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Insatisfechos ante las antropologías filosóficas disponibles, en este artículo proponemos el esbozo de una antropología fundamental e invitamos a continuar la empresa. La crítica a las antropologías tradicionales es común en otros autores y nos ayuda a justificar la elaboración de una nueva antropología que calificamos de “reológica”. Sus primeros objetivos son 1) mostrar que la res humana es “física” y por tanto no “dual” como han creído casi todas las antropologías y 2) mostrar que si hay algo fundamentalmente humano no está en las categorías clásicas de “psique”, “reflexividad”, etc., sino en lo que llamamos “experienciar”, i.e. probar físicamente realidad, algo que no hacen el resto de res. Se trata de una propuesta metafísica y no “psicologista”. Por tanto, explicaremos brevemente qué es reología y, usándola como herramienta, esbozaremos algunas directrices que delimiten una futura investigación reológica de la realidad humana.

ABSTRACT Introduction: to evaluate the long-term impact of bariatric surgery in the elderly population. Methods: a retrospective study including all patients older than 60 years who underwent Roux-en-Y gastric bypass (RYGB) at our center and maintained a follow-up longer than 1 year. Clinical and laboratory variables were studied to assess remission of obesity and its comorbidities, as well as variables directly related to the surgical procedure itself, including early and late complications. Results: fifty-six patients were studied, mostly female (76,8%), with a mean age of 64.02 ± 3.34. A rate of complications of 37,5% was observed, with 10,7% requiring hospital admission and emergency surgery. The mean excess weight loss (%EWL) was 74.22% ± 26.76. The remission rates of hypertension and diabetes mellitus were 26.08% and 54.54%, respectively. There was significant difference in BMI reduction (12.25 ± 5.42, p

Eukaryotic transcriptional networks are often large and contain several levels of feedback regulation. Many of these networks have the ability to generate and maintain several distinct transcriptional states across multiple cell divisions and to switch between them. In certain instances, switching between cell states is stochastic, occurring in a small subset of cells of an isogenic population in a seemingly homogenous environment. Given the scarcity and unpredictability of switching in these cases, investigating the determining molecular events is challenging. White-opaque switching in the fungal species Candida albicans is an example of stably inherited cell states that are determined by a complex transcriptional network and can serve as an experimentally accessible model system to study characteristics important for stochastic cell fate switching in eukaryotes. In standard lab media, genetically identical cells maintain their cellular identity (either "white" or "opaque") through thousands of cell divisions, and switching between the states is rare and stochastic. By isolating populations of white or opaque cells, previous studies have elucidated the many differences between the 2 stable cell states and identified a set of transcriptional regulators needed for cell type switching and maintenance of the 2 cell types. Yet, little is known about the molecular events that determine the rare, stochastic switching events that occur in single cells. We use microfluidics combined with fluorescent reporters to directly observe rare switching events between the white and opaque states. We investigate the stochastic nature of switching by beginning with white cells and monitoring the activation of Wor1, a master regulator and marker for the opaque state, in single cells and throughout cell pedigrees. Our results indicate that switching requires 2 stochastic steps; first an event occurs that predisposes a lineage of cells to switch. In the second step, some, but not all, of those predisposed cells rapidly express high levels of Wor1 and commit to the opaque state. To further understand the rapid rise in Wor1, we used a synthetic inducible system in Saccharomyces cerevisiae into which a controllable C. albicans Wor1 and a reporter for its transcriptional control region have been introduced. We document that Wor1 positive autoregulation is highly cooperative (Hill coefficient > 3), leading to rapid activation and producing an "all or none" rather than a graded response. Taken together, our results suggest that reaching a threshold level of a master regulator is sufficient to drive cell type switching in single cells and that an earlier molecular event increases the probability of reaching that threshold in certain small lineages of cells. Quantitative molecular analysis of the white-opaque circuit can serve as a model for the general understanding of complex circuits.

