Scaling the high latitudes: evolution, diversification, and dispersal of Coryphella nudibranchs across the Northern Hemisphere.

Nudibranch molluscs Coryphella are widely distributed and species-rich gastropod group lacking fossil record and displaying a complex distribution across both Southern and Northern hemispheres. In this paper we provide a detailed review of the morphology, ecology, and distribution of Coryphella, estimation of divergence times between species, an ancestral area reconstruction, and a population analysis of widely distributed trans-Arctic species Coryphella verrucosa to investigate the evolution, phylogeographic patterns and reconstruct possible historical routes of oceanic dispersal. The inclusion of a larger sample size and five molecular markers has revealed a complex evolutionary history of Coryphella, shaped by transgression, vicariance, and dietary shifts, and overall driven by the pervasive effect of glacial cycles. We also revealed the presence of additional cryptic diversity, which suggests that further sampling may produce additional species in this group of nudibranchs. Tree calibration indicates the genus Coryphella originates in the middle Miocene in the Pacific Ocean and the early divergence within this group also occurred in the Pacific, specifically in different regions of the North Pacific. The ancestral area reconstruction inferred five independent instances of transgression from the Pacific Ocean to the Atlantic via different migration routes, including the Panamanian seaway and the Bering Strait. Among them, we identified three cases of successful transition to the Arctic waters from the North Pacific via the Bering Strait, associated with interglacial conditions of middle Pleistocene. Consequently, Pleistocene glacial cycles likely prompted pulses of boreal faunal elements to disperse southwards followed by range disjunction and temporary isolation of distant populations and resulting in allopatric speciation. Evidence from the population structure of contemporary trans-Arctic species suggests an occurrence of independent recolonization pathways of Arctic waters from both southernly and northernly refugia after the Last Glacial Maximum.

Panmixia and local endemism: a revision of the Eubranchus rupium species complex with a description of new species.

Species of the genus Eubranchus Forbes, 1838 (Mollusca: Gastropoda: Nudibranchia) are common faunistic elements of boreal benthic ecosystems, associated with hydroid communities. Recent studies have suggested that the widely distributed trans-Arctic E. rupium (Møller, 1842) constitutes a complex of at least three candidate species, but the detailed taxonomy of the complex remains unresolved. The purpose of the present paper is to conduct an integrative taxonomic study including molecular genetic methods (a phylogenetic analysis using COI , 16S rRNA and histone H3 with application of species delimitation methods) and morphological study (light and scanning electron microscopy) of E. rupium and closely related species. The specific aims of this study were to establish the species boundaries, morphological variability, and the phylogeographic structure within this group. The phylogeographic analysis included a TCS -based network analysis, an analysis of molecular variance (AMOVA), divergence time estimations, and ancestral area reconstructions. We demonstrate that specimens initially identified as E. rupium included three distinctive species: the nominal E. rupium with an amphiboreal range, the new species Eubranchus novik sp. nov. from the Sea of Japan, for which a taxonomic description is provided in this paper, and Eubranchus sp. from the northern Kuril Islands, which requires the collection and study of additional material for formal description. Our results confirm the amphiboreal distribution of E. rupium , as no geographic structure was found across Pacific, Arctic and Atlantic populations, and the results of the AMOVA analysis showed no differences between groups of samples from different geographic regions. The divergence of the 'Eubrancus rupium species complex' is estimated from the late Miocene or the Miocene-Pliocene boundary to the late Pliocene. It is hypothesised that the most probable ancestral region for the Eubranchus rupium species complex is the north-western Pacific, and the subsequent speciation likely occurred due to dispersal followed by allopatric speciation. ZooBank: urn:lsid:zoobank.org:pub:228E0C46-0BF7-4DDD-9C00-67B50E298D65.

The Complete Genome Sequences of 7 Species of Nudibranchs (Nudibranchia, Gastropoda).

