The human-mediated introduction of marine non-indigenous species is a centuries- if not millennia-old phenomenon, but was only recently acknowledged as a potent driver of change in the sea. We ...provide a synopsis of key historical milestones for marine bioinvasions, including timelines of (a) discovery and understanding of the invasion process, focusing on transfer mechanisms and outcomes, (b) methodologies used for detection and monitoring, (c) approaches to ecological impacts research, and (d) management and policy responses. Early (until the mid-1900s) marine bioinvasions were given little attention, and in a number of cases actively and routinely facilitated. Beginning in the second half of the 20th century, several conspicuous non-indigenous species outbreaks with strong environmental, economic, and public health impacts raised widespread concerns and initiated shifts in public and scientific perceptions. These high-profile invasions led to policy documents and strategies to reduce the introduction and spread of non-indigenous species, although with significant time lags and limited success and focused on only a subset of transfer mechanisms. Integrated, multi-vector management within an ecosystem-based marine management context is urgently needed to address the complex interactions of natural and human pressures that drive invasions in marine ecosystems.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Our vision of cancer has changed during the past decades. Indeed tumors are now perceived as complex entities where tumoral and stromal components interact closely. Among the different elements of ...tumor stroma the cellular component play a primordial role. Bone Marrow derived mesenchymal cells (MSCs) are attracted to tumor sites and support tumor growth. Endothelial cells (ECs) play a major role in angiogenesis. While the literature documents many aspects of the cross talk between stromal and cancer cells, the role of direct hetero-cellular contact is not clearly established. Recently, Tunneling nanotubes (TnTs) have been shown to support cell-to-cell transfers of plasma membrane components, cytosolic molecules and organelles within cell lines. Herein, we have investigated the formation of heterocellular TnTs between stromal (MSCs and ECs) and cancer cells. We demonstrate that TnTs occur between different cancer cells, stromal cells and cancer-stromal cell lines. We showed that TnTs-like structure occurred in 3D anchorage independent spheroids and also in tumor explant cultures. In our culture condition, TnTs formation occurred after large membrane adhesion. We showed that intercellular transfers of cytoplasmic content occurred similarly between cancer cells and MSCs or ECs, but we highlighted that the exchange of mitochondria occurred preferentially between endothelial cells and cancer cells. We illustrated that the cancer cells acquiring mitochondria displayed chemoresistance. Our results illustrate the perfusion-independent role of the endothelium by showing a direct endothelial to cancer cell mitochondrial exchange associated to phenotypic modulation. This supports another role of the endothelium in the constitution of the metastatic niche.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Resting stages of plankton were sampled in the surficial sediments in the port of Haifa, Israel, on the eve of a major port enlargement project. We recorded the structure of the assemblages and ...examined their relationship with different environments within the port. Our findings reveal a remarkably high diversity coupled with low density and the highest number of oligotrich ciliate cyst types recorded from marine sediments. Near the eutrophic and highly polluted zone of the Kishon estuary ciliates were more abundant than elsewhere in the port, whereas dinoflagellates' abundance was reduced, and these trends held true both for full and empty cysts. Some harmful or potentially toxic species, such as Scrippsiella acuminata, were widespread in the port. The toxigenic species include Alexandrium minutum, Gymnodinium uncatenatum and Lingulodinium polyedrum. Active cells of the unarmoured, bloom-forming Akashiwo sanguinea were identified in the cultures obtained from the incubated sediments.
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•The first survey of resting stages sampled off the Mediterranean coast of Israel.•Species richness (80 morphotypes) is remarkably high for the Mediterranean Sea.•Germination from sediment slurries added 22.4% to total species richness.•Eutrophy/pollution/dredging determined cyst assemblages.•Potentially toxic species were identified, portending the risk of toxic blooms.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Of the 452 multicellular non-indigenous species (NIS) recorded off the Israeli Mediterranean coast, nearly 90% are considered to have been introduced through the Suez Canal (Erythraean NIS). The ...Israeli shelf serves as an important way station and breeding ground for Erythraean NIS, with 260 and 91 species already recorded in the greater Levant Sea and Central Mediterranean, respectively. The positive relationship between time since first record and spread indicates that Erythraean NIS populations may not be at equilibrium and are likely to spread further. Thus, the greater NIS numbers recorded in the past half century augur a sizable invasion debt. A review of the policy of the State of Israel concerning marine NIS, as reflected in recent official documents and regulations, reveals how these enhance their establishment, proliferation and spread in Israeli waters and in waters under the jurisdiction of other Mediterranean States. The continued role of the enlarged Suez Canal as corridor for invasion, and the increasing temperature of Mediterranean seawater, portend unceasing propagule pressure and likely rising establishment success of species not yet introduced. Recognition that factors driving the introduction and establishment of marine NIS are increasing, and the large-sized accrued invasion debt, impel us to urge the Contracting Parties to Barcelona Convention to undertake prevention and control measures to curb marine introductions into the Mediterranean Sea.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
Human‐driven extinctions of native species and introductions of nonindigenous ones have significantly modified the world's biota, often already before the onset of scientific monitoring. Focusing on the Eastern Mediterranean Sea, we analyzed an 18‐year‐long dataset on live‐collected mollusks and compared it to historical biodiversity information reconstructed from decades‐ to centuries‐old accumulations of empty shells preserved on the seafloor. We found that the living species assemblage, even at the beginning of monitoring, was already very different from what lived in the region historically. Our results highlight that scientists must combine different sources of information to accurately describe and understand biodiversity changes.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The pleiotropic cytokine, transforming growth factor (TGF)-β, and CD4
CD25
Foxp3
regulatory T cells (Tregs) play a critical role in actively suppressing antitumor immune responses. Evidence shows ...that TGF-β produced by tumor cells promotes tolerance via expansion of Tregs. Our group previously demonstrated that blockade of TGF-β signaling with a small molecule TGF-β 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.