Three large-scale networks are considered essential to cognitive flexibility: the ventral and dorsal attention (VANet and DANet) and salience (SNet) networks. The ventrolateral prefrontal cortex (vlPFC) is a known component of the VANet and DANet, but there is a gap in the current knowledge regarding its involvement in the SNet. Herein, we used a translational and multimodal approach to demonstrate the existence of a SNet node within the vlPFC. First, we used tract-tracing methods in non-human primates (NHP) to quantify the anatomical connectivity strength between different vlPFC areas and the frontal and insular cortices. The strongest connections were with the dorsal anterior cingulate cortex (dACC) and anterior insula (AI) – the main cortical SNet nodes. These inputs converged in the caudal area 47/12, an area that has strong projections to subcortical structures associated with the SNet. Second, we used resting-state functional MRI (rsfMRI) in NHP data to validate this SNet node. Third, we used rsfMRI in the human to identify a homologous caudal 47/12 region that also showed strong connections with the SNet cortical nodes. Taken together, these data confirm a SNet node in the vlPFC, demonstrating that the vlPFC contains nodes for all three cognitive networks: VANet, DANet, and SNet. Thus, the vlPFC is in a position to switch between these three networks, pointing to its key role as an attentional hub. Its additional connections to the orbitofrontal, dorsolateral, and premotor cortices, place the vlPFC at the center for switching behaviors based on environmental stimuli, computing value, and cognitive control.

The severe consequences of the Zika virus (ZIKV) infections resulting in congenital Zika syndrome in infants and the autoimmune Guillain–Barre syndrome in adults warrant the development of safe and efficacious vaccines and therapeutics. Currently, there are no approved treatment options for ZIKV infection. Herein, we describe the development of a bacterial ferritin-based nanoparticle vaccine candidate for ZIKV. The viral envelope (E) protein domain III (DIII) was fused in-frame at the amino-terminus of ferritin. The resulting nanoparticle displaying the DIII was examined for its ability to induce immune responses and protect vaccinated animals upon lethal virus challenge. Our results show that immunization of mice with a single dose of the nanoparticle vaccine candidate (zDIII-F) resulted in the robust induction of neutralizing antibody responses that protected the animals from the lethal ZIKV challenge. The antibodies neutralized infectivity of other ZIKV lineages indicating that the zDIII-F can confer heterologous protection. The vaccine candidate also induced a significantly higher frequency of interferon (IFN)-γ positive CD4 T cells and CD8 T cells suggesting that both humoral and cell-mediated immune responses were induced by the vaccine candidate. Although our studies showed that a soluble DIII vaccine candidate could also induce humoral and cell-mediated immunity and protect from lethal ZIKV challenge, the immune responses and protection conferred by the nanoparticle vaccine candidate were superior. Further, passive transfer of neutralizing antibodies from the vaccinated animals to naïve animals protected against lethal ZIKV challenge. Since previous studies have shown that antibodies directed at the DIII region of the E protein do not to induce antibody-dependent enhancement (ADE) of ZIKV or other related flavivirus infections, our studies support the use of the zDIII-F nanoparticle vaccine candidate for safe and enhanced immunological responses against ZIKV.

Bone marrow transplantation is a treatment for a variety of hematological and non-hematological diseases. For the transplant success, it is mandatory to have a thriving engraftment of transplanted cells, which directly depends on their homing. The present study proposes an alternative method to evaluate the homing and engraftment of hematopoietic stem cells using bioluminescence imaging and inductively coupled plasma mass spectrometry (ICP-MS) associated with superparamagnetic iron oxide nanoparticles. We have identified an enriched population of hematopoietic stem cells in the bone marrow following the administration of Fluorouracil (5-FU). Lately, the cell labeling with nanoparticles displayed the greatest internalization status when treated with 30 µg Fe/mL. The quantification by ICP-MS evaluate the stem cells homing by identifying 3.95 ± 0.37 µg Fe/mL in the control and 6.61 ± 0.84 µg Fe/mL in the bone marrow of transplanted animals. In addition, 2.14 ± 0.66 mg Fe/g in the spleen of the control group and 2.17 ± 0.59 mg Fe/g in the spleen of the experimental group was also measured. Moreover, the bioluminescence imaging provided the follow up on the hematopoietic stem cells behavior by monitoring their distribution by the bioluminescence signal. Lastly, the blood count enabled the monitoring of animal hematopoietic reconstitution and ensured the transplantation effectiveness.

