Autotrophic adaptive laboratory evolution of the acetogen Clostridium autoethanogenum delivers the gas-fermenting strain LAbrini with superior growth, products, and robustness.

Microbes able to convert gaseous one-carbon (C1) waste feedstocks are increasingly important to transition to the sustainable production of renewable chemicals and fuels. Acetogens are interesting biocatalysts since gas fermentation using Clostridium autoethanogenum has been commercialised. However, most acetogen strains need complex nutrients, display slow growth, and are not robust for bioreactor fermentations. In this work, we used three different and independent adaptive laboratory evolution (ALE) strategies to evolve the wild-type C. autoethanogenum to grow faster, without yeast extract and to be robust in operating continuous bioreactor cultures. Multiple evolved strains with improved phenotypes were isolated on minimal media with one strain, named "LAbrini", exhibiting superior performance regarding the maximum specific growth rate, product profile, and robustness in continuous cultures. Whole-genome sequencing of the evolved strains identified 25 mutations. Of particular interest are two genes that acquired seven different mutations across the three ALE strategies, potentially as a result of convergent evolution. Reverse genetic engineering of mutations in potentially sporulation-related genes CLAU_3129 (spo0A) and CLAU_1957 recovered all three superior features of our ALE strains through triggering significant proteomic rearrangements. This work provides a robust C. autoethanogenum strain "LAbrini" to accelerate phenotyping and genetic engineering and to better understand acetogen metabolism.

RNA-Seq Data Analysis: A Practical Guide for Model and Non-Model Organisms.

RNA sequencing (RNA-seq) has emerged as a powerful tool for assessing genome-wide gene expression, revolutionizing various fields of biology. However, analyzing large RNA-seq datasets can be challenging, especially for students or researchers lacking bioinformatics experience. To address these challenges, we present a comprehensive guide to provide step-by-step workflows for analyzing RNA-seq data, from raw reads to functional enrichment analysis, starting with considerations for experimental design. This is designed to aid students and researchers working with any organism, irrespective of whether an assembled genome is available. Within this guide, we employ various recognized bioinformatics tools to navigate the landscape of RNA-seq analysis and discuss the advantages and disadvantages of different tools for the same task. Our protocol focuses on clarity, reproducibility, and practicality to enable users to navigate the complexities of RNA-seq data analysis easily and gain valuable biological insights from the datasets. Additionally, all scripts and a sample dataset are available in a GitHub repository to facilitate the implementation of the analysis pipeline. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Analysis of data from a model plant with an available reference genome Basic Protocol 2: Gene ontology enrichment analysis Basic Protocol 3: De novo assembly of data from non-model plants.

Follow-up for 3 years of a pediatric population diagnosed in 2018 with mother-to-child transmission of HIV in 8 Latin American countries in the PLANTAIDS cohort.

INTRODUCTION: The frequency of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) in Latin America has decreased considerably. However, new infections continue to be recorded, and the pediatric population remains one of the most vulnerable groups in this region. The main objective of the study was to describe the clinical, epidemiological and psychosocial characteristics of new diagnoses of HIV MTCT in 2018 in the PLANTAIDS network (Paediatric Network for Prevention, Early Detection and Treatment of HIV in Children) during the 3 years following diagnosis. METHODOLOGY: Retrospective, multicenter, descriptive study based on a 3-year follow-up of patients diagnosed with HIV infection due to MTCT in 2018 in 10 hospitals in 8 Latin American countries (Costa Rica, Ecuador, Mexico, Honduras, El Salvador, Panama, Guatemala and Venezuela). The hospitals belonged to the PLANTAIDS network, which is included in CYTED (Ibero-American Programme of Science and Technology for Development). RESULTS: The study population comprised 72 pediatric patients (38.9% male). The median age at diagnosis was 2.4 years (IQR: 0.8-5.4). There were 35 cases of opportunistic infections corresponding to 25 patients (34.7%), with tuberculosis being the most common. Adequate childhood vaccination coverage was achieved in 80.5%. There were 3 cases of acute SARS-CoV-2 infection, and these were asymptomatic or mildly symptomatic. According to the Centers for Disease Control and Prevention (CDC) classification, the most frequent clinical-immunological stage at all check-ups was C1. Three patients died from opportunistic infections and/or advanced HIV infection. CONCLUSIONS: It is important to diagnose HIV infection early in pediatrics, since early initiation of ART is associated with a decrease in mortality. Despite this, HIV infection has a poor prognosis in children, necessitating adequate follow-up to ensure adherence to health care and ART, although it can sometimes prove difficult in children.

