Phytoplankton size structure is key for the ecology and biogeochemistry of pelagic ecosystems, but the relationship between cell size and maximum growth rate (μmax) is not yet well understood. We ...used cultures of 22 species of marine phytoplankton from five phyla, ranging from 0.1 to 106 μm3 in cell volume (Vcell), to determine experimentally the size dependence of growth, metabolic rate, elemental stoichiometry and nutrient uptake. We show that both μmax and carbon‐specific photosynthesis peak at intermediate cell sizes. Maximum nitrogen uptake rate (VmaxN) scales isometrically with Vcell, whereas nitrogen minimum quota scales as Vcell0.84. Large cells thus possess high ability to take up nitrogen, relative to their requirements, and large storage capacity, but their growth is limited by the conversion of nutrients into biomass. Small species show similar volume‐specific VmaxN compared to their larger counterparts, but have higher nitrogen requirements. We suggest that the unimodal size scaling of phytoplankton growth arises from taxon‐independent, size‐related constraints in nutrient uptake, requirement and assimilation.
The universal temperature dependence of metabolic rates has been used to predict how ocean biology will respond to ocean warming. Determining the temperature sensitivity of phytoplankton metabolism ...and growth is of special importance because this group of organisms is responsible for nearly half of global primary production, sustains most marine food webs, and contributes to regulate the exchange of CO2 between the ocean and the atmosphere. Phytoplankton growth rates increase with temperature under optimal growth conditions in the laboratory, but it is unclear whether the same degree of temperature dependence exists in nature, where resources are often limiting. Here we use concurrent measurements of phytoplankton biomass and carbon fixation rates in polar, temperate and tropical regions to determine the role of temperature and resource supply in controlling the large-scale variability of in situ metabolic rates. We identify a biogeographic pattern in phytoplankton metabolic rates, which increase from the oligotrophic subtropical gyres to temperate regions and then coastal waters. Variability in phytoplankton growth is driven by changes in resource supply and appears to be independent of seawater temperature. The lack of temperature sensitivity of realized phytoplankton growth is consistent with the limited applicability of Arrhenius enzymatic kinetics when substrate concentrations are low. Our results suggest that, due to widespread resource limitation in the ocean, the direct effect of sea surface warming upon phytoplankton growth and productivity may be smaller than anticipated.
We apply a recently developed quasi-diabatic (QD) propagation scheme to simulate proton-coupled electron transfer (PCET) reactions. This scheme enables a direct interface between an accurate diabatic ...dynamics approach and the adiabatic vibronic states of the coupled electron–proton subsystem. It explicitly avoids theoretical efforts to preconstruct diabatic states for the transferring electron and proton or reformulate a diabatic dynamics method to the adiabatic representation, both of which are nontrivial tasks. Using a partial linearized path-integral approach and symmetrical quasi-classical approach as the diabatic dynamics methods, we demonstrate that the QD propagation scheme provides accurate vibronic dynamics of PCET reactions and reliably predicts the correct reaction mechanism without any a priori assumptions. This work demonstrates the possibility to directly simulate challenging PCET reactions by using accurate diabatic dynamics approaches and adiabatic vibronic information.
The Red Sea depicts a north–south gradient of positively correlated temperature and nutrient concentration. Despite its overall oligotrophic characteristics, primary production rates in the Red Sea ...vary considerably. In this study, based on five cruises and a 2‐year time series (2016–2018) sampling in the Central Red Sea, we determined phytoplankton photosynthetic rates (PP) by using 13C as a tracer and derived phytoplankton net growth rates (μ) and chlorophyll a (Chl a)‐normalized photosynthesis (PB). Our results indicate a ninefold variation (14–125 mgC m−2 h−1) in depth‐integrated primary production and reveal a marked seasonality in PP, PB, and μ. Depth‐integrated PP remained <30 mg C m−2 h−1 during spring and summer, and peaked in autumn–winter, particularly in the southernmost stations (~17°N). In surface waters, phytoplankton grew at a slow rate (0.2 ± 0.02 d−1), with the population doubling every 3.5 days, on average. However, during the autumn–winter period, when Chl a concentrations peaked in the central and southern regions, μ increased to values between 0.60 and 0.84 d−1, while PB reached its maximum rate (7.8 mgC mg Chl a−1 h−1). We used path analysis to resolve direct vs. indirect components between correlations. Our results show that nutrient availability modulates the photosynthetic performance and growth of phytoplankton communities and that PB and μ fluctuations are not directly associated with temperature changes. Our study suggests that similarly to other oligotrophic warm seas, phosphorus concentration exerts a key role in defining photosynthetic rates and the biomass levels of phytoplankton communities in the region.
