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1.
Microorganisms ; 12(5)2024 Apr 28.
Article in English | MEDLINE | ID: mdl-38792714

ABSTRACT

It was in the 1800s when the first public publications about the infection and treatment of gonorrhoea were released. However, the first prevention programmes were only published a hundred years later. In the 1940s, the concept of vaccination was introduced into clinical prevention programmes to address early sulphonamide resistance. Since then, tons of publications on Neisseria gonorrhoeae are undisputed, around 30,000 publications today. Currently, the situation seems to be just as it was in the last century, nothing has changed or improved. So, what are we doing wrong? And more importantly, what might we do? The review presented here aims to review the current situation regarding the resistance mechanisms, prevention programmes, treatments, and vaccines, with the challenge of better understanding this special pathogen. The authors have reviewed the last five years of advancements, knowledge, and perspectives for addressing the Neisseria gonorrhoeae issue, focusing on new therapeutic alternatives.

2.
Plant Physiol ; 2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38478585

ABSTRACT

Hydroxylated monoterpenes (HMTPs) are differentially emitted by tomato (Solanum lycopersicum) plants resisting bacterial infection. We have studied the defensive role of these volatiles in the tomato response to bacteria, whose main entrance are through stomatal apertures. Treatments with some HMTPs resulted in stomatal closure and pathogenesis-related protein 1 (PR1) induction. Particularly, α-terpineol induced stomatal closure in a salicylic acid (SA) and abscisic acid-independent manner and conferred resistance to bacteria. Interestingly, transgenic tomato plants overexpressing or silencing the monoterpene synthase MTS1, which displayed alterations in the emission of HMTPs, exhibited changes in the stomatal aperture but not in plant resistance. Measures of both 2-C-methyl-D-erythritol-2,4-cyclopyrophosphate (MEcPP) and SA levels revealed competition for MEcPP by the methylerythritol phosphate (MEP) pathway and SA biosynthesis activation, thus explaining the absence of resistance in transgenic plants. These results were confirmed by chemical inhibition of the MEP pathway, which alters MEcPP levels. Treatments with BTH, a SA functional analogue, conferred enhanced resistance to transgenic tomato plants overexpressing MTS1. Additionally, these MTS1 overexpressors induced PR1 gene expression and stomatal closure in neighbouring plants. Our results confirm the role of HMTPs in both intra and inter-plant immune signalling and reveal a metabolic crosstalk between the MEP and SA pathways in tomato plants.

3.
Hortic Res ; 11(1): uhad248, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38239809

ABSTRACT

Biotic and abiotic stresses can severely limit crop productivity. In response to drought, plants close stomata to prevent water loss. Furthermore, stomata are the main entry point for several pathogens. Therefore, the development of natural products to control stomata closure can be considered a sustainable strategy to cope with stresses in agriculture. Plants respond to different stresses by releasing volatile organic compounds. Green leaf volatiles, which are commonly produced across different plant species after tissue damage, comprise an important group within volatile organic compounds. Among them, (Z)-3-hexenyl butyrate (HB) was described as a natural inducer of stomatal closure, playing an important role in stomatal immunity, although its mechanism of action is still unknown. Through different genetic, pharmacological, and biochemical approaches, we here uncover that HB perception initiates various defence signalling events, such as activation of Ca2+ permeable channels, mitogen-activated protein kinases, and production of Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-mediated reactive oxygen species. Furthermore, HB-mediated stomata closure was found to be independent of abscisic acid biosynthesis and signalling. Additionally, exogenous treatments with HB alleviate water stress and improve fruit productivity in tomato plants. The efficacy of HB was also tested under open field conditions, leading to enhanced resistance against Phytophthora spp. and Pseudomonas syringae infection in potato and tomato plants, respectively. Taken together, our results provide insights into the HB signalling transduction pathway, confirming its role in stomatal closure and plant immune system activation, and propose HB as a new phytoprotectant for the sustainable control of biotic and abiotic stresses in agriculture.

