Keratin 20 positive SDH-deficient renal cell carcinoma: a case report and literature review.

This study aims to broaden the morphological scope of SDH-deficient renal cell carcinoma and to assist clinicians and pathologists in better understanding this entity to prevent misdiagnosis. This study used immunohistochemistry staining and the first-generation sequencing Sanger method for gene detection. It retrospectively analysed the clinical pathology, molecular characteristics, biological behaviour, and treatment information of one case of SDH-deficient renal cell carcinoma. The patient was a 57-year-old female with right back pain for more than 20 days and had no personal or family history of kidney tumours. In addition, the tumour cells had clear boundaries in morphology, and residual normal renal tubules could be seen around them. There were also ossification and adipose tissue around the tumour centre. The tumour cells were arranged in a glandular tubular and cord-like manner. Vacuolar and eosinophilic inclusion bodies could be observed in the cytoplasm. The nucleus was regular, the chromatin distribution was fine, and there were no obvious nucleoli. They were low-grade nuclei. In addition, no atypical mitosis or necrosis could been found. Furthermore, immunohistochemistry staining showed SDHB-negative and keratin 20 -positive tumour. Meanwhile, the first-generation sequencing also pointed out the presence of SDHB gene mutations in the tumour. After 12 months of follow-up, there was no evidence of disease recurrence in the patient. SDH-deficient renal cell carcinoma is a rare tumour associated with SDH gene germline mutations, and suspected cases should undergo SDHB immunohistochemistry staining. Most SDH-deficient renal cell carcinomas have a good prognosis, but undifferentiated cases require long-term follow-up.

Enhanced Delivery of Biomolecules into Caco2 Cells Based on the Cell-Penetrating Ability of Keratin Peptides.

Keratin, as a promising bioresource, possesses significant potential for diverse biological applications due to its favorable biocompatibility, low toxicity, biodegradability, and cell adhesion ability. However, there are few studies on the cell-penetrating ability of keratin peptides (KEPs) for biomolecule delivery. Therefore, this study explored the cell-penetrating ability of KEPs with different molecular weights (Mw) on Caco2 cells using fluorescein-labeled insulin (FITC-INS) as the target intracellular biomolecule. The potential cell-penetrating mechanism was elaborated by combining cellular investigation with the physicochemical characterization of KEPs. The result shows that the KEPs <3 kDa (KEP1) exhibited the highest cell-penetrating ability at 2 mg/mL, allowing efficient delivery of FITC-INS into Caco2 cells without covalent bonding. The cellular uptake mechanism was energy-dependent, mainly involving macropinocytosis. The further fractionation of KEP1 reveals that the most effective components consisted of 8-19 amino acids, including specific hydrophobic peptides (e.g., RVVIEPSPVVV and IIIQPSPVVV), PPII amphipathic peptides (e.g., PPPVVVTFP and FIQPPPVVV), and Cys-rich peptides (e.g., LCAPTPCGPTPL and CLPCRPCGPTPL). Additionally, analysis of the secondary and tertiary structure and amino acid composition illustrated that KEP1 exhibited rich hydrophobic residues and disulfide bonds, which probably contributed to its cell-penetrating ability, as opposed to its small particle size and electrostatic interactions. This study reveals the cell-penetrating ability of KEPs, thus highlighting their potential as biomaterials for noncovalently delivering biomolecules.

Acne-related UVA-induced facial fluorescence: An exploratory study from physiological properties to tissue structure information.

UVA-induced facial fluorescence (UVAF) is recognized as an objective measurement technique to quantify the severity of acne. However, notable inconsistencies in quantitative outcomes have been observed in various studies, possibly due to the fact that different colors of fluorescence represent different pathophysiological implications. This study investigated the pathophysiological importance of UVAF color differences and improved its reliability in assessing acne severity. MIDOO Smart Skin Imager was used to capture UVAF and analyze the correlation between fluorescence colors and acne lesions. Techniques such as two-photon excited fluorescence microscopy, scanning electron microscopy, western blot, and high performance liquid chromatography-mass spectrometry (HPLC-MS/MS) were used to examine the biochemical composition and structure of comedonal plugs and follicular casts associated with different fluorescence colors. We found that green fluorescence correlates with non-inflammatory acne lesions (comedones), while orange-red fluorescence shows no correlation with either type of lesion. Green fluorescence is associated with higher levels of keratin, indicating keratinization, while orange-red fluorescence is associated with porphyrin from S. epidermidis. UVAF color differences - orange-red are from porphyrins and green from keratin. This distinction helps to understand the structural and physiological bases of facial fluorescence, with potential implications for clinical evaluations of acne.

