Diverse values of nature for sustainability.

Twenty-five years since foundational publications on valuing ecosystem services for human well-being1,2, addressing the global biodiversity crisis3 still implies confronting barriers to incorporating nature's diverse values into decision-making. These barriers include powerful interests supported by current norms and legal rules such as property rights, which determine whose values and which values of nature are acted on. A better understanding of how and why nature is (under)valued is more urgent than ever4. Notwithstanding agreements to incorporate nature's values into actions, including the Kunming-Montreal Global Biodiversity Framework (GBF)5 and the UN Sustainable Development Goals6, predominant environmental and development policies still prioritize a subset of values, particularly those linked to markets, and ignore other ways people relate to and benefit from nature7. Arguably, a 'values crisis' underpins the intertwined crises of biodiversity loss and climate change8, pandemic emergence9 and socio-environmental injustices10. On the basis of more than 50,000 scientific publications, policy documents and Indigenous and local knowledge sources, the Intergovernmental Platform on Biodiversity and Ecosystem Services (IPBES) assessed knowledge on nature's diverse values and valuation methods to gain insights into their role in policymaking and fuller integration into decisions7,11. Applying this evidence, combinations of values-centred approaches are proposed to improve valuation and address barriers to uptake, ultimately leveraging transformative changes towards more just (that is, fair treatment of people and nature, including inter- and intragenerational equity) and sustainable futures.

Phytoplankton responses to dust addition in the Fe-Mn co-limited eastern Pacific sub-Antarctic differ by source region.

The seasonal availability of light and micronutrients strongly regulates productivity in the Southern Ocean, restricting biological utilization of macronutrients and CO2 drawdown. Mineral dust flux is a key conduit for micronutrients to the Southern Ocean and a critical mediator of multimillennial-scale atmospheric CO2 oscillations. While the role of dust-borne iron (Fe) in Southern Ocean biogeochemistry has been examined in detail, manganese (Mn) availability is also emerging as a potential driver of past, present, and future Southern Ocean biogeochemistry. Here, we present results from fifteen bioassay experiments along a north-south transect in the undersampled eastern Pacific sub-Antarctic zone. In addition to widespread Fe limitation of phytoplankton photochemical efficiency, we found further responses following the addition of Mn at our southerly stations, supporting the importance of Fe-Mn co-limitation in the Southern Ocean. Moreover, addition of different Patagonian dusts resulted in enhanced photochemical efficiency with differential responses linked to source region dust characteristics in terms of relative Fe/Mn solubility. Changes in the relative magnitude of dust deposition, combined with source region mineralogy, could hence determine whether Fe or Mn limitation control Southern Ocean productivity under future as well as past climate states.

Microfluidic Surgery in Single Cells and Multicellular Systems.

Microscale surgery on single cells and small organisms has enabled major advances in fundamental biology and in engineering biological systems. Examples of applications range from wound healing and regeneration studies to the generation of hybridoma to produce monoclonal antibodies. Even today, these surgical operations are often performed manually, but they are labor intensive and lack reproducibility. Microfluidics has emerged as a powerful technology to control and manipulate cells and multicellular systems at the micro- and nanoscale with high precision. Here, we review the physical and chemical mechanisms of microscale surgery and the corresponding design principles, applications, and implementations in microfluidic systems. We consider four types of surgical operations: (1) sectioning, which splits a biological entity into multiple parts, (2) ablation, which destroys part of an entity, (3) biopsy, which extracts materials from within a living cell, and (4) fusion, which joins multiple entities into one. For each type of surgery, we summarize the motivating applications and the microfluidic devices developed. Throughout this review, we highlight existing challenges and opportunities. We hope that this review will inspire scientists and engineers to continue to explore and improve microfluidic surgical methods.

Characterization of the Nonlinear Electrophoretic Behavior of Colloidal Particles in a Microfluidic Channel.

