Representing Vulnerabilities in Contemporary Literature includes a collection of chapters exploring the ways in which recent literary representations of vulnerability may problematize its ...visibilization from an ethical and aesthetic perspective. Recent technological and scientific developments have accentuated human vulnerability in many and different ways at a cross-national, and even cross-species level. Disability, technological, and ecological vulnerabilities are new foci of interest that add up to gender, precarity, and trauma, among others, as forms of vulnerability in this volume. The literary visualization of these vulnerabilities might help raise social awareness of one's own vulnerabilities as well as those of others so as to bring about global solidarity based on affinity and affect. However, the literary representation of forms of vulnerability might also deepen stigmatization phenomena and trivialize the spectacularization of vulnerability by blunting readers' affective response toward those products that strive to hold their attention and interest in an information-saturated, global entertainment market.
Matrix metalloproteinases (MMPs) are a large family of zinc-endopeptidases which play important roles in multiple physiological and pathological processes. These enzymes are widely distributed in all ...kingdoms of life and have likely evolved from a single-domain protein which underwent successive rounds of duplication, gene fusion and exon shuffling events to generate the multidomain architecture and functional diversity currently exhibited by MMPs. Proper regulation of these enzymes is required to prevent their unwanted activity in a variety of disorders, including cancer, arthritis and cardiovascular diseases. Multiple hormones, cytokines and growth factors are able to induce
MMP expression, although the tissue specificity of the diverse family members is mainly achieved by the combination of different transcriptional control mechanisms. The integration of multiple signaling pathways, coupled with the cooperation between several
cis-regulatory elements found at the
MMP promoters facilitates the strict spatiotemporal control of
MMP transcriptional activity. Additionally, epigenetic mechanisms, such as DNA methylation or histone acetylation, may also contribute to
MMP regulation. Likewise, post-transcriptional regulatory processes including mRNA stability, protein translational efficiency, and microRNA-based mechanisms have been recently described as modulators of
MMP gene expression. Parallel studies have led to the identification of
MMP polymorphisms and mutations causally implicated in the development of different genetic diseases. These genomic analyses have been further extended through the generation of animal models of gain- or loss-of-function for MMPs which have allowed the identification of novel functions for these enzymes and the establishment of causal relationships between MMP dysregulation and development of different human diseases. Further genomic studies of MMPs, including functional analysis of gene regulation and generation of novel animal models will help to answer the multiple questions still open in relation to a family of enzymes which strongly influence multiple events in life and disease.
Marine ecosystems are in decline. New transformational changes in governance are urgently required to cope with overfishing, pollution, global changes, and other drivers of degradation. Here we ...explore social, political, and ecological aspects of a transformation in governance of Chile's coastal marine resources, from 1980 to today. Critical elements in the initial preparatory phase of the transformation were (i) recognition of the depletion of resource stocks, (ii) scientific knowledge on the ecology and resilience of targeted species and their role in ecosystem dynamics, and (iii) demonstration-scale experimental trials, building on smaller-scale scientific experiments, which identified new management pathways. The trials improved cooperation among scientists and fishers, integrating knowledge and establishing trust. Political turbulence and resource stock collapse provided a window of opportunity that triggered the transformation, supported by new enabling legislation. Essential elements to navigate this transformation were the ability to network knowledge from the local level to influence the decision-making processes at the national level, and a preexisting social network of fishers that provided political leverage through a national confederation of artisanal fishing collectives. The resultant governance scheme includes a revolutionary national system of marine tenure that allocates user rights and responsibilities to fisher collectives. Although fine tuning is necessary to build resilience of this new regime, this transformation has improved the sustainability of the interconnected social—ecological system. Our analysis of how this transformation unfolded provides insights into how the Chilean system could be further developed and identifies generalized pathways for improved governance of marine resources around the world.
Tao Lin’s novel Taipei (2013) can be described as a picture of transhuman existence in the current digital world. However, its poetics of failure does not seem to adjust to the typically utopian ...visions that have often been related to transhumanism. Instead, the novel’s aesthetic approach resists diverse forms of transhumanist universalism in ways that are closer to the theoretical premises of critical posthumanism and agential materialism. In this article, I analyze Lin’s use of accountable metaphors and poetic failure in Taipei as a means to resist uncritical claims to transhumanist, universalist aesthetics.
