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1.
J Fungi (Basel) ; 10(5)2024 May 08.
Article in English | MEDLINE | ID: mdl-38786693

ABSTRACT

Cryptococcus neoformans is a lethal fungus that primarily affects the respiratory system and the central nervous system. One of the main virulence factors is the capsule, constituted by the polysaccharides glucuronoxylomannan (GXM) and glucuronoxylomanogalactan (GXMGal). Polysaccharides are immunomodulators. One of the target cell populations for modulation are macrophages, which are part of the first line of defense and important for innate and adaptive immunity. It has been reported that macrophages can be modulated to act as a "Trojan horse," taking phagocytosed yeasts to strategic sites or having their machinery activation compromised. The scarcity of information on canine cryptococcosis led us to assess whether the purified capsular polysaccharides from C. neoformans would be able to modulate the microbicidal action of macrophages. In the present study, we observed that the capsular polysaccharides, GXM, GXMGal, or capsule total did not induce apoptosis in the DH82 macrophage cell line. However, it was possible to demonstrate that the phagocytic activity was decreased after treatment with polysaccharides. In addition, recovered yeasts from macrophages treated with polysaccharides after phagocytosis could be cultured, showing that their viability was not altered. The polysaccharides led to a reduction in ROS production and the mRNA expression of IL-12 and IL-6. We observed that GXMGal inhibits MHC class II expression and GXM reduces ERK phosphorylation. In contrast, GXMGal and GXM were able to increase the PPAR-γ expression. Furthermore, our data suggest that capsular polysaccharides can reduce the microbicidal activity of canine macrophages DH82.

2.
Microorganisms ; 12(4)2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38674664

ABSTRACT

The SARS-CoV-2 P.1 variant, responsible for an outbreak in Manaus, Brazil, is distinguished by 12 amino acid differences in the S protein, potentially increasing its ACE-2 affinity and immune evasion capability. We investigated the innate immune response of this variant compared to the original B.1 strain, particularly concerning cytokine production. Blood samples from three severe COVID-19 patients were analyzed post-infection with both strains. Results showed no significant difference in cytokine production of mononuclear cells and neutrophils for either variant. While B.1 had higher cytopathogenicity, neither showed viral replication in mononuclear cells. Structural analyses of the S protein highlighted physicochemical variations, which might be linked to the differences in infectivity between the strains. Our studies point to the increased infectivity of P.1 could stem from altered immunogenicity and receptor-binding affinity.

3.
Comput Biol Med ; 174: 108454, 2024 May.
Article in English | MEDLINE | ID: mdl-38608326

ABSTRACT

BACKGROUND: Effective and timely detection is vital for mitigating the severe impacts of Sexually Transmitted Infections (STI), including syphilis and HIV. Cyclic Voltammetry (CV) sensors have shown promise as diagnostic tools for these STI, offering a pathway towards cost-effective solutions in primary health care settings. OBJECTIVE: This study aims to pioneer the use of Fourier Descriptors (FDs) in analyzing CV curves as 2D closed contours, targeting the simultaneous detection of syphilis and HIV. METHODS: Raw CV signals are filtered, resampled, and transformed into 2D closed contours for FD extraction. Essential shape characteristics are captured through selected coefficients. A complementary geometrical analysis further extracts features like curve areas and principal axes lengths from CV curves. A Mahalanobis Distance Classifier is employed for differentiation between patient and control groups. RESULTS: The evaluation of the proposed method revealed promising results with classification performance metrics such as Accuracy and F1-Score consistently achieving values rounded to 0.95 for syphilis and 0.90 for HIV. These results underscore the potential efficacy of the proposed approach in differentiating between patient and control samples for STI detection. CONCLUSION: By integrating principles from biosensors, signal processing, image processing, machine learning, and medical diagnostics, this study presents a comprehensive approach to enhance the detection of both syphilis and HIV. This setts the stage for advanced and accessible STI diagnostic solutions.


