Nuclear lamin isoforms differentially contribute to LINC complex-dependent nucleocytoskeletal coupling and whole-cell mechanics.

The ability of a cell to regulate its mechanical properties is central to its function. Emerging evidence suggests that interactions between the cell nucleus and cytoskeleton influence cell mechanics through poorly understood mechanisms. Here we conduct quantitative confocal imaging to show that the loss of A-type lamins tends to increase nuclear and cellular volume while the loss of B-type lamins behaves in the opposite manner. We use fluorescence recovery after photobleaching, atomic force microscopy, optical tweezer microrheology, and traction force microscopy to demonstrate that A-type lamins engage with both F-actin and vimentin intermediate filaments (VIFs) through the linker of nucleoskeleton and cytoskeleton (LINC) complexes to modulate cortical and cytoplasmic stiffness as well as cellular contractility in mouse embryonic fibroblasts (MEFs). In contrast, we show that B-type lamins predominantly interact with VIFs through LINC complexes to regulate cytoplasmic stiffness and contractility. We then propose a physical model mediated by the lamin­LINC complex that explains these distinct mechanical phenotypes (mechanophenotypes). To verify this model, we use dominant negative constructs and RNA interference to disrupt the LINC complexes that facilitate the interaction of the nucleus with the F-actin and VIF cytoskeletons and show that the loss of these elements results in mechanophenotypes like those observed in MEFs that lack A- or B-type lamin isoforms. Finally, we demonstrate that the loss of each lamin isoform softens the cell nucleus and enhances constricted cell migration but in turn increases migration-induced DNA damage. Together, our findings uncover distinctive roles for each of the four major lamin isoforms in maintaining nucleocytoskeletal interactions and cellular mechanics.

CscoreTool-M infers 3D sub-compartment probabilities within cell population.

MOTIVATION: Computational inference of genome organization based on Hi-C sequencing has greatly aided the understanding of chromatin and nuclear organization in three dimensions (3D). However, existing computational methods fail to address the cell population heterogeneity. Here we describe a probabilistic-modeling-based method called CscoreTool-M that infers multiple 3D genome sub-compartments from Hi-C data. RESULTS: The compartment scores inferred using CscoreTool-M represents the probability of a genomic region locating in a specific sub-compartment. Compared to published methods, CscoreTool-M is more accurate in inferring sub-compartments corresponding to both active and repressed chromatin. The compartment scores calculated by CscoreTool-M also help to quantify the levels of heterogeneity in sub-compartment localization within cell populations. By comparing proliferating cells and terminally differentiated non-proliferating cells, we show that the proliferating cells have higher genome organization heterogeneity, which is likely caused by cells at different cell-cycle stages. By analyzing 10 sub-compartments, we found a sub-compartment containing chromatin potentially related to the early-G1 chromatin regions proximal to the nuclear lamina in HCT116 cells, suggesting the method can deconvolve cell cycle stage-specific genome organization among asynchronously dividing cells. Finally, we show that CscoreTool-M can identify sub-compartments that contain genes enriched in housekeeping or cell-type-specific functions. AVAILABILITY AND IMPLEMENTATION: https://github.com/scoutzxb/CscoreTool-M.

High quality mapping of chromatin at or near the nuclear lamina from small numbers of cells reveals cell cycle and developmental changes of chromatin at the nuclear periphery.

The chromatin associated with the nuclear lamina (NL) is referred to as lamina-associated domains (LADs). Here, we present an adaptation of the tyramide-signal amplification sequencing (TSA-seq) protocol, which we call chromatin pull down-based TSA-seq (cTSA-seq), that can be used to map chromatin regions at or near the NL from as little as 50 000 cells. The cTSA-seq mapped regions are composed of previously defined LADs and smaller chromatin regions that fall within the Hi-C defined B-compartment containing nuclear peripheral heterochromatin. We used cTSA-seq to map chromatin at or near the assembling NL in cultured cells progressing through early G1. cTSA-seq revealed that the distal ends of chromosomes are near or at the reassembling NL during early G1, a feature similar to those found in senescent cells. We expand the use of cTSA-seq to the mapping of chromatin at or near the NL from fixed-frozen mouse cerebellar tissue sections. This mapping reveals a general conservation of NL-associated chromatin and identifies global and local changes during cerebellar development. The cTSA-seq method reported here is useful for analyzing chromatin at or near the NL from small numbers of cells derived from both in vitro and in vivo sources.

