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Abstract The yield of pearl millet, a resilient cereal crop crucial for African food security, is severely impacted by the root parasitic weed Striga hermonthica, which requires host-released hormones, called strigolactones (SLs), for seed germination. Herein, we identify four SLs present in the Striga-susceptible line SOSAT-C88-P10 (P10) but absent in the resistant 29Aw (Aw). We generate chromosome-scale genome assemblies, including four gapless chromosomes for each line. The Striga-resistant Aw lacks a 0.7 Mb genome segment containing two putative CARLACTONOIC ACID METHYLTRANSFERASE1 (CLAMT1) genes, which may contribute to SL biosynthesis. Functional assays show that P10CLAMT1b produces the SL-biosynthesis intermediate methyl carlactonoate (MeCLA) and that MeCLA is the precursor of P10-specific SLs. Screening a diverse pearl millet panel confirms the pivotal role of the CLAMT1 section for SL diversity and Striga susceptibility. Our results reveal a reason for Striga susceptibility in pearl millet and pave the way for generating resistant lines through marker-assisted breeding or direct genetic modification.

Abstract Many functional aspects of the protein kinase p38α have been illustrated by more than three hundred structures determined in the presence of reducing agents. These structures correspond to free forms and complexes with activators, substrates, and inhibitors. Here we report the conformation of an oxidized state with an intramolecular disulfide bond between Cys119 and Cys162 that is conserved in vertebrates. The structure of the oxidized state does not affect the conformation of the catalytic site, but alters the docking groove by partially unwinding and displacing the short αD helix due to the movement of Cys119 towards Cys162. The transition between oxidized and reduced conformations provides a mechanism for fine-tuning p38α activity as a function of redox conditions, beyond its activation loop phosphorylation. Moreover, the conformational equilibrium between these redox forms reveals an unexplored cleft for p38α inhibitor design that we describe in detail.

Abstract In the last century, vitamin A was identified that included the nutritional relevant vitamin A1 / provitamin A1, as well as the vitamin A2 pathway concept. Globally, nutritional guidelines have focused on vitamin A1 with simplified recommendations and calculations based solely on vitamin A. The vitamin A / provitamin A terminology described vitamin A with respect to acting as a precursor of 11-cis-retinal, the chromophore of the visual pigment, as well as retinoic acid(s), being ligand(s) of the nuclear hormone receptors retinoic acid receptors (RARs) α, β and γ. All-trans-retinoic acid was conclusively shown to be the endogenous RAR ligand, while the concept of its isomer 9-cis-retinoic acid, being “the” endogenous ligand of the retinoid-X receptors (RXRs), remained inconclusive. Recently, 9-cis-13,14-dihydroretinoic acid was conclusively reported as an endogenous RXR ligand, and a direct nutritional precursor was postulated in 2018 and further confirmed by Rühl, Krezel and de Lera in 2021. This was further termed vitamin A5/X / provitamin A5/X. In this review, a new vitamin A5/X / provitamin A5/X concept is conceptualized in parallel to the vitamin A(1) / provitamin A(1) concept for daily dietary intake and towards dietary guidelines, with a focus on the existing national and international regulations for the physiological and nutritional relevance of vitamin A5/X. The aim of this review is to summarize available evidence and to emphasize gaps of knowledge regarding vitamin A5/X, based on new and older studies and proposed future directions as well as to stimulate and propose adapted nutritional regulations.

Abstract p38α is a versatile protein kinase that can control numerous processes and plays important roles in the cellular responses to stress. Dysregulation of p38α signaling has been linked to several diseases including inflammation, immune disorders and cancer, suggesting that targeting p38α could be therapeutically beneficial. Over the last two decades, numerous p38α inhibitors have been developed, which showed promising effects in pre-clinical studies but results from clinical trials have been disappointing, fueling the interest in the generation of alternative mechanisms of p38α modulation. Here, we report the in silico identification of compounds that we refer to as non-canonical p38α inhibitors (NC-p38i). By combining biochemical and structural analyses, we show that NC-p38i efficiently inhibit p38α autophosphorylation but weakly affect the activity of the canonical pathway. Our results demonstrate how the structural plasticity of p38α can be leveraged to develop therapeutic opportunities targeting a subset of the functions regulated by this pathway.

Unraveling the nature of dark matter (DM) stands as a primary objective in modern physics. Here we present evidence suggesting deviations from the collisionless cold DM (CDM) paradigm. It arises from the radial distribution of stars in six ultrafaint dwarf (UFD) galaxies measured with the Hubble Space Telescope. After a trivial renormalization in size and central density, the six UFDs show the same stellar distribution, which happens to have a central plateau or core. Assuming spherical symmetry and isotropic velocities, the Eddington inversion method proves the observed distribution to be inconsistent with the characteristic potentials of CDM particles. Under such assumptions, the observed innermost slope of the stellar profile discards the UFDs to reside in a CDM potential at a ≥97% confidence level. The extremely low stellar mass of these galaxies, 10 ^3 –10 ^4 M _⊙ , prevents stellar feedback from modifying the shape of a CDM potential. Other conceivable explanations for the observed cores, like deviations from spherical symmetry and isotropy, tidal forces, and the exact form of the used CDM potential, are disfavored by simulations and/or observations. Thus, the evidence suggests that collisions among DM particles or other alternatives to CDM are likely shaping these galaxies. Many of these alternatives produce cored gravitational potentials, shown here to be consistent with the observed stellar distribution.

