Biodiversity patterns of the coral reef cryptobiota around the Arabian Peninsula.

The Arabian Peninsula accounts for approximately 6% of the world's coral reefs. Some thrive in extreme environments of temperature and salinity. Using 51 Autonomous Reef Monitoring Structure (ARMS), a standardized non-destructive monitoring device, we investigated the spatial patterns of coral reef cryptobenthic diversity in four ecoregions around the Arabian Peninsula and analyzed how geographical and/or environmental drivers shape those patterns. The mitochondrial cytochrome c oxidase subunit I (COI) gene was used to identify Amplicon Sequence Variants and assign taxonomy of the cryptobenthic organisms collected from the sessile and mobile fractions of each ARMS. Cryptobenthic communities sampled from the two ecoregions in the Red Sea showed to be more diverse than those inhabiting the Arabian (Persian) Gulf and the Gulf of Oman. Geographic distance revealed a stronger relationship with beta diversity in the Mantel partial correlation than environmental distance. However, the two mobile fractions (106-500 µm and 500-2000 µm) also had a significant correlation between environmental distance and beta diversity. In our study, dispersal limitations explained the beta diversity patterns in the selected reefs, supporting the neutral theory of ecology. Still, increasing differences in environmental variables (environmental filtering) also had an effect on the distribution patterns of assemblages inhabiting reefs within short geographic distances. The influence of geographical distance in the cryptofauna assemblages makes these relevant, yet usually ignored, communities in reef functioning vulnerable to large scale coastal development and should be considered in ecosystem management of such projects.

Photonic Molecule Approach to Multiorbital Topology.

The concepts of topology provide a powerful tool to tailor the propagation and localization of the waves. While electrons have only two available spin states, engineered degeneracies of photonic modes provide novel opportunities resembling spin degrees of freedom in condensed matter. Here, we tailor such degeneracies for the array of femtosecond laser written waveguides in the optical range exploiting the idea of photonic molecules: clusters of strongly coupled waveguides. In our experiments, we observe unconventional topological modes protected by the Z3 invariant arising due to the interplay of interorbital coupling and geometric dimerization mechanism. We track multiple topological transitions in the system with the change in the lattice spacings and excitation wavelength. This strategy opens an avenue for designing novel types of photonic topological phases and states.

Responses of the coral reef cryptobiome to environmental gradients in the Red Sea.

An essential component of the coral reef animal diversity is the species hidden in crevices within the reef matrix, referred to as the cryptobiome. These organisms play an important role in nutrient cycling and provide an abundant food source for higher trophic levels, yet they have been largely overlooked. Here, we analyzed the distribution patterns of the mobile cryptobiome (>2000 µm) along the latitudinal gradient of the Saudi Arabian coast of the Red Sea. Analysis was conducted based on 54 Autonomous Reef Monitoring Structures. We retrieved a total of 5273 organisms, from which 2583 DNA sequences from the mitochondrially encoded cytochrome c oxidase I were generated through sanger sequencing. We found that the cryptobiome community is variable over short geographical distances within the basin. Regression tree models identified sea surface temperature (SST), percentage cover of hard coral and turf algae as determinant for the number of operational taxonomic units present per Autonomous Reef Monitoring Structures (ARMS). Our results also show that the community structure of the cryptobiome is associated with the energy available (measured as photosynthetic active radiation), sea surface temperature, and nearby reef habitat characteristics (namely hard corals, turf and macroalgae). Given that temperature and reef benthic characteristics affect the cryptobiome, current scenarios of intensive climate change are likely to modify this fundamental biological component of coral reef functioning. However, the trajectory of change is unknow and can be site specific, as for example, diversity is expected to increase above SST of 28.5°C, and with decreasing hard coral and turf cover. This study provides a baseline of the cryptobenthic community prior to major coastal developments in the Red Sea to be used for future biodiversity studies and monitoring projects. It can also contribute to better understand patterns of reef biodiversity in a period where Marine Protected Areas are being discussed in the region.