Using BALB/c, FoxP3eGFP and Rag
mice, we performed FACS analysis to determine if SM16 blocked de novo TGF-β-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.
SM16 abrogates TGF-β-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.
These findings suggest that blockade of TGF-β 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
.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Analyses of marine alien species based on national/regional datasets are of paramount importance for the success of regulation on the prevention and management of invasive alien species. Yet in the ...extant data systems the criteria for the inclusion of records are seldom explicit, and frequently inconsistent in their definitions, spatial and temporal frames and comprehensiveness. Agreed-upon uniform guiding principles, based on solid and transparent scientific criteria, are therefore required in order to provide policy makers with validated and comparable data. Following a meta-analysis on the records of marine alien species in the Mediterranean Sea, we recommend a judicious approach to compiling the data. Here, three categories of uncertainty were identified: species' taxonomic identification, species' actual occurrence in the area, and its status as an alien. In proposing guiding principles to standardize such datasets, we aim to encourage discourse on logical, standardized and transparent criteria to substantiate records of alien species.
•We cross-compare inventories of marine alien species in the Mediterranean Sea.•We analyze uncertainty in taxonomic identity, alien status and species occurrence.•Standard criteria for compiling inventories of marine alien species are proposed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The once plentiful population of the tufted ghost crab, Ocypode cursor, a legally protected species, suffered a steep decline along the densely populated Mediterranean coast of Israel.
Here we ...assessed the effects of recreational disturbance on crab populations in three sandy shore nature reserves and adjacent bathing beaches with differing accessibility during the summers of 2020–2021, employing burrow counts and burrow opening diameter as proxies for population abundance and population size structure.
A total 6270 burrows were identified, counted and their opening diameter measured during the study period. The number of burrows was greatest close by the waterline and diminished landwards; this landwards decline was notable in the smallest burrows (<20 mm), representing the youngest population fraction. Comparison of population abundance between the surveyed nature reserves and adjacent bathing beaches revealed greater numbers in the former. However, a pronounced postweekend reduction in the number of burrows was apparent in nature reserves during both survey years, across sites and months and clearly indicates elevated recreational activity. The number of burrows in the nature reserve nearest to main population centres and abutting a popular bathing beach was smaller compared with the peripheral nature reserves.
We observed no postsunrise activity of adult crabs, though in strictly access‐restricted beaches, crabs were active diurnally. We thus suggest that the crabs shifted their diel activity patterns as avoidance response to chronic anthropogenic disturbance, enduring a forced curfew and a temporal habitat loss.
If the sandy nature reserves are to function as true refugia for the tufted ghost crab, restorative management is to include significant conservation and mitigation intervention measurements/actions.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Tumors employ strategies to escape immune control. The principle aim of most cancer immunotherapies is to restore effective immune surveillance. Among the different processes regulating immune ...escape, tumor microenvironment-associated soluble factors, and/or cell surface-bound molecules are mostly responsible for dysfunctional activity of tumor-specific CD8
T cells. These dynamic immunosuppressive networks prevent tumor rejection at several levels, limiting also the success of immunotherapies. Nevertheless, the recent clinical development of immune checkpoint inhibitors or of molecules modulating cellular targets and immunosuppressive enzymes highlights the great potential of approaches based on the selective disruption of immunosuppressive networks. Currently, the administration of different categories of immunotherapy in combination regimens is the ultimate modality for impacting the survival of cancer patients. With the advent of immune checkpoint inhibitors, designed to mount an effective antitumor immune response, profound changes occurred in cancer immunotherapy: from a global stimulation of the immune system to a specific targeting of an immune component. This review will specifically highlight the players, the mechanisms limiting an efficient antitumor response and the current immunotherapy modalities tailored to target immune suppressive pathways. We also discuss the ongoing challenges encountered by these strategies and provide suggestions for circumventing hurdles to new immunotherapeutic approaches, including the use of relevant biomarkers in the optimization of immunotherapy regimens and the identification of patients who can benefit from defined immune-based approaches.
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