Einkorn genomics sheds light on history of the oldest domesticated wheat.

Einkorn (Triticum monococcum) was the first domesticated wheat species, and was central to the birth of agriculture and the Neolithic Revolution in the Fertile Crescent around 10,000 years ago1,2. Here we generate and analyse 5.2-Gb genome assemblies for wild and domesticated einkorn, including completely assembled centromeres. Einkorn centromeres are highly dynamic, showing evidence of ancient and recent centromere shifts caused by structural rearrangements. Whole-genome sequencing analysis of a diversity panel uncovered the population structure and evolutionary history of einkorn, revealing complex patterns of hybridizations and introgressions after the dispersal of domesticated einkorn from the Fertile Crescent. We also show that around 1% of the modern bread wheat (Triticum aestivum) A subgenome originates from einkorn. These resources and findings highlight the history of einkorn evolution and provide a basis to accelerate the genomics-assisted improvement of einkorn and bread wheat.

Deciphering salt stress responses in Solanum pimpinellifolium through high-throughput phenotyping.

Soil salinity is a major environmental stressor affecting agricultural productivity worldwide. Understanding plant responses to salt stress is crucial for developing resilient crop varieties. Wild relatives of cultivated crops, such as wild tomato, Solanum pimpinellifolium, can serve as a useful resource to further expand the resilience potential of the cultivated germplasm, S. lycopersicum. In this study, we employed high-throughput phenotyping in the greenhouse and field conditions to explore salt stress responses of a S. pimpinellifolium diversity panel. Our study revealed extensive phenotypic variations in response to salt stress, with traits such as transpiration rate, shoot mass, and ion accumulation showing significant correlations with plant performance. We found that while transpiration was a key determinant of plant performance in the greenhouse, shoot mass strongly correlated with yield under field conditions. Conversely, ion accumulation was the least influential factor under greenhouse conditions. Through a Genome Wide Association Study, we identified candidate genes not previously associated with salt stress, highlighting the power of high-throughput phenotyping in uncovering novel aspects of plant stress responses. This study contributes to our understanding of salt stress tolerance in S. pimpinellifolium and lays the groundwork for further investigations into the genetic basis of these traits, ultimately informing breeding efforts for salinity tolerance in tomato and other crops.

Medical and aesthetic improvement of photodamaged skin by the combination of intense pulsed light and photodynamic therapy with 10% aminolevulinic acid hydrochloride gel.

OBJECTIVE: To evaluate the efficacy and safety of photodynamic therapy (PDT) with the novel 10% aminolevulinic acid (ALA) hydrochloride gel (10% ALA gel) and BF-RhodoLED® light (635 nm; 37 J/cm2 ) in combination with intense pulsed light (IPL) to augment the medical and aesthetic improvement of photodamaged skin of the décolleté. METHODS: This was a single-site prospective, randomized, intraindividual split chest pilot study with 20 female subjects with moderate to severe photodamage of the décolleté. Subjects were randomized to ALA-PDT + IPL to one split-side of the chest and ALA-PDT only to the contralateral side. Three blinded raters assessed aesthetic improvement using the global aesthetic improvement scale (GAIS). RESULTS: Eighteen subjects completed the study. Superior GAIS results were achieved on the ALA-PDT + IPL treatment side than on the ALA-PDT only treatment side (p < 0.001) after 24 weeks of follow-up. CONCLUSIONS: ALA-PDT using 10% ALA hydrochloride gel and BF-RhodoLED® light had superior rejuvenation effects on the décolleté when combined with IPL compared to ALA-PDT alone.

Prospective study of intense pulsed light versus pulsed dye laser with or without blue light in the activation of PDT for the treatment of actinic keratosis and photodamage.