Taipei (2013), de Tao Lin, podría describirse como un retrato de la existencia transhumana en el mundo digital actual. Sin embargo, su enfoque estético desde la perspectiva de la poética del fracaso no parece ajustarse a las típicas visiones utópicas que se relacionan con el transhumanismo. En vez de eso, dicho enfoque parece dar la impresión de resistir las diversas formas del universalismo transhumanista de un modo que estaría más cercano a las premisas teóricas del posthumanismo crítico y el materialismo agencial. En este artículo analizo el uso narrativo de la metáfora responsable y la poética del fracaso en Taipei como un modo de resistir supuestos complacientes con la estética universalista del transhumanismo.
This study explores the potential of Spanish germplasm for the development of hybrids adapted to southern Europe, a new region for hybrid barley (Hordeum vulgare). A set of 140 locally adapted, ...advanced breeding lines, developed in a Spanish public breeding program, were evaluated for their potential to widen the germplasm available for hybrid barley development. A subset of 24 lines was introduced into three‐way hybrid combinations and tested in a field trial network of four locations and 2 yr. The hybrid performance of the rest of the lines was estimated based on genomic prediction models. No three‐way hybrid exceeded the best check. We succeeded in identifying lines with high general combining ability, which could produce promising two‐way hybrids. Some were among those tested in the field, whereas others resulted from genomic predictions, validating the strategy followed of mining locally adapted breeding lines. Rachis brittleness detected in field trials revealed a low but detrimental effect of the presence of alternative brittle mutations in the hybrid combination. The success of hybrid breeding in southern Europe requires further investigation of the underlying heterotic patterns, and appropriate management of brittle genes through prebreeding, to widen the germplasm accessible for hybrid barley breeding.
Core Ideas
A combination of field testing and genomic prediction successfully mined local germplasm for hybrid development.
Reduced expression of local diversity and heterosis in three‐way hybrids hampered obtaining superior hybrids.
High‐yielding, widely adapted, parental lines for the development of promising two‐way hybrids were identified.
Field‐estimation of rachis fragility indicates risk of grain loss in hybrids with alternative brittle mutations.
The success of hybrid barley in southern Europe requires managing flowering time and studying heterotic patterns.
Abstract
Telomerase RNA (
TERC
) has a noncanonical function in myelopoiesis binding to a consensus DNA binding sequence and attracting RNA polymerase II (RNA Pol II), thus facilitating myeloid gene ...expression. The CR4/CR5 domain of
TERC
is known to play this role, since a mutation of this domain found in dyskeratosis congenita (DC) patients decreases its affinity for RNA Pol II, impairing its myelopoietic activity as a result. In this study, we report that two aptamers, short single-stranded oligonucleotides, based on the CR4/CR5 domain were able to increase myelopoiesis without affecting erythropoiesis in zebrafish. Mechanistically, the aptamers functioned as full
terc;
that is, they increased the expression of master myeloid genes, independently of endogenous
terc
, by interacting with RNA Pol II and with the
terc
-binding sequences of the regulatory regions of such genes, enforcing their transcription. Importantly, aptamers harboring the CR4/CR5 mutation that was found in DC patients failed to perform all these functions. The therapeutic potential of the aptamers for treating neutropenia was demonstrated in several preclinical models. The findings of this study have identified two potential therapeutic agents for DC and other neutropenic patients.
Wavelength dispersive X-ray fluorescence (WD-XRF) spectrometry has been widely used for elemental quantification of mortars and cements. In this kind of instrument, samples are usually prepared as ...pellets or fused beads and the whole volume of sample is measured at once. In this work, the usefulness of a dual energy dispersive X-ray fluorescence spectrometer (ED-XRF), working at two lateral resolutions (1 mm and 25 μm) for macro and microanalysis respectively, to develop quantitative methods for the elemental characterization of mortars and concretes is demonstrated. A crucial step before developing any quantitative method with this kind of spectrometers is to verify the homogeneity of the standards at these two lateral resolutions. This new ED-XRF quantitative method also demonstrated the importance of matrix effects in the accuracy of the results being necessary to use Certified Reference Materials as standards. The results obtained with the ED-XRF quantitative method were compared with the ones obtained with two WD-XRF quantitative methods employing two different sample preparation strategies (pellets and fused beads). The selected ED-XRF and both WD-XRF quantitative methods were applied to the analysis of real mortars. The accuracy of the ED-XRF results turn out to be similar to the one achieved by WD-XRF, except for the lightest elements (Na and Mg). The results described in this work proved that μ-ED-XRF spectrometers can be used not only for acquiring high resolution elemental map distributions, but also to perform accurate quantitative studies avoiding the use of more sophisticated WD-XRF systems or the acid extraction/alkaline fusion required as destructive pretreatment in Inductively coupled plasma mass spectrometry based procedures.
