Miracle-dz/UniFAR-FTUs huggingface dataset:
Epigenetic Regulatory Mechanisms Distinguish Retinoic Acid-mediated Transcriptional Responses in Stem Cells and Fibroblasts*

Retinoic acid (RA), a vitamin A metabolite, regulates transcription by binding to RA receptor (RAR) and retinoid X receptor (RXR) heterodimers. This transcriptional response is determined by receptor interactions with transcriptional regulators and chromatin modifying proteins. We compared transcriptional responses of three RA target genes (Hoxa1, Cyp26a1, RARβ2) in primary embryo fibroblasts (mouse embryonic fibroblasts), immortalized fibroblasts (Balb/c3T3), and F9 teratocarcinoma stem cells. Hoxa1 and Cyp26a1 transcripts are not expressed, but RARβ2 transcripts are induced by RA in mouse embryonic fibroblasts and Balb/c3T3 cells. Retinoid receptors (RARγ, RXRα), coactivators (pCIP (NCOA3, SRC3)), and p300 and RNA polymerase II are recruited only to the RARβ2 RA response element (RARE) in Balb/c3T3, whereas these proteins are recruited to RAREs of all three genes by RA in F9 cells. In F9, RA reduces polycomb (PcG) protein Suz12 and the associated H3K27me3 repressive epigenetic modification at the RAREs of all three genes. In contrast, in Balb/c3T3 cells cultured in the +/−RA, Suz12 is not associated with the Hoxa1, RARβ2, and Cyp26a1 RAREs, whereas slow levels of the H3K27me3 mark are seen at these RAREs. Thus, Suz12 is not required for gene repression in the absence of RA. Even though the Hoxa1 RARE and proximal promoter show high levels of H3K9,K14 acetylation in Balb/c3T3, the Hoxa1 gene is not transcriptionally activated by RA. In Balb/c3T3, CpG islands are methylated in the Cyp26a1 promoter region but not in the Hoxa1 promoter or in these promoters in F9 cells. We have delineated the complex mechanisms that control RA-mediated transcription in fibroblasts versus stem cells.
Antenatal care in developing countries: promises achievements and missed opportunities. An analysis of trends levels and differentials 1990-2001.

The antenatal period offers opportunities for delivering health information and services that can significantly enhance the health of women and their infants but its potential remains insufficiently exploited. Whereas women themselves appear to have embraced the concept of care during pregnancy with enthusiasm when such services are available the care they are offered often falls short of the ideal by a long way in terms of content and probably also quality. Antenatal visits offer entry points for a range of other programmes – such as nutrition malaria HIV/AIDS and TB – as well as for obstetric care. Greater efforts are needed to improve the content and quality of services offered. In addition increased attention is needed to ensure that particular groups of women specifically those living in rural areas the poor and the less educated obtain better access to antenatal services. (excerpt)
Purinergic Receptor-mediated Rapid Depletion of Nuclear Phosphorylated Akt Depends on Pleckstrin Homology Domain Leucine-rich Repeat Phosphatase, Calcineurin, Protein Phosphatase 2A, and PTEN Phosphatases*

