Complex petal spot formation in the Beetle Daisy (Gorteria diffusa) relies on spot-specific accumulation of malonylated anthocyanin regulated by paralogous GdMYBSG6 transcription factors.

Gorteria diffusa has elaborate petal spots that attract pollinators through sexual deception, but how G. diffusa controls spot development is largely unknown. Here, we investigate how pigmentation is regulated during spot formation. We determined the anthocyanin composition of G. diffusa petals and combined gene expression analysis with protein interaction assays to characterise R2R3-MYBs that likely regulate pigment production in G. diffusa petal spots. We found that cyanidin 3-glucoside pigments G. diffusa ray floret petals. Unlike other petal regions, spots contain a high proportion of malonylated anthocyanin. We identified three subgroup 6 R2R3-MYB transcription factors (GdMYBSG6-1,2,3) that likely activate the production of spot pigmentation. These genes are upregulated in developing spots and induce ectopic anthocyanin production upon heterologous expression in tobacco. Interaction assays suggest that these transcription factors regulate genes encoding three anthocyanin synthesis enzymes. We demonstrate that the elaboration of complex spots in G. diffusa begins with the accumulation of malonylated pigments at the base of ray floret petals, positively regulated by three paralogous R2R3-MYB transcription factors. Our results indicate that the functional diversification of these GdMYBSG6s involved changes in the spatial control of their transcription, and modification of the duration of GdMYBSG6 gene expression contributes towards floral variation within the species.

Comparative Genomics of the Waterfowl Innate Immune System.

Animal species differ considerably in their ability to fight off infections. Finding the genetic basis of these differences is not easy, as the immune response is comprised of a complex network of proteins that interact with one another to defend the body against infection. Here, we used population- and comparative genomics to study the evolutionary forces acting on the innate immune system in natural hosts of the avian influenza virus (AIV). For this purpose, we used a combination of hybrid capture, next- generation sequencing and published genomes to examine genetic diversity, divergence, and signatures of selection in 127 innate immune genes at a micro- and macroevolutionary time scale in 26 species of waterfowl. We show across multiple immune pathways (AIV-, toll-like-, and RIG-I -like receptors signalling pathways) that genes involved genes in pathogen detection (i.e., toll-like receptors) and direct pathogen inhibition (i.e., antimicrobial peptides and interferon-stimulated genes), as well as host proteins targeted by viral antagonist proteins (i.e., mitochondrial antiviral-signaling protein, [MAVS]) are more likely to be polymorphic, genetically divergent, and under positive selection than other innate immune genes. Our results demonstrate that selective forces vary across innate immune signaling signalling pathways in waterfowl, and we present candidate genes that may contribute to differences in susceptibility and resistance to infectious diseases in wild birds, and that may be manipulated by viruses. Our findings improve our understanding of the interplay between host genetics and pathogens, and offer the opportunity for new insights into pathogenesis and potential drug targets.

Evolutionary Algorithms for Parameter Optimization-Thirty Years Later.

Thirty years, 1993-2023, is a huge time frame in science. We address some major developments in the field of evolutionary algorithms, with applications in parameter optimization, over these 30 years. These include the covariance matrix adaptation evolution strategy and some fast-growing fields such as multimodal optimization, surrogate-assisted optimization, multiobjective optimization, and automated algorithm design. Moreover, we also discuss particle swarm optimization and differential evolution, which did not exist 30 years ago, either. One of the key arguments made in the paper is that we need fewer algorithms, not more, which, however, is the current trend through continuously claiming paradigms from nature that are suggested to be useful as new optimization algorithms. Moreover, we argue that we need proper benchmarking procedures to sort out whether a newly proposed algorithm is useful or not. We also briefly discuss automated algorithm design approaches, including configurable algorithm design frameworks, as the proposed next step toward designing optimization algorithms automatically, rather than by hand.

Demographic consequences of heterogeneity in conspecific density dependence among mast-fruiting tropical trees.

