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  • 1
    In: Physical Review Letters, American Physical Society (APS), Vol. 129, No. 7 ( 2022-8-8)
    Type of Medium: Online Resource
    ISSN: 0031-9007 , 1079-7114
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    Language: English
    Publisher: American Physical Society (APS)
    Publication Date: 2022
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  • 2
    In: American Journal of Ophthalmology, Elsevier BV, Vol. 164 ( 2016-04), p. 29-36
    Type of Medium: Online Resource
    ISSN: 0002-9394
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    Language: English
    Publisher: Elsevier BV
    Publication Date: 2016
    detail.hit.zdb_id: 2019600-3
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  • 3
    In: American Journal of Ophthalmology, Elsevier BV, Vol. 160, No. 6 ( 2015-12), p. 1133-1141.e9
    Type of Medium: Online Resource
    ISSN: 0002-9394
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    Language: English
    Publisher: Elsevier BV
    Publication Date: 2015
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  • 4
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 378, No. 6623 ( 2022-12-02)
    Abstract: Madagascar is one of the world’s foremost biodiversity hotspots. Its unique assemblage of plants, animals, and fungi—the majority of which evolved on the island and occur nowhere else—is both diverse and threatened. After human arrival, the island’s entire megafauna became extinct, and large portions of the current flora and fauna may be on track for a similar fate. Conditions for the long-term survival of many Malagasy species are not currently met because of multiple anthropogenic threats. ADVANCES We review the extinction risk and threats to biodiversity in Madagascar, using available international assessment data as well as a machine learning analysis to predict the extinction risks and threats to plant species lacking assessments. Our compilation of global International Union for Conservation of Nature (IUCN) Red List assessments shows that overexploitation alongside unsustainable agricultural practices affect 62.1 and 56.8% of vertebrate species, respectively, and each affects nearly 90% of all plant species. Other threats have a relatively minor effect today but are expected to increase in coming decades. Because only one-third (4652) of all Malagasy plant species have been formally assessed, we carried out a neural network analysis to predict the putative status and threats for 5887 unassessed species and to evaluate biases in current assessments. The percentage of plant species currently assessed as under threat is probably representative of actual numbers, except in the case of the ferns and lycophytes, where significantly more species are estimated to be threatened. We find that Madagascar is home to a disproportionately high number of Evolutionarily Distinct and Globally Endangered (EDGE) species. This further highlights the urgency for evidence-based and effective in situ and ex situ conservation. Despite these alarming statistics and trends, we find that 10.4% of Madagascar’s land area is protected and that the network of protected areas (PAs) covers at least part of the range of 97.1% of terrestrial and freshwater vertebrates with known distributions (amphibians, freshwater fishes, reptiles, birds, and mammal species combined) and 67.7% of plant species (for threatened species, the percentages are 97.7% for vertebrates and 79.6% for plants). Complementary to this, ex situ collections hold 18% of vertebrate species and 23% of plant species. Nonetheless, there are still many threatened species that do not occur within PAs and are absent from ex situ collections, including one amphibian, three mammals, and seven reptiles, as well as 559 plants and more yet to be assessed. Based on our updated vegetation map, we find that the current PA network provides good coverage of the major habitats, particularly mangroves, spiny forest, humid forest, and tapia, but subhumid forest and grassland-woodland mosaic have very low areas under protection (5.7 and 1.8% respectively). OUTLOOK Madagascar is among the world’s poorest countries, and its biodiversity is a key resource for the sustainable future and well-being of its citizens. Current threats to Madagascar’s biodiversity are deeply rooted in historical and present social contexts, including widespread inequalities. We therefore propose five opportunities for action to further conservation in a just and equitable way. First, investment in conservation and restoration must be based on evidence and effectiveness and be tailored to meet future challenges through inclusive solutions. Second, expanded biodiversity monitoring, including increased dataset production and availability, is key. Third, improving the effectiveness of existing PAs—for example through community engagement, training, and income opportunities—is more important than creating new ones. Fourth, conservation and restoration should not focus solely on the PA network but should also include the surrounding landscapes and communities. And finally, conservation actions must address the root causes of biodiversity loss, including poverty and food insecurity. In the eyes of much of the world, Madagascar’s biodiversity is a unique global asset that needs saving; in the daily lives of many of the Malagasy people, it is a rapidly diminishing source of the most basic needs for subsistence. Protecting Madagascar’s biodiversity while promoting social development for its people is a matter of the utmost urgency Visual representation of five key opportunities for conserving and restoring Madagascar’s rapidly declining biodiversity identified in this Review. The dashed lines point to representative vegetation types where these recommendations could have tangible effects, but the opportunities are applicable across Madagascar. ILLUSTRATION: INESSA VOET
