IL-10 suppresses T cell expansion while promoting tissue-resident memory cell formation during SARS-CoV-2 infection in rhesus macaques.

The regulation of inflammatory responses and pulmonary disease during SARS-CoV-2 infection is incompletely understood. Here we examine the roles of the prototypic pro- and anti-inflammatory cytokines IFNγ and IL-10 using the rhesus macaque model of mild COVID-19. We find that IFNγ drives the development of 18fluorodeoxyglucose (FDG)-avid lesions in the lungs as measured by PET/CT imaging but is not required for suppression of viral replication. In contrast, IL-10 limits the duration of acute pulmonary lesions, serum markers of inflammation and the magnitude of virus-specific T cell expansion but does not impair viral clearance. We also show that IL-10 induces the subsequent differentiation of virus-specific effector T cells into CD69+CD103+ tissue resident memory cells (Trm) in the airways and maintains Trm cells in nasal mucosal surfaces, highlighting an unexpected role for IL-10 in promoting airway memory T cells during SARS-CoV-2 infection of macaques.

Coupled C, H, N, S and Fe biogeochemical cycles operating in the continental deep subsurface of the Iberian Pyrite Belt.

Microbial activity is a major contributor to the biogeochemical cycles that make up the life support system of planet Earth. A 613 m deep geomicrobiological perforation and a systematic multi-analytical characterization revealed an unexpected diversity associated with the rock matrix microbiome that operates in the subsurface of the Iberian Pyrite Belt (IPB). Members of 1 class and 16 genera were deemed the most representative microorganisms of the IPB deep subsurface and selected for a deeper analysis. The use of fluorescence in situ hybridization allowed not only the identification of microorganisms but also the detection of novel activities in the subsurface such as anaerobic ammonium oxidation (ANAMMOX) and anaerobic methane oxidation, the co-occurrence of microorganisms able to maintain complementary metabolic activities and the existence of biofilms. The use of enrichment cultures sensed the presence of five different complementary metabolic activities along the length of the borehole and isolated 29 bacterial species. Genomic analysis of nine isolates identified the genes involved in the complete operation of the light-independent coupled C, H, N, S and Fe biogeochemical cycles. This study revealed the importance of nitrate reduction microorganisms in the oxidation of iron in the anoxic conditions existing in the subsurface of the IPB.

Live-imaging provides an atlas of cellular growth dynamics in the stamen.

Development of multicellular organisms is a complex process involving precise coordination of growth among individual cells. Understanding organogenesis requires measurements of cellular behaviors over space and time. In plants, such a quantitative approach has been successfully used to dissect organ development in both leaves and external floral organs, such as sepals. However, the observation of floral reproductive organs is hampered as they develop inside tightly closed floral buds, and are therefore difficult to access for imaging. We developed a confocal time-lapse imaging method, applied here to Arabidopsis (Arabidopsis thaliana), which allows full quantitative characterization of the development of stamens, the male reproductive organs. Our lineage tracing reveals the early specification of the filament and the anther. Formation of the anther lobes is associated with a temporal increase of growth at the lobe surface that correlates with intensive growth of the developing locule. Filament development is very dynamic and passes through three distinct phases: (1) initial intense, anisotropic growth, and high cell proliferation; (2) restriction of growth and proliferation to the filament proximal region; and (3) resumption of intense and anisotropic growth, displaced to the distal portion of the filament, without cell proliferation. This quantitative atlas of cellular growth dynamics provides a solid framework for future studies into stamen development.

Continuous relative phases of walking with an articulated passive ankle-foot prosthesis in individuals with a unilateral transfemoral and transtibial amputation: an explorative case-control study.

