Mediterranean winter rainfall in phase with African monsoons during the past 1.36 million years.

Mediterranean climates are characterized by strong seasonal contrasts between dry summers and wet winters. Changes in winter rainfall are critical for regional socioeconomic development, but are difficult to simulate accurately1 and reconstruct on Quaternary timescales. This is partly because regional hydroclimate records that cover multiple glacial-interglacial cycles2,3 with different orbital geometries, global ice volume and atmospheric greenhouse gas concentrations are scarce. Moreover, the underlying mechanisms of change and their persistence remain unexplored. Here we show that, over the past 1.36 million years, wet winters in the northcentral Mediterranean tend to occur with high contrasts in local, seasonal insolation and a vigorous African summer monsoon. Our proxy time series from Lake Ohrid on the Balkan Peninsula, together with a 784,000-year transient climate model hindcast, suggest that increased sea surface temperatures amplify local cyclone development and refuel North Atlantic low-pressure systems that enter the Mediterranean during phases of low continental ice volume and high concentrations of atmospheric greenhouse gases. A comparison with modern reanalysis data shows that current drivers of the amount of rainfall in the Mediterranean share some similarities to those that drive the reconstructed increases in precipitation. Our data cover multiple insolation maxima and are therefore an important benchmark for testing climate model performance.

Historical DNA solves century-old mystery on sessility in freshwater gastropods.

Extinction rates are increasing unabatedly but resources available for conservation action are limited. Therefore, some conservationists are pushing for ecology- and evolution-based conservation choices, prioritizing taxa with phylogenetic and trait-based originality. Extinction of original taxa may result in a disproportionate loss of evolutionary innovations and potentially prevent transformative changes in living systems. Here, we generated historical DNA data from an almost 120-year-old syntype of the enigmatic sessile snail Helicostoa sinensis from the Three Gorges region of the Yangtze River (PR China), using a next-generation sequencing protocol developed for ancient DNA. In a broader phylogenetic context, we assessed the phylogenetic and trait-based originality of this enigmatic taxon to solve the century-old puzzle of sessility in freshwater gastropods. Our multi-locus data confirm the phylogenetic and trait-based originality of H. sinensis. It is an ultra-rare, subfamily-level taxon (Helicostoinae stat. nov.) within the family Bithyniidae, which exhibits the evolutionary innovation of sessility. While we conservatively classify H. sinensis as "Critically Endangered", there is mounting evidence of the biological annihilation of this endemic species. Although rapidly rising extinction rates in invertebrates are increasingly recognized, the potential loss of originality in these "little things that run the world" has received little attention. We therefore call for comprehensive surveys of originality in invertebrates, particularly from extreme environments such as rapids of large rivers, as a basis for urgently needed ecology- and evolution-based conservation decisions.

Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer.

T cells directed against mutant neo-epitopes drive cancer immunity. However, spontaneous immune recognition of mutations is inefficient. We recently introduced the concept of individualized mutanome vaccines and implemented an RNA-based poly-neo-epitope approach to mobilize immunity against a spectrum of cancer mutations. Here we report the first-in-human application of this concept in melanoma. We set up a process comprising comprehensive identification of individual mutations, computational prediction of neo-epitopes, and design and manufacturing of a vaccine unique for each patient. All patients developed T cell responses against multiple vaccine neo-epitopes at up to high single-digit percentages. Vaccine-induced T cell infiltration and neo-epitope-specific killing of autologous tumour cells were shown in post-vaccination resected metastases from two patients. The cumulative rate of metastatic events was highly significantly reduced after the start of vaccination, resulting in a sustained progression-free survival. Two of the five patients with metastatic disease experienced vaccine-related objective responses. One of these patients had a late relapse owing to outgrowth of ß2-microglobulin-deficient melanoma cells as an acquired resistance mechanism. A third patient developed a complete response to vaccination in combination with PD-1 blockade therapy. Our study demonstrates that individual mutations can be exploited, thereby opening a path to personalized immunotherapy for patients with cancer.

