An important principle of environmental science is that changes in single components of systems are likely to have consequences elsewhere in the same systems. In the sea, food web data are one of the ...few foundations for predicting such indirect effects, whether of fishery exploitation or following recovery in marine protected areas (MPAs). We review the available literature on one type of indirect interaction in benthic marine ecosystems, namely trophic cascades, which involve three or more trophic levels connected by predation. Because many indirect effects have been revealed through fishery exploitation, in some cases we include humans as trophic levels. Our purpose is to establish how widespread cascades might be, and infer how likely they are to affect the properties of communities following the implementation of MPAs or intensive resource exploitation. We review 39 documented cascades (eight of which include humans as a trophic level) from 21 locations around the world; all but two of the cascades are from shallow systems underlain by hard substrata (kelp forests, rocky subtidal, coral reefs and rocky intertidal). We argue that these systems are well represented because they are accessible and also amenable to the type of work that is necessary. Nineteen examples come from the central-eastern and north-eastern Pacific, while no well-substantiated benthic cascades have been reported from the NE, CE or SW Atlantic, the Southern Oceans, E Indian Ocean or NW Pacific. The absence of examples from those zones is probably due to lack of study. Sea urchins are very prominent in the subtidal examples, and gastropods, especially limpets, in the intertidal examples; we suggest that this may reflect their predation by fewer specialist predators than is the case with fishes, but also their conspicuousness to investigators. The variation in ecological resolution amongst studies, and in intensity of study amongst systems and regions, indicates that more cascades will likely be identified in due course. Broadening the concept of cascades to include pathogenic interactions would immediately increase the number of examples. The existing evidence is that cascade effects are to be expected when hard-substratum systems are subject to artisanal resource exploitation, but that the particular problems of macroalgal overgrowth on Caribbean reefs and the expansion of coralline barrens in the Mediterranean rocky-sublittoral will not be readily reversed in MPAs, probably because factors other than predation-based cascades have contributed to them in the first place. More cascade effects are likely to be found in the soft-substratum systems that are crucial to so many large-scale fisheries, when opportunities such as those of MPAs and fishing gradients become available for study of such systems, and the search is widened to less conspicuous focal organisms such as polychaetes and crustaceans.
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BFBNIB, NUK, PNG, UL, UM, UPUK
Heparanase is regarded as a promising target for anticancer drugs and Ronepastat is one of the most promising heparanase inhibitors insert in clinical study for Multiple Myeloma Therapy. To improve ...its pharmacokinetic/pharmacodynamic profile, as well to have an antidote able to neutralize its activity in case of over dosages or intolerance, a new class of its derivatives was obtained inserting non-carbohydrate moieties of different length between the polysaccharide chain and biotin or its derivatives. In vitro these novel derivatives maintain the anti-heparanase activity without induced toxicity. The newly synthesized compounds retained the ability to attenuate the growth of CAG myeloma tumors in mice with potency similar, or in one case even higher than that of the reference compound Roneparstat as well as inhibited metastatic dissemination (lung colonization) of murine B16-F10 melanoma cells in vivo.
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•Heparanase is regarded as a promising target for anticancer drugs and Ronepastat is one of one of its most promising inhibitors.•A new class of biotinylated N-acetyl-gs-heparin have been synthetized through a linker of different functional groups.•Compounds were characterized by NMR and evaluation of molecular weight.•“in vitro” and “in vivo” tests showed that the chemical modifications introduced do not hinder their biological activity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
With increased use of antiretroviral therapy (ART), HIV mortality rates are declining and people living with HIV (PLWH) are surviving longer. We characterized CD4 recovery and viral suppression among ...adults aged < 50 and ≥ 50 years living with HIV who initiated ART in the African Cohort Study (AFRICOS).