BACKGROUND: Exposure to ultraviolet (UV) light from the sun is known to have a deleterious effect on the skin. Repeated insults to the dermal matrix from UV radiation result in the clinical signs of photodamage, including changes in skin elasticity, color, and texture. UV radiation also leads to the accumulation of DNA mutations and promotes tumor development, resulting in the formation of cutaneous precancerous and cancerous lesions. Continuous-wave incoherent blue light, intense pulsed light (IPL), and pulsed dye laser (PDL) are safe and efficacious light sources commonly used for aminolevulinic acid photodynamic therapy (PDT). The aim of this study was to prospectively evaluate the efficacy of PDT for the treatment of photodamage and actinic keratoses using four different combinations of light sources: PDL, PDL + blue light, IPL, and IPL + blue light. STUDY: A total of 220 patients with either photodamage or actinic keratosis (AK) were recruited from the Miami Dermatology Laser Institute (Miami, FL) and were assigned prospectively to undergo one PDT treatment with one of the four light options: PDL, PDL + blue light, IPL or IPL + blue light. Of the 220 patients enrolled in treatment groups, 214 patients completed the study. Of the 214 patients, 88 received treatment for AK, and 126 received treatment for photodamage. All patients gave their consent to participate in the study and to allow their photographs to be utilized for the purpose of scientific presentations. RESULTS: Treatment with IPL resulted in a 70.8% reduction of actinic keratoses at a 1-month follow-up. Treatment with IPL and blue light 84.4% reduction of actinic keratoses at 1 month follow up. Treatment with PDL 70.5% reduction of actinic keratoses at 1 month follow up. Treatment with PDL and blue light 69.3% reduction of actinic keratoses at 1 month follow up. Treatment with IPL resulted in an improvement score of 2.9. Treatment with IPL and blue light resulted in an improvement score of 3.0. Treatment PDL resulted in an improvement score of 1.5. Treatment with PDL and blue light resulted in an improvement score of 1.8. CONCLUSION: Although all four treatment groups led to some improvement in signs of photoaging, IPL + blue light again demonstrated increased efficacy when compared to IPL, PDL, and PDL + blue light treatment groups. Results from our study were limited by an unequal distribution between treatment groups and a lack of follow-up beyond a 1-month period and warrant further research.

Analysis of port-wine birthmark vascular characteristics by location: Utility of optical coherence tomography mapping.

INTRODUCTION: Port-wine birthmarks (PWBs) are congenital capillary malformations that can be located on any area of the body. Vascular features include vessel size, depth, and density, which can greatly differ between patients, individual lesions, and even sites within the same lesion. Previous studies have determined that the location of PWB lesions has impacted their clinical response to laser treatment. OBJECTIVE: We utilized dynamic optical coherence tomography (D-OCT) to measure in vivo vessel diameter, density, and superficial plexus depth in patients of all ages with PWB on various sites of the body. We hypothesized that these vascular characteristics would differ according to body location. MATERIALS AND METHODS: Patients who had a PWB and presented to clinic at three sites for treatment with the pulsed dye laser (PDL) were enrolled into the study. A D-OCT scanner was utilized for noninvasive, in vivo imaging of PWB lesions. The depth of the top portion of the superficial vascular plexus was estimated as the depth at which the vessel density reaches 50% of the maximum. Vessel diameter and density were calculated by incorporated software algorithm. RESULTS: A total of 108 patients were enrolled into the study. There was a total of 204 measurements of PWB lesions. Of all patients, 56.5% (n = 61) reported having a previous treatment with PDL. Of all D-OCT scans, 62.3% (n = 127) were located on the head, 14.2% (n = 29) the upper extremities, 8.3% (n = 17) the lower extremities, 7.8% (n = 16) the trunk, and 7.8% (n = 15) the neck. All locations were compared for each vascular characteristic. For superficial plexus depth, lesions on the head were significantly shallower than those on the upper extremities (217 vs. 284 µm; p < 0.001) and lower extremities (217 vs. 309 µm; p < 0.001). For vessel diameter, lesions on the head had significantly larger vessels than those on the upper extremities (100 vs. 72 µm; p = 0.001). For vessel density, lesions on the head had significantly denser vessels than those on the trunk (19% vs. 9.6%; p = 0.039) and upper extremities (19% vs. 9.3%; p < 0.001) CONCLUSIONS: PWB lesions have distinct vascular characteristics, which can be associated with their body location. This includes superficial vascular plexus depth as well as vessel diameter and density.

