Identification of Smad Response Elements in the Promoter of Goldfish FSHβ Gene and Evidence for Their Mediation of Activin and GnRH Stimulation of FSHβ Expression

As an essential hormone regulating gonads in vertebrates, the biosynthesis and secretion of follicle-stimulating hormone (FSH) is controlled by a variety of endocrine and paracrine factors in both mammalian and non-mammalian vertebrates. Activin was initially discovered in the ovary for its specific stimulation of FSH secretion by the pituitary cells. Our earlier studies in fish have shown that activin stimulates FSHβ but suppresses LHβ expression in both the goldfish and zebrafish. Further experiments showed that the regulation of FSHβ in fish occurred at the promoter level involving Smads, in particular Smad3. To further understand the mechanisms by which activin/Smad regulates FSHβ transcription, the present study was undertaken to analyze the promoter of goldfish FSHβ gene (fshb) with the aim to identify potential cis-regulatory elements responsible for activin/Smad stimulation. Both serial deletion and site-directed mutagenesis were used, and the promoter activity was tested in the LβT-2 cells, a murine gonadotroph cell line. The reporter constructs of goldfish FSHβ promoter-SEAP (secreted alkaline phosphatase) were co-transfected with an expression plasmid for Smads (2 or 3) followed by measurement of SEAP activity in the medium. Two putative Smad responsive elements were identified in the promoter at distal and proximal regions, respectively. The distal site contained a consensus Smad binding element (AGAC, −1675/−1672) whereas the proximal site (GACCTTGA, −212/−205) was identical to an SF-1 binding site reported in humans, which was preceded by a sequence (AACACTGA) highly conserved between fish and mammals. The proximal site also seemed to be involved in mediating stimulation of FSHβ expression by gonadotropin-releasing hormone and its potential interaction with activin. In conclusion, we have identified two potential cis-regulatory elements in the promoter of goldfish FSHβ that are responsible for activin-induced expression of the gene. Since activin stimulation of FSHβ expression is functionally conserved in fish and mammals, our findings contribute to the understanding of the fundamental mechanisms of this regulation across vertebrates

A combined finite element-Langevin dynamics (FEM-LD) approach for analyzing the mechanical response of bio-polymer networks

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In-vitro and in-silico evaluations of heterocyclic-containing diarylpentanoids as Bcl-2 inhibitors against LoVo colorectal cancer cells

In the present study, we investigated the in-vitro anti-cancer potential of six diarylpentanoids against a panel of BRAF- and KRAS-mutated colorectal cancer cell lines including T84, SW620, LoVo, HT29, NCI-H508, RKO, and LS411N cells. Structure-activity relationship study suggested that the insertions of tetrahydro-4H-thiopyran-4-one and brominated phenyl moieties are essential for better cytotoxicity. Among the evaluated analogs, 2e has been identified as the lead compound due to its low IC50 values of approximately 1 µM across all cancer cell lines and high chemotherapeutic index of 7.1. Anti-proliferative studies on LoVo cells showed that 2e could inhibit cell proliferation and colony formations by inducing G2/M cell cycle arrest. Subsequent cell apoptosis assay confirmed that 2e is a Bcl-2 inhibitor that could induce intrinsic cell apoptosis by creating a cellular redox imbalance through its direct inhibition on the Bcl-2 protein. Further molecular docking studies revealed that the bromophenyl moieties of 2e could interact with the Bcl-2 surface pocket through hydrophobic interaction, while the tetrahydro-4H-thiopyran-4-one fragment could form additional Pi-sulfur and Pi-alkyl interactions in the same binding site. In all, the present results suggest that 2e could be a potent lead that deserves further modification and investigation in the development of a new Bcl-2 inhibitor

Energy Consumption and Economic Growth Nexus in China : Autoregressive Distributed Lag (ARDL)

This paper intends to investigate the nexus between energy consumption, carbon dioxide emission, total export and economic growth of China from 1971 to 2014. This study adopted Autoregressive Distributed Lag (ARDL) bounds test to examine the existence of short-run and long-run relationships among the variables. Empirical findings indicated that energy consumption contribute to economic growth while carbon dioxide emission is impeding the growth. There is a positive long-run relationship between both energy consumption and total export with economic growth of China. However, a negative relationship is observed between carbon dioxide emissions and economic growth. Hence, in terms of policy recommendation, policymakers can implement a balance environment-economic policy; reduce the carbon dioxide emission by imposing carbon tax; promote renewable energy among the industries and households and promoting reserves forest policy is needed for aspiration of sustainable growth for both environmental and economic

The Market for Organic Black Tea in Germany and the United States

This market research paper has been prepared under the supervision of Prof. Dr. Wolfgang Veit of TH Köln and Prof. Dr. Carol Scovotti of University of Wisconsin-Whitewater in the course of the inter-university cross-border collaboration student research project “Export Opportunity Surveys (EOS)”. This study explores organic black tea export opportunities to the German and US markets

