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1.
Nature ; 632(8025): 522-527, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39143343

RESUMEN

Terahertz (THz) wireless communication holds immense potential to revolutionize future 6G to XG networks with high capacity, low latency and extensive connectivity. Efficient THz beamformers are essential for energy-efficient connections, compensating path loss, optimizing resource usage and enhancing spectral efficiency. However, current beamformers face several challenges, including notable loss, limited bandwidth, constrained spatial coverage and poor integration with on-chip THz circuits. Here we present an on-chip broadband THz topological beamformer using valley vortices for waveguiding, splitting and perfect isolation in waveguide phased arrays, featuring 184 densely packed valley-locked waveguides, 54 power splitters and 136 sharp bends. Leveraging neural-network-assisted inverse design, the beamformer achieves complete 360° azimuthal beamforming with gains of up to 20 dBi, radiating THz signals into free space with customizable user-defined beams. Photoexciting the all-silicon beamformer enables reconfigurable control of THz beams. The low-loss and broadband beamformer enables a 72-Gbps chip-to-chip wireless link over 300 mm and eight simultaneous 40-Gbps wireless links. Using four of these links, we demonstrate point-to-4-point real-time HD video streaming. Our work provides a complementary metal-oxide-semiconductor-compatible THz topological photonic integrated circuit for efficient large-scale beamforming, enabling massive single-input multiple-output and multiple-input and multiple-output systems for terabit-per-second 6G to XG wireless communications.

2.
Nature ; 631(8019): 142-149, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38926573

RESUMEN

Interindividual genetic variation affects the susceptibility to and progression of many diseases1,2. However, efforts to study how individual human brains differ in normal development and disease phenotypes are limited by the paucity of faithful cellular human models, and the difficulty of scaling current systems to represent multiple people. Here we present human brain Chimeroids, a highly reproducible, multidonor human brain cortical organoid model generated by the co-development of cells from a panel of individual donors in a single organoid. By reaggregating cells from multiple single-donor organoids at the neural stem cell or neural progenitor cell stage, we generate Chimeroids in which each donor produces all cell lineages of the cerebral cortex, even when using pluripotent stem cell lines with notable growth biases. We used Chimeroids to investigate interindividual variation in the susceptibility to neurotoxic triggers that exhibit high clinical phenotypic variability: ethanol and the antiepileptic drug valproic acid. Individual donors varied in both the penetrance of the effect on target cell types, and the molecular phenotype within each affected cell type. Our results suggest that human genetic background may be an important mediator of neurotoxin susceptibility and introduce Chimeroids as a scalable system for high-throughput investigation of interindividual variation in processes of brain development and disease.


Asunto(s)
Corteza Cerebral , Quimera , Predisposición Genética a la Enfermedad , Neurotoxinas , Organoides , Femenino , Humanos , Masculino , Linaje de la Célula/efectos de los fármacos , Corteza Cerebral/citología , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , Quimera/genética , Etanol/efectos adversos , Etanol/toxicidad , Variación Genética , Células-Madre Neurales/citología , Células-Madre Neurales/efectos de los fármacos , Células-Madre Neurales/metabolismo , Neurotoxinas/toxicidad , Organoides/citología , Organoides/efectos de los fármacos , Organoides/metabolismo , Fenotipo , Células Madre Pluripotentes/citología , Células Madre Pluripotentes/efectos de los fármacos , Células Madre Pluripotentes/metabolismo , Donantes de Tejidos , Ácido Valproico/efectos adversos , Ácido Valproico/toxicidad , Predisposición Genética a la Enfermedad/genética
3.
Nature ; 633(8029): 327-331, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39169194

