Lassa antiviral LHF-535 protects guinea pigs from lethal challenge.

LHF-535 is a small molecule antiviral currently in development for the treatment of Lassa fever, a zoonotic disease endemic in West Africa that generates significant morbidity and mortality. Current treatment options are inadequate, and there are no approved therapeutics or vaccines for Lassa fever. LHF-535 was evaluated in a lethal guinea pig model of Lassa pathogenesis, using once-daily administration of a fixed dose (50 mg/kg/day) initiating either 1 or 3 days after inoculation with a lethal dose of Lassa virus.

Safety and Pharmacokinetics of LHF-535, a Potential Treatment for Lassa Fever, in Healthy Adults.

LHF-535 is a small-molecule antiviral currently under development as a therapeutic option to treat Lassa fever and other viral hemorrhagic fevers of arenavirus origin. The human safety and pharmacokinetics of LHF-535 were evaluated in two phase 1 trials in healthy volunteers. The first study was a double-blind, single ascending dose trial that evaluated weight-based oral doses ranging from 0.

Disparate expression specificities coded by a shared Hox-C enhancer.

Can a single regulatory sequence be shared by two genes undergoing functional divergence? Here we describe a single promiscuous enhancer within the Antennapedia Complex, EO053, that directs aspects of the expression of two adjacent genes, (a ortholog) and (a divergent paralog), with disparate spatial and temporal expression patterns. We were unable to separate the -like and -like specificities within EO053, and we identify sequences affecting both expression patterns. Importantly, genomic deletion experiments demonstrate that EO053 cooperates with additional - and -specific enhancers to regulate the mRNA expression of both genes.

Evolutionary emergence of Hairless as a novel component of the Notch signaling pathway.

Suppressor of Hairless [Su(H)], the transcription factor at the end of the Notch pathway in , utilizes the Hairless protein to recruit two co-repressors, Groucho (Gro) and C-terminal Binding Protein (CtBP), indirectly. Hairless is present only in the Pancrustacea, raising the question of how Su(H) in other protostomes gains repressive function. We show that Su(H) from a wide array of arthropods, molluscs, and annelids includes motifs that directly bind Gro and CtBP; thus, direct co-repressor recruitment is ancestral in the protostomes.

Lateral inhibition: Two modes of non-autonomous negative autoregulation by neuralized.

Developmental patterning involves the progressive subdivision of tissue into different cell types by invoking different genetic programs. In particular, cell-cell signaling is a universally deployed means of specifying distinct cell fates in adjacent cells. For this mechanism to be effective, it is essential that an asymmetry be established in the signaling and responding capacities of the participating cells.