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1.
Nature ; 622(7982): 321-328, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37794189

RESUMEN

Scientists have grappled with reconciling biological evolution1,2 with the immutable laws of the Universe defined by physics. These laws underpin life's origin, evolution and the development of human culture and technology, yet they do not predict the emergence of these phenomena. Evolutionary theory explains why some things exist and others do not through the lens of selection. To comprehend how diverse, open-ended forms can emerge from physics without an inherent design blueprint, a new approach to understanding and quantifying selection is necessary3-5. We present assembly theory (AT) as a framework that does not alter the laws of physics, but redefines the concept of an 'object' on which these laws act. AT conceptualizes objects not as point particles, but as entities defined by their possible formation histories. This allows objects to show evidence of selection, within well-defined boundaries of individuals or selected units. We introduce a measure called assembly (A), capturing the degree of causation required to produce a given ensemble of objects. This approach enables us to incorporate novelty generation and selection into the physics of complex objects. It explains how these objects can be characterized through a forward dynamical process considering their assembly. By reimagining the concept of matter within assembly spaces, AT provides a powerful interface between physics and biology. It discloses a new aspect of physics emerging at the chemical scale, whereby history and causal contingency influence what exists.


Asunto(s)
Evolución Biológica , Modelos Teóricos , Física , Selección Genética , Humanos , Evolución Cultural , Invenciones , Origen de la Vida , Física/métodos , Animales
2.
PLoS Genet ; 20(4): e1011232, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38669270

RESUMEN

Animals often grow and develop in unpredictable environments where factors like food availability, temperature, and oxygen levels can fluctuate dramatically. To ensure proper sexual maturation into adulthood, juvenile animals need to adapt their growth and developmental rates to these fluctuating environmental conditions. Failure to do so can result in impaired maturation and incorrect body size. Here we describe a mechanism by which Drosophila larvae adapt their development in low oxygen (hypoxia). During normal development, larvae grow and increase in mass until they reach critical weight (CW), after which point a neuroendocrine circuit triggers the production of the steroid hormone ecdysone from the prothoracic gland (PG), which promotes maturation to the pupal stage. However, when raised in hypoxia (5% oxygen), larvae slow their growth and delay their maturation to the pupal stage. We find that, although hypoxia delays the attainment of CW, the maturation delay occurs mainly because of hypoxia acting late in development to suppress ecdysone production. This suppression operates through a distinct mechanism from nutrient deprivation, occurs independently of HIF-1 alpha and does not involve dilp8 or modulation of Ptth, the main neuropeptide that initiates ecdysone production in the PG. Instead, we find that hypoxia lowers the expression of the EGF ligand, spitz, and that the delay in maturation occurs due to reduced EGFR/ERK signaling in the PG. Our study sheds light on how animals can adjust their development rate in response to changing oxygen levels in their environment. Given that hypoxia is a feature of both normal physiology and many diseases, our findings have important implications for understanding how low oxygen levels may impact animal development in both normal and pathological situations.


Asunto(s)
Proteínas de Drosophila , Drosophila melanogaster , Ecdisona , Factor de Crecimiento Epidérmico , Larva , Transducción de Señal , Animales , Ecdisona/metabolismo , Larva/crecimiento & desarrollo , Larva/genética , Larva/metabolismo , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Factor de Crecimiento Epidérmico/metabolismo , Factor de Crecimiento Epidérmico/genética , Drosophila melanogaster/crecimiento & desarrollo , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Hipoxia/metabolismo , Regulación del Desarrollo de la Expresión Génica , Receptores ErbB/metabolismo , Receptores ErbB/genética , Oxígeno/metabolismo , Pupa/crecimiento & desarrollo , Pupa/metabolismo , Pupa/genética
3.
Nucleic Acids Res ; 52(12): 6994-7011, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38828775

