History and Current State of Neurosurgery in the Gambia.

BACKGROUND: Despite global efforts to improve surgical care access, many low- and middle-income countries, especially in neurosurgery, face significant shortages. The Gambia exemplifies this, with only 1 fully qualified neurosurgeon serving its population of 2.5 million people. This scarcity results in higher morbidity and mortality. OBJECTIVE: We aim to document the history and current state of neurosurgery in the Gambia to raise awareness and promote neurosurgery development. METHODS: The study reviews the Gambia's health care system, infrastructure, neurosurgical history, workforce, disease burden, and progress, with information derived from reference sources as well as author experience and interviews with key partners in Gambian health care. RESULTS: Neurosurgery in the Gambia began in the 1970s, facing constraints due to competing health care demands. Significant progress occurred much later in the early 2010s, marked by the initiation of Banjul Neuro Missions and the establishment of a dedicated neurosurgery unit. We report significant progress with neurosurgical interventions in the past few years showcasing the unit's dedication to advancing neurosurgical care in the Gambia. However, challenges persist, including a lack of trained neurosurgeons, equipment shortages such as ventilators and diagnostic imaging. Financial barriers for patients, particularly related to the costs of computer tomography scans, pose significant hurdles, impacting the timely diagnosis and intervention for neurological conditions. CONCLUSIONS: Neurosurgery in the Gambia is progressing, but challenges like equipment scarcity hinder further progress. We emphasize the need for addressing cost barriers, improving infrastructure, and fostering research. Engaging the government and international collaborations are vital for sustained development in Gambian neurosurgery.

Updating Chimpanzee Nesting Data at Mount Assirik (Niokolo Koba National Park, Senegal): Implications for Conservation.

The Niokolo Koba National Park (NKNP) is the largest protected area in Senegal and lies at the northern limit of the chimpanzee's range in West Africa. Recent information on nesting behavior and factors influencing nesting behavior is available for several sites outside NKNP. However, the information available for NKNP is obsolete. Considering that the adequate management of chimpanzee populations cannot be achieved without strong scientific knowledge, it is essential to update data on chimpanzee, Pan troglodytes verus, nesting behavior in NKNP. For this reason, we surveyed their habitat in Mt. Assirik and recorded 626 chimpanzee nests. The results of the study showed that chimpanzees nest more often in closed-canopy habitats such as gallery forests. The average nest height observed in this study was 8.07 ± 0.36 m, varying between 2 and 20 m, which is well below the heights described in most sites where chimpanzees cohabit with large carnivores. Botanical surveys confirmed that chimpanzees select tree species bearing their nests. In Assirik, 12 of the 37 tree species bearing nests are the most used. The nest decay rate (or the time it takes for a nest to go from the fresh to the skeletal stage) at Assirik averaged 68.8 ± 5.8 days.

Reciprocity and beyond: Explaining meat transfers in savanna-dwelling chimpanzees at Fongoli, Senegal.

OBJECTIVES: To understand the function of food sharing among our early hominin ancestors, we can turn to our nonhuman primate relatives for insight. Here, we examined the function of meat sharing by Fongoli chimpanzees, a community of western chimpanzees (Pan troglodytes verus) in southeastern Sénégal. MATERIALS AND METHODS: We tested three non-mutually exclusive hypotheses that have been used to explain patterns of food sharing: kin selection, generalized reciprocity, and meat-for-mating opportunities. We analyzed meat sharing events (n = 484) resulting from hunts, along with data on copulations, age-sex class, and kinship to determine which variables predict the likelihood of meat sharing during this study period (2006-2019). RESULTS: We found full or partial support for kin selection, direct reciprocity, and meat-for-mating-opportunities. However, the analyses reveal that reciprocity and a mother/offspring relationship were the strongest predictors of whether or not an individual shared meat. CONCLUSIONS: The results of this study emphasize the complexity of chimpanzee meat sharing behaviors, especially at a site where social tolerance offers increased opportunities for meat sharing by individuals other than dominant males. These findings can be placed in a referential model to inform hypotheses about the sensitivity of food sharing to environmental pressures, such as resource scarcity in savanna landscapes.