Beginning in January 2013, PLWH at twelve clinics in Kenya, Uganda, Tanzania and Nigeria underwent medical history review, CD4 and viral load testing as part of the ongoing African Cohort Study (AFRICOS). ART-naïve PLWH who initiated ART within 30 days of enrollment and had at least one year of follow-up were included in these analyses. To compare ART response in participants < 50 years and ≥ 50 years old, changes in CD4 count and viral load suppression after ART initiation were examined at different time points using linear and binomial regression with generalized estimating equations. Variables for time since ART initiation and the interaction between age group and time on ART were included in the model to evaluate longitudinal changes in CD4 recovery and viral suppression by age.
Between January 2013 and September 2019, 2918 PLHV were enrolled in the cohort. Of these, 443 were ART naïve and initiated on ART within 30 days of enrollment, with 90% (n = 399) aged < 50 years old at ART initiation. At ART initiation, participants aged 50 and older had a higher median CD4 count compared to participants younger than 50 years of age although it did not reach statistical significance (306 cells/mm
, IQR:130-547 vs. 277cells/mm
, IQR: 132-437). In adjusted models examining CD4 recovery and viral suppression there were no significant differences by age group over time. By the end of follow-up viral suppression was high among both groups of adults (96% of adults ≥ 50 years old and 92% of adults < 50 years old).
This study found no difference in long-term CD4 recovery or viral suppression by age at ART initiation. We found that particularly among younger adults participants had lower median CD4 counts at ART initiation, suggesting the importance of identifying and putting this population on treatment earlier in the disease course.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Although psychological distress and cognitive dysfunction are well documented in adults with multiple sclerosis (MS), they are poorly understood in children with the disease. Psychosocial difficulty ...experienced by children and adolescents with MS involves factors common to all chronic illnesses in children, as well as MS-specific factors. The psychosocial manifestations of the disease may affect the patient's self-image, role functioning, mood, and cognition to adversely affect schooling, interpersonal relationships, and treatment compliance. Furthermore, the impact of having a family member with MS may affect overall family functioning. Assessment and interventions for psychosocial and cognitive problems in pediatric MS should be multidisciplinary in nature and address the child's functioning at home, school, and among peers, as well as the effect on the family.
Background
Understanding and treating vernal keratoconjunctivitis (VKC) has been a challenge because the pathogenesis is unclear and antiallergic therapy often unsuccessful. The aim of the study was ...to analyze peptide profiles in human tears using mass spectrometry to elucidate compositional differences between healthy subjects and patients affected by VKC.
Methods
Tears were collected from healthy subjects and VKC patients. Digested samples were treated with iTRAQ (isobaric tag for relative and absolute quantitation). Separation of tryptic peptides was realized using a MicroHPLC interfaced with a microfraction collector. MS and MS/MS mass spectra were performed using a MALDI TOF/TOF 4800 Applied Biosystem spectrometer. Protein Pilot™ software with Paragon™ algorithm v4.1.46 or GPS™ with Mascot engine was used as search engines with SwissProt or IPI human as the databases.
Results
A significant number of peptides were examined, and 78 proteins were successfully identified. In all VKC samples, levels of serum albumin, transferrin, and hemopexin were found up to 100 times higher than control tear levels and correlated to the severity of disease. Hemopexin, transferrin, mammaglobin B, and secretoglobin 1D were found significantly over‐expressed in VKC samples compared with the control samples. Tear samples from patients treated with topical cyclosporine or corticosteroids showed a dramatic reduction in these protein levels.