A human, allogeneic cortical bone screw for distal interphalangeal joint (DIP) arthrodesis: a retrospective cohort study with at least 10 months follow-up.

INTRODUCTION: The prime requisites of a good digital arthrodesis are a painless and stable union in a proper position. Arthrodesis of the distal interphalangeal joint of the fingers is not without potential complications including nonunion, malunion, and deep tissue infections. The Shark Screw® is a human, cortical bone allograft for osteosynthesis and an alternative to metal or bioabsorbable devices in orthopedics and trauma surgery. The primary hypothesis is that the fusion and complication rate, using the Shark Screw®, is at least similar to those reported in the literature, using metal or bioabsorbable screws. MATERIAL AND METHODS: This retrospective cohort study analyzes the fusion and complication rate and the patient satisfaction of distal interphalangeal joint arthrodesis of 27 fingers with the human allogeneic cortical bone screw. Complications, Disabilities of Arm, Shoulder, and Hand Questionnaire (Quick-DASH) score and Michigan Hand Outcomes Questionnaire (MHQ) score, grip and pinch strength and fusion angle were investigated. RESULTS: The mean follow-up was 23 months. At 6 weeks after surgery, fusion was obtained for all fingers. There was no surgical complication that required revision surgery. An average fusion angle of 13.6° ± 10.7° was measured. VAS pain score decreased significantly from 6.9 before surgery to 0.14 after surgery. The Quick-DASH score decreased from 10.7 to 7.8. The MHQ score improved in all sub-scores. CONCLUSION: The complication rates, using the Shark Screw® for DIP joint arthrodesis, are lower compared to the results reported in the literature for other surgical techniques. Complications related to the human allograft cortical bone screw itself were not observed. The bone screw is completely remodeled into the host bone and further hardware removal is not necessary. LEVEL OF EVIDENCE: IV.

Drivers of diversification in freshwater gastropods vary over deep time.

Unravelling the drivers of species diversification through geological time is of crucial importance for our understanding of long-term evolutionary processes. Numerous studies have proposed different sets of biotic and abiotic controls of speciation and extinction rates, but typically they were inferred for a single, long geological time frame. However, whether the impact of biotic and abiotic controls on diversification changes over time is poorly understood. Here, we use a large fossil dataset, a multivariate birth-death model and a comprehensive set of biotic and abiotic predictors, including a new index to quantify tectonic complexity, to estimate the drivers of diversification for European freshwater gastropods over the past 100 Myr. The effects of these factors on origination and extinction are estimated across the entire time frame as well as within sequential time windows of 20 Myr each. Our results find support for temporal heterogeneity in the factors associated with changes in diversification rates. While the factors impacting speciation and extinction rates vary considerably over time, diversity-dependence and topography are consistently important. Our study highlights that a high level of heterogeneity in diversification rates is best captured by incorporating time-varying effects of biotic and abiotic factors.

Population collapse in viviparid gastropods of the Lake Victoria ecoregion started before the Last Glacial Maximum.

Ecosystems of Lake Victoria and riparian communities have been strongly disrupted by the introduction of the invasive Nile perch and its fishing industry. Beyond this invasion and other recent anthropogenic stressors, the Lake Victoria ecoregion also underwent phases of pronounced aridity over the Late Pleistocene, lastly during the Last Glacial Maximum (LGM). The consequences of recent and historic environmental change have been canvassed for the adaptive radiation of haplochromine cichlids occupying the ecoregion, but their effect on freshwater invertebrate diversity remains largely unknown. Here, we use 15 microsatellite loci and approximate Bayesian computation to test whether viviparid gastropods experienced a population bottleneck during the LGM, as did cichlids. Clustering analyses support three viviparid gene pools in the Lake Victoria ecoregion, gathering specimens from 1) Lake Albert and the White Nile, 2) the Victoria Nile and Lake Kyoga and 3) Lake Victoria and tributaries. The last group contains the highest genetic diversity, but all groups have a considerable number of private alleles and are inferred to predate the LGM. Examinations of demographic history reveal a 190- to 500-fold population decline that started ~ 125-150 ka ago, thus substantially before the LGM bottleneck documented in haplochromine cichlids. Population collapses in viviparids are an order of magnitude more severe than declines in cichlids and have not been halted by the re-establishment of freshwater ecosystems since the LGM. Recent anthropogenic ecosystem deterioration is causing homogenization of previously diversified microhabitats, which may contribute to (local) extinction and enhanced gene flow among species within gene pools.