Gastrointestinal parasites of baboons (Papio papio) in Niokolo-Koba National Park, Senegal.

Background: Primates can harbor parasites that could be pathogenic or not for humans and primates themselves. It is necessary to know the parasitological situation of the primates that are under surveillance in the park. Aim: To estimate the prevalence and diversity of gastrointestinal parasites, including zoonotic potential parasites, in baboons in the Niokolo-Koba National Park located in Senegal. Method: Fecal samples (n = 50) from two groups of baboons (A and B) were collected in October 2019. The samples were processed using the flotation technique and the modified Ritchie method. Slides were examined microscopically and the parasite identification was based on morphology, color, and parasite content. Results: A total of seven nematodes (Strongyloides sp., Trichirus sp., Ancylostoma sp., Mammo monogamus, Enterobius sp., Strongyloides stercoralis, Strongyle digestif), one cestode (Bertiella sp.), and one trematode (Fasciolopsis sp.) were identified. The overall prevalence was 78%, while the prevalence of poly-infected samples was 49%. The parasite with zoonotic potential, S. stercoralis, was identified in group B samples. Trichuris sp., which is common and pathogenic to humans and primates, was present with prevalence of 52% and of 32% in groups A and B, respectively. Conclusion: These results suggest that baboons are infested with zoonotic parasites and this situation could expose people working in this park to infection. Contact between humans and these baboons or their feces could expose them to infection with zoonotic parasites.

A climate-based model for tick life cycle: positive semigroup theory on Cauchy problem approach.

The distribution of ticks is essentially determined by the presence of climatic conditions and ecological contexts suitable for their survival and development. We build a model that explicitly takes into account each physiological state through a system of infinite differential equations where tick population density are structured on an infinite discrete set. We suppose that intrastage development process is temperature dependent (Arrhenius temperatures function) and that larvae hatching and adult mortality are temperature and water vapor deficit dependent. We analysed mathematically the model and have explicit the [Formula: see text] of the tick population.

PDGFRα-induced stromal maturation is required to restrain postnatal intestinal epithelial stemness and promote defense mechanisms.

After birth, the intestine undergoes major changes to shift from an immature proliferative state to a functional intestinal barrier. By combining inducible lineage tracing and transcriptomics in mouse models, we identify a prodifferentiation PDGFRαHigh intestinal stromal lineage originating from postnatal LTßR+ perivascular stromal progenitors. The genetic blockage of this lineage increased the intestinal stem cell pool while decreasing epithelial and immune maturation at weaning age, leading to reduced postnatal growth and dysregulated repair responses. Ablating PDGFRα in the LTBR stromal lineage demonstrates that PDGFRα has a major impact on the lineage fate and function, inducing a transcriptomic switch from prostemness genes, such as Rspo3 and Grem1, to prodifferentiation factors, including BMPs, retinoic acid, and laminins, and on spatial organization within the crypt-villus and repair responses. Our results show that the PDGFRα-induced transcriptomic switch in intestinal stromal cells is required in the first weeks after birth to coordinate postnatal intestinal maturation and function.

[Atrial fibrillation in three cardiological reference centers in Dakar: Senegal data from the AFRICA register survey]. / La fibrillation atriale dans trois centres cardiologiques de référence de Dakar: données sénégalaises de l'enquête du registre AFRICA.