RESUMEN

The clinical success of PARP1/2 inhibitors (PARPi) prompts the expansion of their applicability beyond homologous recombination deficiency. Here, we demonstrate that the loss of the accessory subunits of DNA polymerase epsilon, POLE3 and POLE4, sensitizes cells to PARPi. We show that the sensitivity of POLE4 knockouts is not due to compromised response to DNA damage or homologous recombination deficiency. Instead, POLE4 loss affects replication speed leading to the accumulation of single-stranded DNA gaps behind replication forks upon PARPi treatment, due to impaired post-replicative repair. POLE4 knockouts elicit elevated replication stress signaling involving ATR and DNA-PK. We find POLE4 to act parallel to BRCA1 in inducing sensitivity to PARPi and counteracts acquired resistance associated with restoration of homologous recombination. Altogether, our findings establish POLE4 as a promising target to improve PARPi driven therapies and hamper acquired PARPi resistance.


Asunto(s)
Proteína BRCA1 , ADN Polimerasa II , Replicación del ADN , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Humanos , Proteína BRCA1/genética , Proteína BRCA1/metabolismo , ADN Polimerasa II/metabolismo , ADN Polimerasa II/genética , Replicación del ADN/efectos de los fármacos , Daño del ADN , Línea Celular Tumoral , Recombinación Homóloga/genética , Recombinación Homóloga/efectos de los fármacos , Resistencia a Antineoplásicos/genética
4.
Nucleic Acids Res ; 52(3): 1136-1155, 2024 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-38038252

RESUMEN

Maintaining chromatin integrity at the repetitive non-coding DNA sequences underlying centromeres is crucial to prevent replicative stress, DNA breaks and genomic instability. The concerted action of transcriptional repressors, chromatin remodelling complexes and epigenetic factors controls transcription and chromatin structure in these regions. The histone chaperone complex ATRX/DAXX is involved in the establishment and maintenance of centromeric chromatin through the deposition of the histone variant H3.3. ATRX and DAXX have also evolved mutually-independent functions in transcription and chromatin dynamics. Here, using paediatric glioma and pancreatic neuroendocrine tumor cell lines, we identify a novel ATRX-independent function for DAXX in promoting genome stability by preventing transcription-associated R-loop accumulation and DNA double-strand break formation at centromeres. This function of DAXX required its interaction with histone H3.3 but was independent of H3.3 deposition and did not reflect a role in the repression of centromeric transcription. DAXX depletion mobilized BRCA1 at centromeres, in line with BRCA1 role in counteracting centromeric R-loop accumulation. Our results provide novel insights into the mechanisms protecting the human genome from chromosomal instability, as well as potential perspectives in the treatment of cancers with DAXX alterations.


Asunto(s)
Centrómero , Roturas del ADN de Doble Cadena , Chaperonas Moleculares , Proteínas Nucleares , Estructuras R-Loop , Proteína Nuclear Ligada al Cromosoma X , Niño , Humanos , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Centrómero/metabolismo , Cromatina , Proteínas Co-Represoras/metabolismo , ADN , Histonas/genética , Histonas/metabolismo , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Proteínas Nucleares/metabolismo , Factores de Transcripción/metabolismo , Proteína Nuclear Ligada al Cromosoma X/genética , Proteína Nuclear Ligada al Cromosoma X/metabolismo
5.
Proc Natl Acad Sci U S A ; 120(23): e2211787120, 2023 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-37252982

RESUMEN

Understanding the local chemical ordering propensity in random solid solutions, and tailoring its strength, can guide the design and discovery of complex, paradigm-shifting multicomponent alloys. First, we present a simple thermodynamic framework, based solely on binary enthalpies of mixing, to select optimal alloying elements to control the nature and extent of chemical ordering in high-entropy alloys (HEAs). Next, we couple high-resolution electron microscopy, atom probe tomography, hybrid Monte-Carlo, special quasirandom structures, and density functional theory calculations to demonstrate how controlled additions of Al and Ti and subsequent annealing drive chemical ordering in nearly random equiatomic face-centered cubic CoFeNi solid solution. We establish that short-range ordered domains, the precursors of long-range ordered precipitates, inform mechanical properties. Specifically, a progressively increasing local order boosts the tensile yield strengths of the parent CoFeNi alloy by a factor of four while also substantially improving ductility, which breaks the so-called strength-ductility paradox. Finally, we validate the generality of our approach by predicting and demonstrating that controlled additions of Al, which has large negative enthalpies of mixing with the constituent elements of another nearly random body-centered cubic refractory NbTaTi HEA, also introduces chemical ordering and enhances mechanical properties.