Miocene geologic dynamics of the Australian Sahul Shelf determined the biogeographic patterns of freshwater planorbid snails (Miratestinae) in the Indo-Australian Archipelago.

The complex geological and climatic processes that have shaped the Indo-Australian Archipelago since the Cenozoic likely also gave rise to its species-rich biota. Strictly freshwater organisms might be particularly suitable for understanding the influence of these abiotic factors on their biogeography in such a insular setting as their distribution may reflect past abiotic events at large and small geographical scales. We here investigate the historical biogeography of the Miratestinae, a subfamily of Planorbidae. These freshwater gastropods are widely distributed in the eastern IAA from Australia, New Guinea, the Moluccas, and Sulawesi to the Philippines. The first comprehensive molecular phylogeny of the Miratestinae was inferred based on two mitochondrial and two nuclear genetic markers using maximum likelihood and Bayesian inference. Four species delimitation methods were applied to identify molecular operational taxonomic units (MOTUs). Divergence times were inferred using an uncorrelated lognormal relaxed-clock model by applying a taxon- and marker-specific substitution rate. Ancestral geographic ranges were estimated based on the dated phylogeny using BioGeoBEARS. The species delimitation revealed a total of 23 MOTUs, 16 of which might represent species new to science. The BioGeoBEARS analyses suggest an Australian origin for the Miratestinae at c. 22 Ma and identified jump dispersal to be the main process of colonization. The first colonization events from Australia to the IAA occurred in the Middle-Late Miocene (12-13 Ma), whereas intra-island diversification took mainly place since the Late Miocene-Pliocene. Colonization and diversification events remarkably coincide with major geologic events that shaped the geography of the region. The increasing availability of landmasses along the Sahul Shelf likely promoted stepping-stone dispersal to New Guinea, Sulawesi and the Philippines as early as the islands emerged. Major geological and climatic events such as the amalgamation of the island Sulawesi, the regional aridification in Australia or the uplift of massive mountain ranges in New Guinea likely played a considerable role for intra-island diversification.

Global Diversification Dynamics Since the Jurassic: Low Dispersal and Habitat-Dependent Evolution Explain Hotspots of Diversity and Shell Disparity in River Snails (Viviparidae).

The Viviparidae, commonly known as River Snails, is a dominant group of freshwater snails with a nearly worldwide distribution that reaches its highest taxonomic and morphological diversity in Southeast Asia. The rich fossil record is indicative of a probable Middle Jurassic origin on the Laurasian supercontinent where the group started to diversify during the Cretaceous. However, it remains uncertain when and how the biodiversity hotspot in Southeast Asia was formed. Here, we used a comprehensive genetic data set containing both mitochondrial and nuclear markers and comprising species representing 24 out of 28 genera from throughout the range of the family. To reconstruct the spatiotemporal evolution of viviparids on a global scale, we reconstructed a fossil-calibrated phylogeny. We further assessed the roles of cladogenetic and anagenetic events in range evolution. Finally, we reconstructed the evolution of shell features by estimating ancestral character states to assess whether the appearance of sculptured shell morphologies was driven by major habitat shifts. The molecular phylogeny supports the monophyly of the three subfamilies, the Bellamyinae, Lioplacinae, and Viviparinae, but challenges the currently accepted genus-level classification in several cases. The almost global distribution of River Snails has been influenced both by comparatively ancient vicariance and more recent founder events. In Southeast Asia, Miocene dispersal was a main factor in shaping the modern species distributions. A recurrent theme across different viviparid taxa is that many species living in lentic waters exhibit sculptured shells, whereas only one strongly sculptured species is known from lotic environments. We show that such shell sculpture is habitat-dependent and indeed evolved several times independently in lentic River Snails. Considerably high transition rates between shell types in lentic habitats probably caused the co-occurrence of morphologically distinct shell types in several lakes. In contrast, directional evolution toward smooth shells in lotic habitats, as identified in the present analyses, explains why sculptured shells are rarely found in these habitats. However, the specific factors that promoted changes in shell morphology require further work. [biogeographical analyses; fossil-calibrated phylogeny; fossil-constrained analyses; Southeast Asia; stochastic character mapping.].