Subject(s)
HIV Infections , Syphilis , Humans , Syphilis/diagnosis , HIV Infections/diagnosis , Fourier Analysis , Electrochemical Techniques/methods , Signal Processing, Computer-Assisted
4.
CRISPR J ; 7(2): 88-99, 2024 04.
Article in English | MEDLINE | ID: mdl-38564197

ABSTRACT

Rhodnius prolixus is currently the model vector of choice for studying Chagas disease transmission, a debilitating disease caused by Trypanosoma cruzi parasites. However, transgenesis and gene editing protocols to advance the field are still lacking. Here, we tested protocols for the maternal delivery of CRISPR-Cas9 (clustered regularly spaced palindromic repeats/Cas-9 associated) elements to developing R. prolixus oocytes and strategies for the identification of insertions and deletions (indels) in target loci of resulting gene-edited generation zero (G0) nymphs. We demonstrate successful gene editing of the eye color markers Rp-scarlet and Rp-white, and the cuticle color marker Rp-yellow, with highest effectiveness obtained using Receptor-Mediated Ovary Transduction of Cargo (ReMOT Control) with the ovary-targeting BtKV ligand. These results provide proof of concepts for generating somatic mutations in R. prolixus and potentially for generating germ line-edited lines in triatomines, laying the foundation for gene editing protocols that could lead to the development of novel control strategies for vectors of Chagas disease.


Subject(s)
Chagas Disease , Rhodnius , Animals , Female , Gene Editing/methods , Rhodnius/genetics , Rhodnius/parasitology , CRISPR-Cas Systems , Insect Vectors/parasitology , Chagas Disease/genetics , Chagas Disease/parasitology
5.
J Clin Med ; 13(2)2024 Jan 14.
Article in English | MEDLINE | ID: mdl-38256593

ABSTRACT

INTRODUCTION: The advantages of single-stage treatment of cholecystocholedocholithiasis are well established, but the conditions for carrying out treatment on an outpatient basis require a review of concepts and practices of medical corporations. OBJECTIVE: To evaluate the practice of treating cholecystocholedocholithiasis by laparoendoscopy on an outpatient basis with cost analysis. METHOD: A retrospective study was conducted on patients with cholecystocholedocholithiasis treated by combined laparoscopic cholecystectomy and endoscopic choledocholithotomy from January 2015 to January 2019. After collecting data from physical and digital medical records, the patients were divided into two groups-AR (n = 42)-ambulatory regimen and HR (n = 28)-hospitalization regimen-which were compared in terms of demographic, clinical and treatment variables and their results, as well as in terms of costs. RESULTS: The mean age of the AR group was lower than that of the HR group and the physical status of the AR patients was better when assessed according to the American Society of Anesthesiologists (ASA) (p = 0.01). There was no difference between groups regarding the risk of choledocholithiasis (p = 0.99). For the AR group, the length of stay was shorter: 11.29 h × 65.21 h (p = 0.02), as was the incidence of postoperative complications assessed by applying the Clavien-Dindo classification: 3 (7.1%) × 11 (39.2%) (p < 0.01). The total mean costs were higher for the HR group (USD 2489.93) than the AR group (USD 1650.98) (p = 0.02). CONCLUSION: Outpatient treatment of cholecystocholedocholithiasis by laparoendoscopy is safe and viable for most cases, has a lower cost and can support the reorientation of training and practice of hepatobiliary surgeons.

6.
Mol Cell ; 84(3): 584-595.e6, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38244546

ABSTRACT

The most abundant N6-methyladenosine (m6A) modification on mRNAs is installed non-stoichiometrically across transcripts, with 5' untranslated regions (5' UTRs) being the least conductive. 5' UTRs are essential for translation initiation, yet the molecular mechanisms orchestrated by m6A remain poorly understood. Here, we combined structural, biochemical, and single-molecule approaches and show that at the most common position, a single m6A does not affect translation yields, the kinetics of translation initiation complex assembly, or start codon recognition both under permissive growth and following exposure to oxidative stress. Cryoelectron microscopy (cryo-EM) structures of the late preinitiation complex reveal that m6A purine ring established stacking interactions with an arginine side chain of the initiation factor eIF2α, although with only a marginal energy contribution, as estimated computationally. These findings provide molecular insights into m6A interactions with the initiation complex and suggest that the subtle stabilization is unlikely to affect the translation dynamics under homeostatic conditions or stress.


