Cryptic diversity and phylogeographic patterns of Mediodactylus species in the Eastern Mediterranean region.

Cryptic diversity poses a great obstacle in our attempts to assess the current biodiversity crisis and may hamper conservation efforts. The gekkonid genus Mediodactylus, a well-known case of hidden species and genetic diversity, has been taxonomically reclassified several times during the last decade. Focusing on the Mediterranean populations, a recent study within the M. kotschyi species complex using classic mtDNA/nuDNA markers suggested the existence of five distinct species, some being endemic and some possibly threatened, yet their relationships have not been fully resolved. Here, we generated genome-wide SNPs (using ddRADseq) and applied molecular species delimitation approaches and population genomic analyses to further disentangle these relationships. Τhe most extensive nuclear dataset, so far, encompassing 2,360 loci and âˆ¼ 699,000 bp from across the genome of Mediodactylus gecko, enabled us to resolve previously obscure phylogenetic relationships among the five, recently elevated, Mediodactylus species and to support the hypothesis that the taxon includes several new, undescribed species. Population genomic analyses within each of the proposed species showed strong genetic structure and high levels of genetic differentiation among populations.

Anti-TNF-α induced paradoxical psoriasis in patients with ankylosing spondylitis: a systematic review.

OBJECTIVES: The approval of TNF-a inhibitors (TNFi) was a breakthrough in the treatment of ankylosing spondylitis (AS). Although also effective in psoriasis, drug-related adverse events of onset of psoriasiform skin lesions - paradoxical psoriasis (PP) under TNFi have been reported. METHODS: We performed an electronic data search in MEDLINE via Pubmed and Cochrane library scientific databases from inception to January 2023, following the PRISMA guidelines. We assessed the distinct characteristics and frequency of risks for PP appearance in AS patients treated with different TNFi. RESULTS: PP was found in 0.5-1% of TNFi-treated AS patients and the latency period was 2-11 months. The safest TNFi in terms of PP induction was certolizumab, whereas the one most commonly associated with PP was infliximab. CONCLUSIONS: PP is an uncommon adverse reaction to TNFi treatment in AS patients and responds well to drug withdrawal. More large data studies need to be conducted though, to shed light on PP nature and management.

Experimental Parasite Infection Causes Genome-Wide Changes in DNA Methylation.

Parasites are arguably among the strongest drivers of natural selection, constraining hosts to evolve resistance and tolerance mechanisms. Although, the genetic basis of adaptation to parasite infection has been widely studied, little is known about how epigenetic changes contribute to parasite resistance and eventually, adaptation. Here, we investigated the role of host DNA methylation modifications to respond to parasite infections. In a controlled infection experiment, we used the three-spined stickleback fish, a model species for host-parasite studies, and their nematode parasite Camallanus lacustris. We showed that the levels of DNA methylation are higher in infected fish. Results furthermore suggest correlations between DNA methylation and shifts in key fitness and immune traits between infected and control fish, including respiratory burst and functional trans-generational traits such as the concentration of motile sperm. We revealed that genes associated with metabolic, developmental, and regulatory processes (cell death and apoptosis) were differentially methylated between infected and control fish. Interestingly, genes such as the neuropeptide FF receptor 2 and the integrin alpha 1 as well as molecular pathways including the Th1 and Th2 cell differentiation were hypermethylated in infected fish, suggesting parasite-mediated repression mechanisms of immune responses. Altogether, we demonstrate that parasite infection contributes to genome-wide DNA methylation modifications. Our study brings novel insights into the evolution of vertebrate immunity and suggests that epigenetic mechanisms are complementary to genetic responses against parasite-mediated selection.

Tail regeneration alters the digestive performance of lizards.