Evaluating the In Vitro Activity and Safety of Modified LfcinB Peptides as Potential Colon Anticancer Agents: Cell Line Studies and Insect-Based Toxicity Assessments.

Anticancer peptides are increasingly being considered as alternative treatments for cancer due to their potency, selectivity, and low toxicity. Previously, the peptide LfcinB (21-25)Pal showed in vitro anticancer effects against the Caco-2 colon cancer cell line (half-maximal inhibitory concentration (IC50): 86 µM). In this study, we developed modifications to the peptide sequence to increase its anticancer activity. Sequence modifications were made such as the inclusion of amino hexanoic acid (Ahx), N-terminal biotinylation, acetylation, and substitutions of Orn for Arg and/or d-Arg by l-Arg. The molecules were synthesized using manual solid-phase peptide synthesis (SPPS), and their synthetic feasibility (SAScore) ranged from 6.2 to 7.6. The chromatographic purities of the synthesized peptides were greater than 89%. We found that Ahx-RWQWRWQWR and RWQWRWQW-Orn showed activity against both Caco-2 and HT-29 cell lines and decreased IC50 values by approx. 50% in Caco-2 cells (IC50: 40 µM) when compared to the parent peptide RWQWRWQWR. Moreover, the modified peptides demonstrated lower hemolytic effects, with values <10% at 200 µg/mL. Toxicity was assessed using the Galleria mellonella model and the half-maximal lethal dose (LD50) for the best peptides was >100 mg/kg, indicating that their toxicity is classified as moderately toxic or lower. In contrast, cisplatin showed an LD50 of 13 mg/Kg. The designed anticancer peptides presented good in vitro activity and low toxicity, making them promising molecules for future drug development studies.

Pentoxifylline Inhibits TNF-α/TGF-ß1-Induced Epithelial-Mesenchymal Transition via Suppressing the NF-κB Pathway and SERPINE1 Expression in CaSki Cells.

Cervical cancer (CC) is one of the most common and deadly types of female cancer worldwide. Late diagnosis in CC increases the risk of tumor cells spreading to distant organs (metastasis). The epithelial-mesenchymal transition (EMT) is a fundamental process of cancer metastasis. Inflammation can lead to tumor progression, EMT induction, and metastasis. The inflammatory microenvironment is a potent inducer of EMT; inflammatory cytokines such as Tumor Necrosis Factor-alpha (TNF-α) and Transforming growth factor-beta (TGF-ß1) activate transcriptional factors such as STAT3, Snail, Smad, and the Nuclear Factor kappa light-chain-enhancer of activated beta cells (NF-κΒ), which drive EMT. Anti-inflammatory compounds may be an option in the disruption of EMT. PenToXifylline (PTX) possesses potent anti-inflammatory effects by inhibiting NF-κB activity. In addition, PTX exerts an anti-fibrotic effect by decreasing Smad2/3/4. We hypothesize that PTX could exert anti-EMT effects. CaSki human cervical tumor cells were exposed to TNF-α 10 ng/mL and TGF-ß1 alone or in combination for 5 days. Our results revealed that TNF-α and TGF-ß1 induced N-cadherin and Vimentin, confirming the induction of EMT. Furthermore, the combination of cytokines synergized the expression of mesenchymal proteins, enhanced IκBα and p65 phosphorylation, and upregulated Serpin family E member 1 (SERPINE1) mRNA. PTX pretreatment prior to the addition of TNF-α and TGF-ß1 significantly reduced N-cadherin and Vimentin levels. To our knowledge, this is the first time that this effect of PTX has been reported. Additionally, PTX reduced the phosphorylation of IκB-α and p65 and significantly decreased SERPINE1 expression, cell proliferation, migration, and invasion. In conclusion, PTX may counteract EMT in cervical cancer cells by decreasing the NF-κB and SERPINE1.

Realizing integration in structural biology: The 2022 ISBUC Annual Meeting.

This meeting report presents the 2022 Annual Meeting of the cluster for Integrative Structural Biology at the University of Copenhagen (ISBUC) and discusses the cluster approach to interdisciplinary research management. This approach successfully facilitates cross-faculty and inter-departmental collaboration. Innovative integrative research collaborations ignited by ISBUC, as well as research presented at the meeting, are showcased.