Akt is an important oncoprotein, and data suggest a critical role for nuclear Akt in cancer development. We have previously described a rapid (3–5 min) and P2X7-dependent depletion of nuclear phosphorylated Akt (pAkt) and effects on downstream targets, and here we studied mechanisms behind the pAkt depletion. We show that cholesterol-lowering drugs, statins, or extracellular ATP, induced a complex and coordinated response in insulin-stimulated A549 cells leading to depletion of nuclear pAkt. It involved protein/lipid phosphatases PTEN, pleckstrin homology domain leucine-rich repeat phosphatase (PHLPP1 and -2), protein phosphatase 2A (PP2A), and calcineurin. We employed immunocytology, immunoprecipitation, and proximity ligation assay techniques and show that PHLPP and calcineurin translocated to the nucleus and formed complexes with Akt within 3 min. Also PTEN translocated to the nucleus and then co-localized with pAkt close to the nuclear membrane. An inhibitor of the scaffolding immunophilin FK506-binding protein 51 (FKBP51) and calcineurin, FK506, prevented depletion of nuclear pAkt. Furthermore, okadaic acid, an inhibitor of PP2A, prevented the nuclear pAkt depletion. Chemical inhibition and siRNA indicated that PHLPP, PP2A, and PTEN were required for a robust depletion of nuclear pAkt, and in prostate cancer cells lacking PTEN, transfection of PTEN restored the statin-induced pAkt depletion. The activation of protein and lipid phosphatases was paralleled by a rapid proliferating cell nuclear antigen (PCNA) translocation to the nucleus, a PCNA-p21cip1 complex formation, and cyclin D1 degradation. We conclude that these effects reflect a signaling pathway for rapid depletion of pAkt that may stop the cell cycle.
Maternal education as a factor in child mortality.

According to available evidence maternal education plays a major role in determining the level of infant and child mortality but little has been done to explain this phenomenon. 2 surveys conducted in Nigeria have shed much light on the relationship between child mortality and education of the mother. The surveys confirm that maternal education is the single most significant determinant of child mortality but they make it clear that maternal education cannot be employed as a proxy for general social and econmic change. There are at least 3 explanations for the phenomenon under discussion: 1) educated mothers break with tradition about illness and adopt many of the alternatives in child care and treatment becoming available in a rapidly changing society; 2) an educated mother is more capable of manipulating the modern world; and 3) the education of women greatly changes the traditional balance of familial relationships with profound effects on child care. Everywhere in West Africa the impact of education is so decisive because it changes not only the educated but the attitudes of others toward them. The education of a female is like to change her maternal indulgence into maternal protective action and she is more likely than her uneducated counterpart to feel personal responsibility. A woman with education is more apt to challenge her mother-in-law and the mother-in-law is less inclined to fight the challenge. Changes in nutrition play a part in a decline in infant and child mortality and the education of women is crucial in this respect.
Root Secretion of Defense-related Proteins Is Development-dependent and Correlated with Flowering Time*

Proteins found in the root exudates are thought to play a role in the interactions between plants and soil organisms. To gain a better understanding of protein secretion by roots, we conducted a systematic proteomic analysis of the root exudates of Arabidopsis thaliana at different plant developmental stages. In total, we identified 111 proteins secreted by roots, the majority of which were exuded constitutively during all stages of development. However, defense-related proteins such as chitinases, glucanases, myrosinases, and others showed enhanced secretion during flowering. Defense-impaired mutants npr1-1 and NahG showed lower levels of secretion of defense proteins at flowering compared with the wild type. The flowering-defective mutants fca-1, stm-4, and co-1 showed almost undetectable levels of defense proteins in their root exudates at similar time points. In contrast, root secretions of defense-enhanced cpr5-2 mutants showed higher levels of defense proteins. The proteomics data were positively correlated with enzymatic activity assays for defense proteins and with in silico gene expression analysis of genes specifically expressed in roots of Arabidopsis. In conclusion, our results show a clear correlation between defense-related proteins secreted by roots and flowering time.
The experience of leishmanization in the Islamic Republic of Iran.

Leishmanization programmes in a hyperendemic area (Isfahan) and a high-risk group (army recruits and the Revolutionary Guard) are described and their effectiveness and complications are discussed. A trial of a non-living crude vaccine is outlined. More than two million people underwent leishmanization and it was found to reduce the incidence of the disease between one-sixth and one-eighth of its original level. The procedure is recommended whenever people are at a very high risk of contracting the disease. (authors)
Wariant wczesnej repolaryzacji: aspekty epidemiologiczne, mechanizm powstawania oraz diagnostyka różnicowa