The role of conspecific density dependence (CDD) in the maintenance of species richness is a central focus of tropical forest ecology. However, tests of CDD often ignore the integrated effects of CDD over multiple life stages and their long-term impacts on population demography. We combined a 10-year time series of seed production, seedling recruitment and sapling and tree demography of three dominant Southeast Asian tree species that adopt a mast-fruiting phenology. We used these data to construct individual-based models that examine the effects of CDD on population growth rates (λ) across life-history stages. Recruitment was driven by positive CDD for all species, supporting the predator satiation hypothesis, while negative CDD affected seedling and sapling growth of two species, significantly reducing λ. This negative CDD on juvenile growth overshadowed the positive CDD of recruitment, suggesting the cumulative effects of CDD during seedling and sapling development has greater importance than the positive CDD during infrequent masting events. Overall, CDD varied among positive, neutral and negative effects across life-history stages for all species, suggesting that assessments of CDD on transitions between just two stages (e.g. seeds seedlings or juveniles mature trees) probably misrepresent the importance of CDD on population growth and stability.

Symptoms in Pectus Deformities: A Scoring System for Subjective Physical Complaints.

Background The literature is silent on the relationship between symptoms and the Haller index. Nor is there a classification of the severity of the physical complaints. Materials and Methods Retrospectively, data from 128 patients (102 funnel, 25 pigeon chest patients, and 1 mixed type) were evaluated. To objectify the symptoms, we developed a score to describe the level of physical ailments. This score includes 10 different symptoms as well as the situation or frequency in which they occur and an impact factor. This depends on how much they affect everyday life. Results Pectus excavatum patients express physical complaints more frequently than pectus carinatum patients who actually suffer more from psychological stress. We could not find a correlation between the Haller index and symptoms or levels of ailment. Conclusion Pectus deformities are likely to cause physical and psychological complaints. Since the subjective symptoms did not show any correlation to the chest severity index, they are supposed to be independent from the deformity's extent.

Sternocostal dislocation following open correction of pectus excavatum-"stairway phenomenon": complication management by means of sternocostal locking titanium plate osteosynthesis.

INTRODUCTION: Some open surgical methods describe complete sternocostal dissection with subsequent resynthesis. Lack of consolidation with painful sternocostal instability and retrosternal dislocation of sternal rib tips are possible complications. MATERIALS AND METHODS: Seven patients with symptomatic unilateral sternocostal dislocation were included in this study. After diagnosis, confirmed by three-dimensional computed tomography (CT), patients underwent open surgery. All affected ribs were reset and fixed to the sternum with the aid of titanium implants. RESULTS: The patients had, on average, unilateral dislocation of 3.4 rib joints with 15.4 mm retrosternal dislocation, which was fixed with 2.3 plates. A titanium splint was also employed. The recurrent nature of the problem made procedures very time-consuming (average operation time: 3 hours 25 minutes). One patient suffered strong intraoperative bleeding requiring transfusion of blood products and access enlargement. Follow-up examinations showed high patient satisfaction (grade of 1.7; rating scale 1-6). Remaining rib instabilities were observed just as infrequently as were material failures. The sternocostal rib splint in the costal cartilage became loose and was removed. One patient exhibited a pectoral muscle asymmetry. No other complications were observed. CONCLUSION: The term "stairway phenomenon" describes the dislocation of sternocostal joints. Observed after open pectus excavatum correction it can trigger substantial physical complaints. Thus, preserving those joints during pectus repair is strongly recommended. Locking titanium plates are a safe alternative to sternocostal suture fixation and is characterized by high patient satisfaction.

Is there a role for rare variants in DRD4 gene in the susceptibility for ADHD? Searching for an effect of allelic heterogeneity.

Although several studies have demonstrated an association between the 7-repeat (7R) allele in the 48-bp variable number of tandem repeats (VNTRs) in the exon 3 at dopamine receptor D4 (DRD4) gene and attention-deficit/hyperactivity disorder (ADHD), others failed to replicate this finding. In this study, a total of 786 individuals with ADHD were genotyped for DRD4 exon 3 VNTR. All 7R homozygous subjects were selected for VNTR re-sequencing. Subjects homozygous for the 4R allele were selected paired by age, ancestry and disorder subtypes in order to have a sample as homogeneous as possible with 7R/7R individuals. Using these criteria, 103 individuals (66 with ADHD and 37 control individuals) were further investigated. An excess of rare variants were observed in the 7R alleles of ADHD patient when compared with controls (P=0.031). This difference was not observed in 4R allele. Furthermore, nucleotide changes that predict synonymous and non-synonymous substitutions were more common in the 7R sample (P=0.008 for total substitutions and P=0.043 for non-synonymous substitutions). In silico prediction of structural/functional alterations caused by these variants have also been observed. Our findings suggest that not only repeat length but also DNA sequence should be assessed to better understand the role of DRD4 exon 3 VNTR in ADHD genetic susceptibility.

