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CAR links hypoxia signaling to improved survival after myocardial infarction
Freiberg Fabian,Thakkar Meghna,Hamann Wiebke,Jacobo Lopez Carballo,Jüttner Rene,Voss Felizia K.,Becher Peter M.,Westermann Dirk,Tschöpe Carsten,Heuser Arnd,Rocks Oliver,Robert Fischer,Gotthardt Michae 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-
The coxsackievirus and adenovirus receptor (CAR) mediates homo- and heterotopic interactions between neighboring cardiomyocytes at the intercalated disc. CAR is upregulated in the hypoxic areas surrounding myocardial infarction (MI). To elucidate whether CAR contributes to hypoxia signaling and MI pathology, we used a gain- and loss-of-function approach in transfected HEK293 cells, H9c2 cardiomyocytes and CAR knockout mice. CAR overexpression increased RhoA activity, HIF-1α expression and cell death in response to chemical and physical hypoxia. In vivo, we subjected cardiomyocyte-specific CAR knockout (KO) and wild-type mice (WT) to coronary artery ligation. Survival was drastically improved in KO mice with largely preserved cardiac function as determined by echocardiography. Histological analysis revealed a less fibrotic, more compact lesion. Thirty days after MI, there was no compensatory hypertrophy or reduced cardiac output in hearts from CAR KO mice, in contrast to control mice with increased heart weight and reduced ejection fraction as signs of the underlying pathology. Based on these findings, we suggest CAR as a therapeutic target for the improved future treatment or prevention of myocardial infarction.
Solution Structure of a Sponge-Derived Cystine Knot Peptide and Its Notable Stability
Li, Huayue,Su, Mingzhi,Hamann, Mark T.,Bowling, John J.,Kim, Hyung Sik,Jung, Jee H. American Chemical Society and American Society of 2014 Journal of natural products Vol.77 No.2
<P>A novel cystine knot peptide, asteropsin E (ASPE), was isolated from an <I>Asteropus</I> sp. marine sponge. The primary, secondary, and tertiary structures of ASPE were determined by high-resolution 2D NMR spectroscopy (900 MHz). With the exception of an <I>N</I>-terminal modification, ASPE shares properties with the previously reported asteropsins A–D, that is, the absence of basic residues, a highly acidic nature, conserved structurally important residues (including two <I>cis</I>-prolines), and a highly conserved tertiary structural framework. ASPE was found to be remarkably stable to gastrointestinal tract enzymes (chymotrypsin, elastase, pepsin, and trypsin) and to human plasma.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jnprdf/2014/jnprdf.2014.77.issue-2/np400899a/production/images/medium/np-2013-00899a_0009.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/np400899a'>ACS Electronic Supporting Info</A></P>
Yasmin Gundelach,Elke Kalscheuer,Henning Hamann,Martina Hoedemaker 대한수의학회 2011 JOURNAL OF VETERINARY SCIENCE Vol.12 No.3
Factors affecting bacteriological cure rates (BCR) and new intramammary infections (IMI) during the dry period as well as clinical mastitis (CM) during early lactation were investigated in 414 German Holstein dairy cows receiving dry cow therapy. Cows were treated with either benethamine benzylpenicillin (300,000 IU), penethamate hydriodide (100,000 IU), and framycetin sulphate (100 mg, n = 136), or cefquinome (150 mg, n = 135), or benzathine cloxacillin (1,280 mg, n = 143). Overall BCR, IMI, and CM at parturition were 86.4%, 20.7%, and 4.3%, respectively. The three antibiotic treatments differed only in BCR, with cloxacillin yielding better results than the others. Udder quarters from cows with > 4 lactations had a higher risk of IMI and CM at calving. Chronic changes in udder tissues were linked to a lower BCR and were associated with a higher risk of CM during early lactation. The risk of CM at calving was higher in udder quarters with unspecific or subclinical mastitis before drying off. In conclusion, with antibiotic dry cow therapy, age and health status of the udder appear to be major determinants of IMI and CM during the dry period and early lactation, while BCR was associated with the antibiotic type and udder tissue status.