Contemporary findings in the field of insulator-based electrokinetics have demonstrated that in systems under the influence of direct current (DC) fields, dielectrophoresis (DEP) is not the main electrokinetic mechanism responsible for particle manipulation but rather the sum of electroosmosis, linear and nonlinear electrophoresis. Recent microfluidic studies have brought forth a methodology capable of experimentally estimating the nonlinear electrophoretic mobility of colloidal particles. This methodology, however, is limited to particles that fit two conditions: (i) the particle charge has the same sign as the channel wall charge and (ii) the magnitude of the particle ζ-potential is lower than that of the channel wall. The present work aims to expand upon this methodology by including particles whose ζ-potential has a magnitude larger than that of the wall, referred to as "type 2" particles, as well as to report findings on particles that appear to still be under the influence of the linear electrophoretic regime even at extremely high electric fields (∼6000 V/cm), referred to as "type 3" particles. Our findings suggest that both particle size and charge are key parameters in the determination of nonlinear electrophoretic properties. Type 2 microparticles were all found to be small (diameter ∼ 1 µm) and highly charged, with ζ-potentials above -60 mV; in contrast, type 3 microparticles were all large with ζ-potentials between -40 and -50 mV. However, it was also hypothesized that other nonconsidered parameters could be influencing the results, especially at higher electric fields (>3000 V/cm). The present work also aims to identify the current limitations in the experimental determination of µEP,NL and propose a framework for future work to address the current gaps in the evolving topic of nonlinear electrophoresis of colloidal particles.

Dependence of Nonlinear Electrophoresis on Particle Size and Electrical Charge.

This study focuses on the dependence of nonlinear electrophoretic migration of particles on the particle size and particle electrical charge. This is the first report of the experimental assessment of the mobilities of the nonlinear electrophoretic velocity of colloidal polystyrene microparticles under two distinct electric field dependences. A total of nine distinct types of polystyrene microparticles of varying size and varying electrical charge were divided into two groups to study separately the effects of particle size and the effects of particle charge. The mobilities of the nonlinear electrophoretic velocity of each particle type were determined in both the cubic and 3/2 regimes (µEP,NL(3) and µEP,NL(3/2)). The results unveiled that both mobilities had similar relationships with particle size and charge. The magnitude of both µEP,NL(3) and µEP,NL(3/2) increased with increasing particle size and decreased with increasing magnitude of particle charge. However, the observed trends were not perfect as discussed in the Results and Discussion section but still provide valuable information. These findings will aid in the design of future size-based and charge-based separations of particles and microorganisms.

Electropatterning-Contemporary developments for selective particle arrangements employing electrokinetics.

The selective positioning and arrangement of distinct types of multiscale particles can be used in numerous applications in microfluidics, including integrated circuits, sensors and biochips. Electrokinetic (EK) techniques offer an extensive range of options for label-free manipulation and patterning of colloidal particles by exploiting the intrinsic electrical properties of the target of interest. EK-based techniques have been widely implemented in many recent studies, and various methodologies and microfluidic device designs have been developed to achieve patterning two- and three-dimensional (3D) patterned structures. This review provides an overview of the progress in electropatterning research during the last 5 years in the microfluidics arena. This article discusses the advances in the electropatterning of colloids, droplets, synthetic particles, cells, and gels. Each subsection analyzes the manipulation of the particles of interest via EK techniques such as electrophoresis and dielectrophoresis. The conclusions summarize recent advances and provide an outlook on the future of electropatterning in various fields of application, especially those with 3D arrangements as their end goal.

Equilibration time improves the sperm variables of wild ruminant ejaculated and epididymal sperm cryopreserved by ultra-rapid freezing.

