Roles of leptin on energy balance and thermoregulation in Eothenomys miletus

Leptin is a hormone mainly synthesized and secreted by white adipose tissue (WAT), which regulates various physiological processes. To investigate the role of leptin in energy balance and thermoregulation in Eothenomys miletus, voles were randomly divided into leptin-injected and PBS-injected groups and placed at 25°C ± 1°C with a photoperiod of 12 L:12 D. They were housed under laboratory conditions for 28 days and compared in terms of body mass, food intake, water intake, core body temperature, interscapular skin temperature, resting metabolic rate (RMR), nonshivering thermogenesis (NST), liver and brown adipose tissue (BAT) thermogenic activity, and serum hormone levels. The results showed that leptin injection decreased body mass, body fat, food intake, and water intake. But it had no significant effect on carcass protein. Leptin injection increased core body temperature, interscapular skin temperature, resting metabolic rate, non-shivering thermogenesis, mitochondrial protein content and cytochrome C oxidase (COX) activity in liver and brown adipose tissue, uncoupling protein 1 (UCP1) content and thyroxin 5′-deiodinase (T45′-DII) activity in brown adipose tissue significantly. Serum leptin, triiodothyronine (T3), thyrotropin-releasing hormone (TRH) and corticotropin-releasing hormone (CRH) concentrations were also increased significantly. Correlation analysis showed that serum leptin levels were positively correlated with core body temperature, body mass loss, uncoupling protein 1 content, thyroxin 5′-deiodinase activity, nonshivering thermogenesis, and negatively correlated with food intake; thyroxin 5′-deiodinase and triiodothyronine levels were positively correlated, suggesting that thyroxin 5′-deiodinase may play an important role in leptin-induced thermogenesis in brown adipose tissue. In conclusion, our study shows that exogenous leptin is involved in the regulation of energy metabolism and thermoregulation in E. miletus, and thyroid hormone may play an important role in the process of leptin regulating energy balance in E. miletus

Mechanistic study of endothelium independent vasodilation effects of wogonin

Scutellaria baicalensis Georgi, locally known as HuangQin, and commonly as Baikal or Chinese skullcap, is an important herb in Chinese traditional medicine. The flavonoids from this plant are main active substances responsible for its medicinal applications. Wogonin is one such active ingredient derived from this plant. Here, we investigated the mechanism of the vasodilation effect of wogonin on isolated rat thoracic aortas. For this study, endothelium intact and endothelium removed thoracic aortic rings were prepared from rats. Using a tension transducer, the tension of the rat thoracic aortic rings was recorded. Results showed that wogonin is able to relax the endothelium-intact aortic rings, but L-NAME, indomethacin (Indo), and methylene blue (MB) could not reduce the tension in these rings. Wogonin was also able to relax endotheliumremoved rings. However, treatment with tetraethylammonium (TEA), BaCl2, glibenclamide (Gly), 4-aminopyridine (4-AP), and verapamil (Ver) had no effect on vasodilation induced by wogonin. Using wogonin to pre-treat endothelium-removed aortic rings reduced the contraction induced by K+. Pre-treatment of endothelium-removed aortic rings with wogonin markedly reduced the contraction induced by 10-6 M PE in Ca2+-free solution. It could be concluded that L-type calcium channels and intracellular Ca2+ release is inhibited by wogonin

Mechanistic study of endothelium independent vasodilation effects of wogonin

34-40Scutellaria baicalensis Georgi, locally known as HuangQin, and commonly as Baikal or Chinese skullcap, is an important herb in Chinese traditional medicine. The flavonoids from this plant are main active substances responsible for its medicinal applications. Wogonin is one such active ingredient derived from this plant. Here, we investigated the mechanism of the vasodilation effect of wogonin on isolated rat thoracic aortas. For this study, endothelium intact and endothelium removed thoracic aortic rings were prepared from rats. Using a tension transducer, the tension of the rat thoracic aortic rings was recorded. Results showed that wogonin is able to relax the endothelium-intact aortic rings, but L-NAME, indomethacin (Indo), and methylene blue (MB) could not reduce the tension in these rings. Wogonin was also able to relax endotheliumremoved rings. However, treatment with tetraethylammonium (TEA), BaCl2, glibenclamide (Gly), 4-aminopyridine (4-AP), and verapamil (Ver) had no effect on vasodilation induced by wogonin. Using wogonin to pre-treat endothelium-removed aortic rings reduced the contraction induced by K+. Pre-treatment of endothelium-removed aortic rings with wogonin markedly reduced the contraction induced by 10-6 M PE in Ca2+-free solution. It could be concluded that L-type calcium channels and intracellular Ca2+ release is inhibited by wogonin

Significant association between polymorphism of the erythropoietin gene promoter and myelodysplastic syndrome