4.
Macromol Biosci ; 24(1): e2300109, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37401723

ABSTRACT

Developing biomaterials for corneal repair and regeneration is crucial for maintaining clear vision. The cornea, a specialized tissue, relies on corneal keratocytes, that respond to their mechanical environment. Altering stiffness affects keratocyte behavior, but static stiffness alone cannot capture the dynamic properties of in vivo tissue. This study proposes that the cornea exhibits time-dependent mechanical properties, similar to other tissues, and aims to replicate these properties in potential therapeutic matrices. First, the cornea's stress relaxation properties are investigated using nanoindentation, revealing 15% relaxation within 10 seconds. Hydrogel dynamicity is then modulated using a specially formulated alginate-PEG and alginate-norbornene mixture. The tuning of the hydrogel's dynamicity is achieved through a photoinitiated norbornene-norbornene dimerization reaction, resulting in relaxation times ranging from 30 seconds to 10 minutes. Human primary corneal keratocytes are cultured on these hydrogels, demonstrating reduced αSMA (alpha smooth muscle actin) expression and increased filopodia formation on slower relaxing hydrogels, resembling their native phenotype. This in vitro model can enable the optimization of stress relaxation for various cell types, including corneal keratocytes, to control tissue formation. Combining stress relaxation optimization with stiffness assessment provides a more accurate tool for studying cell behavior and reduces mechanical mismatch with native tissues in implanted constructs.


Subject(s)
Alginates , Hydrogels , Humans , Hydrogels/pharmacology , Alginates/pharmacology , Sulfhydryl Compounds , Cornea , Norbornanes , Tissue Engineering/methods
5.
Cult Health Sex ; : 1-16, 2023 Dec 06.
Article in English | MEDLINE | ID: mdl-38056488

ABSTRACT

Research documents how abortion can be emotionally difficult and stigmatising, but generally has not considered whether and how involvement in abortion may be a source of positive emotions, including pleasure, belonging and even joy. The absence of explorations that start from the possibility of abortion pleasure and joy represents an epistemic foreclosure. Moreover, it highlights how social science literature has tended to emphasise the negative aspects of abortion care in ways that produce or amplify normative negative associations. In this paper, we investigate the positive emotions, pleasure and joy of abortion involvement by drawing on interviews conducted in 2019 with 28 abortion accompaniers in Argentina, Chile, and Ecuador about their experiences accompanying abortions after 17 weeks' gestation. Abortion accompaniment is a response to unsafe and/or inaccessible abortion whereby volunteer activists guide abortion seekers through a medication abortion. Interviewees described how the practice of accompaniment generated positive emotions by building a feminist community, shared intimacy among women, and witnessing aborting people claim their strength. Importantly, these positive emotional experiences of involvement with abortion were not distinct from the broader marginalisation of abortion but were, instead, rooted in its marginalisation.

6.
Article in English | MEDLINE | ID: mdl-37962789

ABSTRACT

Testicular cancer (TCa) is a rare malignancy affecting young men worldwide. Sociodemographic factors, especially socioeconomic level (SEL) and healthcare access, seem to impact TCa incidence and outcomes, particularly among Hispanic populations. However, limited research has explored these variables in Hispanic groups. This study aimed to investigate sociodemographic and clinical factors in Mexico and their role in health disparities among Hispanic TCa patients. We retrospectively analyzed 244 Mexican TCa cases between 2007 and 2020 of a representative cohort with diverse social backgrounds from a national reference cancer center. Logistic regression identified risk factors for fatality: non-seminoma histology, advanced stage, and lower education levels. Age showed a significant trend as a risk factor. Patient delay and healthcare distance lacked significant associations. Inadequate treatment response and chemotherapy resistance were more likely in advanced stages, while higher education positively impacted treatment response. Cox regression highlighted non-seminoma histology, below-median SEL, higher education, and advanced-stage survival rates. Survival disparities emerged based on tumor histology and patient SEL. This research underscores the importance of comprehensive approaches that integrate sociodemographic, biological, and environmental factors to address health disparities improving outcomes through personalized interventions in Hispanic individuals with TCa.

