BackgroundSubthreshold depression has a considerable impact on individuals’ subjective well-being and psychosocial functioning and is a predictor of major depressive disorder. Internet-based cognitive behavioural treatments (iCBTs) have been used to reduce the symptoms of subthreshold depression. This meta-analysis aims to systematically review evidence indicating the efficacy of iCBT programs on the improvement of depressive symptoms in this population.MethodsArticles published from January 2005 to July 2016 were searched in the following databases: Medline, PubMed, Web of Science, ScienceDirect, PsycArticles and the Cochrane Central Register of Controlled Trials. Only randomized controlled trials comparing the efficacy of iCBT programs with control groups for participants with subthreshold depression were selected. Both quantitative and qualitative analyses were conducted to examine the efficacy of iCBT interventions.ResultsTenarticles from 8 randomized controlled trials were identified in this systematic review. The results suggested that iCBT programs had a superior efficacy compared to results from a non-active control group at the post-intervention stage (SMD = − 0.28, CI [− 0.42, − 0.14]; I2 = 49 %). However, evidence on the long-term efficacy of iCBT programs is still insufficient and needs further exploration.ConclusionThere has been substantial evidence that iCBT intervention has a superior short-term efficacy compared to the results of control groups, while its long-term efficacy of iCBT for subthreshold depressive symptoms is inconclusive and must be examined in further research.Trial registrationThe protocol of this review has been registered with the International Prospective Register of Systematic Reviews (PROSPERO), Protocol No. CRD42015023390.

The 2014–15 Ebola virus (EBOV) outbreak in West Africa highlighted the urgent need for specific therapeutic interventions for infected patients. The human-mouse chimeric monoclonal antibody (mAb) cocktail ZMapp™, previously shown to be efficacious in EBOV (variant Kikwit) lethally infected nonhuman primates (NHPs) when administration was initiated up to 5 days, was used in some patients during the outbreak. Here we show that a two-antibody cocktail, MIL77E, is fully protective in NHPs when administered at 50 mg/kg 3 days after challenge with a lethal dose of EBOV, variant Makona, the virus responsible for the ongoing 2014–15 outbreak, while a similar formulation of ZMapp™ protected 2 of 3 NHPs. The chimeric MIL77E mAb cocktail is produced in engineered CHO cells and is based on mAbs c13C6 and c2G4 from ZMapp™. The use of only 2 antibodies in MIL77E opens the door to a pan-ebolavirus cocktail.

Late blight caused by the oomycete fungus Phytophthora infestans (Pi) is the most serious obstacle to potato (Solanum tuberosum) production in the world. A super race isolate, CN152, which was identified from Sichuan Province, China, could overcome nearly all known late blight resistance genes and caused serious damage in China. The potato genotype SD20 was verified to be highly resistant to CN152; however, the molecular regulation network underlying late blight resistance pathway remains unclear in SD20. Here, we performed a time-course experiment to systematically profile the late blight resistance response genes using RNA-sequencing in SD20. We identified 3354 differentially expressed genes (DEGs), which mainly encoded transcription factors and protein kinases, and also included four NBS-LRR genes. The late blight responsive genes showed time-point-specific induction/repression. Multi-signaling pathways of salicylic acid, jasmonic acid, and ethylene signaling pathways involved in resistance and defense against Pi in SD20. Gene Ontology and KEGG analyses indicated that the DEGs were significantly enriched in metabolic process, protein serine/threonine kinase activity, and biosynthesis of secondary metabolites. Forty-three DEGs were involved in immune response, of which 19 were enriched in hypersensitive response reaction, which could play an important role in broad-spectrum resistance to Pi infection. Experimental verification confirmed the induced expression of the responsive genes in the late blight resistance signaling pathway, such as WRKY, ERF, MAPK, and NBS-LRR family genes. Our results provided valuable information for understanding late blight resistance mechanism of potato.

Glycoprotein Ib␣ (GP Ib␣), the ligand binding subunit of the platelet glycoprotein Ib-IX-V complex, is sulfated on three tyrosine residues (Tyr-276, Tyr-278, and Tyr-279). This posttranslational modification is known to be critical for von Willebrand factor (vWF) binding; yet it remains unclear whether it provides a specific structure or merely contributes negative charges. To investigate this issue, we constructed cell lines expressing GP Ib␣ polypeptides with the three tyrosine residues converted to either Glu or Phe and studied the ability of these mutants to bind vWF in the presence of modulators or shear stress. The mutants were expressed normally on the cell surface as GP Ib-IX complexes, with the conformation of the ligand-binding domain preserved, as judged by the binding of conformation-sensitive monoclonal antibodies. In contrast to their normal expression, both mutants were functionally abnormal. Cells expressing the Phe mutant failed to bind vWF in the presence of either ristocetin or botrocetin. These cells adhered to and rolled on immobilized vWF only when their surface receptor density was increased to twice the level that supported adhesion of cells expressing the wild-type receptor and even then only 20% as many rolled and rolled significantly faster than wild-type cells. Cells expressing the Glu mutant, on the other hand, were normal with respect to ristocetin-induced vWF binding and adhesion to immobilized vWF but were markedly defective in botrocetin-induced vWF binding. These results indicate that GP Ib␣ tyrosine sulfation influences the interaction of this polypeptide with vWF primarily by contributing negative charges under physiological conditions and when the interaction is induced by ristocetin but contributes a specific structure to the botrocetin-induced interaction.The platelet receptor for von Willebrand factor (vWF), 1 the glycoprotein (GP) Ib-IX-V complex, is composed of four polypeptide subunits (GP Ib␣, GP Ib␤, GP IX, and GP V (1, 2)) encoded by four separate genes (3-6). GP Ib␣ is the largest subunit within the complex and so far the only subunit implicated in ligand binding, being capable of binding vWF (7), ␣-thrombin (7), P-selectin (8), and leukocyte Mac-1 (9). The ligand-binding region resides within ϳ300 amino acids at the GP Ib␣ N terminus and is held high above the cell membrane by a stiff, highly O-glycosylated mucin-like domain ( Fig. 1) (3, 10). The ligandbinding region can be divided into three distinct structural subdomains that are all implicated in vWF binding (7): seven tandem leucine-rich repeats, disulfide loops flanking the leucine-rich repeats, and a highly negatively charged sequence spanning residues Asp-269 to Asp-287 (3, 10). Three tyrosine residues (Tyr-276, Tyr-278, and Tyr-279) are embedded in this negatively charged sequence (2, 7) and each is fully sulfated, a modification critical for the binding of vWF and ␣-thrombin (11-13).Tyrosine sulfation is a widespread posttranslational modification of proteins (14 -20), but few studies have addressed its e...