| 1. |
- Wang, Teng-Wei, et al.
(author)
-
Autochthony and isotopic niches of benthic fauna at shallow-water hydrothermal vents
- 2022
-
In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 12:1
-
Journal article (peer-reviewed)abstract
- The food webs of shallow-water hydrothermal vents are supported by chemosynthetic and photosynthetic autotrophs. However, the relative importance of these two basal resources for benthic consumers and its changes along the physicochemical gradient caused by vent plumes are unknown. We used stable carbon and nitrogen isotopes (i.e., δ13C and δ15N) and Bayesian mixing models to quantify the dietary contribution of basal resources to the benthic fauna at the shallow-water vents around Kueishan Island, Taiwan. Our results indicated that the food chains and consumer production at the shallow-water vents were mainly driven by photoautotrophs (total algal contribution: 26–54%) and zooplankton (19–34%) rather than by chemosynthetic production (total contribution: 14–26%). Intraspecific differences in the trophic support and isotopic niche of the benthic consumers along the physicochemical gradient were also evident. For instance, sea anemone Anthopleura sp. exhibited the greatest reliance on chemosynthetic bacteria (26%) and photoautotrophs (66%) near the vent openings, but zooplankton was its main diet in regions 150–300 m (32–49%) and 300–700 m (32–78%) away from the vent mouths. The vent-induced physicochemical gradient structures not only the community but also the trophic support and isotopic niche of vent consumers.
|
|
| 2. |
- Chan, Karen, et al.
(author)
-
Impacts of ocean acidification on survival, growth, and swimming behaviors differ between larval urchins and brittlestars
- 2016
-
In: ICES Journal of Marine Science. - : Oxford University Press (OUP). - 1054-3139 .- 1095-9289. ; 73:3, s. 951-961
-
Journal article (peer-reviewed)abstract
- Ocean acidification (OA) is widely recognized as an increasing threat to marine ecosystems. Many marine invertebrates have dual-phase life cycles in which planktonic larvae connect and sustain otherwise disconnected benthic adult populations. Many planktonic larvae are particularly sensitive to environmental stresses including OA. Here, we compared the developmental dynamics, survivorship, and swimming behaviours of plutei of two ecologically important echinoderm species that naturally experience variability in ambient pH: the purple urchin Strongylocentrotus purpuratus and the infaunal brittlestar Amphiura filiformis. Sensitivity to decreased pH differed between these two species and between maternal lineages. Larvae of both species experienced increased mortality and reduced growth rate under low pH conditions. However, larval brittlestars appeared more sensitive and experienced over 80% mortality after 7-d exposure to pH 7.7. Larval urchins from one maternal lineage underwent highly synchronized budding (release of blastula-like particles) at low pH. Observed budding temporarily increased numerical density and reduced individual size, leading to differences in growth and mortality rates between the two half-sibling groups and another population. Swimming speeds of larval brittlestars were reduced in decreased pH. In contrast, acidification had either no effect or positive effect on swimming speeds of larval urchins. The observed differences between species may be a reflection of pre-exposure in their natural habitats: larval brittlestars experience a relatively stable in situ pH environment, whereas larval urchins are occasionally exposed to low pH in upwelling regions. Urchins may therefore exhibit short-term compensatory responses such as budding and increased swimming speed. Natural selection could act upon the significant variations we observed between maternal lineages, resulting in more resilient populations confronting chronic exposure to OA.
|
|
| 3. |
- Chan, Karen, et al.