Despite numerous efforts over the last three decades, nucleic acid-based therapeutics still lack delivery platforms in the clinical stage. Cell-penetrating peptides (CPPs) may offer solutions as potential delivery vectors. We have previously shown that designing a “kinked” structure in the peptide backbone resulted in a CPP with efficient in vitro transfection properties. Further optimization of the charge distribution in the C-terminal part of the peptide led to potent in vivo activity with the resultant CPP NickFect55 (NF55). Currently, the impact of the linker amino acid was further investigated in the CPP NF55, with the aim to discover potential transfection reagents for in vivo application. Taking into account the expression of the delivered reporter in the lung tissue of mice, and the cell transfection in the human lung adenocarcinoma cell line, the new peptides NF55-Dap and NF55-Dab* have a high potential for delivering nucleic acid-based therapeutics to treat lung associated diseases, such as adenocarcinoma.

Artificial intelligence is playing an increasingly important role in the invention and innovation processes of our society. To date, though, much of the academic discussion on the interaction of artificial intelligence and the patent system focuses on the patentability of inventions produced by artificial intelligence. Little attention has been paid to organizations that are seeking to use artificial intelligence to defeat the patentability of otherwise patent-worthy inventions by mass producing prior art. This Note seeks to highlight the consequences of allowing mass-produced, AI-generated prior art to render valuable inventions unpatentable. Specifically, this Note concludes that AI-generated prior art decreases the incentive for researchers to disclose valuable knowledge through the patent system without providing an adequate substitute source of such knowledge. This Note also examines a number of patent law doctrines that should, but likely will not, prevent deficient AI-generated prior art from rendering valuable inventions unpatentable. To resolve these issues, this Note proposes a solution that modifies the current novelty inquiry and breathes new life into the patent law doctrine of conception. This solution advances the patent system's purpose of promoting technological advancement while still allowing artificial intelligence to play a large role in that technological advancement., INTRODUCTION 522 I. THE DIFFERING REQUIREMENTS FOR PATENTABILITY AND PRIOR ART 525 A. The Utilitarian Justification for Patent Law 525 B. What Is Prior Art? 526 1. The Practical Requirements [...]

Abstract Background Wound healing is one of the defining features of life and is seen not only in tissues but also within individual cells. Understanding wound response at the single-cell level is critical for determining fundamental cellular functions needed for cell repair and survival. This understanding could also enable the engineering of single-cell wound repair strategies in emerging synthetic cell research. One approach is to examine and adapt self-repair mechanisms from a living system that already demonstrates robust capacity to heal from large wounds. Towards this end, Stentor coeruleus, a single-celled free-living ciliate protozoan, is a unique model because of its robust wound healing capacity. This capacity allows one to perturb the wounding conditions and measure their effect on the repair process without immediately causing cell death, thereby providing a robust platform for probing the self-repair mechanism. Results Here we used a microfluidic guillotine and a fluorescence-based assay to probe the timescales of wound repair and of mechanical modes of wound response in Stentor. We found that Stentor requires ~ 100–1000 s to close bisection wounds, depending on the severity of the wound. This corresponds to a healing rate of ~ 8–80 μm2/s, faster than most other single cells reported in the literature. Further, we characterized three distinct mechanical modes of wound response in Stentor: contraction, cytoplasm retrieval, and twisting/pulling. Using chemical perturbations, active cilia were found to be important for only the twisting/pulling mode. Contraction of myonemes, a major contractile fiber in Stentor, was surprisingly not important for the contraction mode and was of low importance for the others. Conclusions While events local to the wound site have been the focus of many single-cell wound repair studies, our results suggest that large-scale mechanical behaviors may be of greater importance to single-cell wound repair than previously thought. The work here advances our understanding of the wound response in Stentor and will lay the foundation for further investigations into the underlying components and molecular mechanisms involved.