Dynamic conservation of forest genetic resources in 33 European countries.

Dynamic conservation of forest genetic resources (FGR) means maintaining the genetic diversity of trees within an evolutionary process and allowing generation turnover in the forest. We assessed the network of forests areas managed for the dynamic conservation of FGR (conservation units) across Europe (33 countries). On the basis of information available in the European Information System on FGR (EUFGIS Portal), species distribution maps, and environmental stratification of the continent, we developed ecogeographic indicators, a marginality index, and demographic indicators to assess and monitor forest conservation efforts. The pan-European network has 1967 conservation units, 2737 populations of target trees, and 86 species of target trees. We detected a poor coincidence between FGR conservation and other biodiversity conservation objectives within this network. We identified 2 complementary strategies: a species-oriented strategy in which national conservation networks are specifically designed for key target species and a site-oriented strategy in which multiple-target units include so-called secondary species conserved within a few sites. The network is highly unbalanced in terms of species representation, and 7 key target species are conserved in 60% of the conservation units. We performed specific gap analyses for 11 tree species, including assessment of ecogeographic, demographic, and genetic criteria. For each species, we identified gaps, particularly in the marginal parts of their distribution range, and found multiple redundant conservation units in other areas. The Mediterranean forests and to a lesser extent the boreal forests are underrepresented. Monitoring the conservation efficiency of each unit remains challenging; however, <2% of the conserved populations seem to be at risk of extinction. On the basis of our results, we recommend combining species-oriented and site-oriented strategies.

The evolution of flower colour.

Flowers are the most commonly seen colourful elements of the natural world, and in this primer we explain the evolution of their spectacular range of colours. To understand flower colour, we first explain what colour is and how a flower can have different colours in the eyes of different observers. We briefly introduce the molecular and biochemical basis of flower colour, which is primarily based on well-characterised pigment synthesis pathways. We then consider the evolution of flower colour over four timescales - its origin and deep evolution, its macroevolution, its microevolution and finally, the recent effects of human behaviour on flower colour and its evolution. Because flower colour is so evolutionarily labile, and at the same time so striking to the human eye, it is an exciting subject for current and future research efforts.

Use of potassium polyaspartate on white wines: Interaction with proteins and aroma compounds.

The precipitation of tartaric salts represents one of the main visual sensory faults of white wines. It can be prevented by cold stabilization or adding some adjuvants, such as potassium polyaspartate (KPA). KPA is a biopolymer that can limit the precipitation of tartaric salts linking the potassium cation, however, it could interact also with other compounds affecting wine quality. The present work aims to study the effect of potassium polyaspartate on proteins and aroma compounds of two white wines, at different storage temperatures (4 °C and 16 °C). The KPA addition showed positive effects on the quality of wines, with a significant decrease of unstable proteins (up to 92%), also related to better wine protein stability indices. A Logistic function well described the effect of KPA and storage temperature on protein concentration (R2 > 0.93; NRMSD: 1.54-3.82%). Moreover, the KPA addition allowed the preservation of the aroma concentration and no adversely effects were pointed out. Alternatively to common enological adjuvants, KPA could be considered a multifunctional product against tartaric and protein instability of white wines, avoiding adverse effects on their aroma profile.

Multiple gene co-options underlie the rapid evolution of sexually deceptive flowers in Gorteria diffusa.

Gene co-option, the redeployment of an existing gene in an unrelated developmental context, is an important mechanism underlying the evolution of morphological novelty. In most cases described to date, novel traits emerged by co-option of a single gene or genetic network. Here, we show that the integration of multiple co-opted genetic elements facilitated the rapid evolution of complex petal spots that mimic female bee-fly pollinators in the sexually deceptive South African daisy Gorteria diffusa. First, co-option of iron homeostasis genes altered petal spot pigmentation, producing a color similar to that of female pollinators. Second, co-option of the root hair gene GdEXPA7 enabled the formation of enlarged papillate petal epidermal cells, eliciting copulation responses from male flies. Third, co-option of the miR156-GdSPL1 transcription factor module altered petal spot placement, resulting in better mimicry of female flies resting on the flower. The three genetic elements were likely co-opted sequentially, and strength of sexual deception in different G. diffusa floral forms strongly correlates with the presence of the three corresponding morphological alterations. Our findings suggest that gene co-options can combine in a modular fashion, enabling rapid evolution of novel complex traits.