Adaptive Synaptic Memory via Lithium Ion Modulation in RRAM Devices

Biologically plausible computing systems require fine- grain tuning of analog synaptic characteristics. In this study, lithium- doped silicate resistive random access memory with a titanium nitride (TiN) electrode mimicking biological synapses is demonstrated. Biological plausibility of this RRAM device is thought to occur due to the low ionization energy of lithium ions, which enables controllable forming and filamentary retraction spontaneously or under an applied voltage. The TiN electrode can effectively store lithium ions, a principle widely adopted from battery construction, and allows state- dependent decay to be reliably achieved. As a result, this device offers multi- bit functionality and synaptic plasticity for simulating various strengths in neuronal connections. Both short- term memory and long- term memory are emulated across dynamical timescales. Spike- timing- dependent plasticity and paired- pulse facilitation are also demonstrated. These mechanisms are capable of self- pruning to generate efficient neural networks. Time- dependent resistance decay is observed for different conductance values, which mimics both biological and artificial memory pruning and conforms to the trend of the biological brain that prunes weak synaptic connections. By faithfully emulating learning rules that exist in human’s higher cortical areas from STDP to synaptic pruning, the device has the capacity to drive forward the development of highly efficient neuromorphic computing systems.In this study, lithium- doped silicate resistive random access memory with a titanium nitride (TiN) electrode is shown to mimic biological synapses. The TiN electrode effectively stores lithium ions, a principle widely adopted from battery construction, and enables reliable state- dependent decay. This device offers multi- bit functionality and synaptic plasticity, short- term memory and long- term memory, spike- timing- dependent plasticity and paired- pulse facilitation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163426/3/smll202003964-sup-0001-SuppMat.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163426/2/smll202003964_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163426/1/smll202003964.pd

Benzoate Catabolite Repression of the Phenol Degradation in Acinetobacter calcoaceticus PHEA-2

Acinetobacter calcoaceticus PHEA-2 exhibited a delayed utilization of phenol in the presence of benzoate. Benzoate supplementation completely inhibited phenol degradation in a benzoate 1,2-dioxygenase knockout mutant. The mphR encoding the transcriptional activator and mphN encoding the largest subunit of multi-component phenol hydroxylase in the benA mutant were significantly downregulated (about 7- and 70-fold) on the basis of mRNA levels when benzoate was added to the medium. The co-transformant assay of E. coli JM109 with mphK::lacZ fusion and the plasmid pETR carrying mphR gene showed that MphR did not activate the mph promoter in the presence of benzoate. These results suggest that catabolite repression of phenol degradation by benzoate in A. calcoaceticus PHEA-2 is mediated by the inhibition of the activator protein MphR

Cytochrome P450-mediated co-metabolism of fluoroquinolones by Haematococcus lacustris for simultaneously promoting astaxanthin and lipid accumulation

Microalgae-based antibiotic removal treatment has attracted attention because of its low carbon and sustainable advantages. The microalgal co-metabolism system with a suitable carbon source leads to enhanced performance of pollutant removal. However, currently, limited knowledge is available for the removal of fluoroquinolone using a microalgae-mediated co-metabolism system. In this study, we first investigated that the biotic processes by alga Haematococcus lacustris in the co-metabolism system by adding glycerol would be the main contributors responsible for the removal of 10 mg/L ofloxacin (OFL) with the efficiency of 79.73% and the removal of 10 mg/ L enrofloxacin (ENR) with the efficiency of 54.10%, respectively. Furthermore, we found that pyruvate from glycerol was converted into substrates and precursors, thereby resulting in the significant accumulations of microalgal astaxanthin and lipid. The astaxanthin content of H. lacustris was achieved at 4.81% and 4.69% treated with OFL and ENR in the presence of glycerol, with 16.04% and 14.55% of lipid content, respectively. The proposed metabolites and pathways were identified to plausibly explain the biodegradation of fluoroquinolone by H. lacustris. The molecular analyses demonstrated that cytochrome P450 (CYP450) enzymes are responsible for the biodegradation of fluoroquinolone, and it was further verified that fluoroquinolones might insert into CYP450 to finally form an efficient and tight binding conformation by molecular dynamic simulation. These findings provide a microalgae-based route for feasible and sustainable biodegradation of antibiotics using a co-metabolism strategy comprising glycerol as a carbon source, with the synergistic accumulation of valuable products.peer-reviewe

Synthesis of flavone-based compounds as ros-dependent apoptosis inducers in colorectal cancer

Apoptosis is essential for maintaining cell homeostasis. It hinders the cancer cells survival and excessive ROS can induce DNA damage in cancer cells, which lead to apoptosis. Therefore, targeting apoptosis may be a universal cancer therapeutic technique. Twelve flavone-based compounds were synthesised and characterised. All compounds were evaluated for cytotoxicity against four human cancer cell lines: kidney, breast, colorectal, and bladder cancer cells. Only compound 8 exhibited excellent cytotoxicity against all investigated cancer cell lines, with notably potent cytotoxicity against colorectal (SW620) cells (IC50: 3.2 μM) and higher cytotoxicity than control (IC50: 4.2 μM). Mechanistic analyses such as colony formation, cell cycle arrests and flow cytometry analyses demonstrated an increase in intracellular ROS-induced apoptosis in SW620 cells, which is a potential mode of action for compound 8. Western blot research confirmed the apoptotic mechanism of 8 by showing overexpression of c-PARP, BAD, BAK, and AMPK and downregulation of BCL-2 and AKT. Taken together, the data showed that 8 induces apoptosis by increasing ROS. According to this study, a 4-chloromethyl substituent at the C3-phenyl group may be required for 8's cytotoxicity since other para substituents are inactive. Therefore, structure-activity analysis of 8 in related proteins can be studied