Subject(s)
Adenosine/analogs & derivatives , Peptide Chain Initiation, Translational , Protein Biosynthesis , 5' Untranslated Regions , Cryoelectron Microscopy , RNA, Messenger/genetics , RNA, Messenger/metabolism , Codon, Initiator/genetics
7.
J Dent ; 141: 104827, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38159901

ABSTRACT

OBJECTIVES: To synthesize and characterize a novel dentin adhesive containing Beta-Tricalcium Phosphate (ß-TCP) nanoparticles and test its ability to reduce dentin permeability (dP). METHODS: Experimental adhesives were prepared by mixing Bis-GMA, TEGDMA, HEMA (50/25/25 wt.%), photo-initiators, and inhibitors. The following groups were tested: Experimental adhesives without ß-TCP (Exp.); with 10 wt.% ß-TCP (Exp.10 wt.% ß-TCP); with 15 wt.% ß-TCP (Exp.15 wt.% ß-TCP), Scotchbond Multi-Purpose (SBMP) and Clearfil SE Protect Bond (CFPB). Degree of conversion (DC%, 10 and 20 s); Flexural Strength (FS), Knoop Hardness (KHN), and Cell Viability (OD%) tests were performed. dP was evaluated by hydraulic conductance, using human dentin disks (n=12), at three-time intervals: post-EDTA (T0); post-treatment (T1); and post-erosion/abrasion cycling (T2). Data were statistically analyzed (α=0.05). RESULTS: For all groups, exposure time for 20 s presented a higher DC% than for 10 s. For FS, filled adhesives did not differ from unfilled and from CFPB. Experimental adhesives did not differ among them and showed lower KHN than the commercial products. Cell viability did not differ among adhesives, except Exp. 15 wt.%, which showed lower OD% than Exp., Exp. 10% and, CFPB. For dP, only Exp.10 and 15 wt.% ß-TCP did not present difference between the times T1 and T2. After cycling, Exp.10 wt.% ß-TCP presented lower permeability than Exp. and CFPB. CONCLUSIONS: The incorporation of 10 wt.% ß-TCP nanoparticles into the resin-based dental material did not affect its mechanical properties and biocompatibility, and promoted the greatest reduction in dentin permeability, sustaining this effect under erosive/abrasive challenges. CLINICAL SIGNIFICANCE: A novel resin-based dental material containing ß-TCP nanoparticles was able to reduce dentin permeability, maintaining its efficacy after erosive/abrasive challenges. The synthesized material did not affect dental pulp cell viability and might be promising for other conditions that require dental remineralization, such as tooth wear and dental caries.


Subject(s)
Calcium Phosphates , Dental Bonding , Dental Caries , Nanoparticles , Humans , Dentin-Bonding Agents/chemistry , Dentin Permeability , Resin Cements/pharmacology , Resin Cements/chemistry , Materials Testing , Dentin/chemistry , Tensile Strength , Dental Cements/chemistry
8.
Rev. bras. cir. cardiovasc ; 39(1): e20230046, 2024. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1521677

ABSTRACT

ABSTRACT Luis Tavares revolutionized cardiac surgery, always bringing the most modern instruments and equipment from his travels to England - surgical forceps, scissors, scalpels, etc. He always insisted that he was not just a thoracic surgeon, for his work extended over a wide field and created three important cardiac surgery centers which promoted a great development of cardiology. He carried out the first open heart surgery (atrial septal defect) employing extracorporeal circulation and closure of a ventricular septal defect with deep surface hypothermia of north and northeast Brazil. He promoted an intense scientific exchange program between Recife and England, resulting in significant advances in medicine, and participated directly in the creation of HEMOPE), leading to radical changes and improvements in blood therapy in the whole country. The PROCAPE, inaugurated in 2006, was the result of the cardiac center created by him in early 1970 at Hospital Oswaldo Cruz and can be considered the second largest public-university cardiology center in Brazil. He is thus widely regarded as an outstanding name in medicine in the 20th century and one of the fathers of modern cardiac surgery in Brazil.

