Structure of the hDmc1-ssDNA filament reveals the principles of its architecture

In eukaryotes, meiotic recombination is a major source of genetic diversity, but its defects in humans lead to abnormalities such as Down's, Klinefelter's and other syndromes. Human Dmc1 (hDmc1), a RecA/Rad51 homologue, is a recombinase that plays a crucial role in faithful chromosome segregation during meiosis. The initial step of homologous recombination occurs when hDmc1 forms a filament on single-stranded (ss) DNA. However the structure of this presynaptic complex filament for hDmc1 remains unknown. To compare hDmc1-ssDNA complexes to those known for the RecA/Rad51 family we have obtained electron microscopy (EM) structures of hDmc1-ssDNA nucleoprotein filaments using single particle approach. The EM maps were analysed by docking crystal structures of Dmc1, Rad51, RadA, RecA and DNA. To fully characterise hDmc1-DNA complexes we have analysed their organisation in the presence of Ca2+, Mg2+, ATP, AMP-PNP, ssDNA and dsDNA. The 3D EM structures of the hDmc1-ssDNA filaments allowed us to elucidate the principles of their internal architecture. Similar to the RecA/Rad51 family, hDmc1 forms helical filaments on ssDNA in two states: extended (active) and compressed (inactive). However, in contrast to the RecA/Rad51 family, and the recently reported structure of hDmc1-double stranded (ds) DNA nucleoprotein filaments, the extended (active) state of the hDmc1 filament formed on ssDNA has nine protomers per helical turn, instead of the conventional six, resulting in one protomer covering two nucleotides instead of three. The control reconstruction of the hDmc1-dsDNA filament revealed 6.4 protein subunits per helical turn indicating that the filament organisation varies depending on the DNA templates. Our structural analysis has also revealed that the N-terminal domain of hDmc1 accomplishes its important role in complex formation through domain swapping between adjacent protomers, thus providing a mechanistic basis for coordinated action of hDmc1 protomers during meiotic recombination

Ideal Internal Carotid Artery Trapping Technique without Bypass in a Patient with Insufficient Collateral Flow.

Internal carotid artery (ICA) trapping can be used for treating intracranial giant aneurysm, blood blister-like aneurysms and ICA rupture during the surgery. We present a novel ICA trapping technique which can be used with insufficient collaterals flow via anterior communicating artery (AcoA) and posterior communicating artery (PcoA). A patient was admitted with severe headache and the cerebral angiography demonstrated a typical blood blister-like aneurysm at the contralateral side of PcoA. For trapping the aneurysm, the first clip was placed at the ICA just proximal to the aneurysm whereas the distal clip was placed obliquely proximal to the origin of the PcoA to preserve blood flow from the PcoA to the distal ICA. The patient was completely recovered with good collaterals filling to the right ICA territories via AcoA and PcoA. This technique may be an effective treatment option for trapping the aneurysm, especially when the PcoA preservation is mandatory

Eccrine angiomatous hamartoma: a review of ten cases.

BACKGROUND: Eccrine angiomatous hamartoma (EAH) is a rare benign nodular lesion characterized by the proliferation of eccrine and vascular structures, generally capillaries, in the middle and deep dermis. It may be congenital or appear later in childhood, but rarely arises in adulthood. OBJECTIVE: To investigate the clinicopathologic features of EAH in Korean patients. METHODS: Ten cases of EAH diagnosed at Ajou University Hospital and Gangnam Severance Hospital in Korea from 2007 to 2010 were retrospectively reviewed. RESULTS: The age range of patients was between 5 and 66 years with an equal number of male and female patients. Apart from two congenital cases, the onset was late, ranging from 6 months to 65 years of age. All lesions were solitary and located on the distal extremities. Nine cases appeared as a yellow-brown nodule or plaque resembling a callus. Neither hyperhidrosis nor hypertrichosis was documented. Apart from the typical histological findings of EAH, prominent mucin deposition, fat component and nerve infiltration were observed. CONCLUSION: This is one of the largest single case series of EAH in the literature. Clinically, resemblance to callosities and the frequent occurrence in the adulthood were the unique features in our series

