bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel polyoxins generated by heterologously expressing polyoxin biosynthetic gene cluster in the sanN inactivated mutant of Streptomyces ansochromogenes
Authors: Li Jine , Li Lei , Feng Chi , Chen Yihua , Tan Huarong 
Published: October 2012

Abstract

Background
Polyoxins are potent inhibitors of chitin synthetases in fungi and insects. The gene cluster responsible for biosynthesis of polyoxins has been cloned and sequenced from Streptomyces cacaoi and tens of polyoxin analogs have been identified already.

Results
The polyoxin biosynthetic gene cluster from Streptomyces cacaoi was heterologously expressed in the sanN inactivated mutant of Streptomyces ansochromogenes as a nikkomycin producer. Besides hybrid antibiotics (polynik A and polyoxin N) and some known polyoxins, two novel polyoxin analogs were accumulated. One of them is polyoxin P that has 5-aminohexuronic acid with N-glycosidically bound thymine as the nucleoside moiety and dehydroxyl-carbamoylpolyoxic acid as the peptidyl moiety. The other analog is polyoxin O that contains 5-aminohexuronic acid bound thymine as the nucleoside moiety, but recruits polyoximic acid as the sole peptidyl moiety. Bioassay against phytopathogenic fungi showed that polyoxin P displayed comparatively strong inhibitory activity, whereas the inhibitory activity of polyoxin O was weak under the same testing conditions.

Conclusion
Two novel polyoxin analogs (polyoxin P and O) were generated by the heterologous expression of polyoxin biosynthetic gene cluster in the sanN inactivated mutant of Streptomyces ansochromogenes. Polyoxin P showed potent antifungal activity,while the activity of polyoxin O was weak. The strategy presented here may be available for other antibiotics producers.
Long-term storage limits PCR-based analyses of malaria parasites in archival dried blood spots
Authors: Hwang Joyce , Jaroensuk Juthamas , Leimanis Mara L , Russell Bruce , McGready Rose , Day Nicholas , Snounou George , Nosten Francois , Imwong Mallika 
Published: October 2012

Abstract

Background
Blood samples collected in epidemiological and clinical investigations and then stored, often at room temperature, as blood spots dried on a filter paper have become one of the most popular source of material for further molecular analyses of malaria parasites. The dried blood spots are often archived so that they can be used for further retrospective investigations of parasite prevalence, or as new genetic markers come to the fore. However, the suitability of the template obtained from dried blood spots that have been stored for long periods for DNA amplification is not known.

Methods
DNA from 267 archived blood spots collected over a period of 12 years from persons with microscopically confirmed Plasmodium falciparum infection was purified by one of two methods, Chelex and Qiagen columns. These templates were subjected to highly sensitive nested PCR amplification targeting three parasite loci that differ in length and/or copy number.

Results
When a 1.6 kb fragment of the parasites’ small subunit ribosomal RNA was targeted (primary amplification), the efficiency of P. falciparum detection decreased in samples archived for more than six years, reaching very low levels for those stored for more than 10 years. Positive amplification was generally obtained more often with Qiagen-extracted templates. P. falciparum could be detected in 32 of the 40 negative Qiagen-extracted templates when a microsatellite of about 180 bp was targeted. The remaining eight samples gave a positive amplification when a small region of 238 bp of the higher copy number (20 to 200) mitochondrial genome was targeted.

Conclusions
The average length of DNA fragments that can be recovered from dried blood spots decreases with storage time. Recovery of the DNA is somewhat improved, especially in older samples, by the use of a commercial DNA purification column, but targets larger than 1.5 kb are unlikely to be present 10 years after the initial blood collection, when the average length of the DNA fragments present is likely to be around a few hundred bp. In conclusion, the utility of archived dried blood spots for molecular analyses decreases with storage time.
The alveolar epithelial differentiation of glandular inner lining cells in a mucoepidermoid carcinoma of the lung: a case report
Authors: Xu Hong-Tao , Lin Xu-Yong , Li Qing-Chang , Wang En-Hua 
Published: October 2012

