Ecological baselines in the Eastern Mediterranean Sea shifted long before the availability of observational time series.

Native biodiversity loss and invasions by nonindigenous species (NIS) have massively altered ecosystems worldwide, but trajectories of taxonomic and functional reorganization remain poorly understood due to the scarcity of long-term data. Where ecological time series are available, their temporal coverage is often shorter than the history of anthropogenic changes, posing the risk of drawing misleading conclusions on systems' current states and future development. Focusing on the Eastern Mediterranean Sea, a region affected by massive biological invasions and the largest climate change-driven collapse of native marine biodiversity ever documented, we followed the taxonomic and functional evolution of an emerging "novel ecosystem", using a unique dataset on shelled mollusks sampled in 2005-2022 on the Israeli shelf. To quantify the alteration of observed assemblages relative to historical times, we also analyzed decades- to centuries-old ecological baselines reconstructed from radiometrically dated death assemblages, time-averaged accumulations of shells on the seafloor that constitute natural archives of past community states. Against expectations, we found no major loss of native biodiversity in the past two decades, suggesting that its collapse had occurred even earlier than 2005. Instead, assemblage taxonomic and functional richness increased, reflecting the diversification of NIS whose trait structure was, and has remained, different from the native one. The comparison with the death assemblage, however, revealed that modern assemblages are taxonomically and functionally much impoverished compared to historical communities. This implies that NIS did not compensate for the functional loss of native taxa, and that even the most complete observational dataset available for the region represents a shifted baseline that does not reflect the actual magnitude of anthropogenic changes. While highlighting the great value of observational time series, our results call for the integration of multiple information sources on past ecosystem states to better understand patterns of biodiversity loss in the Anthropocene.

Treatment-related mortality in children with cancer in low-income and middle-income countries: a systematic review and meta-analysis.

BACKGROUND: Approximately 90% of children with cancer live in low-income and middle-income countries (LMICs), where 5-year survival is lower than 20%. Treatment-related mortality in high-income countries is approximately 3-5%; however, in LMICs, treatment-related mortality has been reported in up to 45% of children with cancer. This study aimed to systematically explore the burden of treatment-related mortality in children with cancer in LMICs and to explore the association between country income level and treatment-related mortality. METHODS: For this systematic review and meta-analysis we identified articles published between Jan 1, 2010, and June 22, 2021, describing treatment-related mortality in paediatric patients (aged 0-21 years) with cancer in LMICs. We searched PubMed, Trip, Web of Science, Embase, and the WHO Global Metric Index databases. The search was limited to full-text articles and excluded case reports (<10 patients) and haematopoietic stem-cell transplantation recipients. Two reviewers independently screened studies for eligibility, extracted data from included publications, and evaluated data quality. Random and mixed-effects models were used to estimate treatment-related mortality burden and trends. The Cochran-Q statistic was used to assess heterogeneity between studies. This study is registered on PROSPERO (CRD42021264849). FINDINGS: Of 13 269 identified abstracts, 501 studies representing 68 351 paediatric patients with cancer were included. The treatment-related mortality estimate was 6·82% (95% CI 5·99-7·64), accounting for 30·9% of overall mortality (4437 of 14 358 deaths). Treatment-related mortality was inversely related to country income. Treatment-related mortality was 14·19% (95% CI 9·65-18·73) in low-income countries, 9·21% (7·93-10·49) in lower-middle-income countries, and 4·47% (3·42-5·53) in upper-middle-income countries (Cochran-Q 42·39, p<0·0001). In upper-middle-income countries, the incidence of treatment-related mortality decreased over time (slope -0·002, p=0·0028); however, outcomes remained unchanged in low-income (p=0·21) and lower-middle-income countries (p=0·16). INTERPRETATION: Approximately one in 15 children receiving cancer treatment in LMICs die from treatment-related complications. Although treatment-related mortality has decreased in upper-middle-income countries over time, it remains unchanged in LMICs. There is an urgent need for targeted supportive care interventions to reduce global disparities in childhood cancer survival. FUNDING: American Lebanese Syrian Associated Charities and National Cancer Institute.

The Feasibility of Using Comic-Based Concussion Discharge Instructions: Gauging Likeability and Knowledge Improvement Among Adolescents and Parents.