Non-natural amino acids into LfcinB-derived peptides: effect in their (i) proteolytic degradation and (ii) cytotoxic activity against cancer cells.

The dimeric peptide 26[F]: (RRWQWRFKKLG)2-K-Ahx has exhibited a potent cytotoxic effect against breast cancer cell lines, with position 26 (F) being the most relevant for anti-cancer activity. In this investigation, six analogues of the 26[F] peptide were synthesized in which the 26th position was replaced by non-natural hydrophobic amino acids, finding that some modifications increased the resistance to proteolytic degradation exerted by trypsin or pepsin. Additionally, these modifications increased the cytotoxic effect against breast cancer cells and generated cell death mediated by apoptosis pathways, activating caspases 8 and 9, and did not compromise the integrity of the cytoplasmic membrane. Finally, it was found that the modified peptides have a broad spectrum of action, since they also have a cytotoxic effect against the HeLa human cervical cancer cell line. Peptide 26[F] was inoculated in mice by ip administration and the lethal dose 50 (LD50) was between 70 and 140 mg kg-1. While for the 26[1-Nal]: (RRWQWR-1-Nal-KKLG)2-K-Ahx peptide, a dose-response test was performed, and the survival rate was 100%. These results suggested that these peptides are safe in this animal model and could be considered as promissory to develop a treatment against breast cancer.

Defining the regulatory mechanisms of sigma factor RpoS degradation in Azotobacter vinelandii and Pseudomonas aeruginosa.

In several Gram-negative bacteria, the general stress response is mediated by the alternative sigma factor RpoS, a subunit of RNA polymerase that confers promoter specificity. In Escherichia coli, regulation of protein levels of RpoS involves the adaptor protein RssB, which binds RpoS for presenting it to the ClpXP protease for its degradation. However, in species from the Pseudomonadaceae family, RpoS is also degraded by ClpXP, but an adaptor has not been experimentally demonstrated. Here, we investigated the role of an E. coli RssB-like protein in two representative Pseudomonadaceae species such as Azotobacter vinelandii and Pseudomonas aeruginosa. In these bacteria, inactivation of the rssB gene increased the levels and stability of RpoS during exponential growth. Downstream of rssB lies a gene that encodes a protein annotated as an anti-sigma factor antagonist (rssC). However, inactivation of rssC in both A. vinelandii and P. aeruginosa also increased the RpoS protein levels, suggesting that RssB and RssC work together to control RpoS degradation. Furthermore, we identified an in vivo interaction between RssB and RpoS only in the presence of RssC using a bacterial three-hybrid system. We propose that both RssB and RssC are necessary for the ClpXP-dependent RpoS degradation during exponential growth in two species of the Pseudomonadaceae family.

DCIS: When is accelerated partial breast irradiation an option? A meta-analysis on outcomes and eligibility.

BACKGROUND: The natural history of DCIS may not be progression to invasive breast cancer (IBC). Accelerated partial breast irradiation (APBI) has emerged as an alternative to whole breast radiotherapy (WBRT). The purpose of this study was to assess the impact of APBI on DCIS patients. MATERIALS AND METHODS: Eligible studies from 2012 to 2022 were identified in PubMed, Cochrane Library, ClinicalTrials, and ICTRP. A meta-analysis was done comparing recurrence rates, breast-related mortality rates, and adverse events of APBI versus WBRT. A subgroup analysis of 2017 ASTRO Guidelines "Suitable" and "Unsuitable" groups was performed. Forest plots and quantitative analysis were done. RESULTS: Six studies were eligible (3 on APBI versus WBRT, 3 on APBI suitability). All had a low risk of bias and publication bias. The cumulative incidence was the following for APBI and WBRT respectively: IBTR was 5.7% and 6.3% with odds ratio of 1.09, 95% CI [0.84, 1.42], mortality rate was 4.9% and 5.05%, and adverse events was 48.87% and 69.63%. All had no statistical significance between groups. Adverse events were found to favor the APBI arm. Recurrence rate was significantly less in the Suitable group with an odds ratio 2.69, 95% CI [1.56, 4.67], favoring it over the Unsuitable group. CONCLUSION: APBI was comparable to WBRT in terms of recurrence rate, breast cancer-related mortality rate, and adverse events. APBI was not inferior to WBRT and showed better safety in terms of skin toxicity. Patients classified as suitable for APBI had significantly lesser recurrence rate.