Benzopyran hydrazones with dual PPARα/γ or PPARα/δ agonism and an anti-inflammatory effect on human THP-1 macrophages.

Peroxisome proliferator-activated receptors (PPARs) play a major role in regulating inflammatory processes, and dual or pan-PPAR agonists with PPARγ partial activation have been recognised to be useful to manage both metabolic syndrome and metabolic dysfunction-associated fatty liver disease (MAFLD). Previous works have demonstrated the capacity of 2-prenylated benzopyrans as PPAR ligands. Herein, we have replaced the isoprenoid bond by hydrazone, a highly attractive functional group in medicinal chemistry. In an attempt to discover novel and safety PPAR activators, we efficiently prepared benzopyran hydrazone/hydrazine derivatives containing benzothiazole (series 1) or 5-chloro-3-(trifluoromethyl)-2-pyridine moiety (series 2) with a 3- or 7-carbon side chain at the 2-position of the benzopyran nucleus. Benzopyran hydrazones 4 and 5 showed dual hPPARα/γ agonism, while hydrazone 14 exerted dual hPPARα/δ agonism. These three hydrazones greatly attenuated inflammatory markers such as IL-6 and MCP-1 on the THP-1 macrophages via NF-κB activation. Therefore, we have discovered novel hits (4, 5 and 14), containing a hydrazone framework with dual PPARα/γ or PPARα/δ partial agonism, depending on the length of the side chain. Benzopyran hydrazones emerge as potential lead compounds which could be useful for treating metabolic diseases.

Synthesis of 2-aminopropyl benzopyran derivatives as potential agents against triple-negative breast cancer.

Synthesis of three series of 2-aminopropyl derivatives containing a benzopyran nucleus was performed to evaluate their performance against triple-negative breast cancer cell lines (MDA-MB-231 and MDA-MB-436) and normal breast epithelial cells (MCF10A). For the three series, the cytotoxic activity was as follows: N-methylated derivatives (tertiary amines) 5b, 6b, and 7b > secondary amine benzopyrans 5, 6, and 7 > quaternary amine salts 5c, 6c, and 7c > free phenolic derivatives 5a, 6a, and 7a. The structure-activity relationship showed the importance of the presence of an amine group and a p-fluorobenzyloxy substituent in the chromanol ring (IC50 values from 1.5 µM to 58.4 µM). In addition, 5a, 5b, 6a, and 7b displayed slight selectivity towards tumor cells. Compounds 5, 5a, 5b, 6, 6a, 6c, 7, and 7b showed apoptotic/necrotic effects due to, at least in part, an increase in reactive oxygen species generation, whereas 5b, 5c, 6b, 7a, and 7c caused cell cycle arrest in the G1 phase. Further cell-based mechanistic studies revealed that 5a, 6a, and 7b, which were the most promising compounds, downregulated the expression of Bcl-2, while 5b downregulated the expression of cyclins CCND1 and CCND2. Therefore, 2-aminopropyl benzopyran derivatives emerge as new hits and potential leads for developing useful agents against breast cancer.

New protocol for rapid cassava multiplication in field conditions: a perspective on speed breeding.