OBJECTIVE: The objective of this study was to evaluate feasibility of supplementing emergency department (ED) concussion discharge instructions for adolescents and parents with a newly created educational comic and a publicly available comic-based video at an outpatient sports neurology clinic. METHODS: We created a gender-neutral, 2-page comic to augment text-only ED concussion discharge instructions. A sample of patients evaluated at a sports neurology clinic and their parents/guardians participated. Patients and their parents were randomized to view either the comic only or both the comic and publicly available comic-based video. Patients and parents completed preintervention and postintervention surveys to assess likeability and concussion knowledge including concussion definition, symptoms, return-to-ED criteria, and resuming normal activity. Data were analyzed using descriptive and comparative statistics. RESULTS: A total of 57 patients (47.4% female; mean age, 15 years) and 37 guardians were enrolled. Most (73%) concussions were sports related, with the majority having sought care within 24 hours in an ED (80%). Over half (51%) had experienced 2 or more prior concussions. Overall, 31 adolescents and 20 guardians viewed both comic and video, whereas 26 adolescents and 17 guardians viewed the comic only. Both comic and video were favorably reviewed, but a higher proportion of respondents rated the video more positively than the comic for likability (P < 0.01), comprehensibility (P < 0.05), and increasing understanding (P < 0.05). Patients' knowledge of some concussion symptoms emphasized in the comic increased after reading (emotional changes, P = 0.02; vomiting, P = 0.04). CONCLUSIONS: Patients showed increased concussion knowledge using the favorably endorsed comic-based discharge instructions. Using comic-based supplemental discharge tools may optimize concussion education for adolescents.

Barriers to the early integration of palliative care in pediatric oncology in 11 Eurasian countries.

BACKGROUND: The early integration of palliative care significantly improves quality of life for children with cancer. However, cultural, structural, and socioeconomic barriers can delay the integration of palliative care into cancer care, particularly in low-income and middle-income countries. To date, little is known regarding the timing of and barriers to palliative care integration in Eurasia. METHODS: The Assessing Doctors' Attitudes on Palliative Treatment (ADAPT) survey evaluates physician perceptions regarding palliative care integration into pediatric oncology in Eurasia. This evidence-based survey was adapted to the regional context; iteratively reviewed by US and regional panelists; and piloted in English, Russian, and Mongolian. After distribution to physicians caring for children with cancer, statistical analysis was complemented by qualitative analysis of open-ended responses. RESULTS: A total of 424 physician responses were received from 11 countries in the Eurasian region. Study findings demonstrated wide variability in access to palliative care experts across countries (18%-96%), with the majority of providers (64%) reporting that the initial palliative care consultation typically occurs when curative options are no longer available. Providers desired an earlier initial palliative care consultation than what currently occurs in their setting (P < .001). Primary barriers to timely consultation included limited access to palliative care services and specialists, lack of physician education, and perceived family resistance. CONCLUSIONS: The current study is the first to identify physician perceptions of the delayed timing of palliative care integration into childhood cancer care and associated barriers in Eurasia. These findings will inform the development of targeted interventions to mitigate local structural and cultural barriers to access and facilitate earlier palliative care integration in the region.

A multicountry assessment in Eurasia: Alignment of physician perspectives on palliative care integration in pediatric oncology with World Health Organization guidelines.

BACKGROUND: The World Health Organization (WHO) advocates for early integration of palliative care for all children with life-threatening illness. Provider awareness and misperceptions, however, can impede this imperative. In the Eurasian region, little is known about physician knowledge and perspectives on palliative care. METHODS: The Assessing Doctors' Attitudes on Palliative Treatment survey was developed as an evidence-based and culturally relevant assessment of physician perceptions on palliative care integration into childhood cancer care in Eurasia. Iteratively tested by American and Eurasian palliative care experts, the survey was culturally adapted, translated, and piloted in English, Russian, and Mongolian. The survey was distributed to physicians caring for children with cancer. Fifteen statements were scored in accordance with WHO guidelines to evaluate provider knowledge. The statistical analysis was complemented by a qualitative analysis of open-ended responses. RESULTS: This study received 424 responses from 11 countries in Eurasia. The mean alignment between provider perspectives and WHO recommendations was 70% (range, 7%-100%). Significant independent predictors of higher alignment included country, prior palliative care education, and greater experience with patient death. Respondents primarily described palliative care as end-of-life care and symptom management. Two-thirds of respondents (67%) reported not feeling confident about delivering at least 1 component of palliative care. CONCLUSIONS: This is the first study assessing physician perspectives and knowledge of palliative care in Eurasia and reveals wide variability in alignment with WHO guidelines and limited confidence in providing palliative care. Study findings will inform targeted educational interventions, which must be tailored to the local political, economic, and cultural context.

