Vertebrate color vision requires spectrally selective opsin-based pigments, expressed in distinct cone photoreceptor populations. In primates and in fish, spectrally divergent opsin genes may reside in head-to-tail tandem arrays. Mechanisms underlying differential expression from such arrays have not been fully elucidated. Regulation of human red () vs. green () opsins is considered a stochastic event, whereby upstream enhancers associate randomly with promoters of the proximal or distal gene, and one of these associations becomes permanent. We demonstrate that, distinct from this stochastic model, the endocrine signal thyroid hormone (TH) regulates differential expression of the orthologous zebrafish / array, and of the tandemly quadruplicated /// array. TH treatment caused dramatic, dose-dependent increases in abundance of , the proximal member of the array, and reduced Fluorescent reporters permitted direct visualization of individual cones switching expression from to Athyroidism increased and reduced , except within a small ventral domain of that was likely sustained by retinoic acid signaling. Changes in abundance and distribution in athyroid zebrafish were rescued by TH, demonstrating plasticity of cone phenotype in response to this signal. TH manipulations also regulated the array, with athyroidism reducing abundance of distal members. Interestingly, the opsins encoded by the proximal gene and distal genes are sensitive to longer wavelengths than other members of their respective arrays; therefore, endogenous TH acts upon each opsin array to shift overall spectral sensitivity toward longer wavelengths, underlying coordinated changes in visual system function during development and growth.

Soil organisms are a crucial part of the terrestrial biosphere. Despite their importance for ecosystem functioning, few quantitative, spatially explicit models of the active belowground community currently exist. In particular, nematodes are the most abundant animals on Earth, filling all trophic levels in the soil food web. Here we use 6,759 georeferenced samples to generate a mechanistic understanding of the patterns of the global abundance of nematodes in the soil and the composition of their functional groups. The resulting maps show that 4.4 ± 0.64 × 10 nematodes (with a total biomass of approximately 0.3 gigatonnes) inhabit surface soils across the world, with higher abundances in sub-Arctic regions (38% of total) than in temperate (24%) or tropical (21%) regions. Regional variations in these global trends also provide insights into local patterns of soil fertility and functioning. These high-resolution models provide the first steps towards representing soil ecological processes in global biogeochemical models and will enable the prediction of elemental cycling under current and future climate scenarios.

HIV remains incurable because of viral persistence in latent reservoirs that are inaccessible to antiretroviral therapy. A potential curative strategy is to reactivate viral gene expression in latently infected cells. However, no drug so far has proven to be successful in vivo in reducing the reservoir, and therefore new anti-latency compounds are needed. We explored the role of microRNAs (miRNAs) in latency maintenance and their modulation as a potential anti-latency strategy. Latency models based on treating resting CD4 T cells with chemokine (C-C motif) ligand 19 (CCL19) or interleukin-7 (IL7) before HIV infection and next-generation sequencing were used to identify the miRNAs involved in HIV latency. We detected four upregulated miRNAs (miRNA-98, miRNA-4516, miRNA-4488, and miRNA-7974). Individual or combined inhibition of these miRNAs was performed by transfection into cells latently infected with HIV. Viral replication, assessed 72 h after transfection, did not increase after miRNA modulation, despite miRNA inhibition and lack of toxicity. Furthermore, the combined modulation of five miRNAs previously associated with HIV latency was not effective in these models. Our results do not support the modulation of miRNAs as a useful strategy for the reversal of HIV latency. As shown with other drugs, the potential of miRNA modulation as an HIV reactivation strategy could be dependent on the latency model used.