Se estudió la biomasa de macroalgas en la bahía de Cienfuegos con el objetivo de determinar su variación espacio-temporal. Los valores medios de biomasa oscilaron entre 7.5 (Playa Alegre en febrero-01) y 1055 gm -2 (Junco Sur en octubre 00). El grupo de las formas carnosas fue el dominante en todas las estaciones de colecta, representado principalmente por las especies Hypnea spinella (C. Agardh) Kützing, Acanthophora spicifera (M. Vahl) Børgesen, Gracilaria blodgettii Harvey, y Chondrophycus papillosus (C. Agardh) Garbary & Harper. El lóbulo norte, caracterizado por mayor impacto de la urbanización e industrialización, presentó menor diversidad de macroalgas en comparación con la estación del lóbulo sur. Hypnea spinella y Gracilaria spp, especies tolerantes a amplios rangos de condiciones ecológicas fueron dominantes en las estaciones del lóbulo norte. En la estación ubicada en el lóbulo sur se registró la mayor diversidad. Esta estación evidencia mejores condiciones oceánicas, lo cual está sustentado por la abundancia de Chondrophycus papillosus (C. Agardh) Garbary & Harper, característica de aguas más limpias. Se observó una notable variación temporal en los valores de biomasa en todas las estaciones. En las estaciones del lóbulo norte se registró el mayor valor de biomasa en el período lluvioso, lo cual puede ser debido a una mayor entrada de nutrientes durante ese período. En la estación del lóbulo sur se registró el mayor valor de biomasa en el período de seca, registrándose un sobrecrecimiento de un alga verde filamentosa que al parecer fue estimulado por una mayor transparencia y disposición de luz en el agua en esta época del año.

La experiencia de manejo ha evidenciado que hay varias herramientas en el campo de las ciencias naturales y sociales que pueden contribuir al éxito del proceso de manejo integrado de las zonas costeras (MIZC). Entre ellas, los programas de monitoreo hidrológicos juegan un papel importante, puesto que éstos, al contar con un diseño basado en los posibles impactos de los usos del sistema, sin duda pueden brindar el conocimiento suficiente para garantizar una confiable interpretación de resultados que se traducen en la captación de los cambios en las áreas y recursos bajo manejo. En particular, la Bahía de Cienfuegos cuenta, desde 1990, con un programa permanente de monitoreo hidrológico cuya eficacia recientemente fue evaluada; sin embargo éste adolece de una adecuada integración de su información al manejo integrado de esta bahía. Por consiguiente, este trabajo, partiendo del análisis de las condiciones internas existentes; tiene como objetivo: proponer un esquema coherente y completo con enfoque interdisciplinario e intersectorial para las posibles soluciones a los problemas que se identifiquen, lo cual se exige en cualquier programa para el MIZC.

Desde hace tres décadas, la bahía de Cienfuegos, Cuba, ha sido contaminada por metales pesados como consecuencia del desarrollo industrial. Esta situación se vio empeorada, con el último derrame accidental de una solución arsenical proveniente de la Empresa de Fertilizantes Nitrogenados de Cienfuegos en el 2001. Por esta razón, el objetivo de este trabajo es evaluar la concentración de Arsénico (As) en diferentes especies de macroalgas existentes en bancos naturales de la bahía de Cienfuegos como un paso inicial para fortalecer el actual Programa de Monitoreo de la Calidad Ambiental de este ecosistema, al brindar una efectiva herramienta para el bio- monitoreo de este metal. Las estaciones de muestreo estuvieron ubicadas en zonas de playas donde asisten con frecuencia las comunidades aledañas y población en general, excepto para la estación #1 que representó el punto de referencia, por corresponder al sitio de vertimiento del residual. Las muestras de macroalgas recibieron un pretratamiento de limpieza y secado a 40 o C; la determinación de As se realizó por una combinación de métodos: el APHA AWWA WCPCF del Estándar Métodos y una norma cubana establecida para este metal, NEIB 1014.272:89. Los resultados obtenidos permitieron establecer un rango de concentración de este metal que osciló entre 0.044 registrado por Enteromorpha flexuosa y 11.834 mg AsTotal /kg registrado por Gracilaria blodgettii, siendo esta ultima especie una excelente propuesta para la bioindicación de metales pesados en este ecosistema.

Summary: In the adult mammalian brain, most neural stem cells (NSCs) are held in a reversible state of quiescence, which is essential to avoid NSC exhaustion and determine the appropriate neurogenesis rate. NSCs of the mouse adult subependymal niche provide neurons for olfactory circuits and can be found at different depths of quiescence, but very little is known on how their quiescence-to-activation transition is controlled. Here, we identify the atypical cyclin-dependent kinase (CDK) activator RingoA as a regulator of this process. We show that the expression of RingoA increases the levels of CDK activity and facilitates cell cycle entry of a subset of NSCs that divide slowly. Accordingly, RingoA-deficient mice exhibit reduced olfactory neurogenesis with an accumulation of quiescent NSCs. Our results indicate that RingoA plays an important role in setting the threshold of CDK activity required for adult NSCs to exit quiescence and may represent a dormancy regulator in adult mammalian tissues.

This paper presents a threat management methodology for Unmanned Aircraft Systems (UAS) operating in the civil airspace. The work is framed within an Unmanned Traffic Management (UTM) system based on the U-space initiative. We propose a new method that focuses on providing the required automated decision-making during real-time threat management and conflict resolution, which is one of the main gaps in the current U-space ecosystem. Our method is capable of handling all commonplace UTM threats, as well as selecting optimal mitigation actions, trading off efficiency and safety. Our implementation is open-source and fully integrated in a UTM software architecture, implementing U-space services related to emergency management and tactical deconfliction. We demonstrate our methodology through a set of realistic use cases with actual UAS operating in civil airspace. For that, we performed field experiments in an aerodrome with segregated airspace, and we showcased that the methodology is capable of autonomously managing heterogeneous threats in real time.

Plant organ growth results from the combined activity of cell division and cell expansion. The co-ordination of these two processes depends on the interplay between multiple hormones that determine the final organ size. Using the semidominant Hairy Sheath Frayed1 (Hsf1) maize mutant that hypersignals the perception of cytokinin (CK), we show that CK can reduce leaf size and growth rate by decreasing cell division. Linked to CK hypersignaling, the Hsf1 mutant has an increased jasmonic acid (JA) content, a hormone that can inhibit cell division. The treatment of wild-type seedlings with exogenous JA reduces maize leaf size and growth rate, while JA-deficient maize mutants have increased leaf size and growth rate. Expression analysis revealed the increased transcript accumulation of several JA pathway genes in the Hsf1 leaf growth zone. A transient treatment of growing wild-type maize shoots with exogenous CK also induced the expression of JA biosynthetic genes, although this effect was blocked by the co-treatment with cycloheximide. Together, our results suggest that CK can promote JA accumulation, possibly through the increased expression of specific JA pathway genes.