Diversification dynamics of freshwater bivalves (Unionidae: Parreysiinae: Coelaturini) indicate historic hydrographic connections throughout the East African Rift System.

Invertebrates are exceptionally diverse, but many are in decline because of anthropogenic changes to their habitat. This situation is particularly problematic for taxa that are not well monitored or taxonomically poorly understood, because the lack of knowledge hampers conservation. Despite their important functional role in freshwater ecosystems, African bivalves of the family Unionidae remain poorly studied compared to their highly threatened relatives in Europe, the U.S.A. and Canada. To resolve relationships and to study diversification dynamics in space and time, we performed time-calibrated phylogenetic studies and biogeographical modeling on the unionids from the East African Rift System and surroundings, including representatives of all currently recognized Afrotropical genera except for Brazzaea (and Unio from southern Africa). Our analyses indicate that all sampled Afrotropical unionids belong to the tribe Coelaturini (subfamily Parreysiinae), as does the genus Moncetia from Lake Tanganyika, which is currently attributed to the family Iridinidae. Colonization of Africa from Eurasia by Parreysiinae occurred ~17 Ma ago, and the subsequent diversification of Coelaturini in Africa continued at a steady pace, although net diversification decreased over time as more niches and ecoregions became occupied. Clades in Coelaturini largely reflect drainage basins, with the oldest lineages and highest regional diversity occurring in Lake Tanganyika, followed by the Congo Basin watershed in general. The species assemblage of Lake Tanganyika reflects multiple independent events of colonization and intralacustrine diversification since the Late Miocene or Early Pliocene. The clades of other regions, including that containing the species from Lake Malawi, are comparatively young. Biogeographical analyses indicate that the colonization history was mainly driven by cladogenesis in sympatry, whereas few anagenetic events contributed to the modern distribution of Coelaturini. Ancestral range estimations demonstrate that Coelaturini originated in the Victoria and/or Tanganyika ecoregions, and that the Congo Basin played an essential role in the colonization of Africa by Coelaturini.

Biological water quality assessment in the degraded Mutara rangelands, northeastern Rwanda.

Rwanda is a heavily overpopulated country that also suffers from overstocking with livestock, especially following the return of war refuges after the civil war (1991-1995). At present, approximately 20% of the human population in Nyagatare District in northeastern Rwanda has no access to clean drinking water and sanitation. We used a biotic index based on the presence of selected families of aquatic macroinvertebrates, derived from the "Tanzania River Scoring System" (TARISS), to assess water quality at N = 55 sites in the Mutara grasslands in Nyagatare District. Poor water quality became evident across most sampling sites both in the Muvumba (mean ± SE TARISS score 5.25 ± 0.10) and Karangazi Rivers (4.79 ± 0.12). Using a general linear model, we asked whether direct effects of land use forms and input of anthropogenic wastewater have an impact on water quality. Our results found no immediate effects of both forms of disturbance/pollution, probably because overall water quality was already poor. Our study is intended to serve as a starting point for continuous monitoring of water quality in the Mutara rangelands in NE Rwanda. The method applied here is cost-efficient, requires only basic equipment, and training local students to apply this technique can provide a solid basis for its implementation in future surveys related to public health.