9.
Front Sports Act Living ; 5: 1244168, 2023.
Article in English | MEDLINE | ID: mdl-38077283

ABSTRACT

Our aim was to investigate if using a warm-up routine that included parachute-resisted sprints with large hand-paddles improves 50 m freestyle performance in trained collegiate swimmers. Twelve swimmers (23.9 ± 2.2 years, 179 ± 7 cm, 77.1 ± 10.6 kg) participated in the study and completed two 50-m freestyle races, each preceded by a different warm-up routine, either control (CON) or experimental (EXP). The warm-up routines consisted of 500 m of swimming at self-selected speed, followed by four 10 s sprints with 1 min rest intervals. During EXP, sprints were performed using large hand-paddles and a swimming parachute, while during CON, sprints were performed freely. Performance and technique were assessed during the 50 m freestyle races. We found no significant differences in 25- and 50 m performance times (CON: 12.6 ± 0.8 vs. EXP: 12.5 ± 0.8 s, ES = 0.125; and CON: 26.8 ± 1.6 vs. EXP: 26.7 ± 1.7 s, ES = 0.06, respectively) between the two conditions. Mean stroke length (CON: 2.04 ± 0.21 vs. EXP: 2.02 ± 0.22 m·cycle-1, ES = 0.09), stroke frequency (CON: 55.4 ± 5.3 vs. EXP: 56.3 ± 5.2 cycles s-1, ES = 0.17), and propulsive time (CON: 0.62 ± 0.07 vs. EXP: 0.61 ± 0.06 s, ES = 0.15) were also not different between conditions. It is possible that the CON warm-up routine induced the priming effects that lead to PAPE, or that the EXP warm-up routine primed the athletes further but also induced greater fatigue, resulting in no significant effects on swimming performance. Our findings suggest that parachute-resisted sprints with hand-paddles during warm-up do not enhance 50 m freestyle swimming performance in trained collegiate swimmers. Coaches and practitioners should consider exploring different warm-up protocols to identify what works best for their athletes.

10.
Braz J Cardiovasc Surg ; 39(1): e20230046, 2023 11 09.
Article in English | MEDLINE | ID: mdl-37944009

ABSTRACT

Luis Tavares revolutionized cardiac surgery, always bringing the most modern instruments and equipment from his travels to England - surgical forceps, scissors, scalpels, etc. He always insisted that he was not just a thoracic surgeon, for his work extended over a wide field and created three important cardiac surgery centers which promoted a great development of cardiology. He carried out the first open heart surgery (atrial septal defect) employing extracorporeal circulation and closure of a ventricular septal defect with deep surface hypothermia of north and northeast Brazil. He promoted an intense scientific exchange program between Recife and England, resulting in significant advances in medicine, and participated directly in the creation of HEMOPE), leading to radical changes and improvements in blood therapy in the whole country. The PROCAPE, inaugurated in 2006, was the result of the cardiac center created by him in early 1970 at Hospital Oswaldo Cruz and can be considered the second largest public-university cardiology center in Brazil. He is thus widely regarded as an outstanding name in medicine in the 20th century and one of the fathers of modern cardiac surgery in Brazil.


Subject(s)
Cardiac Surgical Procedures , Cardiology , Heart Septal Defects, Atrial , Thoracic Surgery , Humans , Cardiac Surgical Procedures/history , Thoracic Surgery/history , Extracorporeal Circulation
11.
Photodiagnosis Photodyn Ther ; 44: 103883, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37944626

ABSTRACT

BACKGROUND: The objective of this study was to evaluate the effect of bleaching techniques, including or not the use of violet light (405-410 nm), on resin-based composites' color, surface roughness, nanohardness, and elastic modulus. METHODS: Ninety-six disk-shaped specimens (12 mm x 2 mm; n = 12) were prepared using Filtek Z350 XT (Z350) and IPS Empress Direct (ED) resin-based composites. After 24 h, specimens were stained in red wine for 28 days. After staining, specimens were divided into four experimental groups: 40 % Hydrogen Peroxide (HP); Violet Light (VL); 40 % Hydrogen Peroxide associated with Violet Light (HP+VL), and a control group - no treatment (NT). Specimens were evaluated at six experimental times: initial (24 h after light curing); after staining and after the 1st, 2nd, 3rd, and 4th bleaching sessions regarding the color change (ΔE00, L*, a*, b*, and WID); roughness (Ra), nanohardness and elastic modulus (GPa). Two-way analysis of variance for repeated measures was performed (α=0.05 %). RESULTS: There was a statistically significant difference between staining and the 1st bleaching session for all ED groups (p<0.05). After the last bleaching session, there were no differences between the experimental and the control groups of both resin-based composites. Bleaching using violet light did not change the roughness, nanohardness and elastic modulus of the tested resin-based composites (p>0.05). CONCLUSIONS: Although hydrogen peroxide and violet light remove pigments from resin-based composites without affecting their surface roughness, nanohardness, and elastic modulus, the color change was similar to the one obtained by immersion in distilled water.