Wariant wczesnej repolaryzacji (ERV lub ERPV) jest zagadkowym fenomenem elektrokardiograficznym, cechującym sie widocznym w wielu odprowadzeniach uniesieniem punktu J oraz odcinka ST. Ostatnio ponownie wzroslo zainteresowanie ERV z powodu jego podobienstwa do arytmogennego zespolu Brugadow. Niewiele wiadomo na temat epidemiologii ERV, a w kilkunastu badaniach udowodniono, ze zjawisko to wiąze sie z dobrym rokowaniem klinicznym. Obydwa wspomniane powyzej zespoly wykazują pewne podobienstwa, do ktorych mozna zaliczyc lezące u ich podstaw mechanizmy jonowe, analogiczne odpowiedzi na zmiany czestości rytmu serca, stopien aktywacji ukladu wspolczulnego, podobne reakcje na zastosowanie sympatykomimetykow (test z izoprotenerolem), blokerow kanalow sodowych oraz lekow z grupy beta-adrenolitykow. Powyzsze obserwacje sprzyjają powstawaniu hipotez mowiących o tym, ze ERV moze nie miec az tak lagodnego charakteru, jak tradycyjnie zakladano. Ponadto istnieją prace, w ktorych udowodniono, ze uniesienie odcinka ST u ludzi glownie jest spowodowane wplywem centralnej aktywacji z zakresu ukladu wspolczulnego zarowno w warunkach spoczynkowych, jak i podczas obciązenia fizjologicznego oraz farmakologicznego. Dysfunkcja centralnego ukladu wspolczulnego formalnie skutkuje obserwowanymi w wielu odprowadzeniach uniesieniami odcinka ST lub punktu J (co w piśmiennictwie nazwano falą J), ktore ulegają obnizeniu lub spadkowi ponizej wyjściowej linii izoelektrycznej podczas infuzji niskich dawek izoprotenerolu. W niniejszym artykule autorzy opisali cechy charakterystyczne ERV oraz glowne roznice w odniesieniu do ostrego zapalenia osierdzia, ostrego niedokrwienia/uszkodzenia mieśnia sercowego oraz zespolu Brugadow.
The EpCAMhigh/CD44high colorectal carcinoma stem cell phenotype is not preferentially expressed in tumour buds

1. Kojima A, Mikami Y, Sudo T et al. Gastric morphology and immunophenotype predict poor outcome in mucinous adenocarcinoma of the uterine cervix. Am. J. Surg. Pathol. 2007; 31; 664–672. 2. Wells M, Ostör AG, Crum CP et al. Pathology and genetics of tumours of the breast and female genital organs. In Tavassoli FA, Stratton MR eds. WHO classification of tumours. Lyon: IARC Press, 2003. 3. Young RH, Clement PB. Endocervical adenocarcinoma and its variants: their morphology and differential diagnosis. Histopathology 2002; 41; 185–207. 4. Ishii K, Hosaka N, Toki T et al. A new view of the so-called adenoma malignum of the uterine cervix. Virchows Arch. 1998; 432; 315–322. 5. Zhao S, Hayasaka T, Osakabe M et al. Mucin expression in nonneoplastic and neoplastic glandular epithelia of the uterine cervix. Int. J. Gynecol. Pathol. 2003; 22; 393–397. 6. Mikami Y, Kiyokawa T, Hata S et al. Gastrointestinal immunophenotype in adenocarcinomas of the uterine cervix and related glandular lesions: a possible link between lobular endocervical glandular hyperplasia ⁄ pyloric gland metaplasia and ‘adenoma malignum’. Mod. Pathol. 2004; 17; 962–972. 7. Fukushima M, Shimano S, Yamakawa Y et al. The detection of human papillomavirus (HPV) in a case of minimal deviation adenocarcinoma of the uterine cervix (adenoma malignum) using in situ hybridization. Jpn. J. Clin. Oncol. 1990; 20; 407– 412. 8. Ferguson AW, Svoboda-Newman SM, Frank TS. Analysis of human papillomavirus infection and molecular alterations in adenocarcinoma of the cervix. Mod. Pathol. 1998; 11; 11– 18. 9. Toki T, Zhai YL, Park JS, Fujii S. Infrequent occurrence of highrisk human papillomavirus and of p53 mutation in minimal deviation adenocarcinoma of the cervix. Int. J. Gynecol. Pathol. 1999; 18; 215–219. 10. Park KJ, Lamb C, Oliva E, Soslow RA, Kiyokawa T. Unusual endocervical adenocarcinomas: an immunohistochemical analysis with molecular detection of human papillomavirus. Mod. Pathol. 2008; 21; 217A. 11. Vang R, Gown AM, Farinola M et al. p16 expression in primary ovarian mucinous and endometrioid tumors and metastatic adenocarcinomas in the ovary: utility for identification of metastatic HPV-related endocervical adenocarcinomas. Am. J. Surg. Pathol. 2007; 31; 653–663. The EpCAM/CD44 colorectal carcinoma stem cell phenotype is not preferentially expressed in tumour buds
Crystal Structures of a Group II Chaperonin Reveal the Open and Closed States Associated with the Protein Folding Cycle*♦