Stitching a new garment: Considering the future of the speech-language therapy profession globally.

Providing equitable support for people experiencing communication disability (CD) globally is a historical and contemporary challenge for the speech-language therapy profession. A group of speech-language therapists (SLTs) with ongoing and sustained experiences in Majority and Minority World contexts participated in five virtual meetings in 2021. The aim of these meetings was to develop provocative statements that might spur a global discussion among individuals and organisations that support people experiencing CD. The following questions were discussed: What is our vision for the future of the profession globally? What are the global challenges around access to speech-language therapy services?Four main themes emerged: (1) the need to centre people experiencing CD as the focal point of services, (2) participation, (3) equity and (4) community. The themes relate to the need for a process of de-imperialism in the profession. Suggestions were made to develop more suitable terminology and to establish a global framework that promotes more equitable access to communication services. We seek the adoption of approaches that focus on reciprocal global engagement for capacity strengthening. Alternative models of culturally sustaining and equitable service delivery are needed to create impact for people experiencing CD, and their families worldwide.Contribution: Provocative statements were developed to prompt global conversations among speech-language therapy professionals and associations. We encourage readers to consider the questions posed, share their viewpoints and initiate positive change towards a global strategy.

Ustekinumab in the treatment of patients with hidradenitis suppurativa: multicenter case series and systematic review.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic debilitating autoinflammatory skin disease. Adalimumab is the only biologic agent available to treat HS, but lack of response is observed in some patients. Ustekinumab may be useful to treat patients with HS who do not respond to adalimumab. OBJECTIVE: The objectives of this study were: (1) to retrospectively evaluate the therapeutic outcomes of ustekinumab in a multicenter series of patients with HS and (2) to assess all published scientific evidence on its utilization in patients with HS. METHODS: We evaluated the therapeutic outcomes of 10 patients with HS treated with ustekinumab and conducted a systematic review of published epidemiological studies on ustekinumab-treated patients with HS. RESULTS: In the case series, an improvement in the Physician Global Assessment score was observed in 70% (7/10) patients and an improvement in the Numerical Pain Rating Scale in 80% (8/10). In the systematic review, clinical improvement in disease severity was reported in 76% (34/45) patients and symptomatic improvement in 84% (38/45). No severe ustekinumab-related adverse event was recorded. CONCLUSION: These findings suggest that ustekinumab may be an effective and safe option for patients with HS who fail to respond to first-line therapies.

Low-Input High-Molecular-Weight DNA Extraction for Long-Read Sequencing From Plants of Diverse Families.

Long-read DNA sequencing technologies require high molecular weight (HMW) DNA of adequate purity and integrity, which can be difficult to isolate from plant material. Plant leaves usually contain high levels of carbohydrates and secondary metabolites that can impact DNA purity, affecting downstream applications. Several protocols and kits are available for HMW DNA extraction, but they usually require a high amount of input material and often lead to substantial DNA fragmentation, making sequencing suboptimal in terms of read length and data yield. We here describe a protocol for plant HMW DNA extraction from low input material (0.1 g) which is easy to follow and quick (2.5 h). This method successfully enabled us to extract HMW from four species from different families (Orchidaceae, Poaceae, Brassicaceae, Asteraceae). In the case of recalcitrant species, we show that an additional purification step is sufficient to deliver a clean DNA sample. We demonstrate the suitability of our protocol for long-read sequencing on the Oxford Nanopore Technologies PromethION® platform, with and without the use of a short fragment depletion kit.

Application of plant allylpolyalkoxybenzenes in synthesis of antimitotic phenstatin analogues.

Phenstatin and its derivatives with the modified ring A have been synthesized, using plant allylpolyalkoxybenzenes as a starting material. The targeted molecules were evaluated in a phenotypic sea urchin embryo assay for antiproliferative activity. It was found that phenstatin ring A modifications yielded antimitotic compounds. The most effective myristicin derivative 7d (combretastatin A-2 analogue) was determined to be ca. 10 times more potent than phenstatin, displaying antimitotic tubulin-destabilizing activity at the same concentration range as combretastatins. In contrast to combretastatins, 7d featured the steric stability with potential for further design as anticancer agent.