Exotic Keratin Pearl Degradation Mechanism by Giant Cells in Oral Squamous Cell Carcinoma and its Plausible Hypothesis.

Introduction: Oral squamous cell carcinoma (OSCC) is a formidable malignancy in the Indian subcontinent, characterized by high morbidity and mortality, with a dismal 5-year survival rate of 40-50%. The tumor's histopathological heterogeneity is well documented, particularly in its differentiation status, which ranges from well-differentiated lesions with prominent keratin pearls to poorly differentiated forms lacking such structures. Objectives: Existing literature has elucidated the role of neutrophils and macrophages in the degradation of keratin pearls, the involvement of multinucleated giant cells (MNGCs) in this process remains cryptic. Case report: This study reports a novel case of a 49-year-old male with moderately differentiated OSCC, characterized by ulcerative growth in the left buccal mucosa. Histopathological analysis revealed neoplastic cell infiltration, keratinization, and abnormal mitoses, alongside the degradation of keratin pearls by large foreign body and Langhans MNGCs. This intricate keratin pearl degradation by MNGCs in OSCC highlights tumor heterogeneity and aggressiveness, offering profound insights into surgical, radiotherapy, and chemotherapy strategies. Surgeons must meticulously consider this process as a marker of aggressive behavior, warranting precise surgical planning and a multidisciplinary approach for optimal outcomes. Conclusion: This case emphasizes the critical role of foreign body and Langhans MNGCs in the degradation of keratin pearls within OSCC, revealing a hitherto unrecognized facet of tumor biology. This discovery holds profound implications for understanding OSCC progression, prognosis, and therapeutic responsiveness, warranting further investigation into the molecular mechanisms underpinning this process.

The Effects of an Oral Supplementation of a Natural Keratin Hydrolysate on Skin Aging: A Randomized, Double-Blind, Placebo-Controlled Clinical Study in Healthy Women.

BACKGROUND: Keratin hydrolysates are active components used in food supplements to alleviate aging signs on skin, hair, and nails. AIMS: This randomized, double-blind, placebo-controlled study evaluates a novel keratin hydrolysate obtained from poultry feathers. This feather keratin hydrolysate (FKH) results in a characteristic mix of free L-amino acids (≥ 83.5%). FKH was administered as a food supplement to a panel of adult women showing aging physiological signs. METHODS: Participants were randomly assigned in three groups to receive daily dosages of 500 or 1000 mg of FKH or placebo for 90 days. Parameters of skin roughness, wrinkle features, deep skin moisturization, skin maximum elongation and elasticity, skin thickness, skin anisotropy, skin density, gloss of skin, hair and nails, and nail hardness were evaluated. Subjects also answered a questionnaire related to the treatment efficacy perception. RESULTS: Both FKH treatments showed a significant improvement of all parameters compared to day 0 and to placebo, with an exception for fiber anisotropy and fiber density which showed a significant improvement compared to day 0 and a tendency to improve compared to placebo. These measurements were bolstered by the results of a self-assessment questionnaire, showing an overall set of positive answers for both treatments compared to placebo. CONCLUSIONS: Oral supplementation of FKH for 90 days is associated with an improvement in the appearance of facial skin, hair, and nails. This study highlights the benefits of free L-amino acids mix as potential aminobiotics and not just as building blocks of proteins, suggesting a new perspective of nutricosmetic food.

Versatile Keratin Fibrous Adsorbents with Rapid-Response Shape-Memory Features for Sustainable Water Remediation.

Biodegradable shape-memory polymers derived from protein substrates are attractive alternatives with strong potential for valorization, although their reconstruction remains a challenge due to the poor processability and inherent instability. Herein, based on Maillard reaction and immobilization, a feather keratin fibrous adsorbent featuring dual-response shape-memory is fabricated by co-spinning with pullulan, heating, and air-assisted spraying ZIF-8-NH2. Maillard reaction between the amino group of keratin and the carbonyl group of pullulan improves the mechanics and thermal performance of the adsorbent. ZIF-8-NH2 immobilization endows the adsorbent with outstanding multipollutant removal efficiency (over 90%), water stability, and photocatalytic degradation and sterilization performance. Furthermore, the adsorbent can be folded to 1/12 of its original size to save space for transportation and allow for rapid on-demand unfolding (12 s) upon exposure to water and ultraviolet irradiation to facilitate the adsorption and photocatalytic activity with a larger water contact area. This research provides new insight for further applications of keratin-based materials with rapid shape-memory features.