Global dissemination of mcr-like genes represents a serious threat to public health since it jeopardizes the effectiveness of colistin, an antibiotic used as a last-resort treatment against highly antibiotic-resistant bacteria. In 2017, a mcr-1-positive isolate was found in Chile for the first time. Herein we report the genetic features of this strain (UCO-457) by whole-genome sequencing (WGS) and conjugation experiments. The UCO-457 strain belonged to ST4204 and carried a 285 kb IncI2-type plasmid containing the mcr-1 gene. Moreover, this plasmid was transferred by conjugation to an E. coli J53 strain at high frequency. The isolate harbored the cma, iroN, and iss virulence genes and did carry resistance genes to rimethoprim/sulfamethoxazole and fluoroquinolones. Other antibiotic resistance determinants such as β-lactamases-encoding genes were not detected, making the isolate highly susceptible to these antibiotics. Our results revealed that such susceptible isolates could be acting as platforms to disseminate plasmid-mediated colistin resistance. Based on this evidence, we consider that mcr-like prevalence deserves urgent attention and should be examined not only in highly resistant bacteria but also in extensively-drug (XDR) and pan-drug resistant isolates (PDR).

Northern coastal Ecuador has seen rapid market integration since the initiation of a road system in the late 1990 s connecting the region to the Andean mountains. We previously demonstrated that, between 2003 and 2013, living in a relatively remote (less accessible) community was protective against stunting in children under five. Our objectives were to characterize trends in BMI among rural adults over the same period, and to examine the co-occurrence of adult overweight or obesity (OB/OW) and child stunting.

Breast-conserving treatment (BCT) have emerged as an alternative to mastectomy in patients with ipsilateral breast tumor recurrence (IBTR). We evaluated survival outcomes and treatment-related toxicity in a series of 40 patients with IBTR, who underwent tumorectomy plus interstitial brachytherapy (APBI) as a salvage treatment.

This paper presents a study carried out to determine the feasibility to obtain bioethanol from an industrial algae waste. The influence of some parameters on acid hydrolysis was studied. The results indicated that the overall hydrolysis ability is a function of the combined action of acid concentration, temperature and reaction time. The hydrolysates with higher amount of reducing sugars were used for ethanolic fermentation using S. Cerevisiae. The highest bioethanol yield 11.6 g/g was obtained at 70 min, a sulphuric acid concentration of 9% wt. and acid/dried algae ratio of 7. The present study showed that the industrial waste of Euchema Spinosum contains carbohydrates that can be converted into bioethanol with an efficiency of 75%. Moreover, the potential of the residue after acid hydrolysis process as sustainable solid fuel regarding its properties was analysed. The results were compared with those obtained from the literature and discussed according to international standards.

Identification of HER2-positive breast cancers with high anti-HER2 sensitivity could help de-escalate chemotherapy. Here, we tested a clinically applicable RNA-based assay that combines ERBB2 and the HER2-enriched (HER2-E) intrinsic subtype in HER2-positive disease treated with dual HER2-blockade without chemotherapy.

the incidence of obstetric sphincter tears has risen to 15-30% and the prevalence of anal incontinence (AI) symptoms after childbirth may be as high as 40%. The present study evaluates the correlation between obstetric injuries detected by endoanal ultrasound (3D-EUS) and AI symptoms, as well as their impact on the quality of life (QOL) of women after childbirth.

The nuclear proliferation marker Ki67 assayed by immunohistochemistry has multiple potential uses in breast cancer, but an unacceptable level of inter-laboratory variability has hampered its clinical utility. The International Ki67 in Breast Cancer Working Group has undertaken a systematic program to determine whether Ki67 measurement can be analytically validated and standardized across laboratories. This study addresses whether acceptable scoring reproducibility can be achieved on excision whole sections.

Optimal pain management is crucial to the postoperative recovery process. We aimed to evaluate the efficacy and safety of intravenous oxycodone with intravenous fentanyl, morphine, sufentanil, pethidine, and hydromorphone for acute postoperative pain.

Ionotropic receptors (IRs) are a large, divergent subfamily of ionotropic glutamate receptors (iGluRs) that are expressed in diverse peripheral sensory neurons and function in olfaction, taste, hygrosensation and thermosensation. Analogous to the cell biological properties of their synaptic iGluR ancestors, IRs are thought to form heteromeric complexes that localise to the ciliated dendrites of sensory neurons. IR complexes are composed of selectively expressed 'tuning' receptors and one of two broadly expressed co-receptors (IR8a or IR25a). While the extracellular ligand-binding domain (LBD) of tuning IRs is likely to define the stimulus specificity of the complex, the role of this domain in co-receptors is unclear.

