Anti-PD-1 elicits regression of undifferentiated pleomorphic sarcomas with UV-mutation signatures

Undifferentiated pleomorphic sarcoma (UPS), an aggressive soft-tissue sarcoma of adults, has been characterized by low tumor mutational burden (TMB) and high copy number alterations. Clinical trials of programmed death-1 (PD-1) blockade in UPS have reported widely varying efficacy. We describe two patients with recurrent scalp UPS that experienced clinical benefit from PD-1 blockade. These tumors had high TMB with a UV-induced mutational pattern. Analysis of additional head and neck UPS cases identified five out of seven tumors with high TMB and an ultraviolet (UV) mutational signature. Head and neck UPS tumors also had increased programmed death-ligand 1 (PD-L1) expression and CD8+ T cell infiltration as compared with UPS tumors arising from other sites. In summary, we found that UPS tumors of the head and neck, but not elsewhere, have a PD-L1+, T-cell-inflamed tumor microenvironment and high TMB, suggesting that these tumors represent a distinct genetic subgroup of UPS for which immune checkpoint inhibitor therapy might be effective.

Epitope spreading toward wild-type melanocyte-lineage antigens rescues suboptimal immune checkpoint blockade responses

Although immune checkpoint inhibitors (ICIs), such as anti–programmed cell death protein–1 (PD-1), can deliver durable antitumor effects, most patients with cancer fail to respond. Recent studies suggest that ICI efficacy correlates with a higher load of tumor-specific neoantigens and development of vitiligo in patients with melanoma. Here, we report that patients with low melanoma neoantigen burdens who responded to ICI had tumors with higher expression of pigmentation-related genes. Moreover, expansion of peripheral blood CD8+ T cell populations specific for melanocyte antigens was observed only in patients who responded to anti–PD-1 therapy, suggesting that ICI can promote breakdown of tolerance toward tumor-lineage self-antigens. In a mouse model of poorly immunogenic melanomas, spreading of epitope recognition toward wild-type melanocyte antigens was associated with markedly improved anti–PD-1 efficacy in two independent approaches: introduction of neoantigens by ultraviolet (UV) B radiation mutagenesis or the therapeutic combination of ablative fractional photothermolysis plus imiquimod. Complete responses against UV mutation-bearing tumors after anti–PD-1 resulted in protection from subsequent engraftment of melanomas lacking any shared neoantigens, as well as pancreatic adenocarcinomas forcibly overexpressing melanocyte-lineage antigens. Our data demonstrate that somatic mutations are sufficient to provoke strong antitumor responses after checkpoint blockade, but long-term responses are not restricted to these putative neoantigens. Epitope spreading toward T cell recognition of wild-type tumor-lineage self-antigens represents a common pathway for successful response to ICI, which can be evoked in neoantigen-deficient tumors by combination therapy with ablative fractional photothermolysis and imiquimod.

UV Mutagenesis as a Strategy to Enhance Growth and Lipid Productivity of Chlorella sp. 042

Microalgae appeared to be an alternative feedstock for renewable biodiesel production due to their capability to accumulate considerable amounts of lipids. In this study, mutagenesis using UVC light with different periods was applied to Chlorella sp. 042 to produce a microalgae strain with high lipid productivity of 45, 60, and 75 min. The Nile red fluorescence method was conducted to select a Chlorella sp. mutant with high neutral lipid and generated one mutant from every UV mutation period, M45-06, M60-02, and M75-21. All of the mutants have higher growth rates than the wild type. Chlorella sp. 042 M60-02 achieved the highest lipid productivity, with 34 mg L-1 day-1. Furthermore, as other major biochemical components, carbohydrate and protein contents were determined. Our results showed that all the mutants enhance their carbohydrate and protein contents compared to the wild type. However, mutations for more than 60 min do not intensely change the protein content of mutant microalgae. Gas chromatography-mass spectrophotometry analysis revealed that M60-02 mutant has similar FAME profiles with the wild type, which contain palmitic acid (C16:0), stearic acid (C 18:0), oleic acid (C18:1), and linoleic acid (C18:2). These results demonstrate that the UV mutation of Chlorella sp. 042 for 60 min is suitable as a source of biodiesel production.