Bathing water quality has become a matter of concern due to health risks. This study sought to assess water quality in bathing areas from the southeastern coast of the Cienfuegos province, Cuba. Certain physical, chemical, and biological parameters (salinity, temperature, pH, oxygen saturation, N-NH4+, N-NO2-, N-NO3-, P-PO43-, COD, BOD5, fats and oils, chlorophyll-a, thermotolerant and total coliforms, and phytoplankton) were measured on five beaches during 2019-2020 in both rainy and dry seasons. A water quality index (WQI) was calculated using the the results of an eutrophication index (EI) and subsequently analyzed. Cluster analysis (CA) and principal components analysis (PCA) were conducted to interpret water quality variations. The WQI values ranged between fair and good, with significant differences between seasons. Multivariate analyses demonstrated the influence of river contributions on water quality indicators based on the results of the CA and the first principal component (PC1) correlated with Sal, DO, total and thermotolerant coliforms, and certain nutrients. PCA also reflected the increase in BOD5 levels during the summer based on PC2, while the PC3 correlated with COD and response parameters (chlorophyll-a and phytoplankton) were linked to the trophic status. The assessment of trophic status showed non-eutrophic conditions. The abundance and diversity of phytoplankton in these beaches was low (128.5 x 103 cells L-1, total mean value), following the normative definitions of the water framework directive. Harmful algal species occurred in low numbers (1.88 x 103 cells L-1, total mean value), but certain species could represent a risk of dermatitis to bathers. The application of different classification schemes allowed for a comprehensive assessment of water quality in this coastal zone, helping to identify the need for monitoring and further ecological study on harmful algae species.

In this work, we have studied structural and magnetic properties of LaFeO3 as a function of the particle size d, from bulk (d >> 1 µm) to nanoscale (d ≈ 30 nm). A large number of twins were observed for large particles that disappear for small particle sizes. This could be related to the softening of the FeO6 distortion as particle size decreases. It was observed that the bulk sample showed spin canting that disappeared for d ~ 125 nm and can be associated with the smoothening of the orthorhombic distortion. On the other hand, for d < 60 nm, the surface/volume ratio became high and, despite the high crystallinity of the nanoparticle, a notable exchange effect bias appeared, originated by two magnetic interactions: spin glass and antiferromagnetism. This exchange bias interaction was originated by the formation of a “magnetic core–shell”: the broken bonds at the surface atoms give place to a spin glass behavior, whereas the inner atoms maintain the antiferromagnetic G-type order. The LaFeO3 bulk material was synthesized by the ceramic method, whereas the LaFeO3 nanoparticles were synthesized by the sol-gel method; the particle size was varied by annealing the samples at different temperatures. The physical properties of the materials have been investigated by XRD, HRTEM, TGA, and AC and DC magnetometry.

Non-standard thermostatistical formalisms derived from generalizations of the Boltzmann–Gibbs entropy have attracted considerable attention recently. Among the various proposals, the one that has been most intensively studied, and most successfully applied to concrete problems in physics and other areas, is the one associated with the Sq non-additive entropies. The Sq-based thermostatistics exhibits a number of peculiar features that distinguish it from other generalizations of the Boltzmann–Gibbs theory. In particular, there is a close connection between the Sq-canonical distributions and the micro-canonical ensemble. The connection, first pointed out in 1994, has been subsequently explored by several researchers, who elaborated this facet of the Sq-thermo-statistics in a number of interesting directions. In the present work, we provide a brief review of some highlights within this line of inquiry, focusing on micro-canonical scenarios leading to Sq-canonical distributions. We consider works on the micro-canonical ensemble, including historical ones, where the Sq-canonical distributions, although present, were not identified as such, and also more resent works by researchers who explicitly investigated the Sq-micro-canonical connection.

This article presents a team of multiple Unmanned Aerial Vehicles (UAVs) to perform cooperative missions for autonomous construction. In particular, the UAVs have to build a wall made of bricks that need to be picked and transported from different locations. First, we propose a novel architecture for multi-robot systems operating in outdoor and unstructured environments, where robustness and reliability play a key role. Then, we describe the design of our aerial platforms and grasping mechanisms to pick, transport and place bricks. The system was particularly developed for the Mohamed Bin Zayed International Robotics Challenge (MBZIRC), where Challenge 2 consisted of building a wall cooperatively with multiple UAVs. However, our approach is more general and extensible to other multi-UAV applications involving physical interaction, like package delivery. We present not only our results in the final stage of MBZIRC, but also our simulations and field experiments throughout the previous months to the competition, where we tuned our system and assessed its performance.

ABSTRACT In this study, we present computational procedures to solve problems for the maximization of production and net income from crops or trees in a randomly generated agroforestry system with limited inputs, based on the Logarithmic Barrier Method. The results obtained showed numerical consistency for viability and optimality of both problems in the agroforestry scenarios tested, as well as promoted conditions to solve the problems with real data.