Crop productivity can be expressed as the product of the amount of radiation intercepted, radiation use efficiency and harvest index. Genetic variation for components of radiation use efficiency has ...rarely been explored due to the lack of appropriate equipment to determine parameters at the scale needed in plant breeding. On the other hand, responses of the photosynthetic apparatus to environmental conditions have not been extensively investigated under field conditions, due to the challenges posed by the fluctuating environmental conditions. This study applies a rapid, low-cost, and reliable high-throughput phenotyping tool to explore genotypic variation for photosynthetic performance of a set of hybrid barleys and their parents under mild water-stress and unstressed field conditions. We found differences among the genotypic sets that are relevant for plant breeders and geneticists. Hybrids showed lower leaf temperature differential and higher non-photochemical quenching, resembling closer the male parents. The combination of traits detected in hybrids seems favorable, and could indicate improved photoprotection and better fitness under stress conditions. Additionally, we proved the potential of a low-cost, field-based phenotyping equipment to be used routinely in barley breeding programs for early screening for stress tolerance.
The primary objective is to determine the efficacy of a single dose of ivermectin, administered to low risk, non-severe COVID-19 patients in the first 48 hours after symptom onset to reduce the ...proportion of patients with detectable SARS-CoV-2 RNA by Polymerase Chain Reaction (PCR) test from nasopharyngeal swab at day 7 post-treatment. The secondary objectives are: 1.To assess the efficacy of ivermectin to reduce the SARS-CoV-2 viral load in the nasopharyngeal swab at day 7 post treatment.2.To assess the efficacy of ivermectin to improve symptom progression in treated patients.3.To assess the proportion of seroconversions in treated patients at day 21.4.To assess the safety of ivermectin at the proposed dose.5.To determine the magnitude of immune response against SARS-CoV-2.6.To assess the early kinetics of immunity against SARS-CoV-2.
SAINT is a single centre, double-blind, randomized, placebo-controlled, superiority trial with two parallel arms. Participants will be randomized to receive a single dose of 400 μg/kg ivermectin or placebo, and the number of patients in the treatment and placebo groups will be the same (1:1 ratio).
The population for the study will be patients with a positive nasopharyngeal swab PCR test for SARS-CoV-2, with non-severe COVID-19 disease, and no risk factors for progression to severity. Vulnerable populations such as pregnant women, minors (i.e.; under 18 years old), and seniors (i.e.; over 60 years old) will be excluded. Inclusion criteria 1. Patients diagnosed with COVID-19 in the emergency room of the Clínica Universidad de Navarra (CUN) with a positive SARS-CoV-2 PCR. 2. Residents of the Pamplona basin ("Cuenca de Pamplona"). 3. The patient must be between the ages of 18 and 60 years of age. 4. Negative pregnancy test for women of child bearing age*. 5. The patient or his/her representative, has given informed consent to participate in the study. 6. The patient should, in the PI's opinion, be able to comply with all the requirements of the clinical trial (including home follow up during isolation). Exclusion criteria 1. Known history of ivermectin allergy. 2. Hypersensitivity to any component of ivermectin. 3. COVID-19 pneumonia. Diagnosed by the attending physician.Identified in a chest X-ray. 4. Fever or cough present for more than 48 hours. 5. Positive IgG against SARS-CoV-2 by rapid diagnostic test. 6. Age under 18 or over 60 years. 7. The following co-morbidities (or any other disease that might interfere with the study in the eyes of the PI): Immunosuppression.Chronic Obstructive Pulmonary Disease.Diabetes.Hypertension.Obesity.Acute or chronic renal failure.History of coronary disease.History of cerebrovascular disease.Current neoplasm. 8. Recent travel history to countries that are endemic for Loa loa (Angola, Cameroon, Central African Republic, Chad, Democratic Republic of Congo, Ethiopia, Equatorial, Guinea, Gabon, Republic of Congo, Nigeria and Sudan). 9. Current use of CYP 3A4 or P-gp inhibitor drugs such as quinidine, amiodarone, diltiazem, spironolactone, verapamil, clarithromycin, erythromycin, itraconazole, ketoconazole, cyclosporine, tacrolimus, indinavir, ritonavir or cobicistat. Use of critical CYP3A4 substrate drugs such as warfarin. *Women of child bearing age may participate if they use a safe contraceptive method for the entire period of the study and at least one month afterwards. A woman is considered to not have childbearing capacity if she is post-menopausal (minimum of 2 years without menstruation) or has undergone surgical sterilization (at least one month before the study). The trial is currently planned at a single center, Clínica Universidad de Navarra, in Navarra (Spain), and the immunology samples will be analyzed at the Barcelona Institute for Global Health (ISGlobal), in Barcelona (Spain). Participants will be recruited by the investigators at the emergency room and/or COVID-19 area of the CUN. They will remain in the trial for a period of 28 days at their homes since they will be patients with mild disease. In the interest of public health and to contain transmission of infection, follow-up visits will be conducted in the participant's home by a clinical trial team comprising nursing and medical members. Home visits will assess clinical and laboratory parameters of the patients.