Subject(s)
Photochemotherapy , Tooth Bleaching Agents , Tooth Bleaching , Tooth Bleaching/methods , Hydrogen Peroxide , Tooth Bleaching Agents/pharmacology , Materials Testing , Surface Properties , Photochemotherapy/methods , Photosensitizing Agents , Composite Resins , Color
12.
IJID Reg ; 9: 88-94, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37953882

ABSTRACT

Objectives: Previously, we presented the effectiveness of ChAdOx1 nCoV-19 half-dose (HD) immunization for preventing new COVID-19 cases. Here, we evaluated the administration of an HD of ChAdOx1 nCoV-19 in the primary immunization protocol (up to two doses) in reducing moderate and severe cases, hospitalizations, and deaths when compared to the administration of full doses (FD) after a long-term follow-up. Methods: We evaluated data from 29,469 participants between January 2021 and November 2022 who received an HD or FD vaccine and crossed this information with their medical records to identify those who developed moderate or severe cases. All participants were classified into four groups according to their immunization status and followed 500 days after the last vaccine administration. Results: The propensity-score matching analysis indicates that the administration of the two HDs of ChAdOx1 nCoV-19 was equivalent to the use of two FDs to reduce moderate and severe COVID-19 cases. The relative risk of being infected and developing moderate or severe conditions after the administration of at least one HD or FD was similar 150 or 500 days after the administration of the immunizers. Conclusion: Administering two HDs can be used safely as a cost-effective alternative to the primary immunization protocol.

13.
Article in English | MEDLINE | ID: mdl-37917303

ABSTRACT

Recognizing the variety of borders that gather and divide our world, such as geographical, temporal, social and psychological, the study highlights that the transit across these borders drives changes and continuities that contribute to human development. The research emphasizes the relevance of reviewing both the individual singularities and the shared aspects of border crossing experiences. The matching of these approaches allows building theoretical models referring to those experiences. Thus, this article aims to review borders crossing as a developmental and abductively generalizable process. Through the analogy between Abductive Generalization and photogrammetry, the study proposes an innovative way of representing these complex experiences. Three ways of border crossing - spatial displacement, imagination and social interactions - are explored in terms of their developmental potential. Using a case study of psychologists in a humanitarian non-governmental organization - NGO, an abductively generalized model is presented highlighting the spatial, cultural and psychological dimensions involved. In addition, the study proposes a three-dimensional helical model of development inspired by photogrammetry, incorporating principles of this technique to improve the understanding on the border crossing process. By recognizing mesogenetic influences, such as institutional and cultural dimensions, the article puts forward an interdisciplinary approach to understand development through border crossing. The models presented may potentially drive future research and interventions in Semiotic Cultural Psychology, enriching the promotion of human development in different border contexts. The study fosters the extension of this work by including several perspectives, methods and paradigms.

14.
Front Public Health ; 11: 1201725, 2023.
Article in English | MEDLINE | ID: mdl-37680278

ABSTRACT

Syphilis is an infectious disease that can be diagnosed and treated cheaply. Despite being a curable condition, the syphilis rate is increasing worldwide. In this sense, computational methods can analyze data and assist managers in formulating new public policies for preventing and controlling sexually transmitted infections (STIs). Computational techniques can integrate knowledge from experiences and, through an inference mechanism, apply conditions to a database that seeks to explain data behavior. This systematic review analyzed studies that use computational methods to establish or improve syphilis-related aspects. Our review shows the usefulness of computational tools to promote the overall understanding of syphilis, a global problem, to guide public policy and practice, to target better public health interventions such as surveillance and prevention, health service delivery, and the optimal use of diagnostic tools. The review was conducted according to PRISMA 2020 Statement and used several quality criteria to include studies. The publications chosen to compose this review were gathered from Science Direct, Web of Science, Springer, Scopus, ACM Digital Library, and PubMed databases. Then, studies published between 2015 and 2022 were selected. The review identified 1,991 studies. After applying inclusion, exclusion, and study quality assessment criteria, 26 primary studies were included in the final analysis. The results show different computational approaches, including countless Machine Learning algorithmic models, and three sub-areas of application in the context of syphilis: surveillance (61.54%), diagnosis (34.62%), and health policy evaluation (3.85%). These computational approaches are promising and capable of being tools to support syphilis control and surveillance actions.