Manejo de tejidos blandos en trauma de miembros inferiores: a propósito de un caso / Soft tissue management in lower limb trauma: about a case

Los miembros inferiores están sujetos frecuentemente a traumas que ocasionan daño de estructuras vitales y que pueden dejar secuelas funcionales y estéticas en las personas. Las lesiones de tejidos blandos son las que asientan en la piel, tejido celular subcutáneo, aponeurosis, músculos, vasos y nervios. Del manejo oportuno y adecuado de las lesiones que se presenten posteriores a un trauma de tejidos blandos dependerá el resultado, el tiempo de recuperación, costos de hospitalización y sobre todo la preservación de las funciones de locomoción y sostén del miembro afectado

The lower limbs are frequently exposed to traumas that cause vital structures damage and can leave functional and aesthetic sequelae in patients. Soft tissue lesions are those that affect the skin, subcutaneous cellular tissue, fascia, muscles, vessels, and nerves. The result, recovery time, hospitalization costs and, above all, the preservation of the locomotion and support functions of the affected limb will depend on the timely and adequate management of injuries that occur after a soft tissue trauma.

Ataque de nervios: The impact of sociodemographic, health history, and psychological dimensions on Puerto Rican adults.

Introduction: Ataque de nervios (ADN) is a cultural syndrome prevalent in Puerto Ricans characterized as an episode of intense emotional upset due to overwhelming stress. Methods: The Ataque de Nervios Questionnaire, developed at the Center for the Study and Treatment for Fear and Anxiety (CETMA), served as the diagnostic tool for this retrospective secondary data analysis. We evaluated three models regarding ADN's function as a marker of (1) sociodemographic vulnerability, (2) health history risk, and (3) psychological vulnerability. This last model was subdivided to assess the scores of screening tests regarding anxiety (Anxiety Sensitivity Inventory, Beck Anxiety Inventory, and State-Trait Anxiety Inventory), affect (Beck Depression Inventory, Emotional Dysregulation Scale, Positive and Negative Affective Schedule), personality (NEO Five-Factor Inventory), and trauma (considering the responses to the Childhood Trauma Questionnaire and the Life Event Checklist). Results: Our study sample had a total of 121 Puerto Rican adult patients from CETMA out of which 75% had ADN. We differentiated subjects according to their ADN status with t-tests and Mann-Whitney U tests and evaluated our models using logistic regressions. People with ADN showed more anxiety, depressive symptoms, emotional dysregulation, and negative affect than those without ADN. They also revealed lower positive affect and agreeableness. Highly extraverted but minimally agreeable personalities related to ADN. Living with a partner and being employed were risk factors for ADN. Having higher educational levels showed the strongest effect size: it greatly reduced the odds of an ataque. Discussion: These characteristics suggest a distinct profile of ADN seen in employed, educated, adult Puerto Ricans living on the Island experiencing anxiety. Our study provides clinical tools to comprehend our patients' ADN experience, enriching our practice as culturally competent health providers.

Esquizencefalia de diagnóstico prenatal: reporte de caso / Schizencephaly of prenatal diagnosis: case report

La esquizencefalia es una malformación cerebral congénita del grupo de trastornos de migración neuronal, tiene una prevalencia de 1,54/100 000 nacidos vivos, por lo cual, se considera extremadamente rara. El objetivo de este artículo es presentar un caso de esquizencefalia fetal de labio abierto, el subtipo de peor pronóstico, cuya sospecha diagnóstica se realiza con ecografía prenatal y se confirma mediante la resonancia magnética fetal. Actualmente, en Colombia no se cuenta con este tipo de reporte de casos.

Schizencephaly is a congenital brain malformation, which is part of the group of neuronal migration disorders, which has a prevalence of 1,54/100 000 in live births, which is why it is considered extremely rare in Colombia. The objective of this article is to present a case of open-lip fetal schizencephaly, the subtype with the worst prognosis, whose suspected diagnosis is made with prenatal ultrasound and confirmed by fetal magnetic resonance imaging. Currently, this type of report is not available in Colombia.