Vascular characteristics of port wine birthmarks as measured by dynamic optical coherence tomography.

BACKGROUND: Port wine birthmarks (PWBs) are congenital capillary malformations. Vessel characteristics, such as diameter and depth, may impact presentation and outcomes. They can be imaged using dynamic optical coherence tomography, a high-resolution, noninvasive imaging method. PURPOSE: We conducted a cross-sectional observational study to measure in vivo vascular characteristics as a function of PWB color. METHODS: Patients undergoing treatment for PWB were recruited from 3 sites. PWBs were classified by color. Dynamic optical coherence tomography images with calculations were obtained. RESULTS: One hundred eight patients were enrolled. Mean age correlated with PWB color, with birthmarks being lighter in younger patients and darker in older patients (P < .01). Mean superficial plexus depth was significantly shallower in purple PWBs than in pink PWBs. Color was not associated with significant differences in mean superficial vessel density or diameter. Among pink PWBs, each 10-year increase in age was associated with a 10.6-µm increase in superficial plexus depth. Among purple PWBs, each 10-year increase in age was associated with a 16.2-µm reduction in superficial plexus depth. In lesions without prior treatment, vessel density was 12.7% lower in purple PWBs than in pink PWBs. CONCLUSION: Superficial vessels of purple PWBs were significantly closer to the epidermis than those of pink PWBs, which might impact optimal laser parameters.

US Dermatology Resident Responses about the COVID-19 Pandemic: Results from a Nationwide Survey.

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has drastically changed resident training in the United States. Here, we explore the early perceived effects of COVID-19 on dermatology residents through an electronic sample survey and identify possible areas for targeted improvement in lieu of a possible second wave of COVID-19 cases. METHODS: On April 3, 2020, a survey of link with 25 questions was sent to dermatology program coordinators to be disseminated among dermatology residents in the United States. The survey was closed on April 13, 2020. All of the questions were optional and no personal identifiers were collected. RESULTS: A total of 140 dermatology residents from 50 different residency programs across 26 states responded to the survey. The majority of respondents (85%) reported negative effects of COVID-19 on their overall wellness. Despite the majority of residents (92%) speculating that COVID-19 will have negative long-term effects on the US economy, only 33% agreed or strongly agreed that it will affect their job prospects. Teledermatology was widely implemented following the declaration of a national emergency (96% of represented residencies compared with only 30% before the pandemic), with heavy resident involvement. The majority of residents (99%) reported having virtual didactics and that they found them to be beneficial. Most residents were uncomfortable with the prospect of being reassigned to a nondermatology specialty during the pandemic. In addition, 22% of residents believed that their leadership were not transparent and prompt in addressing changes relating to COVID-19. CONCLUSIONS: Dermatology residents were affected negatively by COVID-19 in regard to their well-being, clinical training, and education. Several areas of improvement were identified that could improve our preparedness for a second wave of the virus.

Hotspots in the genomic architecture of field drought responses in wheat as breeding targets.

Wheat can adapt to most agricultural conditions across temperate regions. This success is the result of phenotypic plasticity conferred by a large and complex genome composed of three homoeologous genomes (A, B, and D). Although drought is a major cause of yield and quality loss in wheat, the adaptive mechanisms and gene networks underlying drought responses in the field remain largely unknown. Here, we addressed this by utilizing an interdisciplinary approach involving field water status phenotyping, sampling, and gene expression analyses. Overall, changes at the transcriptional level were reflected in plant spectral traits amenable to field-level physiological measurements, although changes in photosynthesis-related pathways were found likely to be under more complex post-transcriptional control. Examining homoeologous genes with a 1:1:1 relationship across the A, B, and D genomes (triads), we revealed a complex genomic architecture for drought responses under field conditions, involving gene homoeolog specialization, multiple gene clusters, gene families, miRNAs, and transcription factors coordinating these responses. Our results provide a new focus for genomics-assisted breeding of drought-tolerant wheat cultivars.