<p>Abstract</p> <p>Background</p> <p>Myelodysplastic syndrome (MDS) may be induced by certain mutagenic environmental or chemotherapeutic toxins; however, the role of susceptibility genes remains unclear. The G/G genotype of the single-nucleotide polymorphism (SNP) rs1617640 in the erythropoietin (<it>EPO</it>) promoter has been shown to be associated with decreased EPO expression. We examined the association of rs1617640 genotype with MDS.</p> <p>Methods</p> <p>We genotyped the EPO rS1617640 SNP in 189 patients with MDS, 257 with acute myeloid leukemia (AML), 106 with acute lymphoblastic leukemia, 97 with chronic lymphocytic leukemia, 353 with chronic myeloid leukemia, and 95 healthy controls.</p> <p>Results</p> <p>The G/G genotype was significantly more common in MDS patients (47/187; 25.1%) than in controls (6/95; 6.3%) or in patients with other leukemias (101/813; 12.4%) (all <it>P </it>< 0.001). Individuals with the G/G genotype were more likely than those with other genotypes to have MDS (odd ratio = 4.98; 95% CI = 2.04-12.13). Clinical and follow up data were available for 112 MDS patients and 186 AML patients. There was no correlation between EPO promoter genotype and response to therapy or overall survival in MDS or AML. In the MDS group, the GG genotype was significantly associated with shorter complete remission duration, as compared with the TT genotype (<it>P </it>= 0.03). Time to neutrophils recovery after therapy was significantly longer in MDS patients with the G/G genotype (<it>P </it>= 0.02).</p> <p>Conclusions</p> <p>These findings suggest a strong association between the rs1617640 G/G genotype and MDS. Further studies are warranted to investigate the utility of screening for this marker in individuals exposed to environmental toxins or chemotherapy.</p

JAK2 Exon 14 Deletion in Patients with Chronic Myeloproliferative Neoplasms

BACKGROUND: The JAK2 V617F mutation in exon 14 is the most common mutation in chronic myeloproliferative neoplasms (MPNs); deletion of the entire exon 14 is rarely detected. In our previous study of >10,000 samples from patients with suspected MPNs tested for JAK2 mutations by reverse transcription-PCR (RT-PCR) with direct sequencing, complete deletion of exon 14 (Deltaexon14) constituted <1% of JAK2 mutations. This appears to be an alternative splicing mutation, not detectable with DNA-based testing. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the possibility that MPN patients may express the JAK2 Deltaexon14 at low levels (<15% of total transcript) not routinely detectable by RT-PCR with direct sequencing. Using a sensitive RT-PCR-based fluorescent fragment analysis method to quantify JAK2 Deltaexon14 mRNA expression relative to wild-type, we tested 61 patients with confirmed MPNs, 183 with suspected MPNs (93 V617F-positive, 90 V617F-negative), and 46 healthy control subjects. The Deltaexon14 variant was detected in 9 of the 61 (15%) confirmed MPN patients, accounting for 3.96% to 33.85% (mean = 12.04%) of total JAK2 transcript. This variant was also detected in 51 of the 183 patients with suspected MPNs (27%), including 20 of the 93 (22%) with V617F (mean [range] expression = 5.41% [2.13%-26.22%]) and 31 of the 90 (34%) without V617F (mean [range] expression = 3.88% [2.08%-12.22%]). Immunoprecipitation studies demonstrated that patients expressing Deltaexon14 mRNA expressed a corresponding truncated JAK2 protein. The Deltaexon14 variant was not detected in the 46 control subjects. CONCLUSIONS/SIGNIFICANCE: These data suggest that expression of the JAK2 Deltaexon14 splice variant, leading to a truncated JAK2 protein, is common in patients with MPNs. This alternatively spliced transcript appears to be more frequent in MPN patients without V617F mutation, in whom it might contribute to leukemogenesis. This mutation is missed if DNA rather than RNA is used for testing

Effects of Clinically Relevant MPL Mutations in the Transmembrane Domain Revealed at the Atomic Level through Computational Modeling

BACKGROUND: Mutations in the thrombopoietin receptor (MPL) may activate relevant pathways and lead to chronic myeloproliferative neoplasms (MPNs). The mechanisms of MPL activation remain elusive because of a lack of experimental structures. Modern computational biology techniques were utilized to explore the mechanisms of MPL protein activation due to various mutations. RESULTS: Transmembrane (TM) domain predictions, homology modeling, ab initio protein structure prediction, and molecular dynamics (MD) simulations were used to build structural dynamic models of wild-type and four clinically observed mutants of MPL. The simulation results suggest that S505 and W515 are important in keeping the TM domain in its correct position within the membrane. Mutations at either of these two positions cause movement of the TM domain, altering the conformation of the nearby intracellular domain in unexpected ways, and may cause the unwanted constitutive activation of MPL's kinase partner, JAK2. CONCLUSIONS: Our findings represent the first full-scale molecular dynamics simulations of the wild-type and clinically observed mutants of the MPL protein, a critical element of the MPL-JAK2-STAT signaling pathway. In contrast to usual explanations for the activation mechanism that are based on the relative translational movement between rigid domains of MPL, our results suggest that mutations within the TM region could result in conformational changes including tilt and rotation (azimuthal) angles along the membrane axis. Such changes may significantly alter the conformation of the adjacent and intrinsically flexible intracellular domain. Hence, caution should be exercised when interpreting experimental evidence based on rigid models of cytokine receptors or similar systems