7.
ISME J ; 17(12): 2381-2388, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37907733

ABSTRACT

Satellites are mobile genetic elements that are dependent upon the replication machinery of their helper viruses. Bacteriophages have provided many examples of satellite nucleic acids that utilize their helper morphogenic genes for propagation. Here we describe two novel satellite-helper phage systems, Mulch and Flayer, that infect Streptomyces species. The satellites in these systems encode for encapsidation machinery but have an absence of key replication genes, thus providing the first example of bacteriophage satellite viruses. We also show that codon usage of the satellites matches the tRNA gene content of the helpers. The satellite in one of these systems, Flayer, does not appear to integrate into the host genome, which represents the first example of a virulent satellite phage. The Flayer satellite has a unique tail adaptation that allows it to attach to its helper for simultaneous co-infection. These findings demonstrate an ever-increasing array of satellite strategies for genetic dependence on their helpers in the evolutionary arms race between satellite and helper phages.


Subject(s)
Bacteriophages , Streptomyces , Satellite Viruses/genetics , Streptomyces/genetics , Virulence , Helper Viruses/genetics , Bacteriophages/genetics
8.
Front Cell Infect Microbiol ; 13: 1266685, 2023.
Article in English | MEDLINE | ID: mdl-37842006

ABSTRACT

Introduction: The emergence of resistance and interference mechanisms to phage infection can hinder the success of bacteriophage-based applications, but the significance of these mechanisms in phage therapy has not been determined. This work studies the emergence of Salmonella isolates with reduced susceptibility to a cocktail of three phages under three scenarios: i) Salmonella cultures (LAB), ii) biocontrol of cooked ham slices as a model of food safety (FOOD), and iii) oral phage therapy in broilers (PT). Methods: S. Typhimurium ATCC 14028 RifR variants with reduced phage susceptibility were isolated from the three scenarios and conventional and molecular microbiology techniques were applied to study them. Results and discussion: In LAB, 92% of Salmonella isolates lost susceptibility to all three phages 24 h after phage infection. This percentage was lower in FOOD, with 4.3% of isolates not susceptible to at least two of the three phages after seven days at 4°C following phage treatment. In PT, 9.7% and 3.3 % of isolates from untreated and treated broilers, respectively, displayed some mechanism of interference with the life cycle of some of the phages. In LAB and FOOD scenarios, resistant variants carrying mutations in rfc and rfaJ genes involved in lipopolysaccharide synthesis (phage receptor) were identified. However, in PT, the significant decrease of EOP, ECOI, and burst size observed in isolates was prompted by lateral gene transfer of large IncI1 plasmids, which may encode phage defense mechanisms. These data indicate that the acquisition of specific conjugative plasmids has a stronger impact than mutagenesis on the emergence of reduced phage-susceptibility bacteria in certain environments. In spite of this, neither mechanism seems to significantly impair the success of Salmonella biocontrol and oral phage therapy.


Subject(s)
Bacteriophages , Phage Therapy , Salmonella Phages , Animals , Bacteriophages/genetics , Salmonella Phages/genetics , Chickens , Gene Transfer, Horizontal , Mutagenesis , Bacteria
9.
Cells ; 12(15)2023 07 26.
Article in English | MEDLINE | ID: mdl-37566010

ABSTRACT

The human lifespan has increased over the past century; however, healthspans have not kept up with this trend, especially cognitive health. Among nutrients for brain function maintenance, long-chain omega-3 polyunsaturated fatty acids (ω-3 LCPUFA): DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid) must be highlighted, particularly structured forms of EPA and DHA which were developed to improve bioavailability and bioactivity in comparison with conventional ω-3 supplements. This study aims to elucidate the effect of a structured triglyceride form of DHA (DHA-TG) on the healthspan of aged C. elegans. Using a thrashing assay, the nematodes were monitored at 4, 8, and 12 days of adulthood, and DHA-TG improved its motility at every age without affecting lifespan. In addition, the treatment promoted antioxidant capacity by enhancing the activity and expression of SOD (superoxide dismutase) in the nematodes. Lastly, as the effect of DHA-TG was lost in the DAF-16 mutant strain, it might be hypothesized that the effects of DHA need DAF-16/FOXO as an intermediary. In brief, DHA-TG exerted a healthspan-promoting effect resulting in both enhanced physical fitness and increased antioxidant defense in aged C. elegans. For the first time, an improvement in locomotive function in aged wild-type nematodes is described following DHA-TG treatment.