Chaperonins are large protein complexes consisting of two stacked multisubunit rings, which open and close in an ATP-dependent manner to create a protected environment for protein folding. Here, we describe the first crystal structure of a group II chaperonin in an open conformation. We have obtained structures of the archaeal chaperonin from Methanococcus maripaludis in both a peptide acceptor (open) state and a protein folding (closed) state. In contrast with group I chaperonins, in which the equatorial domains share a similar conformation between the open and closed states and the largest motions occurs at the intermediate and apical domains, the three domains of the archaeal chaperonin subunit reorient as a single rigid body. The large rotation observed from the open state to the closed state results in a 65% decrease of the folding chamber volume and creates a highly hydrophilic surface inside the cage. These results suggest a completely distinct closing mechanism in the group II chaperonins as compared with the group I chaperonins.
Faktor Lingkungan dan Perilaku Masyarakat Tentang Malaria di Kecamatan Kupang Timur Kabupaten Kupang

Penelitian ini bertujuan untuk menggambarkan faktor lingkungan dan perilaku masyarakat tentang malaria di Kecamatan Kupang Timur Kabupaten Kupang. Dengan desain studi potong lintang, populasi penelitian adalah seluruh rumah tangga di Kecamatan Kupang Timur dengan metode simple random sampling dan diperoleh 185 rumah tangga yang dijadikan sampel. Hasil penelitian menunjukkan prevalens malaria klinis adalah 108 (14,4%) pada satu tahun terakhir. Gambaran faktor lingkungan rumah penderita malaria yaitu dinding rumah terbuat dari bebak dan papan masing-masing 43,6% dan 7,9%. Selain itu, atap rumah terbuat dari alangalang atau daun lontar (21,1%). Sementara letak rumah dekat dengan breding places nyamuk anopheles, yaitu sawah dan lagoon sebanyak (84%). Gambaran perilaku masyarakat dalam mencegah menceggah malaria menunjukkan 5,7% masyarakat tidak melakukan apapun untuk melindungi diri dari gigitan nyamuk. Sebanyak 74,4% masyarakat kadang-kadang menggunakan kelambu. Dalam hal perilaku pencarian pengobatan, sebanyak 49% masyarakat menggunakan obat tradisional, membeli obat di warung terdekat dan ada yang tidak melakukan apapun. Selain itu, sebagian besar penderita mencari pertolongan kepada tenaga kesehatan setelah lebih dari empat hari mendapat gejala. Disimpulkan bahwa kondisi fisik rumah dan lingkungan sekitar rumah serta perilaku berisiko masyarakat merupakan faktor determinan penting terjadinya terjadi malaria di wilayah Kabupaten Kupang. Disarankan upaya preventif dengan perbaikan lingkungan rumah dan promotif untuk perubahan perilaku perlu di perhatikan secara serius. The aims of this research was to identify the environment factors and the behavior factors related to the malaria in the. Using cross-sectional study design, the population was all households in the Kecamatan Kupang Timur Kabupaten Kupang. Used a simple random quota sampling method, the number of 185 households were as a respondents. The results showed the malaria prevalence was 108 (14.4%) in the past year. The environment a condition which were consists of the homes of people with malaria were made of bebak and boards 43.6% and 7.9% respectively. Besides that, the Roofs house were made of palm leaves (21.1%). The location of the respondent’s house was close to the breeding places which is rice fields and lagoon are 155 (84%). In terms of the community behavior in control malaria showed 5.7% of the community was not did anything to protect themselves from mosquito bites and 74.4% occasional community used mosquito nets have been distributed. Whereas in the case of treatment seeking behavior shows 49% people used a traditional medicine, bought drugs at a nearby shop and there was not do anything. In addition, most of the malaria suferer looked after the health care after more than four days have symptoms. We concluded that the physical and the environment factors as well as behavior is an important determinant factors of malaria in Kupang. Recommended preventive efforts with environmental improvements to the house and promotif for behavior change is important.
p16INK4A overexpression is frequently detected in tumour‐free tonsil tissue without association with HPV

