Seeking Rules Governing Mixed Molecular Crystallization.

Mixed crystals result when components of the structure are randomly replaced by analogues in ratios that can be varied continuously over certain ranges. Mixed crystals are useful because their properties can be adjusted by increments, simply by altering the ratio of components. Unfortunately, no clear rules exist to predict when two compounds are similar enough to form mixed crystals containing substantial amounts of both. To gain further understanding, we have used single-crystal X-ray diffraction, computational methods, and other tools to study mixed crystallizations within a selected set of structurally related compounds. This work has allowed us to begin to clarify the rules governing the phenomenon by showing that mixed crystals can have compositions and properties that vary continuously over wide ranges, even when the individual components do not normally crystallize in the same way. Moreover, close agreement of the results of our experiments and computational modeling demonstrates that reliable predictions about mixed crystallization can be made, despite the complexity of the phenomenon.

Restored immune cell functions upon clearance of senescence in the irradiated splenic environment.

Some studies show eliminating senescent cells rejuvenate aged mice and attenuate deleterious effects of chemotherapy. Nevertheless, it remains unclear whether senescence affects immune cell function. We provide evidence that exposure of mice to ionizing radiation (IR) promotes the senescent-associated secretory phenotype (SASP) and expression of p16INK4a in splenic cell populations. We observe splenic T cells exhibit a reduced proliferative response when cultured with allogenic cells in vitro and following viral infection in vivo. Using p16-3MR mice that allow elimination of p16INK4a -positive cells with exposure to ganciclovir, we show that impaired T-cell proliferation is partially reversed, mechanistically dependent on p16INK4a expression and the SASP. Moreover, we found macrophages isolated from irradiated spleens to have a reduced phagocytosis activity in vitro, a defect also restored by the elimination of p16INK4a expression. Our results provide molecular insight on how senescence-inducing IR promotes loss of immune cell fitness, which suggest senolytic drugs may improve immune cell function in aged and patients undergoing cancer treatment.