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SUMMARYThe black nectar ofMelianthusflowers is thought to serve as a visual attractant to pollinators, but the chemical identity and synthesis of the black pigment are unknown. Here we report that the black nectar contains a natural analog of iron-gall ink, which humans have used since medieval times. Specifically, dark black nectar at anthesis contains high levels of ellagic acid and iron; synthetic solutions of ellagic acid and iron(III) recapitulate the black color of the nectar. Conversely, lightly colored nectars before and after anthesis contain significantly lower levels of ellagic acid and iron, but higher levels of gallic acid. We then explored the possibility of post-secretory synthesis of ellagic acid from gallic acid. Indeed,Melianthusnectar contains a peroxidase that oxidizes gallic acid to form ellagic acid. Reactions containing the nectar peroxidase, gallic acid, hydrogen peroxide, and iron can fully recreate the black color of the nectar. Visual modeling indicates that the black color is both visible and conspicuous to birds within the context of the flower. In summary, the black nectar ofMelianthusis derived from an ellagic acid-Fe complex analogous to iron-gall ink and is likely involved in the attraction of passerine bird pollinators.

Patients with a history of or a predisposition to autoimmune or collagen vascular diseases are inclined to develop drug-induced subacute cutaneous lupus erythematosus (SCLE) due to terbinafine therapy. Here, we report a case of terbinafine-induced SCLE in a male patient, although classic SCLE most commonly affects females, and he did not have a diagnosis of or a history suggestive of a predisposition to autoimmune or collagen vascular diseases. Although the mechanism for terbinafine-induced SCLE has not been fully elucidated, we suggest that there may be distinctive mechanisms of terbinafine-induced SCLE of patients with and without a predisposition to or history of autoimmune or connective tissue diseases, which should be a focus of future research.

Cutaneous sarcomas are uncommon cancers that can have a wide range of clinical symptoms and lead to considerable cutaneous as well as systemic morbidity.The objective of this review article is to discuss epidemiology, clinical features, diagnosis, and therapy of different types of cutaneous sarcomas.Literature was screened to retrieve articles from PubMed/Medline and Google Scholar and related websites. Cross-references from the relevant articles were also considered for review. Review articles, clinical studies, systematic reviews, meta-analyses, and relevant information from selected websites were included.Cutaneous sarcomas have a negative effect on the quality of life. In their diagnosis, clinical presentation and histological evaluation are crucial. Complete surgical removal is the solution for more or less all cutaneous and subcutaneous sarcomas. The prognosis for cutaneous sarcomas is generally favorable since they tend to recur locally with distant metastases only on rare occasions. Patients having advanced disease should be treated in the setting of clinical trials if possible; choices include radiation therapy and systemic medicines. The value of innovative immunotherapy cannot be determined decisively at this time due to a paucity of relevant trials.As cutaneous sarcomas are rarely diagnosed based on clinical findings, histology plays an important role in the diagnosis. They have a relatively favorable prognosis if treated properly. Patients should be treated at specialized centres.

Malignant melanoma and particularly metastatic melanoma represent a diagnostic challenge due to the wide variety of histologic patterns, resemblance to benign entities, and extensive range of clinical presentations. A high index of suspicion for melanoma is important for accurate diagnosis, especially when there is a previous history of malignancy. Here, we present a patient with a history of melanoma and locally metastatic melanoma, who subsequently developed a nodule on his right forearm near the site of his previous melanoma excision. Histologically, the melanoma appeared as granuloma annulare (GA) with benign cytologic features, but was identified as metastatic melanoma using SOX-10 immunohistochemical staining. Other malignancies, including lymphomas, leukemias, sarcomas, and cutaneous metastases of internal malignancies, have mimicked GA and interstitial granulomatous processes. Therefore, further immunohistochemical staining should be performed to assess for metastatic disease in the setting of a histological pattern that resembles a benign granulomatous process in a patient with a history of malignancy, including malignant melanoma.