Recovery of pure PET from wool/PET/elastane textile waste through step-wise enzymatic and chemical processing.

Textile waste is mostly incinerated because few recycling processes are available to recover valuable materials. In this work, a feasible chemo-enzymatic recycling process of wool/polyethylene terephthalate (PET)/elastane blends to recover pure PET is for the first time successfully demonstrated. Two novel enzyme formulations were selected for wool hydrolysis, whereas the recovered amino acids were quantified using high-performance liquid chromatography and two assays (Ninhydrin and Folin-Ciocalteu). Kinetic studies on the amino acid formation alongside reaction observations by scanning electron microscopy proved sufficient removal of wool within 8 hours with the new enzyme formulation, marking an acceleration compared to previous studies. Finally, elastane was separated with a non-hazardous solvent to obtain pure PET. Tensile tests on the recovered PET fibres reveal only slight changes through the enzymatic treatment and no changes induced by the applied solvent. The enzyme formulation was successfully tested on five different post-consumer wool/PET textile waste samples. This valorization approach enhances the circular economy concept for textile waste recycling.

Oxidative Stress and Annexin A2 Differential Expression in Free Fatty Acids-Induced Non-Alcoholic Fatty Liver Disease in HepG2 Cells.

Non-alcoholic fatty liver disease (NAFLD) is a rising global burden, affecting one in four adults. Despite the increasing prevalence of NAFLD, the exact cellular and molecular mechanisms remain unclear, and effective therapeutic strategies are still limited. In vitro models of NAFLD are critical to understanding the pathogenesis and searching for effective therapies; thus, we evaluated the effects of free fatty acids (FFAs) on NAFLD hallmarks and their association with the modulation of Annexin A2 (ANXA2) and Keratin 17 (KRT17) in HepG2 cells. Our results show that oleic and palmitic acids can differentially induce intracellular lipid accumulation, cell death, and promote oxidative stress by increasing lipid peroxidation, protein carbonylation, and antioxidant defense depletion. Moreover, a markedly increased expression of inflammatory cytokines demonstrated the activation of inflammation pathways associated with lipotoxicity and oxidative stress. ANXA2 overexpression and KRT17 nuclear translocation were also observed, supporting the role of both molecules in the progression of liver disease. Taken together, these data provide insights into the interplay between ANXA2 and KRT17 in NAFLD, paving the way for understanding molecular mechanisms involved with the disease and developing new therapeutic strategies.

Impact of Keratins 8 and 18 Genetic Variants on the Severity of Alcoholic Liver Disease.

Alcohol-related liver disease (ALD) affects ∼30% of heavy drinkers and is characterized by liver steatosis, fibrosis, and steatohepatitis. The aggregation of keratins 8 (KRT8) and 18 (KRT18) plays a key role in the formation of Mallory-Denk bodies, a hallmark of ALD. Circulating levels of KRT18 fragments are elevated during ALD, and several KRT8/18 genetic variants have been linked to an increased risk of liver disease. In this study, we explored the relationship between the histologic features of ALD and genetic variants of KRT8/18 in 106 severe patients with ALD from the Hôpitaux Universitaires de Genève. We found a significant over-representation of several KRT8 (rs2070910, rs137898974, rs1065306) and KRT18 (rs17120866, rs1492241) variants located in the noncoding regions of these genes. Increased circulating level of keratins 18 fragments were associated with rs17120866 and alcoholic hepatitis. The combination of several KRT18 variants appeared associated with a poorer prognosis. These results highlight the possible role of KRT18 variants in ALD.

Genomic Sequencing and Functional Analysis of the Ex-Type Strain of Malbranchea zuffiana.