Conclusions
LC MALDI MS and isobaric tag for relative and absolute quantitation technique may be useful in the quantitative and qualitative characterization of the peptidoma of human tears. These techniques may identify target proteins to be used in the diagnosis and management of VKC and other inflammatory ocular surface conditions.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The diagnosis of pediatric multiple sclerosis (MS) is challenging due to its low frequency and the overlap with other acquired childhood demyelinating disorders of the central nervous system. To ...identify potential protein biomarkers which could facilitate the diagnosis, we used two-dimensional gel electrophoresis (2-DE) in combination with mass spectrometry to identify proteins associated with pediatric MS. Plasma samples from nine children with MS and nine healthy subjects, matched in aggregate by age and gender, were analyzed for differences in their patterns of protein expression. We found 12 proteins that were significantly up regulated in the pediatric MS group: alpha-1-acid-glycoprotein 1, alpha-1-B-glycoprotein, transthyretin, apoliprotein-C-III, serum amyloid P component, complement factor-I, clusterin, gelsolin, hemopexin, kininogen-1, hCG1993037-isoform, and vitamin D-binding protein. These results show that 2-DE in combination with mass spectrometry is a highly sensitive technique for the identification of blood-based biomarkers. This proteomic approach could lead to a new panel of diagnostic and prognostic markers in pediatric MS.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
The OSIRIS‐REx Asteroid Sample Return Mission is the third mission in National Aeronautics and Space Administration (NASA)'s New Frontiers Program and is the first U.S. mission to return samples from ...an asteroid to Earth. The most important decision ahead of the OSIRIS‐REx team is the selection of a prime sample‐site on the surface of asteroid (101955) Bennu. Mission success hinges on identifying a site that is safe and has regolith that can readily be ingested by the spacecraft's sampling mechanism. To inform this mission‐critical decision, the surface of Bennu is mapped using the OSIRIS‐REx Camera Suite and the images are used to develop several foundational data products. Acquiring the necessary inputs to these data products requires observational strategies that are defined specifically to overcome the challenges associated with mapping a small irregular body. We present these strategies in the context of assessing candidate sample sites at Bennu according to a framework of decisions regarding the relative safety, sampleability, and scientific value across the asteroid's surface. To create data products that aid these assessments, we describe the best practices developed by the OSIRIS‐REx team for image‐based mapping of irregular small bodies. We emphasize the importance of using 3‐D shape models and the ability to work in body‐fixed rectangular coordinates when dealing with planetary surfaces that cannot be uniquely addressed by body‐fixed latitude and longitude.
Plain Language Summary
The OSIRIS‐REx Asteroid Sample Return Mission must map asteroid (101955) Bennu using the OSIRIS‐REx Camera Suite. Here we present the techniques that are established to accomplish this goal. Mapping helps us find the best place on the surface of Bennu from which to gather a sample. Because asteroids are small bodies with weak gravitational fields, maneuvering a spacecraft around them can be challenging. Considering these complexities, we have found ways to gather images of Bennu needed for creating maps. Additionally, due to the irregular shape of many asteroids, producing 2‐D maps in terms of latitude and longitude may be insufficient for describing their surface geography. To that end, we have developed software that is capable of creating and displaying image maps in 3‐D.
Key Points
The OSIRIS‐REx Asteroid Sample Return Mission performs image‐based mapping of (101955) Bennu to aid in the selection of a sample‐site
We develop observational strategies to perform mapping to address the challenges associated with surveying a small body
We identify pitfalls and best practices for mapping images of small bodies with large concavities, elongated axes, or overhanging terrain
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
In the Mediterranean, the gastropod Dendropoma cristatum (sin. D. petraeum (Monterosato, 1884)) is the primary builder of the vermetid reef, an intertidal bioconstruction of exceptional ecological ...importance. Despite awareness of the need for conservation of this key species, the biology of D. cristatum remains poorly understood. The recruitment of D. cristatum deserves particular attention because the absence of a planktonic larval stage limits its dispersal ability. We examined the temporal pattern of recruitment during the breeding season of D. cristatum from June to September in 2013. Specifically, we compared the two portions of the vermetid reef (i.e. the inner edge and the outer edge) at localities with different exposures to wave motion. The number of recruits peaked in July, when it was significantly higher in the outer than in the inner edge. No differences emerged between localities with different wave exposures; however, the width of the reef was significantly related to the exposure index. Although there are still several gaps in our knowledge of the recruitment dynamics of D. cristatum, this study contributes to characterising recruitment rate variation at small spatial and temporal scales.
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