Chronic inflammation is a major cause of disease. Inflammation resolution is in part directed by the differential stability of mRNAs encoding pro-inflammatory and anti-inflammatory factors. In particular, tristetraprolin (TTP)-directed mRNA deadenylation destabilizes AU-rich element (ARE)-containing mRNAs. However, this mechanism alone cannot explain the variety of mRNA expression kinetics that are required to uncouple degradation of pro-inflammatory mRNAs from the sustained expression of anti-inflammatory mRNAs. Here, we show that the RNA-binding protein CPEB4 acts in an opposing manner to TTP in macrophages: it helps to stabilize anti-inflammatory transcripts harboring cytoplasmic polyadenylation elements (CPEs) and AREs in their 3′-UTRs, and it is required for the resolution of the lipopolysaccharide (LPS)-triggered inflammatory response. Coordination of CPEB4 and TTP activities is sequentially regulated through MAPK signaling. Accordingly, CPEB4 depletion in macrophages impairs inflammation resolution in an LPS-induced sepsis model. We propose that the counterbalancing actions of CPEB4 and TTP, as well as the distribution of CPEs and AREs in their target mRNAs, define transcript-specific decay patterns required for inflammation resolution. Thus, these two opposing mechanisms provide a fine-tuning control of inflammatory transcript destabilization while maintaining the expression of the negative feedback loops required for efficient inflammation resolution; disruption of this balance can lead to disease.

We investigate finite systems of N paired fermions, common in atomic nuclei, for example. These systems exhibit quantum mechanical features akin to those of superconductors. We discover, however, some specific N dependent effects that can not be attained in the thermodynamics limit of ordinary superconductivity. In particular, an important fact is uncovered: there is a strong correlation between the temperature T and the number of fermions N. A certain temperature increase ΔT produces, in thermal quantifiers (such as the entropy), quite different effects if N=4 or N=25. In fact, whether a given temperature value should be regarded as high or low can not be ascertained independent of the N value.

Metabolite profiles of chicken breast extracts and water mobility in breasts were studied using proton nuclear magnetic resonance (1H-NMR) spectroscopy and time-domain NMR (TD-NMR) relaxometry, respectively, using normal breast (NB), and wooden breast (WB) and white striping (WS) myopathies in broilers. One thousand eight hundred sixty broilers were raised to commercial standards, receiving the same diets that were formulated as per the different growth stages. At 49 D of age, 200 animals were slaughtered following routine commercial procedures, and at 4 h postmortem, the whole breast (pectoralis major muscle) was removed and visually inspected by an experienced meat inspector who selected NB (without myopathies) and samples with the presence of WS and WB myopathies. Fifteen breasts (5 each of NB, WS, and WB) were analyzed through TD-NMR relaxometry, and samples of approximately 20 g were taken from each breast and frozen at −80°C for metabolite profiling through 1H-NMR spectroscopy. Multivariate statistical analysis was used to evaluate the effect on water relaxometry and metabolite profile in accordance with the presence and type of myopathy in the breast. 1H-NMR data showed that the metabolite profiles in WS and WB breasts were different from each other and from NB. This pilot study shows that myopathies appear to be related to hypoxia, connective tissue deposition, lower mitochondrial function, and greater oxidative stress compared with NB. The longitudinal and transverse relaxation time of the breasts determined by TD-NMR relaxometry was shorter for NB than that for WS and WB, indicating greater water mobility in breasts affected by myopathies. 1H-NMR spectroscopy can be used to differentiate the metabolism of WS, WB, and NB, and TD-NMR has the potential to be a fast, simple, and noninvasive method to distinguish NB from WB and WS. As a practical application, the metabolomic profile as per the occurrence of breast myopathies may be used for a better understanding of these issues, which opens a gap to mitigate the incidence and severity of WS and WB. In addition, the present study brings an opportunity for the development of a new and objective tool to classify the incidence of breast myopathies through TD-NMR relaxometry.

Se hacen consideraciones sobre la fisiopatología y la terapéutica el enfisema ampolloso en base al estudio de una serie de veintiséis pacientes.

Objective: Current treatment for borderline personality disorder (BPD) involves psychological and pharmacological interventions. However, neuromodulation techniques such as repetitive transcranial magnetic stimulation (rTMS) may positively affect BPD symptomatology. The objective of this study was to evaluate the clinical and neuropsychological effects of rTMS on the dorsomedial prefrontal cortex (DMPFC) in BPD patients. Methods: Fourteen patients with BPD were randomized into two groups (active vs. sham) for 15 sessions of rTMS on the DMPFC. Clinical effects were measured using the Borderline Symptoms List (BSL), Clinical Global Impression Scale for BPD (CGI-BPD), Borderline Evaluation of Severity over Time (BEST), Hamilton Depression Rating Scale (HDRS), Hamilton Anxiety Rating Scale (HARS), and Barratt’s Impulsiveness Scale (BIS). Neuropsychological effects were determined by a Stop-Signal Task (SST), the Wisconsin Card-Sorting Test (WCST), and the Iowa Gambling Test (IGT). Results: Within-group comparison showed significant differences (p < 0.05) in CGI-BPD (total score and six of nine psychopathologic domains), BEST, HDRS, HARS, and IGT scores for active modality. Conclusion: The 5 Hz-DMPFC rTMS technique was well tolerated and lessened the severity of BPD symptomatology, especially abandonment, affective issues, interpersonal relationships, suicidal behavior, anger, and paranoid ideation. Cognitive improvement was seen in decision-making. Additional studies are needed to fully evaluate the effects of rTMS on BPD symptomatology. Clinical Trial Registration: NCT03832777.