Klingenberg B, Hafkamp H C, Haesevoets A, Manni J J, Slootweg P J, Weissenborn S J, Klussmann J P & Speel E‐J M (2010) Histopathology 56, 957–967 p16INK4Aoverexpression is frequently detected in tumour‐free tonsil tissue without association with HPV
Crystal Structure of Monomeric Photosystem II from Thermosynechococcus elongatus at 3.6-Å Resolution*

The membrane-embedded photosystem II core complex (PSIIcc) uses light energy to oxidize water in photosynthesis. Information about the spatial structure of PSIIcc obtained from x-ray crystallography was so far derived from homodimeric PSIIcc of thermophilic cyanobacteria. Here, we report the first crystallization and structural analysis of the monomeric form of PSIIcc with high oxygen evolution capacity, isolated from Thermosynechococcus elongatus. The crystals belong to the space group C2221, contain one monomer per asymmetric unit, and diffract to a resolution of 3.6 Å. The x-ray diffraction pattern of the PSIIcc-monomer crystals exhibit less anisotropy (dependence of resolution on crystal orientation) compared with crystals of dimeric PSIIcc, and the packing of the molecules within the unit cell is different. In the monomer, 19 protein subunits, 35 chlorophylls, two pheophytins, the non-heme iron, the primary plastoquinone QA, two heme groups, 11 β-carotenes, 22 lipids, seven detergent molecules, and the Mn4Ca cluster of the water oxidizing complex could be assigned analogous to the dimer. Based on the new structural information, the roles of lipids and protein subunits in dimer formation of PSIIcc are discussed. Due to the lack of non-crystallographic symmetry and the orientation of the membrane normal of PSIIcc perpendicular (∼87°) to the crystallographic b-axis, further information about the structure of the Mn4Ca cluster is expected to become available from orientation-dependent spectroscopy on this new crystal form.
Efectos “in vivo” de Metformina sobre las alteraciones de la microarquitectura ósea asociadas al Síndrome Metabólico inducido por fructosa en ratas

Several clinical studies have demonstrated that the Metabolic Syndrome (MS) is associated with a decrease in bone mineral density, and with an increased risk for non-vertebral osteoporotic fractures. We have re- cently found that orally administered Metformin induces osteogenic effects in rats, promoting osteoblastic differentiation of bone marrow progenitor cells and increasing the repair of bone lesions. In the present work we have evaluated the effects of Fructose-induced MS on bone micro-architecture in rats, and the possible
MD-2 Residues Tyrosine 42, Arginine 69, Aspartic Acid 122, and Leucine 125 Provide Species Specificity for Lipid IVA*