Introduction: atrial fibrillation (AF) is the most common cardiac rhythm disorder. Its prevalence is underestimated in Africa, hence the initiation of the Atrial Fibrillation Registry In Countries of Africa (AFRICA). The aim of our study was to describe, within the framework of the AFRICA registry, the epidemiological, clinical, paraclinical, therapeutic and evolutionary aspects of atrial fibrillation (AF) in Africa, particularly in Senegal. Methods: we performed a cross-sectional, retrospective, multicentric study conducted from January 1st to December 31st 2017, in three referral cardiology wards in Senegal. Results: one hundred and sixty-eight patients, with a mean age of 63 years, were selected, representing a hospital prevalence of 5.99%. There was a predominance of women with sex-ratio of 0.69. High blood pressure was the most frequent risk factor (24.4%). Heart failure was the most frequent circumstance of discovery (59.52%). AF was persistent in 52.24% and valvular AF accounted for 31% and was more frequent in young people (p= 0.005). Left ventricular systolic function was impaired in 55.7%, the left atrium was dilated in 70.83%. The strategy to reduce heart rate was the most used. Patients with CHA2DS2VASC ≥ 2 received anticoagulation with LMWH and oral relay maid mostly of VKA. The complications were dominated by heart failure (66.6%) and ischemic stroke cerebral (28%). Conclusion: atrial fibrillation (AF) is the most frequent cardiac rhythm disorder. It is a major public health concern.

Chimpanzees (Pan troglodytes) in savanna landscapes.

Chimpanzees (Pan troglodytes) are the only great apes that inhabit hot, dry, and open savannas. We review the environmental pressures of savannas on chimpanzees, such as food and water scarcity, and the evidence for chimpanzees' behavioral responses to these landscapes. In our analysis, savannas were generally associated with low chimpanzee population densities and large home ranges. In addition, thermoregulatory behaviors that likely reduce hyperthermia risk, such as cave use, were frequently observed in the hottest and driest savanna landscapes. We hypothesize that such responses are evidence of a "savanna landscape effect" in chimpanzees and offer pathways for future research to understand its evolutionary processes and mechanisms. We conclude by discussing the significance of research on savanna chimpanzees to modeling the evolution of early hominin traits and informing conservation programs for these endangered apes.

The Carcinogen Cadmium Activates Lysine 63 (K63)-Linked Ubiquitin-Dependent Signaling and Inhibits Selective Autophagy.

Signaling, proliferation, and inflammation are dependent on K63-linked ubiquitination-conjugation of a chain of ubiquitin molecules linked via lysine 63. However, very little information is currently available about how K63-linked ubiquitination is subverted in cancer. The present study provides, for the first time, evidence that cadmium (Cd), a widespread environmental carcinogen, is a potent activator of K63-linked ubiquitination, independently of oxidative damage, activation of ubiquitin ligase, or proteasome impairment. We show that Cd induces the formation of protein aggregates that sequester and inactivate cylindromatosis (CYLD) and selective autophagy, two tumor suppressors that deubiquitinate and degrade K63-ubiquitinated proteins, respectively. The aggregates are constituted of substrates of selective autophagy-SQSTM1, K63-ubiquitinated proteins, and mitochondria. These protein aggregates also cluster double-membrane remnants, which suggests an impairment in autophagosome maturation. However, failure to eliminate these selective cargos is not due to alterations in the general autophagy process, as degradation of long-lived proteins occurs normally. We propose that the simultaneous disruption of CYLD and selective autophagy by Cd feeds a vicious cycle that further amplifies K63-linked ubiquitination and downstream activation of the NF-κB pathway, processes that support cancer progression. These novel findings link together impairment of selective autophagy, K63-linked ubiquitination, and carcinogenesis.

Plk1, upregulated by HIF-2, mediates metastasis and drug resistance of clear cell renal cell carcinoma.

Polo-like kinase 1 (Plk1) expression is inversely correlated with survival advantages in many cancers. However, molecular mechanisms that underlie Plk1 expression are poorly understood. Here, we uncover a hypoxia-regulated mechanism of Plk1-mediated cancer metastasis and drug resistance. We demonstrated that a HIF-2-dependent regulatory pathway drives Plk1 expression in clear cell renal cell carcinoma (ccRCC). Mechanistically, HIF-2 transcriptionally targets the hypoxia response element of the Plk1 promoter. In ccRCC patients, high expression of Plk1 was correlated to poor disease-free survival and overall survival. Loss-of-function of Plk1 in vivo markedly attenuated ccRCC growth and metastasis. High Plk1 expression conferred a resistant phenotype of ccRCC to targeted therapeutics such as sunitinib, in vitro, in vivo, and in metastatic ccRCC patients. Importantly, high Plk1 expression was defined in a subpopulation of ccRCC patients that are refractory to current therapies. Hence, we propose a therapeutic paradigm for improving outcomes of ccRCC patients.

