Establishment of a pheasant ( Phasianus colchicus ) spermatogonial stem cell line for the production of interspecies germ line chimeras

Background: Spermatogonial stem cells (SSCs) are important for the production of interspecies germ line chimeras. The interspecies germ cell transfer technique has been suggested as a way to conserve endangered birds. Our objective was to develop a technique for restoring endangered birds by developing interspecies germ line chimeras between pheasant ( Phasianus colchicus ) and chicken ( Gallus gallus ) with SSCs. Results: SSCs were isolated fromthe surgically removed testis of a pheasant. Growth conditions for pheasant SSCs were established by co-culturing STO (SIM mouse embryo-derived thioguanine and ouabain resistant) cells and pheasant SSCs. The colony-forming cells divided and proliferated stably to yield an established SSC line. Pheasant SSCs showed strong reactivity for GDNF family receptor alpha1 (GFR\u3b11) marker. Finally, production of germline chimeras was attempted by transferring pheasant SSCs into recipient embryos. Although final embryo survival was 5.6% (20/354), the initial survival rate was 88% (312/354). To measure the percent transfer of donor SSC to gonads, the pheasant SSCs were labeled with PKH 26 fluorescent dye. We observed 30% donor cells and 9.48% c-kit/CD117-positive cells in the gonads of recipient chickens. Donor SSCs were thus stably engrafted in the recipient gonads. Conclusions: This study showed that SSCs can be used as a tool for the conservation of endangered birds and the production of germline chimeras. Our findings yield insights into howwe may use the pheasant spermatogonial stem cell line for efficient production of interspecies germ line chimeras and ultimately, to the restoration of endangered birds

Samreng – History and a story

Four recordings in which Mr Samreng Mongre provides some historical information and a story. This consists of 1 video file: SDM30-20090102-02_1240_SM_X_Morang The details of this recording are as follows: SDM30-20090102-02_1240_SM_X_Morang_Duration 20' 00" This recording forms part of the cassette numbered SMVDP02JAN0901 and runs from 11'23" to 31'23" on that cassette The contents of this recording are as follows (times on the cassette in brackets): 11':23" (13'52") About how he came to Hashak 2'29" (15'18") About the Tangsa groups; about how Hashak was originally called Hathak 2'46" (25'41") Story 17'03" (31'23") Some elicitation and discussion of linguistic forms 9"42" (end

Novel Carbazole-Piperazine Hybrid Small Molecule Induces Apoptosis by Targeting BCL-2 and Inhibits Tumor Progression in Lung Adenocarcinoma In Vitro and Xenograft Mice Model

Lung cancer is a type of deadly cancer and a leading cause of cancer associated death worldwide. BCL-2 protein is considered as an imperative target for the treatment of cancer due to their significant involvement in cell survival and death. A carbazole-piperazine hybrid molecule ECPU-0001 was designed and synthesized as a potent BCL-2 targeting agent with effective anticancer cancer activity. Interaction of ECPU-001 has been assessed by docking, molecular dynamics (MD) simulation, and thermal shift assay. Further, in vitro and in vivo anticancer activity was executed by cytotoxicity assay, FACS, colony formation and migration assay, western blotting, immunocyto/histochemistry and xenograft nude mice model. Molecular docking and MD simulation study confirmed that ECPU-0001 nicely interacts with the active site of BCL-2 by displaying a Ki value of 5.72 µM and binding energy (ΔG) of –8.35 kcal/mol. Thermal shift assay also validated strong interaction of this compound with BCL-2. ECPU-0001 effectively exerted a cytotoxic effect against lung adenocarnoma cells A459 with an IC50 value of 1.779 µM. Molecular mechanism of action have also been investigated and found that ECPU-0001 induced apoptosis in A459 cell by targeting BCL-2 to induce intrinsic pathway of apoptosis. Administration of ECPU-0001 significantly inhibited progression of tumor in a xenograft model without exerting severe toxicity and remarkably reduced tumor volume as well as tumor burden in treated animals. Our investigation bestowed ECPU-0001 as an effective tumoricidal agent which exhibited impressive anticancer activity in vitro as well as in vivo by targeting BCL-2 associated intrinsic pathway of apoptosis. Thus, ECPU-0001 may provide a valuable input for therapy of lung adenosarcoma in future, however, further extensive investigation of this compound will be needed

Samreng – CALMSEA Wordlist

Two recordings in which Mr Samreng Mongre provides some word lists in the Mungre variety of Tangsa. This consists of 2 sound files: SDM30-2008TascamPN-001 SDM30-2008TascamPN-002 The details of these recordings are as follows: SDM30-2008TascamPN-001_Duration 42’53”, Word list/ sentence elicitation SDM30-2008TascamPN-002_Duration 20’08”, Word list/ sentence elicitatio

Prognostic and Clinicopathological Significance of SERTAD1 in Various Types of Cancer Risk: A Systematic Review and Retrospective Analysis