BACKGROUND: A mechanical ankle-foot prosthesis (Talaris Demonstrator) was developed to improve prosthetic gait in people with a lower-limb amputation. This study aims to evaluate the Talaris Demonstrator (TD) during level walking by mapping coordination patterns based on the sagittal continuous relative phase (CRP). METHODS: Individuals with a unilateral transtibial amputation, transfemoral amputation and able-bodied individuals completed 6 minutes of treadmill walking in consecutive blocks of 2 minutes at self-selected (SS) speed, 75% SS speed and 125% SS speed. Lower extremity kinematics were captured and hip-knee and knee-ankle CRPs were calculated. Statistical non-parametric mapping was applied and statistical significance was set at 0.05. RESULTS: The hip-knee CRP at 75% SS walking speed with the TD was larger in the amputated limb of participants with a transfemoral amputation compared to able-bodied individuals at the beginning and end of the gait cycle (p = 0.009). In people with a transtibial amputation, the knee-ankle CRP at SS and 125% SS walking speeds with the TD were smaller in the amputated limb at the beginning of the gait cycle compared to able-bodied individuals (p = 0.014 and p = 0.014, respectively). Additionally, no significant differences were found between both prostheses. However, visual interpretation indicates a potential advantage of the TD over the individual's current prosthesis. CONCLUSION: This study provides lower-limb coordination patterns in people with a lower-limb amputation and reveals a possible beneficial effect of the TD over the individuals' current prosthesis. Future research should include a well-sampled investigation of the adaptation process combined with the prolonged effects of the TD.

Synthesis and antitubercular activity of novel 4-arylalkyl substituted thio-, oxy- and sulfoxy-quinoline analogues targeting the cytochrome bc1 complex.

A library of 4-substituted quinolines was synthesised based on the structural features of the privileged 4-(benzylthio)-6-methoxy-2-methylquinoline scaffold. Quinoline-based chemical probes have proven to be effective anti-tuberculosis agents with the ability of inhibiting components of Mycobacterium tuberculosis (MTB) respiratory chain including the b subunit of the cytochrome bc1 complex. Novel 4-(arylalkyl)-thio, -oxy and sulfoxy-quinoline analogues were tested for their ability to inhibit the growth of MTB H37Rv and QcrB mutant strains, and the compounds mode of action was investigated. Members of the 4-subtituted thio- and sulfoxyquinoline series exhibited significant growth inhibitory activity in the high nanomolar range against wild-type MTB and induced depletion of intracellular ATP. These probes also showed reduced potency in the QcrB T313I mutant strain, thus indicating the cytochrome bc1 oxidase complex as the molecular target. Interestingly, new 4-(quinolin-2-yl)oxy-quinoline 4i was more selective for the QcrB T313I strain compared to the wild-type strain.

New roles of NO TRANSMITTING TRACT and SEEDSTICK during medial domain development in Arabidopsis fruits.

The gynoecium, the female reproductive part of the flower, is key for plant sexual reproduction. During its development, inner tissues such as the septum and the transmitting tract tissue, important for pollen germination and guidance, are formed. In Arabidopsis, several transcription factors are known to be involved in the development of these tissues. One of them is NO TRANSMITTING TRACT (NTT), essential for transmitting tract formation. We found that the NTT protein can interact with several gynoecium-related transcription factors, including several MADS-box proteins, such as SEEDSTICK (STK), known to specify ovule identity. Evidence suggests that NTT and STK control enzyme and transporter-encoding genes involved in cell wall polysaccharide and lipid distribution in gynoecial medial domain cells. The results indicate that the simultaneous loss of NTT and STK activity affects polysaccharide and lipid deposition and septum fusion, and delays entry of septum cells to their normal degradation program. Furthermore, we identified KAWAK, a direct target of NTT and STK, which is required for the correct formation of fruits in Arabidopsis These findings position NTT and STK as important factors in determining reproductive competence.

Phot0, a plausible primeval pigment on Earth and rocky exoplanets.