Divergence between bread wheat and Triticum militinae in the powdery mildew resistance QPm.tut-4A locus and its implications for cloning of the resistance gene.

A segment of Triticum militinae chromosome 7G harbors a gene(s) conferring powdery mildew resistance which is effective at both the seedling and the adult plant stages when transferred into bread wheat (T. aestivum). The introgressed segment replaces a piece of wheat chromosome arm 4AL. An analysis of segregating materials generated to positionally clone the gene highlighted that in a plant heterozygous for the introgression segment, only limited recombination occurs between the introgressed region and bread wheat 4A. Nevertheless, 75 genetic markers were successfully placed within the region, thereby confining the gene to a 0.012 cM window along the 4AL arm. In a background lacking the Ph1 locus, the localized rate of recombination was raised 33-fold, enabling the reduction in the length of the region containing the resistance gene to a 480 kbp stretch harboring 12 predicted genes. The substituted segment in the reference sequence of bread wheat cv. Chinese Spring is longer (640 kbp) and harbors 16 genes. A comparison of the segments' sequences revealed a high degree of divergence with respect to both their gene content and nucleotide sequence. Of the 12 T. militinae genes, only four have a homolog in cv. Chinese Spring. Possible candidate genes for the resistance have been identified based on function predicted from their sequence.

Transcriptome reprogramming due to the introduction of a barley telosome into bread wheat affects more barley genes than wheat.

Despite a long history, the production of useful alien introgression lines in wheat remains difficult mainly due to linkage drag and incomplete genetic compensation. In addition, little is known about the molecular mechanisms underlying the impact of foreign chromatin on plant phenotype. Here, a comparison of the transcriptomes of barley, wheat and a wheat-barley 7HL addition line allowed the transcriptional impact both on 7HL genes of a non-native genetic background and on the wheat gene complement as a result of the presence of 7HL to be assessed. Some 42% (389/923) of the 7HL genes assayed were differentially transcribed, which was the case for only 3% (960/35 301) of the wheat gene complement. The absence of any transcript in the addition line of a suite of chromosome 7A genes implied the presence of a 36 Mbp deletion at the distal end of the 7AL arm; this deletion was found to be in common across the full set of Chinese Spring/Betzes barley addition lines. The remaining differentially transcribed wheat genes were distributed across the whole genome. The up-regulated barley genes were mostly located in the proximal part of the 7HL arm, while the down-regulated ones were concentrated in the distal part; as a result, genes encoding basal cellular functions tended to be transcribed, while those encoding specific functions were suppressed. An insight has been gained into gene transcription in an alien introgression line, thereby providing a basis for understanding the interactions between wheat and exotic genes in introgression materials.

Sequencing flow-sorted short arm of Haynaldia villosa chromosome 4V provides insights into its molecular structure and virtual gene order.

BACKGROUND: Haynaldia villosa (H. villosa) has been recognized as a species potentially useful for wheat improvement. The availability of its genomic sequences will boost its research and application. RESULTS: In this work, the short arm of H. villosa chromosome 4V (4VS) was sorted by flow cytometry and sequenced using Illumina platform. About 170.6 Mb assembled sequences were obtained. Further analysis showed that repetitive elements accounted for about 64.6% of 4VS, while the coding fraction, which is corresponding to 1977 annotated genes, represented 1.5% of the arm. The syntenic regions of the 4VS were searched and identified on wheat group 4 chromosomes 4AL, 4BS, 4DS, Brachypodium chromosomes 1 and 4, rice chromosomes 3 and 11, and sorghum chromosomes 1, 5 and 8. Based on genome-zipper analysis, a virtual gene order comprising 735 gene loci on 4VS genome was built by referring to the Brachypodium genome, which was relatively consistent with the scaffold order determined for Ae. tauschii chromosome 4D. The homologous alleles of several cloned genes on wheat group 4 chromosomes including Rht-1 gene were identified. CONCLUSIONS: The sequences provided valuable information for mapping and positional-cloning genes located on 4VS, such as the wheat yellow mosaic virus resistance gene Wss1. The work on 4VS provided detailed insights into the genome of H. villosa, and may also serve as a model for sequencing the remaining parts of H. villosa genome.

