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#34563056   2021/09/17 To Up

The Effects of General Anaesthesia and Light on Behavioural Rhythms and GABA Receptor Subunit Expression in the Mouse SCN.

General anaesthesia (GA) is known to affect the circadian clock. However, the mechanisms that underlie GA-induced shifting of the clock are less well understood. Activation of γ-aminobutyric acid (GABA)type A receptors (GABAR) in the suprachiasmatic nucleus (SCN) can phase shift the clock and thus GABA and its receptors represent a putative pathway via which GA exerts its effect on the clock. Here, we investigated the concurrent effects of the inhalational anaesthetic, isoflurane, and light, on mouse behavioural locomotor rhythms and on α1, β3, and γ2 GABAR subunit expression in the SCN of the mouse brain. Behavioural phase shifts elicited by exposure of mice to four hours of GA (2% isoflurane) and light (400 lux) (n = 60) were determined by recording running wheel activity rhythms in constant conditions (DD). Full phase response curves for the effects of GA + light on behavioural rhythms show that phase shifts persist in anaesthetized mice exposed to light. Daily variation was detected in all three GABAR subunits in LD 12:12. The γ2 subunit expression was significantly increased following GA in DD (compared to light alone) at times of large behavioural phase delays. We conclude that the phase shifting effect of light on the mouse clock is not blocked by GA administration, and that γ2 may potentially be involved in the phase shifting effect of GA on the clock. Further analysis of GABAR subunit expression in the SCN will be necessary to confirm its role.
Janelle Chong, James Frederick Cheeseman, Matthew D M Pawley, Andrea Kwakowsky, Guy R Warman

1806 related Products with: The Effects of General Anaesthesia and Light on Behavioural Rhythms and GABA Receptor Subunit Expression in the Mouse SCN.

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#34563047   2021/09/07 To Up

Screening for Copy Number Variations of the 15q13.3 Hotspot in Gene and Expression in Patients with Migraines.

a migraine is a neurological disease. Copy number variation (CNV) is a phenomenon in which parts of the genome are repeated. We investigated the effects of the CNV and gene expression at the location 15q13.3 in the Cholinergic Receptor Nicotinic Alpha 7 Subunit () gene, which we believe to be effective in the migraine clinic.
Mehmet Fatih Özaltun, Sırma Geyik, Şenay Görücü Yılmaz

1617 related Products with: Screening for Copy Number Variations of the 15q13.3 Hotspot in Gene and Expression in Patients with Migraines.

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#34563046   2021/09/07 To Up

Hemopexin Modulates Expression of Complement Regulatory Proteins in Rat Glomeruli.

In systemic hemolysis and in hematuric forms of kidney injury, the major heme scavenging protein, hemopexin (HPX), becomes depleted, and the glomerular microvasculature (glomeruli) is exposed to high concentrations of unbound heme, which, in addition to causing oxidative injury, can activate complement cascades; thus, compounding extent of injury. It is unknown whether unbound heme can also activate specific complement regulatory proteins that could defend against complement-dependent injury. Isolated rat glomeruli were incubated in media supplemented with HPX-deficient (HPX) or HPX-containing (HPX) sera as a means of achieving different degrees of heme partitioning between incubation media and glomerular cells. Expression of heme oxygenase (HO)-1 and of the complement activation inhibitors, decay-accelerating factor (DAF), CD59, and complement receptor-related gene Y (Crry), was assessed by western blot analysis. Expression of HO-1 and of the GPI-anchored DAF and CD59 proteins increased in isolated glomeruli incubated with HPX sera with no effect on Crry expression. Exogenous heme (hemin) did not further induce DAF but increased Crry expression. HPX modulates heme-mediated induction of complement activation controllers in glomeruli. This effect could be of translational relevance in glomerular injury associated with hematuria.
Maria G Detsika, Elias A Lianos

1159 related Products with: Hemopexin Modulates Expression of Complement Regulatory Proteins in Rat Glomeruli.

