Off-Target Effect of doublecortin Family shRNA on Neuronal Migration Associated with Endogenous MicroRNA Dysregulation

Baek, S.,Kerjan, G.,Bielas, Stephanie L.,Lee, J.,Fenstermaker, Ali G.,Novarino, G.,Gleeson, Joseph G. Cell Press 2014 Neuron Vol.82 No.6

Acute gene inactivation using short hairpin RNA (shRNA, knockdown) in developing brain is a powerful technique to study genetic function; however, discrepancies between knockdown and knockout murine phenotypes have left unanswered questions. For example, doublecortin (Dcx) knockdown but not knockout shows a neocortical neuronal migration phenotype. Here we report that in utero electroporation of shRNA, but not siRNA or miRNA, to Dcx demonstrates a migration phenotype in Dcx knockouts akin to the effect in wild-type mice, suggesting shRNA-mediated off-target toxicity. This effect was not limited to Dcx, as it was observed in Dclk1 knockouts, as well as with a fraction of scrambled shRNAs, suggesting a sequence-dependent but not sequence-specific effect. Profiling RNAs from electroporated cells showed a defect in endogenous let7 miRNA levels, and disruption of let7 or Dicer recapitulated the migration defect. The results suggest that shRNA-mediated knockdown can produce untoward migration effects by altering endogenous miRNA pathways.

Aging Alters Hepatic DNA Hydroxymethylation, as Measured by Liquid Chromatography/Mass Spectrometry

Stephanie A. Tammen,Gregory G. Dolnikowski,Lynne M. Ausman,Zhenhua Liu,김경철,Simonetta Filippi,최상운 대한암예방학회 2014 Journal of cancer prevention Vol.19 No.4

Background:Aging is one of the most important risk factors for cancer. It appears that aberrant epigenetic changes might be a commondriver of aging and cancer. Among them are changes in DNA methylation and DNA hydroxymethylation. The 5’ carbon of cytosinesin CpG dinucleotides of DNA can be either methylated or hydroxymethylated. Like 5’-methylcytosine, changes in 5’-hydroxymethylcytosinemay occur due to aging, potentially leading to downstream changes in transcription and cancer development. Methods:We set up a method to measure 5’-methyl-2’-deoxycytidine and 5’-hydroxymethyl-2’-deoxycytidine in DNA using liquidchromatography/mass spectrometry (LC/MS-MS) and used this method to measure the percentage of total cytosine that was eithermethylated or hydroxymethylated in the liver tissues of young and old C57Bl/6 male mice. The DNA was enzymatically hydrolyzed bysequential digestion with nuclease P1, phosphodiesterase I and alkaline phosphatase. The isotopomers [15N3]-2’-deoxycytidine and(methyl-d3, ring-6-d1)-5-methyl-2’-deoxycytidine were added to the DNA hydrolysates as internal standards. DNA methylation andhydroxymethylation were calculated as a percentage of total deoxycytidine in genomic DNA. Results:Within day variations for DNA methylation and hydroxymethylation were 3.45% and 8.40%, while day to day variations were6.14% and 17.68%, respectively. Using this method it was determined that hepatic DNA of old mice had increased levels ofhydroxymethylation relative to young (0.32 ± 0.02% vs. 0.24 ± 0.01%, P= 0.02), with no significant changes in 5’-methylcytosine. Conclusions:DNA hydroxymethylation measured by LC/MS-MS method can be a novel biomarker of aging. It will be useful to investigatethe potential role of DNA hydroxymethylation in the development and prevention of age-associated cancer.

Disrupted network cross talk, hippocampal dysfunction and hallucinations in schizophrenia

Hare, Stephanie M.,Law, Alicia S.,Ford, Judith M.,Mathalon, Daniel H.,Ahmadi, Aral,Damaraju, Eswar,Bustillo, Juan,Belger, Aysenil,Lee, Hyo Jong,Mueller, Bryon A.,Lim, Kelvin O.,Brown, Gregory G.,Preda Elsevier 2018 Schizophrenia Research Vol.199 No.-