Developing novel microsatellite markers by NGS technology for Rhopilema nomadica, an invasive jellyfish.

Twelve microsatellite loci, obtained by whole genome sequencing approach, were developed and validated for the rhizostomatid jellyfish Rhopilema nomadica, the most pernicious invasive species in the Mediterranean Sea. A sample of 40 specimens collected at six locations along the Mediterranean coast of Israel were genotyped and all loci presented suitable outcomes to population genetic studies, revealing 5-19 alleles/locus with clean and reproducible amplifications. Observed and expected heterozygosity ranged 0.0.353 to 0.971 and 0.335 to 0.870, respectively, and the fixation index (inbreeding coefficient) and the polymorphic information content (PIC) ranged between - 0.190 and 0.240 and 0.32 to 0.858, respectively. The new set of microsatellite loci will be used to study long-term changes in the population genetic parameters of this invasive species.

Blockade of TGF-ß signaling to enhance the antitumor response is accompanied by dysregulation of the functional activity of CD4+CD25+Foxp3+ and CD4+CD25-Foxp3+ T cells.

BACKGROUND: The pleiotropic cytokine, transforming growth factor (TGF)-ß, and CD4+CD25+Foxp3+ regulatory T cells (Tregs) play a critical role in actively suppressing antitumor immune responses. Evidence shows that TGF-ß produced by tumor cells promotes tolerance via expansion of Tregs. Our group previously demonstrated that blockade of TGF-ß signaling with a small molecule TGF-ß receptor I antagonist (SM16) inhibited primary and metastatic tumor growth in a T cell dependent fashion. In the current study, we evaluated the effect of SM16 on Treg generation and function. METHODS: Using BALB/c, FoxP3eGFP and Rag-/- mice, we performed FACS analysis to determine if SM16 blocked de novo TGF-ß-induced Treg generation in vitro and in vivo. CD4+ T cells from lymph node and spleen were isolated from control mice or mice maintained on SM16 diet, and flow cytometry analysis was used to detect the frequency of CD4+CD25-FoxP3+ and CD4+CD25+FoxP3+ T cells. In vitro suppression assays were used to determine the ability to suppress naive T cell proliferation in vitro of both CD4+CD25+FoxP3+ and CD4+CD25-FoxP3+ T cell sub-populations. We then examined whether SM16 diet exerted an inhibitory effect on primary tumor growth and correlated with changes in FoxP3+expression. ELISA analysis was used to measure IFN-γ levels after 72 h co-culture of CD4+CD25+ T cells from tumor-bearing mice on control or SM16 diet with CD4+CD25- T cells from naive donors. RESULTS: SM16 abrogates TGF-ß-induced Treg generation in vitro but does not prevent global homeostatic expansion of CD4+ T cell sub-populations in vivo. Instead, SM16 treatment causes expansion of a population of CD4+CD25-Foxp3+ Treg-like cells without significantly altering the overall frequency of Treg in lymphoreplete naive and tumor-bearing mice. Importantly, both the CD4+CD25-Foxp3+ T cells and the CD4+CD25+Foxp3+ Tregs in mice receiving SM16 diet exhibited diminished ability to suppress naive T cell proliferation in vitro compared to Treg from mice on control diet. CONCLUSIONS: These findings suggest that blockade of TGF-ß signaling is a potentially useful strategy for blunting Treg function to enhance the anti-tumor response. Our data further suggest that the overall dampening of Treg function may involve the expansion of a quiescent Treg precursor population, which is CD4+CD25-Foxp3+.