A secretome profile indicative of oleate-induced proliferation of HepG2 hepatocellular carcinoma cells

Increased fatty acid (FA) is often observed in highly proliferative tumors. FAs have been shown to modulate the secretion of proteins from tumor cells, contributing to tumor survival. However, the secreted factors affected by FA have not been systematically explored. Here, we found that treatment of oleate, a monounsaturated omega-9 FA, promoted the proliferation of HepG2 cells. To examine the secreted factors associated with oleate-induced cell proliferation, we performed a comprehensive secretome profiling of oleate-treated and untreated HepG2 cells. A comparison of the secretomes identified 349 differentially secreted proteins (DSPs; 145 upregulated and 192 downregulated) in oleate-treated samples, compared to untreated samples. The functional enrichment and network analyses of the DSPs revealed that the 145 upregulated secreted proteins by oleate treatment were mainly associated with cell proliferation-related processes, such as lipid metabolism, inflammatory response, and ER stress. Based on the network models of the DSPs, we selected six DSPs (MIF, THBS1, PDIA3, APOA1, FASN, and EEF2) that can represent such processes related to cell proliferation. Thus, our results provided a secretome profile indicative of an oleate-induced proliferation of HepG2 cell

The contributions of muscarinic receptors and changes in plasma aldosterone levels to the anti-hypertensive effect of Tulbaghia violacea

Background: Tulbaghia violacea Harv. (Alliaceae) is used to treat various ailments, including hypertension (HTN) in South Africa. This study aims to evaluate the contributions of muscarinic receptors and changes in plasma aldosterone levels to its anti-hypertensive effect. Methods: In the acute experiments, methanol leaf extracts (MLE) of T. violacea (30–120 mg/kg), muscarine (0.16 -10 μg/kg), and atropine (0.02 - 20.48 mg/kg), and/or the vehicle (dimethylsulfoxide (DMSO) and normal saline (NS)) were respectively and randomly administered intravenously in a group of spontaneously hypertensive (SHR) weighing 300 to 350 g and aged less than 5 months. Subsequently, T. violacea (60 mg/kg) or muscarine (2.5 μg/kg) was infused into eight SHRs, 20 min after atropine (5.12 mg/kg) pre-treatment. In the chronic (21 days) experiments, the SHRs were randomly divided into three groups, and given the vehicle (0.2 ml/day of DMSO and NS), T. violacea (60 mg/kg/day) and captopril (10 mg/kg/day) respectively into the peritoneum, to investigate their effects on blood pressure (BP), heart rate (HR), and plasma aldosterone levels. Systolic BP and HR were measured using tail-cuff plethysmography during the intervention. BP and HR were measured via a pressure transducer connecting the femoral artery and the Powerlab at the end of each intervention in the acute experiment; and on day 22 in the chronic experiment. Results: In the acute experiments, T. violacea, muscarine, and atropine significantly (p < 0.05) reduced BP dose-dependently. T. violacea and muscarine produced dose-dependent decreases in HR, while the effect of atropine on HR varied. After atropine pre-treatment, dose-dependent increases in BP and HR were observed with T. violacea; while the BP and HR effects of muscarine were nullified. In the chronic experiments, the T. violaceatreated and captropril-treated groups had signicantly lower levels of aldosterone in plasma when compared to vehicle-treated group. Compared to the vehicle-treated group, significant reduction in BP was only seen in the captopril-treated group; while no difference in HR was observed among the groups. Conclusion: The results obtained in this study suggest that stimulation of the muscarinic receptors and a reduction in plasma aldosterone levels contribute to the anti-hypertesive effect of T. violacea.IS

Incidence and risk factors for rebleeding during cerebral angiography for ruptured intracranial aneurysms.