Abstract
Mucoepidermoid carcinoma is a common malignant epithelial tumor of salivary glands, but relatively rare in lung. The histological features of mucoepidermoid carcinoma of the lung are similar to its counterpart arising from the salivary glands. Here, we reported a special tumor that occurred in the medial segment of the right lower lobe in a 22-year-old man. This tumor exhibited typical features of mucoepidermoid carcinoma with 3 cell types: squamoid cells, mucin-secreting cells and cells of intermediate type. These 3 types of cells organized into cysts, nests, glands and solid patterns. Specially, the inner lining cells of some glandular structures were uniform cuboidal and hobnail-like, similar to the alveolar epithelial cells. Immunohistochemistry staining revealed that the inner lining cells of glandular structures were positive for thyroid transcription factor-1 and surfactant protein-B, used as markers of alveolar epithelial cells, and were negative for p63. These findings for the first time demonstrated a rare alveolar epithelial differentiation of glandular inner lining cells in a mucoepidermoid carcinoma of the lung.

Virtual Slides

The virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/7095988968057804
Osteomyelitis and pyoarthritis resulting from local paracoccidioidomycosis in an immunocompetent patient: a case report
Authors: Michelan Michel Santana , Fernandes Eloy de Ávila , Freitas Leonardo Furtado , Ribeiro Rodrigo Hoeller , Milano Marília Magri , Monteiro Soraya Silveira 
Published: October 2012

Abstract

Introduction
Paracoccidioidomycosis is a type of mycosis that is endemic to Brazil and is triggered by the fungus Paracoccidioides brasiliensis. Isolated bone involvement in this disease is very rare, especially in children. To the best of our knowledge this report documents the first case of an immunocompetent pediatric patient in which paracoccidioidomycosis of the hip articulation was the sole manifestation of the disease (that is, there were no pulmonary or skin lesions).

Case presentation
An 11-year-old Brazilian Caucasian boy from a rural area was examined in the orthopedic ward of our emergency department. Our patient reported a three-month history of pain in the right hip with intermittent claudication and also complained of recurring episodes of intense pain and an inability to walk, which he had been experiencing for the previous five days. He additionally presented with a fever that had persisted for two days. Our patient’s medical history did not include any clinical respiratory manifestations, skin lesions, history of trauma or immunosuppression risk factors.

Conclusions
This is one of the very few reported cases of isolated articular involvement in osteomyelitis in a pediatric immunocompetent patient. Paracoccidioidomycosis should be considered among the differential diagnoses in such cases, especially in cases of patients who reside in rural areas where the condition is considered to be endemic, in order to administer the proper course of treatment in a timely fashion and improve the chances of a favorable prognosis.
Mitochondrial dysfunction associated with increased oxidative stress and α-synuclein accumulation in PARK2 iPSC-derived neurons and postmortem brain tissue
Authors: Imaizumi Yoichi , Okada Yohei , Akamatsu Wado , Koike Masato , Kuzumaki Naoko , Hayakawa Hideki , Nihira Tomoko , Kobayashi Tetsuro , Ohyama Manabu , Sato Shigeto , Takanashi Masashi , Funayama Manabu , Hirayama Akiyoshi , Soga Tomoyoshi , Hishiki Takako , Suematsu Makoto , Yagi Takuya , Ito Daisuke , Kosakai Arifumi , Hayashi Kozo , Shouji Masanobu , Nakanishi Atsushi , Suzuki Norihiro , Mizuno Yoshikuni , Mizushima Noboru , Amagai Masayuki , Uchiyama Yasuo , Mochizuki Hideki , Hattori Nobutaka , Okano Hideyuki 
Published: October 2012

Abstract

Background
Parkinson’s disease (PD) is a neurodegenerative disease characterized by selective degeneration of dopaminergic neurons in the substantia nigra (SN). The familial form of PD, PARK2, is caused by mutations in the parkin gene. parkin-knockout mouse models show some abnormalities, but they do not fully recapitulate the pathophysiology of human PARK2.