Despite the economic and social importance, high-yielding cassava cultivars are only released after extensive research, mainly due to the low multiplication rate. This study aimed to assess the impact of using smaller-sized seed cuttings treated with agrochemicals (8MP) compared to the conventional planting size (16 cm) on genetic parameters, agronomic performance, and the ranking of cassava clones based on yield and growth attributes. The evaluation was carried out in clonal evaluation trial (CET), preliminary yield trial (PYT), and uniform yield trials (UYT). Additionally, a new selection scheme for cassava breeding programs was proposed. A total of 169 clones were evaluated, including 154 improved clones at different stages of selection and 15 local varieties used as checks. Field trials were conducted using both sizes of propagative material (8MP and 16 cm) in each phase of the breeding program. The data were analyzed using mixed models, considering the random effects of genotype and genotype-environment interaction (G×E) to determine variances and heritabilities. Bland-Altman concordance and correlation analysis of selection indices were employed to examine the consistency in the ranking of cassava clones using different seed cutting sizes. The distribution of variance components, heritabilities, means, and range of the 8MP and 16 cm trials in different phases of the cassava breeding program exhibited remarkable similarity, thereby enabling a comparative assessment of similar genetic effects. With a selection intensity of 30%, the concordance in clone ranking was 0.41, 0.57, and 0.85 in CET, PYT, and UYT trials, respectively, when comparing the selection based on 8MP and 16 cm trials. It is worth noting that the ranking of the top 15% remained largely unchanged. Based on the findings, proposed changes in the cassava selection scheme involve increasing the number of trials starting from the CET phase, early incorporation of G×E interaction, elimination of the PYT trial, reduction of the breeding cycle from 5 to 3 years, and a decrease in the time required for variety development from 11 to 9 years. These modifications are expected to lead to cost reduction and enhance the effectiveness of cassava breeding programs.

Luring Triatomines (Hemiptera: Reduviidae) into a Trap: Aliphatic and Aromatic Aldehydes as Attractants of Triatoma infestans.

To assess the attracting capacity of aliphatic and aromatic aldehydes to Triatoma infestans, the Chagas disease vector, laboratory tests were conducted using individual compounds and mixtures to evaluate their potential use in baited traps for intradomicile population dynamics analysis. Commercial samples of hexanal, nonanal, and benzaldehyde were used at 95% purity. The experiments were performed at 25°C and 65% relative humidity using two procedures: a glass arena with filter papers impregnated with 1, 5, and 10 µL of the tested compounds and a double-choice olfactometer. Attraction was scored positively if the insect remained more than 30 seconds on one of the surfaces. The results of the study showed that hexanal was attractive to females at higher concentrations (5-10 µL; P < 0.0001), and IV instar nymphs were only attracted at the highest concentration (10 µL; P < 0.01). Nonanal was attractive to IV instar nymphs at 1 and 5 µL (P < 0.0001), whereas males and females were more attracted at 1 µL (P < 0.01 and P < 0.05, respectively). Benzaldehyde showed significant differences with respect to controls, attracting females at low concentrations (1 µL; P < 0.0001) and IV instar nymphs at 5 and 10 µL (P < 0.0001 and P < 0.001, respectively). In the olfactometer, the 60:40 hexanal/nonanal mixture was the most effective. In conclusion, this study demonstrated that the aliphatic and aromatic aldehydes studied here, both individually and in mixtures, could be used as effective attractants for T. infestans in intradomicile-baited traps. These results suggest that mixtures of these compounds could be implemented in field trials for Chagas disease surveillance.

Development and validation of a hybrid immunoaffinity LC-MS/MS assay for quantitation of total antibody (TAb) from an antibody drug conjugate (ADC) PYX-201 in human plasma.

A hybrid immunoaffinity LC-MS/MS assay was developed and validated for the quantitation of total antibody (TAb) from an antibody drug conjugate (ADC) PYX-201 in human plasma. PYX-201 was proteolyzed using trypsin, and a characteristic peptide fragment PYX-201 P1 with ten amino acids IPPTFGQGTK from the complementarity-determining regions (CDRs) was used as a surrogate for the quantitation of the TAb from PYX-201. Stable isotope labelled (SIL) peptide I(13C6, 15N)PPTFG(13C9, 15N)QGTK was used as the internal standard (IS). We performed chromatographic analysis using a Waters Acquity BEH Phenyl column (2.1 mm × 50 mm, 1.7 µm). Quantification of PYX-201 TAb was carried out on a Sciex triple quadrupole mass spectrometer API 6500 using multiple reaction monitoring (MRM) mode with positive electrospray ionization. To validate PYX-201 TAb, a concentration range of 0.0500 µg/mL to 20.0 µg/mL was used, yielding a correlation coefficient (r) of ≥ 0.9947. For intra-assay measurements, the percent relative error (%RE) ranged from -23.2% to 1.0%, with a coefficient of variation (%CV) of ≤ 14.2%. In terms of inter-assay measurements, the %RE was between -10.5% and -5.7%, with a %CV of ≤ 12.7%. The average recovery of the analyte was determined to be 81.4%, while the average recovery of the internal standard (IS) was 97.2%. Furthermore, PYX-201 TAb demonstrated stability in human plasma and human whole blood under various tested conditions. This assay has been successfully applied to human sample analysis to support a clinical study.