PURPOSE: The purpose was to evaluate the incidence and risk factors for rebleeding during cerebral angiography in ruptured intracranial aneurysms. MATERIALS AND METHODS: Among 1896 patients with ruptured intracranial aneurysms between September 2006 and December 2013, a total of 11 patients who experienced rebleeding of the ruptured aneurysms during digital subtraction angiography (DSA) were recruited in this study. RESULTS: There were 184 patients (9.7%) who had suffered rebleeding prior to the securing procedure. Among them, 11 patients experienced rebleeding during DSA and other 173 patients at a time other than DSA. Eight (72.7%) of the 11 patients experienced rebleeding during three-dimensional rotational angiography (3DRA). The incidence of rebleeding during DSA was 0.6% in patients with ruptured intracranial aneurysms. Multivariate logistic regression analysis showed that aneurysm location in anterior circulation [odds ratio=14.286; 95% confidence interval (CI), 1.877 to 250.0; p=0.048] and higher aspect ratio (odds ratio=3.040; 95% CI, 1.896 to 10.309; p=0.041) remained independent risk factors for rebleeding during DSA. CONCLUSION: Ruptured aneurysms located in anterior circulation with a high aspect ratio might have the risk of rebleeding during DSA, especially during 3DRA

Genome of the facultative scuticociliatosis pathogen Pseudocohnilembus persalinus provides insight into its virulence through horizontal gene transfer

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ The attached file is the published version of the article

Comparison of Short-Term Surgical Outcomes According to Immediately Postoperative Serum Glucose Level in Non-Diabetic Pancreatic Resection Patients

The adequate regulation of postoperative serum glucose level (SGL) is widely accepted; however, the effects for non-diabetic patients who underwent major pancreatic surgery have not yet been established. We discerned the relevance of the immediately postoperative SGL to short-term postoperative outcomes from major pancreatic surgery in non-diabetic patients. Between January 2007 and December 2016, 2259 non-diabetic patients underwent major pancreatic surgery at four tertiary medical centers in Republic of Korea. Based on a SGL of 200 mg/dL, patients were classified into two groups by averaging the results of four SGL tests taken on the first day after surgery, and their short-term postoperative outcomes were analyzed. A 1:1 propensity score matching method was conducted to establish the high SGL group (n = 568) and the normal SGL group (n = 568). The high SGL group experienced a significantly higher rate of level C complications in the Clavien-Dindo classification (CDc) than the normal SGL group (24.1% vs. 16.5%, p = 0.002). Additionally, an SGL of more than 200 mg/dL was associated with a significantly high risk of complications above level C CDc after adjusting for other risk factors (hazard ratio = 1.324, 95% confidence interval = 1.048-1.672, p = 0.019). The regulation of SGL of less than 200 mg/dL in non-diabetic patients early after major pancreatic surgery could be helpful for reducing postoperative complications

Thromboembolic Events Associated with Electrolytic Detachment of Guglielmi Detachable Coils and Target Coils : Comparison with Use of Diffusion-Weighted MR Imaging.

OBJECTIVE: The purpose of this study was to retrospectively evaluate and compare the incidence of diffusion-weighted image (DWI) lesions between the Guglielmi detachable coil (GDC) and the Target coil for treating unruptured intracranial aneurysm. METHODS: From 2010 to 2011, consecutive 222 patients with an intracranial aneurysm underwent coil embolization. Inclusion criterias were : 1) unruptured intracranial aneurysm, 2) one or more GDC or Target coils used with or without other coils, 3) DWI examination within 24 hours after coiling, and 4) coiling performed without a balloon or stent. RESULTS: Ninety patients (92 cases) met the inclusion criteria. DWI lesions were detected in 55 (61.1%) of 90 patients. In the GDC group (n=44), DWI lesions were detected in 31 (70.5%). The average number of DWI lesions was 5.0±8.7 (mean±SD; range, 1-40) in aneurysm-related territory. In the Target coil group (n=48), DWI lesions were detected in 24 (50.0%). The number of DWI lesion was 2.1±5.4 (range, 1-32) in aneurysm-related territory. There was no significant correlation between a number of coils and DWI lesions. No significant differences were also observed in the number of DWI lesions in each group. CONCLUSION: The GDC and Target coils, which have an electrolytic detachable system, showed no differences in the incidence of DWI lesion

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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