The in silico identification and characterization of a bread wheat/Triticum militinae introgression line.

The capacity of the bread wheat (Triticum aestivum) genome to tolerate introgression from related genomes can be exploited for wheat improvement. A resistance to powdery mildew expressed by a derivative of the cross-bread wheat cv. Tähti × T. militinae (Tm) is known to be due to the incorporation of a Tm segment into the long arm of chromosome 4A. Here, a newly developed in silico method termed rearrangement identification and characterization (RICh) has been applied to characterize the introgression. A virtual gene order, assembled using the GenomeZipper approach, was obtained for the native copy of chromosome 4A; it incorporated 570 4A DArTseq markers to produce a zipper comprising 2132 loci. A comparison between the native and introgressed forms of the 4AL chromosome arm showed that the introgressed region is located at the distal part of the arm. The Tm segment, derived from chromosome 7G, harbours 131 homoeologs of the 357 genes present on the corresponding region of Chinese Spring 4AL. The estimated number of Tm genes transferred along with the disease resistance gene was 169. Characterizing the introgression's position, gene content and internal gene order should not only facilitate gene isolation, but may also be informative with respect to chromatin structure and behaviour studies.

Influence of diet on the gut microbiome and implications for human health.

Recent studies have suggested that the intestinal microbiome plays an important role in modulating risk of several chronic diseases, including inflammatory bowel disease, obesity, type 2 diabetes, cardiovascular disease, and cancer. At the same time, it is now understood that diet plays a significant role in shaping the microbiome, with experiments showing that dietary alterations can induce large, temporary microbial shifts within 24 h. Given this association, there may be significant therapeutic utility in altering microbial composition through diet. This review systematically evaluates current data regarding the effects of several common dietary components on intestinal microbiota. We show that consumption of particular types of food produces predictable shifts in existing host bacterial genera. Furthermore, the identity of these bacteria affects host immune and metabolic parameters, with broad implications for human health. Familiarity with these associations will be of tremendous use to the practitioner as well as the patient.

Risk of cutaneous squamous cell carcinoma after treatment of basal cell carcinoma with vismodegib.

BACKGROUND: Vismodegib is a first-in-class agent targeting the hedgehog signaling pathway for treatment of patients with locally advanced basal cell carcinoma (BCC) and metastatic BCC. There have been concerns about the development of squamous cell carcinoma (SCC) in patients treated with this drug. OBJECTIVE: We sought to determine whether treatment with vismodegib is associated with an increase in the risk of cutaneous SCC. METHODS: In this retrospective cohort study, patients treated with vismodegib as part of phase I and II clinical studies were compared with participants from the University of California, San Francisco, Nonmelanoma Skin Cancer Cohort who received standard therapy for primary BCC. In total, 1675 patients were included in the analysis, and the development of SCC after vismodegib exposure was assessed. RESULTS: The use of vismodegib was not associated with an increased risk of subsequent development of SCC (adjusted hazard ratio, 0.57; 95% confidence interval, 0.28-1.16). Covariates including age, sex, history of previous nonmelanoma skin cancer, and number of visits per year were significantly associated with the development of SCC. LIMITATIONS: A limitation of the study was that a historic control cohort was used as a comparator. CONCLUSIONS: Vismodegib was not associated with an increased risk of subsequent SCC when compared with standard surgical treatment of BCC.