Abstract Background Most of our understanding on the social behavior and genomics of bees and other social insects is centered on the Western honey bee, Apis mellifera. The genus Apis, however, is a highly derived branch comprising less than a dozen species, four of which genomically characterized. In contrast, for the equally highly eusocial, yet taxonomically and biologically more diverse Meliponini, a full genome sequence was so far available for a single Melipona species only. We present here the genome sequence of Frieseomelitta varia, a stingless bee that has, as a peculiarity, a completely sterile worker caste. Results The assembly of 243,974,526 high quality Illumina reads resulted in a predicted assembled genome size of 275 Mb composed of 2173 scaffolds. A BUSCO analysis for the 10,526 predicted genes showed that these represent 96.6% of the expected hymenopteran orthologs. We also predicted 169,371 repetitive genomic components, 2083 putative transposable elements, and 1946 genes for non-coding RNAs, largely long non-coding RNAs. The mitochondrial genome comprises 15,144 bp, encoding 13 proteins, 22 tRNAs and 2 rRNAs. We observed considerable rearrangement in the mitochondrial gene order compared to other bees. For an in-depth analysis of genes related to social biology, we manually checked the annotations for 533 automatically predicted gene models, including 127 genes related to reproductive processes, 104 to development, and 174 immunity-related genes. We also performed specific searches for genes containing transcription factor domains and genes related to neurogenesis and chemosensory communication. Conclusions The total genome size for F. varia is similar to the sequenced genomes of other bees. Using specific prediction methods, we identified a large number of repetitive genome components and long non-coding RNAs, which could provide the molecular basis for gene regulatory plasticity, including worker reproduction. The remarkable reshuffling in gene order in the mitochondrial genome suggests that stingless bees may be a hotspot for mtDNA evolution. Hence, while being just the second stingless bee genome sequenced, we expect that subsequent targeting of a selected set of species from this diverse clade of highly eusocial bees will reveal relevant evolutionary signals and trends related to eusociality in these important pollinators.

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is a public health problem lacking an approved pharmacological treatment. Omega-3 fatty acids have shown to reverse NAFLD. Chia is a seed rich in α-linolenic acid (ALA), antioxidants, and fiber; therefore, it could be useful to treat NAFLD. Methods In a single arm experimental design study, the effect of 25 g/day of milled chia was assessed in 25 patients with NAFLD. After two weeks of dietary stabilization (basal condition) and eight weeks of a chia-supplemented isocaloric diet, liver:spleen attenuation index and visceral abdominal fat (VAF) were measured by computed tomography. Lipids, lipoproteins, free fatty acids (FFA), and ALA plasma concentrations were also determined. Results Dietary chia supplementation induced an increase in plasma ALA concentration (75%) and dietary fiber (55%) consumption. After chia supplementation, VAF (9%), body weight (1.4%), total cholesterol (2.5%), non-high density lipoprotein cholesterol (3.2%), and circulating FFA (8%) decreased. Furthermore, NAFLD regressed in 52% of the treated patients (P

Balliella pseudocorticata (Ceramiaceae, Ceramiales) se registra por primera vez para Cuba. Los especímenes fueron recolectados en el litoral arrecifal oriental de la provincia de Cienfuegos, centro-sur de la isla, y fueron identificados por sus características morfológicas distintivas. Recibido: 26-08-2021 Aceptado: 02-11-2021 Publicado: 10-01-2022 Editor: Beatriz Martínez-Daranas

According to the current concordance cosmological model, dark matter (DM) particles are collisionless and produce self-gravitating structures with a central cusp, which, generally, is not observed. The observed density tends to a central plateau or core, explained within the cosmological model through the gravitational feedback of baryons on DM. This mechanism becomes inefficient when decreasing the galaxy’s stellar mass so that in the low-mass regime ( M _⋆ ≪ 10 ^6 M _⊙ ) the energy provided by the baryons is insufficient to modify cusps into cores. Thus, if cores exist in these galaxies they have to reflect departures from the collisionless nature of DM. Measuring the DM mass distribution in these faint galaxies is extremely challenging; however, their stellar mass distribution can be characterized through deep photometry. Here we provide a way of using only the stellar mass distribution to constrain the underlying DM distribution. The so-called Eddington inversion method allows us to discard pairs of stellar distributions and DM potentials requiring (unphysical) negative distribution functions in the phase space. In particular, cored stellar density profiles are incompatible with the Navarro–Frenk–White (NFW) potential expected from collisionless DM if the velocity distribution is isotropic and the system spherically symmetric. Through a case-by-case analysis, we are able to relax these assumptions to consider anisotropic velocity distributions and systems that do not have exact cores. In general, stellar distributions with radially biased orbits are difficult to reconcile with NFW-like potentials, and cores in the baryon distribution tend to require cores in the DM distribution.

Flare frequency distributions represent a key approach to addressing one of the largest problems in solar and stellar physics: determining the mechanism that counterintuitively heats coronae to temperatures that are orders of magnitude hotter than the corresponding photospheres. It is widely accepted that the magnetic field is responsible for the heating, but there are two competing mechanisms that could explain it: nanoflares or Alfvén waves. To date, neither can be directly observed. Nanoflares are, by definition, extremely small, but their aggregate energy release could represent a substantial heating mechanism, presuming they are sufficiently abundant. One way to test this presumption is via the flare frequency distribution, which describes how often flares of various energies occur. If the slope of the power law fitting the flare frequency distribution is above a critical threshold, α = 2 as established in prior literature, then there should be a sufficient abundance of nanoflares to explain coronal heating. We performed >600 case studies of solar flares, made possible by an unprecedented number of data analysts via three semesters of an undergraduate physics laboratory course. This allowed us to include two crucial, but nontrivial, analysis methods: preflare baseline subtraction and computation of the flare energy, which requires determining flare start and stop times. We aggregated the results of these analyses into a statistical study to determine that α = 1.63 ± 0.03. This is below the critical threshold, suggesting that Alfvén waves are an important driver of coronal heating.

The study of nitrogen fixation in sugarcane has a long history that has demonstrated high potential but with substantial variation in results. This 32-month study sought to assess the response of nitrogen fixation associated with sugarcane (Saccharum officinarum L. cvs. ‘Akoki, Honua‘ula, and ‘Ula) to available soil nitrogen. Plants were grown in large pots of perlite along with a fixing and a non-fixing plant control and administered liquid fertigation with varying amounts of isotopically enriched nitrogen. Assessment of nitrogen fixation utilized nitrogen isotope tracing and acetylene reduction assay in the target and control plants. Isotope enrichment and acetylene reduction assay both indicated that nitrogen fixation peaked under low nitrogen application, and declined with higher application rates, with agreement between the two methods. These results suggest that sugarcane engages in a downregulation of nitrogen fixation under high nitrogen availability, potentially explaining the high variation in published experimental results. This suggests that nitrogen management and fertilization strategy can impact the atmospheric inputs of nitrogen in sugarcane cultivation, and the potential to improve nitrogen application efficiency in cropping systems utilizing sugarcane.

