Systematic profiling of staralog response to acquired drug resistant kinase gatekeeper mutations in targeted cancer therapy

Amino Acids - Kinase-targeted therapy has been widely used as a lifesaving strategy for cancer patients. However, many patients treated with targeted cancer drugs are clinically observed to rapidly...     

MAPK signaling regulates c‐MYC for melanoma cell adaptation to asparagine restriction

Amino acid restriction is among promising potential cancer treatment strategies. However, cancer cells employ a multitude of mechanisms to mount resistance to amino acid restriction, which impede the latter’s clinical development. Here we show that MAPK signaling activation in asparagine‐restricted melanoma cells impairs GSK3‐β‐mediated c‐MYC degradation. In turn, elevated c‐MYC supports ATF4 translational induction by enhancing the expression of the amino acid transporter SLC7A5, increasing the uptake of essential amino acids, and the subsequent maintenance of mTORC1 activity in asparagine‐restricted melanoma cells. Blocking the MAPK‐c‐MYC‐SLC7A5 signaling axis cooperates with asparagine restriction to effectively suppress melanoma cell proliferation. This work reveals a previously unknown axis of cancer cell adaptation to asparagine restriction and informs mechanisms that may be targeted for enhanced therapeutic efficacy of asparagine limiting strategies.     

Hybrid Anticancer Peptides DN1 and DN4 Exert Selective Cytotoxicity Against Hepatocellular Carcinoma Cells by Inducing Both Intrinsic and Extrinsic Apoptotic Pathways

International Journal of Peptide Research and Therapeutics - Bioactive peptides have emerged as promising therapeutic alternatives in pharmaceutical industry, especially to fight cancer. Here we...     

Transcriptomic analysis provides insights into candidate genes and molecular pathways involved in growth of Manila clam Ruditapes philippinarum

Functional & Integrative Genomics - Growth is one of the most important traits of aquaculture breeding programs. Understanding the mechanisms underlying growth differences between individuals...     

Curative Effects of Two New Endometrial Ablation Procedures Using Radiofrequency Thermocoagulation for the Treatment of Severe Abnormal Uterine Bleeding

Severe Abnormal Uterine Bleeding (SAUB) is a common gynecological disorder. The clinical characteristics include disordered menstrual cycle and massive bleeding that can cause anemia or secondary infection. Current treatment mainly relies on drug therapy or surgical removal of the uterus, each having its significant disadvantages. How to preserve the uterus, reduce the pain from surgery, and achieve better treatment effects have been well known but remaining as unresolved issues. This study aims at evaluating two types of radiofrequency (RF) thermocoagulation procedures for the treatment of SAUB: the RF-A procedure group included 25 SAUB patients ≥45 years of age treated for amenorrhea; the RF-B procedure group included 51 patients at <45 years of age treated for the control of excessive bleeding. Post-treatment ratings of menstrual satisfaction and pre-/post-treatment menstrual scores—pictorial blood loss assessment chart (PBAC)—and hemoglobin levels were collected; and the mean length of follow-up was 72 months. Also, 38 SAUB patients treated with standard drug regimens served as a control group. The results of the study showed that following RF treatment, the average long-term patient menstrual satisfaction was greater than 92 %. In both the RF groups, PBAC scores and hemoglobin levels were significantly improved from baseline (p < .05). Compared with the control group, PBAC scores and hemoglobin levels were also significantly better for the RF groups at 6–24-month post-operation. Patients experienced no hysterectomy in association with the RF procedures. In conclusion, this pilot study suggests that the novel RF procedures are both safe and effective in treating patients with SAUB. Further investigation is necessary to evaluate their application in broader clinical indication.     

Notes on Michael Schülke’s pselaphine collections from China. – Tyrini. II. Genus Megatyrus Hlavá? & Nomura (Coleoptera,Staphylinidae, Pselaphinae)

Two new species of the tyrine genus Megatyrus Hlaváč & Nomura, Megatyrus schuelkei Yin & Li, sp. n. (based on two males) and Megatyrus tengchongensis Yin & Li, sp. n. (based on one female), from Yunnan, Southwest China are described, illustrated and distinguished from allied species. The body size, form of maxillary palpi, male and female genital structures, and distributional patterns are used to separate the new species.     

Expression of a family 10 xylanase gene from Aspergillus usamii E001 in Pichia pastoris and characterization of the recombinant enzyme

A cDNA gene (Auxyn10A), which encodes a mesophilic family 10 xylanase from Aspergillus usamii E001 (abbreviated to AuXyn10A), was amplified and inserted into the XhoI and NotI sites of pPIC9K^M vector constructed from a parent pPIC9K. The recombinant expression vector, designated pPIC9K^M-Auxyn10A, was transformed into Pichia pastoris GS115. All P. pastoris transformants were spread on a MD plate, and then inoculated on geneticin G418-containing YPD plates for screening multiple copies of integration of the Auxyn10A. One transformant expressing the highest recombinant AuXyn10A (reAuXyn10A) activity of 368.6 U/ml, numbered as P. pastoris GSX10A4-14, was selected by flask expression test. SDS-PAGE assay demonstrated that the reAuXyn10A was extracellularly expressed with an apparent M.W. of 39.8 kDa. The purified reAuXyn10A displayed the maximum activity at pH 5.5 and 50 °C. It was highly stable at a broad pH range of 4.5–8.5, and at a temperature of 45 °C. Its activity was not significantly affected by EDTA and several metal ions except Mn²⁺, which caused a strong inhibition. The K _m and V _max, towards birchwood xylan at pH 5.5 and 50 °C, were 2.25 mg/ml and 6,267 U/mg, respectively. TLC analysis verified that the AuXyn10A is an endo-β-1,4-d-xylanase, which yielded a major product of xylotriose and a small amount of xylose, xylotetraose, and xylopentose from birchwood xylan, but no xylobiose.     

The production of phytolith‐occluded carbon in China's forests: implications to biogeochemical carbon sequestration

The persistent terrestrial carbon sink regulates long‐term climate change, but its size, location, and mechanisms remain uncertain. One of the most promising terrestrial biogeochemical carbon sequestration mechanisms is the occlusion of carbon within phytoliths, the silicified features that deposit within plant tissues. Using phytolith content–biogenic silica content transfer function obtained from our investigation, in combination with published silica content and aboveground net primary productivity (ANPP) data of leaf litter and herb layer in China's forests, we estimated the production of phytolith‐occluded carbon (PhytOC) in China's forests. The present annual phytolith carbon sink in China's forests is 1.7 ± 0.4 Tg CO₂ yr ^{? 1}, 30% of which is contributed by bamboo because the production flux of PhytOC through tree leaf litter for bamboo is 3–80 times higher than that of other forest types. As a result of national and international bamboo afforestation and reforestation, the potential of phytolith carbon sink for China's forests and world's bamboo can reach 6.8 ± 1.5 and 27.0 ± 6.1 Tg CO₂ yr^?1, respectively. Forest management practices such as bamboo afforestation and reforestation may significantly enhance the long‐term terrestrial carbon sink and contribute to mitigation of global climate warming.