A comparative study of the ultrastructural characteristics of the mature spermatozoa of two fellodistomids Tergestia clonacantha and T. laticollis and contribution to the phylogenetic knowledge of the Gymnophalloidea.

The ultrastructure of the mature spermatozoa of Tergestia clonacantha and T. laticollis collected from the digestive tracts of fishes from New Caledonia is described using transmission electron microscopy and compared to that of related species. The spermatozoa of the two species exhibit the general pattern described in most digeneans, namely two axonemes with the 9 + "1" pattern of the Trepaxonemata, nucleus, mitochondrion, cortical microtubules, an external ornamentation of the plasma membrane, spine-like bodies and granules of glycogen. The spermatozoa of T. clonacantha and T. laticollis show the same ultrastructural model with some specificities in each case, particularly in the disposition of the structures in the posterior extremities of the spermatozoon. This study confirms that ultrastructural characters of the mature spermatozoon are useful tools for the phylogenetic analysis of the Digenea.

TITLE: Étude comparative des caractéristiques ultrastructurales des spermatozoïdes mûrs de deux Fellodistomidae, Tergestia clonacantha et T. laticollis, et contribution à la connaissance phylogénétique des Gymnophalloidea. ABSTRACT: L'ultrastructure des spermatozoïdes mûrs de Tergestia clonacantha et T. laticollis, prélevés dans le tube digestif de poissons de Nouvelle-Calédonie, est décrite par microscopie électronique à transmission et comparée à celle d'espèces apparentées. Les spermatozoïdes des deux espèces présentent la structure générale décrite chez la plupart des digènes, à savoir deux axonèmes du type 9 + « 1 ¼ des Trepaxonemata, un noyau, une mitochondrie, des microtubules corticaux, des ornementations externes de la membrane plasmique, des corps épineux et des granules de glycogène. Les spermatozoïdes de T. clonacantha et T. laticollis présentent le même modèle ultrastructural avec quelques spécificités dans chaque cas, notamment dans la disposition des structures aux extrémités postérieures du spermatozoïde. Cette étude confirme que les caractères ultrastructuraux du spermatozoïde mûrs sont des outils utiles pour l'analyse phylogénétique des Digenea.

Extension of Surface Organometallic Chemistry to Metal-Organic Frameworks: Development of a Well-Defined Single Site [(≡Zr-O-)W(═O)(CH2tBu)3] Olefin Metathesis Catalyst.

We report here the first step by step anchoring of a W(≡CtBu)(CH2tBu)3 complex on a highly crystalline and mesoporous MOF, namely Zr-NU-1000, using a Surface Organometallic Chemistry (SOMC) concept and methodology. SOMC allowed us to selectively graft the complex on the Zr6 clusters and characterize the obtained single site material using state of the art experimental methods including extensive solid-state NMR techniques and HAADF-STEM imaging. Further FT-IR spectroscopy revealed the presence of a W═O moiety arising from the in situ reaction of the W≡CtBu functionality with the coordinated water coming from the 8-connected hexanuclear Zr6 clusters. All the steps leading to the final grafted molecular complex have been identified by DFT. The obtained material was tested for gas phase and liquid phase olefin metathesis and exhibited higher catalytic activity than the corresponding catalysts synthesized by different grafting methods. This contribution establishes the importance of applying SOMC to MOF chemistry to get well-defined single site catalyst on MOF inorganic secondary building units, in particular the in situ synthesis of W═O alkyl complexes from their W carbyne analogues.

Spermatological characteristics of Sclerodistomoides pacificus (Digenea, Sclerodistomoididae) a parasite of the flying fish Cheilopogon pinnatibarbatus (Teleostei, Exocoetidae).