Anti-inflammatory effects and improved metabolic derangements in ob/ob mice by a newly synthesized prenylated benzopyran with pan-PPAR activity.

BACKGROUND AND PURPOSE: Selective peroxisome proliferator-activated receptors (PPARs) are widely used to treat metabolic complications; however, the limited effect of PPARα agonists on glucose metabolism and the adverse effects associated with selective PPARγ activators have stimulated the development of novel pan-PPAR agonists to treat metabolic disorders. Here, we synthesized a new prenylated benzopyran (BP-2) and evaluated its PPAR-activating properties, anti-inflammatory effects and impact on metabolic derangements. EXPERIMENTAL APPROACH: BP-2 was used in transactivation assays to evaluate its agonism to PPARα, PPARß/δ and PPARγ. A parallel-plate flow chamber was employed to investigate its effect on TNFα-induced leukocyte-endothelium interactions. Flow cytometry and immunofluorescence were used to determine its effects on the expression of endothelial cell adhesion molecules (CAMs) and chemokines and p38-MAPK/NF-κB activation. PPARs/RXRα interactions were determined using a gene silencing approach. Analysis of its impact on metabolic abnormalities and inflammation was performed in ob/ob mice. KEY RESULTS: BP-2 displayed strong PPARα activity, with moderate and weak activity against PPARß/δ and PPARγ, respectively. In vitro, BP-2 reduced TNFα-induced endothelial ICAM-1, VCAM-1 and fractalkine/CX3CL1 expression, suppressed mononuclear cell arrest via PPARß/δ-RXRα interactions and decreased p38-MAPK/NF-κB activation. In vivo, BP-2 improved the circulating levels of glucose and triglycerides in ob/ob mice, suppressed T-lymphocyte/macrophage infiltration and proinflammatory markers in the liver and white adipose tissue, but increased the expression of the M2-like macrophage marker CD206. CONCLUSION AND IMPLICATIONS: BP-2 emerges as a novel pan-PPAR lead candidate to normalize glycemia/triglyceridemia and minimize inflammation in metabolic disorders, likely preventing the development of further cardiovascular complications.

Multiplex Hybrid Antigen-Capture LC-MRM Quantification in Sera and Nasal Lining Fluid of AZD7442, a SARS-CoV-2-Targeting Antibody Combination.

AZD7442 (tixagevimab [AZD8895]/cilgavimab [AZD1061]) is a monoclonal antibody (mAb) combination in development for the prevention and treatment of coronavirus disease 2019. Traditionally, bioanalysis of mAbs is performed using ligand binding assays (LBAs), which offer sensitivity, robustness, and ease of implementation. However, LBAs frequently require generation of critical reagents that typically take several months. Instead, we developed a highly sensitive (5 ng/mL limit of quantification) method using a hybrid LBA-liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) approach for quantification of the two codosed antibodies in serum and nasal lining fluid (NLF), a rare matrix. The method was optimized by careful selection of multiple reaction monitoring, capture reagents, magnetic beads, chromatographic conditions, evaluations of selectivity, and matrix effect. The final assay used viral spike protein receptor-binding domain as capture reagent and signature proteotypic peptides from the complementarity-determining region of each mAb for detection. In contrast to other methods of similar/superior sensitivity, our approach did not require multidimensional separations and can be operated in an analytical flow regime, ensuring high throughput and robustness required for clinical analysis at scale. The sensitivity of this method significantly exceeds typical sensitivity of ∼100 ng/mL for analytical flow 1D LBA-LC-MS/MS methods for large macromolecules, such as antibodies. Furthermore, infection and vaccination status did not impact method performance, ensuring method robustness and applicability to a broad patient population. This report demonstrated the general applicability of the hybrid LBA-LC-MS/MS approach to platform quantification of antibodies with high sensitivity and reproducibility, with specialized extension to matrices of increasing interest, such as NLF.