Subject(s)
Docosahexaenoic Acids , Fatty Acids, Omega-3 , Humans , Animals , Adult , Aged , Docosahexaenoic Acids/pharmacology , Docosahexaenoic Acids/metabolism , Antioxidants/pharmacology , Caenorhabditis elegans/metabolism , Triglycerides
10.
ACS Biomater Sci Eng ; 9(8): 5006-5014, 2023 08 14.
Article in English | MEDLINE | ID: mdl-37490420

ABSTRACT

Coronary artery disease affects millions worldwide. Bypass surgery remains the gold standard; however, autologous tissue is not always available. Hence, the need for an off-the-shelf graft to treat these patients remains extremely high. Using melt spinning, we describe here the fabrication of tubular scaffolds composed of microfibers aligned in the circumferential orientation mimicking the organized extracellular matrix in the tunica media of arteries. By variation of the translational extruder speed, the angle between fibers ranged from 0 to ∼30°. Scaffolds with the highest angle showed the best performance in a three-point bending test. These constructs could be bent up to 160% strain without kinking or breakage. Furthermore, when liquid was passed through the scaffolds, no leakage was observed. Suturing of native arteries was successful. Mesenchymal stromal cells were seeded on the scaffolds and differentiated into vascular smooth muscle-like cells (vSMCs) by reduction of serum and addition of transforming growth factor beta 1 and ascorbic acid. The scaffolds with a higher angle between fibers showed increased expression of vSMC markers alpha smooth muscle actin, calponin, and smooth muscle protein 22-alpha, whereas a decrease in collagen 1 expression was observed, indicating a positive contractile phenotype. Endothelial cells were seeded on the repopulated scaffolds and formed a tightly packed monolayer on the luminal side. Our study shows a one-step fabrication for ECM-mimicking scaffolds with good handleability, leak-free property, and suturability; the excellent biocompatibility allowed the growth of a bilayered construct. Future work will explore the possibility of using these scaffolds as vascular conduits in in vivo settings.


Subject(s)
Tissue Engineering , Tissue Scaffolds , Endothelial Cells , Extracellular Matrix/metabolism , Cell Differentiation
11.
New Phytol ; 239(6): 2292-2306, 2023 09.
Article in English | MEDLINE | ID: mdl-37381102

ABSTRACT

Carotenoids are photoprotectant pigments and precursors of hormones such as strigolactones (SL). Carotenoids are produced in plastids from geranylgeranyl diphosphate (GGPP), which is diverted to the carotenoid pathway by phytoene synthase (PSY). In tomato (Solanum lycopersicum), three genes encode plastid-targeted GGPP synthases (SlG1 to SlG3) and three genes encode PSY isoforms (PSY1 to PSY3). Here, we investigated the function of SlG1 by generating loss-of-function lines and combining their metabolic and physiological phenotyping with gene co-expression and co-immunoprecipitation analyses. Leaves and fruits of slg1 lines showed a wild-type phenotype in terms of carotenoid accumulation, photosynthesis, and development under normal growth conditions. In response to bacterial infection, however, slg1 leaves produced lower levels of defensive GGPP-derived diterpenoids. In roots, SlG1 was co-expressed with PSY3 and other genes involved in SL production, and slg1 lines grown under phosphate starvation exuded less SLs. However, slg1 plants did not display the branched shoot phenotype observed in other SL-defective mutants. At the protein level, SlG1 physically interacted with the root-specific PSY3 isoform but not with PSY1 and PSY2. Our results confirm specific roles for SlG1 in producing GGPP for defensive diterpenoids in leaves and carotenoid-derived SLs (in combination with PSY3) in roots.