Adopting modern gene-editing technologies for trait improvement in agriculture requires important workflow developments, yet these developments are not often discussed. Using tropical crop systems as a case study, we describe a workflow broken down into discrete processes with specific steps and decision points that allow for the practical application of the CRISPR-Cas gene editing platform in a crop of interest. While we present the steps of developing genome-edited plants as sequential, in practice parts can be done in parallel, which are discussed in this perspective. The main processes include 1) understanding the genetic basis of the trait along with having the crop’s genome sequence, 2) testing and optimization of the editing reagents, development of efficient 3) tissue culture and 4) transformation methods, and 5) screening methods to identify edited events with commercial potential. Our goal in this perspective is to help any lab that wishes to implement this powerful, easy-to-use tool in their pipeline, thus aiming to democratize the technology.

9-cis-13,14-dihydroretinoic acid (9CDHRA), acts as an endogenous ligand of the retinoid X receptors (RXRs), and is an active form of a suggested new vitamin, vitamin A5/X. Nutritional-relevance of this pathway as well as its detailed role in vertebrate physiology, remain largely unknown. Since recent GWAS data and experimental studies associated RXR-mediated signaling with depression, we explored here the relevance of RXR and vitamin A5/X-mediated signaling in the control of stress adaptation and depressive-like behaviors in mice. We found that compromised availability of 9CDHRA in Rbp1−/− mice was associated with increased despair in the forced swim and anhedonia in the sucrose preference test. 9CDHRA similarly to synthetic RXR agonist, BMS649, normalized despair behaviors in Rbp1−/− but not Rxrγ−/− mice, supporting involvement of RXR signaling in anti-despair activity of these ligands. Importantly, similarly to BMS649, the 9CDHRA and its nutritional-precursor, 9-cis-13,14-dihydroretinol (vitamin A5/X alcohol), prevented development of depressive-like behaviors in mice exposed to chronic social defeat stress, revealing the beneficial role of RXRs and its endogenous ligand in stress adaptation process. These data point to the need for relevant nutritional, biochemical and pharmacological studies of this signaling pathway in human, both in physiological conditions and in pathologies of stress-related disorders.

Introduction: Dural arteriovenous fistulas are abnormal communications between the arterial and dural sinus vessels or the cortical veins. Multiple dural arteriovenous fistulae have an incidence rate of 6-9%. Their pathophysiology is poorly understood, although there is a consensus on three theories for their formation. The systemic infection caused by SARS-CoV-2 in its severe presentations is associated with a pro-inflammatory state that represents an ideal condition for complications of pre-existing cerebrovascular diseases. Digital subtraction angiography is considered the gold standard to understand the architecture of this lesion. Case Presentation: The patient was a 49-year-old male with a history of multiple head trauma, a 20-year history of tobacco use, tinnitus, and gradual deterioration of higher mental functions. On admission, he presented respiratory distress and was dependent on oxygen. Conclusion: This case presents a bleak picture of the overlap between two devastating diseases as a clear example of the direct and collateral damage of the SARS-CoV-2 pandemic. Coronavirus disease in 2019 does not exclude a previous underlying pathology.

Background One of the challenges has been coping with an increasing need for COVID-19 testing. A COVID-19 screening and testing facility was created. There was a need for increasing throughput of the facility within the existing space and limited resources. Discrete event simulation was used to address this challenge. Methodology A cross-sectional interventional study was done from September 2020 to October 2020. Detailed process mapping with all micro-processes was done. Patient arrival patterns and time taken at each step were measured by two independent observers at random intervals over two weeks. The existing system was simulated and a bottleneck was identified. Two possible alternatives to the problem were simulated and evaluated. Results Scenario 1 showed a maximum throughput of 316. The average milestone times of all the processes after the step of “Preparation of sampling kits” jumped 62%; from 82 to 133 min. Staff state times also showed that staff at this step was stretched and medical lab technicians were underutilized. Scenario 2 simulated the alternative with lesser time spent on sampling kit preparation with a 22.4% increase in throughput, but could have led to impaired quality check. Scenario 3 simulated with increased manpower at the stage of bottleneck with 26.5% increase in throughput and was implemented on-ground. Conclusion Discrete event simulation helped to identify the bottleneck, simulate possible alternative solutions without disturbing the ongoing work, and finally choose the most suitable intervention to increase throughput, without the need for additional space allocation. It therefore helped to optimally utilize resources and get “more from less.”

Several generalizations or extensions of the Boltzmann–Gibbs thermostatistics, based on non-standard entropies, have been the focus of considerable research activity in recent years. Among these, the power-law, non-additive entropies Sq≡k1−∑ipiqq−1(q∈R;S1=SBG≡−k∑ipilnpi) have harvested the largest number of successful applications. The specific structural features of the Sq thermostatistics, therefore, are worthy of close scrutiny. In the present work, we analyze one of these features, according to which the q-logarithm function lnqx≡x1−q−11−q(ln1x=lnx) associated with the Sq entropy is linked, via a duality relation, to the q-exponential function characterizing the maximum-entropy probability distributions. We enquire into which entropic functionals lead to this or similar structures, and investigate the corresponding duality relations.

Within the 2,5-dioxopiperazine-containing natural products generated by “head-to-tail” cyclization of peptides, those derived from tryptophan allow further structural diversification due to the rich chemical reactivity of the indole heterocycle, which can generate tetracyclic fragments of hexahydropyrrolo[2,3-b]indole or pyrrolidinoindoline skeleton fused to the 2,5-dioxopiperazine. Even more complex are the dimeric bispyrrolidinoindoline epi(poly)thiodioxopiperazines (BPI-ETPs), since they feature transannular (poly)sulfide bridges connecting C3 and C6 of their 2,5-dioxopiperazine rings. Homo- and heterodimers composed of diastereomeric epi(poly)thiodioxopiperazines increase the complexity of the family. Furthermore, putative biogenetically generated downstream metabolites with C11 and C11’-hydroxylated cores, as well as deoxygenated and/or oxidized side chain counterparts, have also been described. The isolation of these complex polycyclic tryptophan-derived alkaloids from the classical sources, their structural characterization, the description of the relevant biological activities and putative biogenetic routes, and the synthetic efforts to generate and confirm their structures and also to prepare and further evaluate structurally simple analogs will be reported.