Effects of Alpha-2 Adrenergic Agonist Mafedine on Brain Electrical Activity in Rats after Traumatic Brain Injury.

The search for and development of new neuroprotective (or cerebroprotective) drugs, as well as suitable methods for their preclinical efficacy evaluation, are priorities for current biomedical research. Alpha-2 adrenergic agonists, such as mafedine and dexmedetomidine, are a highly appealing group of drugs capable of reducing neurological deficits which result from brain trauma and vascular events in both experimental animals and human patients. Thus, our aim was to assess the effects of mafedine and dexmedetomidine on the brain's electrical activity in a controlled cortical-impact model of traumatic brain injury (TBI) in rats. The functional status of the animals was assessed by electrocorticography (ECoG), using ECoG electrodes which were chronically implanted in different cortical regions. The administration of intraperitoneal mafedine sodium at 2.5 mg∙kg-1 at 1 h after TBI induction, and daily for the following 6 days, restored interhemispheric connectivity in remote brain regions and intrahemispheric connections within the unaffected hemisphere at post-TBI day 7. Animals that had received mafedine sodium also demonstrated an improvement in cortical responses to photic and somatosensory stimulation. Dexmedetomidine at 25 µg∙kg-1 did not affect the brain's electrical activity in brain-injured rats. Our results confirm the previously described neuroprotective effects of mafedine sodium and suggest that ECoG registration and analysis are a viable method evaluating drug efficacy in experimental animal models of TBI.

Implant-borne rehabilitation for alveolar dental cleft: Retrospective analysis of thirty-nine cases.

INTRODUCTION: Dental rehabilitation of patients with alveolar-dental cleft sequelae is a crucial issue in the final stages of functional and aesthetic management of these patients. The objectives of this study are to establish the success of implant-supported rehabilitations for patients with alveolar dental cleft sequelae followed in the Department of Maxillofacial Surgery and Stomatology of Lille University Hospital and the reasons for not using this type of rehabilitation for others. MATERIALS AND METHOD: Patients treated between January 2009 and December 2018 with implant-supported prostheses at an alveolar dental cleft site were included. Dental implants were placed after a complementary alveolar bone graft. Clinical and radiological criteria regarding periodontal, occlusal and prosthetic status were studied. RESULTS: A total of 12 implants in 8 patients were placed. One of these implants was lost, resulting in an implant survival rate of 91.7%. All patients were able to benefit from functional rehabilitation. DISCUSSION: The present results demonstrate the interest and reliability of implant rehabilitation in these patients. They furthermore highlight financial factors as a barrier to using this solution among the majority of patients in care.

From pullout-techniques to modular elastic stable chest repair: the evolution of an open technique in the correction of pectus excavatum.

BACKGROUND: Traditionally open procedures have been replaced by minimally invasive techniques in the correction of pectus excavatum. Efforts to improve the extent of mobilization of the chest wall and its stabilization have led to constant modifications. There is currently no consensus about the best procedure for correction of pectus excavatum. METHODS: Based on the contributions of a single institution for the last 60 years, we present the various strategies used for the correction of pectus excavatum and the evolution of operational procedures. These approaches are compared with those performed internationally at similar periods. RESULTS: Resections with external extension achieved moderate results and were modified in 1962 to the "Shred" method. The establishment of the "Strut" method in 1963 and, in 1977, its extension with the erection of the lower rib arches significantly improved patient outcomes. The "minimization" of the procedure in 2006 was accompanied by an increase in wound healing disorders and recurrent deformities. Since 2010, elastic stable chest repair (ESCR) has provided lossless mobilization and sternal elevation for healing costosternal pseudarthrosis and allowed correction of complex recurrences with excellent cosmetic-functional results. Strong asymmetric or broad-base deformities can now be stabilized using a modular hybrid technique of transsternal bar and locked plates. CONCLUSIONS: ESCR marks the end of the 60-year development of an open procedure and, after loss-free mobilization of the chest wall by elastic-stable biomechanical management, optimizes the possibility of anatomical reconstruction of the chest wall during initial and re-interventions, achieving a permanent, physiologically stable remodeling of the chest wall.