Ivermectin will be administered to the treatment group at a 400μg/Kg dose (included in the EU approved label of Stromectol and Scabioral). The control group will receive placebo. There is no current data on the efficacy of ivermectin against the virus in vivo, therefore the use of placebo in the control group is ethically justified.
Primary Proportion of patients with a positive SARS-CoV-2 PCR from a nasopharyngeal swab at day 7 post-treatment. Secondary 1.Mean viral load as determined by PCR cycle threshold (Ct) at baseline and on days 4, 7, 14, and 21.2.Proportion of patients with fever and cough at days 4, 7, 14, and 21 as well as proportion of patients progressing to severe disease or death during the trial.3.Proportion of patients with seroconversion at day 21.4.Proportion of drug-related adverse events during the trial.5.Median levels of IgG, IgM, IgA measured by Luminex, frequencies of innate and SARS-CoV-2-specific T cells assessed by flow cytometry, median levels of inflammatory and activation markers measured by Luminex and transcriptomics.6.Median kinetics of IgG, IgM, IgA levels during the trial, until day 28.
Eligible patients will be allocated in a 1:1 ratio using a randomization list generated by the trial statistician using blocks of four to ensure balance between the groups. A study identification code with the format "SAINT-##" (##: from 01 to 24) will be generated using a sequence of random numbers so that the randomization number does not match the subject identifier. The sequence and code used will be kept in an encrypted file accessible only to the trial statistician. A physical copy will be kept in a locked cabinet at the CUN, accessible only to the person administering the drug who will not enrol or attend to patient care. A separate set of 24 envelopes for emergency unblinding will be kept in the study file.
The clinical trial team and the patients will be blinded. The placebo will not be visibly identical, but it will be administered by staff not involved in the clinical care or participant follow up.
The sample size is 24 patients: 12 participants will be randomised to the treatment group and 12 participants to the control group.
Current protocol version: 1.0 dated 16 of April 2020. Recruitment is envisioned to begin by May 14th and end by June 14th.
EudraCT number: 2020-001474-29, registered April 1
. Clinicaltrials.gov: submitted, pending number FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
Two dominant, closely linked and complementary genes, Btr1 and Btr2, control rachis brittleness in barley. Recessive mutations in any of these genes turn the fragile rachis (brittle) into a tough ...rachis phenotype (non‐brittle). The cross of parents with alternative mutations in the btr genes leads to a brittle F1 hybrid that presents grain retention problems. We evaluated rachis fragility through a mechanical test and under natural conditions, in F1 crosses with different compositions at the btr genes. Brittleness was significantly higher in Btr1btr1Btr2btr2 crosses compared to hybrids and inbred parents carrying one of the mutations (btr1btr1Btr2Btr2/Btr1Btr1btr2btr2). This fact could jeopardize the efficient harvest of hybrids bearing alternative mutations, reducing the choice of possible crosses for hybrid barley breeding and hindering the exploitation of potential heterotic patterns. Furthermore, non‐brittle hybrids showed higher brittleness than inbreds, suggesting the presence of other dominant factors affecting the trait. In conclusion, this work encourages a deeper study of the genetic control of the rachis brittleness trait and urges the consideration of rachis tenacity as a target for hybrid barley breeding.
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