Tissue regeneration is a fundamental evolutionary adaptation, which is well known in lizards that can regenerate their entire tail. However, numerous parameters of this process remain poorly understood. Lizard tail serves many functions. Thus, tail autotomy comes with many disadvantages and the need for quick regeneration is imperative. To provide the required energy and materials for caudal tissue building, lizards are expected to undergo a number of physiological and biochemical adjustments. Previous research showed that tail regeneration induces changes in the digestive process. Here, we investigated if and how tail regeneration affects the digestive performance in five wall lizard species deriving from mainland and island sites and questioned whether the association of tail regeneration and digestion is affected by species relationships or environmental features, including predation pressure. We expected that lizards from high predation environments would regenerate their tail faster and modify accordingly their digestive efficiency, prioritizing the digestion of proteins; the main building blocks for tissue repair. Second, we anticipated that the general food shortage on islands would inhibit the process. Our findings showed that all species shifted their digestive efficiency, as predicted. Elongation rate was higher in sites with stronger predation regime and this was also applied to the rate with which protein digestion raised. Gut passage time increases during regeneration so as to improve the nutrient absorbance, but among the islanders, the pace was more intense. The deviations between species should be attributed to the different ecological conditions prevailing on islands rather than to their phylogenetic relationships.

Selection, drift, and introgression shape MHC polymorphism in lizards.

The major histocompatibility complex (MHC) has long served as a model for the evolution of adaptive genetic diversity in wild populations. Pathogen-mediated selection is thought to be a main driver of MHC diversity, but it remains elusive to what degree selection shapes MHC diversity in complex biogeographical scenarios where other evolutionary processes (e.g. genetic drift and introgression) may also be acting. Here we focus on two closely related green lizard species, Lacerta trilineata and L. viridis, to address the evolutionary forces acting on MHC diversity in populations with different biogeographic structure. We characterized MHC class I exon 2 and exon 3, and neutral diversity (microsatellites), to study the relative importance of selection, drift, and introgression in shaping MHC diversity. As expected, positive selection was a significant force shaping the high diversity of MHC genes in both species. Moreover, introgression significantly increased MHC diversity in mainland populations, with a primary direction of gene flow from L. viridis to L. trilineata. Finally, we found significantly fewer MHC alleles in island populations, but maintained MHC sequence and functional diversity, suggesting that positive selection counteracted the effect of drift. Overall, our data support that different evolutionary processes govern MHC diversity in different biogeographical scenarios: positive selection occurs broadly while introgression acts in sympatry and drift when the population sizes decrease.

Tail regeneration affects the digestive performance of a Mediterranean lizard.

In caudal autotomy, lizards shed their tail to escape from an attacking predator. Since the tail serves multiple functions, caudal regeneration is of pivotal importance. However, it is a demanding procedure that requires substantial energy and nutrients. Therefore, lizards have to increase energy income to fuel the extraordinary requirements of the regenerating tail. We presumed that autotomized lizards would adjust their digestion to acquire this additional energy. To clarify the effects of tail regeneration on digestion, we compared the digestive performance before autotomy, during regeneration, and after its completion. Tail regeneration indeed increased gut passage time but did not affect digestive performance in a uniform pattern: though protein income was maximized, lipid and sugar acquisition remained stable. This divergence in proteins may be attributed to their particular role in tail reconstruction, as they are the main building blocks for tissue formation.

Robust Statistical Frontalization of Human and Animal Faces.

The unconstrained acquisition of facial data in real-world conditions may result in face images with significant pose variations, illumination changes, and occlusions, affecting the performance of facial landmark localization and recognition methods. In this paper, a novel method, robust to pose, illumination variations, and occlusions is proposed for joint face frontalization and landmark localization. Unlike the state-of-the-art methods for landmark localization and pose correction, where large amount of manually annotated images or 3D facial models are required, the proposed method relies on a small set of frontal images only. By observing that the frontal facial image of both humans and animals, is the one having the minimum rank of all different poses, a model which is able to jointly recover the frontalized version of the face as well as the facial landmarks is devised. To this end, a suitable optimization problem is solved, concerning minimization of the nuclear norm (convex surrogate of the rank function) and the matrix ℓ 1 norm accounting for occlusions. The proposed method is assessed in frontal view reconstruction of human and animal faces, landmark localization, pose-invariant face recognition, face verification in unconstrained conditions, and video inpainting by conducting experiment on 9 databases. The experimental results demonstrate the effectiveness of the proposed method in comparison to the state-of-the-art methods for the target problems.