Intragenomic variability and extended sequence patterns in the mutational signature of ultraviolet light

ABSTRACTMutational signatures can reveal properties of underlying mutational processes and are important when assessing signals of selection in cancer. Here we describe the sequence characteristics of mutations induced by ultraviolet (UV) light, a major mutagen in several human cancers, in terms of extended (longer than trinucleotide) patterns as well as variability of the signature across chromatin states. Promoter regions display a distinct UV signature with reduced TCG>TTG transitions, and genome-wide mapping of UVB-induced DNA photoproducts (pyrimidine dimers) showed that this may be explained by decreased damage formation at hypomethylated promoter CpG sites. Further, an extended signature model encompassing additional information from longer patterns improves modeling of UV mutation rate, which may enhance discrimination between drivers and passenger events. Our study presents a refined picture of the UV signature and underscores that the characteristics of a single mutational process may vary across the genome.

Evaluation of fermentation potential of wild and UV-mutated yeasts screened from traditional murcha

Murcha (an amylolytic starter) from different parts of Eastern Nepal were screened for fermentative yeasts. The most potential one was UV-mutated (8W lamp at λ = 254 nm and an intensity of 44.21 Wm-2 for 5-50 s) to study the effect of mutation on growth and fermentation properties. Respiratory-deficient mutants (RDMs) that resulted from the mutation were identified by triphenyl tetrazolium chloride (TTC) overlay technique and replica-plated for further isolation. Cell growth, substrate utilization, and ethanol yield of the mutants were compared with normal cells by carrying out fermentation in high-test cane molasses broth of 30 °Bx. An exhaustive screening of the samples resulted in only two murcha viz., from Laxmimarga (LM) and Udayapur (UD), having the desirable fermentation properties. UV-mutation study of UD and LM yeasts (both identified as strains of Saccharomyces cerevisiae) showed 8-12% survival and ~ 22% RDMs yield of the survived cells. Out of the 8 randomly selected RDMs, only UDm4 (colony No. 4 from UD) showed fermentation properties worth further investigation. Comparison of UD, LM and UDm4 by fermenting molasses (high test) broth of 30°Bx showed the least growth of UDm4 but the highest alcohol yield (9% and 16% more compared to UD and LM, respectively). The present finding indicates that it is possible to improve fermentation properties of feral yeasts from murcha by relatively simple UV-mutation approach. Finding the right mutant (the selective screening part), however, may involve considerable time and effort.

KAJIAN KEMAMPUAN MUTAN BAKTERI Pseudomonas sp MENDEGRADASI BENZENA DALAM MIKROKOSMOS AIR TANAH

Mutation induction with UV can increase microbe capacity in do metabolite includes in mendegradasi polutan’s material. mutagenesis UV’s result from isolat wildtipe Pseudomonas sp (ICBB33p) gotten two mutants which is ICBB33 4 and ICBB33 18. To the effect this research is done to test isolat’s ability that mutant bacteria is deep degradation benzene by compares with isolat parental or wildtipe. Mutant application is done on ground water microcosm that contains to concentrate benzene 125 ppm results benzene concentration decreases 17,82 ppm (86%) for ICBB33’S mutant 4 and 13,37 ppm (89%) for ICBB33’S mutant cell 18 , meanwhile parental’s cell stills to remain benzene concentration as big as 35,8 ppm (70%) of startup concentration 125 ppm. Decrease concentrates benzene, followed by population amount step-up bacteria cell and CO’s amount step-up 2 one that resultant.Key word: biodegradasi’s capacity step-up, UV- mutation, benzene, mutant.

Screening for the Strain Galactomyces sp. Producing Bioflocculant by UV Mutagenesis

Strain Galactomyces sp. M-2 from activated sludge was used as parent strain and then UV mutation breeding was performed. Finally we obtained a quality strain UVM8 suitable for the production of bioflocculant which flocculating activity is 92.8%. It showed there is excellent stable flocculating activity for stain UVM8 in the flocculating stability experiment. Further studies showed the best flocculation effect was obtained when C/N ration is 20:2 and pH is 8 in the initial culture medium.