Miracle-dz/UniFAR-FTUs huggingface dataset:
Hemoglobin and Its Scavenger Protein Haptoglobin Associate with ApoA-1-containing Particles and Influence the Inflammatory Properties and Function of High Density Lipoprotein*

Hemoglobin (Hb) uniquely associates with proinflammatory HDL in atherogenic mice and coronary heart disease (CHD) patients. In this paper, we report that Hb and its scavenger proteins, haptoglobin (Hp) and hemopexin (Hx) are significantly increased in apoA-1-containing particles of HDL both in mouse models of hyperlipidemia and in CHD patients, when compared with wild type mice and healthy donors, respectively. We further demonstrate that the association of Hb, Hp, and Hx proteins with HDL positively correlates with inflammatory properties of HDL and systemic inflammation in CHD patients. Interestingly, HDL from Hp−/− mice under atherogenic conditions does not accumulate Hb and is anti-inflammatory, suggesting that (i) Hp is required for the association of Hb with HDL and (ii) Hb·Hp complexes regulate the inflammatory properties of HDL. Moreover, treatment of apoE−/− mice with an apoA-1 mimetic peptide resulted in significant dissociation of Hb·Hp complexes from HDL and improvement of HDL inflammatory properties. Our data strongly suggest that HDL can become proinflammatory via the Hb·Hp pathway in mice and humans, and dissociation of Hb·Hp·Hx complexes from apoA-1-containing particles of HDL may be a novel target for the treatment of CHD.
Capitalising on the social resources within culturally and linguistically diverse communities for mental health promotion: stories of Australian Chinese people

Social capital, generally observed in Chinese cultures, can be considered as the glue that holds together all the norms, trust and social networks that enhance mutual benefit of a collectivistic society. The aim of this paper is to explore the best way to tap into these social resources in mental health promotion. A mixed-method study, consisting of 16 community focus groups and a quantitative survey (n = 528), was conducted among Chinese Australians (recruited from general practices) in metropolitan Sydney. Although the focus groups explored help-seeking behaviours during emotional distress, the survey assessed the prevalence of such episodes. Chinese informants identified ‘family and friends’, ‘cultural values’, ‘spirituality’ and ‘self’ as common ‘helpers’ for managing depressive episodes before professionals were consulted. These ‘helpers’ function as the ‘social capital’ within the Chinese community. Focus group narratives of the low-acculturated Chinese revealed that they turned to close friends and family for help during crises. Highly acculturated Chinese found ‘family values’ most helpful when facing adversity. Survey findings indicated that the self-report rate of lifetime depression in low-acculturated Chinese was significantly lower than that of Australians. These results resonate with Cullen and Whiteford’s (2001) proposition that a higher level of social capital decreases the incidence of depression. Although the links between social capital and mental health require further investigation, the current findings support its role in counteracting emotional distress. There are implications of the current research findings to wider culturally and linguistically diverse communities.
Tumor‐associated macrophages infiltrate plasmacytomas and can serve as cell carriers for oncolytic measles virotherapy of disseminated myeloma

In multiple myeloma, some of the neoplastic plasma cells are diffusely dispersed among the normal bone marrow cells (bone marrow resident), whereas others are located in discrete, well‐vascularized solid tumors (plasmacytomas) that may originate in bone or soft tissue. Interactions between bone marrow‐resident myeloma cells and bone marrow stromal cells (BMSCs) are important determinants of myeloma pathogenesis. However, little is known of the factors sustaining myeloma growth and cell viability at the centers of expanding plasmacytomas, where there are no BMSCs. Histologic sections of 22 plasmacytomas from myeloma patients were examined after immunostaining. Abundant CD68+, CD163+, S100‐negative macrophage infiltrates were identified in all tumors, accompanied by scattered collections of CD3+ T lymphocytes. The CD68+ tumor‐associated macrophages (TAM) accounted for 2–12% of nucleated cells and were evenly distributed through the parenchyma. The TAM generally had dendritic morphology, and each dendrite was in close contact with multiple plasma cells. In some cases, the TAM were strikingly clustered around CD34+ blood vessels. To determine whether cells of the monocytic lineage might be exploitable as carriers for delivery of therapeutic agents to plasmacytomas, primary human CD14+ cells were infected with oncolytic measles virus and administered intravenously to mice bearing KAS6/1 human myeloma xenografts. The cell carriers localized to KAS6/1 tumors, where they transferred MV infection to myeloma cells and prolonged the survival of mice bearing disseminated human myeloma disease. Thus, TAM are a universal stromal component of the plasmacytomas of myeloma patients and may offer a promising new target for therapeutic exploitation. Am. J. Hematol. 2009. © 2009 Wiley‐Liss, Inc.
Defining the function of β‐catenin tyrosine phosphorylation in cadherin‐mediated cell–cell adhesion