Malbranchea is a genus within the order Onygenales (phylum Ascomycota) that includes predominantly saprobic cosmopolitan species. Despite its ability to produce diverse secondary metabolites, no genomic data for Malbranchea spp. are currently available in databases. Therefore, in this study, we obtained, assembled, and annotated the genomic sequence of the ex-type strain of Malbranchea zuffiana (CBS 219.58). For the genomic sequencing, we employed both the Illumina and PacBio platforms, followed by hybrid assembly using MaSuRCA. Quality assessment of the assembly was performed using QUAST and BUSCO tools. Annotation was conducted using BRAKER2, and functional annotation was completed with InterProScan. The resulting genome was of high quality, with a size of 26.46 Mbp distributed across 38 contigs and a BUSCO completion rate of 95.7%, indicating excellent contiguity and assembly completeness. A total of 8248 protein-encoding genes were predicted, with functional annotations assigned to 73.9% of them. Moreover, 82 genes displayed homology with entries in the Pathogen Host Interactions (PHI) database, while 494 genes exhibited similarity to entries in the Carbohydrate-Active Enzymes (CAZymes) database. Furthermore, 30 biosynthetic gene clusters (BGCs) were identified, suggesting significant potential for the biosynthesis of diverse secondary metabolites. Comparative functional analysis with closely related species unveiled a considerable abundance of domains linked to enzymes involved in keratin degradation, alongside a restricted number of domains associated with enzymes engaged in plant cell wall degradation in all studied species of the Onygenales. This genome-based elucidation not only enhances our comprehension of the biological characteristics of M. zuffiana but also furnishes valuable insights for subsequent investigations concerning Malbranchea species and the order Onygenales.

Identification of Key Proteins Related to Cashmere Fiber Diameter by Integrated Proteomics and Bioinformatic Analyses in the Alpas and Alxa Goat Breeds.

BACKGROUND: Goats (Capra hircus) have always been a source of fiber for human use and hold an important place in international high-end textiles. Fiber diameter is the most concerning economic indicator for producers. Understanding the formation mechanism of fiber diameter and its related key proteins can help optimize and control the production of cashmere. METHODS: Cashmere goats (n = 36) of the Alpas (n = 18) and Alxa (n = 18) breeds, with a similar age (2 years old) and live weight (25-26 kg), were selected from the Yiwei White Cashmere Goat Breeding Farm, Erdos, Inner Mongolia. Using phenotypic indicators, we evaluated the diameter of the cashmere fibers in Alxa and Alpas goats. We also used electron microscopy to examine the cashmere fiber's structure and label-free liquid chromatography-tandem mass spectrometry to determine the protein content of the two cashmere fibers. The proteins affecting fiber diameter were identified and analyzed by Western blot, Co-Immunoprecipitation, and bioinformatics analysis. RESULTS: The average diameter of the Alxa breed was smaller (p < 0.05) than that of the Alpas breed (Alxa's cashmere vs. Alpas' cashmere). Proteomics technology enabled the highly confident detection of 171 proteins. A total of 68 differentially expressed proteins were identified in the two types of cashmere; 131 proteins were specifically expressed in Alpas goats, and 40 proteins were specifically expressed in Alxa goats. A key protein group that could cause variations in fiber diameter was found using the protein-protein interaction network. To ascertain the reason for the variation in fiber diameter, a structural study of the major protein groups was carried out. CONCLUSIONS: KRT10, KRT14, KRT17, and KRT82 are the main proteins impacting the diameter difference, and they have a substantial effect on the average fiber diameter.

In vivo confocal microscopic features of canine primary corneal squamous cell carcinoma.

OBJECTIVE: To describe the in vivo confocal microscopy (IVCM) findings in dogs with primary corneal squamous cell carcinoma (SCC). ANIMALS: Eight dogs with primary corneal SCC. PROCEDURES: Dogs diagnosed with primary corneal SCC by histopathology were examined with a modified Heidelberg Retina tomograph and Rostock Cornea Module prior to surgical intervention. The findings from the IVCM examination were correlated with clinical details from ophthalmic examinations and diagnostic test results. RESULTS: Eight eyes from eight dogs with unilateral primary corneal SCC were examined. Corneal lesions were characterized with IVCM by abnormal epithelial cells that were polygonal and enlarged with marked morphological variability and anisocytosis within individual corneas. The abnormal cells displayed variable reflectivity, but most had highly reflective cellular borders and moderately reflective cytoplasm. Cells that were markedly and diffusely hyperreflective were also occasionally observed possibly representing keratinization and dyskeratosis. On IVCM, neoplastic cells were grouped into cords, clusters, and sheets, and nests of neoplastic cells often invaded the underlying corneal stroma. Keratin pearls were a frequent finding and appeared as circular whirls of neoplastic epithelial cells arranged around concentric layers of hyperreflective amorphous material within a dark cyst-like space. Abundant blood vessels and scattered leukocytes were present in all tumors. There was a high degree of morphologic agreement between IVCM analysis and histopathological findings in all cases. CONCLUSIONS: The distinguishing features of primary corneal SCC during IVCM examine were similar to those seen in histopathologic examination of tumor sections, including enlarged and pleomorphic squamous epithelial cells, anisocytosis, keratin pearl formation, and dense vascularization.