RESUMEN

The elemental composition of the lunar surface provides insights into mechanisms of the formation and evolution of the Moon1,2. The chemical composition of lunar regolith have so far been precisely measured using the samples collected by the Apollo, Luna and Chang'e 5 missions, which are from equatorial to mid-latitude regions3,4; lunar meteorites, whose location of origin on the Moon is unknown5,6; and the in situ measurement from the Chang'e 3 and Chang'e 4 missions7-9, which are from the mid-latitude regions of the Moon. Here we report the first in situ measurements of the elemental abundances in the lunar southern high-latitude regions by the Alpha Particle X-ray Spectrometer (APXS) experiment10 aboard the Pragyan rover of India's Chandrayaan-3 mission. The 23 measurements in the vicinity of the Chandrayaan-3 landing site show that the local lunar terrain in this region is fairly uniform and primarily composed of ferroan anorthosite (FAN), a product of the lunar magma ocean (LMO) crystallization. However, observation of relatively higher magnesium abundance with respect to calcium in APXS measurements suggests the mixing of further mafic material. The compositional uniformity over a few tens of metres around the Chandrayaan-3 landing site provides an excellent ground truth for remote-sensing observations.

4.
EMBO J ; 43(15): 3175-3191, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38886581

RESUMEN

Endothelial cell responses to fluid shear stress from blood flow are crucial for vascular development, function, and disease. A complex of PECAM-1, VE-cadherin, VEGF receptors (VEGFRs), and Plexin D1 located at cell-cell junctions mediates many of these events. However, available evidence suggests that another mechanosensor upstream of PECAM-1 initiates signaling. Hypothesizing that GPCR and Gα proteins may serve this role, we performed siRNA screening of Gα subunits and found that Gαi2 and Gαq/11 are required for activation of the junctional complex. We then developed a new activation assay, which showed that these G proteins are activated by flow. We next mapped the Gα residues required for activation and developed an affinity purification method that used this information to identify latrophilin-2 (Lphn2/ADGRL2) as the upstream GPCR. Latrophilin-2 is required for all PECAM-1 downstream events tested. In both mice and zebrafish, latrophilin-2 is required for flow-dependent angiogenesis and artery remodeling. Furthermore, endothelial-specific knockout demonstrates that latrophilin plays a role in flow-dependent artery remodeling. Human genetic data reveal a correlation between the latrophilin-2-encoding Adgrl2 gene and cardiovascular disease. Together, these results define a pathway that connects latrophilin-dependent G protein activation to subsequent endothelial signaling, vascular physiology, and disease.


Asunto(s)
Uniones Intercelulares , Mecanotransducción Celular , Receptores Acoplados a Proteínas G , Receptores de Péptidos , Animales , Humanos , Ratones , Células Endoteliales/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Uniones Intercelulares/metabolismo , Uniones Intercelulares/genética , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores de Péptidos/metabolismo , Receptores de Péptidos/genética , Estrés Mecánico , Pez Cebra/metabolismo , Pez Cebra/genética
5.
Mol Cell ; 80(6): 971-979.e7, 2020 12 17.
Artículo en Inglés | MEDLINE | ID: mdl-33248026

RESUMEN

CRISPR-Cas adaptive immune systems provide prokaryotes with defense against viruses by degradation of specific invading nucleic acids. Despite advances in the biotechnological exploitation of select systems, multiple CRISPR-Cas types remain uncharacterized. Here, we investigated the previously uncharacterized type I-D interference complex and revealed that it is a genetic and structural hybrid with similarity to both type I and type III systems. Surprisingly, formation of the functional complex required internal in-frame translation of small subunits from within the large subunit gene. We further show that internal translation to generate small subunits is widespread across diverse type I-D, I-B, and I-C systems, which account for roughly one quarter of CRISPR-Cas systems. Our work reveals the unexpected expansion of protein coding potential from within single cas genes, which has important implications for understanding CRISPR-Cas function and evolution.


