Discovery and Optimization of Potent and Orally Available CTP Synthetase Inhibitors for Use in Treatment of Diseases Driven by Aberrant Immune Cell Proliferation.

Herein, we report the discovery of a first-in-class chemotype 2-(alkylsulfonamido)thiazol-4-yl)acetamides that act as pan-selective inhibitors of cytidine 5'-triphosphate synthetase (CTPS1/2), critical enzymes in the pyrimidine synthesis pathway. Weak inhibitors identified from a high-throughput screening of 240K compounds have been optimized to a potent, orally active agent, compound , which has shown significant pharmacological responses at 10 mg/kg dose BID in a well-established animal model of inflammation.

Cryopreservation of Pyramimonas mucifera.

Background: It is important to appreciate microalgal diversity, better understand their ecosystem functioning and therefore implement conservation measures. The National Biodiversity Act of South Africa has a marine and coastal component which promotes such investigations.

Objective: To develop a cryostorage method for the marine unicellular algal species Pyramimonas mucifera.

Responses of the Buds of Three South African Sweet Potato (Ipomoea batatas) Accessions to Different Cryoprotectants.

Background: Plant Vitrification Solution 2 (PVS2) was reported to be a successful cryoprotectant solution in regenerating plantlets from sweet potato shoot tips after cryostorage. However, this was not the case for the South African sweet potato accessions.

Objective: This study assessed the responses of buds of sweet potato to different concentrations of the components of PVS2 both individually and in combination.

The salt glands of Tamarix usneoides E. Mey. ex Bunge (South African Salt Cedar).

Tamarix usneoides is a halophyte tree endemic to south-western Africa. This species is known to excrete a range of ions from specialized glandular structures on its leaves. To understand the mechanisms involved in the transport, sequestration and excretion of ions by the glands, a study was performed on salt gland distribution and ultrastructure.

Cold pretreatment amplifies the responses of in vitro Eucalyptus grandis shoots to cryopreparative drying.

Background: Eucalyptus grandis is an important commercial forestry species in South Africa. Little is known about its response (which is both drought and cold sensitive) to cold exposure and subsequent drying.

Objective: The study was to investigate the responses of E.

Programmed cell death and necrosis during cryopreparative drying of in vitro Eucalyptus grandis axillary buds.

In preparation for cryopreservation, Eucalyptus grandis in vitro axillary buds were dried over silica gel. Pretreatment of the buds with 5 mg per L ABA resulted in partial resistance to water loss (0.76 to 0.

Effect of medium salt concentration on differentiation and maturation of somatic embryos of cassava (Manihot esculenta Crantz).

Culture of cassava somatic embryos on media with an altered macro- and micro-nutrient salt concentration affected embryo development and germination capability. In the tests, quarter-, half-, full- or double-strength Murashige and Skoog (MS) media were compared. The maximum number of somatic embryos differentiated from a proliferative nodular embryogenic callus (NEC) on either half- or full-strength MS medium, and the greatest numbers of cotyledonary stage embryos were formed on full-strength MS medium.

The sequence of the preparative procedures affects the success of cryostorage of cassava somatic embryos.

Cassava primary somatic embryos were prepared for cryostorage using both physical drying and cryoprotectant application stages. The effects of the sequence by which these preparative events were applied to the material was investigated. The drying of the somatic embryos before the application of the cryoprotectants resulted in a significantly higher viability after cryostorage than when the material was first exposed to the cryoprotectants and then dried.

In defence of aldehyde-osmium fixation and critical-point drying for characterization of seed-storage fungi by scanning electron microscopy.

Low-temperature scanning electron microscopy cannot be used as a general approach when resolution of definitive surface features is required for fungal characterization, because of the production of a pervading exudate by some of the species, strains or varieties. As the resolution of the light microscope is obviously limiting, scanning electron microscopy remains the best microscopical mode. Results are presented for four species within the Aspergillus flavus group which indicate that minimal (if any) distortion or collapse can be achieved with concomitant preservation of surface morphology, when particular precautions are taken during fixation and critical-point drying.