Despite decades of research, prognosis for SCLC patients remains poor, and treatment options limited. SCLC is an immunogenic tumor with high somatic mutation rates due to tobacco exposure resulting ...in potential neo-antigens, the presence of suppressed immune responses, and occurrence of paraneoplastic disorders. The use of T cell immune-checkpoint inhibitors (anti-PD1: nivolumab, pembrolizumab; anti-PD-L1: atezolizumab, durvalumab; anti-CTLA-4: ipilimumab, tremelimumab) have shown promising antitumor activity with the potential to prolong survival in SCLC patients. In fact, atezolizumab when combined with chemotherapy has achieved the milestone of being the first drug to improve survival in patients with newly diagnosed extensive-stage SCLC. Other immunotherapeutic approaches evaluated in clinical trials for SCLC include the use of cytokines, cancer vaccines, antiganglioside therapies, TLR9 inhibition, anti-Notch signaling, and anti-CD47. This review discusses the rationale and clinical evidence of immunotherapy in SCLC, the conflictive clinical results of novel immunotherapeutic agents and combinatorial therapies under evaluation in SCLC patients.
Expression of misfolded protein in cultured cells frequently leads to the formation of juxtanuclear inclusions that have been termed ‘aggresomes’. Aggresome formation is an active cellular response ...that involves trafficking of the offending protein along microtubules, reorganization of intermediate filaments and recruitment of components of the ubiquitin proteasome system. Whether aggresomes are benevolent or noxious is unknown, but they are of particular interest because of the appearance of similar inclusions in protein deposition diseases. Here we present evidence that aggresomes serve a cytoprotective function and are associated with accelerated turnover of mutant proteins. We show that mutant androgen receptor (AR), the protein responsible for X-linked spinobulbar muscular atrophy, forms insoluble aggregates and is toxic to cultured cells. Mutant AR was also found to form aggresomes in a process distinct from aggregation. Molecular and pharmacological interventions were used to disrupt aggresome formation, revealing their cytoprotective function. Aggresome-forming proteins were found to have an accelerated rate of turnover, and this turnover was slowed by inhibition of aggresome formation. Finally, we show that aggresome-forming proteins become membrane-bound and associate with lysosomal structures. Together, these findings suggest that aggresomes are cytoprotective, serving as cytoplasmic recruitment centers to facilitate degradation of toxic proteins.
The distribution of bioactive trace metals has the potential to enhance or limit primary productivity and carbon export in some regions of the world ocean. To study these connections, the ...concentrations of Cd, Co, Cu, Fe, Mo, Ni, and V were determined for 110 surface water samples collected during the Malaspina 2010 Circumnavigation Expedition (MCE). Total dissolved Cd, Co, Cu, Fe, Mo, Ni, and V concentrations averaged 19.0 ± 5.4 pM, 21.4 ± 12 pM, 0.91 ± 0.4 nM, 0.66 ± 0.3 nM, 88.8 ± 12 nM, 1.72 ± 0.4 nM, and 23.4 ± 4.4 nM, respectively, with the lowest values detected in the Central Pacific and increased values at the extremes of all transects near coastal zones. Trace metal concentrations measured in surface waters of the Atlantic Ocean during the MCE were compared to previously published data for the same region. The comparison revealed little temporal changes in the distribution of Cd, Co, Cu, Fe, and Ni over the last 30 years. We utilized a multivariable linear regression model to describe potential relationships between primary productivity and the hydrological, biological, trace nutrient and macronutrient data collected during the MCE. Our statistical analysis shows that primary productivity in the Indian Ocean is best described by chlorophyll a, NO3, Ni, temperature, SiO4, and Cd. In the Atlantic Ocean, primary productivity is correlated with chlorophyll a, NO3, PO4, mixed layer depth, Co, Fe, Cd, Cu, V, and Mo. The variables salinity, temperature, SiO4, NO3, PO4, Fe, Cd, and V were found to best predict primary productivity in the Pacific Ocean. These results suggest that some of the lesser studied trace elements (e.g., Ni, V, Mo, and Cd) may play a more important role in regulating oceanic primary productivity than previously thought and point to the need for future experiments to verify their potential biological functions.