Keratin 8/18a.1 Expression Influences Embryonic Neural Crest Cell Dynamics and Contributes to Postnatal Corneal Regeneration in Zebrafish.

A complete understanding of neural crest cell mechanodynamics during ocular development will provide insight into postnatal neural crest cell contributions to ophthalmic abnormalities in adult tissues and inform regenerative strategies toward injury repair. Herein, single-cell RNA sequencing in zebrafish during early eye development revealed keratin intermediate filament genes krt8 and krt18a.1 as additional factors expressed during anterior segment development. In situ hybridization and immunofluorescence microscopy confirmed krt8 and krt18a.1 expression in the early neural plate border and migrating cranial neural crest cells. Morpholino oligonucleotide (MO)-mediated knockdown of K8 and K18a.1 markedly disrupted the migration of neural crest cell subpopulations and decreased neural crest cell marker gene expression in the craniofacial region and eye at 48 h postfertilization (hpf), resulting in severe phenotypic defects reminiscent of neurocristopathies. Interestingly, the expression of K18a.1, but not K8, is regulated by retinoic acid (RA) during early-stage development. Further, both keratin proteins were detected during postnatal corneal regeneration in adult zebrafish. Altogether, we demonstrated that both K8 and K18a.1 contribute to the early development and postnatal repair of neural crest cell-derived ocular tissues.

A multicentre clinical trial evaluating the outcomes of two application regimens of a unique keratin-based graft in the treatment of Wagner grade one non-healing diabetic foot ulcers.

Diabetic foot complications that lead to lower extremity amputations pose a significant challenge to the entire global health system. In this multicentre clinical trial, 26 patients with chronic Wagner one diabetic foot ulcers (DFUs) were treated with a unique human keratin matrix graft applied either weekly or bi-weekly, in addition to standard of care. The hypothesis was that bi-weekly application would be similar to weekly application. The primary endpoint was complete wound closure by 12 weeks, and secondary endpoints included healing time, percent area reduction and weekly changes in peripheral neuropathy, pain and quality of life. In the intent-to-treat population, 77% (10/13) of DFUs treated with bi-weekly application healed compared with 69% (9/13) treated with weekly application. The mean time to heal within 12 weeks in the bi-weekly group was 61 days and in the weekly group was 54 days. The mean percent area reduction at 12 weeks was 94.7% in the bi-weekly group compared with 84.8% in the weekly group. The number of grafts used in the bi-weekly group was 3.9 compared with 6.2 in the weekly group. The results of this trial confirm our hypothesis that whether bi-weekly or weekly application of the unique keratin matrix graft is used to treat nonhealing indolent DFUs, there is a high rate of complete healing. Based on these results, future studies should be conducted that further investigate the use of this novel human keratin matrix graft for the treatment of chronic DFUs.

Targeted DNA Sequencing in Diagnosis of Malignant Phyllodes Tumors With Emphasis on Tumors With Keratin and p63 Expression.