We present genome sequences of 7 species of sea slugs from 4 genera. Illumina sequencing was performed on tissue from wild-collected museum specimens. The reads were assembled using a de novo method followed by a finishing step. The raw and assembled data are publicly available via Genbank.

A cryptic radiation of Caribbean sea slugs revealed by integrative analysis: Cyerce 'antillensis' (Sacoglossa: Caliphyllidae) is six distinct species.

Integrative studies have revealed cryptic radiations in several Caribbean lineages of heterobranch sea slugs, raising questions about the evolutionary mechanisms that promote speciation within the tropical Western Atlantic. Cyerce Bergh, 1871 is a genus comprising 12 named species in the family Caliphyllidae that lack the photosynthetic ability of other sacoglossans but are noted for vibrant colours on the large cerata (dorsal leaf-like appendages) that characterize many species. Two species are widely reported from the Caribbean: Cyerce cristallina (Trinchese, 1881) and Cyerce antillensis Engel, 1927. Here, we present an integrative assessment of diversity in Caribbean Cyerce. Four methods of molecular species delimitation supported seven species in samples from the Caribbean and adjacent subtropical Western Atlantic. Six delimited species formed a monophyletic lineage in phylogenetic analyses but were > 9% divergent at the barcoding COI locus and could be differentiated using ecological, reproductive and/or morphological traits. We redescribe C. antillensis, a senior synonym for the poorly known Cyerce habanensis Ortea & Templado, 1988, and describe five new species. Evolutionary shifts in algal host use, penial armature and larval life history might have acted synergistically to promote the rapid divergence of endemic species with restricted distributions in this radiation, substantially increasing global diversity of the genus.

Triazolo[4,5-d]pyrimidin-5-amines based ERK3 inhibitors fail to demonstrate selective effects on adipocyte function.

Extracellular signal-regulated kinase 3 (ERK3 also designated MAPK6 - mitogen-activated protein kinase 6) is a ubiquitously expressed kinase participating in the regulation of a broad spectrum of physiological and pathological processes. Targeted inhibition of the kinase may allow the development of novel treatment strategies for a variety of types of cancer and somatic pathologies, as well as preserving metabolic health, combat obesity and diabetes. We chose and synthesized three triazolo [4,5-d]pyrimidin-5-amines proposed previously as putative ERK3 inhibitors to assess their selectivity and biological effects in terms of metabolic state impact in living cells. As it was previously shown that ERK3 is a major regulator of lipolysis in adipocytes, we focused on this process. Our new results indicate that in addition to the previously identified lipolytic enzyme ATGL, ERK3 also regulates hormone-sensitive lipase (HSL) and monoglyceride lipase (MGL). Moreover, this kinase also promotes the abundance of fatty acid synthase (FASN) as well as protein kinase cAMP-activated catalytic subunit alpha (PKACα). To investigate various effects of putative ERK3 inhibitors on lipolysis, we utilized different adipocyte models. We demonstrated that molecules exhibit lipolysis-modulating effects; however, the effects of triazolo [4,5-d]pyrimidin-5-amines based inhibitors on lipolysis are not dependent on ERK3. Subsequently, we revealed a wide range of the compounds' possible targets using a machine learning-based prediction. Therefore, the tested compounds inhibit ERK3 in vitro, but the biological effect of this inhibition is significantly overlapped and modified by some other molecular events related to the non-selective binding to other targets.

Precise Fingerprint Determination of Vibrational Infrared Spectra in a Series of Co(II) Clathrochelates through Experimental and Theoretical Analyses.

