Diverse organic-mineral associations in Jezero crater, Mars.

The presence and distribution of preserved organic matter on the surface of Mars can provide key information about the Martian carbon cycle and the potential of the planet to host life throughout its history. Several types of organic molecules have been previously detected in Martian meteorites1 and at Gale crater, Mars2-4. Evaluating the diversity and detectability of organic matter elsewhere on Mars is important for understanding the extent and diversity of Martian surface processes and the potential availability of carbon sources1,5,6. Here we report the detection of Raman and fluorescence spectra consistent with several species of aromatic organic molecules in the Máaz and Séítah formations within the Crater Floor sequences of Jezero crater, Mars. We report specific fluorescence-mineral associations consistent with many classes of organic molecules occurring in different spatial patterns within these compositionally distinct formations, potentially indicating different fates of carbon across environments. Our findings suggest there may be a diversity of aromatic molecules prevalent on the Martian surface, and these materials persist despite exposure to surface conditions. These potential organic molecules are largely found within minerals linked to aqueous processes, indicating that these processes may have had a key role in organic synthesis, transport or preservation.

Blastic plasmacytoid dendritic cell neoplasm in a young patient.

Blastic plasmacytoid dendritic cell neoplasm is a rare hematologic neoplasm originating from plasmacytoid dendritic cell precursors that has an aggressive disease course with typically poor prognosis. Herein, we report a man in his early twenties who presented with rapid onset of violaceous nodules and purpuric papules and macules that began on his chest before spreading to his arms, back, face, scalp, and legs. He also exhibited systemic symptoms including weight loss and night sweats. He was diagnosed with blastic plasmacytoid dendritic cell neoplasm and began treatment with aggressive multidrug therapy. Thus far his treatment has resulted in complete resolution of his cutaneous manifestations.

Repeated polyploidization of Gossypium genomes and the evolution of spinnable cotton fibres.

Polyploidy often confers emergent properties, such as the higher fibre productivity and quality of tetraploid cottons than diploid cottons bred for the same environments. Here we show that an abrupt five- to sixfold ploidy increase approximately 60 million years (Myr) ago, and allopolyploidy reuniting divergent Gossypium genomes approximately 1-2 Myr ago, conferred about 30-36-fold duplication of ancestral angiosperm (flowering plant) genes in elite cottons (Gossypium hirsutum and Gossypium barbadense), genetic complexity equalled only by Brassica among sequenced angiosperms. Nascent fibre evolution, before allopolyploidy, is elucidated by comparison of spinnable-fibred Gossypium herbaceum A and non-spinnable Gossypium longicalyx F genomes to one another and the outgroup D genome of non-spinnable Gossypium raimondii. The sequence of a G. hirsutum A(t)D(t) (in which 't' indicates tetraploid) cultivar reveals many non-reciprocal DNA exchanges between subgenomes that may have contributed to phenotypic innovation and/or other emergent properties such as ecological adaptation by polyploids. Most DNA-level novelty in G. hirsutum recombines alleles from the D-genome progenitor native to its New World habitat and the Old World A-genome progenitor in which spinnable fibre evolved. Coordinated expression changes in proximal groups of functionally distinct genes, including a nuclear mitochondrial DNA block, may account for clusters of cotton-fibre quantitative trait loci affecting diverse traits. Opportunities abound for dissecting emergent properties of other polyploids, particularly angiosperms, by comparison to diploid progenitors and outgroups.

MYC amplification in angiosarcomas arising in the setting of chronic lymphedema of morbid obesity.

BACKGROUND: Angiosarcoma is a malignancy of vascular endothelial cells which may arise secondarily as a complication of lymphedema, including chronic lymphedema of morbid obesity. Amplifications in MYC are frequently present in secondary angiosarcoma (arising in irradiated sites and chronic lymphedema) and less frequently in primary cutaneous angiosarcoma. OBJECTIVE: To describe the presence of MYC amplifications in two cases of cutaneous angiosarcoma secondary to chronic lymphedema of morbid obesity. METHODS: This study is a case series of two patients with cutaneous angiosarcoma. Clinical data was retrieved from the medical records. Histopathological analysis of the biopsy specimens was performed, including immunohistochemistry, along with fluorescence in situ hybridization. RESULTS: Angiosarcoma arose in the setting of massive chronic lymphedema complicating morbid obesity without other predisposing risk factors. Both cases exhibited epithelioid cell morphology and high-level MYC amplification. CONCLUSION: We report MYC amplification in two cases of angiosarcoma arising in massive chronic lymphedema of morbid obesity.

The role of imaging in the prevention of wrong-site surgery in dermatology.

Wrong-site surgery in dermatology often results from inaccurate identification of a skin cancer biopsy site. Factors making biopsy-site identification difficult include background actinic damage, delays from biopsy to surgery, and lack of photographic documentation. While other methods exist for biopsy-site identification, photography is the most helpful tool available. Although modern technology has made high-quality photographic equipment ubiquitous and easy to use, photography for biopsy-site identification continues to be underutilized. The authors recommend that photographic documentation of biopsy sites become the standard of care.

