Novel 1,2-dihydroquinazolin-2-ones: Design,synthesis, and biological evaluation against Trypanosoma brucei

In 2014, a published report of the high-throughput screen of >42,000 kinase inhibitors from GlaxoSmithKline against T. brucei identified 797 potent and selective hits. From this rich data set, we selected NEU-0001101 (1) for hit-to-lead optimization. Through our preliminary compound synthesis and SAR studies, we have confirmed the previously reported activity of 1 in a T. brucei cell proliferation assay and have identified alternative groups to replace the pyridyl ring in 1. Pyrazole 24 achieves improvements in both potency and lipophilicity relative to 1, while also showing good in vitro metabolic stability. The SAR developed on 24 provides new directions for further optimization of this novel scaffold for anti-trypanosomal drug discovery.     

Syntactic processing depends on dorsal language tracts

Frontal and temporal language areas involved in syntactic processing are connected by several dorsal and ventral tracts, but the functional roles of the different tracts are not well understood. To identify which white matter tract(s) are important for syntactic processing, we examined the relationship between white matter damage and syntactic deficits in patients with primary progressive aphasia, using multimodal neuroimaging and neurolinguistic assessment. Diffusion tensor imaging showed that microstructural damage to left hemisphere dorsal tracts--the superior longitudinal fasciculus including its arcuate component--was strongly associated with deficits in comprehension and production of syntax. Damage to these dorsal tracts predicted syntactic deficits after gray matter atrophy was taken into account, and fMRI confirmed that these tracts connect regions modulated by syntactic processing. In contrast, damage to ventral tracts--the extreme capsule fiber system or the uncinate fasciculus--was not associated with syntactic deficits. Our findings show that syntactic processing depends primarily on dorsal language tracts.     

Physiological Alterations in Sphenostylis stenocarpa due to Telfairia mosaic virus

Russian Journal of Plant Physiology - Interaction between plant and virus induces significant alterations in the physiology of the plant affecting its performance. African yam bean (AYB) is a high...     

Artificial contrasting of the hip joint in children and adolescents: X-ray anatomic study

The diagnostic capacities of currently available radiation diagnostic techniques in imaging some anatomic structures of the hip joint (HJ) were determined on the basis of studies of 70 sectional sets of HJs in children and adolescents aged 0 to 13 years through X-ray and anatomic comparisons. Magnetic resonance imaging (MRI) is the method of choice in visualizing the cartilaginous and soft-tissue structures of HJ in children and adolescents. MR-arthrography extends the capacities of the technique in imaging the articular surfaces and intraarticular structures of the joint. Contrast enhancement of the HJ cavity during X-ray study and computed tomography may be an alternative to MRI as it makes it possible to well visualize the cartilaginous head of the femur, the cartilaginous borders of the cotyloid cavity, the limbus, etc. Double contrasting enhances the capacities of detailed imaging of the articular surfaces, intraarticular structures, capsules, and ligamentous apparatus of HJ. The studies performed have specified the time course of anatomic changes during HJ growth and defined the method of choice or an alternative procedure of radiation techniques in the diagnosis of these changes, which is of great importance for early detection of pathological changes and for choice of therapeutic and diagnostic policy.