and risk of transformation to myelofibrosis or acute leukemia. Recently it has been described the association between the mutation in the JAK2 gene, located on chromosome 9p24, with the classic myeloproliferative disorders BCR-ABL negative, such as PV, which has brought significant advances in the understanding of the pathophysiology of this group of hematologic malignancies. The mutation causes a change of amino acid V (valine) to F (phenylalanine) at position 617 (JAK2V617F). According to published data, the frequency of JAK2V617F mutation detected in patients with PV is about 95%. JAK2 protein is a cytoplasmic tyrosine kinase, which is associated to the intracelular domain of cytokine receptors, such as Epo and thrombopoietin (Tpo), and growth factors which are essential to the function of these receptors. JAK2 mutation leads to the constitutive receptors activation, independent of connection to their cytokine and / or hypersensitivity to growth factors, with consequent activation of multiple intracellular signaling pathways such as JAK / STAT (Janus Kinase / Signal transducer and transcription activator), the PI3K (phosphatidylinositol 3 kinase) and MAPK (Mitogen-activated protein), involved in the transformation and proliferation of hematopoietic progenitors. Moreover, the cells show changes in terminal differentiation and resistance to in vitro apoptosis which is possibly related to the increasing expression of anti-apoptotic protein Bcl-XL. In addition to the advances in diagnosis, detection of JAK2V617F mutation has contributed to the improvement of classification and treatment in patients with PV. Thus, knowledge of the molecular mechanisms involved in PV has led investigators to the discovery of new drugs targeting molecular defects, allowing new therapeutic approach more efficient and probably less toxic. The aim of this article is to review the current knowledge of clinical and molecular characterization of PV, and its implications on the diagnosis and therapeutic approach of this myeloproliferative disorder

Self-Organized Ni Nanocrystal Embedded in BaTiO3 Epitaxial Film

Ni nanocrystals (NCs) were embedded in BaTiO3 epitaxial films using the laser molecular beam epitaxy. The processes involving the self-organization of Ni NCs and the epitaxial growth of BaTiO3 were discussed. With the in situ monitoring of reflection high-energy electron diffraction, the nanocomposite films were engineered controllably by the fine alternation of the self-organization of Ni NCs and the epitaxial growth of BaTiO3. The transmission electron microscopy and the X-ray diffraction characterization confirmed that the composite film consists of the Ni NCs layers alternating with the (001)/(100)-oriented epitaxial BaTiO3 separation layers

Understanding the Relationship Between Vascular Smooth Muscle Cell Function and the Efficacy of Acupuncture in Treating Cerebral Ischemic Stroke: A Preclinical Meta-Analysis and Systematic Review

Jiang-Peng Cao,1– 3 Yuan-Hao Du,1,2,4 Lan-Yu Jia,5 Xiu-Mei Yin,1– 3 Li-Hong Yang,1,2 Lin-Ling Chen,6 Tao Jiang,1,2 Man Zhang,4 Tian Qiu1– 3 1Department of Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 2National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, People’s Republic of China; 3Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 4School of acupuncture & moxibustion and Tuina, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 5Department of Geriatric medicine, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, People’s Republic of China; 6Department of Traditional Chinese Medicine, Huzhou Central Hospital, Huzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Yuan-Hao Du, Email [email protected]: Cerebral blood flow and vascular structures serve as the fundamental components of brain metabolism and circulation. Acupuncture, an alternative and complementary medical approach, has demonstrated efficacy in treating cerebral ischemic stroke (CIS). Nevertheless, the mechanisms underlying the impact of acupuncture on vascular smooth muscle cell (VSMC) function remain uncertain. The objective of this systematic review and meta-analysis is to assess the alterations in VSMC function following acupuncture stimulation in CIS models.Methods: The databases PubMed, Web of Science, SCOPUS, and EMBASE were queried until November 2022 using a predetermined search strategy. The FORMAT BY SYRCLE guidelines were adhered to, and the risk of bias of the included studies was evaluated using the Risk of Bias tool developed by the Systematic Review Centre for Laboratory Animal Experimentation. The random-effects model was employed to estimate the standardized mean difference (SMD).Results: Eighteen articles are included in this review. Acupuncture showed significant positive effects on the region cerebral blood flow (SMD=8.15 [95% CI, 4.52 to 11.78]) and neurological deficiency (SMD=− 3.75 [95% CI, − 5.54 to − 1.97]). Descriptive analysis showed a probable mechanism of acupuncture stimulation in CIS rats related to VSMC function. Limitations and publication bias were presented in the studies.Conclusion: In this systematic review and meta-analysis, our findings indicate that acupuncture stimulation has the potential to improve regional cerebral blood flow and alleviate neurological deficits, possibly by regulating VSMC function. However, it is important to exercise caution when interpreting these results due to the limitations of animal experimental design and methodological quality.Keywords: acupuncture therapy, vascular smooth muscle cell, vasomotor, cerebral ischemic stroke, systematic revie