Results
Here, we generated induced pluripotent stem cells (iPSCs) from two PARK2 patients. PARK2 iPSC-derived neurons showed increased oxidative stress and enhanced activity of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. iPSC-derived neurons, but not fibroblasts or iPSCs, exhibited abnormal mitochondrial morphology and impaired mitochondrial homeostasis. Although PARK2 patients rarely exhibit Lewy body (LB) formation with an accumulation of α-synuclein, α-synuclein accumulation was observed in the postmortem brain of one of the donor patients. This accumulation was also seen in the iPSC-derived neurons in the same patient.

Conclusions
Thus, pathogenic changes in the brain of a PARK2 patient were recapitulated using iPSC technology. These novel findings reveal mechanistic insights into the onset of PARK2 and identify novel targets for drug screening and potential modified therapies for PD.
Protocol-directed insulin infusion sliding scales improve perioperative hyperglycaemia in critical care
Authors: Hui Man Lin , Kumar Arun , Adams Gary G 
Published: October 2012

AbstractPerioperative hyperglycaemia is associated with poor outcomes in patients undergoing cardiac surgery. Frequent postoperative hyperglycaemia in cardiac surgery patients has led to the initiation of an insulin infusion sliding scale for quality improvement.A systematic review was conducted to determine whether a protocol-directed insulin infusion sliding scale is as safe and effective as a conventional practitioner-directed insulin infusion sliding scale, within target blood glucose ranges.A literature survey was conducted to identify reports on the effectiveness and safety of an insulin infusion protocol, using seven electronic databases from 2000 to 2012: MEDLINE, CINAHL, EMBASE, the Cochrane Library, the Joanna Briggs Institute Library and SIGLE. Data were extracted using pre-determined systematic review and meta-analysis criteria.Seven research studies met the inclusion criteria. There was an improvement in overall glycaemic control in five of these studies. The implementation of protocols led to the achievement of blood glucose concentration targets more rapidly and the maintenance of a specified target blood glucose range for a longer time, without any increased frequency of hyperglycaemia. Of the seven studies, four used controls and three had no controls.In terms of the meta-analysis carried out, four studies revealed a failure of patients reaching target blood glucose levels (P< 0.0005) in the control group compared with patients in the protocol group. The risk of hypoglycaemia was significantly reduced (P<0.00001) between studies.It can be concluded that the protocol-directed insulin infusion sliding scale is safe and improves blood glucose control when compared with the conventional practitioner-directed insulin infusion sliding scale. This study supports the adoption of a protocol-directed insulin infusion sliding scale as a standard of care for post-cardiac surgery patients.
Canid Progesterone Receptors Lack Activation Function 3 Domain-Dependent Activity
Authors: Gracanin Ana , van Wolferen Monique E. , Sartorius Carol A. , Brenkman Arjan B. , Schoonen Willem G. , Mol Jan A. 
Published: October 2012

AbstractProgesterone regulates multiple behavioral, physiological, and pathological aspects of female reproductive biology through its two progesterone receptors (PRs), PR-B and the truncated PR-A. PR-B is necessary for mammary gland development in mice and, compared with PR-A, is overall a stronger transactivator of target genes due to an additional activation function 3 (AF3) domain. In dogs, known for their high sensitivity to progesterone-induced mammary cancer, the PR-B function was studied. Canine PR (cPR)-B appeared to contain multiple mutations within AF3 core sequence motifs and lacks N-terminal ligand-independent posttranslational modifications. Consequently, cPR-B has a weak transactivation potential on progesterone-responsive mouse mammary tumor virus-luc and progesterone response element 2-luc reporters transiently transfected in hamster, human, or canine cells and also on known target genes FKBP5 and SGK in doxycycline-inducible, stable transfected cPR-B in canine mammary cells. The cPR-B function was restored to the level of human PR-B by the replacement of canine AF3 domain with the human one. The lack of AF3 domain-dependent transcriptional activity was unique for canids (gray wolf, red fox, and raccoon dog) and not present in closely related caniform species (brown bear, gray seal, and domestic ferret). Despite the limited transactivation potential, canids develop normal mammary glands and frequently mammary tumors. Therefore, these results question the role of PR-B in breast cancer development and may explain unique features of canid reproduction.
Nuclear Export Signal of Androgen Receptor (NESAR) Regulation of Androgen Receptor Level in Human Prostate Cell Lines via Ubiquitination and Proteasome-Dependent Degradation
Authors: Gong Yanqing , Wang Dan , Dar Javid A. , Singh Prabhpreet , Graham Lara , Liu Weijun , Ai Junkui , Xin Zhongcheng , Guo Yinglu , Wang Zhou 
Published: October 2012