Living in sympatry: The effect of habitat partitioning on the thermoregulation of three Mediterranean lizards.

The ability for effective, accurate and precise thermoregulation is of paramount importance for ectotherms. Sympatric lizards often partition their niche and select different microhabitats. These microhabitats, however, usually differ in their thermal conditions and lizards have to adapt their thermoregulation behavior accordingly. Here, we evaluated the impact of habitat partitioning on the thermal biology of three syntopic, congeneric lacertids (Podarcis peloponnesiacus, P. tauricus and P. muralis) from central Peloponnese, Greece. We assessed thermoregulation effectiveness (E) using the three standard thermal parameters: body (Tb), operative (Te) and preferred (Tpref) temperatures. We hypothesized that the microhabitats used by each species would differ in thermal quality. We also predicted that all species would effectively thermoregulate, as they inhabit a thermally challenging mountain habitat. As expected, the partition of the habitat had an effect on the thermoregulation of lizards since microhabitats had different thermal qualities. All three species were effective and accurate thermoregulators but one of them achieved smaller E values as a result of the lower Tb in the field. This discrepancy could be attributed to the cooler (but more benign) thermal microhabitats that this species occupies.

Partitioning thermal habitat on a vertical rock, a herculean task.

Species occurring in sympatry have to effectively segregate their niche in order to co-exist. In the case of ectotherms in particular, the very important parameter of thermal biology has to be taken into account. Here we investigated the thermoregulatory effectiveness (E) of two endemic Greek lizards (Hellenolacerta graeca and Podarcis peloponnesiacus) that live syntopically on a rocky cliff in the Peloponnese. We presumed that the two species would select different microhabitats, to avoid interspecific competition, and follow a similar thermoregulation pattern as they experience the same conditions. We also expected that E values for both species would differ depending on the season. Overall, we found that the two species had similar E values for each season but differentiated partial thermoregulatory attributes. Though they both occurred in the same types of microhabitat, H. graeca selected higher sites (average 99cm above ground) than P. peloponnesiacus (average 44cm). Also, the latter achieved higher preferred temperatures during summer and winter. Finally, the effectiveness of thermoregulation for both species varied interseasonally and received its highest values during summer, in response to the lowest thermal quality that was observed then. Similar studies stress the importance of thermal shifts for ectotherm co-existence.

Infection risk dictates immunological divergence among populations in a Mediterranean lizard.

The ability of vertebrates to evolve different defence strategies in response to varying parasitism regimes remains poorly understood. Hosts may adopt two different strategies to defend themselves against parasites: tolerance (hosts alleviate the negative fitness consequences of parasite infection) and resistance (hosts strengthen their immune response as parasite burden increases). Both strategies are effective, but fitness has been reported to decline faster in less-tolerant individuals. Here, we assessed the number of splenocytes and the cell-mediated response (proxies for resistance) and body condition (a proxy for tolerance) in four populations of a Greek endemic lizard (Podarcis gaigeae), each exposed to different infection risks (defined as the cumulative effect of parasite burden and duration of exposure). We anticipated that populations with heavy parasite burden would enhance the efficacy of their immune response (resistance) compared to lizards deriving from parasite-poor habitats. We also predicted that populations with longer exposure to parasites would be adopted and be more tolerant. Each factor (duration of exposure and parasite burden) had a distinct effect on the immune response, and thus, our results were rather complicated. Lizards with heavy parasite burden and aperiodic exposure demonstrated resistance, whereas lizards with heavy parasite burden and chronic exposure were more tolerant. Populations with low parasite burden and minimal exposure were more resistant. Our results suggest that the development of some immunological strategies may be differentiated under different infection risks, even within the same species.

The particularities of a remote islet shape the thermoregulatory profile of an endemic Mediterranean lizard.

