Genetics and plasticity of white leaf mark variegation in white clover (Trifolium repens L.).

BACKGROUND AND AIMS: Leaf variegation is common in plants and confers diverse adaptive functions. However, its genetic underpinnings remain largely unresolved; this is particularly true for variegation that arises through modified leaf tissue structure that affects light reflection. White clover is naturally polymorphic for structure-based white leaf mark variegation. It therefore provides a useful system to examine the genetic basis of this phenotype, and to assess potential costs to photosynthetic efficiency resulting from modified leaf structures. This study sought to map the loci controlling the white leaf mark in white clover and evaluate the relationship between white leaf mark, leaf thickness, and photosynthetic efficiency. METHODS: We generated a high-density genetic linkage map from an F3 mapping population, employing reference genome-based SNP markers. White leaf mark was quantified through detailed phenotypic evaluations alongside leaf thickness to test how tissue thickness may affect the variegation phenotype. Quantitative trait locus (QTL) mapping was performed to characterize their genetic bases. Photosynthetic efficiency measurements were used to test for physiological trade-offs between variegation and photosynthetic output. KEY RESULTS: The V locus, a major gene responsible for the white leaf mark polymorphism, was mapped to the distal end of chromosome 5, and several modifier loci were also mapped that contribute additively to variegation intensity. The presence and intensity of white leaf mark was associated with greater leaf thickness; however, increased variegation did not detectably affect photosynthetic efficiency. CONCLUSIONS: We have successfully mapped the major locus governing the white leaf mark in white clover, along with several modifier loci, revealing a complex basis for this structure-based variegation. The apparent absence of compromised photosynthesis in variegated leaves challenges the notion that variegation creates fitness trade-offs between photosynthetic efficiency and other adaptive functions. This finding suggests that other factors may maintain the white leaf mark polymorphism in white clover.

The 730 nm picosecond titanium sapphire laser for treatment of café-au-lait macules in all skin types.

OBJECTIVES: Café-au-lait macules (CALM) are benign birthmarks presenting as uniformly pigmented, well demarcated, brown patches that can be distressing to patients, especially when located in cosmetically sensitive areas. As with all pigmentary lesions in skin of color patients, CALMs have been particularly challenging to treat. Here we present the first case series characterizing treatment parameters and clinical outcomes utilizing the 730-nm picosecond titanium sapphire laser for the treatment of CALMs. This device provides an additional safe and effective treatment option for these challenging cases. METHODS: We performed a retrospective review of patients treated at a single institution between April 2021 and December 2023. Clinical photographs were graded by 3 outside board-certified dermatologists using a 5-point visual analog scale. RESULTS: Fourteen patients (age range: 10 months-66 years, mean age: 27.4 years, Fitzpatrick skin types II-VI) were treated for CALM on the face (11) or body (3). On average, patients received 4.3 treatments, with treatment intervals ranging from 4 to 40 weeks. Treatment remains ongoing with the 730-nm picosecond laser for eight patients. Overall, patients were rated to have a mean improvement of 26%-50%. Two patients (FST III and VI) achieved 100% clearance after 4-5 treatment sessions. Our study included four patients whose CALM were of the smooth bordered "coast of California" subtype, three of whom had a mean improvement rating of only 1%-25%. The fourth patient had near complete resolution. Follow up for these patients has ranged from 6 weeks to 1.5 years. Of the patients treated, one patient experienced transient post-inflammatory hyperpigmentation and another transient post-inflammatory hypopigmentation, while a third patient experienced mild persistent guttate hypopigmentation. Three patients experienced partial recurrence indicating that maintenance treatments may be needed in some patients. CONCLUSION: The 730-nm picosecond titanium sapphire laser is a safe and efficacious treatment option, in the right morphologic setting, to improve the cosmetic appearance of CALMs in a wide range of ages and skin types. To our knowledge, this is the first reported treatment of CALMs with picosecond lasers in FST V and VI patients. Our study also supports prior studies which have found that CALM with smooth-bordered "coast of California" morphology have a poor response to laser therapy as compared to those with jagged or ill-defined bordered "coast of Maine" morphology.

Efficacy of 785-nm Picosecond Titanium Sapphire Laser for Treatment of Brown Nevus of Ota Lesions in FST II-V: A Retrospective Analysis.