6.
Development ; 149(21)2022 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-36205075

RESUMEN

Kidneys develop via iterative branching of the ureteric epithelial tree and subsequent nephrogenesis at the branch points. Nephrons form in the cap mesenchyme as the metanephric mesenchyme (MM) condenses around the epithelial ureteric buds (UBs). Previous work has demonstrated that FGF8 is important for the survival of nephron progenitor cells (NPCs), and early deletion of Fgf8 leads to the cessation of nephron formation, which results in post-natal lethality. We now reveal a previously unreported function of FGF8. By combining transgenic mouse models, quantitative imaging assays and data-driven computational modelling, we show that FGF8 has a strong chemokinetic effect and that this chemokinetic effect is important for the condensation of NPCs to the UB. The computational model shows that the motility must be lower close to the UB to achieve NPC attachment. We conclude that the FGF8 signalling pathway is crucial for the coordination of NPC condensation at the UB. Chemokinetic effects have also been described for other FGFs and may be generally important for the formation of mesenchymal condensates.


Asunto(s)
Riñón , Nefronas , Ratones , Animales , Nefronas/metabolismo , Riñón/metabolismo , Organogénesis , Factores de Crecimiento de Fibroblastos/metabolismo , Células Madre/metabolismo , Ratones Transgénicos , Factor 8 de Crecimiento de Fibroblastos/genética , Factor 8 de Crecimiento de Fibroblastos/metabolismo
7.
Exp Cell Res ; 442(2): 114267, 2024 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-39313176

RESUMEN

The EGF receptors (EGFRs) signaling pathway is essential for tumorigenesis and progression of cancer. Emerging evidence suggests that miRNAs are essential regulators of EGF signaling, influencing various pathway components and tumor behavior. This article discusses the underlying mechanisms and clinical implications of miRNA-mediated regulation of EGF signaling in cancer. miRNAs utilize multiple mechanisms to exert their regulatory effects on EGF signaling. They can target EGF ligands, including EGF and TGF-directly, inhibiting their expression and secretion. In addition, miRNAs can modulate EGF signaling indirectly by targeting EGF receptors, downstream signaling molecules, and transcription factors implicated in regulating the EGF pathway. These miRNAs can disrupt the delicate equilibrium of EGF signaling, resulting in aberrant activation and fostering tumor cell proliferation, survival, angiogenesis, and metastasis. The dysregulation of the expression of specific miRNAs has been linked to clinical outcomes in numerous types of cancer. Specific profiles of miRNA expression have been identified as prognostic markers, reflecting tumor characteristics, invasiveness, metastatic potential, and therapeutic response. These miRNAs can serve as potential therapeutic targets for interventions that modulate EGF signaling and improve patient outcomes. Understanding the intricate relationship between miRNAs and EGF signaling in cancer can transform cancer diagnosis, prognosis, and treatment. The identification of specific miRNAs involved in the regulation of the EGF pathway opens the door to the development of targeted therapies and personalized medicine approaches. In addition, miRNA-based interventions promise to overcome therapeutic resistance and improve the efficacy of existing treatments. miRNAs are crucial regulators of EGF signaling in cancer, affecting tumor behavior and clinical outcomes. Further research is required to decipher the complex network of miRNA-mediated EGF signaling regulation and translate these findings into clinically applicable strategies for enhanced cancer treatment.