Tailoring cells for clinical needs: Meeting report from the Advanced Therapy in Healthcare symposium (October 28-29 2017, Doha, Qatar).

New technologies and therapies designed to facilitate development of personalized treatments are rapidly emerging in the field of biomedicine. Strikingly, the goal of personalized medicine refined the concept of therapy by developing cell-based therapies, the so-called "living drugs". Breakthrough advancements were achieved in this regard in the fields of gene therapy, cell therapy, tissue-engineered products and advanced therapeutic techniques. The Advanced Therapies in Healthcare symposium, organized by the Clinical Research Center Department of Sidra Medicine, in Doha, Qatar (October 2017), brought together world-renowned experts from the fields of oncology, hematology, immunology, inflammation, autoimmune disorders, and stem cells to offer a comprehensive picture of the status of worldwide advanced therapies in both pre-clinical and clinical development, providing insights to the research phase, clinical data and regulatory aspects of these therapies. Highlights of the meeting are provided in this meeting report.

Detection of Human Bocavirus Species 2 and 3 in Bivalve Shellfish in Italy.

Human bocavirus (HBoV) has been shown to be a common cause of respiratory infections and gastroenteritis in children. Recently, HBoVs have been detected in sewage and river waters in Italy and worldwide. However, studies on their presence in other water environments and in bivalve mollusks are not yet available. In this study, 316 bivalve shellfish samples collected in three Italian regions over a 6-year period (2012 to 2017) were analyzed by nested PCR and sequencing using broad-range primer pairs targeting the capsid proteins VP1 and VP2 of HBoV. The virus was detected in 27 samples (8.5% of the total samples), and a statistically significant difference was found within the three regions. A further 13 samples, collected in geographic and temporal proximity to positive samples, were included in the study to assess the spread of HBoV in shellfish production areas at the time of contamination. Twelve of these additional samples were found to be positive for HBoV. All positive samples in this study were characterized as HBoV species 2 (17 samples; 8 different sequences) or species 3 (22 samples; 4 different sequences). This study reports the occurrence of HBoV in bivalve shellfish and shows evidence of considerable spatial spread of the virus throughout shellfish production areas. Further studies are needed to elucidate both the role of HBoV as an agent of gastroenteritis and the risk for foodborne transmission of this virus.IMPORTANCE Human bocavirus is recognized as an important cause of acute respiratory tract infections and has recently been considered an etiological agent of gastroenteritis in the pediatric population. Our findings document that HBoVs are detected in bivalve shellfish with a relevant prevalence and suggest that an assessment of the risk for foodborne transmission of these viruses should be undertaken.

Classification of non-indigenous species based on their impacts: considerations for application in marine management.

Assessment of the ecological and economic/societal impacts of the introduction of non-indigenous species (NIS) is one of the primary focus areas of bioinvasion science in terrestrial and aquatic environments, and is considered essential to management. A classification system of NIS, based on the magnitude of their environmental impacts, was recently proposed to assist management. Here, we consider the potential application of this classification scheme to the marine environment, and offer a complementary framework focussing on value sets in order to explicitly address marine management concerns. Since existing data on marine NIS impacts are scarce and successful marine removals are rare, we propose that management of marine NIS adopt a precautionary approach, which not only would emphasise preventing new incursions through pre-border and at-border controls but also should influence the categorisation of impacts. The study of marine invasion impacts requires urgent attention and significant investment, since we lack the luxury of waiting for the knowledge base to be acquired before the window of opportunity closes for feasible management.

PKD1 Inhibits AMPKα2 through Phosphorylation of Serine 491 and Impairs Insulin Signaling in Skeletal Muscle Cells.