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
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    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2022
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  • 5
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 378, No. 6623 ( 2022-12-02)
    Abstract: The Republic of Madagascar is home to a unique assemblage of taxa and a diverse set of ecosystems. These high levels of diversity have arisen over millions of years through complex processes of speciation and extinction. Understanding this extraordinary diversity is crucial for highlighting its global importance and guiding urgent conservation efforts. However, despite the detailed knowledge that exists on some taxonomic groups, there are large knowledge gaps that remain to be filled. ADVANCES Our comprehensive analysis of major taxonomic groups in Madagascar summarizes information on the origin and evolution of terrestrial and freshwater biota, current species richness and endemism, and the utilization of this biodiversity by humans. The depth and breadth of Madagascar’s biodiversity—the product of millions of years of evolution in relative isolation —is still being uncovered. We report a recent acceleration in the scientific description of species but many remain relatively unknown, particularly fungi and most invertebrates. DIGITIZATION Digitization efforts are already increasing the resolution of species richness patterns and we highlight the crucial role of field- and collections-based research for advancing biodiversity knowledge in Madagascar. Phylogenetic diversity patterns mirror that of species richness and endemism in most of the analyzed groups. Among the new data presented, our update on plant numbers estimates 11,516 described vascular plant species native to Madagascar, of which 82% are endemic, in addition to 1215 bryophyte species, of which 28% are endemic. Humid forests are highlighted as centers of diversity because of their role as refugia and centers of recent and rapid radiations, but the distinct endemism of other areas such as the grassland-woodland mosaic of the Central Highlands and the spiny forest of the southwest is also important despite lower species richness. Endemism in Malagasy fungi remains poorly known given the lack of data on the total diversity and global distribution of species. However, our analysis has shown that ~75% of the fungal species detected by environmental sequencing have not been reported as occurring outside of Madagascar. Among the 1314 species of native terrestrial and freshwater vertebrates, levels of endemism are extremely high (90% overall)—all native nonflying terrestrial mammals and native amphibians are found nowhere else on Earth; further, 56% of the island’s birds, 81% of freshwater fishes, 95% of mammals, and 98% of reptile species are endemic. Little is known about endemism in insects, but data from the few well-studied groups on the island suggest that it is similarly high. The uses of Malagasy species are many, with much potential for the uncovering of useful traits for food, medicine, and climate mitigation. OUTLOOK Considerable work remains to be done to fully characterize Madagascar’s biodiversity and evolutionary history. The multitudes of known and potential uses of Malagasy species reported here, in conjunction with the inherent value of this unique and biodiverse region, reinforce the importance of conserving this unique biota in the face of major threats such as habitat loss and overexploitation. The gathering and analysis of data on Madagascar’s remarkable biota must continue and accelerate if we are to safeguard this unique and highly threatened subset of Earth’s biodiversity. Emergence and composition of Madagascar’s extraordinary biodiversity. Madagascar’s biota is the result of over 160 million years of evolution, mostly in geographic isolation, combined with sporadic long distance immigration events and local extinctions. (Left) We show the age of the oldest endemic Malagasy clade for major groups (from bottom to top): arthropods, bony fishes, reptiles, flatworms, birds, amphibians, flowering plants, mammals, non-flowering vascular plants, and mollusks). Humans arrived recently, some 10,000 to 2000 years (top right) and have directly or indirectly caused multiple extinctions (including hippopotamus, elephant birds, giant tortoises, and giant lemurs) and introduced many new species (such as dogs, zebu, rats, African bushpigs, goats, sheep, rice). Endemism is extremely high and unevenly distributed across the island (the heat map depicts Malagasy palm diversity, a group characteristic of the diverse humid forest). Human use of biodiversity is widespread, including 1916 plant species with reported uses. The scientific description of Malagasy biodiversity has accelerated greatly in recent years (bottom right), yet the diversity and evolution of many groups remain practically unknown, and many discoveries await.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    RVK:
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    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2022
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  • 6
    Online Resource
    Online Resource
    American Chemical Society (ACS) ; 2012
    In:  Molecular Pharmaceutics Vol. 9, No. 6 ( 2012-06-04), p. 1785-1794
    In: Molecular Pharmaceutics, American Chemical Society (ACS), Vol. 9, No. 6 ( 2012-06-04), p. 1785-1794
    Type of Medium: Online Resource
    ISSN: 1543-8384 , 1543-8392
    Language: English
    Publisher: American Chemical Society (ACS)
    Publication Date: 2012
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    SSG: 15,3
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  • 7
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 109, No. 29 ( 2012-07-17)
    Abstract: Our data presented here establish the function and mechanism of regulation of claudin-1 in the perineurial barrier of normal rats as well as in rats with hind paw inflammation. Thus, claudin-1 acts as an important sealing component of the perineurial barrier. Modulation of its regulatory pathway may allow the delivery of drugs or gene therapy vectors to the peripheral nerve, which is of clinical importance because it could facilitate the peripheral application of therapeutics for transport to the CNS. Further, our findings provide a rational basis for resealing the barrier after breakdown of the perineurium under pathophysiological conditions. It is likely that this knowledge can be applied to other physiological barriers, such as the blood–brain or intestinal mucosal barrier. How does hypertonic saline reduce the content of claudin-1? Metalloproteinases (MMPs) have been implicated in the property of hypertonic solutions of opening the blood–brain barrier. MMPs also contain a hemopexin domain (MMP9 PEX) that controls the activity of the enzyme. In our system, MMP9 protein expression was found in the perineurium. Blockade of MMP9 PEX inhibited the facilitating effect of hypertonic saline on analgesia induced by opioids and inhibited the down-regulation of claudin-1. In contrast, perisciatic injection of purified MMP9 PEX protein instead of hypertonic saline had the same effect on nociceptive thresholds or on claudin-1 expression. MMP9 PEX can bind to low-density lipoprotein receptor-related protein-1 (LRP-1) and triggers phosphorylation of intracellular p42/44 ERK ( 5 ). This pathway, including MMP9 PEX binding to LRP-1 and subsequent ERK phosphorylation, is active in the perineurium as well. LPR-1 is expressed abundantly in the perineurium in close proximity to claudin-1. Inhibitors of LRP-1 abolish the effects of hypertonic saline and of MMP9 PEX. In the perineurium, ERK is rapidly phosphorylated after treatment with hypertonic solution or MMP9. When ERK phosphorylation is blocked using an ERK inhibitor, claudin-1 content remains unchanged and no analgesic effects of opioids together with hypertonic solution are detected. The pathway is active in the perineurium as well as in a colonic epithelial cell line: MMP9 PEX treatment increases paracellular transport of ions and small molecules and decreases expression of claudin-1. Perineurial injection of hypertonic solution, as a tool to open the barrier, facilitated an analgesic effect of sodium channel blockers and of opioids in normal rats and rats with hind paw inflammation. Hypertonic pretreatment also enabled certain sodium channel blockers to block the conduction of A- or C-fibers in isolated sciatic nerves from normal rats. The effect in vivo was restricted to nociception, because the drugs did not impair motor function. The perineurial barrier remained functionally open for several hours after treatment with hypertonic saline. In parallel, the content of claudin-1 in the membranes of perineurial cells decreased. That claudin-1 is a ubiquitous sealing protein of the tight junction is known from studies of claudin-1 KO mice that are not viable because of loss of water through the skin. In peripheral nerves, selective targeting of sensory or nociceptive neurons still remains a clinically unachieved goal. Several potentially interesting drugs, including sodium channel (NaV 1.7)-selective blockers ( 2 ) or μ- and δ-opioid receptor-selective agonists ( 3 ), are not effective in vivo, presumably because the delivery of perineurally injected drugs is impeded by the perineurial barrier. Hypertonic solutions have been used to open barriers to enhance drug delivery to the brain. Hypertonic saline also increases perineural permeability and facilitates peripheral opioid analgesia at nerve terminals ( 4 ). Here, we used the perineurial injection of hypertonic saline together