The developmental basis of fingerprint pattern formation and variation.

Fingerprints are complex and individually unique patterns in the skin. Established prenatally, the molecular and cellular mechanisms that guide fingerprint ridge formation and their intricate arrangements are unknown. Here we show that fingerprint ridges are epithelial structures that undergo a truncated hair follicle developmental program and fail to recruit a mesenchymal condensate. Their spatial pattern is established by a Turing reaction-diffusion system, based on signaling between EDAR, WNT, and antagonistic BMP pathways. These signals resolve epithelial growth into bands of focalized proliferation under a precociously differentiated suprabasal layer. Ridge formation occurs as a set of waves spreading from variable initiation sites defined by the local signaling environments and anatomical intricacies of the digit, with the propagation and meeting of these waves determining the type of pattern that forms. Relying on a dynamic patterning system triggered at spatially distinct sites generates the characteristic types and unending variation of human fingerprint patterns.

Limb development genes underlie variation in human fingerprint patterns.

Fingerprints are of long-standing practical and cultural interest, but little is known about the mechanisms that underlie their variation. Using genome-wide scans in Han Chinese cohorts, we identified 18 loci associated with fingerprint type across the digits, including a genetic basis for the long-recognized "pattern-block" correlations among the middle three digits. In particular, we identified a variant near EVI1 that alters regulatory activity and established a role for EVI1 in dermatoglyph patterning in mice. Dynamic EVI1 expression during human development supports its role in shaping the limbs and digits, rather than influencing skin patterning directly. Trans-ethnic meta-analysis identified 43 fingerprint-associated loci, with nearby genes being strongly enriched for general limb development pathways. We also found that fingerprint patterns were genetically correlated with hand proportions. Taken together, these findings support the key role of limb development genes in influencing the outcome of fingerprint patterning.

Insights into digit evolution from a fate map study of the forearm using Chameleon, a new transgenic chicken line.

The cellular and genetic networks that contribute to the development of the zeugopod (radius and ulna of the forearm, tibia and fibula of the leg) are not well understood, although these bones are susceptible to loss in congenital human syndromes and to the action of teratogens such as thalidomide. Using a new fate-mapping approach with the Chameleon transgenic chicken line, we show that there is a small contribution of SHH-expressing cells to the posterior ulna, posterior carpals and digit 3. We establish that although the majority of the ulna develops in response to paracrine SHH signalling in both the chicken and mouse, there are differences in the contribution of SHH-expressing cells between mouse and chicken as well as between the chicken ulna and fibula. This is evidence that, although zeugopod bones are clearly homologous according to the fossil record, the gene regulatory networks that contribute to their development and evolution are not fixed.

Rapid mechanosensitive migration and dispersal of newly divided mesenchymal cells aid their recruitment into dermal condensates.

Embryonic mesenchymal cells are dispersed within an extracellular matrix but can coalesce to form condensates with key developmental roles. Cells within condensates undergo fate and morphological changes and induce cell fate changes in nearby epithelia to produce structures including hair follicles, feathers, or intestinal villi. Here, by imaging mouse and chicken embryonic skin, we find that mesenchymal cells undergo much of their dispersal in early interphase, in a stereotyped process of displacement driven by 3 hours of rapid and persistent migration followed by a long period of low motility. The cell division plane and the elevated migration speed and persistence of newly born mesenchymal cells are mechanosensitive, aligning with tissue tension, and are reliant on active WNT secretion. This behaviour disperses mesenchymal cells and allows daughters of recent divisions to travel long distances to enter dermal condensates, demonstrating an unanticipated effect of cell cycle subphase on core mesenchymal behaviour.

UMAD1 contributes to ESCRT-III dynamic subunit turnover during cytokinetic abscission.