8.
Mol Biol Evol ; 40(3)2023 03 04.
Artículo en Inglés | MEDLINE | ID: mdl-36795614

RESUMEN

Non-structural protein (NS1) is a 350 amino acid long conserved protein in the dengue virus. Conservation of NS1 is expected due to its importance in dengue pathogenesis. The protein is known to exist in dimeric and hexameric states. The dimeric state is involved in its interaction with host proteins and viral replication, and the hexameric state is involved in viral invasion. In this work, we performed extensive structure and sequence analysis of NS1 protein, and uncovered the role of NS1 quaternary states in its evolution. A three-dimensional modeling of unresolved loop regions in NS1 structure is performed. "Conserved" and "Variable" regions within NS1 protein were identified from sequences obtained from patient samples and the role of compensatory mutations in selecting destabilizing mutations were identified. Molecular dynamics (MD) simulations were performed to extensively study the effect of a few mutations on NS1 structure stability and compensatory mutations. Virtual saturation mutagenesis, predicting the effect of every individual amino acid substitution on NS1 stability sequentially, revealed virtual-conserved and variable sites. The increase in number of observed and virtual-conserved regions across NS1 quaternary states suggest the role of higher order structure formation in its evolutionary conservation. Our sequence and structure analysis could enable in identifying possible protein-protein interfaces and druggable sites. Virtual screening of nearly 10,000 small molecules, including FDA-approved drugs, permitted us to recognize six drug-like molecules targeting the dimeric sites. These molecules could be promising due to their stable interactions with NS1 throughout the simulation.


Asunto(s)
Dengue , Mutación , Biología Computacional , Proteínas no Estructurales Virales/genética
9.
BMC Microbiol ; 24(1): 342, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39271995

RESUMEN

PURPOSE: To determine the association of gut microbiome diversity and sight-threatening diabetic retinopathy (STDR) amongst patients with pre-existing diabetes. METHODS: A cross-sectional study was performed, wherein 54 participants selected in total were placed into cases cohort if diagnosed with STDR and those without STDR but had a diagnosis of diabetes mellitus of at least 10-year duration were taken as controls. Statistical analysis comparing the gut microbial alpha diversity between cases and control groups as well as patients differentiated based on previously hypothesized Bacteroidetes/Firmicutes(B/F) ratio with an optimal cut-off 1.05 to identify patients with STDR were performed. RESULTS: Comparing gut microbial alpha diversity did not show any difference between cases and control groups. However, statistically significant difference was noted amongst patients with B/F ratio ≥1.05 when compared to B/F ratio < 1.05; ACE index [Cut-off < 1.05:773.83 ± 362.73; Cut-off > 1.05:728.03 ± 227.37; p-0.016]; Chao1index [Cut-off < 1.05:773.63 ± 361.88; Cut-off > 1.05:728.13 ± 227.58; p-0.016]; Simpson index [Cut-off < 1.05:0.998 ± 0.001; Cut-off > 1.05:0.997 ± 0.001; p-0.006]; Shannon index [Cut-off < 1.05:6.37 ± 0.49; Cut-off > 1.05:6.10 ± 0.43; p-0.003]. Sub-group analysis showed that cases with B/F ratio ≥ 1.05, divided into proliferative diabetic retinopathy (PDR) and clinically significant macular edema (CSME), showed decreased diversity compared to controls (B/F ratio < 1.05). For PDR, all four diversity indices significantly decreased (p < 0.05). However, for CSME, only Shannon and Simpson indices showed significant decrease in diversity (p < 0.05). CONCLUSIONS: Based on clinical diagnosis, decreasing gut microbial diversity was observed among patients with STDR, although not statistically significant. When utilizing B/F ratio, the decreasing gut microbial diversity in STDR patients seems to be associated due to species richness and evenness in PDR when compared to decreasing species richness in CSME.