Long-Term Follow-up of Enhanced Holter- Electrocardiography Monitoring in Acute Ischemic Stroke
Rolf Wachter,Mark Weber-Krüger,Gerhard F. Hamann,Pawel Kermer,Jan Liman,Meinhard Mende,Joachim Seegers,Katrin Wasser,Sonja Gröschel,Timo Uphaus,Holger Poppert,Martin Köhrmann,Markus Zabel,Ulrich Laufs 대한뇌졸중학회 2022 Journal of stroke Vol.24 No.1
Background and Purpose Prolonged electrocardiography (ECG)-monitoring in stroke patients improves the detection of paroxysmal atrial fibrillation (pAF). However, most randomized studies only had short follow-up. We aimed to provide 3-year follow-up data for AF detection and stroke recurrence risk. Methods We randomized 402 patients aged ≥60 years with acute ischemic strokes without AF to either enhanced and prolonged monitoring (EPM; 3×10-day Holter-ECG-monitoring) or standard-of-care (≥24 hours ECG-monitoring). The endpoint of the current analysis was AF within 36 months analyzed by intention to treat. Long-term follow-up was performed for 36 months. Results Two hundred and seventy-four patients (80%) participated in the extended follow-up(median duration of follow-up was 36 months [interquartile range, 12 to 36]). During the first 6 months, more AF was documented in the EPM arm compared to the control arm (13.5% vs. 5.1%; 95% confidence interval, 2.9% to 14.4%; P=0.004). During months 6 to 36, AF was less detected in the EPM intervention arm than in the control arm (2.0% vs. 7.3%; 95% confidence interval, 0.7% to 9.9%; P=0.028). Overall, the detection rate of AF within 36 months was numerically higher within the EPM group (15.0% vs. 11.1%, P=0.30). Numerically less patients in the EPM arm had recurrent ischemic strokes (5.5% vs. 9.1%, P=0.18), transient ischemic attacks (3.0% vs. 4.5%, P=0.44) or died (4.5% vs. 6.6%, P=0.37). Conclusions Enhanced and prolonged ECG monitoring increased AF detection during the first six months, but there was significantly more clinical AF during months 6 to 36 observed in the usual-care arm. This suggests that EPM leads to an earlier detection of clinically relevant AF.
Kim, Sang Hee,Yoon, HeungSik,Kim, Hackjin,Hamann, Stephan Oxford University Press 2015 Social cognitive and affective neuroscience Vol.10 No.9
<P>In this functional neuroimaging study, we investigated neural activations during the process of learning to gain monetary rewards and to avoid monetary loss, and how these activations are modulated by individual differences in reward and punishment sensitivity. Healthy young volunteers performed a reinforcement learning task where they chose one of two fractal stimuli associated with monetary gain (reward trials) or avoidance of monetary loss (avoidance trials). Trait sensitivity to reward and punishment was assessed using the behavioral inhibition/activation scales (BIS/BAS). Functional neuroimaging results showed activation of the striatum during the anticipation and reception periods of reward trials. During avoidance trials, activation of the dorsal striatum and prefrontal regions was found. As expected, individual differences in reward sensitivity were positively associated with activation in the left and right ventral striatum during reward reception. Individual differences in sensitivity to punishment were negatively associated with activation in the left dorsal striatum during avoidance anticipation and also with activation in the right lateral orbitofrontal cortex during receiving monetary loss. These results suggest that learning to attain reward and learning to avoid loss are dependent on separable sets of neural regions whose activity is modulated by trait sensitivity to reward or punishment.</P>
Strain-Induced Spin States in Atomically Ordered Cobaltites
Choi, Woo Seok,Kwon, Ji-Hwan,Jeen, Hyoungjeen,Hamann-Borrero, Jorge E.,Radi, Abdullah,Macke, Sebastian,Sutarto, Ronny,He, Feizhou,Sawatzky, George A.,Hinkov, Vladimir,Kim, Miyoung,Lee, Ho Nyung American Chemical Society 2012 NANO LETTERS Vol.12 No.9