Asunto(s)
Inmunidad Adaptativa/genética , Proteínas Asociadas a CRISPR/genética , Sistemas CRISPR-Cas/genética , Evolución Molecular , Proteínas Asociadas a CRISPR/inmunología , Células Procariotas/inmunología , Células Procariotas/virología , Biosíntesis de Proteínas , Virus/inmunología
6.
Am J Hum Genet ; 111(4): 729-741, 2024 04 04.
Artículo en Inglés | MEDLINE | ID: mdl-38579670

RESUMEN

Glutamine synthetase (GS), encoded by GLUL, catalyzes the conversion of glutamate to glutamine. GS is pivotal for the generation of the neurotransmitters glutamate and gamma-aminobutyric acid and is the primary mechanism of ammonia detoxification in the brain. GS levels are regulated post-translationally by an N-terminal degron that enables the ubiquitin-mediated degradation of GS in a glutamine-induced manner. GS deficiency in humans is known to lead to neurological defects and death in infancy, yet how dysregulation of the degron-mediated control of GS levels might affect neurodevelopment is unknown. We ascertained nine individuals with severe developmental delay, seizures, and white matter abnormalities but normal plasma and cerebrospinal fluid biochemistry with de novo variants in GLUL. Seven out of nine were start-loss variants and two out of nine disrupted 5' UTR splicing resulting in splice exclusion of the initiation codon. Using transfection-based expression systems and mass spectrometry, these variants were shown to lead to translation initiation of GS from methionine 18, downstream of the N-terminal degron motif, resulting in a protein that is stable and enzymatically competent but insensitive to negative feedback by glutamine. Analysis of human single-cell transcriptomes demonstrated that GLUL is widely expressed in neuro- and glial-progenitor cells and mature astrocytes but not in post-mitotic neurons. One individual with a start-loss GLUL variant demonstrated periventricular nodular heterotopia, a neuronal migration disorder, yet overexpression of stabilized GS in mice using in utero electroporation demonstrated no migratory deficits. These findings underline the importance of tight regulation of glutamine metabolism during neurodevelopment in humans.


Asunto(s)
Epilepsia Generalizada , Glutamato-Amoníaco Ligasa , Glutamina , Animales , Humanos , Ratones , Encéfalo/metabolismo , Epilepsia Generalizada/genética , Glutamato-Amoníaco Ligasa/genética , Glutamato-Amoníaco Ligasa/metabolismo , Glutamatos/metabolismo , Glutamina/genética , Glutamina/metabolismo
7.
Nat Methods ; 21(9): 1743-1754, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38965443

RESUMEN

Recent developments of sequencing-based spatial transcriptomics (sST) have catalyzed important advancements by facilitating transcriptome-scale spatial gene expression measurement. Despite this progress, efforts to comprehensively benchmark different platforms are currently lacking. The extant variability across technologies and datasets poses challenges in formulating standardized evaluation metrics. In this study, we established a collection of reference tissues and regions characterized by well-defined histological architectures, and used them to generate data to compare 11 sST methods. We highlighted molecular diffusion as a variable parameter across different methods and tissues, significantly affecting the effective resolutions. Furthermore, we observed that spatial transcriptomic data demonstrate unique attributes beyond merely adding a spatial axis to single-cell data, including an enhanced ability to capture patterned rare cell states along with specific markers, albeit being influenced by multiple factors including sequencing depth and resolution. Our study assists biologists in sST platform selection, and helps foster a consensus on evaluation standards and establish a framework for future benchmarking efforts that can be used as a gold standard for the development and benchmarking of computational tools for spatial transcriptomic analysis.


Asunto(s)
Perfilación de la Expresión Génica , Transcriptoma , Perfilación de la Expresión Génica/métodos , Humanos , Análisis de la Célula Individual/métodos , Animales , Biología Computacional/métodos , Análisis de Secuencia de ARN/métodos , Ratones , Secuenciación de Nucleótidos de Alto Rendimiento/métodos
8.
Nature ; 591(7848): 99-104, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33627875