The half-life of DNA in bone: measuring decay kinetics in 158 dated fossils.

Claims of extreme survival of DNA have emphasized the need for reliable models of DNA degradation through time. By analysing mitochondrial DNA (mtDNA) from 158 radiocarbon-dated bones of the extinct New Zealand moa, we confirm empirically a long-hypothesized exponential decay relationship. The average DNA half-life within this geographically constrained fossil assemblage was estimated to be 521 years for a 242 bp mtDNA sequence, corresponding to a per nucleotide fragmentation rate (k) of 5.50 × 10(-6) per year. With an effective burial temperature of 13.1°C, the rate is almost 400 times slower than predicted from published kinetic data of in vitro DNA depurination at pH 5. Although best described by an exponential model (R(2) = 0.39), considerable sample-to-sample variance in DNA preservation could not be accounted for by geologic age. This variation likely derives from differences in taphonomy and bone diagenesis, which have confounded previous, less spatially constrained attempts to study DNA decay kinetics. Lastly, by calculating DNA fragmentation rates on Illumina HiSeq data, we show that nuclear DNA has degraded at least twice as fast as mtDNA. These results provide a baseline for predicting long-term DNA survival in bone.

Development and mapping of SNP assays in allotetraploid cotton.

A narrow germplasm base and a complex allotetraploid genome have made the discovery of single nucleotide polymorphism (SNP) markers difficult in cotton (Gossypium hirsutum). To generate sequence for SNP discovery, we conducted a genome reduction experiment (EcoRI, BafI double digest, followed by adapter ligation, biotin-streptavidin purification, and agarose gel separation) on two accessions of G. hirsutum and two accessions of G. barbadense. From the genome reduction experiment, a total of 2.04 million genomic sequence reads were assembled into contigs with an N(50) of 508 bp and analyzed for SNPs. A previously generated assembly of expressed sequence tags (ESTs) provided an additional source for SNP discovery. Using highly conservative parameters (minimum coverage of 8× at each SNP and 20% minor allele frequency), a total of 11,834 and 1,679 non-genic SNPs were identified between accessions of G. hirsutum and G. barbadense in genome reduction assemblies, respectively. An additional 4,327 genic SNPs were also identified between accessions of G. hirsutum in the EST assembly. KBioscience KASPar assays were designed for a portion of the intra-specific G. hirsutum SNPs. From 704 non-genic and 348 genic markers developed, a total of 367 (267 non-genic, 100 genic) mapped in a segregating F(2) population (Acala Maxxa × TX2094) using the Fluidigm EP1 system. A G. hirsutum genetic linkage map of 1,688 cM was constructed based entirely on these new SNP markers. Of the genic-based SNPs, we were able to identify within which genome ('A' or 'D') each SNP resided using diploid species sequence data. Genetic maps generated by these newly identified markers are being used to locate quantitative, economically important regions within the cotton genome.

Genetic Analysis of the Transition from Wild to Domesticated Cotton (Gossypium hirsutum L.).

The evolution and domestication of cotton is of great interest from both economic and evolutionary standpoints. Although many genetic and genomic resources have been generated for cotton, the genetic underpinnings of the transition from wild to domesticated cotton remain poorly known. Here we generated an intraspecific QTL mapping population specifically targeting domesticated cotton phenotypes. We used 466 F2 individuals derived from an intraspecific cross between the wild Gossypium hirsutum var. yucatanense (TX2094) and the elite cultivar G. hirsutum cv. Acala Maxxa, in two environments, to identify 120 QTL associated with phenotypic changes under domestication. While the number of QTL recovered in each subpopulation was similar, only 22 QTL were considered coincident (i.e., shared) between the two locations, eight of which shared peak markers. Although approximately half of QTL were located in the A-subgenome, many key fiber QTL were detected in the D-subgenome, which was derived from a species with unspinnable fiber. We found that many QTL are environment-specific, with few shared between the two environments, indicating that QTL associated with G. hirsutum domestication are genomically clustered but environmentally labile. Possible candidate genes were recovered and are discussed in the context of the phenotype. We conclude that the evolutionary forces that shape intraspecific divergence and domestication in cotton are complex, and that phenotypic transformations likely involved multiple interacting and environmentally responsive factors.

Blocking Monocytic Myeloid-Derived Suppressor Cell Function via Anti-DC-HIL/GPNMB Antibody Restores the In Vitro Integrity of T Cells from Cancer Patients.