This work examines the effect of equilibration time with extender on ultra-rapidly frozen-thawed wild ruminant epididymal (origin: Iberian ibex) and ejaculated (origin: mouflon) sperm variables. Sperm samples were prepared either without prior equilibration, or equilibrated for 30 min before freezing. Higher quality (p < 0.05) frozen-thawed spermatozoa were obtained when equilibration was allowed, for ejaculated sperm in terms of sperm motility, acrosome apical ridge integrity, sperm viability, and percentage of normal cells, and for epididymal sperm in terms of linearity and straightness of sperm movement. The sperm head area, head perimeter, head length and head width were smaller (p < 0.01) in the equilibrated than non-equilibrated frozen-thawed epididymal sperm; no such dimensional changes were recorded for ejaculated sperm. In conclusion, equilibration prior to ultra-rapid freezing improves the cryoresistance of sperm cells, although viable sperm cells can be obtained without equilibration. The epididymal sperm showed greater cryoresistance, supporting the idea that it is more resistant to freeze-thawing than ejaculated sperm.

CoBold: a method for identifying different functional classes of transient RNA structure features that can impact RNA structure formation in vivo.

RNA structure formation in vivo happens co-transcriptionally while the transcript is being made. The corresponding co-transcriptional folding pathway typically involves transient RNA structure features that are not part of the final, functional RNA structure. These transient features can play important functional roles of their own and also influence the formation of the final RNA structure in vivo. We here present CoBold, a computational method for identifying different functional classes of transient RNA structure features that can either aid or hinder the formation of a known reference RNA structure. Our method takes as input either a single RNA or a corresponding multiple-sequence alignment as well as a known reference RNA secondary structure and identifies different classes of transient RNA structure features that could aid or prevent the formation of the given RNA structure. We make CoBold available via a web-server which includes dedicated data visualisation.

De novo 4q35.2 duplication containing FAT1 is associated with autism spectrum disorder.

Genetic studies have established a connection between FAT1 (FAT atypical cadherin 1) deletion and variants and autism spectrum disorder (ASD). Here, we describe a 7-year-old girl who sought a neurology consultation in order to be evaluated for ASD and was found to have a de novo 4q35.2 duplication containing the FAT1 gene. Similar to other reported cases of FAT1 variants or deletion, this patient exhibits non-syndromic ASD without facial dysmorphism or brain MRI abnormalities. We suggest also considering FAT1 duplication as a potential ASD cause.

Influence of Seasonal Variability in Flux Attenuation on Global Organic Carbon Fluxes and Nutrient Distributions.

The biological carbon pump is a key component of the marine carbon cycle. This surface-to-deep flux of carbon is usually assumed to follow a simple power law function, which imposes that the surface export flux is attenuated throughout subsurface waters at a rate dictated by the parameterization exponent. This flux attenuation exponent is widely assumed as constant. However, there is increasing evidence that the flux attenuation varies both spatially and seasonally. While the former has received some attention, the consequences of the latter have not been explored. Here we aim to fill the gap with a theoretical study of how seasonal changes in both flux attenuation and sinking speed affect nutrient distributions and carbon fluxes. Using a global ocean-biogeochemical model that represents detritus explicitly, we look at different scenarios for how these varies seasonally, particularly the relative "phase" with respect to solar radiation and the "strength" of seasonality. We show that the sole presence of seasonality in the model-imposed flux attenuation and sinking speed leads to a greater transfer efficiency compared to the non-seasonal flux attenuation scenario, resulting in an increase of over 140% in some cases when the amplitude of the seasonality imposed is 60% of the non-seasonal base value. This work highlights the importance of the feedback taking place between the seasonally varying flux attenuation, sinking speed and other processes, suggesting that the assumption of constant-in-time flux attenuation and sinking speed might underestimate how much carbon is sequestered by the biological carbon pump.

On the synthesis of visual illusions using deep generative models.