Environmental temperatures considerably affect the reptilian ability for thermoregulation and harsh climatic conditions may impose a highly effective body temperature regulation to lizards. Such demanding conditions are more common to extreme mainland habitats (e.g. deserts or mountains). To the contrary, islands have more benign climate conditions thanks to the thermal buffering effect of the surrounding sea. However, this favorable effect may be eliminated in small size islets where the scarcity of thermal shelters and exposure to high winds create challenging conditions. Here we investigate the impact of a tough islet habitat on the thermoregulation of Podarcis levendis, a lacertid lizard endemic to two rocky islets in the north Cretan Sea, Greece. To evaluate the thermoregulatory effectiveness of P. levendis we measured operative and body temperatures in the field and the preferred body temperatures in the lab. Analyses of the thermal data revealed an accurate, precise, and effective thermoregulator, achieving very high thermoregulation values (E =0.91, de¯-db¯ =7.6). This high effectiveness comes to compensate living in an inhospitable habitat as the operative temperatures denote (de =7.79). Our findings, together with the limited published literature, suggested the lack of a general pattern for all insular lizards and indicated a possible deviation for islet habitats.

Ecological explanations to island gigantism: dietary niche divergence, predation, and size in an endemic lizard.

Although rapid evolution of body size on islands has long been known, the ecological mechanisms behind this island phenomenon remain poorly understood. Diet is an important selective pressure for morphological divergence. Here we investigate if selection for novel diets has contributed to the multiple independent cases of island gigantism in the Skyros wall lizard (Podarcis gaigeae) and if diet, predation, or both factors best explain island gigantism. We combined data on body size, shape, bite force, and realized and available diets to address this. Several lines of evidence suggest that diet has contributed to the island gigantism. The larger islet lizards have relatively wider heads and higher bite performance in relation to mainland lizards than would be expected from size differences alone. The proportions of consumed and available hard prey are higher on islets than mainland localities, and lizard body size is significantly correlated with the proportion of hard prey. Furthermore, the main axis of divergence in head shape is significantly correlated with dietary divergence. Finally, a model with only diet and one including diet and predation regime explain body size divergence equally well. Our results suggest that diet is an important ecological factor behind insular body size divergence, but could be consistent with an additional role for predation.

Effects of insularity on digestion: living on islands induces shifts in physiological and morphological traits in island reptiles.

Living on islands entails numerous challenges for animals, among which resource scarcity stands out. In order to survive, animals have to optimize energy acquisition. We examined the impact of insularity on digestion comparing a series of physiological and morphological traits of adult males between insular and mainland populations of the Balkan green lizard. Island lizards had longer gastrointestinal tracts and gut passage times and higher digestive efficiencies. The dissection of the hindgut revealed an unexpected finding, the presence of cecal valves that were more frequent in island lizards. Thanks to all above islanders retain food for longer periods and thus maximize energy income and increase the amount of the extracted nutrients. That way, they secure energy income from the limited, in time and quantity, food resources of the islands.

Molecular systematics and historical biogeography of the green lizards (Lacerta) in Greece: insights from mitochondrial and nuclear DNA.

The green lizards of the genus Lacerta (Sauria, Lacertidae) comprise nine recognized species, which in Europe are mainly restricted to the southern peninsulas. Four of them (L. trilineata, L. viridis, L. bilineata and L. agilis) occur in Greece. The uncertainty of morphological diversification renders the taxonomic assignment into species and subspecies problematic. In this study sequence data derived from two mitochondrial (cytochrome b and 16S rRNA) genes and one nuclear (NKTR) gene were used to (a) evaluate the taxonomic status of the genus Lacerta in Greece with emphasis on L. trilineata group and (b) investigate the evolutionary history of the genus through the application of phylogenetic and phylogeographic analyses, using Gallotia and Timon as outgroups. The phylogenetic analyses revealed the existence of four major clades. The first clade corresponds to L. trilineata group, the second to L. media, the third to L. agilis and the fourth to a complex of L. viridis and L. bilineata. However, the produced phylogenetic relationships are not congruent with the current taxonomy, especially in the first clade in which L. trilineata appeared to be paraphyletic in regard to L. pamphylica. Six distinct lineages were inferred within L. trilineata, despite the current recognition of nine morphological subspecies, the genetic differentiation of which exceeds that of other Lacerta species, imposing a thorough taxonomic revision of the species. Our results suggested a rapid diversification of L. trilineata group during the late Miocene. We believe that the present distribution of the genus in Greece is the result of several dispersal and vicariant events that took place during the late Miocene and early Pliocene.