<P><B>Abstract</B></P> <P>Hallucinations characterize schizophrenia, with approximately 59% of patients reporting auditory hallucinations and 27% reporting visual hallucinations. Prior neuroimaging studies suggest that hallucinations are linked to disrupted communication across distributed (sensory, salience-monitoring and subcortical) networks. Yet, our understanding of the neurophysiological mechanisms that underlie auditory and visual hallucinations in schizophrenia remains limited.</P> <P>This study integrates two resting-state functional magnetic resonance imaging (fMRI) analysis methods – amplitudes of low-frequency fluctuations (ALFF) and functional network connectivity (FNC) – to explore the hypotheses that (1) abnormal FNC between salience and sensory (visual/auditory) networks underlies hallucinations in schizophrenia, and (2) disrupted hippocampal oscillations (as measured by hippocampal ALFF) beget changes in FNC linked to hallucinations. Our first hypothesis was supported by the finding that schizophrenia patients reporting hallucinations have higher FNC between the salience network and an associative auditory network relative to healthy controls. Hippocampal ALFF was negatively associated with FNC between primary auditory cortex and the salience network in healthy subjects, but was positively associated with FNC between these networks in patients reporting hallucinations. These findings provide <I>indirect</I> support favoring our second hypothesis. We suggest future studies integrate fMRI with electroencephalogram (EEG) and/or magnetoencephalogram (MEG) methods to <I>directly probe</I> the temporal relation between altered hippocampal <I>oscillations</I> and changes in cross-network functional communication.</P>

Powder Metallurgy for Light Weight and Ultra-Light Weight Materials

Kieback, B.,Stephani, G.,Weiβgarber, T.,Schubert, T.,Waag, U.,Bohm, A.,Anderson, O.,Gohler, H.,Reinfried, M. The Korean Powder Metallurgy Institute 2003 한국분말재료학회지 (KPMI) Vol.10 No.6

As in other areas of materials technology, the tendency towards light weight constructions becomes more and more important also for powder metallurgy. The development is mainly driven by the automotive industry looking for mass reduction of vehicles as a major factor for fuel economy. Powder metallurgy has to offer a number of interesting areas including the development of sintered materials of light metals. PM aluminium alloys with improved properties are on the way to replace ferrous pars. For high temperature applications in the engine, titanium aluminide based materials offer a great potential, e.g. for exhaust valves. The PM route using elemental powders and reactions sintering is considered to be a cost effective way for net shape parts production. Furthermore it is expected that lower costs for titanium raw materials coming from metallurgical activities will offer new chances for sintered parts with titanium alloys. The field of cellular metals expands with the hollow sphere technique, that can provide materials of many metals and alloys with a great flexibility in structure modifications. These structures are expected to be used in improving the safety (crash absoption) and noise reduction in cars in the near future and offer great potential for many other applications.

The “Sombrero-Shape” Super-Thin Pedicled ALT Flap for Complete Scrotal Reconstruction Following Fournier’s Gangrene

Gianluca Sapino,Stephanie Gonvers,Mario Cherubino,Pietro G. di Summa 대한성형외과학회 2022 Archives of Plastic Surgery Vol.49 No.3

When the scrotal sac is entirely debrided following a Fournier gangrene, testes exposure poses unique challenges for the reconstructive surgeon. Despite the anterolateral thigh (ALT) flap is considered a workhorse in such context, aesthetic results are often suboptimal because of the lack of natural ptosis and patchwork appearance. We describe the use of a super-thin pedicled ALT flap for total scrotal reconstruction, modified according to a peculiar flap design and inset technique. A 42-year-oldmanwas referred to our department for delayed total scrotal reconstruction 8 months after a Fournier gangrene extensive debridement. A super-thin pedicled ALT flap from the right thigh was designed: in the central portion of the ALT, a lateral skin paddle extension was marked to guarantee adequate posterior anchorage during insetting and ptosis of the scrotal sac. This particular flap arrangement has inspired the name “sombrero” as the shape is akin to the famous hat. No secondary refinements were needed, and the patient showed satisfying aesthetic and functional results at 12months’ follow-up. The ALT flap design “sombrero” modification proposed in this article can improve scrotum cosmesis and patient satisfaction in a single-stage single-flap procedure.

New Cellular Metals with Enhanced Energy Absorption: Wire‐Woven Bulk Kagome (WBK)‐Metal Hollow Sphere (MHS) Hybrids

Li, Ming‐,Zhen,Stephani, Gü,nter,Kang, Ki‐,Ju WILEY‐VCH Verlag 2011 Advanced Engineering Materials Vol. No.