<P>Epitaxial strain imposed in complex oxide thin films by heteroepitaxy is recognized as a powerful tool for identifying new properties and exploring the vast potential of materials performance. A particular example is LaCoO<SUB>3</SUB>, a zero spin, nonmagnetic material in the bulk, whose strong ferromagnetism in a thin film remains enigmatic despite a decade of intense research. Here, we use scanning transmission electron microscopy complemented by X-ray and optical spectroscopy to study LaCoO<SUB>3</SUB> epitaxial thin films under different strain states. We observed an unconventional strain relaxation behavior resulting in stripe-like, lattice modulated patterns, which did not involve uncontrolled misfit dislocations or other defects. The modulation entails the formation of ferromagnetically ordered sheets comprising intermediate or high spin Co<SUP>3+</SUP>, thus offering an unambiguous description for the exotic magnetism found in epitaxially strained LaCoO<SUB>3</SUB> films. This observation provides a novel route to tailoring the electronic and magnetic properties of functional oxide heterostructures.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/nalefd/2012/nalefd.2012.12.issue-9/nl302562f/production/images/medium/nl-2012-02562f_0006.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/nl302562f'>ACS Electronic Supporting Info</A></P>
Oh, Joonseok,Liu, Haining,Park, Hyun Bong,Ferreira, Daneel,Jeong, Gil-Saeng,Hamann, Mark T.,Doerksen, Robert J.,Na, MinKyun Elsevier 2017 Biochimica et biophysica acta, General subjects Vol.1861 No.1
<P><B>Abstract</B></P> <P><B>Background</B></P> <P>Inhibition of fatty acid synthase (FAS) is regarded as a sensible therapeutic strategy for the development of optimal anti-cancer agents. Flavonoids exhibit potent anti-neoplastic properties.</P> <P><B>Methods</B></P> <P>The MeOH extract of <I>Sophora flavescens</I> was subjected to chromatographic analyses such as VLC and HPLC for the purification of active flavonoids. The DP4 chemical-shift analysis protocol was employed to investigate the elusive chirality of the lavandulyl moiety of the purified polyphenols. Induced Fit docking protocols and per-residue analyses were utilized to scrutinize structural prerequisites for hampering FAS activity. The FAS-inhibitory activity of the purified flavonoids was assessed via the incorporation of [<SUP>3</SUP>H] acetyl-CoA into palmitate.</P> <P><B>Results</B></P> <P>Six flavonoids, including lavandulyl flavanones, were purified and evaluated for FAS inhibition. The lavandulyl flavanone sophoraflavanone G (<B>2</B>) exhibited the highest potency (IC<SUB>50</SUB> of 6.7±0.2μM), which was more potent than the positive controls. Extensive molecular docking studies revealed the structural requirements for blocking FAS. Per-residue interaction analysis demonstrated that the lavandulyl functional group in the active flavonoids (<B>1</B>–<B>3</B> and <B>5</B>) significantly contributed to increasing their binding affinity towards the target enzyme.</P> <P><B>Conclusion</B></P> <P>This research suggests a basis for the <I>in silico</I> design of a lavandulyl flavonoid-based architecture showing anti-cancer effects via enhancement of the binding potential to FAS.</P> <P><B>General significance</B></P> <P>FAS inhibition by flavonoids and their derivatives may offer significant potential as an approach to lower the risk of various cancer diseases and related fatalities. <I>In silico</I> technologies with available FAS crystal structures may be of significant use in optimizing preliminary leads.</P> <P><B>Highlights</B></P> <P> <UL> <LI> FAS is a pertinent therapeutic target for the development of cancer agents. </LI> <LI> Lavandulyl flavanones exhibited powerful FAS inhibitory activity. </LI> <LI> The lavandulyl functional group contributed to enhancing their binding affinity. </LI> <LI> <I>In silico</I> design and optimization of flavonoid-based FAS inhibitors may be feasible. </LI> </UL> </P>