In view of the existing controversy around the origin of the photosynthesis and, therefore, the first photosynthetic pigments, our work focuses on the theoretical study of a hypothetical first pigment, simpler than those existing today, that collects energy from solar radiation on Earth-like exoplanets. Our theoretical results show that there could exist geochemical conditions that allow the abiotic formation of a primeval pigment that might become sufficiently abundant in the early stages of habitable rocky exoplanets. These conditions would place this pigment before the appearance of life in a very young planet, thanks to chemical routes instead of biochemical transformations. Thus, our results may refute the currently accepted hypothesis that the complex biomolecules that allowed the photosynthesis to be carried out were synthesized through complex and evolved metabolic pathways. In addition, we show that the proposed primeval pigment, which we call Phot0, is also a precursor of the more evolved pigments known today on Earth and demonstrate, for the first time, an abiotic chemical route leading to tetrapyrroles not involving pyrrole derivatives. Our proposal places simple and very abundant raw materials in never-before-proposed geochemical conditions that lead to the formation of biomolecules of biological interest.

Environment Controls Biomolecule Release from Dynamic Covalent Hydrogels.

Moldable hydrogels composed of dynamic covalent bonds are attractive biomaterials for controlled release, as the dynamic exchange of bonds in these networks enables minimally invasive application via injection. Despite the growing interest in the biomedical application of dynamic covalent hydrogels, there is a lack of fundamental understanding as to how the network design and local environment control the release of biomolecules from these materials. In this work, we fabricated boronic-ester-based dynamic covalent hydrogels for the encapsulation and in vitro release of a model biologic (ß-galactosidase). We systematically investigated the role of network properties and of the external environment (temperature and presence of competitive binders) on release from these dynamic covalent hydrogels. We observed that surface erosion (and associated mass loss) governed biomolecule release. In addition, we developed a statistical model of surface erosion based on the binding equilibria in a boundary layer that described the rates of release. In total, our results will guide the design of dynamic covalent hydrogels as biomaterials for drug delivery applications.

Impact of Simulated Martian Conditions on (Facultatively) Anaerobic Bacterial Strains from Different Mars Analogue Sites.

Five bacterial (facultatively) anaerobic strains, namely Buttiauxella sp. MASE-IM-9, Clostridium sp. MASE-IM-4, Halanaerobium sp. MASE-BB-1, Trichococcus sp. MASE-IM-5, and Yersinia intermedia MASE-LG-1 isolated from different extreme natural environments were subjected to Mars relevant environmental stress factors in the laboratory under controlled conditions. These stress factors encompassed low water activity, oxidizing compounds, and ionizing radiation. Stress tests were performed under permanently anoxic conditions. The survival rate after addition of sodium perchlorate (Na-perchlorate) was found to be species-specific. The inter-comparison of the five microorganisms revealed that Clostridium sp. MASE-IM-4 was the most sensitive strain (D10-value (15 min, NaClO4) = 0.6 M). The most tolerant microorganism was Trichococcus sp. MASE-IM-5 with a calculated D10-value (15 min, NaClO4) of 1.9 M. Cultivation in the presence of Na-perchlorate in Martian relevant concentrations up to 1 wt% led to the observation of chains of cells in all strains. Exposure to Na-perchlorate led to a lowering of the survival rate after desiccation. Consecutive exposure to desiccating conditions and ionizing radiation led to additive effects. Moreover, in a desiccated state, an enhanced radiation tolerance could be observed for the strains Clostridium sp. MASE-IM-4 and Trichococcus sp. MASE-IM-5. These data show that anaerobic microorganisms from Mars analogue environments can resist a variety of Martian-simulated stresses either individually or in combination. However, responses were species-specific and some Mars-simulated extremes killed certain organisms. Thus, although Martian stresses would be expected to act differentially on microorganisms, none of the expected extremes tested here and found on Mars prevent the growth of anaerobic microorganisms.

Gynoecium development: networks in Arabidopsis and beyond.