(author)
-
Ocean acidification induces budding in larval sea urchins
- 2013
-
In: Marine Biology. - : Springer Science and Business Media LLC. - 0025-3162 .- 1432-1793. ; 160:8, s. 1-7
-
Journal article (peer-reviewed)abstract
- Ocean acidification (OA), the reduction of ocean pH due to hydration of atmospheric CO2, is known to affect growth and survival of marine invertebrate larvae. Survival and transport of vulnerable planktonic larval stages play important roles in determining population dynamics and community structures in coastal ecosystems. Here, we show that larvae of the purple urchin, Strongylocentrotus purpuratus, underwent high-frequency budding (release of blastula-like particles) when exposed to elevated pCO2 level (>700 μatm). Budding was observed in >50 % of the population and was synchronized over short periods of time (~24 h), suggesting this phenomenon may be previously overlooked. Although budding can be a mechanism through which larval echinoids asexually reproduce, here, the released buds did not develop into viable clones. OA-induced budding and the associated reduction in larval size suggest new hypotheses regarding physiological and ecological tradeoffs between short-term benefits (e.g. metabolic savings and predation escape) and long-term costs (e.g. tissue loss and delayed development) in the face of climate change.
|
|
| 4. |
- Chen, Zhenzhong, et al.
(author)
-
3D hanging spheroid plate for high-throughput CART cell cytotoxicity assay
- 2022
-
In: Journal of Nanobiotechnology. - London, United Kingdom : BioMed Central (BMC). - 1477-3155. ; 20:1
-
Journal article (peer-reviewed)abstract
- Background: Most high-throughput screening (HIS) systems studying the cytotoxic effect of chimeric antigen receptor (CAR) T cells on tumor cells rely on two-dimensional cell culture that does not recapitulate the tumor micro-environment (TME). Tumor spheroids, however, can recapitulate the TME and have been used for cytotoxicity assays of CART cells. But a major obstacle to the use of tumor spheroids for cytotoxicity assays is the difficulty in separating unbound CART and dead tumor cells from spheroids. Here, we present a three-dimensional hanging spheroid plate (3DHSP), which facilitates the formation of spheroids and the separation of unbound and dead cells from spheroids during cytotoxicity assays.Results: The 3DHSP is a 24-well plate, with each well composed of a hanging dripper, spheroid wells, and waste wells. In the dripper, a tumor spheroid was formed and mixed with CART cells. In the 3DHSP, droplets containing the spheroids were deposited into the spheroid separation well, where unbound and dead T and tumor cells were separated from the spheroid through a gap into the waste well by tilting the 3DHSP by more than 20 degrees. Human epidermal growth factor receptor 2 (HER2)-positive tumor cells (BT474 and SKOV3) formed spheroids of approximately 300-350 pm in diameter after 2 days in the 3DHSP. The cytotoxic effects ofT cells engineered to express CAR recognizing HER2 (HER2-CAR T cells) on these spheroids were directly measured by optical imaging, without the use of live/dead fluorescent staining of the cells. Our results suggest that the 3DHSP could be incorporated into a HTS system to screen for CARs that enable T cells to kill spheroids formed from a specific tumor type with high efficacy or for spheroids consisting of tumor types that can be killed efficiently by T cells bearing a specific CAR. Conclusions: The results suggest that the 3DHSP could be incorporated into a HTS system for the cytotoxic effects of CART cells on tumor spheroids.
|
|
| 5. |
- Eckersley, Alexander, et al.
(author)
-
Peptide location fingerprinting identifies species- and tissue-conserved structural remodelling of proteins as a consequence of ageing and disease
- 2022
-
In: Matrix Biology. - : Elsevier B.V.. - 0945-053X .- 1569-1802. ; 114, s. 108-137
-
Journal article (peer-reviewed)abstract
- Extracellular matrices (ECMs) in the intervertebral disc (IVD), lung and artery are thought to undergo age-dependant accumulation of damage by chronic exposure to mechanisms such as reactive oxygen species, proteases and glycation. It is unknown whether this damage accumulation is species-dependant (via differing lifespans and hence cumulative exposures) or whether it can influence the progression of age-related diseases such as atherosclerosis. Peptide location fingerprinting (PLF) is a new proteomic analysis method, capable of the non-targeted identification of structure-associated changes within proteins. Here we applied PLF to publicly available ageing human IVD (outer annulus fibrosus), ageing mouse lung and human arterial atherosclerosis datasets and bioinformatically identified novel target proteins alongside common age-associated differences within protein structures which were conserved between three ECM-rich organs, two species, three IVD tissue regions, sexes and in an age-related disease. We identify peptide yield differences across protein structures which coincide with biological regions, potentially reflecting the functional consequences of ageing or atherosclerosis for macromolecular assemblies (collagen VI), enzyme/inhibitor activity (alpha-2 macroglobulin), activation states (complement C3) and interaction states (laminins, perlecan, fibronectin, filamin-A, collagen XIV and apolipoprotein-B). Furthermore, we show that alpha-2 macroglobulin and collagen XIV exhibit possible shared structural consequences in IVD ageing and arterial atherosclerosis, providing novel links between an age-related disease and intrinsic ageing. Crucially, we also demonstrate that fibronectin, laminin beta chains and filamin-A all exhibit conserved age-associated structural differences between mouse lung and human IVD, providing evidence that ECM, and their associating proteins, may be subjected to potentially similar mechanisms or consequences of ageing across both species, irrespective of differences in lifespan and tissue function. © 2022 The Author(s)
|
|
| 6. |
|
|
| 7. |
- Kappos, Ludwig, et al.