1mg1 mg15010050 50 100 UG21022

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#34562931   2021/09/16 To Up

Genetically Encoded Sensor Cells for the Screening of Glucocorticoid Receptor (GR) Effectors in Herbal Extracts.

Although in vitro sensors provide facile low-cost ways to screen for biologically active targets, their results may not accurately represent the molecular interactions in biological systems. Cell-based sensors have emerged as promising platforms to screen targets in biologically relevant environments. However, there are few examples where cell-based sensors have been practically applied for drug screening. Here, we used engineered cortisol-detecting sensor cells to screen for natural mimetics of cortisol. The sensor cells were designed to report the presence of a target through signal peptide activation and subsequent fluorescence signal translocation. The developed sensor cells were able to detect known biological targets from human-derived analytes as well as natural product extracts, such as deer antlers and ginseng. The multi-use capability and versatility to screen in different cellular environments were also demonstrated. The sensor cells were used to identify novel GR effectors from medicinal plant extracts. Our results suggest that decursin from dongquai had the GR effector function as a selective GR agonist (SEGRA), making it a potent drug candidate with anti-inflammatory activity. We demonstrated the superiority of cell-based sensing technology over in vitro screening, proving its potential for practical drug screening applications that leads to the function-based discovery of target molecules.
Chungwon Kang, Soyoun Kim, Euiyeon Lee, Jeahee Ryu, Minhyeong Lee, Youngeun Kwon

2840 related Products with: Genetically Encoded Sensor Cells for the Screening of Glucocorticoid Receptor (GR) Effectors in Herbal Extracts.

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#34562926   2021/09/14 To Up

Recent Advances in Electrochemical Biosensors: Applications, Challenges, and Future Scope.

The electrochemical biosensors are a class of biosensors which convert biological information such as analyte concentration that is a biological recognition element (biochemical receptor) into current or voltage. Electrochemical biosensors depict propitious diagnostic technology which can detect biomarkers in body fluids such as sweat, blood, feces, or urine. Combinations of suitable immobilization techniques with effective transducers give rise to an efficient biosensor. They have been employed in the food industry, medical sciences, defense, studying plant biology, etc. While sensing complex structures and entities, a large data is obtained, and it becomes difficult to manually interpret all the data. Machine learning helps in interpreting large sensing data. In the case of biosensors, the presence of impurity affects the performance of the sensor and machine learning helps in removing signals obtained from the contaminants to obtain a high sensitivity. In this review, we discuss different types of biosensors along with their applications and the benefits of machine learning. This is followed by a discussion on the challenges, missing gaps in the knowledge, and solutions in the field of electrochemical biosensors. This review aims to serve as a valuable resource for scientists and engineers entering the interdisciplinary field of electrochemical biosensors. Furthermore, this review provides insight into the type of electrochemical biosensors, their applications, the importance of machine learning (ML) in biosensing, and challenges and future outlook.
Anoop Singh, Asha Sharma, Aamir Ahmed, Ashok K Sundramoorthy, Hidemitsu Furukawa, Sandeep Arya, Ajit Khosla

1454 related Products with: Recent Advances in Electrochemical Biosensors: Applications, Challenges, and Future Scope.

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#34562851   2021/09/17 To Up

E484K mutation in SARS-CoV-2 RBD enhances binding affinity with hACE2 but reduces interactions with neutralizing antibodies and nanobodies: Binding free energy calculation studies.