BACKGROUND: Nevus of Ota (NOTA) is a dermal melanocytosis acquired in early childhood or pregnancy. Given their color variability, NOTA often require a combination of wavelengths for successful treatment. Quality-switched lasers have consistently shown efficacy in targeting dermal pigment, while picosecond lasers (PSLs) are an emerging technology for pigmentary disorders. OBJECTIVE: To further elucidate its efficacy, the authors conducted a retrospective review of 17 patients with NOTA treated with a 785-nm PSL for brown NOTA lesions between 2021 and 2023. MATERIALS AND METHODS: The primary end point analyzed clinical improvement based on before and after photography reviewed by 3 board-certified dermatologists using a five-point visual analog scale. RESULTS: Seventeen patients of Fitzpatrick skin types (FSTs) II to V, ranging from ages 14 to 38 years, were included in this study. Patients were treated for an average of 3.2 sessions in 2 to 3-month intervals. Visual analog scale scores demonstrated a mean clearance of 51% to 75%. No pigmentary alterations were noted. CONCLUSION: Because NOTA is common in higher FSTs, the authors believe that the 785-nm PSL is an excellent treatment option for brown NOTA in these skin types. This study highlights the need for further investigation to determine optimal treatment parameters for the color-based laser treatment approach for NOTA.

Cryo-EM structure of the needle filament tip complex of the Salmonella type III secretion injectisome.

Type III secretion systems are multiprotein molecular machines required for the virulence of several important bacterial pathogens. The central element of these machines is the injectisome, a ∼5-Md multiprotein structure that mediates the delivery of bacterially encoded proteins into eukaryotic target cells. The injectisome is composed of a cytoplasmic sorting platform, and a membrane-embedded needle complex, which is made up of a multiring base and a needle-like filament that extends several nanometers from the bacterial surface. The needle filament is capped at its distal end by another substructure known as the tip complex, which is crucial for the translocation of effector proteins through the eukaryotic cell plasma membrane. Here we report the cryo-EM structure of the Salmonella Typhimurium needle tip complex docked onto the needle filament tip. Combined with a detailed analysis of structurally guided mutants, this study provides major insight into the assembly and function of this essential component of the type III secretion protein injection machine.

#CoreCosmeticSpecialties: An analysis of nonsurgical cosmetic procedure hashtags on Instagram.

OBJECTIVES: In this study, we seek to characterize both the account credentials and content type for posts among the most popular nonsurgical cosmetic procedure hashtags on Instagram. METHODS: Twenty-five hashtags related to nonsurgical cosmetic procedures were identified with over 250,000 posts each, ranging from 256,000 to 12.1 million posts per hashtag. The first 10 posts displayed under the "Top" section for each hashtag within Instagram, as sorted by Instagram's proprietary algorithm, were analyzed for account type and content type. Posts unrelated to the cosmetic procedure or with non-English captions were excluded. In total, 680 posts were queried with 250 posts meeting the inclusion criteria. RESULTS: Content creators included nonphysician providers (68%), core cosmetic physicians (12%), noncore cosmetic physicians (8%), and consumers or others (13%). Content type included before and after (45%), self-promotional (23%), educational (17%), personal (5%), entertainment (5%), and promotional (5%). Among the different content creator types, core cosmetic physicians had the largest proportion of educational content at 38%. CONCLUSIONS: High-quality educational content on Instagram from core cosmetic specialties is scarce. By increasing their presence on Instagram, core cosmetic physicians can provide patient education, counteract misinformation, and raise awareness on training and qualifications regarding nonsurgical cosmetic procedures.

Combination 1550 nm non-ablative fractional resurfacing and laser hair removal for treatment of Becker's nevi in skin types III-VI.

OBJECTIVES: Becker's nevus is a cosmetically bothersome benign hamartoma typically associated with basal layer hyperpigmentation and hypertrichosis. We herein present the largest case series characterizing treatment parameters and clinical outcomes of combined 1550 nm non-ablative fractional resurfacing and laser hair removal (long-pulsed neodymium-doped yttrium aluminum garnet or alexandrite) in the treatment of Becker's nevus. This is also the largest case series of laser treatment of Becker's nevus in Fitzpatrick skin types V and VI. METHODS: We performed a retrospective review of patients treated between 2016 and 2021. Clinical photographs were graded by three independent physicians using a 5-point visual analog scale. RESULTS: Twelve patients (mean age: 24.8 years, Fitzpatrick skin types III-VI) were treated for Becker's nevus on the face (4) or the trunk and/or extremities (8). Four patients were Fitzpatrick skin types V or VI. On average, patients received 5.3 treatments in 1-4-month intervals. Ten of the 12 patients had concomitant laser hair removal preceding same-day non-ablative fractional resurfacing (n = 7 with long-pulsed 1064 nm neodymium-doped yttrium aluminum garnet and n = 3 with long-pulsed 755 nm alexandrite). The number of treatments with each modality was determined by patient satisfaction with improvement in hyperpigmentation and hypertrichosis. At follow-up, which ranged from 6 to 40 weeks (mean 10.5 weeks), patients were given a mean improvement score of 51%-75%. No long-term adverse events were encountered in either group. Limitations include a small sample size and a lack of long-term follow-up. CONCLUSION: Combination 1550 nm non-ablative fractional resurfacing and laser hair removal is safe and efficacious in the cosmetic reduction of hyperpigmentation and hypertrichosis associated with Becker's nevus, including those with Fitzpatrick skin types V and VI.