ABSTRACT Fluorine is released into the water environment naturally or by anthropogenic activities. Fluorine promotes health benefits at low concentrations, but it promotes adverse effects ranging from fluorosis to carcinogenic problems at high concentrations. Although fluorine removal from environment can occur through processes such as adsorption, reverse osmosis, and electrodialysis, the phytoremediation emerges as an accessible and environmentally friendly treatment. This research aimed to study the phytoremediation potential of Landoltia punctata for treating water contaminated with fluorine ion (fluoride). The central composite rotatable design was used to assess the effect of three variables in the process: pH ranging from 5 to 9; phosphate concentration from 0 to 10 mg L−1; and nitrate concentration from 0 to 800 mg L−1. The plants were exposed to a fluoride initial concentration of 5 mg L-1 in 3L-vessels that also included Clark's solution for a period of 10 days. Experimentally, removal of up to 21% was observed for the supplied fluoride. Values of the order of 30% for the removed fluoride mass can be predicted by the obtained model. Landoltia punctata is a promising candidate for the phytoremediation of fluoride-contaminated waters.

Abstract Pseudomonas aeruginosa is a common respiratory pathogen in cystic fibrosis (CF) patients which undergoes adaptations during chronic infection towards reduced virulence, which can facilitate bacterial evasion of killing by host cells. However, inflammatory cytokines are often found to be elevated in CF patients, and it is unknown how chronic P. aeruginosa infection can be paradoxically associated with both diminished virulence in vitro and increased inflammation and disease progression. Thus, we investigated the relationship between the stimulation of inflammatory cell death pathways by CF P. aeruginosa respiratory isolates and the expression of key inflammatory cytokines. We show that early respiratory isolates of P. aeruginosa from CF patients potently induce inflammasome signaling, cell death, and expression of IL-1β by macrophages, yet little expression of other inflammatory cytokines (TNF, IL-6 and IL-8). In contrast, chronic P. aeruginosa isolates induce relatively poor macrophage inflammasome signaling, cell death, and IL-1β expression but paradoxically excessive production of TNF, IL-6 and IL-8 compared to early P. aeruginosa isolates. Using various mutants of P. aeruginosa, we show that the premature cell death of macrophages caused by virulent bacteria compromises their ability to express cytokines. Contrary to the belief that chronic P. aeruginosa isolates are less pathogenic, we reveal that infections with chronic P. aeruginosa isolates result in increased cytokine induction due to their failure to induce immune cell death, which results in a relatively intense inflammation compared with early isolates.

Abstract Sow mortality attributable to pelvic organ prolapse (POP) has increased in the U.S. swine industry and continues to worsen. Two main objectives of this study were, (1) to develop a perineal scoring system that can be correlated with POP risk, and (2) identify POP risk-associated biological factors. To assess POP risk during late gestation, sows (n = 213) were scored using a newly developed perineal scoring (PS) system. Sows scored as PS1 (low), PS2 (moderate), or PS3 (high) based on POP risk. Subsequently, 1.5, 0.8, and 23.1% of sows scored PS1, PS2, or PS3, respectively, experienced POP. To identify biomarkers, serum and vaginal swabs were collected from late gestation sows differing in PS. Using GC–MS, 82 serum metabolite differences between PS1 and PS3 animals (P

Antibiotic-resistant bacterial pathogens pose a substantial threat to human health. Here, aided by structural analyses, the authors describe the molecular mechanism behind the activity of a series of compounds that inhibit trans-translation and are effective in eradicating N. gonorrhoeae infection in mice.