RESUMEN

Neuropil is a fundamental form of tissue organization within the brain1, in which densely packed neurons synaptically interconnect into precise circuit architecture2,3. However, the structural and developmental principles that govern this nanoscale precision remain largely unknown4,5. Here we use an iterative data coarse-graining algorithm termed 'diffusion condensation'6 to identify nested circuit structures within the Caenorhabditis elegans neuropil, which is known as the nerve ring. We show that the nerve ring neuropil is largely organized into four strata that are composed of related behavioural circuits. The stratified architecture of the neuropil is a geometrical representation of the functional segregation of sensory information and motor outputs, with specific sensory organs and muscle quadrants mapping onto particular neuropil strata. We identify groups of neurons with unique morphologies that integrate information across strata and that create neural structures that cage the strata within the nerve ring. We use high resolution light-sheet microscopy7,8 coupled with lineage-tracing and cell-tracking algorithms9,10 to resolve the developmental sequence and reveal principles of cell position, migration and outgrowth that guide stratified neuropil organization. Our results uncover conserved structural design principles that underlie the architecture and function of the nerve ring neuropil, and reveal a temporal progression of outgrowth-based on pioneer neurons-that guides the hierarchical development of the layered neuropil. Our findings provide a systematic blueprint for using structural and developmental approaches to understand neuropil organization within the brain.


Asunto(s)
Caenorhabditis elegans/embriología , Caenorhabditis elegans/metabolismo , Neurópilo/química , Neurópilo/metabolismo , Algoritmos , Animales , Encéfalo/citología , Encéfalo/embriología , Caenorhabditis elegans/química , Caenorhabditis elegans/citología , Movimiento Celular , Difusión , Interneuronas/metabolismo , Neuronas Motoras/metabolismo , Neuritas/metabolismo , Neurópilo/citología , Células Receptoras Sensoriales/metabolismo
9.
Chem Rev ; 124(12): 7619-7673, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38683669

RESUMEN

The energy demand for traditional vapor-compressed technology for space cooling continues to soar year after year due to global warming and the increasing human population's need to improve living and working conditions. Thus, there is a growing demand for eco-friendly technologies that use sustainable or waste energy resources. This review discusses the properties of various refrigerants used for adsorption cooling applications followed by a brief discussion on the thermodynamic cycle. Next, sorbents traditionally used for cooling are reviewed to emphasize the need for advanced capture materials with superior properties to improve refrigerant sorption. The remainder of the review focus on studies using engineered nanoporous frameworks (ENFs) with various refrigerants for adsorption cooling applications. The effects of the various factors that play a role in ENF-refrigerant pair selection, including pore structure/dimension/shape, morphology, open-metal sites, pore chemistry and possible presence of defects, are reviewed. Next, in-depth insights into the sorbent-refrigerant interaction, and pore filling mechanism gained through a combination of characterization techniques and computational modeling are discussed. Finally, we outline the challenges and opportunities related to using ENFs for adsorption cooling applications and provide our views on the future of this technology.

10.
Nature ; 584(7819): 102-108, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32728215

RESUMEN

During ontogeny, proliferating cells become restricted in their fate through the combined action of cell-type-specific transcription factors and ubiquitous epigenetic machinery, which recognizes universally available histone residues or nucleotides in a context-dependent manner1,2. The molecular functions of these regulators are generally well understood, but assigning direct developmental roles to them is hampered by complex mutant phenotypes that often emerge after gastrulation3,4. Single-cell RNA sequencing and analytical approaches have explored this highly conserved, dynamic period across numerous model organisms5-8, including mouse9-18. Here we advance these strategies using a combined zygotic perturbation and single-cell RNA-sequencing platform in which many mutant mouse embryos can be assayed simultaneously, recovering robust  morphological and transcriptional information across a panel of ten essential regulators. Deeper analysis of central Polycomb repressive complex (PRC) 1 and 2 components indicates substantial cooperativity, but distinguishes a dominant role for PRC2 in restricting the germline. Moreover, PRC mutant phenotypes emerge after gross epigenetic and transcriptional changes within the initial conceptus prior to gastrulation. Our experimental framework may eventually lead to a fully quantitative view of how cellular diversity emerges using an identical genetic template and from a single totipotent cell.