Allergen content of popular chemical hair relaxers: A product analysis.

BACKGROUND: Chemical hair relaxers are widely utilized by black women, yet little research exists on the allergens present in these products. OBJECTIVE: This study aims to investigate allergen prevalence in the most popular chemical hair relaxers. METHODS: We analysed 41 products from five major retailers, identifying allergens through ingredient lists and comparing them to the 2020 American Contact Dermatitis Group Core allergen series. RESULTS: The most common contact allergens in chemical relaxers include propylene glycol, cetyl steryl alcohol, fragrance, D/L-a-tocopherol, tea tree oil and cocamidopropyl betaine. CONCLUSION: Understanding allergen exposure in products used by individuals with textured hair is needed for managing contact dermatitis in diverse populations. This analysis underscores the presence of potential allergens in hair relaxers, emphasizing the importance of dermatologists' awareness and patient scrutiny of ingredient lists.

Correlation of Orthognathic Surgical Movements to Perception of Facial Appearance in Patients With Cleft Lip and Palate.

STUDY DESIGN: Cephalometric scans were compared before and after surgery to assess the degree of correction. Correlations between skeletal movements and survey outcomes were determined using multivariate regression analysis. OBJECTIVE: This study aims to identify relationships between subjective observer-reported improvements in esthetics and emotional appearance with specific surgical movements. METHODS: Ten patients at a single tertiary institution (average age: 18.1 ± 0.8), 9 males and 1 female, underwent orthognathic repair and had comprehensive cephalometric records. Standardized anterior posterior and lateral pre and postoperative photographs of patients were included in a survey to clinicians to assess noncognitive domains on a Likert Scale (1-10). CLEFT-Q was administered to gauge patient satisfaction in categories of appearance, speech, and quality of life. RESULTS: Per clinicians, multiple domains increased including facial attractiveness (4.1 ± 0.7 versus 7.3 ± 0.7, P < 0.001), friendliness (4.5 ± 0.4 versus 7.3 ± 0.5, P < 0.001), confidence (4.1 ± 0.4 versus 7.1 ± 0.4, P < 0.001), and recommendation for surgery decreased (8.9 ± 0.1 versus 3.6 ± 0.5, P < 0.001). Speech distress decreased with increased SNA and convexity, whereas Psychological and Social scores decreased with an increased ANB. Functional eating and drinking scores increased with maxillary depth. CONCLUSIONS: Orthognathic surgery improves many noncognitive domains in patients with cleft lip and palate as assessed by both patients and clinicians on all aspects of facial attractiveness and perception. These findings demonstrate objective bases of skeletal adjustments for perceived improvements in facial appearance and emotion.

Use it or Lose it: Predictors of Compliance and Satisfaction With Postoperative Nasal Stent Therapy After Primary Cleft Lip Repair.