Diatoms do radiate: evidence for a freshwater species flock.

Due to the ubiquity and high dispersal capacity of unicellular eukaryotes, their often extraordinary diversity found in isolated and long-lived ecosystems such as ancient lakes is typically attributed to multiple colonization events rather than to in situ speciation. However, respective evolutionary studies are very scarce and the often high number of species flocks in ancient lakes across multicellular taxa raises the question whether unicellular species, such as diatoms, may radiate as well. Here, we use an integrative approach that includes molecular data from benthic diatom species of the genus Aneumastus endemic to ancient Lake Ohrid, fossil data obtained from the sediment record of a recent deep-drilling project and biogeographical information to test if this group, indeed, constitutes a species flock. Molecular-clock and phylogenetic analyses indicate a young monophyletic group of several endemic species. Molecular, fossil and biogeographical data strongly suggest a rapid intralacustrine diversification, which was possibly triggered by the emergence of novel habitats. This finding is the first evidence for a species flock in diatoms and suggests that in situ speciation is also a relevant evolutionary process for unicellular eukaryotes in isolated ecosystems.

Origin and diversification of Lake Ohrid's endemic acroloxid limpets: the role of geography and ecology.

BACKGROUND: Ancient Lake Ohrid, located on the Albania-Macedonia border, is the most biodiverse freshwater lake in Europe. However, the processes that gave rise to its extraordinary endemic biodiversity, particularly in the species-rich gastropods, are still poorly understood. A suitable model taxon to study speciation processes in Lake Ohrid is the pulmonate snail genus Acroloxus, which comprises two morphologically distinct and ecologically (vertically) separated endemic species. Using a multilocus phylogenetic framework of Acroloxus limpets from the Euro-Mediterranean subregion, together with molecular-clock and phylogeographic analyses of Ohrid taxa, we aimed to infer their geographic origin and the timing of colonization as well as the role of geography and ecology in intra-lacustrine diversification. RESULTS: In contrast to most other endemic invertebrate groups in Lake Ohrid, the phylogenetic relationships of the endemic Ohrid Acroloxus species indicate that the Balkan region probably did not serve as their ancestral area. The inferred monophyly and estimated divergence times further suggest that these freshwater limpets colonized the lake only once and that the onset of intra-lacustrine diversification coincides with the time when the lake reached deep-water conditions ca 1.3 Mya. However, the difference in vertical distribution of these two ecologically distinct species is not reflected in the phylogeographic pattern observed. Instead, western and eastern populations are genetically more distinct, suggesting a horizontal structure. CONCLUSIONS: We conclude that both geography and ecology have played a role in the intra-lacustrine speciation process. Given the distinct morphology (sculptured vs. smooth shell) and ecology (littoral vs. sublittoral), and the timing of intra-lacustrine diversification inferred, we propose that the onset of deep-water conditions initially triggered ecological speciation. Subsequent geographic processes then gave rise to the phylogeographic patterns observed today. However, the generally weak genetic differentiation observed suggests incipient speciation, which might be explained by the comparatively young age of the lake system and thus the relatively recent onset of intra-lacustrine diversification.

Multilocus Phylogeny of the Afrotropical Freshwater Crab Fauna Reveals Historical Drainage Connectivity and Transoceanic Dispersal Since the Eocene.