Treatment of digital ulcers in systemic sclerosis: recent developments and future perspectives.

Digital ulcers (DUs) comprise the main manifestation of vasculopathy and are a major cause of disability in patients with systemic sclerosis (SSc). A literature search in Web of Science, PubMed and Directory of Open Access Journals was performed in December 2022 to identify articles published in the last decade regarding the management of DUs. Prostacyclin analogues, endothelin antagonists and phosphodiesterase 5 inhibitors have shown promising results both as a stand-alone treatment and in combination for the treatment of existing and prevention of new DUs. Moreover, autologous fat grafting and botulinum toxin injections, although not readily available, can be of use in recalcitrant cases. Many investigational treatments with promising results could pave the way for a paradigm shift in the treatment of DUs in the future. Despite these recent advances, challenges remain. Better-designed trials are of paramount importance to optimise DU treatment in the years to come. Key Points • DUs are a major cause of pain and reduced quality of life in patients with SSc. • Prostacyclin analogues and endothelin antagonists have shown promising results both as a stand-alone treatment and in combination for the treatment of existing and prevention of new DUs. • In the future, a combination of more powerful vasodilatory drugs, perhaps in conjunction with topical approaches, may improve outcomes.

Small Island Effects on the Thermal Biology of the Endemic Mediterranean Lizard Podarcis gaigeae.

Ectotherms are vastly affected by climatic conditions as they rely on external sources of heat to regulate their body temperature, and changes in their habitat thermal quality could seriously affect their overall biology. To overcome the problems of a thermally unfavorable habitat, lizards need to either adjust their thermoregulatory behavior or respond to directional selection and shift their preferred body temperatures. To assess the impact of habitat thermal quality on the thermoregulatory profile, we studied multiple islet and 'mainland' populations of the Skyros wall lizard Podarcis gaigeae, an endemic lacertid to Skyros Archipelago, Greece. We evaluated the effectiveness of thermoregulation (E) using the three main thermal parameters: body (Tb), operative (Te), and preferred (Tpref) temperatures. We first hypothesized that the spatial homogeneity, the scarcity of thermal shelters, and the exposure to higher winds on islets would result in more demanding climate conditions. Second, we anticipated that islet lizards would achieve higher E in response to the lower thermal quality therein. As hypothesized, thermal parameters differed between populations but not in the expected manner. Skyros 'mainland' habitats reached higher temperatures, had more intense fluctuations, and were of lower thermal quality. As a result, lizards showed higher accuracy, precision, and effectiveness of thermoregulation. Noteworthy, we found that lizards from different populations have shifted their thermal profile and preferred body temperatures to cope with the particular conditions prevailing in their habitats. The latter supports the labile view on the evolution of thermoregulation.

Origin matters: Using a local reference genome improves measures in population genomics.

Genome sequencing enables answering fundamental questions about the genetic basis of adaptation, population structure and epigenetic mechanisms. Yet, we usually need a suitable reference genome for mapping population-level resequencing data. In some model systems, multiple reference genomes are available, giving the challenging task of determining which reference genome best suits the data. Here, we compared the use of two different reference genomes for the three-spined stickleback (Gasterosteus aculeatus), one novel genome derived from a European gynogenetic individual and the published reference genome of a North American individual. Specifically, we investigated the impact of using a local reference versus one generated from a distinct lineage on several common population genomics analyses. Through mapping genome resequencing data of 60 sticklebacks from across Europe and North America, we demonstrate that genetic distance among samples and the reference genomes impacts downstream analyses. Using a local reference genome increased mapping efficiency and genotyping accuracy, effectively retaining more and better data. Despite comparable distributions of the metrics generated across the genome using SNP data (i.e. π, Tajima's D and FST ), window-based statistics using different references resulted in different outlier genes and enriched gene functions. A marker-based analysis of DNA methylation distributions had a comparably high overlap in outlier genes and functions, yet with distinct differences depending on the reference genome. Overall, our results highlight how using a local reference genome decreases reference bias to increase confidence in downstream analyses of the data. Such results have significant implications in all reference-genome-based population genomic analyses.