Asunto(s)
Retinopatía Diabética , Microbioma Gastrointestinal , Humanos , Retinopatía Diabética/microbiología , Masculino , Femenino , Estudios Transversales , Persona de Mediana Edad , Bacterias/clasificación , Bacterias/aislamiento & purificación , Bacterias/genética , Adulto , Bacteroidetes/aislamiento & purificación , Bacteroidetes/genética , Bacteroidetes/clasificación , Anciano , Estudios de Casos y Controles , Biodiversidad , Firmicutes/aislamiento & purificación , Firmicutes/clasificación , Firmicutes/genética
10.
Chemistry ; 30(2): e202303175, 2024 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-37793067

RESUMEN

Carbon-centered radicals stabilized by adjacent boron atoms are underexplored reaction intermediates in organic synthesis. This study reports the development of vinyl cyclopropyl diborons (VCPDBs) as a versatile source of previously unknown homoallylic α,α-diboryl radicals via thiyl radical catalyzed diboron-directed ring opening. These diboryl stabilized radicals underwent smooth [3+2] cycloaddition with a variety of olefins to provide diboryl cyclopentanes in good to excellent diastereoselectivity. In contrast to the trans-diastereoselectivity observed with most of the dicarbonyl activated VCPs, the cycloaddition of VCPDBs showed a remarkable preference for formation of cis-cyclopentane diastereomer which was confirmed by quantitative NOE and 2D NOESY studies. The cis-stereochemistry of cyclopentane products enabled a concise intramolecular Heck reaction approach to rare tricyclic cyclopentanoid framework containing the diboron group. The mild reaction conditions also allowed a one-pot VCP ring-opening, cycloaddition-oxidation sequence to afford disubstituted cyclopentanones. Control experiments and DFT analysis of reaction mechanism support a radical mediated pathway and provide a rationale for the observed diastereoselectivity. To the authors' knowledge, these are the first examples of the use of geminal diboryl group as an activator of VCP ring opening and cycloaddition reaction of α-boryl radicals.

11.
Biotechnol Bioeng ; 121(1): 71-81, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37661712

RESUMEN

Many of the infectious diseases are ubiquitous in nature and pose a threat to global and public health. The original cause for such type of serious maladies can be summarized as the scarcity of appropriate analysis and treatment methods. Pulmonary diseases are considered one of the life-threatening lung diseases that affect millions of people globally. It consists of several types, namely, asthma, lung cancer, tuberculosis, chronic obstructive pulmonary disease, and several respiratory-related infections. This is due to the limited access to well-equipped healthcare facilities for early disease diagnosis. This needs the availability of processes and technologies that can help to stop this harmful disease-diagnosing practice. Various approaches for diagnosing various lung diseases have been developed over time, namely, autopsy, chest X-rays, low-dose CT scans, and so forth. The need of the hour is to develop a rapid, simple, portable, and low-cost method for the diagnosis of pulmonary diseases. So nowadays, biosensors have been becoming one of the highest priority research areas as a potentially useful tool for the early diagnosis and detection of many pulmonary lung diseases. In this review article, various types of biosensors and their applications in the diagnosis of lung-related disorders are expansively explained.


Asunto(s)
Asma , Técnicas Biosensibles , Enfermedades Pulmonares , Neoplasias Pulmonares , Enfermedad Pulmonar Obstructiva Crónica , Infecciones del Sistema Respiratorio , Humanos , Enfermedades Pulmonares/diagnóstico , Asma/diagnóstico , Asma/terapia , Pulmón , Técnicas Biosensibles/métodos
12.
Soft Matter ; 20(33): 6608-6617, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39105541

RESUMEN

We investigate the statistical behavior of a system comprising fore-aft symmetric rods confined between two vertically vibrating plates using numerical simulations closely resembling the experimental setup studied by V. Narayan et al., Science, 2007, 317, 105-108. Our focus lies in studying the phase transition of the system from an isotropic phase to a nematic phase as we increase either the rod length or the rod concentration. Our simulations confirm the presence of long-range ordering in the ordered phase. Furthermore, we identify a phase characterized by a periodic ordering profile that disrupts translation symmetry. We also provide a detailed analysis of the translational and rotational diffusive dynamics of the rods. Interestingly, the translational diffusivity of the rods is found to increase with the rod concentration.