AbstractAndrogen receptor (AR) plays a key role in prostate development and carcinogenesis. Increased expression and/or stability of AR is associated with sensitization of prostate cancer cells to low levels of androgens, leading to castration resistance. Hence, understanding the mechanisms regulating AR protein stability is clinically relevant and may lead to new approaches to prevent and/or treat prostate cancer. Using fluorescence microscopy, Western blot, and pulse chase assay, we showed that nuclear export signal (NES)AR, a nuclear export signal in the ligand binding domain (LBD) of AR, can significantly enhance the degradation of fusion protein constructs in PC3 prostate cancer cells. The half-life of GFP-NESAR was less than 3 h, which was 10 times shorter than that of green fluorescent protein (GFP) control. Further analysis showed that NESAR can signal for polyubiquitination and that degradation of NESAR-containing fusion proteins can be blocked by proteasome inhibitor MG132. Ubiquitination of GFP-AR or GFP-LBD was suppressed in the presence of dihydrotestosterone, which is known to suppress NESAR while inducing nuclear localization signal 2 in AR or LBD, suggesting that the export activity of NESAR is required for NESAR-mediated polyubiquitination. Treatment with MG132 also induced aggresome formation of NESAR-containing fusion proteins in perinuclear regions of the transfected PC3 cells, indicating a role for NESAR in inducing unfolded protein responses. The above observations suggest that NESAR plays a key role in AR ubiquitination and proteasome-dependent degradation in prostate cancer cells.
A Clinical Prediction Score to Diagnose Unilateral Primary Aldosteronism
Authors: Küpers Elselien M. , Amar Laurence , Raynaud Alain , Plouin Pierre-François , Steichen Olivier 
Published: October 2012

Abstract

Context:
Adrenal venous sampling is recommended to assess whether aldosterone hypersecretion is lateralized in patients with primary aldosteronism. However, this procedure is invasive, poorly standardized, and not widely available.

Objective:
Our goal was to identify patients' characteristics that can predict unilateral aldosterone hypersecretion in some patients who could hence bypass adrenal venous sampling before surgery.

Design and Setting:
A cross-sectional diagnostic study was performed from February 2009 to July 2010 at a single center specialized in hypertension care.

Patients:
A total of 101 consecutive patients with primary aldosteronism who underwent adrenal venous sampling participated in the study. The autonomy of aldosterone hypersecretion was assessed with the saline infusion test.

Intervention:
Adrenal venous sampling was performed without ACTH infusion but with simultaneous bilateral sampling.

Main Outcome Measures:
Variables independently associated with a lateralized adrenal venous sampling in multivariate logistic regression were used to derive a clinical prediction rule.

Results:
Adrenal venous sampling was successful in 87 patients and lateralized in 49. All 26 patients with a typical Conn's adenoma plus serum potassium of less than 3.5 mmol/liter or estimated glomerular filtration rate of at least 100 ml/min/1.73 m2 (or both) had unilateral primary aldosteronism; this rule had 100% specificity (95% confidence interval, 91–100) and 53% sensitivity (95% confidence interval, 38–68).

Conclusions:
If our results are validated on an independent sample, adrenal venous sampling could be omitted before surgery in patients with a typical Conn's adenoma if they meet at least one of two supplementary biochemical characteristics (serum potassium &lt;3.5 mmol/liter or estimated glomerular filtration rate ≥100 ml/min/1.73 m2).
Down-Regulation of S100A11, a Calcium-Binding Protein, in Human Endometrium May Cause Reproductive Failure
Authors: Liu Xin-Mei , Ding Guo-Lian , Jiang Ying , Pan Hong-Jie , Zhang Dan , Wang Ting-Ting , Zhang Run-Ju , Shu Jing , Sheng Jian-Zhong , Huang He-Feng 
Published: October 2012

Abstract

Background:
Low expression levels of S100A11 proteins were demonstrated in the placental villous tissue of patients with early pregnancy loss, and S100A11 is a Ca2+-binding protein that interprets the calcium fluctuations and elicits various cellular responses.