Abscission is the final stage of cytokinesis whereby the midbody, a thin intercellular bridge, is resolved to separate the daughter cells. Cytokinetic abscission is mediated by the endosomal sorting complex required for transport (ESCRT), a conserved membrane remodelling machinery. The midbody organiser CEP55 recruits early acting ESCRT factors such as ESCRT-I and ALIX (also known as PDCD6IP), which subsequently initiate the formation of ESCRT-III polymers that sever the midbody. We now identify UMAD1 as an ESCRT-I subunit that facilitates abscission. UMAD1 selectively associates with VPS37C and VPS37B, supporting the formation of cytokinesis-specific ESCRT-I assemblies. TSG101 recruits UMAD1 to the site of midbody abscission, to stabilise the CEP55-ESCRT-I interaction. We further demonstrate that the UMAD1-ESCRT-I interaction facilitates the final step of cytokinesis. Paradoxically, UMAD1 and ALIX co-depletion has synergistic effects on abscission, whereas ESCRT-III recruitment to the midbody is not inhibited. Importantly, we find that both UMAD1 and ALIX are required for the dynamic exchange of ESCRT-III subunits at the midbody. Therefore, UMAD1 reveals a key functional connection between ESCRT-I and ESCRT-III that is required for cytokinesis.

Periodic pattern formation during embryonic development.

During embryonic development many organs and structures require the formation of series of repeating elements known as periodic patterns. Ranging from the digits of the limb to the feathers of the avian skin, the correct formation of these embryonic patterns is essential for the future form and function of these tissues. However, the mechanisms that produce these patterns are not fully understood due to the existence of several modes of pattern generation which often differ between organs and species. Here, we review the current state of the field and provide a perspective on future approaches to studying this fundamental process of embryonic development.

Novel Aspects in Pattern Formation Arise from Coupling Turing Reaction-Diffusion and Chemotaxis.

Recent experimental studies on primary hair follicle formation and feather bud morphogenesis indicate a coupling between Turing-type diffusion driven instability and chemotactic patterning. Inspired by these findings we develop and analyse a mathematical model that couples chemotaxis to a reaction-diffusion system exhibiting diffusion-driven (Turing) instability. While both systems, reaction-diffusion systems and chemotaxis, can independently generate spatial patterns, we were interested in how the coupling impacts the stability of the system, parameter region for patterning, pattern geometry, as well as the dynamics of pattern formation. We conduct a classical linear stability analysis for different model structures, and confirm our results by numerical analysis of the system. Our results show that the coupling generally increases the robustness of the patterning process by enlarging the pattern region in the parameter space. Concerning time scale and pattern regularity, we find that an increase in the chemosensitivity can speed up the patterning process for parameters inside and outside of the Turing space, but generally reduces spatial regularity of the pattern. Interestingly, our analysis indicates that pattern formation can also occur when neither the Turing nor the chemotaxis system can independently generate pattern. On the other hand, for some parameter settings, the coupling of the two processes can extinguish the pattern formation, rather than reinforce it. These theoretical findings can be used to corroborate the biological findings on morphogenesis and guide future experimental studies. From a mathematical point of view, this work sheds a light on coupling classical pattern formation systems from the parameter space perspective.

Feather arrays are patterned by interacting signalling and cell density waves.

Feathers are arranged in a precise pattern in avian skin. They first arise during development in a row along the dorsal midline, with rows of new feather buds added sequentially in a spreading wave. We show that the patterning of feathers relies on coupled fibroblast growth factor (FGF) and bone morphogenetic protein (BMP) signalling together with mesenchymal cell movement, acting in a coordinated reaction-diffusion-taxis system. This periodic patterning system is partly mechanochemical, with mechanical-chemical integration occurring through a positive feedback loop centred on FGF20, which induces cell aggregation, mechanically compressing the epidermis to rapidly intensify FGF20 expression. The travelling wave of feather formation is imposed by expanding expression of Ectodysplasin A (EDA), which initiates the expression of FGF20. The EDA wave spreads across a mesenchymal cell density gradient, triggering pattern formation by lowering the threshold of mesenchymal cells required to begin to form a feather bud. These waves, and the precise arrangement of feather primordia, are lost in the flightless emu and ostrich, though via different developmental routes. The ostrich retains the tract arrangement characteristic of birds in general but lays down feather primordia without a wave, akin to the process of hair follicle formation in mammalian embryos. The embryonic emu skin lacks sufficient cells to enact feather formation, causing failure of tract formation, and instead the entire skin gains feather primordia through a later process. This work shows that a reaction-diffusion-taxis system, integrated with mechanical processes, generates the feather array. In flighted birds, the key role of the EDA/Ectodysplasin A receptor (EDAR) pathway in vertebrate skin patterning has been recast to activate this process in a quasi-1-dimensional manner, imposing highly ordered pattern formation.