Key Points
The distribution of trace metals in waters of the global ocean was determined
No multiyear variation in the distribution of trace metals in the Atlantic Ocean was observed
Some metals correlate with primary productivity, suggesting potential metal limitation
Resolving the environmental drivers shaping planktonic communities is
fundamental for understanding their variability, in the present and the
future, across the ocean. More specifically, addressing ...the
temperature-dependence response of planktonic communities is essential as
temperature plays a key role in regulating metabolic rates and thus potentially
defining the ecosystem functioning. Here we quantified plankton metabolic
rates along the Red Sea, a uniquely oligotrophic and warm environment, and
analysed the drivers that regulate gross primary production (GPP), community
respiration (CR), and net community production (NCP). The study was conducted
on six oceanographic surveys following a north–south transect along the
Saudi Arabian coast. Our findings revealed that GPP and CR rates increased
with increasing temperature (R2=0.41 and 0.19, respectively;
p<0.001 in both cases), with a higher activation energy (Ea) for
GPP (1.20±0.17 eV) than for CR (0.73±0.17 eV). The higher Ea
for GPP than for CR resulted in a positive relationship between NCP and
temperature. This unusual relationship is likely driven by the relatively
higher nutrient availability found towards the warmer region (i.e. southern Red Sea), which favours GPP rates above the threshold that
separates autotrophic from heterotrophic communities (1.7 mmol O2 m−3 d−1) in this region. Due to the arid nature, the basin
lacks riverine and terrestrial inputs of organic carbon to subsidise a
higher metabolic response of heterotrophic communities, thus constraining CR
rates. Our study suggests that GPP increases steeply with increasing
temperature in the warm ocean when relatively high nutrient inputs are
present.
AIMS: To assess the anticaries activity of an antioxidant‐rich apple concentrate (ARAC) in an experimental biofilm caries model on enamel. METHODS AND RESULTS: A validated caries model with ...Streptococcus mutans UA159 biofilms was used. Biofilms were formed on enamel slabs during 5 days. To mimic cariogenic challenges, triplicate slabs were exposed three times per day for 5 min to 10% sucrose followed by five additional minutes of exposure to serial dilutions of ARAC in 0·9% NaCl. A triplicate slab exposed to 10% sucrose followed by 0·9% NaCl served as caries‐positive control. Acidogenicity was estimated by medium pH twice per day. After the experimental phase, biofilms were recovered to determine biomass, viable bacteria and intra‐ and extracellular polysaccharides. Slabs were used to estimate demineralization by the percentage of surface microhardness loss (%SHL). Differences among treatments were analysed by anova and Bonferroni test (P < 0·05). Streptococcus mutans biofilms were exposed to ARAC after a cariogenic challenge with sucrose‐induced lower enamel demineralization than the positive control. The highest dilution of ARAC at 1 : 100 000 (v/v) showed the most marked reduction in demineralization of about 57%. Although no differences were observed in the number of bacterial cells, the intracellular polysaccharides or in the biomass (P > 0·05), the highest dilution of the apple concentrate induced significantly lower extracellular polysaccharide formation by the biofilm. CONCLUSIONS: An apple concentrate in low concentrations appears to have a potential anticaries activity on enamel. Data suggest a metabolic rather than an antimicrobial mechanism, but further research is needed. SIGNIFICANCE AND IMPACT OF THE STUDY: Phenolic compounds contained in apple concentrates seem to have anticaries properties that may be effective even in the presence of sucrose and in very low doses. Nutritional interventions that do not require rescinding from sucrose might be derived from these findings.
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