The energetic demands of modern society for clean energy vectors, such as H2, have caused a surge in research associated with homogeneous and immobilized electrocatalysts that may replace Pt. In particular, clathrochelates have shown excellent electrocatalytic properties for the hydrogen evolution reaction (HER). However, the actual mechanism for the HER catalyzed by these d-metal complexes remains an open debate, which may be addressed via Operando spectroelectrochemistry. The prediction of electrochemical properties via density functional theory (DFT) needs access to thermodynamic functions, which are only available after Hessian calculations. Unfortunately, there is a notable lack in the current literature regarding the precise evaluation of vibrational spectra of such complexes, given their structural complexity and the associated tangled IR spectra. In this work, we have performed a detailed theoretical and experimental analysis in a family of Co(II) clathrochelates, in order to establish univocally their IR pattern, and also the calculation methodology that is adequate for such predictions. In summary, we have observed the presence of multiple common bands shared by this clathrochelate family, using the B3LYP functional, the LANL2DZ basis, and effective core potentials (ECP) for heavy atoms. The most important issue addressed in this article was therefore related to the detailed assignment of the fingerprint associated with cobalt(II) clathrochelates, which is a challenging endeavor due to the crowded nature of their spectra.

Platelet-derived lipids promote insulin secretion of pancreatic ß cells.

Hyperreactive platelets are commonly observed in diabetic patients indicating a potential link between glucose homeostasis and platelet reactivity. This raises the possibility that platelets may play a role in the regulation of metabolism. Pancreatic ß cells are the central regulators of systemic glucose homeostasis. Here, we show that factor(s) derived from ß cells stimulate platelet activity and platelets selectively localize to the vascular endothelium of pancreatic islets. Both depletion of platelets and ablation of major platelet adhesion or activation pathways consistently resulted in impaired glucose tolerance and decreased circulating insulin levels. Furthermore, we found platelet-derived lipid classes to promote insulin secretion and identified 20-Hydroxyeicosatetraenoic acid (20-HETE) as the main factor promoting ß cells function. Finally, we demonstrate that the levels of platelet-derived 20-HETE decline with age and that this parallels with reduced impact of platelets on ß cell function. Our findings identify an unexpected function of platelets in the regulation of insulin secretion and glucose metabolism, which promotes metabolic fitness in young individuals.

The genus Pupa Röding, 1798 (Mollusca, Gastropoda, Acteonidae) in New Caledonia with notes on Recent species.

The study of newly collected, live specimens of Pupa (Acteonidae) from New Caledonia and French Polynesia, revealed the presence of six distinct species in this region, including an undescribed species. All these species are re-described and/or named using molecular and morphological evidence as well as a review of the literature and examination of photographs of the type material of described species. Moreover, a review of the literature and type material suggests the existence of six additional species from other geographic regions across the Indo-Pacific. Illustrations of all these species are provided as well as remarks on possible synonymies. This study is the first species-level review of this group using modern taxonomic techniques.

57Fe Mössbauer and DFT study of the electronic and spatial structures of the iron(II) (pseudo)clathrochelates: the effect of ligand field strength.

Combined experimental 57Fe Mössbauer and theoretical DFT study of a series of iron(II)-centered (pseudo)macrobicyclic analogs and homologs was performed. The field strength of the corresponding (pseudo)encapsulating ligand was found to affect both the spin state of a caged iron(II) ion and the electron density at its nucleus. In a row of the iron(II) tris-dioximates, passing from the non-macrocyclic complex to its monocapped pseudomacrobicyclic analog caused an increase both in the ligand field strength and in the electron density at the Fe2+ ion, and, therefore, a decrease in the isomer shift (IS) value (so-called "semiclathrochelate effect"). Its macrobicyclization, giving the quasiaromatic cage complex, caused a further increase in the two former parameters and a decrease in IS (so-called "macrobicyclic effect"). The trend of their IS values was successfully predicted using the performed quantum-chemical calculations and the corresponding linear correlation with the electron density at their 57Fe nuclei was plotted. A variety of different functionals can be successfully used for such excellent prediction. The slope of this correlation was found to be unaffected by the used functional. In contrast, the predictions of both the sign and the values of quadrupole splitting (QS) for them, based on the theoretical calculations of EFG tensors, were found to be a real great challenge, which could not be solved at the moment even in the case of these C3-pseudosymmetric iron(II) complexes with known XRD structures. The latter experimental data allowed us to deduce a sign of the QSs for them. The straightforwarded molecular design of a (pseudo)encapsulating ligand is proposed to control both the spin state and the redox characteristics of an encapsulated metal ion.