Sclerodistomoides pacificus is the only species described now in Sclerodistomoididae. We present in this paper the first ultrastructural data of the mature spermatozoon of a species from the genus Sclerodistomoides. Adult specimens of S. pacificus (Digenea: Hemiuroidea: Sclerodistomoididae), were parasites of the gall-bladder of the teleost fish Cheilopogon pinnatibarbatus captured in the Atlantic Ocean, near Dakar (Senegal). The male gamete is a filiform cell which exhibits a similar ultrastructural organization to that reported in most species belonging to the Hemiuroidea with two axonemes of the 9 + '1' pattern of trepaxonematans, a nucleus, a mitochondrion, external ornamentation of the plasma membrane not associated with cortical microtubules and located in the anterior region of the spermatozoon, and parallel cortical microtubules disposed in one side of the spermatozoon. However, the present study allowed describing for the first time a moniliform mitochondrion in the Hemiuroidea. The presence of a moniliform mitochondrion and the absence of filamentous external ornamentation described in other Hemiuridae: Lecithochirium microstomum, L. musculus and Hemiurus appendiculatus are a good tool for phylogenetic purposes in the Hemiuroidea. Moreover, spermatological organisation and model are discussed in context with those of previous studies in the Hemiuroidea.

Worldwide inequality in access to full text scientific articles: the example of ophthalmology.

BACKGROUND: The problem of access to medical information, particularly in low-income countries, has been under discussion for many years. Although a number of developments have occurred in the last decade (e.g., the open access (OA) movement and the website Sci-Hub), everyone agrees that these difficulties still persist very widely, mainly due to the fact that paywalls still limit access to approximately 75% of scholarly documents. In this study, we compare the accessibility of recent full text articles in the field of ophthalmology in 27 established institutions located worldwide. METHODS: A total of 200 references from articles were retrieved using the PubMed database. Each article was individually checked for OA. Full texts of non-OA (i.e., "paywalled articles") were examined to determine whether they were available using institutional and Hinari access in each institution studied, using "alternative ways" (i.e., PubMed Central, ResearchGate, Google Scholar, and Online Reprint Request), and using the website Sci-Hub. RESULTS: The number of full texts of "paywalled articles" available using institutional and Hinari access showed strong heterogeneity, scattered between 0% full texts to 94.8% (mean = 46.8%; SD = 31.5; median = 51.3%). We found that complementary use of "alternative ways" and Sci-Hub leads to 95.5% of full text "paywalled articles," and also divides by 14 the average extra costs needed to obtain all full texts on publishers' websites using pay-per-view. CONCLUSIONS: The scant number of available full text "paywalled articles" in most institutions studied encourages researchers in the field of ophthalmology to use Sci-Hub to search for scientific information. The scientific community and decision-makers must unite and strengthen their efforts to find solutions to improve access to scientific literature worldwide and avoid an implosion of the scientific publishing model. This study is not an endorsement for using Sci-Hub. The authors, their institutions, and publishers accept no responsibility on behalf of readers.

Towards systematic and evidence-based conservation planning for western chimpanzees.

As animal populations continue to decline, frequently driven by large-scale land-use change, there is a critical need for improved environmental planning. While data-driven spatial planning is widely applied in conservation, as of yet it is rarely used for primates. The western chimpanzee (Pan troglodytes verus) declined by 80% within 24 years and was uplisted to Critically Endangered by the IUCN Red List of Threatened Species in 2016. To support conservation planning for western chimpanzees, we systematically identified geographic areas important for this taxon. We based our analysis on a previously published data set of modeled density distribution and on several scenarios that accounted for different spatial scales and conservation targets. Across all scenarios, typically less than one-third of areas we identified as important are currently designated as high-level protected areas (i.e., national park or IUCN category I or II). For example, in the scenario for protecting 50% of all chimpanzees remaining in West Africa (i.e., approximately 26,500 chimpanzees), an area of approximately 60,000 km2 was selected (i.e., approximately 12% of the geographic range), only 24% of which is currently designated as protected areas. The derived maps can be used to inform the geographic prioritization of conservation interventions, including protected area expansion, "no-go-zones" for industry and infrastructure, and conservation sites outside the protected area network. Environmental guidelines by major institutions funding infrastructure and resource extraction projects explicitly require corporations to minimize the negative impact on great apes. Therefore, our results can inform avoidance and mitigation measures during the planning phases of such projects. This study was designed to inform future stakeholder consultation processes that could ultimately integrate the conservation of western chimpanzees with national land-use priorities. Our approach may help in promoting similar work for other primate taxa to inform systematic conservation planning in times of growing threats.