OBJECTIVE: Postoperative nasal stents (NSs) are used to improve esthetic outcomes after primary or secondary cleft lip repair (CLR). Prior studies have utilized anthropometric measurements or physician assessment to determine the efficacy of NS, but data on caregiver-reported outcomes is limited. This study aims to assess caregiver compliance and satisfaction with postoperative NS. METHODS: The authors designed a survey to collect parent-reported postoperative NS usage outcomes. Parents of infants with cleft lip (CL) who used postoperative NS after primary CLR were approached through social media to complete the survey. Data were analyzed to determine factors impacting compliance, satisfaction, and parent-reported outcomes. RESULTS: Eighty-five parents completed the questionnaire, and 60% reported noncompliance with NS. Parents with male children (odds ratio: 5.08, P = 0.019) and patients with incomplete CL (odds ratio: 5.72, P = 0.006) were more likely to be non-compliant with NS for over a week. Complete CL and use of presurgical molding therapy were each associated with better overall experience with postoperative NS ( P = 0.002 and P = 0.037), higher appearance ratings ( P = 0.005 and P = 0.0008), and greater satisfaction with nostril shape after surgery ( P = 0.016 and P = 0.001). CONCLUSIONS: Despite limited literature related to caregiver-reported outcomes after postoperative NS for primary CLR, the authors' results align with what has been published regarding this topic. These results can help guide surgeons in counseling patients preoperatively. Larger, multi-institutional studies are needed to better delineate and address factors associated with compliance and satisfaction after NS therapy.

Homoeologous exchanges cause extensive dosage-dependent gene expression changes in an allopolyploid crop.

Structural variation is a major source of genetic diversity and an important substrate for selection. In allopolyploids, homoeologous exchanges (i.e. between the constituent subgenomes) are a very frequent type of structural variant. However, their direct impact on gene content and gene expression had not been determined. Here, we used a tissue-specific mRNA-Seq dataset to measure the consequences of homoeologous exchanges (HE) on gene expression in Brassica napus, a representative allotetraploid crop. We demonstrate that expression changes are proportional to the change in gene copy number triggered by the HEs. Thus, when homoeologous gene pairs have unbalanced transcriptional contributions before the HE, duplication of one copy does not accurately compensate for loss of the other and combined homoeologue expression also changes. These effects are, however, mitigated over time. This study sheds light on the origins, timing and functional consequences of homeologous exchanges in allopolyploids. It demonstrates that the interplay between new structural variation and the resulting impacts on gene expression, influences allopolyploid genome evolution.

Xylans Provide the Structural Driving Force for Mucilage Adhesion to the Arabidopsis Seed Coat.

Arabidopsis (Arabidopsis thaliana) seed coat epidermal cells produce large amounts of mucilage that is released upon imbibition. This mucilage is structured into two domains: an outer diffuse layer that can be easily removed by agitation and an inner layer that remains attached to the outer seed coat. Both layers are composed primarily of pectic rhamnogalacturonan I (RG-I), the inner layer also containing rays of cellulose that extend from the top of each columella. Perturbation in cellulosic ray formation has systematically been associated with a redistribution of pectic mucilage from the inner to the outer layer, in agreement with cellulose-pectin interactions, the nature of which remained unknown. Here, by analyzing the outer layer composition of a series of mutant alleles, a tight proportionality of xylose, galacturonic acid, and rhamnose was evidenced, except for mucilage modified5-1 (mum5-1; a mutant showing a redistribution of mucilage pectin from the inner adherent layer to the outer soluble one), for which the rhamnose-xylose ratio was increased drastically. Biochemical and in vitro binding assay data demonstrated that xylan chains are attached to RG-I chains and mediate the adsorption of mucilage to cellulose microfibrils. mum5-1 mucilage exhibited very weak adsorption to cellulose. MUM5 was identified as a putative xylosyl transferase recently characterized as MUCI21. Together, these findings suggest that the binding affinity of xylose ramifications on RG-I to a cellulose scaffold is one of the factors involved in the formation of the adherent mucilage layer.

Meiotic gene evolution: can you teach a new dog new tricks?

Meiosis, the basis of sex, evolved through iterative gene duplications. To understand whether subsequent duplications have further enriched the core meiotic "tool-kit," we investigated the fate of meiotic gene duplicates following whole genome duplication (WGD), a common occurrence in eukaryotes. We show that meiotic genes return to a single copy more rapidly than genome-wide average in angiosperms, one of the lineages in which WGD is most vividly exemplified. The rate at which duplicates are lost decreases through time, a tendency that is also observed genome-wide and may thus prove to be a general trend post-WGD. The sharpest decline is observed for the subset of genes mediating meiotic recombination; however, we found no evidence that the presence of these duplicates is counterselected in two recent polyploid crops selected for fertility. We therefore propose that their loss is passive, highlighting how quickly WGDs are resolved in the absence of selective duplicate retention.