Seven new "cryptic" species of Discodorididae (Mollusca, Gastropoda, Nudibranchia) from New Caledonia.

The study of a well-preserved collection of discodorid nudibranchs collected in Koumac, New Caledonia, revealed the presence of seven species new to science belonging to the genera Atagema, Jorunna, Rostanga, and Sclerodoris, although some of the generic assignments are tentative as the phylogeny of Discodorididae remains unresolved. Moreover, a poorly known species of Atagema originally described from New Caledonia is re-described and the presence of Sclerodoristuberculata in New Caledonia is confirmed with molecular data. All the species described herein are highly cryptic on their food source and in the context of the present study the term "cryptic" is used to denote such species. This paper highlights the importance of comprehensive collecting efforts to identify and document well-camouflaged taxa.

Design of Fluorescent Carbon Dots (CDs) for the Selective detection of Metal-Containing Ions.

The pollution caused by heavy metals (HMs) may occur through both natural processes and anthropogenic activities and is found in complex media. The purpose of this review is to summarize the state-of-art of fluorescent CDs and the sensing applications in a systematic manner. This review intends to provide clues on the origin on the observed selectivity in chemiluminiscence sensors, which was until now a stated but unaddressed question, and still remains open for debate. Indeed, it is tempting to think that CDs possessing functional groups with soft bases at the surface are able to detect soft metal acids, while the opposite is to be suspected for hard acid-base pairs. However, the literature shows several examples where this trend does not hold. We found that such observation is explained by the involvement of dynamic quenching, which does not involve the formation of a non-fluorescent complex, as in the case of static quenching. We have provided an interpretation of published data that was not provided by the original authors and offer guidelines to enable the design of CDs to target ions in solution.

Targeting ERK3/MK5 complex for treatment of obesity and diabetes.

Kinases represent one of the largest druggable families of proteins. Importantly, many kinases are aberrantly activated/de-activated in multiple organs during obesity, which contributes to the development of diabetes and associated diseases. Previous results indicate that the complex between Extracellular-regulated kinase 3 (ERK3) and Mitogen-Activated Protein Kinase (MAPK)-activated protein kinase 5 (MK5) suppresses energy dissipation and promotes fatty acids (FAs) output in adipose tissue and, therefore promotes obesity and diabetes. However, the therapeutic potential of targeting this complex at the systemic level has not been fully explored. Here we applied a translational approach to target the ERK3/MK5 complex in mice. Importantly, deletion of ERK3 in the whole body or administration of MK5-specific inhibitor protects against obesity and promotes insulin sensitivity. Finally, we show that the expression of ERK3 and MK5 correlates with the degree of obesity and that ERK3/MK5 complex regulates energy dissipation in human adipocytes. Altogether, we demonstrate that ERK3/MK5 complex can be targeted in vivo to preserve metabolic health and combat obesity and diabetes.

Phylogenomic resolution of the root of Panpulmonata, a hyperdiverse radiation of gastropods: new insight into the evolution of air breathing.

Transitions to terrestriality have been associated with major animal radiations including land snails and slugs in Stylommatophora (>20 000 described species), the most successful lineage of 'pulmonates' (a non-monophyletic assemblage of air-breathing gastropods). However, phylogenomic studies have failed to robustly resolve relationships among traditional pulmonates and affiliated marine lineages that comprise clade Panpulmonata (Mollusca, Gastropoda), especially two key taxa: Sacoglossa, a group including photosynthetic sea slugs, and Siphonarioidea, intertidal limpet-like snails with a non-contractile pneumostome (narrow opening to a vascularized pallial cavity). To clarify the evolutionary history of the panpulmonate radiation, we performed phylogenomic analyses on datasets of up to 1160 nuclear protein-coding genes for 110 gastropods, including 40 new transcriptomes for Sacoglossa and Siphonarioidea. All 18 analyses recovered Sacoglossa as the sister group to a clade we named Pneumopulmonata, within which Siphonarioidea was sister to the remaining lineages in most analyses. Comparative modelling indicated shifts to marginal habitat (estuarine, mangrove and intertidal zones) preceded and accelerated the evolution of a pneumostome, present in the pneumopulmonate ancestor along with a one-sided plicate gill. These findings highlight key intermediate stages in the evolution of air-breathing snails, supporting the hypothesis that adaptation to marginal zones played an important role in major sea-to-land transitions.