Information on species distribution is recognized as a crucial input for biodiversity conservation and management. To that end, considerable resources have been dedicated towards increasing the quantity and availability of species occurrence data, boosting their use in species distribution modeling and online platforms for their dissemination. Currently, those platforms face the challenge of bringing biology into modeling by making informed decisions that result in meaningful models, based on limited occurrence and ecological data. Here we describe BioModelos, a modeling approach supported by an online system and a core team of modelers, whereby a network of experts contributes to the development of species distribution models by assessing the quality of occurrence data, identifying potentially limiting environmental variables, establishing species' accessible areas and validating modeling predictions qualitatively. Models developed through BioModelos become freely and publicly available once validated by experts, furthering their use in conservation applications. Our approach has been implemented in Colombia since 2013 and it currently consist of a network of nearly 500 experts that collaboratively contribute to enhance the knowledge on the distribution of a growing number of species and it has aided the development of several decision support products such as national risk assessments and biodiversity compensation manuals. BioModelos is an example of operationalization of an essential biodiversity variable at a national level through the implementation of a research infrastructure that enhances the value of open access species data.

This study examines the relationship between regulatory B (Breg) and T (Treg) compartments, which play crucial roles in the maintenance of immune homeostasis in the context of HIV. Using flow cytometry, the phenotypes of different Breg and Treg subsets from HIV-infected and healthy individuals were analyzed, along with the suppressive capacity of Breg. Peripheral blood samples of thirteen HIV+ treatment-naïve individuals, fourteen treated-HIV+ individuals with undetectable viral load and twelve healthy individuals were analyzed. The absolute counts of Breg and Treg subsets were decreased in HIV+ treatment-naïve individuals in comparison to treated-HIV+ and healthy individuals. Interestingly, correlations between Breg subsets (CD24hiCD27+ and PD-L1+ B cells) and IL-10-producing Breg observed in healthy individuals were lost in HIV+ treatment-naïve individuals. However, a correlation between frequencies of CD24hiCD38hi or TIM-1+-Breg subsets and Treg was observed in HIV+ treatment-naïve individuals and not in healthy individuals. Therefore, we hypothesized that various Breg subsets might have different functions during B and T-cell homeostasis during HIV-1 infection. In parallel, stimulated Breg from HIV-infected treatment-naïve individuals presented a decreased ability to suppress CD4+ T-cell proliferation in comparison to the stimulated Breg from treated-HIV+ or healthy individuals. We demonstrate a dysregulation between Breg and Treg subsets in HIV-infected individuals, which might participate in the hyper-activation and exhaustion of the immune system that occurs in such patients.

HER2-positive (+) breast cancers, defined by HER2 overexpression and/or amplification, are often addicted to HER2 to maintain their malignant phenotype. Yet, some HER2+ tumors do not benefit from anti-HER2 therapy. We hypothesize that HER2 amplification levels and PI3K pathway activation are key determinants of response to HER2-targeted treatments without chemotherapy.

Herpes simplex virus encephalitis (HSE) is the most common cause of sporadic fatal encephalitis worldwide and remains a devastating disease despite antiviral therapy. EEG can be an important tool in the diagnosis of HSE, and we propose that it can be used to monitor the progression of the disease in patients with treatment refractory HSE.

The hemolysin (Hly) secretion system of E. coli allows the one-step translocation of hemolysin A (HlyA) from the bacterial cytoplasm to the extracellular medium, without a periplasmic intermediate. In this work, we investigate whether the Hly secretion system of E. coli is competent to secrete a repertoire of functional single-domain VHH antibodies (nanobodies, Nbs), facilitating direct screening of VHH libraries and the purification of selected Nb from the extracellular medium.