Life has always found a way to preserve itself. One strategy that has been developed for this purpose is sexual reproduction. In land plants, the gynoecium is considered to be at the top of evolutionary innovation, since it has been a key factor in the success of the angiosperms. The gynoecium is composed of carpels with different tissues that need to develop and differentiate in the correct way. In order to control and guide gynoecium development, plants have adapted elements of pre-existing gene regulatory networks (GRNs) but new ones have also evolved. The GRNs can interact with internal factors (e.g. hormones and other metabolites) and external factors (e.g. mechanical signals and temperature) at different levels, giving robustness and flexibility to gynoecium development. Here, we review recent findings regarding the role of cytokinin-auxin crosstalk and the genes that connect these hormonal pathways during early gynoecium development. We also discuss some examples of internal and external factors that can modify GRNs. Finally, we make a journey through the flowering plant lineage to determine how conserved are these GRNs that regulate gynoecium and fruit development.

Sevoflurane for Short Painful Procedures in the Neonatal Intensive Care Unit.

OBJECTIVE: The aim of this study is to evaluate the use and safety of a sedation protocol with sevoflurane for short painful procedures in newborns. STUDY DESIGN: This was a prospective and observational study conducted in a tertiary neonatal intensive care unit. Sevoflurane was recommended in patients undergoing an invasive procedure of short length, especially in those with spontaneous breathing or without venous access. Its safety and efficacy was assessed by continuous monitoring of respiratory and hemodynamic variables and clinical data recording. RESULTS: Sevoflurane was used for 39 procedures, the main indications were: intravitreal bevacizumab injection (12), central venous catheterization (11), and biopsy (6). The median administration length was 14 minutes (range: 5-65 minutes). The median minimum dose was 1.5% (range: 1-3%). The median maximum dose was 2.5% (range: 1-6%). An effective control of nociceptive manifestations was achieved in 35 cases (90%). No major adverse effects were noticed. Main adverse effects were hypotension (8), desaturation (4), and apnea (3). All of them were solved by decreasing (14) or discontinuing (1) the administration of sevoflurane. CONCLUSION: Sevoflurane is relatively easy to use and provides an optimal control of pain-related symptoms. Its prescription should be individualized and more long-term follow-up data are needed.

ED-FNN: A New Deep Learning Algorithm to Detect Percentage of the Gait Cycle for Powered Prostheses.

Throughout the last decade, a whole new generation of powered transtibial prostheses and exoskeletons has been developed. However, these technologies are limited by a gait phase detection which controls the wearable device as a function of the activities of the wearer. Consequently, gait phase detection is considered to be of great importance, as achieving high detection accuracy will produce a more precise, stable, and safe rehabilitation device. In this paper, we propose a novel gait percent detection algorithm that can predict a full gait cycle discretised within a 1% interval. We called this algorithm an exponentially delayed fully connected neural network (ED-FNN). A dataset was obtained from seven healthy subjects that performed daily walking activities on the flat ground and a 15-degree slope. The signals were taken from only one inertial measurement unit (IMU) attached to the lower shank. The dataset was divided into training and validation datasets for every subject, and the mean square error (MSE) error between the model prediction and the real percentage of the gait was computed. An average MSE of 0.00522 was obtained for every subject in both training and validation sets, and an average MSE of 0.006 for the training set and 0.0116 for the validation set was obtained when combining all subjects' signals together. Although our experiments were conducted in an offline setting, due to the forecasting capabilities of the ED-FNN, our system provides an opportunity to eliminate detection delays for real-time applications.

Diagnostic accuracy of multiparametric magnetic resonance imaging in detecting extracapsular extension in intermediate and high - risk prostate cancer.