Asunto(s)
Epigénesis Genética , Gástrula/embriología , Gástrula/metabolismo , Gastrulación/genética , Animales , Linaje de la Célula , Femenino , Gástrula/citología , Regulación del Desarrollo de la Expresión Génica , Masculino , Ratones , Mutación , Complejo Represivo Polycomb 1/metabolismo , Complejo Represivo Polycomb 2/metabolismo , Análisis de la Célula Individual , Transcripción Genética
11.
Traffic ; 24(2): 95-107, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36533718

RESUMEN

G protein-coupled receptors (GPCRs) are vital cellular signaling machinery and currently represent ~40% drug targets. Endocytosis of GPCRs is an important process that allows stringent spatiotemporal control over receptor population on the cell surface. Although the role of proteins in GPCR endocytosis is well addressed, the contribution of membrane lipids in this process is rather unexplored. Sphingolipids are essential functional lipids in higher eukaryotes and are implicated in several neurological functions. To understand the role of sphingolipids in GPCR endocytosis, we subjected cells expressing human serotonin1A receptors (an important neurotransmitter GPCR involved in cognitive and behavioral functions) to metabolic sphingolipid depletion using fumonisin B1 , an inhibitor of sphingolipid biosynthetic pathway. Our results, using flow cytometric analysis and confocal microscopic imaging, show that sphingolipid depletion inhibits agonist-induced endocytosis of the serotonin1A receptor in a concentration-dependent manner, which was restored when sphingolipid levels were replenished. We further show that there was no change in the internalization of transferrin, a marker for clathrin-mediated endocytosis, under sphingolipid-depleted condition, highlighting the specific requirement of sphingolipids for endocytosis of serotonin1A receptors. Our results reveal the regulatory role of sphingolipids in GPCR endocytosis and highlight the importance of neurotransmitter receptor trafficking in health and disease.


Asunto(s)
Serotonina , Esfingolípidos , Humanos , Membrana Celular/metabolismo , Endocitosis/fisiología , Receptores Acoplados a Proteínas G/metabolismo , Serotonina/metabolismo , Esfingolípidos/metabolismo
12.
J Cell Sci ; 136(2)2023 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-36601773

RESUMEN

TIM22 pathway cargos are essential for sustaining mitochondrial homeostasis as an excess of these proteins leads to proteostatic stress and cell death. Yme1 is an inner membrane metalloprotease that regulates protein quality control with chaperone-like and proteolytic activities. Although the mitochondrial translocase and protease machinery are critical for organelle health, their functional association remains unexplored. The present study unravels a novel genetic connection between the TIM22 complex and YME1 machinery in Saccharomyces cerevisiae that is required for maintaining mitochondrial health. Our genetic analyses indicate that impairment in the TIM22 complex rescues the respiratory growth defects of cells without Yme1. Furthermore, Yme1 is essential for the stability of the TIM22 complex and regulates the proteostasis of TIM22 pathway substrates. Moreover, impairment in the TIM22 complex suppressed the mitochondrial structural and functional defects of Yme1-devoid cells. In summary, excessive levels of TIM22 pathway substrates could be one of the reasons for respiratory growth defects of cells lacking Yme1, and compromising the TIM22 complex can compensate for the imbalance in mitochondrial proteostasis caused by the loss of Yme1.


Asunto(s)
Proteínas de Transporte de Membrana Mitocondrial , Proteínas de Saccharomyces cerevisiae , Proteínas de Transporte de Membrana Mitocondrial/genética , Proteínas de Transporte de Membrana Mitocondrial/metabolismo , Proteostasis , Proteínas del Complejo de Importación de Proteínas Precursoras Mitocondriales , Proteínas de Saccharomyces cerevisiae/metabolismo , Mitocondrias/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , Proteasas ATP-Dependientes
13.
Nano Lett ; 24(26): 7825-7832, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38885473

RESUMEN

Vertical gate-all-around (V-GAA) represents the ultimate configuration in the forthcoming transistor industry, but it still encounters challenges in the semiconductor community. This paper introduces, for the first time, a dual-input logic gate circuit achieved using 3D vertical transistors with nanoscale sub-20-nm GAA, employing a novel technique for creating contacts and patterning metallic lines at the bottom level without the conventional lift-off process. This involves a two-step oxidation process: patterning the first field oxide to form bottom metal lines and then creating the gate oxide layer on nanowires (NWs), followed by selective removal from the top and bottom of the nanostructures. VGAA-NW transistors, fabricated using the lift-off-free approach, exhibit improved yield and reduced access resistance, leading to an enhanced drive current while maintaining good immunity against short-channel effects. Finally, elementary two-input logic gates within a single cell, using VNW transistors, demonstrate novel possibilities in advanced logic circuitry design and routing options in 3D.