Abstract Introduction Multiple sclerosis (MS) patients of African descent have increased risk for disease progression and may be less responsive to disease-modifying therapy. Methods Patients in the CARE-MS studies received alemtuzumab 12 mg/day [initial alemtuzumab treatment (IAT); baseline: 5 days; 12 months later: 3 days] or subcutaneous interferon beta-1a (SC IFNB-1a) 3 ×/week. Core study outcomes were compared between treatment groups. In the extension study CAMMS03409, SC IFNB-1a-treated patients switched to alemtuzumab [delayed alemtuzumab treatment (DAT)]. Data from IAT and DAT arms were pooled to assess outcomes through 6 years post alemtuzumab initiation; IAT patients had an additional 2 years of follow-up in TOPAZ. Results Of 1200 CARE-MS patients, 43 (4%) were of African descent (35 IAT; 8 DAT) and received alemtuzumab in the 2-year core and/or 6-year extension; 29 (67%) remained on study at the time of analysis (24 IAT patients completed year 8 post alemtuzumab; 5 DAT patients completed year 6 post alemtuzumab). In year 2, annualized relapse rate (ARR; 0.09 versus 0.42), percentage of patients with improved Expanded Disability Status Scale (EDSS; 18% versus 11%), 6-month confirmed disability improvement (CDI; 28% versus 13%), no evidence of disease activity (55% versus 13%), and cumulative brain volume loss (BVL; − 0.55% versus − 1.32%) favored alemtuzumab versus SC IFNB-1a. Alemtuzumab remained efficacious at year 6 (pooled IAT/DAT) and at year 8 (IAT only) post alemtuzumab (ARR: 0.15 and 0.30; improved EDSS: 17% and 25%; CDI: 47% and 55%; BVL: − 1.14% and − 0.70%, respectively). No safety signals were unique to this population. Conclusions Alemtuzumab was efficacious in a small cohort of relapsing-remitting MS patients of African descent over 8 years. Safety was consistent with the overall CARE-MS population, although the small sample size may have prevented the detection of known low-frequency adverse events. ClinicalTrials.gov Registration Numbers CARE-MS I, II, extension, TOPAZ: NCT00530348, NCT00548405, NCT00930553, NCT02255656. Funding Sanofi (Cambridge, MA, USA) and Bayer HealthCare Pharmaceuticals (Leverkusen, Germany).

Mesenchymal cells contribute to tumor angiogenesis by regulating proliferation and migration of endothelial cells. Here, the authors show that mesenchymal stem cells also have the ability to acquire an endothelial phenotype upon TGF-β stimulation via the downstream kinase JNK, and that p38α negatively regulates this process.

Red drupelet reversion (RDR) is a physiological disorder in which blackberry drupelets revert from black to red, losing their commercial value. RDR has been associated with mechanical damage caused by vibrations during transport. The goal of the present study was to construct a portable vibration system to quantify RDR progression in different blackberry cultivars. The system was integrated with an electrical signal generator, a monoaural amplifier, a subwoofer type speaker, and an oscilloscope. This system generates vibration intensities reached during fruit commercial transport (10 Hz and 0.5 g’s). To induce RDR, blackberry clamshells cv. ‘Tupi’ were placed in the portable system and subjected to different vibration times. RDR was observed immediately after fruit was subjected to 5 min vibration. To evaluate RDR progression in different cultivars, blackberry clamshells ‘Ak234′, ‘Am151′, and ‘Tupi’ were subjected to vibration during different times; and analyzed after storage (0 to 5 d). ‘Tupi’ blackberries reverted more rapidly than ‘Am151′ and ‘Ak234′ cultivars, suggesting that ‘Tupi’ was more susceptible to RDR. These results highlight that portable vibration system could be a useful and fast tool to evaluate resistance to RDR in blackberries.

Estableceremos condiciones necesarias y suficientes para que la imagen bajo la función de Gray de un R-código consta-cíclico sea un Fpmcódigo cuasi-cíclico. Estudiamos el anillo de vectores de Witt para obtener una manera de operar las µ-reducciones de las componentes p-ádicas de los elementos de los anillos de Galois de índice de nilpotencia 3, R = GR(p3, m). Analizamos a los anillos de Galois, sus propiedades más relevantes, y en particular la representación p-ádica de sus elementos. Más adelante, examinamos la construcción del anillo de vectores de Witt y sus operaciones, en particular, obtenemos expresiones explícitas para las operaciones de suma y producto de los elementos en el anillo truncado de vectores de Witt de longitud 3, W3(Fpm). Finalmente, utilizamos las operaciones de éstos últimos y un isomorfismo entre GR(p3, m) y W3(Fpm) para operar las µ-reducciones antes descritas.

A significant challenge in mineral raw materials comminution is the improvement of process energy efficiency. Conventional comminution techniques, although globally used, are far from being considered power-efficient. The use of high-voltage electric pulses in comminution is a concept that is worthy of study; despite its lack of industrial-scale validation after several decades of lab-scale research, it seems promising as a pretreatment leading to energy savings. In this article, the Cumulative Kinetic Model methodology is adapted to model the comminution effect in an electrofragmentation device, and study a dunite rock ore. The results show that product particle size distribution (PSD) can be predicted with reasonable accuracy using the proposed model.