Visual illusions expand our understanding of the visual system by imposing constraints in the models in two different ways: i) visual illusions for humans should induce equivalent illusions in the model, and ii) illusions synthesized from the model should be compelling for human viewers too. These constraints are alternative strategies to find good vision models. Following the first research strategy, recent studies have shown that artificial neural network architectures also have human-like illusory percepts when stimulated with classical hand-crafted stimuli designed to fool humans. In this work we focus on the second (less explored) strategy: we propose a framework to synthesize new visual illusions using the optimization abilities of current automatic differentiation techniques. The proposed framework can be used with classical vision models as well as with more recent artificial neural network architectures. This framework, validated by psychophysical experiments, can be used to study the difference between a vision model and the actual human perception and to optimize the vision model to decrease this difference.

Milk-Derived Exosomes as Nanocarriers to Deliver Curcumin and Resveratrol in Breast Tissue and Enhance Their Anticancer Activity.

Dietary (poly)phenols are extensively metabolized, limiting their anticancer activity. Exosomes (EXOs) are extracellular vesicles that could protect polyphenols from metabolism. Our objective was to compare the delivery to breast tissue and anticancer activity in breast cancer cell lines of free curcumin (CUR) and resveratrol (RSV) vs. their encapsulation in milk-derived EXOs (EXO-CUR and EXO-RSV). A kinetic breast tissue disposition was performed in rats. CUR and RSV were analyzed using UPLC-QTOF-MS and GC-MS, respectively. Antiproliferative activity was tested in MCF-7 and MDA-MB-231 breast cancer and MCF-10A non-tumorigenic cells. Cell cycle distribution, apoptosis, caspases activation, and endocytosis pathways were determined. CUR and RSV peaked in the mammary tissue (41 ± 15 and 300 ± 80 nM, respectively) 6 min after intravenous administration of EXO-CUR and EXO-RSV, but not with equivalent free polyphenol concentrations. Nanomolar EXO-CUR or EXO-RSV concentrations, but not free CUR or RSV, exerted a potent antiproliferative effect on cancer cells with no effect on normal cells. Significant (p < 0.05) cell cycle alteration and pro-apoptotic activity (via the mitochondrial pathway) were observed. EXO-CUR and EXO-RSV entered the cells primarily via clathrin-mediated endocytosis, avoiding ATP-binding cassette transporters (ABC). Milk EXOs protected CUR and RSV from metabolism and delivered both polyphenols to the mammary tissue at concentrations compatible with the fast and potent anticancer effects exerted in model cells. Milk EXOs enhanced the bioavailability and anticancer activity of CUR and RSV by acting as Trojan horses that escape from cancer cells' ABC-mediated chemoresistance.

Towards soccer pass feasibility maps: the role of players' orientation.

- Once player tracking has been established as one of the main data sources in soccer, many challenges have emerged for data scientists, who attempt to recognize patterns from 2D trajectories in order to build tools that might help coaches to improve the performance of their teams. For instance, pass models predict where the ball should go next during pass events. However, existing models are mainly fed with players' location and prior data, hence omitting critical pieces of information such as players' body orientation. This paper presents a computational model to obtain pass feasibility maps, where player orientation is exploited and analysed. As a matter of fact, orientation proves to be crucial when modelling field-of-view and correct positioning of players, since it limits the potential receiving area of all candidates. Different proposals are given to evaluate the proposed pass feasibility map, reaching 0.46 and 0.79 in Top1 and Top3 accuracy, respectively, with a + 0.2 boost obtained after merging positional data with orientation.

Onset Time of Local Anesthesia After Single Injection in Toe Nerve Blocks: A Randomized Double-Blind Trial.

PURPOSE: The study was conducted to investigate the onset time and safety profile of four different local anesthetic solutions. DESIGN: Randomized controlled clinical trial study. METHODS: One hundred twelve healthy volunteers were assigned to receive digital block on their second toe. Individuals were randomly assigned to one of the following groups: lidocaine 2%, lidocaine 2% with epinephrine, bupivacaine 0.5%, or bupivacaine 0.5% with epinephrine. Onset time was measured until detecting the absence of pinprick sensation. Oxygen saturation was measured in the infiltrated toe up to 60 minutes. FINDINGS: The subjects in the groups of anesthetics with epinephrine had a significantly lower mean onset time. There were no significant differences regarding oxygen saturation between the groups and no adverse effects were recorded. CONCLUSIONS: The use of anesthetics with epinephrine can be an effective form of local anesthetic for digital blocks when a rapid onset of action, prolonged duration of anesthesia, and vasoconstrictive action are required.