The Cdc48-Vms1 complex maintains 26S proteasome architecture.

The 26S proteasome is responsible for most regulated protein turnover and for the degradation of aberrant proteins in eukaryotes. The assembly of this ~2.5 MDa multicatalytic protease requires several dedicated chaperones and, once assembled, substrate selectivity is mediated by ubiquitin conjugation. After modification with ubiquitin, substrates are escorted to the proteasome by myriad factors, including Cdc48 (cell-division cycle 48). Cdc48 also associates with numerous cofactors, but, to date, it is unclear whether each cofactor facilitates proteasome delivery. We discovered that yeast lacking a conserved Cdc48 cofactor, Vms1 [VCP (valosin-containing protein)/Cdc48-associated mitochondrial stress-responsive], accumulate proteasome-targeted ubiquitinated proteins. Vms1 mutant cells also contain elevated levels of unassembled 20S proteasome core particles and select 19S cap subunits. In addition, we found that the ability of Vms1 to support 26S proteasome assembly requires Cdc48 interaction, and that the loss of Vms1 reduced 26S proteasome levels and cell viability after prolonged culture in the stationary phase. The results of the present study highlight an unexpected link between the Cdc48-Vms1 complex and the preservation of proteasome architecture, and indicate how perturbed proteasome assembly affects the turnover of ubiquitinated proteins and maintains viability in aging cells.

Both the scion and rootstock of grafted grapevines influence the rhizosphere and root endophyte microbiomes, but rootstocks have a greater impact.

BACKGROUND: Soil microorganisms play an extensive role in the biogeochemical cycles providing the nutrients necessary for plant growth. Root-associated bacteria and fungi, originated from soil, are also known to influence host health. In response to environmental stresses, the plant roots exude specific molecules influencing the composition and functioning of the rhizospheric and root microbiomes. This response is host genotype-dependent and is affected by the soil microbiological and chemical properties. It is essential to unravel the influence of grapevine rootstock and scion genotypes on the composition of this microbiome, and to investigate this relationship with plant growth and adaptation to its environment. Here, the composition and the predicted functions of the microbiome of the root system were studied using metabarcoding on ten grapevine scion-rootstock combinations, in addition to plant growth and nutrition measurements. RESULTS: The rootstock genotype significantly influenced the diversity and the structure of the bacterial and fungal microbiome, as well as its predicted functioning in rhizosphere and root compartments when grafted with the same scion cultivar. Based on ß-diversity analyses, 1103P rootstock showed distinct bacterial and fungal communities compared to the five others (RGM, SO4, 41B, 3309 C and Nemadex). The influence of the scion genotype was more variable depending on the community and the investigated compartment. Its contribution was primarily observed on the ß-diversity measured for bacteria and fungi in both root system compartments, as well as for the arbuscular mycorrhizal fungi (AMF) in the rhizosphere. Significant correlations were established between microbial variables and the plant phenotype, as well as with the plant mineral status measured in the petioles and the roots. CONCLUSION: These results shed light on the capacity of grapevine rootstock and scion genotypes to recruit different functional communities of microorganisms, which affect host growth and adaptation to the environment. Selecting rootstocks capable of associating with positive symbiotic microorganisms is an adaptation tool that can facilitate the move towards sustainable viticulture and help cope with environmental constraints.

Microbial dysbiosis in roots and rhizosphere of grapevines experiencing decline is associated with active metabolic functions.