Lipopolysaccharide (LPS) activates the innate immune response through the Toll-like receptor 4 (TLR4)·MD-2 complex. A synthetic lipid A precursor, lipid IVA, induces an innate immune response in mice but not in humans. Both TLR4 and MD-2 are required for the agonist activity of lipid IVA in mice, with TLR4 interacting through specific surface charges at the dimerization interface. In this study, we used site-directed mutagenesis to identify the MD-2 residues that determine lipid IVA species specificity. A single mutation of murine MD-2 at the hydrophobic pocket entrance, E122K, substantially reduced the response to lipid IVA. Combining the murine MD-2 E122K with the murine TLR4 K367E/S386K/R434Q mutations completely abolished the response to lipid IVA, effectively converting the murine cellular response to a human-like response. In human cells, however, simultaneous mutations of K122E, K125L, Y41F, and R69G on human MD-2 were required to promote a response to lipid IVA. Combining the human MD-2 quadruple mutations with the human TLR4 E369K/Q436R mutations completely converted the human MD-2/human TLR4 receptor to a murine-like receptor. Because MD-2 residues 122 and 125 reside at the dimerization interface near the pocket entrance, surface charge differences here directly affect receptor dimerization. In comparison, residues 42 and 69 reside at the MD-2/TLR4 interaction surface opposite the dimerization interface. Surface charge differences there likely affect the binding angle and/or rigidity between MD-2 and TLR4, exerting an indirect influence on receptor dimerization and activation. Thus, surface charge differences at the two MD-2/TLR4 interfaces determine the species-specific activation of lipid IVA.
Blue sclera secondary to severe iron deficiency anemia.

A 54-year-old man presented with 1 week history of dizziness, worsened on standing, generalized weakness and decreased exercise tolerance. He had a history of hypertension and chronic kidney disease. He denied chest pain, shortness of breath, abdominal pain, nausea, vomiting, diarrhea, palpitation, dysuria, hematuria, hematochezia, hematemesis, melena, constipation, weakness or numbness in the extremities, speech or vision changes, incontinence, cough, fever, chills, hemoptysis, hoarseness, drooling, wheezing, abnormalities in bowel and bladder habit. The patient also noted the development of bipedal edema. He had no known drug allergies and takes Aripiprazole for mood disorder. He had no past surgical history and denied drug or alcohol use. Physical examination revealed pale skin with mild jaundice, blue-tinged sclera (Figure 1). The rest of the physical examination was otherwise unremarkable except for bilateral pedal edema and the reporting of dizziness upon moving from lying to seating position. Vital signs at presentation were blood pressure 99/ 48 mmHg, heart rate 81beats per minute, respiratory rate 17 breaths per minute, temperature 97.6 F, finger stick glucose 131 and oxygen saturations 100%. Laboratory tests showed severe anemia with the following values: Hemoglobin and hematocrit H/H of 2.8 g/dl/10%, iron level of 7 lg/dl, blood urea nitrogen of 75 mg/ dl, creatinine of 8.1 mg/dl, reticulocyte count of 1.13%, ferritin of 11.80 ng/ml, haptoglobin of 204 mg/dl, transferrin of 356 mg/dl, TIBC 411, vitamin B12 of 1725 pg/ml and folate of 8.08 of ng/ml. The patient was admitted to the hospital, given a blood transfusion and started on iron supplements. His symptoms improved along with significant improvement of his sclera color and H/H over time. Scleral changes are associated with systemic disease and metabolic conditions such as anemia, liver disease and osteogenesis imperfecta. These changes include pallor, blue-tinged sclera and scleral icterus. There are reports regarding the association of blue sclera with iron deficiency in both children and adults. Blue sclera secondary to iron deficiency was first reported by Sir Osler and later by Barton and Friedman, Kalra et al., and Beghetti et al. Barton and Friedman attempted to validate the association of blue sclera and iron deficiency anemia in infants and young children. Kotsev L et al. studied adult patients with anemia who had proven iron deficiency and found that the presence of blue sclera has a sensitivity of 89%. The presence of blue