β‐catenin is a key protein in cadherin–catenin cell adhesion complex and its tyrosine phosphorylation is believed to cause destruction of junctional apparatus. The broad spectrum of substrates for kinases and phosphatases, however, does not rule out tyrosine phosphorylation of other junctional proteins as the main culprit in reduction of cell adhesion activity. Further, the endogenous β‐catenin perturbs detailed functional analysis of phosphorylated mutant β‐catenin in living cells. To directly evaluate the effect of β‐catenin tyrosine phosphorylation in cell adhesion, we utilized F9 cells in which expression of endogenous β‐catenin and its closely related protein plakoglobin were completely shut down. We also used α‐catenin‐deficient (αD) cells to evaluate the role of α‐catenin on β‐catenin tyrosine phosphorylation. We show that β‐catenin with phosphorylation mutation at 654th tyrosine forms functional cadherin–catenin complex to mediate strong cadherin‐mediated cell adhesion. Moreover, we show that 64th and 86th tyrosines are mainly phosphorylated in F9 cells, especially in the absence of α‐catenin. Phosphorylation of these tyrosine residues, however, does not affect cadherin‐mediated cell adhesion activity. Our data identified a novel site phosphorylated by endogenous tyrosine kinases in β‐catenin. We also demonstrate that tyrosine phosphorylation of β‐catenin might regulate cadherin‐mediated cell adhesion in a more complicated way than previously expected.
Avaliação dos níveis de recessão gengival em estudantes de odontologia da Universidade Federal de Pernambuco

Objectives: The aim of this study was to evaluate, quantitatively, the levels of gingival recession and their prevalence in students of Dentistry of the Federal University of Pernambuco. Methods: The randomized sample consisted of 110 Dentistry Students from third and fourth grades at the Federal University, in the state of Pernambuco, Brazil, who were selected and had been sounded examined to evaluate all their dental elements, considering the four surfaces. The gingival recession was considered present when more than 1mm of root was exposed. Results: The gingival recession was found in 92 (83.6%) students and only 18 (16.4) did not present recession. The vestibular face with 79.3% was most prevalent. The group of more affected teeth were the lower incisors with 22.1%, for sextant, the canines and lower premolars which had presented greater prevalence, 28.8% As far as the maximum measure of found gingival recession was concerned, 41.8% presented maximum values of only 2mm, 36.4% had 3mm and 5.4% with 4mm. Conclusion: The prevalence of gingival contraction was high in the studied population and one of its main factor was traumatic tooth brushing habits.
Salvage therapy for acute myeloid leukemia with fludarabine, cytarabine, and idarubicin with or without gemtuzumab ozogamicin and with concurrent or sequential G‐CSF

The current salvage therapies for relapsed/refractory acute myeloid leukemia (AML) are unsatisfactory. Over the past 7 years, we have used two salvage regimens: fludarabine, cytarabine, and idarubicin with (FLAG‐IM) or without gemtuzumab ozogamicin (GO) (9 mg/m2 on Day 8) (FLAG‐I) in relapsed/refractory AML. Three‐quarters of patients also received concurrent G‐CSF. Seventy‐one patients were treated, 23 with FLAG‐I and 48 with FLAG‐IM. The median duration of follow‐up was 30.6 months. The treatment groups were well balanced with median ages of 48 years (range 18–70) and 47 years (range 20–68), unfavorable cytogenetics in 57% and 35%, prior allogeneic stem cell transplant in 43% and 42%, and CR1 duration <1 year in 60% and 67%, respectively, for FLAG‐I and FLAG‐IM. The complete remission (CR) rate in the FLAG‐I group was 39% with an additional 13% achieving a CRp [overall response rate (ORR) 52%]; the CR rate in the FLAG‐IM group was 29% with an additional 27% achieving a CRp (ORR 56%). The median duration of response (DOR; 16.8 vs. 8.3 months), event‐free survival (EFS; 7.4 vs. 4.1 months), and overall survival (OS; 8.8 vs. 5.0 months) trended to favor FLAG‐I over FLAG‐IM. The patients who received G‐CSF concurrent with chemotherapy had superior overall response rate (ORR; 62% vs. 29%, P = 0.026), median EFS (6.2 vs. 3.4 months, P = 0.010), and OS (8.8 vs. 3.9 months, P = 0.004) when compared with those who sequentially received G‐CSF and chemotherapy, regardless of chemotherapy regimen. The addition of GO, at this dose and schedule, to FLAG‐I failed to improve the outcomes in patients with relapsed/refractory AML. The patients who received G‐CSF concurrently with chemotherapy had improved outcomes. Am. J. Hematol. , 2009. © 2009 Wiley‐Liss, Inc.
Schizosaccharomyces pombe Snf2SR, a novel SNF2 family protein, interacts with Ran GTPase and modulates both RanGEF and RanGAP activities