The ribosome rescue pathways SsrA-SmpB, ArfA, and ArfB mediate tolerance to heat and antibiotic stresses in Azotobacter vinelandii.

Bacteria have a mechanism to rescue stalled ribosomes known as trans-translation consisting of SsrA, a transfer-messenger RNA (tmRNA), and the small protein SmpB. Other alternative rescue mechanisms mediated by ArfA and ArfB proteins are present only in some species. Ribosome rescue mechanisms also play a role in tolerance to antibiotics and various stresses such as heat. This study shows that the genome of the soil bacterium A. vinelandii harbours genes encoding for tmRNA, SmpB, two paralogs of ArfA (arfA1 and arfA2), and ArfB. A number of mutant strains carrying mutations in the ssrA, arfA1, arfA2, and arfB genes were constructed and tested for their growth and susceptibility to heat and the antibiotic tetracycline. We found that the inactivation of both ssrA and one or the two arfA genes was detrimental to growth and caused a higher susceptibility to heat and to the antibiotic tetracycline. Interestingly, the arfB mutant strain was unable to grow after 2 h of incubation at 45°C. Inactivation of arfB in the ssrA-arfA1-arfA2 strain caused a lethal phenotype since the quadruple mutant could not be isolated. Taken together, our data suggest that both arfA1 and arfA2, as well as arfB, are functional as back up mechanisms, and that the ArfB pathway has an essential role that confers A. vinelandii resistance to high temperatures.

Principios bioéticos y actitudes en la atención de pacientes con VIH, del Hopital Clínico Viedma, 2021 / Bioethical principles and attitudes in the care of patients with HIV, Hospital Clínico Viedma, 2021

La infección por el Virus de la inmunodeficiencia humana, el estigma y la discriminación, así como su interrelación con los derechos humanos, se han transformado en los ejes centrales de las campañas contra el SIDA y a favor de los derechos de las personas viviendo con el VIH/SIDA, constituyéndose en uno de los problemas más frecuentes en el área hospitalaria. El presente estudio se realizó para identificar los principios bioéticos y actitudes del personal de enfermería, elementos de valoración y cuidados que implementan el personal para la prevención de las mismas; con el enfoque cualitativo - cuantitativo de tipo descriptivo y transversal, en el servicio de Infectología del HCV, gestión II/2021. Los resultados más significativos del personal de enfermería son: discriminación con el 20%; rechazo, 20%; actitudes negativas, 20% un 27% percibe una mala atención y 13% trato inadecuado, por tanto 100% de la población ha recibido algún tipo de maltrato del personal de enfermería. Pese a que estos conocen los principios bioéticos de autonomía, beneficencia, no maleficencia y equidad con los pacientes, solo en la parte teórica, ya que en la práctica no las aplican. (AU)

Evidence for Light and Tissue Specific Regulation of Genes Involved in Fructan Metabolism in Agave tequilana.

Plant Glycoside Hydrolase Family 32 (PGHF32) contains the fructosyltransferases and fructan exohydrolase enzymes responsible for fructan metabolism, in addition to closely related vacuolar and cell wall acid invertases. Agave species produce complex and dynamic fructan molecules (agavins) requiring 4 different fructosyltransferase activities (1-SST, 1-FFT, 6G-FFT and 6-SFT) for their synthesis. Combined analysis of RNAseq and genome data for A. tequilana led to the characterization of the genes encoding 3 fructosyltransferases for this species and support the hypothesis that no separate 6-SFT type enzyme exists in A. tequilana, suggesting that at least one of the fructosyltransferases identified may have multiple enzymatic activities. Structures for PGHF32 genes varied for A. tequilana and between other plant species but were conserved for different enzyme types within a species. The observed patterns are consistent with the formation of distinct gene structures by intron loss. Promoter analysis of the PGHF32 genes identified abundant putative regulatory motifs for light regulation and tissue-specific expression, and these regulatory mechanisms were confirmed experimentally for leaf tissue. Motifs for phytohormone response, carbohydrate metabolism and dehydration responses were also uncovered. Based on the regulatory motifs, full-length cDNAs for MYB, GATA, DOF and GBF transcription factors were identified and their phylogenetic distribution determined by comparison with other plant species. In silico expression analysis for the selected transcription factors revealed both tissue-specific and developmental patterns of expression, allowing candidates to be identified for detailed analysis of the regulation of fructan metabolism in A. tequilana at the molecular level.