Hierarchical patterning modes orchestrate hair follicle morphogenesis.

Two theories address the origin of repeating patterns, such as hair follicles, limb digits, and intestinal villi, during development. The Turing reaction-diffusion system posits that interacting diffusible signals produced by static cells first define a prepattern that then induces cell rearrangements to produce an anatomical structure. The second theory, that of mesenchymal self-organisation, proposes that mobile cells can form periodic patterns of cell aggregates directly, without reference to any prepattern. Early hair follicle development is characterised by the rapid appearance of periodic arrangements of altered gene expression in the epidermis and prominent clustering of the adjacent dermal mesenchymal cells. We assess the contributions and interplay between reaction-diffusion and mesenchymal self-organisation processes in hair follicle patterning, identifying a network of fibroblast growth factor (FGF), wingless-related integration site (WNT), and bone morphogenetic protein (BMP) signalling interactions capable of spontaneously producing a periodic pattern. Using time-lapse imaging, we find that mesenchymal cell condensation at hair follicles is locally directed by an epidermal prepattern. However, imposing this prepattern's condition of high FGF and low BMP activity across the entire skin reveals a latent dermal capacity to undergo spatially patterned self-organisation in the absence of epithelial direction. This mesenchymal self-organisation relies on restricted transforming growth factor (TGF) ß signalling, which serves to drive chemotactic mesenchymal patterning when reaction-diffusion patterning is suppressed, but, in normal conditions, facilitates cell movement to locally prepatterned sources of FGF. This work illustrates a hierarchy of periodic patterning modes operating in organogenesis.

Effect of Oxytetracycline-Hydrochloride on Phytoplasma Titer and Symptom Progression of the 16SrIV-D Phytoplasma in Cabbage Palms from Florida.

Lethal bronzing (LB) is a phytoplasma disease of palms in Florida, U.S.A. Historically, the use of the antibiotic oxytetracycline-hydrochloride (OTC-HCl) was optimized to treat for LY, and currently label rates for OTC-HCl developed for LY are being used to treat palms preventatively against LB. Because of the economic impact of LB, assessing OTC-HCl against LB is essential for developing and optimizing management options for this disease. In this study, Sabal palmetto palms declining from LB were injected with OTC-HCl to assess efficacy on LB. Four groups of palms were selected that represented healthy palms, early symptomatic palms, palms with moderate symptoms, and palms with late-stage symptoms. Within each group, treatment palms injected with OTC-HCl and a control group with no antibiotics were tested weekly by quantitative PCR for 1 year. For asymptomatic palms, treated palms never developed symptoms or tested positive, whereas one of the control palms did. The early symptomatic palms that were treated had similar levels of phytoplasma to the control group but had much slower symptom development. Palms with moderate symptoms had no difference in titer between the treatment and the control group, but treated palms had much slower symptom development. Palms with late-stage symptoms showed no difference in phytoplasma titer or symptom progression between treated and control palms. These results suggest that label rates of OTC-HCl appear useful as a preventative against LB, but once symptoms develop, label rates cannot cure palms. In the meantime, removal of symptomatic palms is recommended.

Single-setting endoscopic retrograde cholangiopancreatography (ERCP) and cholecystectomy improve the rate of surgical site infection.