Resistance to lysosomotropic drugs used to treat kidney and breast cancers involves autophagy and inflammation and converges in inducing CXCL5.

Lysosomotropic agents such as sunitinib, lapatinib, and chloroquine belong to a drug family that is being used more frequently to treat advanced cancers. Sunitinib is standard care for metastatic renal cell carcinomas (mRCC) and lapatinib is used for trastuzumab/pertuzumab-refractory cancers. However, patients ineluctably relapse with a delay varying from a few months to a few years. To improve reactivity prior to relapse it is essential to identify the mechanisms leading to such variability. We showed previously that sunitinib became sequestered in lysosomes because of its basic pKa. Methods: Modifications to gene expression in response to sunitinib and in sunitinib resistant cells were analyzed by transcriptomic and proteomic analysis. ROS production was evaluated by FACS. Nuclear Factor kappa B (NFkB)-dependent transcriptional regulation of inflammatory gene expression was evaluated with a reporter gene. Correlation of CXCL5 with survival was analyzed with an online available data base (TCGA) and using a cohort of patients enrolled in the SUVEGIL clinical trial (NCT00943839). Results: We now show that sunitinib sequestration in lysosomes induced an incomplete autophagic process leading to activation of the NFkB inflammatory pathway. We defined a subset of inflammatory cytokines that were up-regulated by the drug either after an acute or chronic stimulus. One of the most up-regulated genes in sunitinib-resistant cells was the CXCL5 cytokine. CXCL5 was also induced in RCC by chloroquine and in a model of HER2 positive breast cancer cell lines after acute or chronic treatment with lapatinib. CXCL5 correlated to shorter survival in RCC and to the most aggressive forms of breast cancers. The levels of CXCL5 present in the plasma of patients treated with sunitinib were predictive of the efficacy of sunitinib but not of the VEGF-directed antibody bevacizumab. Conclusion: This translational study identified CXCL5 as a biomarker of efficacy of lysosomotropic drugs, a potential asset for personalized medicine.

Informing Protection Efforts for Critically Endangered Chimpanzees (Pan troglodytes verus) and Sympatric Mammals amidst Rapid Growth of Extractive Industries in Senegal.

Updated information on Critically Endangered western chimpanzees (Pan troglodytes verus) in Senegal is urgently needed, given that gold mining is rapidly transforming landscapes and livelihoods. Specifically, biodiversity assessments will better elucidate the chimpanzee extinction risk here and yield baselines for monitoring. We compared mammal species richness between Fongoli (unprotected) and Assirik in Niokolo-Koba National Park to assess the efficacy of the only nationally protected area where chimpanzees range in this country. The primary habitat difference between these sites was the degree of human activity. Although Assirik and Fongoli had similar mammal assemblages and were equivalent in primate species richness, the protected area was higher in species richness overall, particularly for ungulates and carnivores. The protected status and management plan of Niokolo-Koba almost certainly resulted in fewer mammal extinctions. In unprotected areas, the flexible behavioural responses of chimpanzees to human-driven landscape dynamics is likely essential to their long-term survival. Furthermore, the near absence of chimpanzee killings in this country greatly facilitates conservation efforts. Given that mineral extraction is a key development strategy in Senegal, we encourage primatologists to collaborate with mining stakeholders to ensure that sustainability programming includes contributions from experts in savannah chimpanzee behavior and ecology.

[VEGF-C and lymphatic vessels: a double-edged sword in tumor development and metastasis]. / VEGF-C et vaisseaux lymphatiques - Une épée à double tranchant dans le développement tumoral et la dissémination métastatique.