Estimating COVID-19 cases in Puerto Rico using an automated surveillance system.

Due to concerns regarding limited testing and accuracy of estimation of COVID-19 cases, we created an automated surveillance system called "Puerto Rico Epidemiological Evaluation and Prevention of COVID-19 and Influenza" (PREPCOVI) to evaluate COVID-19 incidence and time trends across Puerto Rico. Automated text message invitations were sent to random phone numbers with Puerto Rican area codes. In addition to reported COVID-19 test results, we used a published model to classify cases from specific symptoms (loss of smell and taste, severe persistent cough, severe fatigue, and skipped meals). Between 18 November 2020, and 24 June 2021, we sent 1,427,241 messages, 26.8% were reached, and 6,975 participants answered questions about the last 30 days. Participants were aged 21-93 years and represented 97.4% of the municipalities. PREPCOVI total COVID-19 cases were higher among women and people aged between 21 and 40 years and in the Arecibo and Bayamón regions. COVID-19 was confirmed, and probable cases decreased over the study period. Confirmed COVID-19 cases ranged from 1.6 to 0.2% monthly, although testing rates only ranged from 30 to 42%. Test positivity decreased from 13.2% in November to 6.4% in March, increased in April (11.1%), and decreased in June (1.5%). PREPCOVI total cases (6.5%) were higher than cases reported by the Puerto Rico Department of Health (5.3%) for similar time periods, but time trends were similar. Automated surveillance systems and symptom-based models are useful in estimating COVID-19 cases and time trends, especially when testing is limited.

The burned patient in times of COVID-19: proposal derived from lessons learned.

COVID-19 is a public health problem, so any burn patient who is managed as an outpatient or requires hospital management is a potential carrier of SARS-CoV-2. Burn patients are susceptible to COVID-19 due to the burn and its immunosuppressive effect, the procedures they undergo and other factors related to the burn, which makes them at high risk of contracting the disease and transmitting it, especially to the healthcare team involved in its management. Therefore, it is important to organize strategies in the services that care for burn patients during the COVID-19 pandemic. The objective of this paper is to present a proposal for response, organizational management and strategic planning in a burns service in times of COVID-19, based on the lessons and experience acquired.

La COVID-19 es un problema de salud pública, por lo que cualquier paciente quemado que se maneje como externo o que requiera manejo hospitalario es un potencial portador del SARS-CoV-2. El paciente quemado es susceptible a la COVID-19 debido a la quemadura y a su efecto inmunodepresor, a los procedimientos a los que es sometido y a otros factores inherentes a la quemadura, lo que le hace un paciente con alto riesgo de contraer la enfermedad y trasmitirla, especialmente al equipo de salud que está involucrado en su manejo. Por lo anterior, es importante organizar estrategias en los servicios que atienden pacientes con quemaduras durante la pandemia de COVID-19. El objetivo de este trabajo es presentar una propuesta para la respuesta, el manejo organizativo y la planeación estratégica en un servicio de quemados en tiempos de COVID-19, basándonos en las lecciones aprendidas y la experiencia adquirida.

A Photoswitchable Ligand Targeting the ß1 -Adrenoceptor Enables Light-Control of the Cardiac Rhythm.

Catecholamine-triggered ß-adrenoceptor (ß-AR) signaling is essential for the correct functioning of the heart. Although both ß1 - and ß2 -AR subtypes are expressed in cardiomyocytes, drugs selectively targeting ß1 -AR have proven this receptor as the main target for the therapeutic effects of beta blockers in the heart. Here, we report a new strategy for the light-control of ß1 -AR activation by means of photoswitchable drugs with a high level of ß1 -/ß2 -AR selectivity. All reported molecules allow for an efficient real-time optical control of receptor function in vitro. Moreover, using confocal microscopy we demonstrate that the binding of our best hit, pAzo-2, can be reversibly photocontrolled. Strikingly, pAzo-2 also enables a dynamic cardiac rhythm management on living zebrafish larvae using light, thus highlighting the therapeutic and research potential of the developed photoswitches. Overall, this work provides the first proof of precise control of the therapeutic target ß1 -AR in native environments using light.

Gut Microbial Ecology of Five Species of Sympatric Desert Rodents in Relation to Herbivorous and Insectivorous Feeding Strategies.