INTRODUCTION: Cholecystectomy is a common surgical procedure. The presence of common bile duct stones complicates treatment, often requiring a second procedure for stone retrieval. For such patients, endoscopic retrograde cholangiopancreatography (ERCP) provides adequate therapy, and can be performed before, after, or at the same time as cholecystectomy. In 2013, duodenoscopes were implicated by the Centers for Disease Control and Prevention in transmission of carbapenem-resistant Enterobacteriaceae. In this study, we sought to determine if the addition of ERCP to cholecystectomy was associated with higher rates of surgical site infections and microbial resistance. HYPOTHESIS: Adding ERCP to cholecystectomy increases the SSI rate. METHODS: For this retrospective review, we used the SSI surveillance database at our tertiary-care academic hospital. Cholecystectomy cases between 2010 and 2015 were included in the analysis. SSI was diagnosed using criteria of CDC's National Healthcare Safety Network (NHSN). We applied a logistic regression model to our data (SAS Studio software, v3.4, Enterprise Edition). RESULTS: Our 6-year study period included 2201 cholecystectomies. The SSI rate was 4.1 times higher for patients who underwent open cholecystectomy as compared with laparoscopic cholecystectomy (95% CI 1.61-10.24). When adjusted for wound class and procedure type, the SSI rate was significantly higher for patients who underwent ERCP within 60 days before cholecystectomy (P = 0.04; OR 2.2; CI 1.04-4.49). Rates of resistant pathogens were significantly higher in patients who underwent ERCP in addition to cholecystectomy (1.1% vs. 0.2%, P = 0.02, Fisher's exact test). CONCLUSIONS: ERCP performed in the same setting as cholecystectomy carries no increased risk of SSI and should be the treatment of choice in patients with choledocholithiasis. ERCP performed separately within 60 days before cholecystectomy doubles the risk of SSI. Contaminated equipment might play a role, but other factors are likely at play, and should be taken into account when selecting treatment pathways for patients with choledocholithiasis.

How Misapplication of the Hydrologic Unit Framework Diminishes the Meaning of Watersheds.

Hydrologic units provide a convenient but problematic nationwide set of geographic polygons based on subjectively determined subdivisions of land surface areas at several hierarchical levels. The problem is that it is impossible to map watersheds, basins, or catchments of relatively equal size and cover the whole country. The hydrologic unit framework is in fact composed mostly of watersheds and pieces of watersheds. The pieces include units that drain to segments of streams, remnant areas, noncontributing areas, and coastal or frontal units that can include multiple watersheds draining to an ocean or large lake. Hence, half or more of the hydrologic units are not watersheds as the name of the framework "Watershed Boundary Dataset" implies. Nonetheless, hydrologic units and watersheds are commonly treated as synonymous, and this misapplication and misunderstanding can have some serious scientific and management consequences. We discuss some of the strengths and limitations of watersheds and hydrologic units as spatial frameworks. Using examples from the Northwest and Southeast United States, we explain how the misapplication of the hydrologic unit framework has altered the meaning of watersheds and can impair understanding associations between spatial geographic characteristics and surface water conditions.

Role of Endophytic Entomopathogenic Fungi in Mediating Host Selection, Biology, Behavior, and Management of Tarnished Plant Bug, Lygus lineolaris (Hemiptera: Miridae).

Non-insecticidal control strategies using entomopathogens, nematodes, and endophytes provide sustainable and safer alternatives for managing crop pests. This study investigated the potential of different fungal endophytes, specifically Beauveria bassiana strains, in colonizing cotton plants and their efficacy against tarnished plant bug, Lygus lineolaris. The effect of endophytes on plant growth parameters and cotton yield were measured during different plant growth stages. The entomopathogenicity of these fungi was studied in diet cup bioassays using L. lineolaris adults. The behavior of adult males and females toward endophytic cotton squares was analyzed using olfactometer assays. The experiments showed that the fungal endophytes colonized the plant structures of cotton plants, which resulted in an increase in the number of cotton squares, plant height, and weight compared to control plants. B. bassiana strains/isolates such as GHA, NI-8, and JG-1 caused significant mortality in Lygus adults compared to controls. Also, male and female Lygus adults exhibited repellence behavior towards endophytic cotton squares containing JG-1 isolate of B. bassiana and to other B. bassiana strains such as NI-8, GHA, and SPE-120. No differences were observed in the survival and development of L. lineolaris second-instar nymphs on endophytic cotton, and no yield differences were observed in the field experiments.

A Symptom-Based Natural Language Processing Surveillance Pipeline for Post-COVID-19 Patients.

Post-acute sequelae of SARS CoV-2 (PASC) are a group of conditions in which patients previously infected with COVID-19 experience symptoms weeks/months post-infection. PASC has substantial societal burden, including increased healthcare costs and disabilities. This study presents a natural language processing (NLP) based pipeline for identification of PASC symptoms and demonstrates its ability to estimate the proportion of suspected PASC cases. A manual case review to obtain this estimate indicated our sample incidence of PASC (13%) was representative of the estimated population proportion (95% CI: 19±6.22%). However, the high number of cases classified as indeterminate demonstrates the challenges in classifying PASC even among experienced clinicians. Lastly, this study developed a dashboard to display views of aggregated PASC symptoms and measured its utility using the System Usability Scale. Overall comments related to the dashboard's potential were positive. This pipeline is crucial for monitoring post-COVID-19 patients with potential for use in clinical settings.