SERTAD/TRIP-Br genes are considered as a key nuclear transcriptional player in diverse mechanisms of cell including carcinogenesis. The Oncomine™-Online Platform was used for differential expression and biological insights. Kaplan-Meier survival estimated by KM-plotter/cBioPortal/PrognoScan with 95% CI. SERTAD1 was found significantly elevated levels in most of tumor samples. Kaplan-Meier Plotter results distinctly showed the SERTAD1 over-expression significantly reduced median overall-survival (OS) of patients in liver (n = 364/Logrank-test p = 0.0015), ovarian (n = 655/Logrank-test p = 0.00011) and gastric (n = 631/Logrank-test p = 0.1866). Increased level of SERTAD1 has a significantly higher survival rate in the initial time period, but after 100 months slightly reduced OS (n = 26/Logrank-test p = 0.34) and RFS in HER2 positive breast cancer patients. In meta-analysis, cancer patients with higher SERTAD1 mRNA fold resulted worse overall survival than those with lower SERTAD1 levels. Heterogeneity was observed in the fixed effect model analysis DFS [Tau2 = 0.0.073, Q (df = 4) = 15.536 (p = 0.004), I2 = 74.253], DSS [Tau2 = 1.015, Q (df = 2) = 33.214, (p = 0.000), I2 = 93.973], RFS [Tau2 = 0.492, Q (df = 7) = 71.133 (p = 0.000), I2 = 90.159] (Figure 5). OS [Tau2 = 0.480, Q (df = 17) = 222.344 (p = 0.000), I2 = 92.354]. Lastly, SERTAD1 involved in several signaling cascades through interaction and correlation with many candidate factors as well as miRNAs. This meta-analysis demonstrates a robust evidence of an association between higher or lower SERTAD1, alteration and without alteration of SERTAD1 in cancers in terms of survival and cancer invasiveness

Discovery of Natural Phenol Catechin as a Multitargeted Agent Against SARS-CoV-2 For the Plausible Therapy of COVID-19

The global pandemic crisis, COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has claimed the lives of millions of people across the world. Development and testing of anti-SARS-CoV-2 drugs or vaccines, are not turned to be realistic in the timeframe needed to combat this pandemic. Thus, rigorous efforts are still ongoing for the drug repurposing as a clinical treatment strategy to control COVID-19. Here we report a comprehensive computational approach to identify the multi-targeted drug molecules against the SARS-CoV-2 proteins, which are crucially involved in the viral-host interaction, replication of the virus inside the host, disease progression and transmission of coronavirus infection. Virtual screening of 72 FDA approved potential antiviral drugs against the target proteins: Spike (S) glycoprotein, human angiotensin-converting enzyme 2 (hACE2), 3-chymotrypsin-like cysteine protease (3CLpro), Cathepsin L, Nucleocapsid protein, RNA-dependent RNA polymerase (RdRp) and nonstructural protein 6 (NSP6) resulted in the selection of seven drugs which preferentially binds to the target proteins. Further, the molecular interactions determined by MD simulation, free energy landscape and the binding free energy estimation, using MM-PBSA revealed that among 72 drug molecules, catechin (flavan-3-ol) can effectively bind to 3CLpro, Cathepsin L, RBD of S protein, NSP-6, and Nucleocapsid protein. It is more conveniently involved in key molecular interactions, showing binding free energy (ΔGbind) in the range of -5.09 kcal/mol (Cathepsin L) to -26.09 kcal/mol (NSP6). At the binding pocket, catechin is majorly stabilized by the hydrophobic interactions, displays ΔEvdW values -7.59 to -37.39 kcal/mol. Thus, the structural insights of better binding affinity and favourable molecular interaction of catechin towards multiple target proteins, signifies that catechin can be potentially explored as a multitargeted agent in the rational design of effective therapies against COVID-19.<br /

Novel Triazole-Piperazine Hybrid Molecules Induce Apoptosis <i>via</i> Activation of the Mitochondrial Pathway and Exhibit Antitumor Efficacy in Osteosarcoma Xenograft Nude Mice Model

Mitochondria impart a crucial role in the regulation of programmed cell death and reactive oxygen species (ROS) generation, besides serving as a primary energy source. Mitochondria appeared as an important target for the therapy of cancer due to their significant contribution to cell survival and death. Here, we report the design and synthesis of a novel series of triazole-piperazine hybrids as potent anticancer agents. MCS-5 emerged as an excellent anticancer agent which showed better anticancer activity than the standard drug doxorubicin in <i>in vitro</i> and <i>in vivo</i> studies. MCS-5 displayed an IC₅₀ value of 1.92 μM and induced apoptosis in Cal72 (human osteosarcoma cell line) cells by targeting the mitochondrial pathway. This compound arrested the G2/M phase of the cell cycle and induced ROS production and mitochondrial potential collapse in Cal72 cells. MCS-5 displayed excellent anticancer activity in the Cal72 xenograft nude mice model, where it significantly reduced tumor progression, leading to enhanced life span in treated animals compared to control and doxorubicin treated animals without exerting noticeable toxicity. In addition, a 2DG optical probe guided study clearly evoked that MCS-5 remarkably reduced tumor metastasis in the Cal72 xenograft nude mice model. These results indicate that MCS-5 appeared as a novel chemical entity which is endowed with excellent <i>in vitro</i> as well as <i>in vivo</i> anticancer activity and may contribute significantly to the management of cancer in the future

Identification and In-silico Annotation of Functional Single Nucleotide Polymorphisms (SNPs) of the Candidate Gene Association with the Canine Transmissible Venereal Tumor Disease

ABSTRACT Canine transmissible venereal tumor (CTVT) is a histiocytic tumor of the dog that mainly affects the external genitalia, commonly found at tropical and subtropical zones. In the present investigation, we undertook this work mainly to perform a computational analysis of snSNP in the BTNL2 to identify the possible mutations and proposed the model structure of the mutant protein. Four deleterious mutations were identified in BTNL2 in 109 and 319 residual positions. Moreover, we constructed the homolgus structure of native and mutant proteins to predicate the stability. I-Mutant was used for routine analysis of protein stability and for the single site mutation analysis. It was found that mutation of L to S at residual position 109 and A to T at 319 residue position has shown maximum negative effect on the protein stability and considered for further analysis. The mutational effect on the protein function was analyzed by project HOPE. It was found that the wild-type residue is very conserved, but a few other residue types have been observed at this position too. Based on conservation scores this mutation is probably damaging to the protein. The present investigation was further used for molecular expect of the CTVT infection which might be useful in diagnosis and prevention of CTVT in canine