Charge Condensation and Lattice Coupling Drives Stripe Formation in Nickelates

Revealing the predominant driving force behind symmetry breaking in correlated materials is sometimes a formidable task due to the intertwined nature of different degrees of freedom. This is the case for La_{2-x}Sr_{x}NiO_{4+δ}, in which coupled incommensurate charge and spin stripes form at low temperatures. Here, we use resonant x-ray photon correlation spectroscopy to study the temporal stability and domain memory of the charge and spin stripes in La_{2-x}Sr_{x}NiO_{4+δ}. Although spin stripes are more spatially correlated, charge stripes maintain a better temporal stability against temperature change. More intriguingly, charge order shows robust domain memory with thermal cycling up to 250 K, far above the ordering temperature. These results demonstrate the pinning of charge stripes to the lattice and that charge condensation is the predominant factor in the formation of stripe orders in nickelates

HPRT Mutations in Lymphocytes from 1,3-Butadiene-Exposed Workers in China

BACKGROUND: 1,3-Butadiene (BD) is an important industrial chemical and an environmental and occupational pollutant. The carcinogenicity of BD in rodents has been proved, but its carcinogenic and mutagenic molecular mechanism(s) are not fully elucidated in humans. OBJECTIVES: In the present study, we compared the mutation frequencies and exon deletions of BD-exposed workers with that of control subjects in China to identify the characteristic mutations associated with BD exposure in the human HPRT (hypoxanthine–guanine–phosphoribosyltransferase) gene. METHODS: Seventy-four workers exposed to BD via inhalation and 157 matched controls were evaluated in Nanjing, China. Molecular analysis of HPRT mutant T lymphocytes from BDexposed workers and nonexposed control subjects was conducted to identify changes in the structure of the HPRT gene. A total of 783 HPRT mutants were analyzed by multiplex polymerase chain reaction, in which 368 HPRT mutants were isolated from BD-exposed workers and 415 mutants from control subjects. RESULTS: The BD-exposed workers showed a higher mutation frequency (18.2 ± 9.4 × 10 –6) than the control subjects (12.7 ± 7.3 × 10 –6), but the difference was not significant (p> 0.05). The frequency of exon deletions in BD-exposed workers (27.4%) was significantly higher than that in control subjects (12.5%) (p < 0.05), which mainly included multiplex exon deletions (2–8 exons). CONCLUSIONS: The results of the present study suggest that BD should increase the frequency of large deletions of HPRT gene in human lymphocytes This change confirms and supports the previous findings in BD-exposed workers. KEY WORDS: 1,3-butadiene, BD, exon deletion, HPRT gene, lymphocyte, occupational exposure. Environ Health Perspect 116:203–208 (2008). doi:10.1289/ehp.10353 available vi

Synthesis and Application of Carbon–Iron Oxide Microspheres’ Black Pigments in Electrophoretic Displays

Carbon–iron oxide microspheres’ black pigments (CIOMBs) had been prepared via ultrasonic spray pyrolysis of aqueous solutions containing ferrous chloride and glucose. Due to the presence of carbon, CIOMBs not only exhibited remarkably acid resistance, but also could be well dispersed in both polar solvents and nonpolar solvent. Finally, dispersions of hollow CIOMBs in tetrachloroethylene had successfully been applied in electrophoretic displays

Carbon-Coated SnO2 Nanorod Array for Lithium-Ion Battery Anode Material

Carbon-coated SnO2 nanorod array directly grown on the substrate has been prepared by a two-step hydrothermal method for anode material of lithium-ion batteries (LIBs). The structural, morphological and electrochemical properties were investigated by means of X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and electrochemical measurement. When used as anodes for LIBs with high current density, as-obtained array reveals excellent cycling stability and rate capability. This straightforward approach can be extended to the synthesis of other carbon-coated metal oxides for application of LIBs