AMP-activated protein kinase (AMPK) is an energy-sensing enzyme whose activity is inhibited in settings of insulin resistance. Exposure to a high glucose concentration has recently been shown to increase phosphorylation of AMPK at Ser(485/491) of its α1/α2 subunit; however, the mechanism by which it does so is not known. Diacylglycerol (DAG), which is also increased in muscle exposed to high glucose, activates a number of signaling molecules including protein kinase (PK)C and PKD1. We sought to determine whether PKC or PKD1 is involved in inhibition of AMPK by causing Ser(485/491) phosphorylation in skeletal muscle cells. C2C12 myotubes were treated with the PKC/D1 activator phorbol 12-myristate 13-acetate (PMA), which acts as a DAG mimetic. This caused dose- and time-dependent increases in AMPK Ser(485/491) phosphorylation, which was associated with a ∼60% decrease in AMPKα2 activity. Expression of a phosphodefective AMPKα2 mutant (S491A) prevented the PMA-induced reduction in AMPK activity. Serine phosphorylation and inhibition of AMPK activity were partially prevented by the broad PKC inhibitor Gö6983 and fully prevented by the specific PKD1 inhibitor CRT0066101. Genetic knockdown of PKD1 also prevented Ser(485/491) phosphorylation of AMPK. Inhibition of previously identified kinases that phosphorylate AMPK at this site (Akt, S6K, and ERK) did not prevent these events. PMA treatment also caused impairments in insulin-signaling through Akt, which were prevented by PKD1 inhibition. Finally, recombinant PKD1 phosphorylated AMPKα2 at Ser(491) in cell-free conditions. These results identify PKD1 as a novel upstream kinase of AMPKα2 Ser(491) that plays a negative role in insulin signaling in muscle cells.

To bridge or not to bridge the multisensory time gap: bimanual coordination to sound and touch with temporal lags.

Living in a complex and multisensory environment involves constant interaction between perception and action. There is evidence that multisensory integration is governed by temporal factors, such as physiological synchrony between cross-modal stimuli favouring multisensory benefit, and the existence of a range of asynchrony between the stimuli which affords their binding (the temporal window of integration). These factors were examined in this study in a bimanual sensorimotor synchronization task with cross-modal stimuli. Participants synchronized each hand to a pair of audio-tactile stimuli, in which the asynchrony between onsets of auditory and tactile stimuli was systematically manipulated. In cross-modal conditions, they were instructed to tap either to the auditory stimuli or to tactile stimuli. The results reported a temporal window of integration of 160 ms centred around 40 and 80 ms (tactile first). Moreover, the temporal interval between the auditory and tactile stimuli affected the stability of bimanual coordination and of synchronization exclusively when participants were instructed to synchronize with tactile stimuli. Overall, the results indicate that both physiological asynchrony and temporal window of integration apply to cross-modal integration in a bimanual synchronization task. In addition, it shows the effect of auditory dominance onto multisensory temporal processes. This study sheds light on the role of temporal factors in multisensory processes when perception and actions are rhythmic and coupled.

Recommendations for developing and applying genetic tools to assess and manage biological invasions in marine ecosystems.

The European Union's Marine Strategy Framework Directive (MSFD) aims to adopt integrated ecosystem management approaches to achieve or maintain "Good Environmental Status" for marine waters, habitats and resources, including mitigation of the negative effects of non-indigenous species (NIS). The Directive further seeks to promote broadly standardized monitoring efforts and assessment of temporal trends in marine ecosystem condition, incorporating metrics describing the distribution and impacts of NIS. Accomplishing these goals will require application of advanced tools for NIS surveillance and risk assessment, particularly given known challenges associated with surveying and monitoring with traditional methods. In the past decade, a host of methods based on nucleic acids (DNA and RNA) analysis have been developed or advanced that promise to dramatically enhance capacity in assessing and managing NIS. However, ensuring that these rapidly evolving approaches remain accessible and responsive to the needs of resource managers remains a challenge. This paper provides recommendations for future development of these genetic tools for assessment and management of NIS in marine systems, within the context of the explicit requirements of the MSFD. Issues considered include technological innovation, methodological standardization, data sharing and collaboration, and the critical importance of shared foundational resources, particularly integrated taxonomic expertise. Though the recommendations offered here are not exhaustive, they provide a basis for future intentional (and international) collaborative development of a genetic toolkit for NIS research, capable of fulfilling the immediate and long term goals of marine ecosystem and resource conservation.

GMP-grade α-TEA lysine salt: a 28-Day oral toxicity and toxicokinetic study with a 28-Day recovery period in Beagle dogs.