13.
J Chem Phys ; 161(3)2024 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-39017427

RESUMEN

Upon osmotic compression, rotationally symmetric faceted colloidal particles can form translationally ordered, orientationally disordered rotator mesophases. This study explores the mechanism of rotator-to-crystal phase transitions where orientational order is gained in a translationally ordered phase, using rotator-phase forming truncated cubes as a testbed. Monte Carlo simulations were conducted for two selected truncations (s), one for s = 0.527 where the rotator and crystal lattices are dissimilar and one for s = 0.572 where the two phases have identical lattices. These differences set the stage for a qualitative difference in their rotator-crystal transitions, highlighting the effect of lattice distortion on phase transition kinetics. Our simulations reveal that significant lattice deviatoric effects could hinder the rotator-to-crystal transition and favor arrangements of lower packing fraction instead. Indeed, upon compression, it is found that for s = 0.527, the rotator phase does not spontaneously transition into the stable, densely packed crystal due to the high lattice strains involved but instead transitions into a metastable solid phase to be colloquially referred to as "orientational salt" for short, which has a similar lattice as the rotator phase and exhibits two distinct particle orientations having substitutional order, alternating regularly throughout the system. This study paves the way for further analysis of diffusionless transformations in nanoparticle systems and how lattice-distortion could influence crystallization kinetics.

14.
BMC Med Imaging ; 24(1): 32, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38317098

RESUMEN

Chest radiographs are examined in typical clinical settings by competent physicians for tuberculosis diagnosis. However, this procedure is time consuming and subjective. Due to the growing usage of machine learning techniques in applied sciences, researchers have begun applying comparable concepts to medical diagnostics, such as tuberculosis screening. In the period of extremely deep neural nets which comprised of hundreds of convolution layers for feature extraction, we create a shallow-CNN for screening of TB condition from Chest X-rays so that the model is able to offer appropriate interpretation for right diagnosis. The suggested model consists of four convolution-maxpooling layers with various hyperparameters that were optimized for optimal performance using a Bayesian optimization technique. The model was reported with a peak classification accuracy, F1-score, sensitivity and specificity of 0.95. In addition, the receiver operating characteristic (ROC) curve for the proposed shallow-CNN showed a peak area under the curve value of 0.976. Moreover, we have employed class activation maps (CAM) and Local Interpretable Model-agnostic Explanations (LIME), explainer systems for assessing the transparency and explainability of the model in comparison to a state-of-the-art pre-trained neural net such as the DenseNet.


Asunto(s)
Aprendizaje Automático , Tuberculosis , Humanos , Teorema de Bayes , Radiografía , Tamizaje Masivo , Tuberculosis/diagnóstico por imagen
15.
Clin Exp Ophthalmol ; 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38937978

RESUMEN

BACKGROUND: Paediatric vitreoretinal pathology is distinct from adult cases in both presentation and surgical planning. Here we aim to report the aetiology and epidemiology in children 0-18 years requiring vitreoretinal surgery at a major tertiary paediatric hospital in Queensland, Australia. METHODS: Retrospective review of cases requiring vitreoretinal surgery between May 2015 and October 2022 was conducted. Demographics, ocular and medical history, surgical pathology, procedures performed, and epidemiology data were retrieved. Patients were grouped into three main aetiologies: traumatic, syndromic, or secondary. RESULTS: A total of 124 patients, the majority male (87, 70.2%) with a mean age of 10.3 years underwent vitreoretinal surgery. Trauma accounted for 32.3% of cases requiring surgery of which 47% were due to a penetrating eye injury. 35.5% were associated with a syndromic cause with common aetiology including coats, congenital cataract, sticklers, and retinopathy of prematurity. 32.3% developed secondary pathology and retinal detachment was the primary cause for surgery (55%). The average time from symptom onset to presentation was 30 days (SD 56.88) with patients living an average of 306.2 km (SD 558.9) away from the Queensland Children's Hospital. Older age was significantly associated with increased days to presentation in the traumatic group (p < 0.05). CONCLUSIONS: This study provides an insight into the aetiology and epidemiology of paediatric vitreoretinal presentations in Queensland, Australia.