The objective of this study was to explore the effect of woody breast (WB) on quality characteristics of chicken meatballs paired with the feasibility of its inclusion. Cook loss (CL), color (CIE L*, a*, b*), texture (hardness, springiness, chewiness and resilience), low-field NMR (bound water, immobilized water, and free water), microstructure, and sensory characteristics of chicken meatballs with different WB inclusion levels (0%, 25%, 50%, 75%, 100%) were analyzed. The results showed that the impairment of product quality traits such as CL, color, texture (hardness, chewiness), free water, microstructure, and sensory scores (appearance, organization, total score) increased as the percentage of WB meat increased in the product formulation, particularly when the WB incorporation level exceeded 25%. Indeed, cook loss, L*, a*, b* parameters, bound water, and immobilized water increased when the WB inclusion level was higher than 25% (P ≤ 0.05). However, free water, sensory characteristics, hardness, and chewiness parameters decreased (P ≤ 0.05). The microstructure of chicken meatballs also changed as the proportion of WB meat increased. Even though data suggest that the inclusion of WB meat up to 30% could be feasible to produce acceptable chicken meatballs, the optimal maximum incorporation rate of WB meat into chicken meatball recipes was 25% based on economic feasibility and final overall quality.

Nectar is a primary reward mediating plant–animal mutualisms to improve plant fitness and reproductive success. Four distinct trichomatic nectaries develop in cotton (Gossypium hirsutum), one floral and three extrafloral, and the nectars they secrete serve different purposes. Floral nectar attracts bees for promoting pollination, while extrafloral nectar attracts predatory insects as a means of indirect protection from herbivores. Cotton therefore provides an ideal system for contrasting mechanisms of nectar production and nectar composition between different nectary types. Here, we report the transcriptome and ultrastructure of the four cotton nectary types throughout development and compare these with the metabolomes of secreted nectars. Integration of these datasets supports specialization among nectary types to fulfill their ecological niche, while conserving parallel coordination of the merocrine-based and eccrine-based models of nectar biosynthesis. Nectary ultrastructures indicate an abundance of rough endoplasmic reticulum positioned parallel to the cell walls and a profusion of vesicles fusing to the plasma membranes, supporting the merocrine model of nectar biosynthesis. The eccrine-based model of nectar biosynthesis is supported by global transcriptomics data, which indicate a progression from starch biosynthesis to starch degradation and sucrose biosynthesis and secretion. Moreover, our nectary global transcriptomics data provide evidence for novel metabolic processes supporting de novo biosynthesis of amino acids secreted in trace quantities in nectars. Collectively, these data demonstrate the conservation of nectar-producing models among trichomatic and extrafloral nectaries.

Importance: Melanoma is diagnosed in approximately 200,000 people within the US each year and is responsible for more than 6,850 deaths. Currently, clinical suspicion guides biopsy decisions and melanoma is confirmed in approximately 4% of biopsied lesions. A non-invasive two-gene expression test (2-GEP) was shown to enhance the physical exam by evaluating genomic atypia to guide biopsy decisions. This study examines the corresponding histopathology of real-world 2-GEP-positive cases. Methods: Cutaneous lesions suspicious for melanoma (n=3,418) were 2-GEP tested by 90 licensed clinicians in real-world practice. 2-GEP-positive lesions (genomically atypical as indicated by the detection of LINC and/or PRAME) were biopsied in 316 out of 324 (97.5%) cases and 313 pathology reports were available for analysis. Results: Biopsied 2-GEP-positive lesions were separated into diagnostic subgroups based on corresponding pathology reports. The prevalence of melanoma in biopsies of 2-GEP-positive lesions was 18.7%. Gene expression of both LINC and PRAME was present in ever-increasing percentages of melanocytic lesions as pathology reports demonstrated increasing levels of atypia. Notably, 47.5% of the histopathologically-confirmed melanomas demonstrated this double positive genomic signature while 23.7% were single-positive for LINC and 28.8% were single-positive for PRAME. Discussion: These data show that biopsied 2-GEP-positive lesions are enriched almost five-fold for advanced histopathologic features compared to those biopsied based solely on visual assessment criteria. The close correlation between genomic atypia and atypical pathology should be considered when planning treatment of a 2-GEP-positive lesion. Consideration of genomic atypia may be a superior approach to guide biopsy decisions and manage pigmented lesions.