BACKGROUND: Alpha-tocopheryloxyacetic acid (α-TEA) is a semi-synthetic derivative of naturally occurring vitamin E (alpha-tocopherol) that can be delivered via an oral route. Preclinical in vitro and in vivo data demonstrated that α-TEA is a potent anti-tumor agent with a safe toxicity profile in mice. We report a comprehensive study to evaluate the toxokinetics of good manufacturing practice (GMP)-grade α-TEA in dogs after daily oral administration for 28 days, followed by a 28-day recovery period. METHODS: Male and female beagle dogs received capsules of α-TEA Lysine Salt at doses of 100, 300, 1500 mg/kg/day. α-TEA plasma levels were determined by high-performance liquid chromatography (HPLC) with mass spectrometric detection. During the treatment, animals were observe for clinical signs, food consumption, body weight, and subjected to ophthalmoscopic, and electrocardiographic assessments. At the end of the dosing period, blood was taken and toxicokinetic analyses and histopathology assessments were performed when animals were necropsied. RESULTS: Our findings showed that there was no α-TEA-related mortality or moribundity. At the highest dose, increases in white blood cells and fibrinogen levels were observed. These levels returned to normal at the end of the recovery period. Histopathological evaluation of major organs revealed no significant lesions related to α-TEA-treatment. CONCLUSION: We demonstrate that for designing clinical trials in patients, the highest non-severely toxic dose (HNSTD) of α-TEA is 1500 mg/kg/day in Beagle dogs and this data informed the design of dose-escalation studies of α-TEA in patients with advanced cancer.

Metabolic signatures differentiate ovarian from colon cancer cell lines.

BACKGROUND: In this era of precision medicine, the deep and comprehensive characterization of tumor phenotypes will lead to therapeutic strategies beyond classical factors such as primary sites or anatomical staging. Recently, "-omics" approached have enlightened our knowledge of tumor biology. Such approaches have been extensively implemented in order to provide biomarkers for monitoring of the disease as well as to improve readouts of therapeutic impact. The application of metabolomics to the study of cancer is especially beneficial, since it reflects the biochemical consequences of many cancer type-specific pathophysiological processes. Here, we characterize metabolic profiles of colon and ovarian cancer cell lines to provide broader insight into differentiating metabolic processes for prospective drug development and clinical screening. METHODS: We applied non-targeted metabolomics-based mass spectroscopy combined with ultrahigh-performance liquid chromatography and gas chromatography for the metabolic phenotyping of four cancer cell lines: two from colon cancer (HCT15, HCT116) and two from ovarian cancer (OVCAR3, SKOV3). We used the MetaP server for statistical data analysis. RESULTS: A total of 225 metabolites were detected in all four cell lines; 67 of these molecules significantly discriminated colon cancer from ovarian cancer cells. Metabolic signatures revealed in our study suggest elevated tricarboxylic acid cycle and lipid metabolism in ovarian cancer cell lines, as well as increased ß-oxidation and urea cycle metabolism in colon cancer cell lines. CONCLUSIONS: Our study provides a panel of distinct metabolic fingerprints between colon and ovarian cancer cell lines. These may serve as potential drug targets, and now can be evaluated further in primary cells, biofluids, and tissue samples for biomarker purposes.

Breast cancer cells promote a notch-dependent mesenchymal phenotype in endothelial cells participating to a pro-tumoral niche.