<P><B>Abstract</B></P><P>Two types of new cellular metals are fabricated by assembling layer by layer helically‐formed wires with metal hollow sphere (MHS) arrays. In the finished configuration, the MHSs are located in small tetrahedrons or octahedrons of the inner space of a wire‐woven bulk Kagome (WBK) structure. Compression tests reveal excellent energy absorption, which is attributed to combination of suppression of strut buckling in the WBK and moving plastic hinge occurring in the MHSs. The WBK‐MHS hybrids outperform competitors in deformation energy absorption.</P>

Poster Session : PS 0302 ; Geriatrics : Non-Pharmacological Interventions for the Treatment of Primary Insomnia in the Elderly: A Literature Review

( Su Shian Lee ),( Stephanie Ward ),( Madan G Saha ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background: Elderly people experience a high prevalence of insomnia and poor sleep quality. Though the risks of hypnosedatives are well documented in this population, its use is highly prevalent. This paper provides an overview of non-pharmacological strategies available, and their evidence of effectiveness for the treatment of insomnia in the elderly. Methods: A literature search was performed using electronic searches on Medline, PsychINFO, EMBASE, Pubmed and the Cochrane library databases from 1995 till 2014. Relevant publications were also sought from citations and through manual searches of review articles. Search limiters were age above 60 years and English language. Key meta-analyses, systematic reviews, interventional and observational studies were identifi ed, reviewed, and available evidences summarized. Results: To improve symptoms of insomnia, there is evidence to suggest that in cognitively intact people, cognitive behavioural therapy (CBT) is effective. This review revealed confi icting evidence in regards to the effectiveness of physical exercises, bright light therapy and thermal manipulations for the treatment of insomnia. In residential care facilities, noise reduction strategy as a stand-alone therapy for insomnia was not effective but minimizing nocturnal interventions such as incontinence and pressure care, reduced night-time sleep disruptions. Conclusion: With the exception of CBT, there is currently limited evidence to suggest that bright light therapy, physical exercises and thermal manipulation are effective for treatment of insomnia in the elderly. This is due to small number of studies, small sample sizes, short follow-up, and strict patient selection criteria in reviewed studies. However, given its lack of adverse effects in contrast to hypnosedatives, non-pharmacological interventions may be considered as the fi rst line intervention for insomnia in the elderly.

Outpatient cervical brachytherapy in the setting of ongoing antiplatelet therapy or oral anticoagulation

Vladimir Valakh,Vladimir Valakh,Stephanie A. Munns,Mark G. Trombetta 대한부인종양학회 2018 Journal of Gynecologic Oncology Vol.29 No.3

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Synergistic Operation of the CAR2 ( Ornithine Transaminase ) Promoter Elements in Saccharomyces cerevisiae

(Heui Dong Park),(Stephanie Scott),(Rajendra Rai),(Rosemary Dorrington),(Terrance G. Cooper) 경북대학교 유전공학연구소 2000 遺傳工學硏究所報 Vol.14 No.-

The sensory-motor auditory visual education (SAVE) program for adults with prior concussions: a prospective case study

Emily D. Drake,Angela S. Seckington,Stephanie G.B. Sullivan,Shannan Behrens 한국한의학연구원 2020 Integrative Medicine Research Vol.9 No.2

Background: The Sensory-Motor Auditory Visual Education (SAVE) Program is an intervention that utilizes an accelerated multisensory integration process to facilitate neuroplasticity. This study aimed to determine if the SAVE Program might benefit individuals with residual symptoms from a prior concussion. Methods: The study consists of two 1-hour sessions per day for 5 consecutive days. Five individuals were recruited and completed a symptom questionnaire, static postural assessment, auditory detection assessment, peripheral vision assessment, and a battery of computerized cognitive tests. Results: Following the treatment program, 5 individuals showed significant (p < 0.05) improvements in various reported symptoms, significant (p < 0.05) improvements in recognizing colors further from the center of a target, and better detection of an auditory stimulus in the right ear. All tested cognitive domains improved, except for episodic memory accuracy and choice reaction time. The most notable improvements were in planning latency (29.94%), planning accuracy (19%), and working memory accuracy (34.30%). The results of the balance assessment were mixed. Conclusion: The results suggested that the SAVE Program may be a beneficial treatment of residual symptoms from a prior concussion. However, the intrinsic caveats of a case series require more rigorous research.