Phylogenetic reconstruction, divergence time estimations and ancestral range estimation were undertaken for 66% of the Afrotropical freshwater crab fauna (Potamonautidae) based on four partial DNA loci (12S rRNA, 16S rRNA, cytochrome oxidase one [COI], and histone 3). The present study represents the most comprehensive taxonomic sampling of any freshwater crab family globally, and explores the impact of paleodrainage interconnectivity on cladogenesis among freshwater crabs. Phylogenetic analyses of the total evidence data using maximum-likelihood (ML), maximum parsimony (MP), and Bayesian inference (BI) produced a robust statistically well-supported tree topology that reaffirmed the monophyly of the Afrotropical freshwater crab fauna. The estimated divergence times suggest that the Afrotropical Potamonautidae diverged during the Eocene. Cladogenesis within and among several genera occurred predominantly during the Miocene, which was associated with major tectonic and climatic ameliorations throughout the region. Paleodrainage connectivity was observed with specimens from the Nilo-Sudan and East African coast proving to be sister to specimens from the Upper Guinea Forests in West Africa. In addition, we observed strong sister taxon affinity between specimens from East Africa and the Congo basin, including specimens from Lake Tanganyika, while the southern African fauna was retrieved as sister to the Angolan taxa. Within the East African clade we observed two independent transoceanic dispersal events, one to the Seychelles Archipelago and a second to Madagascar, while we observe a single transoceanic dispersal event from West Africa to São Tomé. The ancestral area estimation suggested a West African/East African ancestral range for the family with multiple dispersal events between southern Africa and East Africa, and between East Africa and Central Africa The taxonomic implications of our results are discussed in light of the widespread paraphyly evident among a number of genera.

Recurrent camouflaged invasions and dispersal of an Asian freshwater gastropod in tropical Africa.

BACKGROUND: Non-indigenous taxa currently represent a large fraction of the species and biomass of freshwater ecosystems. The accumulation of invasive taxa in combination with other stressors in these ecosystems may alter the habitats to which native taxa are adapted, which could elicit evolutionary changes in native populations and their ecological interactions. Assessing ecological and evolutionary consequences of invasions simultaneously may therefore be the most effective approach to study taxa with complex invasion histories. Here we apply such an integrated approach to the cerithioid gastropod Melanoides tuberculata, a model system in invasion biology. RESULTS: Molecular phylogenetics and ancestral range reconstructions allowed us to identify several independent Asian invasions in Lakes Malawi and Tanganyika, the Congo River, Nigeria and Cameroon. Some invasive M. tuberculata populations display much variation in shell morphology, and overlap in morphospace with M. tuberculata populations native to Africa. Experiments confirmed great ecophenotyic plasticity in some invasive populations, which, in combination with the overlap in disparity with native populations, masks invaders and their dispersal through Africa. Finally, the results of geographic modeling indicate that cryptic M. tuberculata invasions occurred primarily in densely populated areas. CONCLUSIONS: We reveal the continental nature of invasions of Asian M. tuberculata to Africa. Several of the affected ecosystems have high endemicity in Cerithioidea: Lake Tanganyika has an unparalleled diversity in freshwater cerithioids (>10 endemic genera) and the Congo Basin and Lake Malawi are home to the two largest endemic species clusters of Melanoides in Africa (~12 and ~8 species, respectively). Cerithioids perform ecologically important functions in the benthic ecosystems of African freshwaters, but invaders and ecosystem change pose risks to their native diversity. We draw suggestions for more effective conservation strategies from our integrated approach.

Conquest of the deep, old and cold: an exceptional limpet radiation in Lake Baikal.

Lake Baikal is the deepest, oldest and most speciose ancient lake in the world. The lake is characterized by high levels of molluscan species richness and endemicity, including the limpet family Acroloxidae with 25 endemic species. Members of this group generally inhabit the littoral zone, but have been recently found in the abyssal zone at hydrothermal vents and oil-seeps. Here, we use mitochondrial and nuclear data to provide a first molecular phylogeny of the Lake Baikal limpet radiation, and to date the beginning of intra-lacustrine diversification. Divergence time estimates suggest a considerably younger age for the species flock compared with lake age estimates, and the beginning of extensive diversification is possibly related to rapid deepening and cooling during rifting. Phylogenetic relationships and divergence time estimates do not clearly indicate when exactly the abyssal was colonized but suggest a timeframe coincident with the formation of the abyssal in the northern basin (Middle to Late Pleistocene).