Entomopathogenicity of Ascomycete Fungus Cordyceps militaris on the Cotton Bollworm, Helicoverpa zea (Boddie) (Lepidoptera: Noctuidae).

This study investigated the exposure of the cotton bollworm, Helicoverpa zea (Boddie) (Lepidoptera: Noctuidae) to a novel pathogenic fungal agent historically associated with human medicinal value, a commercial strain of Cordyceps militaris ((L.) Fr.) Vuill. (Hypocreales). A series of comparative studies were conducted to evaluate the efficacy of two different exposure methods using four concentrations (n × 109, n × 108, n × 107, n × 106) of C. militaris, where n × 109 provided a concentration of approximately 420 ± 37 spores per mm2 with 398 ± 28 viable spores. Survival of cotton bollworms of all stages was not affected by C. militaris at any concentration 1 d post-exposure. The greatest reduction in survival and highest sporulation rates were observed primarily on or after 7 d post-exposure for early instars (first and second). Significant declines in the survival of early instars were observed for all concentrations at 7 d, and 95% mortality by 10 d, with the exception of the fifth instars that experienced a less severe reduction in survival (35%) when exposed to any concentrations used in the study. Survival of late instars (third to fifth) ranged from 44% to 68% on day 10, while adult survival was near 99% across the duration of the experiment. The relatively narrow range observed for both the lethal concentration and sporulation of second, third, and fifth instar cotton bollworms exposed to the C. militaris strain may demonstrate potential field application for control of larval populations of cotton bollworms.

Early Season Monitoring of Tarnished Plant Bug, Lygus lineolaris, in Wild Hosts Using Pheromone Traps.

The tarnished plant bug, Lygus lineolaris (Hemiptera: Miridae), has a wide host range of over 700 plant species, including 130 crops of economic importance. During early spring, managing the field edges with weeds and other wild hosts is important in preventing early-season infestations of L. lineolaris in cotton to prevent damage to the squares and other fruiting structures. Scouting fields for L. lineolaris is time- and labor-intensive, and end-user variability associated with field sampling can lead to inaccuracies. Insect traps that combine visual cues and pheromones are more accurate, sustainable, and economically feasible in contrast to traditional insect detection methods. In this study, we investigated the application of red or white sticky cards baited with the female-produced sex pheromone to monitor overwintering L. lineolaris populations in early spring. Field experiments demonstrated that the red sticky cards baited with a pheromone blend containing hexyl butyrate, (E)-2-hexenyl butyrate, and (E)-4-oxo-2-hexenal in 4:10:7 ratio are highly effective in trapping L. lineolaris adults in early spring before the row crops are planted, and in monitoring their movement into a cotton crop. The monitoring of L. lineolaris should help growers to make judicious decisions on insecticide applications to control early pest infestations, thereby reducing economic damage to cotton.

A chromosome scale assembly of the tarnished plant bug, Lygus lineolaris (Palisot de Beauvois), genome.

OBJECTIVE: The tarnished plant bug (TPB), Lygus lineolaris (Palisot de Beauvois) (Hemiptera: Miridae), is a pest damaging many cultivated crops in North America. Although partial transcriptome data are available for this pest, a genome assembly was not available for this species. This assembly of a high-quality chromosome-length genome of TPB is aimed to develop the genetic resources that can provide the foundation required for advancing research on this species. RESULTS: The initial genome of TPB assembled with paired-end nucleotide sequences generated with Illumina technology was scaffolded with Illumina HiseqX reads generated from a proximity ligated (HiC) library to obtain a high-quality genome assembly. The final assembly contained 3963 scaffolds longer than 1 kbp to yield a genome of 599.96 Mbp. The N50 of the TPB genome assembly was 35.64 Mbp and 98.68% of the genome was assembled into 17 scaffolds larger than 1 Mbp. This megabase scaffold number is the same as the number of chromosomes observed in karyotyping of this insect. The TPB genome is known to have high repetitive DNA content, and the reduced assembled genome size compared to flowcytometric estimates of approximately 860 Mbp may be due to the collapsed assembly of highly similar regions.