Snf2SR, a suppressor of rna1ts, which is a temperature‐sensitive mutation in Schizosaccharomyces pombe RanGAP (GTPase activating protein), possesses both the SNF2 and the helicase domains conserved in the chromatin remodeling SNF2 ATPase/helicase protein family. We have now clarified a function of Snf2SR. Snf2SR indeed showed DNA‐stimulated ATPase activity, proving that it is a member of the SNF2 ATPase/helicase family. Consistent with this role, Snf2SR was localized in the nucleus and cell fractionation analysis revealed that Snf2SR was tightly associated with the nuclear matrix. The disruption of snf2SR+ was detrimental for a cell proliferation of S. pombe. Snf2SR that did not enhance RanGAP activity by itself, but abolished histone‐H3‐mediated RanGAP inhibition, as previously reported for the histone H3 methyltransferase, Clr4, another rna1ts suppressor. In contrast to Clr4, Snf2SR directly bound to the GDP‐bound form of the S. pombe Ran homologue Spi1 and enhanced the nucleotide exchange activity of Pim1, the S. pombe RanGEF (guanine nucleotide exchange factor). Over‐expression of Spi1‐G18V, a Ran GTPase mutant fixed in the GTP‐bound form, was lethal to S. pombe Δsnf2SR. Together, our results indicate that Snf2SR is involved in the Ran GTPase cycle in vivo.
Regulation of apoptosis and neurite extension by FKBP38 is required for neural tube formation in the mouse

FKBP38 (also known as FKBP8) is a transmembrane chaperone protein that inhibits apoptosis by recruiting the anti‐apoptotic proteins Bcl‐2 and Bcl‐xL to mitochondria. We have now generated mice harboring a loss‐of‐function mutation in Fkbp38. The Fkbp38−/– mice die soon after birth manifesting defects in neural tube closure in the thoraco‐lumbar‐sacral region (spina bifida) as well as skeletal defects including scoliosis, rib deformities, club foot and curled tail. The neuroepithelium is disorganized and that formation of dorsal root ganglia is defective in Fkbp38−/– embryos, likely as a result of an increased frequency of apoptosis and aberrant migration of neuronal cells. Furthermore, the extension of nerve fibers in the spinal cord is abnormal in the mutant embryos. To explore the mechanisms underlying these characteristics, we screened for proteins that interact with FKBP38 in the yeast two‐hybrid system and thereby identified protrudin, a protein that promotes process formation by regulating membrane trafficking. Protrudin was found to be hyperphosphorylated in the brain of Fkbp38−/– mice, suggesting that FKBP38 regulates protrudin‐dependent membrane recycling and neurite outgrowth. Together, our findings suggest that FKBP38 is required for neuroectodermal organization during neural tube formation as a result of its anti‐apoptotic activity and regulation of neurite extension.
Member of the membrane‐bound O‐acyltransferase (MBOAT) family encodes a lysophospholipid acyltransferase with broad substrate specificity