The pandemic of the COVID-19 disease caused by SARS-CoV-2 has led to more than 200 million infections and over 4 million deaths worldwide. The progress in the developments of effective vaccines and neutralizing antibody therapeutics brings hopes to eliminate the threat of COVID-19. However, SARS-CoV-2 continues to mutate, and several new variants have been emerged. Among the various naturally-occurring mutations, the E484K mutation shared by many variants attracted serious concerns, which may potentially enhance the receptor binding affinity and reduce the immune response. In the present study, the molecular mechanism behind the impacts of E484K mutation on the binding affinity of the receptor-binding domain (RBD) with the receptor human angiotensin-converting enzyme 2 (hACE2) was investigated by using the molecular dynamics (MD) simulations combined with the molecular mechanics-generalized Born surface area (MMGBSA) method. Our results indicate that the E484K mutation results in more favorable electrostatic interactions compensating the burial of the charged and polar groups upon the binding of RBD with hACE2, which significantly improves the RBD-hACE2 binding affinity. Besides that, the E484K mutation also causes the conformational rearrangements of the loop region containing the mutant residue, which leads to tighter binding interface of RBD with hACE2 and formation of some new hydrogen bonds. The tighter binding interface and the new hydrogen bonds formation also contribute to the improved binding affinity of RBD to the receptor hACE2. In addition, six neutralizing antibodies and nanobodies complexed with RBD were selected to explore the effects of E484K mutation on the recognition of these antibodies to RBD. The simulation results show that the E484K mutation significantly reduces the binding affinities to RBD for most of the studied neutralizing antibodies/nanobodies, and the decrease in the binding affinities is mainly owing to the unfavorable electrostatic interactions caused by the mutation. Our studies revealed that the E484K mutation may improve the binding affinity between RBD and the receptor hACE2, implying more transmissibility of the E484K-containing variants, and weaken the binding affinities between RBD and the studied neutralizing antibodies/nanobodies, indicating reduced effectiveness of these antibodies/nanobodies. Our results provide valuable information for the effective vaccine development and antibody/nanobody drug design.
Wei Bu Wang, Yu Liang, Yu Qin Jin, Jing Zhang, Ji Guo Su, Qi Ming Li

2745 related Products with: E484K mutation in SARS-CoV-2 RBD enhances binding affinity with hACE2 but reduces interactions with neutralizing antibodies and nanobodies: Binding free energy calculation studies.

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#34562816   2021/09/22 To Up

c-Kit inhibitors for unresectable or metastatic mucosal, acral or chronically sun-damaged melanoma: a systematic review and one-arm meta-analysis.

Activating genomic alterations of the receptor tyrosine kinase KIT are found preferentially in certain melanoma subtypes such as acral and mucosal melanoma or melanoma arising in chronically sun-damaged skin. However, the therapeutic value of c-Kit inhibitors for these subtypes currently remains unclear.
Theresa Steeb, Anja Wessely, Anne Petzold, Christoph Kohl, Michael Erdmann, Carola Berking, Markus V Heppt

1722 related Products with: c-Kit inhibitors for unresectable or metastatic mucosal, acral or chronically sun-damaged melanoma: a systematic review and one-arm meta-analysis.

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#34562797   2021/09/21 To Up

Dynamics of local gene regulations in synovial fluid leukocytes from horses with lipopolysaccharide-induced arthritis.

The role of resident cells such a synoviocytes and chondrocytes in intra-articular inflammation is well-characterized, however the in vivo gene expression patterns of cells (predominantly leukocytes) in the synovial fluid (SF) of an inflamed joint have never previously been investigated. The aim of this study was to investigate gene expression in SF leukocytes from the inflamed joint cavity after intra-articular lipopolysaccharide (LPS) injection in horses to improve our understanding of the temporal regulation of the intra-articular inflammatory response. Gene expression was investigated in SF samples available from six horses 2, 4, 8 16 and 24 h after experimental induction of inflammation in the radiocarpal joint by lipopolysaccharide (LPS) injection. Leukocytic expression of 43 inflammation-related genes was studied using microfluidic high throughput qPCR (Fluidigm®). Expression of 26 genes changed significantly over the 24 h study period, including pro- and anti-inflammatory genes such as interleukin (IL)1, IL6, tumor necrosis factor (TNF), cyclooxygenase 2 (COX2), IL1 receptor antagonist (IL1RN), IL10, and superoxide dismutase 2 (SOD2), chemokine genes, apoptosis-related genes, and genes related to cartilage turnover (matrix metalloproteinase 8 and tissue inhibitor of metalloproteinase 1). The inflammatory responses appeared to be regulated, as an early increase (at 2 h) in expression of the pro-inflammatory genes IL1, IL6, TNF and COX2 was rapidly followed by increased expression (at 4 h) of several anti-inflammatory genes (IL10, IL1RN and SOD2). Similarly, both pro- and anti-apoptotic gene expression as well as expression of chondrodegenerative and chondroprotective genes were activated in SF leukocytes. Thus, the inflammatory response in leukocytes infiltrating the joint in the acute stage of arthritis was well orchestrated in this single-hit LPS-induced arthritis model. This study is the first to describe gene expression patterns in SF-derived leukocytes in vivo during severe joint inflammation, and the results thus expand our knowledge of basic inflammatory mechanisms in the early local response in an inflamed joint.
Marie Walters, Kerstin Skovgaard, Pia Haubro Andersen, Peter M H Heegaard, Stine Jacobsen