Subject(s)
Syphilis , Humans , Syphilis/diagnosis , Syphilis/prevention & control , Databases, Factual , Health Policy , Machine Learning , Public Health
15.
Braz J Cardiovasc Surg ; 38(5): e20220372, 2023 08 04.
Article in English | MEDLINE | ID: mdl-37540104

ABSTRACT

Joaquim de Souza Cavalcanti was a pioneer among us - the Brazilian State of Pernambuco and North-Northeast region - in cardiac surgery in its initial phase (Blalock-Taussig surgery and mitral valvulotomy), in thoracic surgery (pneumectomy, lung lobectomy and segmentectomy, lung decortication, and mediastinal tumor resection), and in numerous techniques and operative tactics in general surgery.


Subject(s)
Cardiac Surgical Procedures , Thoracic Surgery , Humans , Lung , Cardiac Surgical Procedures/methods , Brazil , Retrospective Studies
16.
J Sports Med Phys Fitness ; 63(10): 1051-1068, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37410446

ABSTRACT

INTRODUCTION: Eccentric cycling (ECCCYC) has attracted considerable interest due to its potential applicability for exercise treatment/training of patients with poor exercise tolerance as well as healthy and trained individuals. Conversely, little is known about the acute physiological responses to this exercise modality, thus challenging its proper prescription. This study aimed to provide precise estimates of the acute physiological responses to ECCCYC in comparison to traditional concentric cycling (CONCYC). EVIDENCE ACQUISITION: Searches were performed until November 2021 using the PubMed, Embase, and ScienceDirect databases. Studies that examined individuals' cardiorespiratory, metabolic, and perceptual responses to ECCCYC and CONCYC sessions were included. Bayesian multilevel meta-analysis models were used to estimate the population mean difference between acute physiological responses from ECCCYC and CONCYC bouts. Twenty-one studies were included in this review. EVIDENCE SYNTHESIS: The meta-analyses showed that ECCCYC induced lower cardiorespiratory (i.e., V̇O2, V̇E, and HR), metabolic (i.e., [BLa]), and perceptual (i.e., RPE) responses than CONCYC performed at the same absolute power output, while greater cardiovascular strain (i.e., greater increases in HR, Q, MAP, [norepinephrine], and lower SV) was detected when compared to CONCYC performed at the same V̇O2. CONCLUSIONS: The prescription of ECCCYC based on workloads used in the CONCYC sessions may be considered safe and, therefore, feasible for the rehabilitation of individuals with poor exercise tolerance. However, the prescription of ECCCYC based on the V̇O2 obtained during CONCYC sessions should be conducted with caution, especially in clinical settings, since there is a high probability of additional cardiovascular overload in this condition.


Subject(s)
Bicycling , Exercise , Humans , Bayes Theorem , Exercise/physiology , Bicycling/physiology , Oxygen Consumption/physiology , Heart Rate/physiology , Muscle, Skeletal/physiology , Muscle Contraction/physiology
17.
Sci Rep ; 13(1): 11112, 2023 Jul 10.
Article in English | MEDLINE | ID: mdl-37430127

ABSTRACT

Transport in non-Hermitian quantum systems is studied. The goal is a better understanding of transport in non-Hermitian systems like the Lieb lattice due to its flat bands and the integrability of the Ising chain which allows transport in that model to be computed analytically. This is a very special feature that is not present in a generic non-Hermitian system. We obtain the behaviour of the spin conductivity as a function of the non-Hermitian parameters of each system with aim to verify the influence of variation them on conductivity. For all models analyzed: Ising model as well as noninteracting fermion models, we obtain a little influence of the non-Hermitian parameters on conductivity and thus, a small effect over transport coefficients. Furthermore, we obtain an influence of opening of the gap in the spectrum in these models on longitudinal conductivity as well.