BACKGROUND: Endothelial cells (ECs) are responsible for creating a tumor vascular niche as well as producing angiocrine factors. ECs demonstrate functional and phenotypic heterogeneity when located under different microenvironments. Here, we describe a tumor-stimulated mesenchymal phenotype in ECs and investigate its impact on tumor growth, stemness, and invasiveness. METHODS: Xenograft tumor assay in NOD/SCID mice and confocal imaging were conducted to show the acquisition of mesenchymal phenotype in tumor-associated ECs in vivo. Immunocytochemistry, qPCR and flow cytometry techniques showed the appearance of mesenchymal traits in ECs after contact with breast tumor cell lines MDA-MB231 or MCF-7. Cell proliferation, cell migration, and sphere formation assays were applied to display the functional advantages of mesenchymal ECs in tumor growth, invasiveness, and enrichment of tumor initiating cells. qPCR and western blotting were used to investigate the mechanisms underlying EC mesenchymal transition. RESULTS: Our results showed that co-injection of ECs and tumor cells in NOD/SCID mice significantly enhanced tumor growth in vivo with tumor-associated ECs expressing mesenchymal markers while maintaining their intrinsic endothelial trait. We also showed that a mesenchymal phenotype is possibly detectable in human neoplastic breast biopsies as well as ECs pre-exposed to tumor cells (ECs(Mes)) in vitro. The ECs(Mes) acquired prolonged survival, increased migratory behavior and enhanced angiogenic properties. In return, ECs(Mes) were capable of enhancing tumor survival and invasiveness. The mesenchymal phenotypes in ECs(Mes) were the result of a contact-dependent transient phenomenon and reversed upon removal of the neoplastic contexture. We showed a synergistic role for TGFß and notch pathways in this phenotypic change, as simultaneous inhibition of notch and TGFß down-regulated Smad1/5 phosphorylation and Jag1(KD) tumor cells were unable to initiate the process. CONCLUSIONS: Overall, our data proposed a crosstalk mechanism between tumor and microenvironment where tumor-stimulated mesenchymal modulation of ECs enhanced the constitution of a transient mesenchymal/endothelial niche leading to significant increase in tumor proliferation, stemness, and invasiveness. The possible involvement of notch and TGFß pathways in the initiation of mesenchymal phenotype may propose new stromal targets.

Biology of a new xenoma-forming gonadotropic microsporidium in the invasive blotchfin dragonet Callionymus filamentosus.

A gonadotropic microsporidian parasite, Obruspora papernae gen. et sp. nov. (Microsporidia: Enterocytozoonidae), is described from Callionymus filamentosus (Teleostei: Callionymidae) in the Mediterranean Sea. The host, a Red Sea invasive species which entered the Mediterranean through the Suez Canal, was first collected in the Levant Basin in 1953, whereas its parasite went unobserved until 2008. Analysis of partial small subunit ribosomal gene sequences (SSU rDNA) placed the new species within the Nucleospora, Desmozoon, and Paranucleospora clade, and as it differs from each of them, it is assigned to a new genus. The development of the parasite is described, and the biological mechanisms underlying this parasite-host system are analyzed. Prevalence of infection approached 80% in female samples throughout most of the year. Males showed no signs of infection, but parasite rDNA was detected in male internal organs. The parasite-induced xenomas progressively occupied and eventually replaced much of the ovary, in some cases producing effective castration. Despite high levels of parasite infection, current trawl fishery statistics indicate that the abundance of Mediterranean populations of the host remains high. The parasite impact on the host population dynamics is unclear. Possible effects of the new microsporidian parasite on the reproductive effort of C. filamentosus and the potential role of another parasite, the ectoparasitic copepod Lernanthropus callionymicola, as an additional host in the life cycle of O. papernae, require further investigation.

On the identity of Cancer urania Herbst, 1801 (Crustacea: Decapoda: Brachyura: Leucosiidae).

Cancer urania Herbst, 1801, is the type species of the leucosiid genus Coleusia Galil, 2006. Its identity has been a subject of confusion due to various taxonomical and nomenclatural issues. We redescribe the species, discuss its complex history and taxonomy, and a female syntype is designated as the lectotype of the species to clarify any lingering ambiguities concerning the type material of Cancer urania Herbst, 1801.

A new species of Coleusia Galil, 2006 (Decapoda: Brachyura: Leucosiidae) from southern Asia.

A new species of leucosiid crab of the genus Coleusia Galil, 2006, is described from South and Southeast Asia. Coleusia huilianae n. sp. is distinguished from the superficially similar C. urania (Herbst, 1801) in the shape of the apical process of the first male gonopod which is digitate and curved laterally in the former (beak-like and curved interiorly in the latter); possessing smaller and sparser granulation on the posterior and lower margin of the cheliped and ambulatory meri; and the granulation is entirely missing from the lower external surface of the palm.

Including a diverse set of voices to address biological invasions.

Inclusivity is fundamental to progress in understanding and addressing the global phenomena of biological invasions because inclusivity fosters a breadth of perspectives, knowledge, and solutions. Here, we report on how the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES) assessment on invasive alien species (IAS) prioritized inclusivity, the benefits of this approach, and the remaining challenges.