Glycerophospholipids in biological membranes are metabolically active and participate in a series of deacylation–reacylation reactions, which may lead to accumulation of polyunsaturated fatty acids (PUFAs) at the sn‐2 position of the glycerol backbone. The reacylation reaction is believed to be catalyzed by acyl‐coenzyme A (acyl‐CoA):lysophospholipid acyltransferase. Very recently, we have shown that Caenorhabditis elegans mboa‐7, which belongs to the membrane‐bound O‐acyltransferase (MBOAT) family, encodes lysophosphatidylinositol (LPI)‐specific acyltransferase (LPIAT). In this study, we found that knockdown of another member of the MBOAT family in C. elegans, named mboa‐6, reduced incorporation of exogenous PUFAs into phosphatidylcholine (PC), phosphatidylserine (PS) and phosphatidylethanolamine (PE) in C. elegans. Knockdown of a human mboa‐6 homologue, referred to as MBOAT5, also impaired the incorporation of PUFAs into PC, PS and PE in HeLa cells. In in vitro assays, lysoPC (LPC), lysoPS (LPS) and lysoPE (LPE) acyltransferase activities using [14C]arachidonoyl‐CoA were significantly reduced in the microsomes of MBOAT5 knockdown cells. Conversely, over‐expression of MBOAT5 in human embryonic kidney (HEK) 293 cells resulted in great increases in LPC, LPS and LPE acyltransferase activities but not in LPIAT or lysophosphatidic acid (LPA) acyltransferase (LPAAT) activities. These results indicate that human MBOAT5 is a lysophospholipid acyltransferase acting preferentially on LPC, LPS and LPE.
BCL11A is a SUMOylated protein and recruits SUMO‐conjugation enzymes in its nuclear body

BCL11A/EVI9 is a zinc‐finger protein predominantly expressed in brain and hematopoietic cells. Previous studies show that BCL11A is involved in acute myelomonocytic leukemia and chronic lymphoid leukemia in mouse and human, respectively. Moreover, BCL11A is localized in the characteristic nuclear body in which BCL6 is co‐localized. However, the significance of BCL11A in leukemogenesis and nuclear function remains unknown. In this study we show that BCL11A interacts with UBC9, a small ubiquitin‐like modifier (SUMO) E2 conjugating enzyme, and recruits SUMO1 into the nuclear body. A lysine residue at amino acid 634 of BCL11A is SUMOylated but not required for the SUMO1 recruitment. The N‐terminal region of BCL11A is responsible for SUMO1 recruitment as well as its nuclear body formation. We also show that SENP2, a SUMO specific peptidase, is co‐localized in the nuclear body. These results suggest that BCL11A could be involved in the SUMO conjugation system, and that BCL11A might play an important role in protein modification.
Bone morphogenetic protein‐2 enhances Wnt/β‐catenin signaling‐induced osteoprotegerin expression

Wnt/β‐catenin signaling plays an important role in the developing skeletal system. Our previous studies demonstrated that Wnt/β‐catenin signaling inhibits the ability of bone morphogenetic protein (BMP)‐2 to suppress myotube formation in the multipotent mesenchymal cell line C2C12 and that this inhibition is mediated by Id1. In this study, we examined the role of intracellular signaling by Wnt/β‐catenin and BMP‐2 in regulating the expression of osteoprotegerin (OPG) and of the receptor activator of NFκB ligand (RANKL). OPG expression was induced by Wnt/β‐catenin signaling in C2C12 cells and osteoblastic MC3T3‐E1 cells. Silencing of glycogen synthase kinase‐3β also increased OPG expression. In contrast, R expression was suppressed by Wnt/β‐catenin signaling. In a transfection assay, β‐catenin induced the activity of a reporter gene, a 1.5 kb fragment of the 5′‐flanking region of the OPG gene. Deletion and mutation analysis revealed that Wnt/β‐catenin signaling regulates transcription of OPG via a promoter region containing two Wnt/β‐catenin responsive sites. BMP‐2 enhanced Wnt/β‐catenin‐dependent transcriptional activation of the OPG promoter. In response to BMP‐2 stimulation, Smad 1 and 4 interacted with Wnt/β‐catenin responsive sites. These results show that the regulation of OPG expression is mediated through two transcription pathways that involve the OPG promoter.
Bridging the gap: identifying needs and aspirations of indigenous students to facilitate entry to USQ

[Executive Summary]: The negative trend of enrolment of Indigenous students into tertiary study indicated gaps between their current achievement and knowledge levels and university requirements for admission. This study was designed to determine the perceived needs, aspirations and knowledge of Indigenous secondary school students when considering admission to university; investigate remedial strategies in order to make university a more attractive choice for Indigenous students; and ascertain the types of assistance and support the Indigenous students would like to receive in order to meet the enrolment requirements as well as completion of study at university. Focus groups were conducted with 50 Indigenous students in years 10 to 12 within the Toowoomba District and surveys conducted with 30 first year Indigenous undergraduate and Indigenous Higher Education Pathways Program (IHEPP) students at the University of Southern Queensland. The findings indicate that the school students were not aware of the IHEPP and university programs. Scholarships and bursaries need to be developed and publicised. Tutorial assistance, learning support e.g., assignment preparation, multicultural activities, childcare facilities, and group accommodation, need to be promoted. The university needs to further establish and maintain relationships with local Indigenous communities and staff working within the university have to understand the ‘cultural dimension’ impacting on Indigenous students and their families.
Contact dermatitis from compositae plants