Subject(s)
Diterpenes , Solanum lycopersicum , Solanum lycopersicum/genetics , Geranylgeranyl-Diphosphate Geranylgeranyltransferase/genetics , Geranylgeranyl-Diphosphate Geranylgeranyltransferase/metabolism , Farnesyltranstransferase , Carotenoids/metabolism , Protein Isoforms , Plant Leaves/metabolism
12.
J Gastrointest Oncol ; 14(2): 692-704, 2023 Apr 29.
Article in English | MEDLINE | ID: mdl-37201039

ABSTRACT

Background: The combination of trifluridine and tipiracil is indicated in patients with metastatic colorectal cancer previously treated or non-candidates to chemotherapy and biological therapies. This study in routine clinical practice aimed to describe the effectiveness and safety of trifluridine and tipiracil and identify prognostic factors in patients with metastatic colorectal cancer in Spain. Methods: This analysis was a retrospective, observational, multicenter study that included patients aged ≥18 years who had received treatment with trifluridine/tipiracil for metastatic colorectal cancer in third- or subsequent lines. Results: Overall, 294 were evaluated. Trifluridine/tipiracilmedian (minimum, maximum) treatment duration was 3.5 (1.0-29.0) months, and 128 (43.5%) patients received subsequent treatments. One hundred (34%) patients showed disease control rate, and the median progression-free survival and overall survival from trifluridine/tipiracil treatment onset were 3.7 and 7.5 months, respectively. The most frequently reported adverse events were asthenia (all grades, 57.9%) and neutropenia (all grades, 51.3%). A 39.1% and 4.4% of the participants had a dose reduction and a treatment interruption due to toxicity. Patients with age ≥65 years, low tumor burden, ≤2 metastasis sites, treatment dose reduction, neutropenia, and ≥6 cycles, had significantly higher overall survival, progression-free survival, and response rate. Conclusions: This real-life study indicates that trifluridine/tipiracil shows effectiveness and safety in treating patients with metastatic colorectal cancer. The results show a profile of metastatic colorectal cancer patients with previously unknown prognostic factors who have a more significant benefit from treatment with trifluridine/tipiracil in routine clinical practice.

13.
Biofabrication ; 15(3)2023 04 14.
Article in English | MEDLINE | ID: mdl-36947889

ABSTRACT

In recent years, engineering biomimetic cellular microenvironments have been a top priority for regenerative medicine. Collagen II, which is arranged in arches, forms the predominant fiber network in articular cartilage. Due to the shortage of suitable microfabrication techniques capable of producing 3D fibrous structures,in vitroreplication of the arch-like cartilaginous tissue constitutes one of the major challenges. Hence, in the present study, we report a 3D bioprinting approach for fabricating arch-like constructs using two types of bioinks, gelatin methacryloyl (GelMa) and silk fibroin-gelatin (SF-G). The bioprinted SF-G constructs displayed increased proliferation of the encapsulated human bone marrow-derived mesenchymal stem cells compared to the GelMA constructs. Biochemical assays, gene, and protein expression exhibited the superior role of SF-G in forming the fibrous collagen network and chondrogenesis. Protein-protein interaction study using Metascape evaluated the function of the proteins involved. Further GeneMANIA and STRING analysis using Col 2A1, SOX 9, ACAN, and the genes upregulated on day 21 in RT-PCR, i.e.ß-catenin, TGFßR1, Col 1A1 in SF-G and PRG4, Col 10A1, MMP 13 in GelMA validated ourin vitroresults. These findings emphasized the role of SF-G in regulating the Wnt/ß-catenin and TGF-ßsignaling pathways. Hence, the 3D bioprinted arch-like constructs possess a substantial potential for cartilage regeneration.


Subject(s)
Bioprinting , Cartilage, Articular , Fibroins , Humans , Gelatin/chemistry , Fibroins/chemistry , beta Catenin , Biomimetics , Bioprinting/methods , Tissue Engineering/methods , Tissue Scaffolds/chemistry , Printing, Three-Dimensional , Hydrogels/chemistry
14.
Nat Commun ; 14(1): 1381, 2023 Mar 13.
Article in English | MEDLINE | ID: mdl-36914623