Moynihan's Lump as an unusual variant of right hepatic artery during a laparoscopic cholecystectomy approach. A case report.

INTRODUCTION AND IMPORTANCE: One of the most important measures during the cholecystectomy procedure is based on a "Culture for Safe Cholecystectomy (CSC)". Vascular injury reports an open surgery conversion rate of 0 to 1.9% and a mortality of less than 0.02%. The caterpillar or Moynihan's hump configuration is characterized by a tortuous right hepatic artery (RHA) running proximal and/or parallel to the cystic duct and predisposes to a small and/or short cystic artery (CA). CASE PRESENTATION: A 65-year-old woman with no relevant clinical history underwent a laparoscopic cholecystectomy (LC) for cholelithiasis; during the procedure a caterpillar or Moynihan's hump was identified. CLINICAL DISCUSSION: Anatomical variations represent 20-50% of all cases; therefore, CVS is required. The incidence of caterpillar or Moynihan's hump varies between 1% and 13% of all cases. To date, the scientific literature on this topic is limited. The most accepted etiology is related to embryological formation. CONCLUSION: Biliary and arterial variations are more frequent than we think, so an anatomical knowledge, CSC and CVS represent a fundamental rule, increasing the safety of the surgical procedure.

A phosphoproteomic approach reveals that PKD3 controls PKA-mediated glucose and tyrosine metabolism.

Members of the protein kinase D (PKD) family (PKD1, 2, and 3) integrate hormonal and nutritional inputs to regulate complex cellular metabolism. Despite the fact that a number of functions have been annotated to particular PKDs, their molecular targets are relatively poorly explored. PKD3 promotes insulin sensitivity and suppresses lipogenesis in the liver of animals fed a high-fat diet. However, its substrates are largely unknown. Here we applied proteomic approaches to determine PKD3 targets. We identified more than 300 putative targets of PKD3. Furthermore, biochemical analysis revealed that PKD3 regulates cAMP-dependent PKA activity, a master regulator of the hepatic response to glucagon and fasting. PKA regulates glucose, lipid, and amino acid metabolism in the liver, by targeting key enzymes in the respective processes. Among them the PKA targets phenylalanine hydroxylase (PAH) catalyzes the conversion of phenylalanine to tyrosine. Consistently, we showed that PKD3 is activated by glucagon and promotes glucose and tyrosine levels in hepatocytes. Therefore, our data indicate that PKD3 might play a role in the hepatic response to glucagon.

Protein Kinase D2 drives chylomicron-mediated lipid transport in the intestine and promotes obesity.

Lipids are the most energy-dense components of the diet, and their overconsumption promotes obesity and diabetes. Dietary fat content has been linked to the lipid processing activity by the intestine and its overall capacity to absorb triglycerides (TG). However, the signaling cascades driving intestinal lipid absorption in response to elevated dietary fat are largely unknown. Here, we describe an unexpected role of the protein kinase D2 (PKD2) in lipid homeostasis. We demonstrate that PKD2 activity promotes chylomicron-mediated TG transfer in enterocytes. PKD2 increases chylomicron size to enhance the TG secretion on the basolateral side of the mouse and human enterocytes, which is associated with decreased abundance of APOA4. PKD2 activation in intestine also correlates positively with circulating TG in obese human patients. Importantly, deletion, inactivation, or inhibition of PKD2 ameliorates high-fat diet-induced obesity and diabetes and improves gut microbiota profile in mice. Taken together, our findings suggest that PKD2 represents a key signaling node promoting dietary fat absorption and may serve as an attractive target for the treatment of obesity.