OBJECTIVES: To evaluate the diagnostic performance of preoperative multiparametric magnetic resonance imaging (mp-MRI) as a predictor of extracapsular extension (ECE) and unfavorable Gleason score (GS) in patients with intermediate and high-risk prostate cancer (PCa). MATERIALS AND METHODS: Patients with clinically localized PCa who underwent radical prostatectomy (RP) and had preoperative mp-MRI between May-2011 and December-2013. Mp-MRI was evaluated according to the European Society of Urogenital Radiology MRI prostate guidelines by two different readers. Histopathological RP results were the standard reference. RESULTS: 79 patients were included; mean age was 61 and median preoperative prostate-specific antigen (PSA) 7.0. On MRI, 28% patients had ECE evidenced in the mp-MRI, 5% seminal vesicle invasion (SVI) and 4% lymph node involvement (LNI). At RP, 39.2% had ECE, 26.6% SVI and 12.8% LNI. Sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of mp-MRI for ECE were 54.9%, 90.9%, 76%, 81% and 74.1% respectively; for SVI values were 19.1%, 100%, 77.3%, 100% and 76.1% respectively and for LNI 20%, 98.4%, 86.7%, 66.7% and 88.7%. CONCLUSIONS: Major surgical decisions are made with digital rectal exam (DRE) and ultrasound studies before the use of Mp-MRI. This imaging study contributes to rule out gross extraprostatic extension (ECE, SVI, LNI) without competing with pathological studies. The specificity and NPV are reasonable to decide surgical approach. A highly experienced radiology team is needed to provide accurate estimations of tumor extension and aggressiveness.

Individual and sex distinctiveness in bark calls of domestic chinchillas elicited in a distress context.

Animals obtain information about their social environment by means of communication signals, which provide relevant subtle cues for individual recognition. An important requisite for this process is the existence of larger between- than within-emitter signal variation. Acoustic signals are complex traits susceptible of variation in their spectral and temporal components, implying that signal distinctiveness can result from differences in single or various acoustic components. In this study, domestic chinchillas were induced to vocalize in a distress context to describe the acoustic characteristics of the bark calls, and to determine features that denote the potential value of this vocalization for individual and/or sexual recognition. The results demonstrate that the variation in spectral and temporal components of the bark calls of chinchillas elicited under a distress context is larger between than within individuals, suggesting the potential of these signals for distinctiveness between individual signalers, although the potential of this call type for sex distinctiveness is quite limited. These results combined with previous studies on auditory capabilities of chinchillas contribute to position this rodent as a valuable model species for studying auditory-vocal interactions.

Ample active acoustic space of a frog from the South American temperate forest.

The efficiency of acoustic communication depends on the power generated by the sound source, the attributes of the environment across which signals propagate, the environmental noise and the sensitivity of the intended receivers. Eupsophus emiliopugini, an anuran from the temperate austral forest communicates by means of an advertisement call of moderate intensity within the range for anurans. To estimate the range over which these frogs communicate effectively, we conducted measurements of call sound levels and of auditory thresholds to pure tones and to synthetic conspecific calls. The results show that E. emiliopugini produces advertisement calls of about 84 dB SPL at 0.25 m from the caller. The signals are affected by attenuation as they propagate, reaching average values of about 47 dB SPL at 8 m from the sound source. Midbrain multi-unit recordings show quite sensitive audiograms within the anuran range, with thresholds of about 44 dB SPL for synthetic imitations of conspecific calls, which would allow communication at distances beyond 8 m. This is an extended range as compared to E. calcaratus, a related syntopic species for which a previous study has shown to be restricted to active acoustic spaces shorter than 2 m. The comparison reveals divergent strategies for related taxa communicating amid the same environment.

Thermoregulatory capacities and torpor in the South American marsupial, Dromiciops gliroides.

