Distribution of mutation rates challenges evolutionary predictability.

Natural selection is commonly assumed to act on extensive standing genetic variation. Yet, accumulating evidence highlights the role of mutational processes creating this genetic variation: to become evolutionarily successful, adaptive mutants must not only reach fixation, but also emerge in the first place, i.e.

Cancer immune therapy with PD-1-dependent CD137 co-stimulation provides localized tumour killing without systemic toxicity.

Expression of the cell surface receptor CD137 has been shown to enhance anti-cancer T cell function via engagement with its natural ligand 4-1BBL. CD137 ligation with engineered ligands has emerged as a cancer immunotherapy strategy, yet clinical development of agonists has been hindered by either toxicity or limited efficacy. Here we show that a CD137/PD-1 bispecific antibody, IBI319, is able to overcome these limitations by coupling CD137 activation to PD-1-crosslinking.

IBI112, a selective anti-IL23p19 monoclonal antibody, displays high efficacy in IL-23-induced psoriasiform dermatitis.

Psoriasis is a highly prevalent inflammatory skin disease. Plaque psoriasis is the most common type of psoriasis, and the interleukin (IL)-23/IL-17 axis plays a key role in disease progression. In this article, we describe IBI112, a highly potent anti-IL-23 monoclonal antibody under clinical development, which efficiently neutralizes IL23p19, a subunit of IL-23, to abrogate IL-23 binding to its receptor and block downstream signal transducer and activator of transcription 3 (STAT3) phosphorylation.

Comparison between best-response dynamics and replicator dynamics in a social-ecological model of lake eutrophication.

Social-ecological models are often used to investigate the mutual interactions between an ecological system and human behaviour at a collective level. The social system is widely represented either by the replicator dynamics or by the best-response dynamics. We investigate the consequences of choosing one or the other with the example of a social-ecological model for eutrophication in shallow lakes, where the anthropogenic discharge of pollutants into the water is determined by a behavioural model using the replicator or a best-response dynamics.

Separate seasons of infection and reproduction can lead to multi-year population cycles.

Many host-pathogen systems are characterized by a temporal order of disease transmission and host reproduction. For example, this can be due to pathogens infecting certain life cycle stages of insect hosts; transmission occurring during the aggregation of migratory birds; or plant diseases spreading between planting seasons. We develop a simple discrete-time epidemic model with density-dependent transmission and disease affecting host fecundity and survival.

An Immunosuppressive Tick Salivary Gland Protein DsCystatin Interferes With Toll-Like Receptor Signaling by Downregulating TRAF6.

Ticks, blood-feeding arthropods, and secrete immunosuppressive molecules that inhibit host immune responses and provide survival advantages to pathogens. In this study, we characterized the immunosuppressive function of a novel tick salivary protein, DsCystatin, from of China. DsCystatin directly interacted with human Cathepsins L and B and inhibited their enzymatic activities.

Functional characterization of two defensins, HlDFS1 and HlDFS2, from the hard tick Haemaphysalis longicornis.

Background: Ticks are second to mosquitoes as vectors of human arthropod-borne diseases. Ticks rely heavily on antimicrobial peptides (AMPs) to defend against microbes and defensins are major components of innate immunity in ticks.

Results: Two novel defensin genes, named HlDFS1 and HlDFS2, were identified from a cDNA library of the hard tick Haemaphysalis longicornis collected in southeast China.

DEAD-Box Helicase DDX25 Is a Negative Regulator of Type I Interferon Pathway and Facilitates RNA Virus Infection.

Dengue is a mosquito-borne viral disease that rapidly spread in tropic and subtropic area in recent years. DEAD (Glu-Asp-Ala-Glu)-box RNA helicases have been reported to play important roles in viral infection, either as cytosolic sensors of viral nucleic acids or as essential host factors for the replication of different viruses. In this study, we reported that DDX25, a DEAD-box RNA helicase, plays a proviral role in DENV infection.

The evolution of parasitic and mutualistic plant-virus symbioses through transmission-virulence trade-offs.

Virus-plant interactions range from parasitism to mutualism. Viruses have been shown to increase fecundity of infected plants in comparison with uninfected plants under certain environmental conditions. Increased fecundity of infected plants may benefit both the plant and the virus as seed transmission is one of the main virus transmission pathways, in addition to vector transmission.

Glycosphingolipid GM3 is Indispensable for Dengue Virus Genome Replication.

Dengue virus (DENV) causes the most prevalent arthropod-borne viral disease of humans worldwide. Glycosphingolipids (GSLs) are involved in virus infection by regulating various steps of viral-host interaction. However, the distinct role of GSLs during DENV infection remains unclear.

Unexpected talaroenamine derivatives and an undescribed polyester from the fungus Talaromyces stipitatus ATCC10500.

Chemical investigation of the fungus Talaromyces stipitatus ATCC 10500, whose genome has been sequenced, led to the isolation of four undescribed talaroenamines B-E along with the known talaroenamine A. Their structures were elucidated on the basis of spectroscopic studies including mass spectrometry, extensive 2D NMR and electronic circular dichroism (ECD). Interestingly, talaroenamine A had previously been isolated from the strain of T.