Functionally non-redundant paralogs spe-47 and spe-50 encode FB-MO associated proteins and interact with him-8.

The activation of C. elegans spermatids to crawling spermatozoa is affected by a number of genes including spe-47. Here, we investigate a paralog to spe-47: spe-50, which has a highly conserved sequence and expression, but which is not functionally redundant to spe-47. Phylogenetic analysis indicates that the duplication event that produced the paralogs occurred prior to the radiation of the Caenorhabditis species included in the analysis, allowing a long period for the paralogs to diverge in function. Furthermore, we observed that knockout mutations in both genes, either alone or together, have little effect on sperm function. However, hermaphrodites harboring both knockout mutations combined with a third mutation in the him-8 gene are nearly self-sterile due to a sperm defect, even though they have numerous apparently normal sperm within their spermathecae. We suggest that the sperm in these triple mutants are defective in fusing with oocytes, and that the effect of the him-8 mutation is unclear but likely due to its direct or indirect effect on local chromatin structure and function.

Diacylglycerol-evoked activation of PKC and PKD isoforms in regulation of glucose and lipid metabolism: a review.

Protein kinase C (PKC) and Protein kinase D (PKD) isoforms can sense diacylglycerol (DAG) generated in the different cellular compartments in various physiological processes. DAG accumulates in multiple organs of the obese subjects, which leads to the disruption of metabolic homeostasis and the development of diabetes as well as associated diseases. Multiple studies proved that aberrant activation of PKCs and PKDs contributes to the development of metabolic diseases. DAG-sensing PKC and PKD isoforms play a crucial role in the regulation of metabolic homeostasis and therefore might serve as targets for the treatment of metabolic disorders such as obesity and diabetes.

The adrenergic-induced ERK3 pathway drives lipolysis and suppresses energy dissipation.

Obesity-induced diabetes affects >400 million people worldwide. Uncontrolled lipolysis (free fatty acid release from adipocytes) can contribute to diabetes and obesity. To identify future therapeutic avenues targeting this pathway, we performed a high-throughput screen and identified the extracellular-regulated kinase 3 (ERK3) as a hit. We demonstrated that ß-adrenergic stimulation stabilizes ERK3, leading to the formation of a complex with the cofactor MAP kinase-activated protein kinase 5 (MK5), thereby driving lipolysis. Mechanistically, we identified a downstream target of the ERK3/MK5 pathway, the transcription factor FOXO1, which promotes the expression of the major lipolytic enzyme ATGL. Finally, we provide evidence that targeted deletion of ERK3 in mouse adipocytes inhibits lipolysis, but elevates energy dissipation, promoting lean phenotype and ameliorating diabetes. Thus, ERK3/MK5 represents a previously unrecognized signaling axis in adipose tissue and an attractive target for future therapies aiming to combat obesity-induced diabetes.

An integrative approach to the systematics of the Berthella californica species complex (Heterobranchia: Pleurobranchidae).

Berthella californica (W. H. Dall, 1900) is a widespread species of heterobranch sea slug distributed across the North Pacific Ocean, from Korea and Japan to the Galapagos Islands. Two distinct morphotypes are observed in B. californica, which differ in external coloration, egg-mass morphology and geographic distribution (with the exception of a small range overlap in Southern California). Molecular and morphological data obtained in this study reveals that these two morphotypes constitute distinct species. The name B. californica (type locality: San Pedro, California) is retained for the southern morphotype, whereas the name Berthella chacei (J. Q. Burch, 1944) (type locality: Crescent City, California) is resurrected for the northern morphotype. Moreover, molecular phylogenetic analyses recovered B. californica as sister to Berthellina, in a well-supported clade separate from Berthella, suggesting that the classification of B. californica may need additional revision.