with the sodium channel blocker TTX or Protoxin-II, or the opioid receptor agonist [D-Ala2, N -Me-Phe4,Gly5-ol]-enkephalin (DAMGO) (agonist for μ-opioid receptors) or [D-Pen2, d-Pen5] -enkephalin (DPDPE) (agonist for δ-opioid receptors) to unravel the opening of the perineurial barrier in full mechanistic detail ( Fig. P1 ). Peripheral nerves are separated from the environment by the perineurial barrier, which protects against nerve damage by molecules like cytokines and protons that impair nerve conduction. However, this barrier also impedes drug delivery to the nerves. The perineurial barrier is formed by a basal membrane and a layer of perineurial cells, which express tight-junction proteins that limit the permeability of this barrier. For example, the tight-junction proteins claudin-1, claudin-5, and occludin are expressed at lower levels during peripheral nerve injury when the perineurial barrier is transiently damaged ( 1 ). How this occurs at the molecular level is unknown. Here, we demonstrate that claudin-1 is the major sealing component of the perineurial barrier. This finding could potentially help researchers develop more effective methods for delivering therapeutic agents to the peripheral nerve.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2012
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  • 8
    Online Resource
    Online Resource
    Elsevier BV ; 2018
    In:  Additive Manufacturing Vol. 24 ( 2018-12), p. 67-75
    In: Additive Manufacturing, Elsevier BV, Vol. 24 ( 2018-12), p. 67-75
    Type of Medium: Online Resource
    ISSN: 2214-8604
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2018
    detail.hit.zdb_id: 2777285-8
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  • 9
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 9 ( 2022-6-9)
    Abstract: An estimated 20–25% of the population is affected by chronic, non-communicable inflammatory skin diseases. Chronic skin inflammation has many causes. Among the most frequent chronic inflammatory skin diseases are atopic dermatitis, psoriasis, urticaria, lichen planus, and hidradenitis suppurativa, driven by a complex interplay of genetics and environmental factors. Autoimmunity is another important cause of chronic skin inflammation. The autoimmune response may be mainly T cell driven, such as in alopecia areata or vitiligo, or B cell driven in chronic spontaneous urticaria, pemphigus and pemphigoid diseases. Rare causes of chronic skin inflammation are autoinflammatory diseases, or rheumatic diseases, such as cutaneous lupus erythematosus or dermatomyositis. Whilst we have seen a significant improvement in diagnosis and treatment, several challenges remain. Especially for rarer causes of chronic skin inflammation, early diagnosis is often missed because of low awareness and lack of diagnostics. Systemic immunosuppression is the treatment of choice for almost all of these diseases. Adverse events due to immunosuppression, insufficient therapeutic responses and relapses remain a challenge. For atopic dermatitis and psoriasis, a broad spectrum of innovative treatments has been developed. However, treatment responses cannot be predicted so far. Hence, development of (bio)markers allowing selection of specific medications for individual patients is needed. Given the encouraging developments during the past years, we envision that many of these challenges in the diagnosis and treatment of chronic inflammatory skin diseases will be thoroughly addressed in the future.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2775999-4
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  • 10
    In: Life, MDPI AG, Vol. 11, No. 8 ( 2021-07-26), p. 748-
    Abstract: While autologous bone is still the gold standard for treatment of bone defects, its availability is limited. Sufficient numbers of mesenchymal stroma cells (MSC) may be an alternative. Small volumes of bone marrow aspirate (BMA) were harvested with two different needle systems comparing the yield and regenerative potency of the MSCs. BMA (10 mL) was aspirated from the posterior iliac crest of 12 patients with degenerative spinal disc disease using both needle systems in each patient: the Jamshidi needle (JAM) and on the contralateral side the Marrow Cellution® Needle (AMC). Number of mononuclear cells (MNCs) and regeneration capacity (colony-forming unit/CFU) were determined. MSCs were characterized for surface markers and their differentiation into trilineages. There was no significant difference between the two harvesting needles regarding the quantity of MNCs in BMA: 5.2 ± 1.8 × 109 MNC/mL for AMC vs. 4.8 ± 2.5 × 109 MNC/mL for JAM, p = 0.182. The quantity of CFUs per ml BMA was similar for both groups: 3717 ± 5556 for AMC and 4305 ± 5507 for JAM (p = 0.695). The potency of MSCs expressed as colony-forming potential per 106 MNC resulted in 0.98 ± 1.51 for AMC and 1.00 ± 0.96 for JAM (p = 0.666). Regardless of the needle design, 10 mL bone marrow aspirate contains a sufficient number of about 40,000 MSCs that can be used to enhance bone healing.
    Type of Medium: Online Resource
    ISSN: 2075-1729
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
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