During periods of adverse conditions small endotherms depend on a continuous supply of food and energy to maintain body temperature. Thus, rapid and reversible phenotypic modifications at different organizational levels are key for an efficient use of resources and survival. In this study, we provide a quantitative description of thermoregulatory capacities and energy-saving strategies in the Chilean marsupial Dromiciops gliroides. In particular, we evaluated the effect of thermal acclimation on basal metabolic rate (BMR), thermal conductance (C) and torpor patterns, as well as the presence of non-shivering thermogenesis (NST) as a rewarming mechanism in this marsupial. Non-significant effects of thermal acclimation were observed in BMR, C and body mass, but cold-acclimated individuals exhibited significantly longer torpor bouts. Also, minimum body temperature during torpor, inter-bout body temperature and arousal rewarming rate were lower in cold-acclimated animals. Furthermore, we found that D. gliroides did not display NST in response to Norepinephrine. Hence, despite the high regulation of torpor of other species, D. gliroides shows low flexibility in the ability to adjust energy expenditure and insulation properties, and (as in other marsupials) NST do not seems to be important as thermoregulatory mechanism.

Exploring the effects of competition and predation on the success of biological invasion through mathematical modeling.

Biological invasions are a major cause of species extinction and biodiversity loss. Exotic predators are the type of introduced species that have the greatest negative impact, causing the extinction of hundreds of native species. Despite this, they continue to be intentionally introduced by humans. Understanding the causes that determine the success of these invasions is a challenge within the field of invasion biology. Mathematical models play a crucial role in understanding and predicting the behavior of exotic species in different ecosystems. This study examines the effect of predation and competition on the invasion success of an exotic generalist predator in a native predator-prey system. Considering that the exotic predator both consumes the native prey and competes with the native predator, it is necessary to study the interplay between predation and competition, as one of these interspecific interactions may either counteract or contribute to the impact of the other on the success of a biological invasion. Through a mathematical model, represented by a system of ordinary differential equations, it is possible to describe four different scenarios upon the arrival of the exotic predator in a native predator-prey system. The conditions for each of these scenarios are described analytically and numerically. The numerical simulations are performed considering the American mink (Mustela vison), an invasive generalist predator. The results highlight the importance of considering the interplay between interspecific interactions for understanding biological invasion success.

Association of Acidotolerant Cyanobacteria to Microbial Mats below pH 1 in Acidic Mineral Precipitates in Río Tinto River in Spain.

This report describes acidic microbial mats containing cyanobacteria that are strongly associated to precipitated minerals in the source area of Río Tinto. Río Tinto (Huelva, Southwestern Spain) is an extreme acidic environment where iron and sulfur cycles play a fundamental role in sustaining the extremely low pH and the high concentration of heavy metals, while maintaining a high level of microbial diversity. These multi-layered mineral deposits are stable all year round and are characterized by a succession of thick greenish-blue and brownish layers mainly composed of natrojarosite. The temperature and absorbance above and below the mineral precipitates were followed and stable conditions were detected inside the mineral precipitates. Different methodologies, scanning and transmission electron microscopy, immunological detection, fluorescence in situ hybridization, and metagenomic analysis were used to describe the biodiversity existing in these microbial mats, demonstrating, for the first time, the existence of acid-tolerant cyanobacteria in a hyperacidic environment of below pH 1. Up to 0.46% of the classified sequences belong to cyanobacterial microorganisms, and 1.47% of the aligned DNA reads belong to the Cyanobacteria clade.

Two orthogonal differentiation gradients locally coordinate fruit morphogenesis.

Morphogenesis requires the coordination of cellular behaviors along developmental axes. In plants, gradients of growth and differentiation are typically established along a single longitudinal primordium axis to control global organ shape. Yet, it remains unclear how these gradients are locally adjusted to regulate the formation of complex organs that consist of diverse tissue types. Here we combine quantitative live imaging at cellular resolution with genetics, and chemical treatments to understand the formation of Arabidopsis thaliana female reproductive organ (gynoecium). We show that, contrary to other aerial organs, gynoecium shape is determined by two orthogonal, time-shifted differentiation gradients. An early mediolateral gradient controls valve morphogenesis while a late, longitudinal gradient regulates style differentiation. Local, tissue-dependent action of these gradients serves to fine-tune the common developmental program governing organ morphogenesis to ensure the specialized function of the gynoecium.