Image-based phenotyping of cassava roots for diversity studies and carotenoids prediction.

Phenotyping to quantify the total carotenoids content (TCC) is sensitive, time-consuming, tedious, and costly. The development of high-throughput phenotyping tools is essential for screening hundreds of cassava genotypes in a short period of time in the biofortification program. This study aimed to (i) use digital images to extract information on the pulp color of cassava roots and estimate correlations with TCC, and (ii) select predictive models for TCC using colorimetric indices. Red, green and blue images were captured in root samples from 228 biofortified genotypes and the difference in color was analyzed using L*, a*, b*, hue and chroma indices from the International Commission on Illumination (CIELAB) color system and lightness. Colorimetric data were used for principal component analysis (PCA), correlation and for developing prediction models for TCC based on regression and machine learning. A high positive correlation between TCC and the variables b* (r = 0.90) and chroma (r = 0.89) was identified, while the other correlations were median and negative, and the L* parameter did not present a significant correlation with TCC. In general, the accuracy of most prediction models (with all variables and only the most important ones) was high (R2 ranging from 0.81 to 0.94). However, the artificial neural network prediction model presented the best predictive ability (R2 = 0.94), associated with the smallest error in the TCC estimates (root-mean-square error of 0.24). The structure of the studied population revealed five groups and high genetic variability based on PCA regarding colorimetric indices and TCC. Our results demonstrated that the use of data obtained from digital image analysis is an economical, fast, and effective alternative for the development of TCC phenotyping tools in cassava roots with high predictive ability.

Generalized tympanism in a horse and its possible association with Sarcina-like microorganism: A case report.

Background: Sarcina spp. is a Gram-positive, coccoid microorganism that forms tetrads or octets, and is observed with a characteristic "bundle" arrangement. The most recognized species are Sarcina ventriculi and Sarcina maxima. It has been described as part of the normal microbiota in horses and cats, but it has also been linked to abomasal bloat in goats, lambs, and calves, although its causality has not been proven yet. Case Description: This work presents the case of a 3-months-old female horse that died of generalized tympanism. Macroscopic findings showed mild cyanosis and abundant gas in the lumen of the stomach, and small and large bowel. Microscopically, high numbers of Gram-positive microorganisms compatible with Sarcina spp. in the gastric lumen and on the surface of the small and large bowel were observed, along with mild inflammation. Conclusion: The severe tympanism was the only relevant lesion observed and could explain the death of the animal. Although it is not possible to determine a relationship between these lesions and Sarcina spp., it is interesting to highlight that the high amount of these bacteria could be associated with gas production and tympanism. It is important to continue investigating the role of Sarcina spp. in horses, and its possible link with tympanism.

Synthesis and biological studies of "Polycerasoidol" and "trans-δ-Tocotrienolic acid" derivatives as PPARα and/or PPARγ agonists.