When grapevine decline, characterized by a premature decrease in vigor and yield and sometimes plant death, cannot be explained by pathological or physiological diseases, one may inquire whether the microbiological status of the soil is responsible. Previous studies have shown that the composition and structure of bacterial and fungal microbial communities in inter-row soil are affected in areas displaying vine decline, compared to areas with non-declining vines within the same plot. A more comprehensive analysis was conducted in one such plot. Although soil chemical parameters could not directly explain these differences, the declining vines presented lower vigor, yield, berry quality, and petiole mineral content than those in non-declining vines. The bacterial and fungal microbiome of the root endosphere, rhizosphere, and different horizons of the bulk soil were explored through enzymatic, metabolic diversity, and metabarcoding analysis in both areas. Despite the lower microbial diversity and richness in symptomatic roots and soil, higher microbial activity and enrichment of potentially both beneficial bacteria and pathogenic fungi were found in the declining area. Path modeling analysis linked the root microbial activity to berry quality, suggesting a determinant role of root microbiome in the berry mineral content. Furthermore, certain fungal and bacterial taxa were correlated with predicted metabolic pathways and metabolic processes assessed with Eco-Plates. These results unexpectedly revealed active microbial profiles in the belowground compartments associated with stressed vines, highlighting the interest of exploring the functional microbiota of plants, and more specifically roots and rhizosphere, under stressed conditions.

BuGZ exhibits guanine nucleotide exchange factor activity toward tubulin.

α- and ß-tubulin form heterodimers, with GTPase activity, that assemble into microtubules. Like other GTPases, the nucleotide-bound state of tubulin heterodimers controls whether the molecules are in a biologically active or inactive state. While α-tubulin in the heterodimer is constitutively bound to GTP, ß-tubulin can be bound to either GDP (GDP-tubulin) or GTP (GTP-tubulin). GTP-tubulin hydrolyzes its GTP to GDP following assembly into a microtubule and, upon disassembly, must exchange its bound GDP for GTP to participate in subsequent microtubule polymerization. Tubulin dimers have been shown to exhibit rapid intrinsic nucleotide exchange in vitro, leading to a commonly accepted belief that a tubulin guanine nucleotide exchange factor (GEF) may be unnecessary in cells. Here, we use quantitative binding assays to show that BuGZ, a spindle assembly factor, binds tightly to GDP-tubulin, less tightly to GTP-tubulin, and weakly to microtubules. We further show that BuGZ promotes the incorporation of GTP into tubulin using a nucleotide exchange assay. The discovery of a tubulin GEF suggests a mechanism that may aid rapid microtubule assembly dynamics in cells.

Skin tone representation in dermatologic direct-to-consumer advertisements: a cross-sectional analysis and call to action.

Background: Direct-to-consumer advertisements (DTCAs) in medical marketing serve as a prominent modality to deliver information to an increasingly diverse audience of consumers and increase prescription sales. In dermatology, advertisements have the potential to shape the public's opinions, aid in the understanding of skin conditions, and raise awareness of available treatments. Objective: To investigate and characterize the representation of skin tones in DTCAs. Methods: Nielsen ratings were utilized to identify the networks most watched by Black viewers in 2022. Programming on NBCUniversal, ABC, CBS, and FOX that aired in the District of Columbia, suburban Maryland, and Northern Virginia from June 2022 to July 2022 was reviewed for DTCAs. DTCAs were then analyzed to determine the skin tones of models and skin conditions depicted on models with darkly pigmented skin. Results: Of the 106 DTCAs related to dermatologic conditions, there were 13 unique advertisements featuring 32 unique models. Four advertisements depicted the skin condition on darkly pigmented skin tones. Using the Monk Skin Tone (MST) scale to assess the 32 unique individuals, only 25% (n = 8) were rated at an MST 7 or above, and 6.25% (n = 2) were rated at an MST 10. Limitations: This study has the limitation of only sampling DTCAs from Washington, District of Columbia which does not fully represent all dermatology-related DTCAs in the United States. Conclusion: Results of this content analysis demonstrate that the number of persons of color within dermatologic DTCAs is 23%, whereas there are 13.6% Black individuals in the 2021 US census. This suggests that DTCAs are becoming more diverse since 2018. However, findings also show that the vast majority of DTCAs do not include models with darkly pigmented skin, and there remains a lack of advertisements depicting skin disease among people of color. Given the role of DTCAs in informing and aiding patients' requests for prescription drugs, representation of all skin tones is essential for this communication to be effective, especially in the field of dermatology.