Injection of filler material has become routine in dermatology in improving the appearance of rhytides and increasing skin volume associated with aging. While the vast majority of injections are accomplished without complications, foreign body reactions may develop in a certain percentage of individuals. We recently encountered a 65-year-old woman with recurrent malignant melanoma who presented with marked thickening along the sides of her face for approximately 2 months. She recently received nivolumab infusions for recurrent malignant melanoma and noted that symptoms worsened after each infusion. She reported having had cosmetic procedures done three years prior, one of which was an injection of a long-lasting dermal filler, polymethylmethacrylate microsphere enhanced bovine collagen (Bellafill). A biopsy of two areas revealed nodular infiltrates of histiocytes with small round lobules recognizable as polymethylmethacrylate microspheres. Based on clinical and histopathologic findings, a diagnosis of granulomatous dermatitis filler reaction was rendered. Nivolumab is a PD-1 checkpoint inhibitor that disrupts T-cell inhibitory pathways leading to increased immune activation. In this case, the immune activation triggered a florid granulomatous reaction to the filler the patient had been injected with 3 years previously. We present this case as the second report of this phenomenon and the first in the dermatologic literature. This is a newly recognized side effect of PD-1 checkpoint immunotherapy and patients who are about to initiate such therapy who have had filler injections should be warned about this potential complication.

The humans have been disproportionately affected by the coronavirus disease (COVID-19) pandemic. The novel coronavirus or the severe acute respiratory syndrome coronavirus 2 (SARS-COV2) causing coronavirus disease (COVID-19) has spread across the globe. Androgens have been suggested to have a role in COVID-19 pathogenesis.The objective of this review article is to study the link between androgens and COVID-19.PubMed and Google Scholar search was performed to retrieve literature related to the topic. Review articles, clinical trials, retrospective studies, observational studies, and case-control studies were considered for the review.Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected men are more inclined to be hospitalized for intensive care unit (ICU) as compared with women. This difference in the ICU admissions provides some clue for possible influence of androgens in the severity of COVID-19. The contribution of androgen and androgen receptor in COVID-19 disease and its severity, as well as the numerous medications targeting androgen and its receptor for lowering COVID-19 disease severity, are discussed in this review. Available literature suggests the role of androgen in the pathogenesis and severity of COVID-19. Sensitivity for androgen may be an important factor in regulating the severity of COVID-19 disease.There is a scope for the development of COVID-19 treatments based on androgen suppression. Clinical trials may furnish pivotal data and add more evidence-based options for the management of COVID-19.

Floral nectar is a sugary solution produced by nectaries to attract and reward pollinators. Nectar metabolites, such as sugars, are synthesized within the nectary during secretion from both pre-stored and direct phloem-derived precursors. In addition to sugars, nectars contain nitrogenous compounds such as amino acids; however, little is known about the role(s) of nitrogen (N) compounds in nectary function. In this study, we investigated N metabolism in Cucurbita pepo (squash) floral nectaries in order to understand how various N-containing compounds are produced and determine the role of N metabolism in nectar secretion. The expression and activity of key enzymes involved in primary N assimilation, including nitrate reductase (NR) and alanine aminotransferase (AlaAT), were induced during secretion in C. pepo nectaries. Alanine (Ala) accumulated to about 35% of total amino acids in nectaries and nectar during peak secretion; however, alteration of vascular nitrate supply had no impact on Ala accumulation during secretion, suggesting that nectar(y) amino acids are produced by precursors other than nitrate. In addition, nitric oxide (NO) is produced from nitrate and nitrite, at least partially by NR, in nectaries and nectar. Hypoxia-related processes are induced in nectaries during secretion, including lactic acid and ethanolic fermentation. Finally, treatments that alter nitrate supply affect levels of hypoxic metabolites, nectar volume and nectar sugar composition. The induction of N metabolism in C. pepo nectaries thus plays an important role in the synthesis and secretion of nectar sugar.

Purpose: A clinical hurdle for dermatopathology is the accurate diagnosis of melanocytic neoplasms. While histopathologic assessment is frequently sufficient, high rates of diagnostic discordance are reported. The development and validation of a 35-gene expression profile (35-GEP) test that accurately differentiates benign and malignant pigmented lesions is described. Methods: Lesion samples were reviewed by at least three independent dermatopathologists and included in the study if 2/3 or 3/3 diagnoses were concordant. Diagnostic utility of 76 genes was assessed with quantitative RT-PCR; neural network modeling and cross-validation were utilized for diagnostic gene selection using 200 benign nevi and 216 melanomas for training. To reflect the complex biology of melanocytic neoplasia, the 35-GEP test was developed to include an intermediate-risk zone. Results: Validation of the 35-GEP was performed in an independent set of 273 benign and 230 malignant lesions. The test demonstrated 99.1% sensitivity, 94.3% specificity, 93.6% positive predictive value and 99.2% negative predictive value. 96.4% of cases received a differential result and 3.6% had intermediate-risk. Conclusions: The 35-GEP test was developed to refine diagnoses of melanocytic neoplasms by providing clinicians with an objective tool. A test with these accuracy metrics could alleviate uncertainty in difficult-to-diagnose lesions leading to decreased unnecessary procedures while appropriately identifying at-risk patients.

