Cooperativity among Short Amyloid Stretches in Long Amyloidogenic Sequences

Amyloid fibrillar aggregates of polypeptides are associated with many neurodegenerative diseases. Short peptide segments in protein sequences may trigger aggregation. Identifying these stretches and examining their behavior in longer protein segments is critical for understanding these diseases and obtaining potential therapies. In this study, we combined machine learning and structure-based energy evaluation to examine and predict amyloidogenic segments. Our feature selection method discovered that windows consisting of long amino acid segments of ∼30 residues, instead of the commonly used short hexapeptides, provided the highest accuracy. Weighted contributions of an amino acid at each position in a 27 residue window revealed three cooperative regions of short stretch, resemble the β-strand-turn-β-strand motif in A-βpeptide amyloid and β-solenoid structure of HET-s(218–289) prion (C). Using an in-house energy evaluation algorithm, the interaction energy between two short stretches in long segment is computed and incorporated as an additional feature. The algorithm successfully predicted and classified amyloid segments with an overall accuracy of 75%. Our study revealed that genome-wide amyloid segments are not only dependent on short high propensity stretches, but also on nearby residues

Expression of COX2 and multidrug resistance protein 2 (MRP2) in medullary thyroid carcinomas (MTC),

13th International Thyroid Congress (ITC) Buenos Aires, Argentina. Published on THYROID, S-144, P276. ISBN/ISSN:1050-7256. Impact Factor = 2,27

Bilateral cyclic cheek lesions related to premenstrual syndrome: a multifactorial pathogenesis?

Introduction Cheek biting is a chronic, usually innocuous, self-inXicted injury that often occurs as a parafunctional habit. Case report We report an unusual case of bilateral cyclic cheek lesions in a 34-year-old woman characterized by hyperkeratinization near the biting edges of the teeth and hematic lesions accompanied by a cheek swelling sensation, without pain and burning. The lesions coincided with a premenstrual syndrome, characterized by Xuid retention Introduction Cheek biting is a chronic, usually innocuous, self-inXicted injury that often occurs as a parafunctional habit. Case report We report an unusual case of bilateral cyclic cheek lesions in a 34-year-old woman characterized by hyperkeratinization near the biting edges of the teeth and hematic lesions accompanied by a cheek swelling sensation, without pain and burning. The lesions coincided with a premenstrual syndrome, characterized by Xuid retentionrelated symptoms, such as leg swelling, breast tenderness, bloatedness with abdominal girth variation and weight gain. Conclusions We concluded that the excessive water retention caused a little widespread swelling, present at cheeks level also, that associated with a temporary bruxism (perhaps related to psychological stress typical of premenstrual syndrome) was probably responsible for the cyclic cheek lesions. Therefore, an oral exam by the womens health care provider may be valuable in cases of premenstrual syndrome

COX2 INHIBITION PROMOTES MULTIDRUG RESISTANCE PROTEIN 2 (MRP2) EXPRESSION IN MEDULLARY THYROID CARCINOMAS (MTC).

20TH European Congress of Pathology (ECP), PARIS, FRANCE, Published on VIRCHOWS ARCHIVES VOL. 447, N.2, P-592, PAG. 419, ISBN/ISSN: 0945-6317. IMPACT FACTOR = 1,70

Allelic loss at 7q21 is a frequent and early event in thyroid follicular tumors

Poster presentation Abs no. P137 JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION. Impact Factor = 1.59

HGF/c-met system targeting PI3K/AKT and STAT3/phosphorylated-STAT3 pathways in pituitary adenomas: an immunohistochemical characterization in view of targeted therapies

The ligand/receptor hepatocyte growth factor (HGF)/c-met signaling system promotes cellular growth and angiogenesis through PI3K/phosphor-Akt and STAT3/phosphor-STAT3 downstream effectors. In this study, we have evaluated the expression of molecules of the HGF/c-met pathway in pituitary adenomas (PA). The expression of HGF, c-met, PI3K (p85 alpha subunit) pAkt, STAT3, and pSTAT3 was analyzed by immunohistochemistry in an archival series of 30 PA (12 non-functioning and 18 functioning; 25 macroadenomas and 5 microadenomas). PAs expressed all six proteins in tumor epithelial cells. The proportion of c-met(+ve) cells was greater than HGF(+ve) cells (49 +/- A 19 vs 34 +/- A 17 %, P < 0.01), the pAkt(+ve) cells greater than PI3K(+ve) cells (39 +/- A 16.0 vs 1.3 +/- A 0.5 %, P < 0.001), and the STAT3(+ve) cells greater than active pSTAT3(+ve) cells (14 +/- A 8 vs 7 +/- A 6 %, P < 0.01). Furthermore, endothelial Akt immunostaining was detected on the vascular surface area of 17 PAs, in macroadenomas more frequently than in microadenomas (82 vs 18 %). The percentage of immunostained endothelial cells was greater in macro than in microadenomas (19 +/- A 7 and 7 +/- A 3 %; P < 0.05). In conclusion, HGF and c-met are widely expressed in PA, and correlate with pAkt expression. These data, together with the finding of pAkt immunostaining on microvascular areas related to tumor size, suggest a major role of the pAKT signaling in tumor growth and angiogenesis. There might be practical implications for the targeted therapy of PA

Serum hepatocyte growth factor is increased in Hashimoto's thyroiditis whether or not it is associated with nodular goiter as compared with healthy non-goitrous individuals

BACKGROUND: Some growth factors and cytokines are known to cooperate with TSH in thyroid nodular growth, but few data are available on their circulating levels in Hashimoto's thyroiditis (HT). AIM: To evaluate in HT patients whether thyroid nodules are associated with variations in serum levels of hepatocyte growth factor (HGF) and interleukin-6 (IL-6). SUBJECTS AND METHODS: Serum levels of HGF and IL-6 were measured by enzyme-linked immunosorbent assay in 176 euthyroid subjects, subdivided into 4 groups: A) HT patients with nodular goiter (no.=42); B) non-goitrous HT patients (no.=36); C) non-HT patients with nodular goiter (no.=48), and D) healthy subjects without thyroid disease (no.=50). RESULTS: The highest concentrations of serumHGF were found in patients with nodular goiter, irrespective of the presence of associated HT (groups A and C). Nevertheless, in group A serum HGF levels were significantly higher than in group C (860.8+/-333.6 pg/ml vs 691.5+/-156 pg/ml, p<0.01). Moreover, though serum HGF levels in group B (578.3+/-217 pg/ml) were lower than in group A, they were significantly higher than in healthy controls (group D, 512.7+/-170.4 pg/ml, p<0.001). Serum IL-6 levels were similar in the two HT groups (A and B), and increased with respect to groups C and D. CONCLUSIONS: Serum HGF is increased in HT, especially associated to thyroid nodules, as compared with healthy non-goitrous individuals