An Analysis of Laser Therapy for the Treatment of Nonmelanoma Skin Cancer.

BACKGROUND: Skin cancer remains the most prevalent type of cancer in the United States, and its burden on the health care system remains substantial. Standard treatments such as cryosurgery, electrodessication and curettage, topical and photodynamic therapies, and surgical excision including Mohs micrographic surgery are not without inherent morbidity, including risk of bleeding, infection, and scar. OBJECTIVE: Lasers may be an alternative for treatment of nonmelanoma skin cancer, and this paper reviews this therapeutic option. METHODS: A comprehensive search in the Cochrane Library, MEDLINE, and PUBMED databases was performed to identify relevant literature investigating the role of laser therapy in the treatment of nonmelanoma skin cancer. RESULTS: New literature regarding laser treatment of nonmelanoma skin cancer is emerging, demonstrating promising clinical outcomes. The greatest efficacy has been seen with vascular-selective and ablative lasers in the treatment of basal cell carcinomas. Some success has been reported for laser treatment of squamous cell carcinoma, but data are less convincing. In summary, laser therapy offers an alternative treatment option for nonmelanoma skin cancer; however, its clinical efficacy is variable and, at this time, remains less than currently accepted standards of care. CONCLUSION: Further studies are needed to optimize parameters, determine maximum efficacy, and provide long-term follow-up.

Update on the Systemic Risks of Superpotent Topical Steroids.

INTRODUCTION: The potential for systemic effects due to percutaneous absorption of superpotent topical steroids has been a longstanding concern. The Food and Drug Administration currently recommends limiting the use of superpotent topical steroids to 50g per week for 2 or 4 consecutive weeks depending on the formulation, which is mostly based on the exact duration with which phase 3 clinical trials were allowed to be conducted per the FDA. This article reviews all published clinical incidence of adrenal adverse effects in the medical literature, specifically Cushing's syndrome (CS) and pathologic adrenal suppression (PAAS), to try to ascertain a more realistic limit for the safe use of superpotent topical steroids as it pertains to its potential systemic effects.

METHODS: Literature search was conducted using PubMed. Only cases of CS and PAAS secondary to the use of Class I superpotent topical steroids were included. Pediatric cases and full articles unavailable in English were excluded.

RESULTS: There were a total of 14 cases of CS and 5 cases of subsequent PAAS found in the current literature.

DISCUSSION: From our review of these cases, if the amount used per week is within FDA guidelines, it appears that patients needed to use superpotent topical steroids for far greater than 2 or 4 weeks to develop CS or PAAS. CS did not necessarily predict occurrence of PAAS, but in all cases CS appeared to be a prerequisite for developing PAAS. All cases of CS and all but one case of PAAS were reversible. If excessive amount of greater than 50g per week is avoided, it appears that superpotent topical steroids may be safe to use consecutively for months, perhaps even years, without causing systemic effects.

J Drugs Dermatol. 2017;16(7):643-648.

Use of an oral phosphodiesterase-4 inhibitor (apremilast) for the treatment of chronic, severe atopic dermatitis: a case report.

Atopic dermatitis (AD) is a common inflammatory dermatosis characterized by pruritus, erythema, induration, and lichenification. Current treatment options for generalized atopic dermatitis are limited and have potentially serious adverse effects, especially in patients with severe, chronic AD who frequently require systemic anti-inflammatory agents. Apremilast, an oral phosphodiesterase-4 inhibitor, was FDA approved in September 2014 for the treatment of moderate-to-severe plaque psoriasis. However, its upstream anti-inflammatory effects, ease of use as an oral agent, and mild side-effect profile make it an interesting treatment option for AD as well. Herein, we present a patient with a life-long history of AD recalcitrant to topical steroids and cyclosporine who attained subjective and objective improvement in pruritus and erythema after 10-week treatment with apremilast.