2-Prenylated benzopyrans represent a class of natural and synthetic compounds showing a wide range of significant activities. Polycerasoidol is a natural prenylated benzopyran isolated from the stem bark of Polyalthia cerasoides (Annonaceae) that exhibits dual PPARα/γ agonism and an anti-inflammatory effect by inhibiting mononuclear leukocyte adhesion to the dysfunctional endothelium. Herein, we report the synthesis of three new series of prenylated benzopyrans containing one (series 1), two (series 2, "polycerasoidol" analogs) and three (series 3, "trans-δ-tocotrienolic acid" analogs) isoprenoid units in the hydrocarbon side chain at the 2-position of the chroman-6-ol (6-hydroxy-dihydrobenzopyran) scaffold. Isoprenoid moieties were introduced through a Grignard reaction sequence, followed by Johnson-Claisen rearrangement and subsequent Wittig olefination. hPPAR transactivation activity and the structure activity relationships (SAR) of eleven novel synthesized 2-prenylated benzopyrans were explored. PPAR transactivation activity demonstrated that the seven-carbon side chain analogs (series 1) displayed selectivity for hPPARα, while the nine-carbon side chain analogs (polycerasoidol analogs, series 2) did so for hPPARγ. The side chain elongation to 11 or 13 carbons (series 3) resulted in weak dual PPARα/γ activation. Therefore, 2-prenylated benzopyrans of seven- and nine-carbon side chain (polycerasoidol analogs) are good lead compounds for developing useful candidates to prevent cardiovascular diseases associated with metabolic disorders.

Diagnóstico y tratamiento multidisciplinario de melanoma temprano y localmente avanzado. Consenso de expertos. Asociación Colombiana de Hematología y Oncología (ACHO) / Diagnosis and multidisciplinary treatment of early-stage and locally advanced melanoma: Expert consensus, Colombian Association of Hemato-Oncology (ACHO)

Resumen Introducción: El melanoma ocasiona el 75% de las muertes por cáncer de piel. Según GLOBOCAN, en 2018 se presentaron 287.723 casos nuevos de melanoma, con una mortalidad de 60.712 casos, que equivale al 20% del total de los casos incidentes. Las alternativas para el tratamiento del melanoma se fundamentan en la estatificación de la enfermedad, y en las características moleculares de la enfermedad. Objetivo: Consensuar, por común acuerdo de expertos, sugerencias para el diagnóstico y manejo de melanoma temprano basadas en la evidencia y ajustadas al contexto colombiano. Métodos: Se llevó a cabo un consenso de expertos multidisciplinario, constituido por 19 oncólogos clínicos, 2 cirujanos de mama y tejidos blandos, 2 dermatólogos, 2 patólogos y 2 radioterapeutas, miembros activos de la Asociación Colombiana de Hemato Oncología (ACHO). Este consenso se realizó en 4 etapas: 1. Estructuración de 29 preguntas, que se calificaron de 1 a 9. 2. Reenvío de las preguntas no consensuadas. 3. Análisis y discusión de las respuestas. 4. Las respuestas no consensuadas se llevaron a un consenso nominal. Resultados: Se discutieron 29 preguntas relacionadas con el diagnóstico y tratamiento de melanoma temprano, se construyeron sugerencias basadas en evidencia utilizada por los expertos y en guías de manejo de oncología reconocidas internacionalmente, adaptadas al contexto y realidad colombianos. Conclusiones: Se presentan sugerencias multidisciplinarias para el diagnóstico y tratamiento de melanoma temprano, las cuales debe considerarse para orientar la toma de decisiones y homogenizar la práctica clínica de acuerdo al contexto colombiano y a las características propias del sistema de salud del país. Este es un documento académico y no regulatorio.

Abstract Introduction: Melanoma causes 75% of deaths from skin cancer. In 2018, according to GLOBOCAN, 287,723 new melanoma cases were registered, with a mortality of 60,712 cases, which is equivalent to 20% of all incident cases. Alternatives for the treatment of melanoma are based on disease staging and the molecular characteristics of the disease. Objective: To establish a consensus by common agreement of experts and construct suggestions for the diagnosis and management of early-stage melanoma based on evidence and adjusted to the Colombian context. Methods: A multidisciplinary expert consensus was established, wth the participation of 19 clinical oncologists, 2 soft tissue surgeons, 2 dermatologists, 2 pathologists, and 2 radiotherapists, active members of the Colombian Association of Hemato-Oncology (ACHO). This consensus was carried out in four stages: 1) Structuring of 29 questions, which were scored from 1 to 9; 2) Resubmission of non-consensual questions; 3) Analysis and discussion of responses; and 4) Validation of non-consensual responses by nominal consensus. Results: Twenty-nine questions related to the diagnosis and treatment of early-stage melanoma were discussed in order to construct suggestions based on evidence proven by experts, as well as on internationally recognized oncology management guidelines adapted to the Colombian context and reality. Conclusions: Multidisciplinary suggestions are offered for the diagnosis and treatment of early-stage melanoma, which should be considered in order to guide decision-making and homogenize clinical practice according to the Colombian context and the characteristics of the Colombian health care system. This is an academic and non-regulatory document.