14.
Genes Dev ; 31(1): 12-17, 2017 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-28115466

RESUMEN

Global DNA demethylation is a hallmark of embryonic epigenetic reprogramming. However, embryos engage noncanonical DNA methylation maintenance mechanisms to ensure inheritance of exceptional epigenetic germline features to the soma. Besides the paradigmatic genomic imprints, these exceptions remain ill-defined, and the mechanisms ensuring demethylation resistance in the light of global reprogramming remain poorly understood. Here we show that the Y-linked gene Rbmy1a1 is highly methylated in mature sperm and resists DNA demethylation post-fertilization. Aberrant hypomethylation of the Rbmy1a1 promoter results in its ectopic activation, causing male-specific peri-implantation lethality. Rbmy1a1 is a novel target of the TRIM28 complex, which is required to protect its repressive epigenetic state during embryonic epigenetic reprogramming.


Asunto(s)
Metilación de ADN/genética , Desarrollo Embrionario/genética , Epigénesis Genética/genética , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Proteínas de Unión al ARN/metabolismo , Proteínas Represoras/genética , Animales , Células Cultivadas , Reprogramación Celular/genética , Implantación del Embrión/genética , Embrión de Mamíferos , Femenino , Regulación del Desarrollo de la Expresión Génica , Impresión Genómica/genética , Masculino , Mutación , Regiones Promotoras Genéticas/genética , Proteínas de Unión al ARN/genética , Espermatozoides/metabolismo , Proteína 28 que Contiene Motivos Tripartito
15.
Kidney Int ; 105(2): 281-292, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37923131

RESUMEN

Lesion scores on procurement donor biopsies are commonly used to guide organ utilization for deceased-donor kidneys. However, frozen sections present challenges for histological scoring, leading to inter- and intra-observer variability and inappropriate discard. Therefore, we constructed deep-learning based models to recognize kidney tissue compartments in hematoxylin & eosin-stained sections from procurement needle biopsies performed nationwide in years 2011-2020. To do this, we extracted whole-slide abnormality features from 2431 kidneys and correlated with pathologists' scores and transplant outcomes. A Kidney Donor Quality Score (KDQS) was derived and used in combination with recipient demographic and peri-transplant characteristics to predict graft loss or assist organ utilization. The performance on wedge biopsies was additionally evaluated. Our model identified 96% and 91% of normal/sclerotic glomeruli respectively; 94% of arteries/arterial intimal fibrosis; 90% of tubules. Whole-slide features of Sclerotic Glomeruli (GS)%, Arterial Intimal Fibrosis (AIF)%, and Interstitial Space Abnormality (ISA)% demonstrated strong correlations with corresponding pathologists' scores of all 2431 kidneys, but had superior associations with post-transplant estimated glomerular filtration rates in 2033 and graft loss in 1560 kidneys. The combination of KDQS and other factors predicted one- and four-year graft loss in a discovery set of 520 kidneys and a validation set of 1040 kidneys. By using the composite KDQS of 398 discarded kidneys due to "biopsy findings", we suggest that if transplanted, 110 discarded kidneys could have had similar survival to that of other transplanted kidneys. Thus, our composite KDQS and survival prediction models may facilitate risk stratification and organ utilization while potentially reducing unnecessary organ discard.