(author)
-
Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study
- 2018
-
In: The Lancet. - 0140-6736 .- 1474-547X. ; 391, s. 1263-1273
-
Journal article (peer-reviewed)abstract
- © 2018 Elsevier Ltd Background: No treatment has consistently shown efficacy in slowing disability progression in patients with secondary progressive multiple sclerosis (SPMS). We assessed the effect of siponimod, a selective sphingosine 1-phosphate (S1P) receptor 1,5 modulator, on disability progression in patients with SPMS. Methods: This event-driven and exposure-driven, double-blind, phase 3 trial was done at 292 hospital clinics and specialised multiple sclerosis centres in 31 countries. Using interactive response technology to assign numbers linked to treatme nt arms, patients (age 18–60 years) with SPMS and an Expanded Disability Status Scale score of 3·0–6·5 were randomly assigned (2:1) to once daily oral siponimod 2 mg or placebo for up to 3 years or until the occurrence of a prespecified number of confirmed disability progression (CDP) events. The primary endpoint was time to 3-month CDP. Efficacy was assessed for the full analysis set (ie, all randomly assigned and treated patients); safety was assessed for the safety set. This trial is registered with ClinicalTrials.gov, number NCT01665144. Findings: 1651 patients were randomly assigned between Feb 5, 2013, and June 2, 2015 (1105 to the siponimod group, and 546 to the placebo group). One patient did not sign the consent form, and five patients did not receive study drug, all of whom were in the siponimod group. 1645 patients were included in the analyses (1099 in the siponimod group and 546 in the placebo). At baseline, the mean time since first multiple sclerosis symptoms was 16·8 years (SD 8·3), and the mean time since conversion to SPMS was 3·8 years (SD 3·5); 1055 (64%) patients had not relapsed in the previous 2 years, and 918 (56%) of 1651 needed walking assistance. 903 (82%) patients receiving siponimod and 424 (78%) patients receiving placebo completed the study. 288 (26%) of 1096 patients receiving siponimod and 173 (32%) of 545 patients receiving placebo had 3-month CDP (hazard ratio 0·79, 95% CI 0·65–0·95; relative risk reduction 21%; p=0·013). Adverse events occurred in 975 (89%) of 1099 patients receiving siponimod versus 445 (82%) of 546 patients receiving placebo; serious adverse events were reported for 197 (18%) patients in the siponimod group versus 83 (15%) patients in the placebo group. Lymphopenia, increased liver transaminase concentration, bradycardia and bradyarrhythmia at treatment initiation, macular oedema, hypertension, varicella zoster reactivation, and convulsions occurred more frequently with siponimod than with placebo. Initial dose titration mitigated cardiac first-dose effects. Frequencies of infections, malignancies, and fatalities did not differ between groups. Interpretation: Siponimod reduced the risk of disability progression with a safety profile similar to that of other S1P modulators and is likely to be a useful treatment for SPMS. Funding: Novartis Pharma AG.
|
|