The differential diagnosis of malignant spindle cell neoplasms in the breast most frequently rests between malignant phyllodes tumor (MPT) and metaplastic carcinoma (MBC). Diagnosis of MPT can be challenging due to diffuse stromal overgrowth, keratin (CK) and/or p63 immunopositivity, and absent CD34 expression, which can mimic MBC, especially in core biopsies. Distinction of MPT from MBC has clinical implications, with differences in surgical approach, chemotherapy, and radiation. In this study, we evaluated MPTs (78 tumors, 64 patients) for stromal CK, p63, and CD34 expression and profiled a subset (n = 31) by targeted next-generation DNA sequencing, with comparison to MBC (n = 44). Most MPTs (71%) were CK+ and/or p63+, including 32% CK+ (25/77 focal) and 65% p63+ (32/66 focal, 10/66 patchy, and 1/66 diffuse). Thirty percent of MPTs expressed both CK and p63 (20/66), compared with 95% of MBCs (40/42, P < .001). CK and/or p63 were positive in CD34+ and CD34- MPTs. Recurrent genetic aberrations in MPTs involved TERT, TP53, MED12, CDKN2A, chromatin modifiers, growth factor receptors/ligands, and phosphoinositide-3 kinase (PI-3K) and MAPK pathway genes. Only MED12 (39%, 12/31) and SETD2 (13%, 4/31) were exclusively mutated in MPTs and not MBCs (P < .001 and P = .044, respectively), whereas PIK3R1 mutations were only found in MBCs (37%, 13/35, P < .001). Comparative literature review additionally identified ARID1B, EGFR, FLNA, NRAS, PDGFRB, RAD50, and RARA alterations enriched or exclusively in MPTs vs MBCs. MED12 was mutated in MPTs with diffuse stromal overgrowth (53%, 9/17), CD34- MPTs (41%, 7/17), and CK+ and/or p63+ MPTs (39%, 9/23), including 36% of CD34- MPTs with CK and/or p63 expression. Overall, MED12 mutation and/or CD34 expression were observed in 68% (21/31) MPTs, including 61% (14/23) of CK+ and/or p63+ tumors. Our results emphasize the prevalence of CK and p63 expression in MPTs and demonstrate the diagnostic utility of next-generation DNA sequencing, especially in MPTs with confounding factors that can mimic MBC.

Low temperature carbonization and synergistic flame retardancy of cotton fabric coated by phosphorus­nitrogen flame retardants.

To solve the problems of flammability and smoldering of cotton fabric, its flame-retardant finishing was executed with biomass wool keratin (WK) and cyclic phosphate ester (CPE) through the soaking and baking process. The synergistic mechanism of WK low-temperature melting and CPE catalytic dehydration prompted the formation of protective carbonization layer on cotton fabric surface, and this protective layer reduced its pyrolysis rate, inhibited the production of combustible materials and improved its flame retardancy. The results of synchronous thermal analysis indicate that the initial decomposition temperature of WK and CPE is lower than that of cotton fabric, and they precede the endothermic degradation before fabric main body. This effectively promotes the low-temperature carbonization of cotton fabric and inhibits its pyrolysis. The initial decomposition temperature of WK/CPE treated fabrics advances by 47.9 °C-97.8 °C, presenting significant low-temperature carbonization trend. Moreover, they form 3.0 %-20.0 % aromatic structural char before the pyrolysis of cotton cellulose due to the low-temperature dehydration and carbonization reactions. The damage length after vertical burning is only 4.0 cm for treated fabric with five layers, its after-flame and smoldering disappear, and its limiting oxygen index value increases to 28.7 %. This research provides an effective idea for the flammability and smoldering problems of cotton fabric.

Effects of KRTAP20-1 Gene Variation on Wool Traits in Chinese Tan Sheep.

Chinese Tan sheep lambs are recognised for having tight 'spring-like' curly wool when young, but this phenotype disappears with age. This wool consists of shorter, fine wool fibres (which are usually unmedullated) and heterotypic hair fibres (which are frequently medullated), which are referred to as 'halo hair'. Both the wool and hair fibres consist of α-keratin proteins embedded in a keratin-associated protein (KAP) matrix. Of these KAPs, the KAP20-1 gene (designated KRTAP20-1) and its effect on four fibre traits (mean fibre curvature, mean fibre diameter, fibre diameter standard deviation, and coefficient of variation of fibre diameter) of Tan lambs was studied. Seven previously identified KRTAP20-1 variants (A, B, D, E, F, G, and H) of KRTAP20-1 were revealed, but the previously identified variant C was not present. Of the seven variants detected, only two (A and G) were common and present at frequencies greater than 5%, and the effect of these on the fibre traits of the finer wool fibres was assessed. It was found that variant G was associated with an increased mean fibre curvature in these wool fibres. This suggests that KRTAP20-1 might possibly be expressed differentially in the two fibre types, which may be of future value in breeding.

Exploring Variation in Ovine KRTAP19-5 and Its Effect on Fine Wool Fibre Curvature in Chinese Tan Sheep.