Asunto(s)
Aprendizaje Profundo , Trasplante de Riñón , Obtención de Tejidos y Órganos , Humanos , Trasplante de Riñón/efectos adversos , Estudios Retrospectivos , Selección de Donante , Riñón/patología , Donantes de Tejidos , Biopsia , Fibrosis , Supervivencia de Injerto
16.
Funct Integr Genomics ; 24(4): 117, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38918231

RESUMEN

The role of messenger RNA (mRNA) in biological systems is extremely versatile. However, it's extremely short half-life poses a fundamental restriction on its application. Moreover, the translation efficiency of mRNA is also limited. On the contrary, circular RNAs, also known as circRNAs, are a common and stable form of RNA found in eukaryotic cells. These molecules are synthesized via back-splicing. Both synthetic circRNAs and certain endogenous circRNAs have the potential to encode proteins, hence suggesting the potential of circRNA as a gene expression machinery. Herein, we aim to summarize all engineering aspects that allow exogenous circular RNA (circRNA) to prolong the time that proteins are expressed from full-length RNA signals. This review presents a systematic engineering approach that have been devised to efficiently assemble circRNAs and evaluate several aspects that have an impact on protein production derived from. We have also reviewed how optimization of the key components of circRNAs, including the topology of vector, 5' and 3' untranslated sections, entrance site of the internal ribosome, and engineered aptamers could be efficiently impacting the translation machinery for molecular and metabolic reprogramming. Collectively, molecular and metabolic reprogramming present a novel way of regulating distinctive cellular features, for instance growth traits to neoplastic cells, and offer new possibilities for therapeutic inventions.


Asunto(s)
ARN Circular , ARN Circular/genética , ARN Circular/metabolismo , Humanos , Animales , Biosíntesis de Proteínas , Reprogramación Metabólica
17.
J Nutr ; 154(10): 2932-2947, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39209112

RESUMEN

BACKGROUND: Limited information on the co-prevalence of undernutrition, micronutrient deficiencies, overnutrition, and abnormal levels of noncommunicable disease biomarkers at the same time in children and adolescents in India hinders efforts to comprehensively address their health. OBJECTIVES: This study aimed to examine the prevalence and correlates of double burden of malnutrition (DBM) and triple burden of malnutrition (TBM) among children and adolescents (5-19 y) to inform policies and programs. METHODS: A total of 17,599 children (5-9 y) and 16,184 adolescents (10-19 y) with available biomarker data from the Comprehensive National Nutrition Survey were included. Malnutrition was defined based on either undernutrition based on anthropometry, overnutrition/abnormal metabolic markers, and anemia/micronutrient deficiency. DBM was defined as the coexistence of any 2 forms of malnutrition. DBM+ was defined as the coexistence of undernutrition and/or micronutrient deficiency along with overnutrition. TBM was defined as having the coexistence of all 3 forms of malnutrition. The prevalence of DBM, DBM+, and TBM was estimated accounting for probabilistic selection. We used mixed-effect binomial regression to determine correlates of DBM/TBM in children and adolescents separately. RESULTS: The prevalence of DBM, DBM+, and TBM was 50.8%, 37.2%, and 14.4%, respectively, in children and 53.4%, 36.1%, and 12.7%, respectively, in adolescents. The prevalence of DBM+ was significantly higher in girls compared to in boys in the 5-9 y age group. In children, being in a disadvantaged caste group, having a lower wealth index, having inadequate diet diversity, having no maternal schooling, and having a recent history of acute illness were associated with DBM. In adolescents, being in a disadvantaged caste group, maternal occupation, and lower paternal age were correlated with DBM. A similar set of variables was associated with TBM in both age groups. CONCLUSIONS: The prevalence of DBM and TBM is substantial in children and adolescents in India and varies across states. Socioeconomic factors and acute illness were the main correlates for DBM and TBM.


Asunto(s)
Desnutrición , Encuestas Nutricionales , Humanos , India/epidemiología , Adolescente , Niño , Femenino , Masculino , Prevalencia , Preescolar , Desnutrición/epidemiología , Estado Nutricional , Adulto Joven , Hipernutrición/epidemiología , Factores Socioeconómicos , Trastornos de la Nutrición del Niño/epidemiología
18.
Chemphyschem ; 25(20): e202400283, 2024 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-38634178