16.
Chaos ; 34(8)2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39213012

RESUMEN

Coupled oscillators models help us in understanding the origin of synchronization phenomenon prevalent in both natural and artificial systems. Here, we study the coupled Kuramoto oscillator model having phase lag and adaptation in higher-order interactions. We find that the type of transition to synchronization changes from the first-order to second-order through tiered synchronization depending on the adaptation parameters. Phase lag enables this transition at a lower exponent of the adaptation parameters. Moreover, an interplay between the adaptation and phase lag parameters eliminates tiered synchronization, facilitating a direct transition from the first to second-order. In the thermodynamic limit, the Ott-Antonsen approach accurately describes all stationary and (un)stable states, with analytical results matching those obtained from numerical simulations for finite system sizes.

17.
Pain Manag Nurs ; 25(5): 538-548, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38719655

RESUMEN

BACKGROUND: Breast cancer is the most commonly diagnosed cancer among women globally, with significant impacts on physical, emotional, and functional well-being. Traditional rehabilitation methods may not fully address the multifaceted challenges faced by breast cancer survivors (BCSs), prompting exploration into innovative approaches such as Virtual Reality (VR) technology. OBJECTIVE: The present review aims to assess the effectiveness of VR in alleviating pain, improving Range of Motion (ROM), enhancing muscle strength, and augmenting the overall quality of life in patients undergoing breast cancer rehabilitation. METHODS: A comprehensive review of existing literature was conducted, focusing on studies investigating the use of VR in breast cancer rehabilitation. PubMed, Scopus, PEDro and Google scholar were searched for articles addressing VR interventions targeting pain management, ROM improvement, muscle strength enhancement, and quality of life enhancement in breast cancer patients. RESULTS: Findings yielded total 12 articles matching the selection criteria. VR technology has shown promising results in addressing the multifaceted needs of breast cancer patients. VR also serves as a distraction tool, positively impacting psychological well-being and mitigating negative psychological symptoms associated with the disease. CONCLUSION: VR represents a non-pharmacological approach to pain management and rehabilitation in breast cancer patients. Its ability to engage emotional, cognitive, and attention processes contributes to its effectiveness in enhancing overall quality of life. Further research is warranted to elucidate the long-term benefits and optimal utilization of VR technology in breast cancer rehabilitation programs.


Asunto(s)
Neoplasias de la Mama , Fuerza Muscular , Manejo del Dolor , Calidad de Vida , Rango del Movimiento Articular , Realidad Virtual , Humanos , Neoplasias de la Mama/psicología , Neoplasias de la Mama/complicaciones , Calidad de Vida/psicología , Femenino , Fuerza Muscular/fisiología , Manejo del Dolor/métodos , Manejo del Dolor/normas
18.
Chem Biodivers ; : e202402053, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39351913

RESUMEN

Klebsiella pneumoniae has emerged as a significant multidrug-resistant pathogen, classified as a critical priority by the World Health Organization. The rising rates of antibiotic resistance have led to increased therapeutic failures, diminishing the effectiveness of existing antibiotics. Consequently, there is an urgent need for alternative treatments to effectively inhibit the growth of K. pneumoniae and mitigate associated diseases. Phytochemicals have demonstrated potential advantages over traditional antibiotics, prompting their exploration as innovative therapeutic agents. This study aimed to identify phytochemicals that can inhibit dapB, a vital enzyme in the lysine biosynthesis pathway of K. pneumoniae, which is essential for protein synthesis and the cross-linking of the bacterial peptidoglycan cell wall. We screened 17,934 phytochemicals based on Lipinski's Rule of Five, along with their Absorption, Distribution, Metabolism, Excretion properties and toxicological parameters. Next, we conducted triplicate docking studies against dapB to evaluate the library further. The most promising molecules then underwent 100 ns Molecular Dynamics simulations in triplicate, followed by binding free energy calculations to identify potential dapB inhibitors. This in silico analysis highlighted limonin as a promising inhibitor of dapB in K. pneumoniae. Further experimental validation is crucial to enhance limonin's potential as a novel therapeutic agent against K. pneumoniae-associated diseases.