Eighty patients (58 males and 22 females) suspected of compositae contact dermatitis and 22 controls were investigated using ethanolic plants extracts. , Fifty four (68%) patients and none of the controls had positive patch tests. Forty five (56%) of these patients showed positive reactions with, extracts of only a single Compositae plant. Parthenium hysterophorus produced positive reactions in 51%, Chrysanthemum morifolium in 23%, Dahlia pinnata in 9% and Tagetes indica in 4% patients. The highest number (84%) of patients with positive patch tests were exposed to these plants during their occupation.
The assessment of human organic cation transporter 1 (hOCT1) mRNA expression in patients with chronic myelogenous leukemia is affected by the proportion of different cells types in the analyzed cell population†

The monitoring of hOCT1 mRNA expression in patients with chronic myelogenous leukemia (CML) was used for predicting the response to imatinib treatment. However, different cell populations from patients who received various degrees of pretreatment were used for this analysis. Therefore, several biases in the results and their interpretation may arise. We investigated hOCT1 mRNA expression in different cell populations of peripheral blood (PB) from healthy volunteers and in imatinib nave de novo CML patients by analyzing changes in hOCT1 mRNA expression during the first 6 months of imatinib therapy. The hOCT1 mRNA expression was significantly higher in PB polymorphonuclears compared to mononuclears. The hOCT1 mRNA expression in total PB leukocytes is, therefore, preferentially determined by the percentage of polymorphonuclears. Expression in each analyzed group of cells was always significantly lower in imatinib nave de novo CML patients compared to healthy volunteers. This difference disappeared after the initiation of imatinib therapy, suggesting that CML tumor burden and the degree of pretreatment at the time of monitoring were both influencing factors.
Pain rate and social circumstances rather than cumulative organ damage determine the quality of life in adults with sickle cell disease†

Due to the significant morbidity associated with sickle cell disease (SCD), sickle cell patients have a reduced quality of life (QoL). Even though pain is considered an important determinant of QoL in sickle cell patients, factors such as organ damage and socioeconomic circumstances may also be important. Therefore, we determined the contribution of chronic organ damage and sickle cell-related complications to QoL and also analyzed the effect of vaso-occlusive crises and socioeconomic circumstances on QoL. Consecutive adult sickle cell patients were included. QoL was represented in a physical component scale (PCS) and a mental component scale (MCS) and assessed with SF-36 forms. Higher pain rates were related to lower QoL scores. Both occupation and the level of education were significantly related to PCS while no relation with MCS or pain rate was found. Thirty-five percent of the patients were unemployed when compared with 6% of the general population and 16% of immigrants without SCD. Neither genotype nor the presence of chronic organ damage were significantly related to QoL. In conclusion, a reduced QoL was mainly determined by pain rate, occupation, and educational level. Chronic organ damage, although a major factor determining life expectancy in SCD, was not a determinant of QoL.
Functional Consequences of the Subdomain Organization of the Sulfs*

Sulf-1 and Sulf-2 are novel extracellular sulfatases that act on internal glucosamine 6-O-sulfate modifications within heparan sulfate proteoglycans and regulate their interactions with various signaling molecules, including Wnt ligands. Although the Sulfs are multidomain proteins, there is limited information available about how the subdomains contribute to their enzymatic and signaling activities. In this study, we found that both human Sulfs were synthesized as prepro-enzymes and cleaved by a furin-type proteinase to form disulfide-bond linked heterodimers of 75- and 50-kDa subunits. The mature Sulfs were secreted into conditioned medium, as well as retained on the cell membrane. Although the catalytic center resides in the N-terminal 75-kDa subunit, the C-terminal 50-kDa subunit was indispensable for both arylsufatase and glucosamine 6-O-sulfate-endosulfatase activity. We found that the hydrophilic regions of the Sulfs were essential for endosulfatase activity but not for arylsulfatase activity. Using Edman sequencing, we identified furin-type proteinase cleavage sites in Sulf-1 and Sulf-2. Deletion of these sequences resulted in uncleavable forms of Sulfs. The uncleavable Sulfs retained enzymatic activity. However, they were unable to potentiate Wnt signaling, which may be due to their defective localization into lipid rafts on the plasma membrane.