Synthesis of 2-Prenylated Alkoxylated Benzopyrans by Horner-Wadsworth-Emmons Olefination with PPARα/γ Agonist Activity.

We have synthesized series of 2-prenylated benzopyrans as analogues of the natural polycerasoidol, a dual PPARα/γ agonist with anti-inflammatory effects. The prenylated side chain consists of five or nine carbons with an α-alkoxy-α,ß-unsaturated ester moiety. Prenylation was introduced via the Grignard reaction, followed by Johnson-Claisen rearrangement, and the α-alkoxy-α,ß-unsaturated ester moiety was introduced by the Horner-Wadsworth-Emmons reaction. Synthetic derivatives showed high efficacy to activate both hPPARα and hPPARγ as dual PPARα/γ agonists. These prenylated benzopyrans emerge as lead compounds potentially useful for preventing cardiometabolic diseases.

Strain induced localization to delocalization transition on a Lieb photonic ribbon lattice.

Ribbon lattices are kind of transition systems in between one and two dimensions, and their study is crucial to understand the origin of different emerging properties. In this work, we study a Lieb ribbon lattice and the localization-delocalization transition occurring due to a reduction of lattice distances (compression) and the corresponding flat band deformation. We observe how above a critical compression ratio the energy spreads out and propagates freely across the lattice, therefore transforming the system from being a kind of insulator into a conductor. We implement an experiment on a photonic platform and show an excellent agreement with the predicted phenomenology. Our findings suggest and prove experimentally the use of compression or mechanical deformation of lattices to switch the transport properties of a given system.

Regional heterogeneity of astrocyte morphogenesis dictated by the formin protein, Daam2, modifies circuit function.

Astrocytes display extraordinary morphological complexity that is essential to support brain circuit development and function. Formin proteins are key regulators of the cytoskeleton; however, their role in astrocyte morphogenesis across diverse brain regions and neural circuits is unknown. Here, we show that loss of the formin protein Daam2 in astrocytes increases morphological complexity in the cortex and olfactory bulb, but elicits opposing effects on astrocytic calcium dynamics. These differential physiological effects result in increased excitatory synaptic activity in the cortex and increased inhibitory synaptic activity in the olfactory bulb, leading to altered olfactory behaviors. Proteomic profiling and immunoprecipitation experiments identify Slc4a4 as a binding partner of Daam2 in the cortex, and combined deletion of Daam2 and Slc4a4 restores the morphological alterations seen in Daam2 mutants. Our results reveal new mechanisms regulating astrocyte morphology and show that congruent changes in astrocyte morphology can differentially influence circuit function.

Antimicrobial Activity, in silico Molecular Docking, ADMET and DFT Analysis of Secondary Metabolites from Roots of Three Ethiopian Medicinal Plants.

