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Malignant diseases of the skin
Published in Rashmi Sarkar, Anupam Das, Sumit Sethi, Concise Dermatology, 2021
Anupam Das, Yasmeen Jabeen Bhat
Clinical features: Lentigo maligna is a slowly progressive, pre-neoplastic disorder of melanocytes, which develops insidiously on exposed areas of skin, particularly the skin of the face. The lesion itself is a pigmented macule with a well-defined, rounded or polycylic edge, which may be up to 5 cm in diameter or even larger (Figure 13.14). A characteristic feature is the varying shades of brown and black contained within the lesion – a feature known as variegation.
The skin
Published in C. Simon Herrington, Muir's Textbook of Pathology, 2020
Malignant melanoma in situ (MMIS) represents an early intraepithelial stage of malignant melanoma. It presents as a slowly growing, asymmetrical, irregular, relatively flat pigmented lesion with colour variegation. Lentigo maligna and superficial spreading are the two main clinicopathological forms of intraepithelial melanoma which differ in the anatomical distribution, histological characteristics and risks of progression. Lentigo maligna arises on chronically sun-damaged skin usually of the facial region of elderly patients. Superficial spreading type of MMIS more commonly affects non-sun damaged areas of the skin like the back. Of the two subtypes, lentigo maligna tends to have a more indolent course and can sometimes remain in this stage over decades before acquiring the potential to metastasize. Indeed, some view lentigo maligna as a broad histological spectrum of which some but not all are atypical enough to warrant a diagnosis of MMIS.
Malignant disease of the skin
Published in Ronald Marks, Richard Motley, Common Skin Diseases, 2019
Lentigo maligna is a slowly progressive, pre-neoplastic disorder of melanocytes, which develops insidiously on exposed areas of skin, particularly the skin of the face. The lesion itself is a pigmented macule with a well-defined, rounded or polycylic edge, which may be up to 5 cm in diameter or even larger (Fig. 15.16). A characteristic feature is the varying shades of brown and black contained within the lesion – a feature known as variegation. The differential diagnosis includes seborrhoeic wart, simple senile lentigo and pigmented solar keratosis (see Table 15.3).
Affinity maturation of antibodies by combinatorial codon mutagenesis versus error-prone PCR
Published in mAbs, 2020
Jan Fredrik Simons, Yoong Wearn Lim, Kyle P. Carter, Ellen K. Wagner, Nicholas Wayham, Adam S. Adler, David S. Johnson
In this study, we used an established yeast scFv sorting protocol6 to evaluate two mutagenesis methods for affinity maturation: epPCR across the full V(D)J versus combinatorial NNK codon mutagenesis (VariantFind) directed against CDRs. We used the protocols to attempt to affinity-mature four antibodies against four different immuno-oncology protein targets (CTLA-4, OX40, PD-1, and PD-L1). We used long-read high throughput sequencing (Pacific Biosciences) before and after sorting to accurately quantify the frequency of each amino acid mutation across the full heavy and light chain V(D)J sequences. We estimate that the VariantFind libraries contained 3–5 × 105 possible scFv variants, and the epPCR libraries theoretically as many as 1010 potential variants. Though each variegation method produced very different amino acid mutation profiles, neither method was distinctly superior at identifying antibodies with improved KD. Generally, our methods produced affinity-matured scFv more efficiently than affinity-matured full-length antibodies, suggesting that some mutations that improve scFv affinity do not necessarily improve full-length antibody binding. We also observed that improvements in KD against soluble antigen did not necessarily translate into improvements in binding to cell surface-expressed antigen or ability to modulate in vitro cellular activation.
Precopulatory Sexual Cannibalism and Other Accidents: Evolution, Material Trans Theory, and Natural Law
Published in Studies in Gender and Sexuality, 2018
John Beatty (2010) carried this further, showing the special importance of variation as such for the EES. Darwin’s theory required the existence of a constant welter of variations as a background condition of evolution by natural selection. Without random variation, there would be no new traits for selection to pick up. The problem was that although Darwin could point to some examples of variation in nature, he generally was relying on macro-level observations. For Darwin’s theory to have real power, it needed deep variation. T. H. Morgan’s microscopy research on fruit flies in the 1920s provided an extremely powerful data set in defense of this hypothesis. This data set told a story of constant variegation within species domains (Beatty, 2010, p. 31).
Induction of novel inflorescence traits in Chrysanthemum through 60Co gamma irradiation
Published in International Journal of Radiation Biology, 2020
Mohit Kumar Setia, Madhu Bala, Simrat Singh
Induced mutagenesis holds special relevance in breeding for novel traits in vegetatively propagated ornamental crops species due to their highly heterozygous nature and polyploidy genetic makeup. Some of the novel traits, such as flower color, shape, leaf variegation, and other esthetic phenotypic characters can be easily detected, isolated and maintained indefinitely (Broertjes 1968). Generally, bud sports or natural spontaneous mutations have significantly enriched the germplasm of many commercially important ornamental crops, particularly Chrysanthemum, which is believed to have evolved one-third of its commercial cultivars through somatic mutations (Wasscher 1956). The modern day cultivated chrysanthemums (family Asteraceae) characterized by capitulum inflorescence, have evolved from hybridization since 2500 years ago, among wild genotypes from China and Japan (Kher 1977). Interspecific crosses, open pollination, intervarietal hybridization, spontaneous, and induced mutations also have contributed to the present day genetic diversity in Chrysanthemums. Chrysanthemum ranks third in world cut flower trade and retained first position in China and Japan, being its primary centers of origin (Datta and Janakiram 2015). The garden Chrysanthemum is a popular commercial flower crop of India cultivated in 20.55 thousand hectare area with an average annual production of 188.81 thousand Metric tons loose flowers and 1.5 million cut flowers (Handbook 2019). The Chrysanthemum exhibit wide variation in flower color, flower morphology, plant height and leaf shape, besides its robust adaptability to grow in diverse agro-climatic regions (Nazeer and Khoshoo 1982).