Lethal Concentration and Sporulation by Contact and Direct Spray of the Entomopathogenic Fungus Beauveria bassiana on Different Stages of Nezara viridula (Heteroptera: Pentatomidae).

The southern green stink bug, Nezara viridula (L.) (Heteroptera: Pentatomidae) is the most significant pest of soybean worldwide. The present study was conducted to compare the effectiveness of a Delta native strain NI8 of Beauveria bassiana by contact and direct spray on nymphs (2nd to 5th instar) and adults of N. viridula. Water control and four concentrations of B. bassiana were used to evaluate the survival, mortality, and molting percentage and to estimate median lethal concentration (LC50), median lethal sporulation (LS50), and resistance ratio (RR50). Direct spray at all concentrations observed the greatest reduction in survival on all life stages. Mortality and sporulation were positively correlated by concentration, while molting was highly variable with a significantly lower negative correlation on insects that were directly sprayed. Pathogenicity exhibited reduction as young stages developed and emerged to adult. The LC50 (Contact: 612 spores/mm2; Direct spray: 179 spores/mm2) and LS50 (Contact: 1960 spores/mm2 Spray: 3.3 × 106) values showed that adults of N. viridula were highly resistant than any other life stage when exposed to either contact or direct spray. Fourth instar was the most susceptible (LC50: Contact: 18 spores/mm2; Direct spray: 23 spores/mm2) (LS50: Contact: 53 spores/mm2; Direct spray: 26 spores/mm2) followed by second, third, and fifth instars.

Susceptibility of Different Life Stages of Kudzu Bug Megacopta cribraria (F.) (Hemiptera: Plataspidae) to Two Different Native Strains of Beauveria bassiana.

This is the first study that examined and compared the survival, LC50, and RR50 estimates of Megacopta cribraria F. (Hemiptera: Plataspidae) nymphs and adults that were exposed to two native Beauveria bassiana isolates (Previously codified as NI8 and KUDSC strains) at four concentrations. The greatest reduction in survival and mortality was observed primarily on or after 10 d post-exposure to B. bassiana isolates. Survival of early instars (2nd, 3rd) were not affected by either strains or concentration at 3 d and 5 d post-exposure. Survival of later instars (5th) and adults was significantly reduced when exposed to the KUDSC strain at all concentrations. Comparison of dose−mortality values (LC50) using resistance ratios (RR50) were significantly different between life stages of the kudzu bug for both strains of B. bassiana. The LC50 values showed that kudzu bug adults are more susceptible than any other life stage when exposed to either strain. The KUDSC strain was more pathogenic than NI8 10 d after exposure, but NI8 exhibited significantly higher pathogenicity than KUDSC 20 d after exposure. Our results suggest potential field application of B. bassiana for kudzu bug control and their integration into pest management strategies to suppress them before they cause economic damage to soybean crops.

The EDA-deficient mouse has Zymbal's gland hypoplasia and acute otitis externa.

In mice, rats, dogs and humans, the growth and function of sebaceous glands and eyelid Meibomian glands depend on the ectodysplasin signalling pathway. Mutation of genes encoding the ligand EDA, its transmembrane receptor EDAR and the intracellular signal transducer EDARADD leads to hypohidrotic ectodermal dysplasia, characterised by impaired development of teeth and hair, as well as cutaneous glands. The rodent ear canal has a large auditory sebaceous gland, the Zymbal's gland, the function of which in the health of the ear canal has not been determined. We report that EDA-deficient mice, EDAR-deficient mice and EDARADD-deficient rats have Zymbal's gland hypoplasia. EdaTa mice have 25% prevalence of otitis externa at postnatal day 21 and treatment with agonist anti-EDAR antibodies rescues Zymbal's glands. The aetiopathogenesis of otitis externa involves infection with Gram-positive cocci, and dosing pregnant and lactating EdaTa females and pups with enrofloxacin reduces the prevalence of otitis externa. We infer that the deficit of sebum is the principal factor in predisposition to bacterial infection, and the EdaTa mouse is a potentially useful microbial challenge model for human acute otitis externa.