19.
J Vector Borne Dis ; 61(3): 420-425, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38634367

RESUMEN

BACKGROUND OBJECTIVES: Dengue fever is a mosquito-bome illness that affects millions of people worldwide every year. With no vaccination available, early detection and treatment are critical. It is found in 112 countries and poses a risk to travellers, particularly in metropolitan areas. Laboratory diagnoses vary according to objectives, resources, and schedule, with sensitivity and specificity must be balanced for effective testing. METHODS: The current study is a cross-sectional diagnostic study and samples from suspected patients of dengue was collected from May to November 2023 and transported to laboratory. RT-PCR and Dengue Duo Rapid test diagnosis techniques were used and total 48 clinical samples were included in this study. RESULTS: A total of 48 clinical samples were collected. Blood was collected from the suspected cases of dengue and further subjected to different molecular and serological parameters. Serum was separated from all blood samples. RNA was isolated by silica column extraction method which is further utilized as a template for amplification and detection of dengue serotyping. Master Mix was prepared for the amplification and detection of dengue virus by Rotor-Gene Q Real-Time PCR Machine and further serological profiling of positive dengue cases was studied by conventional PCR. INTERPRETATION CONCLUSION: Our laboratory effectively standardized an RT-PCR-based approach for molecular identification of dengue virus in clinical specimens. This adaptive technique, which uses numerous primer sets, displayed good specificity and sensitivity in serotype detection. The technology provides for quick and reliable identification of dengue virus infections, allowing for targeted treatment and preventative actions for successful disease management in highly populated regions.


Asunto(s)
Virus del Dengue , Dengue , Sensibilidad y Especificidad , Humanos , Dengue/diagnóstico , Dengue/virología , Virus del Dengue/genética , Virus del Dengue/aislamiento & purificación , Virus del Dengue/inmunología , Estudios Transversales , ARN Viral/genética , ARN Viral/sangre , Pronóstico , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Serotipificación/métodos , Serogrupo , Femenino , Masculino , Anticuerpos Antivirales/sangre
20.
J Environ Manage ; 369: 122341, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39236613

RESUMEN

Thermochemical treatment is rapidly emerging as an alternative method for the management of stabilised sewage sludges (biosolids) to effectively reduce waste volume, degrade contaminants, and generate valuable products, particularly biochar and hydrochar. Biosolids-derived char has a relatively high concentration of heavy metals compared with agricultural chars but is still applied to land due to its beneficial properties and ability to retain metals. However, non-agricultural applications can provide additional economic and environmental benefits, promote sustainability and support a circular economy. This review identifies extensive non-agricultural opportunity for biosolids biochar, including adsorption, catalysis, energy storage systems, biological process enhancement, and as additives for rubber compounding and construction. Biosolids chars have received limited attention vs agricultural char, and we draw on both areas of literature, as well as evaluating differences between agricultural and biosolids chars. A key opportunity for biosolids biochar in comparison with other materials and agricultural chars is its sustainable and low-cost nature, relatively high metals content, improving catalyst properties, and ability to modify in various stages to tune it to specific applications. The specific opportunities for hydrochar have only received limited attention. Research needs to include better understanding of the benefits and limitations for specific applications, as well as adjacent drivers, including society, regulation, and market and economics.


Asunto(s)
Carbón Orgánico , Aguas del Alcantarillado , Aguas del Alcantarillado/química , Carbón Orgánico/química , Metales Pesados/análisis , Agricultura/métodos , Adsorción , Catálisis
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