Liberating more than light: Laser removal of branding tattoos is impactful in the recovery of sex trafficking survivors.

OBJECTIVES: Sex trafficking involves the use of force, fraud, or coercion to compel another person to engage in commercial sex acts. In 2020, 16,658 individuals were identified as sex trafficking victims in the United States, with thousands more not reported. Many victims are branded by their traffickers with tattoos conveying ownership, including names, symbols, and barcodes. We have partnered with local non-profits in Houston supporting sex trafficking survivors by providing pro bono laser tattoo removal, however we believe there is a greater need at a national level to support these survivors, allowing them to reclaim their bodies. METHODS: An online survey aimed at assessing the need and potential impact for pro bono branding tattoo laser removal services was distributed to United States organizations that support sex trafficking survivors. RESULTS: Forty organizations based in the Northeast (15%), Midwest (20%), South (45%), and West (20%) responded. Organizations support on average 81 survivors annually, ranging from 3 to 600 survivors, and estimate that 47% of survivors have branding tattoos. Among survivors with branding tattoos, approximately 67% were identified at an appropriate recovery stage to undergo laser removal. On a scale of 1-10 with 10 being the most impactful on recovery, removal of branding tattoos received an average impact score of 9.2. On a scale of 1-10, with 10 being the most need, pro bono services for laser removal received an average need score of 9.1. Qualitative responses provided several insights: laser removal may be associated with enhanced healing compared to tattoo cover-up, and survivors frequently move during their recovery process thus a successful removal campaign would require a nationwide network of partnering laser surgeons. CONCLUSIONS: Approximately 1 in 2 sex trafficking survivors are estimated to have branding tattoos and the removal of these tattoos is recognized as highly impactful on recovery. We propose a philanthropic campaign which involves the American Society for Laser Medicine and Surgery (ASLMS) establishing a national directory to connect sex trafficking survivors seeking removal of branding tattoos with interested ASLMS board-certified physician members.

Treatment of Nevus of Ota in Black patients with the 1064 nm QS or picosecond laser and nonablative fractional photothermolysis.

OBJECTIVES: Nevus of Ota is a benign melanocytic lesion that presents as a unilateral blue gray to brown facial patch favoring the distribution of the first two branches of the trigeminal nerve. Incidence is highest in Asian and Black populations, however, the overwhelming majority of studies are limited to diagnosis and treatment in Asian patients. We herein present 10 Black patients with Fitzpatrick skin types (FST) V and VI who underwent laser treatment for Nevus of Ota. METHODS: We performed a retrospective review of Black patients presenting with Nevus of Ota. Race was self-designated by all patients and documented in the medical record at the time of initial consultation. Primary outcomes were based on improvement using before and after photographs which were graded by three independent board-certified dermatologists using a 5-point visual analog scale. RESULTS: Ten FST V or VI patients with an age range of 9 months to 45 years were treated for Nevus of Ota. All patients were treated with the 1064 nm Q-switched neodymium doped yttrium aluminum garnet (QS Nd:YAG) and on average received 4.7 treatments at 2-10 month intervals. Fluence ranged from 1.8 to 2.3 J/cm2 , and total pulse count ranged from 510.9 to 776.6. 2/10 patients were additionally treated with 1550 nm nonablative fractional resurfacing (NAFR), and 1/10 patients underwent combination therapy with both NAFR and 1064 nm picosecond laser therapy. Overall, patients saw a mean improvement of 51%-75% at follow-up 5-254 weeks (mean 51.5 weeks) after treatment. Three patients experienced mild guttate hypopigmentation in treated areas. No other long-term adverse events were encountered. CONCLUSION: 1064 nm QS Nd:YAG laser therapy is a safe and efficacious treatment for Nevus of Ota in patients with FST V and VI. When patient improvement plateaus, combining therapy with 1550 nm NAFR or transitioning to 1064 nm picosecond laser may be of benefit. Patients should be counseled on the risk of guttate hypopigmentation. This is the largest case series to date of Black patients with Nevus of Ota, highlighting the need for further investigation to determine optimal device settings and treatment parameters for this population.

A polymorphic helix of a Salmonella needle protein relays signals defining distinct steps in type III secretion.