Disjunct distributions of freshwater snails testify to a central role of the Congo system in shaping biogeographical patterns in Africa.

BACKGROUND: The formation of the East African Rift System has decisively influenced the distribution and evolution of tropical Africa's biota by altering climate conditions, by creating basins for large long-lived lakes, and by affecting the catchment and drainage directions of river systems. However, it remains unclear how rifting affected the biogeographical patterns of freshwater biota through time on a continental scale, which is further complicated by the scarcity of molecular data from the largest African river system, the Congo. RESULTS: We study these biogeographical patterns using a fossil-calibrated multi-locus phylogeny of the gastropod family Viviparidae. This group allows reconstructing drainage patterns exceptionally well because it disperses very poorly in the absence of existing freshwater connections. Our phylogeny covers localities from major drainage basins of tropical Africa and reveals highly disjunct sister-group relationships between (a) the endemic viviparids of Lake Malawi and populations from the Middle Congo as well as between (b) the Victoria region and the Okavango/Upper Zambezi area. CONCLUSIONS: The current study testifies to repeated disruptions of the distribution of the Viviparidae during the formation of the East African Rift System, and to a central role of the Congo River system for the distribution of the continent's freshwater fauna during the late Cenozoic. By integrating our results with previous findings on palaeohydrographical connections, we provide a spatially and temporarily explicit model of historical freshwater biogeography in tropical Africa. Finally, we review similarities and differences in patterns of vertebrate and invertebrate dispersal. Amongst others we argue that the closest relatives of present day viviparids in Lake Malawi are living in the Middle Congo River, thus shedding new light on the origin of the endemic fauna of this rift lake.

Translation of the cell adhesion molecule ALCAM in axonal growth cones - regulation and functional importance.

ALCAM is a cell adhesion molecule that is present on extending axons and has been shown to be crucial for elongation and navigation of retinal ganglion cell (RGC) axons. In the present study, we show that ALCAM mRNA is present in axonal growth cones of RGCs in vivo and in vitro, and that translation of ALCAM occurs in RGC growth cones separated from their soma. This growth cone translation is regulated by the 3'-untranslated region (3'-UTR) of ALCAM and depends on the activity of the kinases ERK and TOR (target of rapamycin). We also investigated the impact of the growth cone translation of ALCAM on axonal functions. Growth cone translation of ALCAM is crucial for the enhanced elongation of axons extending in contact with ALCAM protein. The local translation of ALCAM in the growth cone is able to rapidly counterbalance experimentally induced ALCAM internalization, thereby contributing to the maintenance of constant ALCAM levels in the plasma membrane. Assays where RGC axons have the choice to grow on laminin or both ALCAM and laminin - as is the case in the developing retina - reveal that the axonal preference for ALCAM-containing lanes depends on translation of ALCAM in growth cones. Taken together, these results show for the first time that translation of a cell adhesion molecule in growth cones, as well as the impact of this local translation on the behavior of axon and growth cone.

Exploring the interplay between climate change and schistosomiasis transmission dynamics.

