Discovery of VU6024578/BI02982816: An mGlu Positive Allosteric Modulator with Efficacy in Preclinical Antipsychotic and Cognition Models.

Herein, we report progress toward a metabotropic glutamate receptor subtype 1 (mGlu) positive allosteric modulator (PAM) clinical candidate and the discovery of VU6024578/BI02982816. From a weak high-throughput screening hit (VU0538160, EC > 10 μM, 71% Glu), optimization efforts improved functional potency over 185-fold to deliver the selective (inactive on mGlu) and CNS penetrant (rat K = 0.99, K = 0.

Mass-Rearing Conditions Do Not Always Reduce Genetic Diversity: The Case of the Mexican Fruit Fly, .

The application of the sterile insect technique (SIT) requires the adaptation of insects to mass-rearing conditions. It is generally accepted that this adaptation may include a reduction in genetic diversity and an associated loss of desirable characteristics for the effective performance of sterile insects in the field. Here, we compare the genetic diversity of two mass-reared strains of the Mexican fruit fly, and a wild (WIL) population collected near Tapachula, Mexico, using seven DNA microsatellites as molecular genetic markers.

Positive allosteric modulators (PAMs) of the group II metabotropic glutamate receptors: Design, synthesis, and evaluation as ex-vivo tool compounds.

This letter describes synthesis and evaluation of two series of dual mGlu/mGlu positive allosteric modulators with moderate mGlu potency and robust mGlu potency in thallium flux assays. These compounds were profiled their ability to modulate mGlu-mediated signaling in central neurons by co-application of a selective mGlu NAM to isolate mGlu-selective effects. Using acute mouse brain slices from the prefrontal cortex, potentiation of group II mGlu receptor agonist Ca signaling in PFC pyramidal cells with either the dual mGlu/mGlu PAM 16e or 23d demonstrated effects mediated selectively via mGlu.

Genetic and Ecological Relationships of (Diptera: Tephritidae) Populations in Southern Mexico.

Knowledge of the influence of evolutionary factors that promote either the differentiation or cohesion of pest insect populations is critical for the improvement of control strategies. Here, we explore the extent to which genetic differentiation occurs between populations of the Mexican fruit fly, , in association with four plant hosts (, , and ) in the Soconusco region of Chiapas (Mexico). Using variants from six enzymatic loci, we obtained measures of genetic diversity for three sample arrangements: (1) by sex per locality, (2) by locality and (3) by host.

Historical perspective on the synonymization of the four major pest species belonging to the Bactrocera dorsalis species complex (Diptera, Tephritidae).

An FAO/IAEA-sponsored coordinated research project on integrative taxonomy, involving close to 50 researchers from at least 20 countries, culminated in a significant breakthrough in the recognition that four major pest species, Bactrocera dorsalis, Bactrocera philippinensis, Bactrocera papayae and Bactrocera invadens, belong to the same biological species, Bactrocera dorsalis. The successful conclusion of this initiative is expected to significantly facilitate global agricultural trade, primarily through the lifting of quarantine restrictions that have long affected many countries, especially those in regions such as Asia and Africa that have large potential for fresh fruit and vegetable commodity exports. This work stems from two taxonomic studies: a revision in 1994 that significantly increased the number of described species in the Bactrocera dorsalis species complex; and the description in 2005 of Bactrocera invadens, then newly incursive in Africa.