Serotonin and systemic sclerosis. An emerging player in pathogenesis.

OBJECTIVES: Systemic sclerosis (SSc) is a complex, autoimmune disease characterized by multiple organ fibrosis and vasculopathy. Experimental and clinical evidence indicates that serotonin is crucially involved in the fibrotic process and mediates vascular manifestations such as Raynaud's phenomenon (RP) or pulmonary arterial hypertension (PAH), all key features of SSc. In this review, we summarize the current knowledge on the potential contribution of serotonin in SSc pathogenesis and provide a rationale for further investigation of this molecule as a therapeutic target. METHODS: Medline and Cochrane databases were searched from inception to April 2021 using the search terms (systemic sclerosis OR scleroderma OR Raynaud OR Pulmonary arterial hypertension) AND serotonin. RESULTS: Serotonin, a key molecule in an array of central and peripheral functions, has a multifaceted role in regulating fibrosis and vasculopathy. Experimental data suggest that serotonin drives fibrosis in the skin and visceral organs, promotes platelet aggregation, induces vasoconstriction and increases pulmonary vascular resistance. Earlier human trials regarding drugs that inhibit serotonin signaling produced mixed results. However, recent advances in the understanding of the underlying molecular mechanisms could help identify novel therapeutics targeting the serotonin pathway and inform future clinical trials. CONCLUSIONS: Serotonin may be a mediator in both fibrosis and vasculopathy. Further exploration of the potential role of serotonin in SSc is justified.

Chronic Spontaneous and Inducible Urticaria Associated With Mycoplasma pneumoniae Infection.

Acute childhood urticaria is a common disorder that has been associated with infections. In a few children, it may last for more than six weeks, thereafter it is characterized as chronic urticaria (CU). We report two cases, one suffering from chronic spontaneous urticaria and one chronic inducible urticarias (dermographism and cold urticaria). Both children had concomitant respiratory symptoms that were associated with Mycoplasma pneumoniae (MP) infection. Urticarias' symptoms and signs were refractory to regular antihistamines dose but showed marked improvement or complete resolution following clarithromycin administration. CU response to antibiotics pointed strongly to a potential causative role of MP in the pathogenesis of chronic spontaneous and chronic inducible urticarias. It is not clear if MP was the etiopathogenic cause or just the trigger. Nevertheless, refractory to antihistamines urticarias associated with MP infection may respond to antibiotics, which should be considered as an alternative therapeutic approach.

Recovering Joint and Individual Components in Facial Data.

A set of images depicting faces with different expressions or in various ages consists of components that are shared across all images (i.e., joint components) imparting to the depicted object the properties of human faces as well as individual components that are related to different expressions or age groups. Discovering the common (joint) and individual components in facial images is crucial for applications such as facial expression transfer and age progression. The problem is rather challenging when dealing with images captured in unconstrained conditions in the presence of sparse non-Gaussian errors of large magnitude (i.e., sparse gross errors or outliers) and contain missing data. In this paper, we investigate the use of a method recently introduced in statistics, the so-called Joint and Individual Variance Explained (JIVE) method, for the robust recovery of joint and individual components in visual facial data consisting of an arbitrary number of views. Since the JIVE is not robust to sparse gross errors, we propose alternatives, which are (1) robust to sparse gross, non-Gaussian noise, (2) able to automatically find the individual components rank, and (3) can handle missing data. We demonstrate the effectiveness of the proposed methods to several computer vision applications, namely facial expression synthesis and 2D and 3D face age progression 'in-the-wild'.