Schistosomiasis, a neglected tropical disease caused by parasitic worms, poses a major public health challenge in economically disadvantaged regions, especially in Sub-Saharan Africa. Climate factors, such as temperature and rainfall patterns, play a crucial role in the transmission dynamics of the disease. This study presents a deterministic model that aims to evaluate the temporal and seasonal transmission dynamics of schistosomiasis by examining the influence of temperature and rainfall over time. Equilibrium states are examined to ascertain their existence and stability employing the center manifold theory, while the basic reproduction number is calculated using the next-generation technique. To validate the model's applicability, demographic and climatological data from Uganda, Kenya, and Tanzania, which are endemic East African countries situated in the tropical region, are utilized as a case study region. The findings of this study provide evidence that the transmission of schistosomiasis in human populations is significantly influenced by seasonal and monthly variations, with incidence rates varying across countries depending on the frequency of temperature and rainfall. Consequently, the region is marked by both schistosomiasis emergencies and re-emergences. Specifically, it is observed that monthly mean temperatures within the range of 22-27 °C create favorable conditions for the development of schistosomiasis and have a positive impact on the reproduction numbers. On the other hand, monthly maximum temperatures ranging from 27 to 33 °C have an adverse effect on transmission. Furthermore, through sensitivity analysis, it is projected that by the year 2050, factors such as the recruitment rate of snails, the presence of parasite egg-containing stools, and the rate of miracidia shedding per parasite egg will contribute significantly to the occurrence and control of schistosomiasis infections. This study highlights the significant influence of seasonal and monthly variations, driven by temperature and rainfall patterns, on the transmission dynamics of schistosomiasis. These findings underscore the importance of considering climate factors in the control and prevention strategies of schistosomiasis. Additionally, the projected impact of various factors on schistosomiasis infections by 2050 emphasizes the need for proactive measures to mitigate the disease's impact on vulnerable populations. Overall, this research provides valuable insights to anticipate future challenges and devise adaptive measures to address schistosomiasis transmission patterns.

Control of schistosomiasis by the selective competitive and predatory intervention of intermediate hosts: A mathematical modeling approach.

Schistosomiasis, a freshwater-borne neglected tropical disease, disproportionately affects impoverished communities mainly in the tropical regions. Transmission involves humans and intermediate host (IH) snails. This manuscript introduces a mathematical model to probe schistosomiasis dynamics and the role of non-host snail competitors and predators as biological control agents for IH snails. The numerical analyses include investigations into steady-state conditions and reproduction numbers associated with uncontrolled scenarios, as well as scenarios involving non-host snail competitors and/or predators. Sensitivity analysis reveals that increasing snail mortality rates is a key to reducing the IH snail population and control of the transmission. Results show that specific snail competitors and/or predators with strong competition/predation abilities reduce IH snails and the subsequent infectious cercaria populations, reduce the transmission, and possibly eradicate the disease, while those with weaker abilities allow disease persistence. Hence our findings advocate for the effectiveness of snail competitors with suitable competitive pressures and/or predators with appropriate predatory abilities as nature-based solutions for combating schistosomiasis, all while preserving IH snail biodiversity. However, if these strategies are implemented at insignificant levels, IH snails can dominate, and disease persistence may pose challenges. Thus, experimental screening of potential (native) snail competitors and/or predators is crucial to assess the likely behavior of biological agents and determine the optimal biological control measures for IH snails.

A machine learning approach for modeling the occurrence of the major intermediate hosts for schistosomiasis in East Africa.

Schistosomiasis, a prevalent water-borne disease second only to malaria, significantly impacts impoverished rural communities, primarily in Sub-Saharan Africa where over 90% of the severely affected population resides. The disease, majorly caused by Schistosoma mansoni and S. haematobium parasites, relies on freshwater snails, specifically Biomphalaria and Bulinus species, as crucial intermediate host (IH) snails. Targeted snail control is advisable, however, there is still limited knowledge about the community structure of the two genera especially in East Africa. Utilizing a machine learning approach, we employed random forest to identify key features influencing the distribution of both IH snails in this region. Our results reveal geography and climate as primary factors for Biomphalaria, while Bulinus occurrence is additionally influenced by soil clay content and nitrogen concentration. Favorable climate conditions indicate a high prevalence of IHs in East Africa, while the intricate connection with geography might signify either dispersal limitations or environmental filtering. Predicted probabilities demonstrate non-linear patterns, with Bulinus being more likely to occur than Biomphalaria in the region. This study provides foundational framework insights for targeted schistosomiasis prevention and control strategies in the region, assisting health workers and policymakers in their efforts.