The gut microbial communities of mammals provide numerous benefits to their hosts. However, given the recent development of the microbiome field, we still lack a thorough understanding of the variety of ecological and evolutionary factors that structure these communities across species. Metabarcoding is a powerful technique that allows for multiple microbial ecology questions to be investigated simultaneously. Here, we employed DNA metabarcoding techniques, predictive metagenomics, and culture-dependent techniques to inventory the gut microbial communities of several species of rodent collected from the same environment that employ different natural feeding strategies [granivorous pocket mice (Chaetodipus penicillatus); granivorous kangaroo rats (Dipodomys merriami); herbivorous woodrats (Neotoma albigula); omnivorous cactus mice (Peromyscus eremicus); and insectivorous grasshopper mice (Onychomys torridus)]. Of particular interest were shifts in gut microbial communities in rodent species with herbivorous and insectivorous diets, given the high amounts of indigestible fibers and chitinous exoskeleton in these diets, respectively. We found that herbivorous woodrats harbored the greatest microbial diversity. Granivorous pocket mice and kangaroo rats had the highest abundances of the genus Ruminococcus and highest predicted abundances of genes related to the digestion of fiber, representing potential adaptations in these species to the fiber content of seeds and the limitations to digestion given their small body size. Insectivorous grasshopper mice exhibited the greatest inter-individual variation in the membership of their microbiomes, and also exhibited the highest predicted abundances of chitin-degrading genes. Culture-based approaches identified 178 microbial isolates (primarily Bacillus and Enterococcus), with some capable of degrading cellulose and chitin. We observed several instances of strain-level diversity in these metabolic capabilities across isolates, somewhat highlighting the limitations and hidden diversity underlying DNA metabarcoding techniques. However, these methods offer power in allowing the investigation of several questions concurrently, thus enhancing our understanding of gut microbial ecology.

[Clinical cases of Guillain-Barré and Miller-Fisher syndromes linked to COVID-19]. / Casos clínicos de los síndromes de Guillain-Barré y Miller-Fisher relacionados con la COVID-19.

coronavirus disease 2019 (COVID-19), caused by the new coronavirus SARS-CoV-2, has been associated with the development of neurological diseases such as Guillain-Barré syndrome (GBS) and its variants. In the present work, two cases of demyelinating syndromes associated with COVID-19 are reported. Clinical cases: 53-year-old male with GBS and and 29-year-old female with Miller-Fisher syndrome (MFS) variant, respectively. Both patients presented the classic neurological signs and symptoms of demyelinating polyneuropathy that characterizes the syndromes. From the paraclinical biochemical tests, the increase of proteins in cerebrospinal fluid was distinctive. The positivity of the RT-qPCR for SARS-CoV-2 suggested the association of GBS and MFS with COVID-19. Both patients were treated with intravenous immunoglobulin showing improvement. Electromyography performed weeks ahead still showed chronic demyelinating involvement. Conclusion: The cases of GBS and MFS, along with other similar cases reported around the world, provide further evidence for SARS-CoV-2 as a new possible etiology of these rare neurological diseases.

Introducción: la enfermedad por coronavirus del 2019 (COVID-19), causada por el nuevo coronavirus SARS-CoV-2, se ha asociado con el desarrollo de enfermedades neurológicas como el síndrome de Guillain-Barré (SGB) y sus variantes. En el presente trabajo se reportan dos casos de síndromes desmielizantes asociados con la COVID-19. Casos clínicos: hombre de 53 años con SGB y mujer de 29 años con la variante del síndrome de Miller-Fisher (SMF), respectivamente. Ambos presentaron los signos y síntomas neurológicos clásicos de polineuropatía desmielinizante que caracterizan a estos síndromes. De las pruebas bioquímicas paraclínicas, el aumento de proteínas en líquido cefalorraquídeo fue distintiva. La positividad de la RT-qPCR para el SARS-CoV-2 indicó la asociación de los SGB y SMF con la COVID-19. Ambos pacientes se trataron con inmunoglobulina intravenosa y mostraron mejoría. La electromiografía realizada en semanas posteriores aún mostraba afectación desmielinizante crónica. Conclusión: los casos de los SGB y SMF, junto con otros casos similares reportados en todo el mundo, proporcionan más evidencia para el SARS-CoV-2 como nueva posible etiología de estas raras enfermedades neurológicas.