RESUMEN

Halocarbons have important industrial applications, but because of their contribution to global warming and the fact that they can cause ozone depletion, they are considered highly toxic. Hence, the techniques that can capture and recover the used halocarbons with energy-efficient methods have been recently received greater attention. In this contribution, we report the capture of dichlorodifluoromethane (R12), which has high global warming and ozone depletion potential, using covalent organic polymers (COPs). The defect-engineered COPs were synthesized and demonstrated outstanding sorption capacities, ~226 wt % of R12 combined with linear-shaped adsorption isotherms. We further identified the plausible microscopic adsorption mechanism of the investigated COPs via grand canonical Monte Carlo simulations applied to non-defective and a collection of atomistic models of the defective COPs. The modeling work suggests that significant R12 adsorption performance is attributed to a gradual increment of porosities due to isolated/interconnected micro-/meso-pore channels and the change of the long-range ordering of both COPs. The successive hierarchical-pore-filling mechanism promotes R12 molecular adsorption via moderate van der Waals adsorbate-adsorbent interactions in the micropores of both COPs at low pressure followed by adsorbate-adsorbate interactions in the extra-voids created at moderate to high pressure ranges. This continuous pore-filling mechanism makes defective COPs as promising sorbents for halocarbon adsorption.

19.
J Microsc ; 294(3): 420-439, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38747464

RESUMEN

In September 2023, the two largest bioimaging networks in the Americas, Latin America Bioimaging (LABI) and BioImaging North America (BINA), came together during a 1-week meeting in Mexico. This meeting provided opportunities for participants to interact closely with decision-makers from imaging core facilities across the Americas. The meeting was held in a hybrid format and attended in-person by imaging scientists from across the Americas, including Canada, the United States, Mexico, Colombia, Peru, Argentina, Chile, Brazil and Uruguay. The aims of the meeting were to discuss progress achieved over the past year, to foster networking and collaborative efforts among members of both communities, to bring together key members of the international imaging community to promote the exchange of experience and expertise, to engage with industry partners, and to establish future directions within each individual network, as well as common goals. This meeting report summarises the discussions exchanged, the achievements shared, and the goals set during the LABIxBINA2023: Bioimaging across the Americas meeting.

20.
Eur J Haematol ; 113(4): 400-415, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39030954

RESUMEN

PURPOSE: Localized gastrointestinal tract amyloidosis is uncommon and little is known regarding this entity. There is no current standard of care for the management of localized amyloidosis. The objective of this study was to evaluate the characteristics, available treatments, outcomes and surveillance of these patients. METHODS: We conducted a systematic review of cases reported in the literature from 1962 to 2021. Patients with gastrointestinal amyloidosis reported in English literature were included in the analysis. We described and summarized the patient's characteristics, treatments, clinical presentations, outcomes and surveillance. RESULTS: The systematic review of reported clinical cases included 62 patients. In these patients, the most common site of amyloid deposition was the stomach (42%). The median age of diagnosis is 64.4 years old; there is a 2:1 prevalence among males (63%) to females (37%); abdominal pain is the most common type of presentation (41%), although patients could also be asymptomatic. There is a high curative rate (100%) with resection alone. Among patients treated with a type of systemic therapy, 80% achieved a complete response. The minority of cases reported a type of surveillance post treatment, and among those 62% pursued serial clinical evaluations alone. CONCLUSION: To our knowledge, this is the first and largest systematic review of the literature in gastrointestinal tract amyloidosis. This is more common among males and seems to have an excellent curative rate (100%) with surgery alone. Systemic therapy is an option for those with non-resectable amyloidomas. Serial clinical evaluations should be part of the standard surveillance care in these patients.


Asunto(s)
Amiloidosis , Manejo de la Enfermedad , Enfermedades Gastrointestinales , Humanos , Amiloidosis/terapia , Amiloidosis/diagnóstico , Amiloidosis/etiología , Enfermedades Gastrointestinales/diagnóstico , Enfermedades Gastrointestinales/terapia , Enfermedades Gastrointestinales/etiología , Enfermedades Gastrointestinales/epidemiología , Masculino , Resultado del Tratamiento , Femenino , Persona de Mediana Edad , Anciano , Evaluación de Síntomas , Tracto Gastrointestinal/patología
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