Type III protein-secretion machines are essential for the interactions of many pathogenic or symbiotic bacterial species with their respective eukaryotic hosts. The core component of these machines is the injectisome, a multiprotein complex that mediates the selection of substrates, their passage through the bacterial envelope, and ultimately their delivery into eukaryotic target cells. The injectisome is composed of a large cytoplasmic complex or sorting platform, a multiring base embedded in the bacterial envelope, and a needle-like filament that protrudes several nanometers from the bacterial surface and is capped at its distal end by the tip complex. A characteristic feature of these machines is that their activity is stimulated by contact with target host cells. The sensing of target cells, thought to be mediated by the distal tip of the needle filament, generates an activating signal that must be transduced to the secretion machine by the needle filament. Here, through a multidisciplinary approach, including solid-state NMR (SSNMR) and cryo electron microscopy (cryo-EM) analyses, we have identified critical residues of the needle filament protein of a Salmonella Typhimurium type III secretion system that are involved in the regulation of the activity of the secretion machine. We found that mutations in the needle filament protein result in various specific phenotypes associated with different steps in the type III secretion process. More specifically, these studies reveal an important role for a polymorphic helix of the needle filament protein and the residues that line the lumen of its central channel in the control of type III secretion.

Feeling the burn: Sunburn recall in staphylococcal scalded skin syndrome.

Staphylococcal scalded skin syndrome (SSSS) occurs primarily in infants and young children due to hematogenous dissemination of Staphylococcus aureus (S. aureus) exfoliative toxin resulting in painful erythema and superficial desquamation of the skin. Herein, we discuss a 7-year-old patient with SSSS in classic locations who additionally presented with photodistributed erythema without desquamation on the chest, arms, and back in locations of a recently healed sunburn. In this report, we discuss sunburn recall phenomenon as a result of SSSS.

Baptism of Fire: Modeling the Effects of Prescribed Fire on Lyme Disease.

Recently, tick-borne illnesses have been trending upward and are an increasing source of risk to people's health in the United States. This is due to range expansion in tick habitats as a result of climate change. Thus, it is imperative to find a practical and cost-efficient way of managing tick populations. Prescribed burns are a common form of land management that can be cost-efficient if properly managed and can be applied across large amounts of land. In this study, we present a compartmental model for ticks carrying Lyme disease and uniquely incorporate the effects of prescribed fire using an impulsive system to investigate the effects of prescribed fire intensity (high and low) and the duration between burns. Our study found that fire intensity has a larger impact in reducing tick population than the frequency between burns. Furthermore, burning at high intensity is preferable to burning at low intensity whenever possible, although high-intensity burns may be unrealistic due to environmental factors. Annual burns resulted in the most significant reduction in infectious nymphs, which are the primary carriers of Lyme disease.

Pediatric maculopapular cutaneous mastocytosis: Retrospective review of signs, symptoms, and associated conditions.

BACKGROUND/OBJECTIVES: Though maculopapular cutaneous mastocytosis is the most common form of pediatric mastocytosis, it remains unclear which patients will experience severe symptoms. We sought to better define the presentation and the cutaneous and systemic signs and symptoms in patients with maculopapular cutaneous mastocytosis. METHODS: We analyzed retrospective data on 227 patients diagnosed with maculopapular cutaneous mastocytosis prior to age 15 years from five US clinical sites. We collected data on signs, symptoms, age of onset, and laboratory testing. RESULTS: Median age of onset of maculopapular cutaneous mastocytosis was 3 months, with 94% of patients presenting prior to age 2 (range 0-15 years). Patients presenting before age 2 had significantly lower serum tryptase level (P = .019). Greater number of skin lesions (P = .006), number of reported skin signs and symptoms (P < .001), and higher tryptase levels (P < .001) were associated with more systemic symptoms. CONCLUSION: Children with maculopapular cutaneous mastocytosis, who have greater skin involvement, higher serum tryptase level, and more skin signs and symptoms, are more likely to have systemic symptoms.

The case of missing skin: Congenital Volkmann ischemic contracture.

Congenital Volkmann ischemic contracture (CVIC) is an exceedingly rare neonatal compartment syndrome caused by intrauterine ischemia and external compression. It presents at birth with necrotic cutaneous lesions and neurologic impairment, typically in a distal upper extremity. Diagnosis and treatment are often delayed in neonates, leading to long-term neurologic sequelae. We present a rare case of CVIC in order to raise awareness of its presentation and management in hopes of improving outcomes.

Maternal obesity reduces placental autophagy marker expression in uncomplicated pregnancies.