BACKGROUND: Uvaria scheffleri (Annonaceae), Clematis burgensis (Ranunculaceae), and Euphorbia schimperiana (Euphorbiaceae) are medicinal plants traditionally used to treat cough, tuberculosis, asthma, sore throat and skin infections. METHODS: Silica gel column chromatographic separation was used to isolate compounds. Crude extract and isolated compounds were evaluated for antimicrobial activity against Staphylococcus aureus, Escherichia coli, and Candida albicans via the broth dilution method. Docking studies were performed with E. coli DNA-Gyrase B and human DNA topoisomerase IIα by using AutoDock Vina. ADMET were predicted by SwissADME, PreADMET, and OSIRIS Property predictions. The optimized structures and molecular electrostatic potential surface of the isolated compounds were predicted by DFT analysis using B3LYP/6-31G basis levels. RESULTS: Silica gel column chromatographic separation afforded five compounds 1-5 of which N-methyl-2,3-bis(2-hydroxybenzyl)-1Н-indol (1) is reported herein for the first time, along with known C-benzylated dihydrochalcone uvaretin (2), bis(2-ethylheptyl) phthalate (3), lupeol (4) and suberosin derivative (5). Dichloromethane roots extract of U. scheffleri showed potent antibacterial activity against S. aureus (MIC = 6.25 µg/mL) compared to gentamicin (MIC=5 µg/mL). In silico, molecular docking analysis of compounds (1and 3-5) showed strong interaction with E. coli DNA gyrase B with a binding energy value ranging from -6.9 to -6.0 kcal/mol compared to ciprofloxacin -7.2 kcal/mol, whereas analysis against human topoisomerase IIα showed binding energy value ranging from -5.9 to -5.3 kcal/mol compared to vosaroxin (-6.2 kcal/mol). CONCLUSION: The results obtained suggest that N-methyl-2,3-bis(2-hydroxybenzyl)-1Н-indol (1) and coumarin (5) are potential topoisomerase II α inhibitors and might be used as anticancer agents. The ADMET studies showed the highest drug-likeness properties for studied compounds other than bis(2-ethylheptyl) phthalate (3). DFT calculations suggested that studied compounds showed the lowest gap energy and were chemically reactive, and isolated compounds may serve as potential drug candidates that corroborate with the traditional uses of studied plants.

IVEN: A quantitative tool to describe 3D cell position and neighbourhood reveals architectural changes in FGF4-treated preimplantation embryos.

Architectural changes at the cellular and organism level are integral and necessary to successful development and growth. During mammalian preimplantation development, cells reduce in size and the architecture of the embryo changes significantly. Such changes must be coordinated correctly to ensure continued development of the embryo and, ultimately, a successful pregnancy. However, the nature of such transformations is poorly defined during mammalian preimplantation development. In order to quantitatively describe changes in cell environment and organism architecture, we designed Internal Versus External Neighbourhood (IVEN). IVEN is a user-interactive, open-source pipeline that classifies cells into different populations based on their position and quantifies the number of neighbours of every cell within a dataset in a 3D environment. Through IVEN-driven analyses, we show how transformations in cell environment, defined here as changes in cell neighbourhood, are related to changes in embryo geometry and major developmental events during preimplantation mammalian development. Moreover, we demonstrate that modulation of the FGF pathway alters spatial relations of inner cells and neighbourhood distributions, leading to overall changes in embryo architecture. In conjunction with IVEN-driven analyses, we uncover differences in the dynamic of cell size changes over the preimplantation period and determine that cells within the mammalian embryo initiate growth phase only at the time of implantation.

First report of a subcutaneous infection by Cryptococcus neoformans (former Cryptococcus neoformans var. grubii) in a cat in Costa Rica.

This is a case report of a feline animal that presented with a skin infection on the neck from which Cryptococcus neoformans (former C. neoformans var. grubii) was isolated and identified. The cat presented two nodular tumors, approximately 2 cm in diameter, raised, solid, with a slightly irregular surface and a reddish color with white areas. Histologically, these tumors corresponded to granulomatous dermatitis and panniculitis with the presence of a large number of intralesional yeasts. From identification with biochemical and spectroscopic techniques of these lesion samples, it was determined that the etiological agent was C. neoformans. There is little information on this variety of Cryptococcus causing subcutaneous infection without involvement of other organs, and the presence of this pathogen in the few reports available has not been reliably determined. This is the first report of a cat affected by C. neoformans in Costa Rica.