A Cdc48p-associated factor modulates endoplasmic reticulum-associated degradation, cell stress, and ubiquitinated protein homeostasis.

The hexameric AAA-ATPase, Cdc48p, catalyzes an array of cellular activities, including endoplasmic reticulum (ER)-associated degradation (ERAD), ER/Golgi membrane dynamics, and DNA replication. Accumulating data suggest that unique Cdc48p partners, such as Npl4p-Ufd1p and Ubx1p/Shp1p (p47 in vertebrates), target Cdc48p for these diverse functions. Other Cdc48p-associated proteins have been identified, but the interplay among these factors and their activities is largely cryptic. We now report on a previously uncharacterized Cdc48p-associated protein, Ydr049p, also known as Vms1p, which binds Cdc48p at both the ER membrane and in the cytosol under non-stressed conditions. Loss of YDR049 modestly slows the degradation of the cystic fibrosis transmembrane conductance regulator but does not impede substrate ubiquitination, suggesting that Ydr049p acts at a postubiquitination step in the ERAD pathway. Consistent with Ydr049p playing a role in Cdc48p substrate release, ydr049 mutant cells accumulate Cdc48p-bound ubiquitinated proteins at the ER membrane. Moreover, YDR049 interacts with genes encoding select UBX (ubiquitin regulatory X) and UFD (ubiquitin fusion degradation) proteins, which are Cdc48p partners. Exacerbated growth defects are apparent in some of the mutant combinations, and synergistic effects on the degradation of cystic fibrosis transmembrane conductance regulator and CPY*, which is a soluble ERAD substrate, are evident in specific ydr049-ufd and -ubx mutants. These data suggest that Ydr049p acts in parallel with Cdc48p partners to modulate ERAD and other cellular activities.

Color or money?: The impact of socioeconomic status and race/ethnicity on breast cancer mortality.

BACKGROUND: Although the incidence of breast cancer is highest in White women, Black women die at a higher rate. Our aim was to compare the relative association between race/ethnicity and socioeconomic status on breast cancer mortality. METHODS: We identified female breast cancer patients diagnosed between 2007 - 2011 and followed through 2016 in the SEER database. Patients were grouped into socioeconomic quartiles by a prosperity index. The primary outcome of interest was 5-year cancer-specific survival. RESULTS: A total of 286,520 patients were included. Five-year survival was worst for Black women compared to other races/ethnicities in each socioeconomic quartile. When compared to White women in the lowest quartile, Black women in the lowest quartile, 2nd quartile, and 3rd quartile experienced the lowest 5-year survival rates (Hazard ratio 1.33, 1.23, 1.20; P < 0.01). CONCLUSION: Regarding cancer mortality, only in the most prosperous quartile do Black women achieve a similar outcome to the poorest quartile White women.

Metastatic Acral lentiginous melanoma: A case report and review.

Of the four subtypes of cutaneous melanoma, acral lentiginous melanoma (ALM) is atypical in its presentation. ALM is a rare melanoma subtype that presents on the volar surfaces of the hand and foot. The difficulty of making an early diagnosis of ALM is highlighted by the case seen in our institution. The dire prognosis associated with ALM is postulated to be not only related to its destructive nature, but also due to a lack of patient awareness and vigilance, inadequate physician awareness, and disparity in healthcare access. We present this as a unique account of an ALM lesion in a 76 year old African-American male presenting originally in the left foot that went misdiagnosed for several years. The original lesion was considered to be an ulcerating left great toe lesion with signs typical of osteomyelitis. These clinical findings were corroborated by radiological x-ray evidence. Upon amputation and biopsy for suspected worsening osteomyelitis five years later, the pathological diagnosis of melanoma was finally made.