Detection of climate change-driven trends in phytoplankton phenology.

The timing of the annual phytoplankton spring bloom is likely to be altered in response to climate change. Quantifying that response has, however, been limited by the typically coarse temporal resolution (monthly) of global climate models. Here, we use higher resolution model output (maximum 5 days) to investigate how phytoplankton bloom timing changes in response to projected 21st century climate change, and how the temporal resolution of data influences the detection of long-term trends. We find that bloom timing generally shifts later at mid-latitudes and earlier at high and low latitudes by ~5 days per decade to 2100. The spatial patterns of bloom timing are similar in both low (monthly) and high (5 day) resolution data, although initiation dates are later at low resolution. The magnitude of the trends in bloom timing from 2006 to 2100 is very similar at high and low resolution, with the result that the number of years of data needed to detect a trend in phytoplankton phenology is relatively insensitive to data temporal resolution. We also investigate the influence of spatial scales on bloom timing and find that trends are generally more rapidly detectable after spatial averaging of data. Our results suggest that, if pinpointing the start date of the spring bloom is the priority, the highest possible temporal resolution data should be used. However, if the priority is detecting long-term trends in bloom timing, data at a temporal resolution of 20 days are likely to be sufficient. Furthermore, our results suggest that data sources which allow for spatial averaging will promote more rapid trend detection.

Single-step quantitative susceptibility mapping with variational penalties.

Quantitative susceptibility mapping (QSM) estimates the underlying tissue magnetic susceptibility from the gradient echo (GRE) phase signal through background phase removal and dipole inversion steps. Each of these steps typically requires the solution of an ill-posed inverse problem and thus necessitates additional regularization. Recently developed single-step QSM algorithms directly relate the unprocessed GRE phase to the unknown susceptibility distribution, thereby requiring the solution of a single inverse problem. In this work, we show that such a holistic approach provides susceptibility estimation with artifact mitigation and develop efficient algorithms that involve simple analytical solutions for all of the optimization steps. Our methods employ total variation (TV) and total generalized variation (TGV) to jointly perform the background removal and dipole inversion in a single step. Using multiple spherical mean value (SMV) kernels of varying radii permits high-fidelity background removal whilst retaining the phase information in the cortex. Using numerical simulations, we demonstrate that the proposed single-step methods reduce the reconstruction error by up to 66% relative to the multi-step methods that involve SMV background filtering with the same number of SMV kernels, followed by TV- or TGV-regularized dipole inversion. In vivo single-step experiments demonstrate a dramatic reduction in dipole streaking artifacts and improved homogeneity of image contrast. These acquisitions employ the rapid three-dimensional echo planar imaging (3D EPI) and Wave-CAIPI (controlled aliasing in parallel imaging) trajectories for signal-to-noise ratio-efficient whole-brain imaging. Herein, we also demonstrate the multi-echo capability of the Wave-CAIPI sequence for the first time, and introduce an automated, phase-sensitive coil sensitivity estimation scheme based on a 4-s calibration acquisition. Copyright © 2016 John Wiley & Sons, Ltd.

Big in the benthos: Future change of seafloor community biomass in a global, body size-resolved model.