18.
Medicines (Basel) ; 10(6)2023 Jun 14.
Article in English | MEDLINE | ID: mdl-37367731

ABSTRACT

Cancer cells are characterized by metabolic reprogramming, which enables their survival in of-ten inhospitable conditions. A very well-documented example that has gained attraction in re-cent years and is already considered a hallmark of transformed cells is the reprogramming of carbohydrate metabolism. Such a feature, in association with the differential expression of en-zymes involved in the biosynthesis of glycoconjugates, generically known as glycosyltransfer-ases, contributes to the expression of structurally atypical glycans when compared to those ex-pressed in healthy tissues. The latest studies have demonstrated that glycophenotypic alterations are capable of modulating multifactorial events essential for the development and/or progres-sion of the disease. Herein, we will address the importance of glycobiology in modern medi-cine, focusing on the ability of unusual/truncated O-linked glycans to modulate two complex and essential phenomena for cancer progression: the acquisition of the multidrug resistance (MDR) phenotype and the activation of molecular pathways associated with the epithelial-mesenchymal transition (EMT) process, an event deeply linked with cancer metastasis.

19.
J Biomol Struct Dyn ; : 1-12, 2023 Jun 16.
Article in English | MEDLINE | ID: mdl-37325852

ABSTRACT

Phytases [myo-inositol(1,2,3,4,5,6) hexakisphosphate phosphohydrolases] are phytate-specific phosphatases not present in monogastric animals. Nevertheless, they are an essential supplement to feeding such animals and for human special diets. It is crucial, hence, the biotechnological use of phytases with intrinsic stability and activity at the acid pHs from gastric environments. Here we use Metadynamics (METADY) simulations to probe the conformational space of the Aspergillus nidulans phytase and the differential effects of pH and glycosylation in this same space. The results suggest that strategic combinations of pH and glycosylation affect the stability of native-like conformations and alternate these structures from a metastable to a stable profile. Furthermore, the protein segments previously reported as more thermosensitive in phytases from this family present a pivotal role in the conformational changes at different conditions, especially H2, H5-7, L8, L10, L12, and L17. Also, the glycosylations and the pH-dependent charge balance modulate the mobility and interactions at these same regions, with consequences for the surface solvation and active site exposition. Finally, although the glycosylations have stabilized the native structure and improved the substrate docking at all the studied pHs, the data suggest a higher phytate receptivity at catalytic poses for the unglycosylated structure at pH 6.5 and the glycosylated one at pH 4.5. This behavior agrees with the exact change in optimum pH reported for this enzyme, expressed on low or high glycosylating systems. We hope the results and insights presented here will be helpful in future approaches for rational engineering of technologically promising phytases and intelligent planning of their heterologous expression systems and conditions for use.Communicated by Ramaswamy H. Sarma.

20.
Nature ; 617(7960): 335-343, 2023 05.
Article in English | MEDLINE | ID: mdl-37165241

ABSTRACT

The short arms of the human acrocentric chromosomes 13, 14, 15, 21 and 22 (SAACs) share large homologous regions, including ribosomal DNA repeats and extended segmental duplications1,2. Although the resolution of these regions in the first complete assembly of a human genome-the Telomere-to-Telomere Consortium's CHM13 assembly (T2T-CHM13)-provided a model of their homology3, it remained unclear whether these patterns were ancestral or maintained by ongoing recombination exchange. Here we show that acrocentric chromosomes contain pseudo-homologous regions (PHRs) indicative of recombination between non-homologous sequences. Utilizing an all-to-all comparison of the human pangenome from the Human Pangenome Reference Consortium4 (HPRC), we find that contigs from all of the SAACs form a community. A variation graph5 constructed from centromere-spanning acrocentric contigs indicates the presence of regions in which most contigs appear nearly identical between heterologous acrocentric chromosomes in T2T-CHM13. Except on chromosome 15, we observe faster decay of linkage disequilibrium in the pseudo-homologous regions than in the corresponding short and long arms, indicating higher rates of recombination6,7. The pseudo-homologous regions include sequences that have previously been shown to lie at the breakpoint of Robertsonian translocations8, and their arrangement is compatible with crossover in inverted duplications on chromosomes 13, 14 and 21. The ubiquity of signals of recombination between heterologous acrocentric chromosomes seen in the HPRC draft pangenome suggests that these shared sequences form the basis for recurrent Robertsonian translocations, providing sequence and population-based confirmation of hypotheses first developed from cytogenetic studies 50 years ago9.


Subject(s)
Centromere , Chromosomes, Human , Recombination, Genetic , Humans , Centromere/genetics , Chromosomes, Human/genetics , DNA, Ribosomal/genetics , Recombination, Genetic/genetics , Translocation, Genetic/genetics , Cytogenetics , Telomere/genetics
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