Sheep's wool is known to have unique biological, physical and chemical properties. The fibre primarily consists of proteins, but these have amino acid sequence variation, and at the phenotypic level wool fibre varies considerably. This can affect its utility and value. Unravelling the genetic factors that underpin the protein and phenotypic variability is crucial if we are to contemplate improving wool quality. Accordingly, this study investigates the high glycine and tyrosine content keratin-associated protein 19-5 gene (KRTAP19-5) in sheep. PCR-single strand confirmation polymorphism analysis, coupled with DNA sequencing of a region spanning whole coding sequence, revealed six sequence variants containing seven single nucleotide polymorphisms (SNPs). Five of the SNPs were located within the coding region, with four leading to amino acid changes if expressed. In 247 Chinese Tan sheep derived from 10 sire-lines, and renowned for their distinct 'spring-like' crimped wool at up to approximately 35 days after birth, one of the variants was found to be associated with decreased curvature of the fine wool fibres in the fleece. No associations were detected with other fibre traits or with variation in the heterotypic hair fibres of the Tan sheep. While these findings may be useful for developing gene markers to alter mean wool fibre curvature and improve sheep breeding, many other genes and environmental factors are known to contribute to variation in fibre traits.

Nailing it: Investigation of elephant toenails for retrospective analysis of adrenal and reproductive hormones.

Hormone monitoring of at-risk species can be valuable for evaluation of individual physiological status. Traditional non-invasive endocrine monitoring from urine and faeces typically captures only a short window in time, poorly reflecting long-term hormone fluctuations. We examined toenail trimmings collected from African (Loxodonta africana) and Asian (Elephas maximus) elephants during routine foot care, to determine if long-term hormone patterns are preserved in these slow-growing keratinized tissues. We first measured the growth rate of elephant toenails biweekly for one year, to establish the temporal delay between deposition of hormones into nail tissue (at the proximal nail bed) and collection of toenail trimmings months later (at the distal tip of the nail). In African elephants, toenails grew ~0.18 ± 0.015 mm/day (mean ± SEM) and in Asian elephants, toenails grew ~0.24 ± 0.034 mm/day. This slow growth rate, combined with the large toenail size of elephants, may mean that toenails could contain a 'hormone timeline' of over a year between the nail bed and nail tip. Progesterone, testosterone and cortisol were readily detectable using commercial enzyme immunoassays, and all assays passed validations, indicating that these hormones can be accurately quantified in elephant toenail extract. In most cases, variations in hormone concentrations reflected expected physiological patterns for adult females and males (e.g. ovarian cycling and musth) and matched individual health records from participating zoos. Progesterone patterns aligned with our calculations of temporal delay, aligning with female ovarian cycling from over six months prior. Unexpectedly, male testosterone patterns aligned with current musth status at the time of sample collection (i.e. rather than prior musth status). Though this sample type will require further study, these results indicate that preserved hormone patterns in elephant toenails could give conservationists a new tool to aid management of elephant populations.

Xanthogranulomatous epithelial tumors/keratin-positive giant cell-rich tumors involving the head and neck: report of seven cases and review of the literature.

Xanthogranulomatous epithelial tumor (XGET) and HMGA2::NCOR2 fusion keratin-positive giant cell-rich tumor (KPGCT) are recently described morphologically overlapping rare neoplastic entities characterized by HMGA2::NCOR2 fusions, low-grade biological behavior, and a strong predilection for young females. To date, 47 cases have been reported with only four occurring in head and neck anatomic locations. In this study, we describe the clinicopathologic, immunohistochemical, and molecular findings of seven XGET/KPGCTs occurring in the head and neck region. The patients were six females and one male, aged 3.5-59 years old (median, 25 years). The tumors involved the ear, vocal cord, skull, neck soft tissue, and sinonasal cavity. Tumor sizes ranged from 1.5 to 6.7 cm. Histologically, the tumors were characterized by xanthogranulomatous histiocytes, osteoclast-like giant cells, and keratin-positive epithelioid cells. The XGET/KPGCTs involving the ear was remarkable for more cytologic atypia than previously described. Four cases had the HMGA2::NCOR2 fusion identified by NGS and three had HMGA2 gene locus alterations by FISH. Follow-up information was available for 3 of 7 patients (range 6-46 months). The patient with a vocal cord XGET/KPGCTs developed a local recurrence treated with excision. This study illustrates that XGET/KPGCTs involves the head and neck region as well, where it may be unexpected and hence under-recognized, and expands the anatomic locations of involvement to include unreported sites (ear, vocal cord, and sinonasal tract).