Isotopic response refers to the occurrence of a new, unrelated cutaneous disease occurring at the same location of a previous healed disease. The etiology of isotopic responses is still not completely understood. Theories have included that viral particles may lead to the development of the second disease, the destruction of nerve fibers by herpes zoster may lead to an indirect influence on the immune system, an alteration of microcirculation from inflammation that causes future insults to localize to the same site, and an exaggerated and atypical hypersensitivity reaction to tissue antigens, viral antigens, or immune complex deposition. A wide variety of disease processes have been reported as the second disease in an isotopic response.Here, we discuss a case of an isotopic response following herpes zoster in which the second disease involved a granuloma annulare (GA)-like inflammatory reaction that resolved and recurred. These findings support the theory that the skin affected by herpes zoster is affected in a way that makes it a focus for the manifestation of further skin diseases.

Background and AimsIntraspecific variation in foundation species of forest ecosystems can shape community and ecosystem properties, particularly when that variation has a genetic basis. Traits mediating interactions with other species are predicted by simple allocation models to follow ontogenetic patterns that are rarely studied in trees. The aim of this research was to identify the roles of genotype, ontogeny and genotypic trade-offs shaping growth, defence and reproduction in aspen.MethodsWe established a common garden replicating >500 aspen genets in Wisconsin, USA. Trees were measured through the juvenile period into the onset of reproduction, for growth, defence chemistry (phenolic glycosides and condensed tannins), nitrogen, extrafloral nectaries, leaf morphology (specific leaf area), flower production and foliar herbivory and disease. We also assayed the TOZ19 sex marker and heterozygosity at ten microsatellite loci.Key ResultsWe found high levels of genotypic variation for all traits, and high heritabilities for both the traits and their ontogenetic trajectories. Ontogeny strongly shaped intraspecific variation, and trade-offs among growth, defence and reproduction supported some predictions while contradicting others. Both direct resistance (chemical defence) and indirect defence (extrafloral nectaries) declined during the juvenile stage, prior to the onset of reproduction. Reproduction was higher in trees that were larger, male and had higher individual heterozygosity. Growth was diminished by genotypic allocation to both direct and indirect defence as well as to reproduction, but we found no evidence of trade-offs between defence and reproduction.ConclusionsKey traits affecting the ecological communities of aspen have high levels of genotypic variation and heritability, strong patterns of ontogeny and clear trade-offs among growth, defence and reproduction. The architecture of aspen’s community genetics – its ontogeny, trade-offs and especially its great variability – is shaped by both its broad range and the diverse community of associates, and in turn further fosters that diversity.

Background: There are shortcomings in the quality and accuracy of submitted clinical information on skin biopsy requisition forms (SBRFs). Most SBRFs are completed via electronic medical records (EMR), and the effect of this on the work flow and the quality of submitted clinical information must be evaluated to identify targets in clinician-dermatopathologist communication for improvement.Objective: This review of the literature explored how SBRFs are currently handled by clinicians in the context of EMR, barriers to effective clinician-dermatopathologist communication, and suggestions for improvement.Methods: A literature search was conducted on Medline, Cinahl, and Scopus including the keywords of dermatology*, dermapatholog*, dermatopathology*, and requisition*. 20 articles were retrieved. 17 articles were included from this search and from cross-referencing articles.Results: This review reaffirmed the inadequacy of clinical information provided to dermatopathologists. Standardization of and formal education in completing SBRFs, along with dermatopathologist access to information and images via shared EMR may improve histopathologic interpretation of specimens and allow for cost-effective patient care.Limitations: This review was restricted to the English language. Previous studies have primarily been retrospective study designs and survey studies.Conclusion: The development of user-friendly standardized SBRFs with validated criteria are necessary. Clinician awareness of how to appropriately convey information and terminology on the SBRF may significantly improve the work flow of both clinicians and dermatopathologists and patient outcomes.