2434 related Products with: Dynamics of local gene regulations in synovial fluid leukocytes from horses with lipopolysaccharide-induced arthritis.

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#34562790   2021/09/10 To Up

Endocrine disruption in the sub Antarctic fish Patagonotothen tessellata (Perciformes, Notothenidae) from Beagle Channel associated to anthropogenic impact.

Situated in the sub-Antarctic region, Beagle Channel represents a unique marine ecosystem due to the connection between the Pacific and the Atlantic Oceans, and its proximity to the Antarctic Peninsula. Ushuaia city, the biggest settlement on the channel, exerts an increasing anthropogenic pressure by discharges of urban and industrial effluents. In the present work, we use Patagonotothen tessellata, one of the most abundant and widespread species in the channel, as a bioindicator species in order to evidence anthropic impact from Ushuaia Bay and surrounding areas. We first analyzed and characterized real time gene expression of androgen receptor, estrogen receptor and different forms of vitellogenin (VTG), under laboratory conditions. This was achieved by induction with estradiol of P. tessellata males. Then, the selected genes were used as biomarkers for an environmental biomonitoring study. Morphometric indices and circulating sex steroids (estradiol and testosterone) were also quantified in male fish collected from different sites. The qPCR analysis showed that vtgAb form is more inducible than vtgAa or vtgC forms after estrogen induction. The field survey revealed the up-regulation of vtgAb and the androgen receptor in fish from sites with higher anthropogenic influence. Sex steroids followed seasonal variations according to their reproductive cycle, with higher levels of estradiol and testosterone in winter and summer seasons. The use of biomarkers such as gene expression of VTG demonstrates that fish from Ushuaia Bay are likely to be exposed to endocrine disrupting compounds. To our knowledge, this research is the first attempt to assess the endocrine disruption associated to anthropic impact in a widespread fish of the Beagle Channel and contributes to a better understanding of the reproductive physiology of sub Antarctic ichthyofauna.
Maria Florencia Ferreira, Fabiana L Lo Nostro, Daniel A Fernández, Griselda Genovese

1732 related Products with: Endocrine disruption in the sub Antarctic fish Patagonotothen tessellata (Perciformes, Notothenidae) from Beagle Channel associated to anthropogenic impact.

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#34562771   2021/09/22 To Up

Novel variant in glycophorin c gene protects against ribavirin-induced anemia during chronic hepatitis C treatment.

The current use of ribavirin in difficult-to-cure chronic hepatitis C patients (HCV) and patients with severe respiratory infections is constrained by the issue of ribavirin-induced hemolytic anemia that affects 30% of treated patients, requiring dosage modification or discontinuation. Though some genetic variants have been identified predicting this adverse effect, known clinical and genetic factors do not entirely explain the risk of ribavirin-induced anemia.
Jennifer J Lin, Catrina M Loucks, Jessica N Trueman, Britt I Drögemöller, Galen E B Wright, Eric M Yoshida, Jo-Ann Ford, Samuel S Lee, Richard B Kim, Bandar Al-Judaibi, Ute I Schwarz, Alnoor Ramji, Edward Tam, Colin J Ross, Bruce C Carleton

2188 related Products with: Novel variant in glycophorin c gene protects against ribavirin-induced anemia during chronic hepatitis C treatment.

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