ABSTRACT

Lack of reproducibility hampers molecular devices integration into large-scale circuits. Thus, incorporating operando characterization can facilitate the understanding of multiple features producing disparities in different devices. In this work, we report the realization of hybrid molecular graphene field effect transistors (m-GFETs) based on 11-(Ferrocenyl)undecanethiol (FcC11SH) micro self-assembled monolayers (µSAMs) and high-quality graphene (Gr) in a back-gated configuration. On the one hand, Gr enables redox electron transfer, avoids molecular degradation and permits operando spectroscopy. On the other hand, molecular electrode decoration shifts the Gr Dirac point (VDP) to neutrality and generates a photocurrent in the Gr electron conduction regime. Benefitting from this heterogeneous response, the m-GFETs can implement optoelectronic AND/OR logic functions. Our approach represents a step forward in the field of molecular scale electronics with implications in sensing and computing based on sustainable chemicals.

15.
Healthcare (Basel) ; 10(10)2022 Oct 11.
Article in English | MEDLINE | ID: mdl-36292440

ABSTRACT

The objective of this study was to carry out a reliability generalization meta-analysis of the Internet Gaming Disorder Scale (IGDS) to find out if it presents adequate values that justify its application in its four versions: original and abbreviated with dichotomous or ordinal response. A systematic review including 26 studies that apply this instrument from 2015 to June 2022 was conducted. For each version, a reliability generalization meta-analysis was performed with the random coefficients (RC) and varying coefficients (VC) model. Results showed reliability levels > 0.80 in the ordinal versions (IGDS9P and IGDS27P) and in the dichotomous 27-item version (IGDS27D), while the dichotomous 9-item version (IGDS9D) produced levels > 0.70. High heterogeneity was found in all versions (I2 > 95%; Rb > 90%). Cronbach's α means with both models (RC-VC) did not differ significantly except for the IGDS9D version. It is concluded that, considering the dependence of the results on sample size, abbreviated versions do not guarantee that reliability remains acceptable, and dichotomous versions may provide limited but acceptable reliability. Finally, IGDS27P version is recommended in contexts where high precision is required.

16.
Healthcare (Basel) ; 10(10)2022 Oct 20.
Article in English | MEDLINE | ID: mdl-36292546

ABSTRACT

Prospect Theory (PT) is an alternative, dynamic explanation of the phenomenon of risky decision making. This research presents an overview of PT's history in health fields, including advancements, limitations, and bibliometric data. A systematic and bibliometric review of the scientific literature included in the psychological categories of Web of Science (WoS) was performed following the PRISMA 2020 statement for systematic reviews. A total of 37 studies (10 non-empirical and 27 empirical) were included in the sample. Bibliometric results showed thematic variability and heterogeneity regarding the production, researchers, and methodologies that are used to study PT. The systematic results highlight three main fields of PT research: preventive and screening behaviors, promotion of healthy habits, and COVID-related decision making. Personal and contextual factors which alter the usual pattern specified by PT are also described. To conclude, PT currently has an interdisciplinary character suitable for health promotion, with recent studies broadening its applicability.

17.
Biomater Adv ; 139: 212972, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35882129

ABSTRACT

Smooth muscle cells play a pivotal role in maintaining blood pressure and remodeling of the extracellular matrix. These cells have a characteristic spindle shape and are aligned in the radial direction to aid in the constriction of any artery. Tissue engineered grafts have the potential to recreate this alignment and offer a viable alternative to non-resorbable or autologous grafts. Specifically, with melt spinning small diameter fibers can be created that can align circumferentially on the scaffolds. In this study, a set of simplified equations were formulated to predict the final fiber parameters. Smooth muscle cell alignment was monitored on the fabricated scaffolds. Finally, a co-culture of smooth muscle cells in direct contact with endothelial cells was performed to assess the influence of the smooth muscle cell alignment on the morphology of the endothelial cells. The results show that the equations were able to accurately predict the fiber diameter, distance and angle. Primary vascular smooth muscle cells aligned according to the fiber direction mimicking the native orientation. The co-culture with endothelial cells showed that the aligned smooth muscle cells did not have an influence on the morphology of the endothelial cells. In conclusion, we formulated a series of equations that can predict the fiber parameters during melt spinning. Furthermore, the method described here can create a vascular graft with smooth muscle cells aligned circumferentially that morphologically mimics the native orientation.