Cranial neural crest (NC) contributes to the developing vertebrate eye. By multidimensional, quantitative imaging, we traced the origin of the ocular NC cells to two distinct NC populations that differ in the maintenance of sox10 expression, Wnt signalling, origin, route, mode and destination of migration. The first NC population migrates to the proximal and the second NC cell group populates the distal (anterior) part of the eye. By analysing zebrafish pax6a/b compound mutants presenting anterior segment dysgenesis, we demonstrate that Pax6a/b guide the two NC populations to distinct proximodistal locations. We further provide evidence that the lens whose formation is pax6a/b-dependent and lens-derived TGFβ signals contribute to the building of the anterior segment. Taken together, our results reveal multiple roles of Pax6a/b in the control of NC cells during development of the anterior segment.

Objective: Despite the known benefits of integrated primary care and behavioral health services, integrated behavioral health services have not been readily used in medical clinics in interior Alaska. With minimal resources, we recently developed an integrated primary care–behavioral health program in a medical clinic in interior Alaska to meet clinic and community needs. The objective of this study was to explore initial program outcomes and determine the feasibility of program development and implementation. Methods: We initially conducted a needs assessment for integrating behavioral health services into primary care. Program development was informed by specific clinic needs. Following program implementation, initial program outcomes were tracked with use of data from the electronic health record and patient and provider use and satisfaction surveys. The level of integration of primary care and behavioral health services was evaluated with the Practice Integration Profile. Results: A total of 188 patients were seen by behavioral health consultants during the initial pilot phase, including 44.0% referred for mental health symptoms, 33.1% referred for physical health issues, and 22.3% referred for both mental and physical health issues. The initial program outcomes indicate modest clinical improvement (measured by the nine-item Patient Health Questionnaire) as well as patient and provider satisfaction with the model, and a moderate level of practice integration. Conclusion: On the basis of the initial findings, it appears that our integrated primary care–behavioral health program has the potential to serve an important role in addressing the behavioral health needs of the local population. Our implementation procedure and initial program outcomes suggest that such models are feasible in rural and small-scale settings with minimal overhead costs.

Erythropoietin (EPO) stimulates erythropoiesis and is commonly used to treat anemia. Here Hu et al. find that P38α/JNK signaling restrains erythropoiesis independently of EPO by regulating epigenetic silencing of the proapoptotic protein Bim, and thus identify putative targets for the treatment of anemic disorders resistant to EPO.

Abstract The protein kinase p38α plays a key role in cell homeostasis, and p38α signaling in intestinal epithelial cells protects against colitis‐induced tumorigenesis. However, little is known on the contribution of p38α signaling in intestinal stromal cells. Here, we show that myeloid cell‐specific downregulation of p38α protects mice against inflammation‐associated colon tumorigenesis. The reduced tumorigenesis correlates with impaired detection in the colon of crucial chemokines for immune cell recruitment. We identify insulin‐like growth factor‐1 (IGF‐1) as a novel mediator of the p38α pathway in macrophages. Moreover, using genetic and pharmacological approaches, we confirm the implication of IGF‐1 produced by myeloid cells in colon inflammation and tumorigenesis. We also show a correlation between IGF‐1 pathway activation and the infiltration of myeloid cells with active p38α in colon samples from patients with ulcerative colitis or colon cancer. Altogether, our results uncover an important role for myeloid IGF‐1 downstream of p38α in colitis‐associated tumorigenesis and suggest the interest in evaluating IGF‐1 therapies for inflammation‐associated intestinal diseases, taking into consideration IGF‐1 signaling and immune cell infiltration in patient biopsies.

Summary: Mammary stem and progenitor cells are essential for mammary gland homeostasis and are also candidates for cells of origin of mammary tumors. Here, we have investigated the function of the protein kinase p38α in the mammary gland using mice that delete this protein in the luminal epithelial cells. We show that p38α regulates the fate of luminal progenitor cells through modulation of the transcription factor RUNX1, an important controller of the estrogen receptor-positive cell lineage. We also provide evidence that the regulation of RUNX1 by p38α probably involves the kinase MSK1, which phosphorylates histone H3 at the RUNX1 promoter. Moreover, using a mouse model for breast cancer initiated by luminal cells, we show that p38α downregulation in mammary epithelial cells reduces tumor burden, which correlates with decreased numbers of tumor-initiating cells. Collectively, our results define a key role for p38α in luminal progenitor cell fate that affects mammary tumor formation.

Background: The efficacy of implantable cardioverter-defibrillators (ICD) for primary prevention of sudden cardiac death (SCD) has not been studied in patients with end-stage renal disease (ESRD) and left ventricular dysfunction. We sought to identify predictors of long-term survival among ICD recipients with and without ESRD. Methods: Patients implanted with an ICD at our institution from January 2006 to March 2014 were retrospectively identified. Clinical and demographic characteristics were collected. Patients were stratified by the presence of ESRD at the time of ICD implant. Mortality data were collected from the Social Security Death Index (SSDI). Results: A total of 3453 patients received an ICD at our institution in the pre-specified time period, 184 (5.3%) of whom had ESRD. In general, ESRD patients were sicker and had more comorbidities. Kaplan Meier survival curve showed that ESRD patients had worse survival as compared with non-dialysis patients (p

Taxanes are a mainstay of treatment for breast cancer, but resistance often develops followed by metastatic disease and mortality. Aiming to reveal the mechanisms underlying taxane resistance, we used breast cancer patient-derived orthoxenografts (PDX). Mimicking clinical behavior, triple-negative breast tumors (TNBCs) from PDX models were more sensitive to docetaxel than luminal tumors, but they progressively acquired resistance upon continuous drug administration. Mechanistically, we found that a CD49f+ chemoresistant population with tumor-initiating ability is present in sensitive tumors and expands during the acquisition of drug resistance. In the absence of the drug, the resistant CD49f+ population shrinks and taxane sensitivity is restored. We describe a transcriptional signature of resistance, predictive of recurrent disease after chemotherapy in TNBC. Together, these findings identify a CD49f+ population enriched in tumor-initiating ability and chemoresistance properties and evidence a drug holiday effect on the acquired resistance to docetaxel in triple-negative breast cancer.