Abstract Dispersion and deformation of cratonic fragments within orogens require weakening of the craton margins in a process of decratonization. The orogenic Borborema Province, in NE Brazil, is one of several Brasiliano/Pan-African late Neoproterozoic orogens that led to the amalgamation of Gondwana. A common feature of these orogens is that a period of extension and opening of narrow oceans preceded inversion and collision. For the case of the Borborema Province, the São Francisco Craton was pulled away from its other half, the Benino-Nigerian Shield, during an intermittent extension event between 1.0–0.92 and 0.9–0.82 Ga. This was followed by inversion of an embryonic and confined oceanic basin at ca. 0.60 Ga and transpressional orogeny from ca. 0.59 Ga onwards. Here we investigate the boundary region between the north São Francisco Craton and the Borborema Province and demonstrate how cratonic blocks became physically involved in the orogeny. We combine these results with a wide compilation of U–Pb and Nd-isotopic model ages to show that the Borborema Province consists of up to 65% of strongly sheared ancient rocks affiliated with the São Francisco/Benino-Nigerian Craton, separated by major transcurrent shear zones, with only ≈ 15% addition of juvenile material during the Neoproterozoic orogeny. This evolution is repeated across a number of Brasiliano/Pan-African orogens, with significant local variations, and indicate that extension weakened cratonic regions in a process of decratonization that prepared them for involvement in the orogenies, that led to the amalgamation of Gondwana.

The gastrointestinal health of poultry can be impacted by a variety of factors including their environment. As egg production moves from conventional cage housing (CC) toward cage-free housing (CF), it is important to understand this impact on intestinal health. This study was conducted to determine if housing type impacted intestinal permeability, morphology, and microbial communities in commercial hens across housing systems. Hens were randomly selected from 2 rooms of CC (n = 25) and CF (n = 25) at a commercial facility. Birds were given fluorescein isothiocyanate dextran (FITC-D) by oral gavage to measure intestinal permeability. Jejunal and ileal samples were collected to evaluate villus height, crypt depth, and their ratio. Ileal contents were collected for bacterial DNA isolation and 16S rRNA gene sequencing. Serum FITC-D was similar between housing type (P = 0.709). Hens housed in the CF had increased jejunal villus height and crypt depth compared with hens from the CC (P

Wound repair is a key feature distinguishing living from nonliving matter. Single cells are increasingly recognized to be capable of healing wounds. The lack of reproducible, high-throughput wounding methods has hindered single-cell wound repair studies. This work describes a microfluidic guillotine for bisecting single Stentor coeruleus cells in a continuous-flow manner. Stentor is used as a model due to its robust repair capacity and the ability to perform gene knockdown in a high-throughput manner. Local cutting dynamics reveals two regimes under which cells are bisected, one at low viscous stress where cells are cut with small membrane ruptures and high viability and one at high viscous stress where cells are cut with extended membrane ruptures and decreased viability. A cutting throughput up to 64 cells per minute-more than 200 times faster than current methods-is achieved. The method allows the generation of more than 100 cells in a synchronized stage of their repair process. This capacity, combined with high-throughput gene knockdown in Stentor, enables time-course mechanistic studies impossible with current wounding methods.

Camera trapping is a standard tool in ecological research and wildlife conservation. Study designs, particularly for small-bodied or cryptic wildlife species often attempt to boost low detection probabilities by using non-random camera placement or baited cameras, which may bias data, or incorrectly estimate detection and occupancy. We investigated the ability of non-baited, multi-camera arrays to increase detection probabilities of wildlife. Study design components were evaluated for their influence on wildlife detectability by iteratively parsing an empirical dataset (1) by different sizes of camera arrays deployed (1-10 cameras), and (2) by total season length (1-365 days). Four species from our dataset that represented a range of body sizes and differing degrees of presumed detectability based on life history traits were investigated: white-tailed deer (Odocoileus virginianus), bobcat (Lynx rufus), raccoon (Procyon lotor), and Virginia opossum (Didelphis virginiana). For all species, increasing from a single camera to a multi-camera array significantly improved detection probability across the range of season lengths and number of study sites evaluated. The use of a two camera array increased survey detection an average of 80% (range 40-128%) from the detection probability of a single camera across the four species. Species that were detected infrequently benefited most from a multiple-camera array, where the addition of up to eight cameras produced significant increases in detectability. However, for species detected at high frequencies, single cameras produced a season-long (i.e, the length of time over which cameras are deployed and actively monitored) detectability greater than 0.75. These results highlight the need for researchers to be critical about camera trap study designs based on their intended target species, as detectability for each focal species responded differently to array size and season length. We suggest that researchers a priori identify target species for which inference will be made, and then design camera trapping studies around the most difficult to detect of those species.