Subject(s)
Tissue Engineering , Tissue Scaffolds , Biomimetics , Endothelial Cells , Myocytes, Smooth Muscle , Tissue Engineering/methods
18.
Cancers (Basel) ; 14(9)2022 Apr 20.
Article in English | MEDLINE | ID: mdl-35565196

ABSTRACT

Despite having a favorable response to platinum-based chemotherapies, ~15% of Testicular Germ-Cell Tumor (TGCT) patients are platinum-resistant. Mortality rates among Latin American countries have remained constant over time, which makes the study of this population of particular interest. To gain insight into this phenomenon, we conducted whole-exome sequencing, microarray-based comparative genomic hybridization, and copy number analysis of 32 tumors from a Mexican cohort, of which 18 were platinum-sensitive and 14 were platinum-resistant. We incorporated analyses of mutational burden, driver mutations, and SNV and CNV signatures. DNA breakpoints in genes were also investigated and might represent an interesting research opportunity. We observed that sensitivity to chemotherapy does not seem to be explained by any of the mutations detected. Instead, we uncovered CNVs, particularly amplifications on segment 2q11.1 as a novel variant with chemosensitivity biomarker potential. Our data shed light into understanding platinum resistance in a Latin-origin population.

19.
Plants (Basel) ; 11(8)2022 Apr 17.
Article in English | MEDLINE | ID: mdl-35448819

ABSTRACT

Legumes are the recommended crops to fight against soil degradation and loss of fertility because of their known positive impacts on soils. Our interest is focused on the identification of plant-growth-promoting endophytes inhabiting nodules able to enhance legume growth in poor and/or degraded soils. The ability of Variovorax paradoxus S110T and Variovorax gossypii JM-310T to promote alfalfa growth in nutrient-poor and metal-contaminated estuarine soils was studied. Both strains behaved as nodule endophytes and improved in vitro seed germination and plant growth, as well as nodulation in co-inoculation with Ensifer medicae MA11. Variovorax ameliorated the physiological status of the plant, increased nodulation, chlorophyll and nitrogen content, and the response to stress and metal accumulation in the roots of alfalfa growing in degraded soils with moderate to high levels of contamination. The presence of plant-growth-promoting traits in Variovorax, particularly ACC deaminase activity, could be under the observed in planta effects. Although the couple V. gossypii-MA11 reported a great benefit to plant growth and nodulation, the best result was observed in plants inoculated with the combination of the three bacteria. These results suggest that Variovorax strains could be used as biofertilizers to improve the adaptation of legumes to degraded soils in soil-recovery programs.

20.
Adv Healthc Mater ; 11(1): e2101576, 2022 01.
Article in English | MEDLINE | ID: mdl-34614297

ABSTRACT

Rational design of hydrogels that balance processability and extracellular matrix (ECM) biomimicry remains a challenge for tissue engineering and biofabrication. Hydrogels suitable for biofabrication techniques, yet tuneable to match the mechanical (static and dynamic) properties of native tissues remain elusive. Dynamic covalent hydrogels possessing shear-thinning/self-healing (processability) and time-dependent cross-links (mechanical properties) provide a potential solution, yet can be difficult to rationally control. Here, the straightforward modular mixing of dynamic cross-links with different timescales (hydrazone and oxime) is explored using rheology, self-healing tests, extrusion printing, and culture of primary human dermal fibroblasts. Maintaining a constant polymer content and cross-linker concentration, the stiffness and stress relaxation can be tuned across two orders of magnitude. All formulations demonstrate a similar flow profile after network rupture, allowing the separation of initial mechanical properties from flow behavior during printing. Furthermore, the self-healing nature of hydrogels with high hydrazone content enables recyclability of printed structures. Last, a distinct threshold for cell spreading and morphology is observed within this hydrogel series, even in multi-material constructs. Simple cross-linker mixing enables fine control and is of general interest for bioink development, targeting viscoelastic properties of specific cellular niches, and as an accessible and flexible platform for designing dynamic networks.


Subject(s)
Bioprinting , Hydrogels , Extracellular Matrix , Humans , Printing, Three-Dimensional , Tissue Engineering , Tissue Scaffolds
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