Objectives:
The objective of the study was to determine S100A11 expression in human endometrium and its roles in endometrial receptivity and embryo implantation.

Methods:
S100A11 expression in human endometrium was analyzed using quantitative RT-PCR, Western blot, and immunohistochemical techniques. The effects of S100A11 on embryo implantation were examined using in vivo mouse model, and JAr (a human choriocarcinoma cell line) spheroid attachment assays. The effects of endometrial S100A11 on factors related to endometrial receptivity and immune responses were examined. Using a fluorescence method, we examined the changes in cytosolic Ca2+ and Ca2+ release from intracellular stores in epidermal growth factor (EGF)-treated endometrial cells transfected with or without S100A11 small interfering RNA.

Results:
S100A11 was expressed in human endometrium. S100A11 protein levels were significantly lower in endometrium of women with failed pregnancy than that in women with successful pregnancy outcomes. The knockdown of endometrial S100A11 not only reduced embryo implantation rate in mouse but also had adverse effects on the expression of factors related to endometrial receptivity and immune responses in human endometrial cells. Immunofluorescence analysis showed that S100A11 proteins were mainly localized in endoplasmic reticulum. The EGF up-regulated endometrial S100A11 expression and promoted the Ca2+ uptake and release from Ca2+ stores, which was inhibited by the knockdown of S100A11.

Conclusions:
Endometrial S100A11 is a crucial intermediator in EGF-stimulated embryo adhesion, endometrium receptivity, and immunotolerance via affecting Ca2+ uptake and release from intracellular Ca2+ stores. Down-regulation of S100A11 may cause reproductive failure.
Vildagliptin Reduces Glucagon during Hyperglycemia and Sustains Glucagon Counterregulation during Hypoglycemia in Type 1 Diabetes
Authors: Farngren Johan , Persson Margaretha , Schweizer Anja , Foley James E. , Ahrén Bo 
Published: October 2012

Abstract

Context:
The dipeptidyl peptidase-4 inhibitor, vildagliptin, inhibits glucagon secretion at hyperglycemia but appears to enhance glucagon counterregulation during hypoglycemia in type 2 diabetes.

Objective:
The objective of the investigation was to study whether vildagliptin also improves α-cell function in type 1 diabetes (T1D).

Patients and Methods:
The study was a single-center, double-blind, randomized, placebo-controlled crossover study involving 28 patients with C-peptide negative and antibody positive T1D [21 males, seven females, glycosylated hemoglobin 57.9 mmol/mol (7.5%)]. Patients received vildagliptin (50 mg twice a day) or placebo as an add-on to their insulin therapy for 4 wk each. On d 28 of the respective treatment period, patients were served a standard meal (500 kcal) to raise the circulating incretin hormone levels followed by a hyperinsulinemic hypoglycemic clamp at 2.5 mmol/liter.

Main Outcome Measure:
The increase in plasma glucagon levels during the 30-min hypoglycemic clamp (min 165–195 of the test) was measured.

Results:
During the meal, glucagon levels were lower with vildagliptin than with placebo (120 min area under the curveglucagon 2.4 ± 0.2 vs. 2.6 ± 0.2 nmol/liter × minutes, P = 0.022 for between group difference). In contrast, during hypoglycemia, the glucagon counterregulation was not reduced by vildagliptin (increase in glucagon 1.5 ± 1.0 pmol/liter with vildagliptin vs. 1.7 ± 0.8 pmol/liter with placebo, P = NS). In addition, the counterregulatory responses in epinephrine, norepinephrine, cortisol, and pancreatic polypeptide were not different between the treatments. During the 4-wk treatment period, vildagliptin reduced the mean glycosylated hemoglobin, whereas there was no change with placebo [between group difference was −3.4 ± 1.0 mmol/mol (−0.32 ± 0.09%; P = 0.002)] from baseline of 57.9 mmol/mol (7.5%).

Conclusions:
Vildagliptin, although inhibiting glucagon secretion during hyperglycemia, does not compromise the glucagon counterregulatory response during hypoglycemia in T1D.