Camera trapping is a standard tool in ecological research and wildlife conservation. Study designs, particularly for small-bodied or cryptic wildlife species often attempt to boost low detection probabilities by using non-random camera placement or baited cameras, which may bias data, or incorrectly estimate detection and occupancy. We investigated the ability of non-baited, multi-camera arrays to increase detection probabilities of wildlife. Study design components were evaluated for their influence on wildlife detectability by iteratively parsing an empirical dataset (1) by different sizes of camera arrays deployed (1-10 cameras), and (2) by total season length (1-365 days). Four species from our dataset that represented a range of body sizes and differing degrees of presumed detectability based on life history traits were investigated: white-tailed deer (Odocoileus virginianus), bobcat (Lynx rufus), raccoon (Procyon lotor), and Virginia opossum (Didelphis virginiana). For all species, increasing from a single camera to a multi-camera array significantly improved detection probability across the range of season lengths and number of study sites evaluated. The use of a two camera array increased survey detection an average of 80% (range 40-128%) from the detection probability of a single camera across the four species. Species that were detected infrequently benefited most from a multiple-camera array, where the addition of up to eight cameras produced significant increases in detectability. However, for species detected at high frequencies, single cameras produced a season-long (i.e, the length of time over which cameras are deployed and actively monitored) detectability greater than 0.75. These results highlight the need for researchers to be critical about camera trap study designs based on their intended target species, as detectability for each focal species responded differently to array size and season length. We suggest that researchers a priori identify target species for which inference will be made, and then design camera trapping studies around the most difficult to detect of those species.

Although diet- and stress-induced perturbations in the microbiome (biotic and abiotic factors) associate with changes in host behavior via the microbiota-gut-brain axis, few mechanisms have been identified. The identification of causative pathways by which the microbiome influences host behavior therefore would benefit from the application of evidence-based conceptual frameworks. One such causal framework is microbial endocrinology which is the study of neuroendocrine axes as avenues of bi-directional neurochemical-based host-microbe crosstalk. As such, we investigated the relationship between diet- and stress-induced alterations in behavior, regional gut serotonergic response, and concomitant changes in the cecal and fecal bacterial populations of male and female mice. Our results demonstrate that sex is a dominant factor in determining compositional changes in the gut microbiome in response to stress and diet modifications. Intestinal serotonergic responses to stress were observed in both sexes but dietary modifications uniquely affected region-specific changes in males and females. Likewise, behavioral alterations diverged between male and female mice. Together, these results demonstrate distinct sex-dependent relationships between cecal and fecal bacterial taxa and behavioral- and serotonergic-responses to stress and diet. The present study demonstrates the importance of including both male and female sexes in the examination of the microbiota-gut-brain axis. As different microbial taxa were identified to associate with the behavioral and gut serotonergic responses of male and female mice, certain bacterial species may hold sex-dependent functional relevance for the host. Future investigations seeking to develop microbiome-based strategies to afford host stress resilience should include sex-based differences in the microbiome.

In this study, EIS data collected from three electrode half-cell configurations was used to qualitatively identify and quantitatively determine the responses of ohmic, kinetic, and mass transfer impedances to buffer concentration, flow rate, and applied potential in an MEC consisting of a bioanode and an abiotic nickel-mesh cathode separated by a microporous membrane. EIS measurements were collected during startup and growth (including an abiotic run) at closed circuit and open circuit conditions to accurately match portions of the EIS spectra with the corresponding physical processes and to quantify kinetic changes as the biofilm matured. Once the MEC reached a target current density of 10 A/m2, a multifactorial experimental design formulated as a Taguchi array was executed to assess the impact of flow rate, buffer concentration, and applied voltage on EIS and performance response variables. Multivariate analysis was conducted to ascertain the relative importance of the independent variables and identify any correlations between process conditions and system response. The liquid flow through the anode was found to be strongly correlated with the impedance parameters and the MEC performance, while applied voltage influenced them to a lesser degree. The results are important from an industrial application perspective and provide insights into parameters important for process optimization.