The lymphatic system is made up of vessels that drain interstitial fluids throughout the body. The circulation of the lymph (liquid in the lymphatic system) in the lymphatic vessels is unidirectional: tissues to the lymph nodes and then to the veins. Ganglia are mechanical filters but also immune barriers that can block the progression of certain pathogens as well as cancer cells. However, most studies on the lymphatic system and cancer highlight the role of the lymphatic network in metastatic dissemination as tumor cells use this network to reach other organs. However, recent studies describe a beneficial role of the lymphatic system and of the vascular endothelial growth factor C (VEGF-C) which is one of the main factors responsible for the development of lymphatic vessels in cancer. In this review, we will illustrate this ambivalent and emerging role of VEGF-C and the lymphatic system in cancer aggressiveness.

VEGFC acts as a double-edged sword in renal cell carcinoma aggressiveness.

Hypoxic zones are common features of metastatic tumors. Due to inactivation of the von Hippel-Lindau gene (VHL), renal cell carcinomas (RCC) show constitutive stabilization of the alpha subunit of the hypoxia-inducible factor (HIF). Thus, RCC represents a model of chronic hypoxia. Development of the lymphatic network is dependent on vascular endothelial growth factor C (VEGFC) and lies at the front line of metastatic spreading. Here, we addressed the role of VEGFC in RCC aggressiveness and the regulation of its expression in hypoxia. Methods: Transcriptional and post transcriptional regulation of VEGFC expression was evaluated by qPCR and with reporter genes. The involvement of HIF was evaluated using a siRNA approach. Experimental RCC were performed with immuno-competent/deficient mice using human and mouse cells knocked-out for the VEGFC gene by a CRISPR/Cas9 method. The VEGFC axis was analyzed with an online available data base (TCGA) and using an independent cohort of patients. Results: Hypoxia induced VEGFC protein expression but down-regulated VEGFC gene transcription and mRNA stability. Increased proliferation, migration, over-activation of the AKT signaling pathway and enhanced expression of mesenchymal markers characterized VEGFC-/- cells. VEGFC-/- cells did not form tumors in immuno-deficient mice but developed aggressive tumors in immuno-competent mice. These tumors showed down-regulation of markers of activated lymphocytes and M1 macrophages, and up-regulation of M2 macrophages markers and programmed death ligand 1 (PDL1). Over-expression of lymphangiogenic genes including VEGFC was linked to increased disease-free and overall survival in patients with non-metastatic tumors, whereas its over-expression correlated with decreased progression-free and overall survival of metastatic patients. Conclusion: Our study revisited the admitted dogma linking VEGFC to tumor aggressiveness. We conclude that targeting VEGFC for therapy must be considered with caution.

Ultrastructure of mature spermatozoa of three Bucephalidae (Prosorhynchus longisaccatus, Rhipidocotyle khalili and Bucephalus margaritae) and phylogenetic implications.

We describe here the mature spermatozoa of three species of bucephalids, namely Bucephalus margaritae, Rhipidocotyle khalili and Prosorhynchus longisaccatus. This study provides the first ultrastructural data on the genera Bucephalus and Rhipidocotyle and enabled us to confirm the model of the mature spermatozoon in the Bucephalinae. The spermatozoon exhibits two axonemes with the 9 + "1" pattern of the Trepaxonemata, one of which is very short, lateral expansion, external ornamentation of the plasma membrane located in the anterior extremity of the spermatozoon and associated with cortical microtubules, spine-like bodies, a mitochondrion, and a nucleus. The maximum number of cortical microtubules is located in the anterior part of the spermatozoon. However, more studies are needed to elucidate if spine-like bodies are present in all the Bucephalinae or not. In the Prosorhynchinae, the mature spermatozoon exhibits a similar ultrastructural pattern. Some differences are observed, particularly the axoneme lengths and the arrangement of the spine-like bodies. The posterior extremity of the spermatozoon in the Bucephalinae exhibits only the nucleus, but prosorhynchines have microtubules.