Memristor Content Addressable Memory: Theory, Design and Application

The memristor has been proposed as the fourth circuit element. Among the emerging nano-technologies, the memristor has become a very promising candidate for building storage structures because of its shorter switching time, higher capacity and lower power consumption. In this thesis, I will first introduce a new memristor model with controllable window functions, which is more authentic and flexible than those existing memristor models. Then I will present my novel design of a Memristor Content Addressable Memory (Memristor-CAM) structure that is based on my own design of Memristor-CAM cells. The major contribution of this work is the fuzzy look-up functionality, which is achieved by summing up the current of the matched cell lines in the Memristor-CAM. In addition, this fuzzy look-up functionality of the new Memristor-CAM design could be further extended in order to fit into a lot of practical applications. With the benefits of memristors, this Memristor-CAM storage structure could reduce the power consumption, increase the capacity and improve the performance of computer memory. My new design is tested in a common experimental design that includes computer simulations and circuit emulations. The results of my experiments support the validity of my contributions and allow further analysis and insights on the behaviours of memristors when different settings are applied

LAPSEN KIELEN KEHITYS KAKSIKIELISESSÄ PERHEESSÄ

Opinnäytetyön kuvaus: Käsittelen opinnäytetyössäni lapsen kielen kehitystä kaksikielisessä perheessä. Tuon esille yhteiskunnan suhtautumisesta kaksikielisyyteen ja millainen merkitys sukulaisilla ja perheellä on lapsen kielen ja kulttuurin omaksumisessa. Lisäksi kuvaan lapsen kielen kehitystä ja miten kaksikielinen lapsi omaksuu kaksi kieltä. Teoreettinen ja käsitteellinen esittely: Käsittelen teoriaosuudessa kaksikielisyyttä ja lapsen kielen kehitystä ja kuinka se etenee. Liitän työhöni Bronfenbrennerin ekologisen teorian. Tarkastelen hieman mitä monikulttuurisuus on. Lisäksi kuvaan mitkä ovat neuvolan, päivähoidon ja koulun tuet kaksikieliselle lapselle ja perheelle. Metodologinen esittely: Kuvaan metodologisessa osiossa opinnäytetyöprosessin etenemistä. Aineiston keruumenetelmänä olen käyttänyt kyselylomaketta sekä haastattelua, jotka olen lähettänyt kahdelle kaksikieliselle perheelle, jotka antavat pohjan tarinalliseen kerrontaan. Pohdintani tukeutuu teoriaan. Keskeiset tutkimustulokset: Tarinoiden perusteella molemmilla perheillä on ollut samantyyliset strategiat kaksikielisyyden opettamisen suhteen. Ympäristöllä on suuri vaikutus lapsen kaksikielisyyteen. Siellä missä lapsi asuu, pysyy vahvempana kielenä se kieli mitä hän enemmän käyttää. Aineiston perusteella kyselyyn vastannut äiti ei ole saanut neuvolassa hänen mielestään tarpeeksi tietoa kaksikielisyyteen liittyvissä asioissa. Kielenkehityksen häiriöt eivät ole riippuvaisia siitä, onko lapsi kaksikielinen tai yksikielinen. Johtopäätökset: Perheen äidin mielestä, Norjan neuvolalla ei ole ollut valmiuksia tukea ja opastaa perhettä kaksikielisyyteen liittyvissä asioissa. Mielestäni päivähoidossa pyritään huomioimaan lapsen yksilölliset tarpeet ja koulu on parhaiten ottanut monikulttuurisuuden huomioon sekä alkanut mukauttamaan opetusta sen suuntaan. Perheen toteuttama kielistrategia on yleinen opetusmenetelmä kaksikielisissä perheissä.Thesis description: In my thesis I concentrate on the child’s bilingual abilities. In my thesis I will write about how the society reacts to bilingualism and what kind of meaning does the relatives and family have on how the child adapts to bilingualism and culture. I will also describ child’s bilingual progress in general as well as how a bilingual child adapts two languages. Theoretical summary: In the theoretical part I deal with bilingualism and child’s language development. I include Bronfenbrenner’s ecological theory in my work. I also look into what multiculturalism is. I looked into what kind of support do child health care and schools give to bilingual families. Methodological summary: In the methological part I describe the process of this thesis. I collected my material by interviewing and sending out a questionnaire to two bilingual families which gives the base for the narrative story. The discussion is based on the theory. Main results: Based on the stories, I concluded that both families have very similar strategies on how to teach bilingualism to their children and that the environment has a huge impact on child’s bilingualism. Usually that language which child uses more is the dominating language. Based on the story, the mother felt that she hasn’t been given enough information about the bilingualism at the child health centre. Also the discruptions in language development are dependent on whether the child is bilingual or unilingual. Conclusions: Based on the mother’s opinion, the child health center hasn’t had enough capacities to support and guide the family on the issues concerning bilingualism. My opinion is that child’s unique needs are more taken into consideration in the daycare center and the school takes multiculturalism into consideration the best. The language strategy that the family executes on its own is common in bilingual families.Liitteenä myös opinnäytetyön kansi