3 research outputs found
Ultrafast Photo-Induced Charge Transfer Unveiled by Two-Dimensional Electronic Spectroscopy
The interaction of exciton and charge transfer (CT) states plays a central
role in photo-induced CT processes in chemistry, biology and physics. In this
work, we use a combination of two-dimensional electronic spectroscopy (2D-ES),
pump-probe measurements and quantum chemistry to investigate the ultrafast CT
dynamics in a lutetium bisphthalocyanine dimer in different oxidation states.
It is found that in the anionic form, the combination of strong CT-exciton
interaction and electronic asymmetry induced by a counter-ion enables CT
between the two macrocycles of the complex on a 30 fs timescale. Following
optical excitation, a chain of electron and hole transfer steps gives rise to
characteristic cross-peak dynamics in the electronic 2D spectra, and we monitor
how the excited state charge density ultimately localizes on the macrocycle
closest to the counter-ion within 100 fs. A comparison with the dynamics in the
radical species further elucidates how CT states modulate the electronic
structure and tune fs-reaction dynamics. Our experiments demonstrate the unique
capability of 2D-ES in combination with other methods to decipher ultrafast CT
dynamics.Comment: 14 pages, 11 figures, and Supporting informatio
The Clinical and Genetic Spectrum of 82 Patients With RAG Deficiency Including a c.256_257delAA Founder Variant in Slavic Countries
Background: Variants in recombination-activating genes (RAG) are common genetic causes of autosomal recessive forms of combined immunodeficiencies (CID) ranging from severe combined immunodeficiency (SCID), Omenn syndrome (OS), leaky SCID, and CID with granulomas and/or autoimmunity (CID-G/AI), and even milder presentation with antibody deficiency. Objective: We aim to estimate the incidence, clinical presentation, genetic variability, and treatment outcome with geographic distribution of patients with the RAG defects in populations inhabiting South, West, and East Slavic countries. Methods: Demographic, clinical, and laboratory data were collected from RAG-deficient patients of Slavic origin via chart review, retrospectively. Recombinase activity was determined in vitro by flow cytometry-based assay. Results: Based on the clinical and immunologic phenotype, our cohort of 82 patients from 68 families represented a wide spectrum of RAG deficiencies, including SCID (n = 20), OS (n = 37), and LS/CID (n = 25) phenotypes. Sixty-seven (81.7%) patients carried RAG1 and 15 patients (18.3%) carried RAG2 biallelic variants. We estimate that the minimal annual incidence of RAG deficiency in Slavic countries varies between 1 in 180,000 and 1 in 300,000 live births, and it may vary secondary to health care disparities in these regions. In our cohort, 70% (n = 47) of patients with RAG1 variants carried p.K86Vfs*33 (c.256_257delAA) allele, either in homozygous (n = 18, 27%) or in compound heterozygous (n = 29, 43%) form. The majority (77%) of patients with homozygous RAG1 p.K86Vfs*33 variant originated from Vistula watershed area in Central and Eastern Poland, and compound heterozygote cases were distributed among all Slavic countries except Bulgaria. Clinical and immunological presentation of homozygous RAG1 p.K86Vfs*33 cases was highly diverse (SCID, OS, and AS/CID) suggestive of strong influence of additional genetic and/or epigenetic factors in shaping the final phenotype. Conclusion: We propose that RAG1 p.K86Vfs*33 is a founder variant originating from the Vistula watershed region in Poland, which may explain a high proportion of homozygous cases from Central and Eastern Poland and the presence of the variant in all Slavs. Our studies in this cohort of RAG1 founder variants confirm that clinical and immunological phenotypes only partially depend on the underlying genetic defect. As access to HSCT is improving among RAG-deficient patients in Eastern Europe, we anticipate improvements in survival