AIM: Obesity has been associated with changes in autophagy and its increasing prevalence among pregnant women is implicated in higher rates of placental-mediated complications of pregnancy such as pre-eclampsia and intrauterine growth restriction. Autophagy is involved in normal placentation, thus changes in autophagy may lead to impaired placental function and development. The aim of this study was to investigate the connection between obesity and autophagy in the placenta in otherwise uncomplicated pregnancies. METHODS: Immunohistochemistry and western blot analysis were done on placental and omental samples from obese (body mass index [BMI] ≥30 kg/m2 ) and normal weight (BMI <25 kg/m2 ) pregnant women with singleton pregnancies undergoing planned Caesarean delivery without labor at term. Samples were analyzed for autophagic markers LC3B and p62 in the peripheral, middle and central regions of the placenta and in omental adipocytes, milky spots and vasculature. RESULTS: As pre-pregnancy BMI increased, there was an increase in both placental and fetal weight as well as decreased levels of LC3B in the central region of the placenta (P = 0.0046). Within the obese patient group, LC3B levels were significantly decreased in the placentas of male fetuses compared to females (P < 0.0001). Adipocytes, compared to milky spots and vasculature, had lower levels of p62 (P = 0.0127) and LC3B (P = 0.003) in obese omenta and lower levels of LC3B in control omenta (P = 0.0071). CONCLUSION: Obesity leads to reduced placental autophagy in uncomplicated pregnancies; thus, changes in autophagy may be involved in the underlying mechanisms of obesity-related placental diseases of pregnancy.

Deep Granuloma Annulare Mimicking Inflamed Cysts in a Teenager.

We describe deep granuloma annulare (DGA) of the forehead mimicking inflamed cysts. Reactive inflammation and sterile purulent drainage may be an underrecognized feature of DGA.

Distinct mechanisms of recognizing endosomal sorting complex required for transport III (ESCRT-III) protein IST1 by different microtubule interacting and trafficking (MIT) domains.

The endosomal sorting complex required for transport (ESCRT) machinery is responsible for membrane remodeling in a number of biological processes including multivesicular body biogenesis, cytokinesis, and enveloped virus budding. In mammalian cells, efficient abscission during cytokinesis requires proper function of the ESCRT-III protein IST1, which binds to the microtubule interacting and trafficking (MIT) domains of VPS4, LIP5, and Spartin via its C-terminal MIT-interacting motif (MIM). Here, we studied the molecular interactions between IST1 and the three MIT domain-containing proteins to understand the structural basis that governs pairwise MIT-MIM interaction. Crystal structures of the three molecular complexes revealed that IST1 binds to the MIT domains of VPS4, LIP5, and Spartin using two different mechanisms (MIM1 mode versus MIM3 mode). Structural comparison revealed that structural features in both MIT and MIM contribute to determine the specific binding mechanism. Within the IST1 MIM sequence, two phenylalanine residues were shown to be important in discriminating MIM1 versus MIM3 binding. These observations enabled us to deduce a preliminary binding code, which we applied to provide CHMP2A, a protein that normally only binds the MIT domain in the MIM1 mode, the additional ability to bind the MIT domain of Spartin in the MIM3 mode.

A novel mechanism of regulating the ATPase VPS4 by its cofactor LIP5 and the endosomal sorting complex required for transport (ESCRT)-III protein CHMP5.

Disassembly of the endosomal sorting complex required for transport (ESCRT) machinery from biological membranes is a critical final step in cellular processes that require the ESCRT function. This reaction is catalyzed by VPS4, an AAA-ATPase whose activity is tightly regulated by a host of proteins, including LIP5 and the ESCRT-III proteins. Here, we present structural and functional analyses of molecular interactions between human VPS4, LIP5, and the ESCRT-III proteins. The N-terminal domain of LIP5 (LIP5NTD) is required for LIP5-mediated stimulation of VPS4, and the ESCRT-III protein CHMP5 strongly inhibits the stimulation. Both of these observations are distinct from what was previously described for homologous yeast proteins. The crystal structure of LIP5NTD in complex with the MIT (microtubule-interacting and transport)-interacting motifs of CHMP5 and a second ESCRT-III protein, CHMP1B, was determined at 1 Å resolution. It reveals an ESCRT-III binding induced moderate conformational change in LIP5NTD, which results from insertion of a conserved CHMP5 tyrosine residue (Tyr(182)) at the core of LIP5NTD structure. Mutation of Tyr(182) partially relieves the inhibition displayed by CHMP5. Together, these results suggest a novel mechanism of VPS4 regulation in metazoans, where CHMP5 functions as a negative allosteric switch to control LIP5-mediated stimulation of VPS4.