Persistence of Disparity in Thyroid Cancer Survival After Adjustments for Socioeconomic Status and Access.

INTRODUCTION: Thyroid cancer incidence has increased substantially in the past 4 decades, estimated at 3.5% annually. Incidence is highest in white patients, yet black patients have the worst survival. Racial/ethnic differences in presentation and outcomes are hypothesized to be a result of differences in access to care. Analyses delineating the relative contribution of access to racial/ethnic survival disparities are scarce. We aimed to explore the association of delay in access to care and early/increased detection with racial/ethnic disparities in thyroid cancer survival. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was queried from 2007 to 2011 for patients with a first primary thyroid cancer diagnosis and up to 5 years of follow-up. Composite scores were generated from county-level variables to capture socioeconomic status and screening habits. Kaplan-Meier analysis and Cox proportional hazards models were utilized for survival analysis. RESULTS: We identified 46,970 patients (67% white, 7% black, 15% Hispanic, 10% Asian or Pacific Islander, and 1% unknown/other). Compared to white patients, black, Hispanic, and Asian or Pacific Islander patients were more likely to present with distant disease (3% vs 5%, 5%, and 6%, respectively; P < .001). After adjusting for sex, age, stage, subtype, tumor size, surgery, radiation, socioeconomics, and screening habits, black patients were the only race/ethnicity found to have increased odds of 5-year mortality compared to white patients (24%, P < .001). CONCLUSION: Thyroid cancer survival is worst for black patients regardless of socioeconomic status or screening habits. Racial/ethnic disparities in survival are not attributable to early detection alone.

Cantaloupe melon genome reveals 3D chromatin features and structural relationship with the ancestral cucurbitaceae karyotype.

Cucumis melo displays a large diversity of horticultural groups with cantaloupe melon the most cultivated type. Using a combination of single-molecule sequencing, 10X Genomics link-reads, high-density optical and genetic maps, and chromosome conformation capture (Hi-C), we assembled a chromosome scale C. melo var. cantalupensis Charentais mono genome. Integration of RNA-seq, MeDip-seq, ChIP-seq, and Hi-C data revealed a widespread compartmentalization of the melon genome, segregating constitutive heterochromatin and euchromatin. Genome-wide comparative and evolutionary analysis between melon botanical groups identified Charentais mono genome increasingly more divergent from Harukei-3 (reticulatus), Payzawat (inodorus), and HS (ssp. agrestis) genomes. To assess the paleohistory of the Cucurbitaceae, we reconstructed the ancestral Cucurbitaceae karyotype and compared it to sequenced cucurbit genomes. In contrast to other species that experienced massive chromosome shuffling, melon has retained the ancestral genome structure. We provide comprehensive genomic resources and new insights in the diversity of melon horticultural groups and evolution of cucurbits.

Assessment of the Readability, Availability, and Quality of Online Patient Education Materials Regarding Uveitis Medications.

Purpose: To assess the availability, quality, and readability of online patient education materials regarding uveitis medications.Methods: The top 10 Google search results for 10 commonly prescribed uveitis medications (prednisone, azathioprine, methotrexate, mycophenolate mofetil, cyclosporine, tacrolimus, chlorambucil, cyclophosphamide, adalimumab, and infliximab) were analyzed for readability and accountability. Readability was assessed with the Flesch reading ease score, Flesch-Kincaid grade level, Gunning Fog Index, Simple Measure of Gobbledygook Index, and Coleman Liau Index. JAMA benchmarks were used to assign websites accountability scores. Statistical analysis was performed with two-tailed t-tests.Results: Of 100 search results, none complied with the recommended sixth-grade reading level across all readability formulas. Only one website satisfied all 4 JAMA benchmarks, two websites were able to satisfy three benchmarks, and the remainder achieved two or less.Conclusions: Online information regarding uveitis medications lacks accountability and is not written at an appropriate level for the average patient.