PURPOSE: Blocking the function of myeloid-derived suppressor cells (MDSC) is an attractive approach for cancer immunotherapy. Having shown DC-HIL/GPNMB to be the T-cell-inhibitory receptor mediating the suppressor function of MDSCs, we evaluated the potential of anti-DC-HIL mAb as an MDSC-targeting cancer treatment. EXPERIMENTAL DESIGN: Patients with metastatic cancer (n = 198) were analyzed by flow cytometry for DC-HIL or PDL1 expression on blood CD14+HLA-DRno/lo MDSCs. Their suppressor function was assessed by in vitro coculture with autologous T cells, and the ability of anti-DC-HIL or anti-PDL1 mAb to reverse such function was determined. Tumor expression of these receptors was examined histologically, and the antitumor activity of the mAb was evaluated by attenuated growth of colon cancers in mice. RESULTS: Patients with metastatic cancer had high blood levels of DC-HIL+ MDSCs compared with healthy controls. Anti-DC-HIL mAb reversed the in vitro function in ∼80% of cancer patients tested, particularly for colon cancer. Despite very low expression on blood MDSCs, anti-PDL1 mAb was as effective as anti-DC-HIL mAb in reversing MDSC function, a paradoxical phenomenon we found to be due to upregulated expression of PDL1 by T-cell-derived IFNγ in cocultures. DC-HIL is not expressed by colorectal cancer cells but by CD14+ cells infiltrating the tumor. Finally, anti-DC-HIL mAb attenuated growth of preestablished colon tumors by reducing MDSCs and increasing IFNγ-secreting T cells in the tumor microenvironment, with similar outcomes to anti-PDL1 mAb. CONCLUSIONS: Blocking DC-HIL function is a potentially useful treatment for at least colorectal cancer with high blood levels of DC-HIL+ MDSCs.See related commentary by Colombo, p. 453.

Vulvar Asymmetry Due to Silicone Migration and Granulomatous Immune Response Following Injection for Buttock Augmentation.

A 34-year-old woman was referred to the authors' dermatology clinic for evaluation of right labial swelling and dyspareunia. Her symptoms began after receiving a liquid silicone injection into the buttocks at a cosmetic plastic surgery clinic that was operating illegally by an unlicensed provider. A single prior debulking surgery had produced only temporary relief of symptoms, and the swelling returned. Work-up including magnetic resonance imaging and skin biopsy revealed migration of the injected silicone from her buttock to the subcutaneous tissue of the right labia majora, with an associated granulomatous immune response to the silicone. To the authors' knowledge, the extent of contiguous soft tissue involvement shown in this case has not yet been reported in the medical literature, nor has the finding of migration from the buttocks to the vulvar tissues to produce such dramatic asymmetry. Treatment with intralesional steroids and minocycline was initiated with improvement noted at one-month follow-up. Large volume and adulterated silicone injections are associated with a host of complications, including silicone migration and granuloma formation. No consensus for treatment exists, but attempted therapies have included surgery, local steroid injections, systemic steroids, tetracycline antibiotics, and other immune modulators. Treatment must be tailored to the individual case, considering the patient's preferences and medical history.

Development of a 63K SNP Array for Cotton and High-Density Mapping of Intraspecific and Interspecific Populations of Gossypium spp.

High-throughput genotyping arrays provide a standardized resource for plant breeding communities that are useful for a breadth of applications including high-density genetic mapping, genome-wide association studies (GWAS), genomic selection (GS), complex trait dissection, and studying patterns of genomic diversity among cultivars and wild accessions. We have developed the CottonSNP63K, an Illumina Infinium array containing assays for 45,104 putative intraspecific single nucleotide polymorphism (SNP) markers for use within the cultivated cotton species Gossypium hirsutum L. and 17,954 putative interspecific SNP markers for use with crosses of other cotton species with G. hirsutum. The SNPs on the array were developed from 13 different discovery sets that represent a diverse range of G. hirsutum germplasm and five other species: G. barbadense L., G. tomentosum Nuttal × Seemann, G. mustelinum Miers × Watt, G. armourianum Kearny, and G. longicalyx J.B. Hutchinson and Lee. The array was validated with 1,156 samples to generate cluster positions to facilitate automated analysis of 38,822 polymorphic markers. Two high-density genetic maps containing a total of 22,829 SNPs were generated for two F2 mapping populations, one intraspecific and one interspecific, and 3,533 SNP markers were co-occurring in both maps. The produced intraspecific genetic map is the first saturated map that associates into 26 linkage groups corresponding to the number of cotton chromosomes for a cross between two G. hirsutum lines. The linkage maps were shown to have high levels of collinearity to the JGI G. raimondii Ulbrich reference genome sequence. The CottonSNP63K array, cluster file and associated marker sequences constitute a major new resource for the global cotton research community.

The dust grains from 9P/Tempel 1 before and after the encounter with Deep Impact.

Gemini-N observed the properties of dust ejected from the nucleus of comet 9P/Tempel 1 before and after its encounter with Deep Impact. Marked changes were seen in the 7.8- to 13-micrometer spectral energy distribution and derived grain properties of the inner coma. A strong, broad silicate feature dominated by emission from amorphous pyroxene, amorphous olivine, and magnesium-rich crystalline olivine had developed by 1 hour after impact. The ejected dust mass is congruent with 10(4) to 10(6) kilograms on the basis of our models. Twenty-six hours later the silicate feature had faded, leaving a smooth featureless spectrum, similar to that observed before the impact, suggesting that the impact did not produce a new active region releasing small particles on the nucleus.