Deep-water benthic communities in the ocean are almost wholly dependent on near-surface pelagic ecosystems for their supply of energy and material resources. Primary production in sunlit surface waters is channelled through complex food webs that extensively recycle organic material, but lose a fraction as particulate organic carbon (POC) that sinks into the ocean interior. This exported production is further rarefied by microbial breakdown in the abyssal ocean, but a residual ultimately drives diverse assemblages of seafloor heterotrophs. Advances have led to an understanding of the importance of size (body mass) in structuring these communities. Here we force a size-resolved benthic biomass model, BORIS, using seafloor POC flux from a coupled ocean-biogeochemistry model, NEMO-MEDUSA, to investigate global patterns in benthic biomass. BORIS resolves 16 size classes of metazoans, successively doubling in mass from approximately 1 µg to 28 mg. Simulations find a wide range of seasonal responses to differing patterns of POC forcing, with both a decline in seasonal variability, and an increase in peak lag times with increasing body size. However, the dominant factor for modelled benthic communities is the integrated magnitude of POC reaching the seafloor rather than its seasonal pattern. Scenarios of POC forcing under climate change and ocean acidification are then applied to investigate how benthic communities may change under different future conditions. Against a backdrop of falling surface primary production (-6.1%), and driven by changes in pelagic remineralization with depth, results show that while benthic communities in shallow seas generally show higher biomass in a warmed world (+3.2%), deep-sea communities experience a substantial decline (-32%) under a high greenhouse gas emissions scenario. Our results underscore the importance for benthic ecology of reducing uncertainty in the magnitude and seasonality of seafloor POC fluxes, as well as the importance of studying a broader range of seafloor environments for future model development.

Parallel transmission pulse design with explicit control for the specific absorption rate in the presence of radiofrequency errors.

PURPOSE: A new framework for the design of parallel transmit (pTx) pulses is presented introducing constraints for local and global specific absorption rate (SAR) in the presence of errors in the radiofrequency (RF) transmit chain. METHODS: The first step is the design of a pTx RF pulse with explicit constraints for global and local SAR. Then, the worst possible SAR associated with that pulse due to RF transmission errors ("worst-case SAR") is calculated. Finally, this information is used to re-calculate the pulse with lower SAR constraints, iterating this procedure until its worst-case SAR is within safety limits. RESULTS: Analysis of an actual pTx RF transmit chain revealed amplitude errors as high as 8% (20%) and phase errors above 3° (15°) for spokes (spiral) pulses. Simulations show that using the proposed framework, pulses can be designed with controlled "worst-case SAR" in the presence of errors of this magnitude at minor cost of the excitation profile quality. CONCLUSION: Our worst-case SAR-constrained pTx design strategy yields pulses with local and global SAR within the safety limits even in the presence of RF transmission errors. This strategy is a natural way to incorporate SAR safety factors in the design of pTx pulses. Magn Reson Med 75:2493-2504, 2016. © 2015 Wiley Periodicals, Inc.

PGC-1α-Dependent Mitochondrial Adaptation Is Necessary to Sustain IL-2-Induced Activities in Human NK Cells.

Human Natural Killer (NK) cells are a specialized heterogeneous subpopulation of lymphocytes involved in antitumor defense reactions. NK cell effector functions are critically dependent on cytokines and metabolic activity. Among various cytokines modulating NK cell function, interleukin-2 (IL-2) can induce a more potent cytotoxic activity defined as lymphokine activated killer activity (LAK). Our aim was to determine if IL-2 induces changes at the mitochondrial level in NK cells to support the bioenergetic demand for performing this enhanced cytotoxic activity more efficiently. Purified human NK cells were cultured with high IL-2 concentrations to develop LAK activity, which was assessed by the ability of NK cells to lyse NK-resistant Daudi cells. Here we show that, after 72 h of culture of purified human NK cells with enough IL-2 to induce LAK activity, both the mitochondrial mass and the mitochondrial membrane potential increased in a PGC-1α-dependent manner. In addition, oligomycin, an inhibitor of ATP synthase, inhibited IL-2-induced LAK activity at 48 and 72 h of culture. Moreover, the secretion of IFN-γ from NK cells with LAK activity was also partially dependent on PGC-1α expression. These results indicate that PGC-1α plays a crucial role in regulating mitochondrial function involved in the maintenance of LAK activity in human NK cells stimulated with IL-2.