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1.
EMBO J ; 42(6): e113018, 2023 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-36786017

RESUMEN

The plant signaling molecule auxin is present in multiple kingdoms of life. Since its discovery, a century of research has been focused on its action as a phytohormone. In land plants, auxin regulates growth and development through transcriptional and non-transcriptional programs. Some of the molecular mechanisms underlying these responses are well understood, mainly in Arabidopsis. Recently, the availability of genomic and transcriptomic data of green lineages, together with phylogenetic inference, has provided the basis to reconstruct the evolutionary history of some components involved in auxin biology. In this review, we follow the evolutionary trajectory that allowed auxin to become the "giant" of plant biology by focusing on bryophytes and streptophyte algae. We consider auxin biosynthesis, transport, physiological, and molecular responses, as well as evidence supporting the role of auxin as a chemical messenger for communication within ecosystems. Finally, we emphasize that functional validation of predicted orthologs will shed light on the conserved properties of auxin biology among streptophytes.


Asunto(s)
Arabidopsis , Ácidos Indolacéticos , Filogenia , Ecosistema , Evolución Molecular , Plantas , Arabidopsis/genética
2.
Nature ; 593(7857): 95-100, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33953416

RESUMEN

The origin and evolution of hominin mortuary practices are topics of intense interest and debate1-3. Human burials dated to the Middle Stone Age (MSA) are exceedingly rare in Africa and unknown in East Africa1-6. Here we describe the partial skeleton of a roughly 2.5- to 3.0-year-old child dating to 78.3 ± 4.1 thousand years ago, which was recovered in the MSA layers of Panga ya Saidi (PYS), a cave site in the tropical upland coast of Kenya7,8. Recent excavations have revealed a pit feature containing a child in a flexed position. Geochemical, granulometric and micromorphological analyses of the burial pit content and encasing archaeological layers indicate that the pit was deliberately excavated. Taphonomical evidence, such as the strict articulation or good anatomical association of the skeletal elements and histological evidence of putrefaction, support the in-place decomposition of the fresh body. The presence of little or no displacement of the unstable joints during decomposition points to an interment in a filled space (grave earth), making the PYS finding the oldest known human burial in Africa. The morphological assessment of the partial skeleton is consistent with its assignment to Homo sapiens, although the preservation of some primitive features in the dentition supports increasing evidence for non-gradual assembly of modern traits during the emergence of our species. The PYS burial sheds light on how MSA populations interacted with the dead.


Asunto(s)
Entierro/historia , Fósiles , Esqueleto/anatomía & histología , Animales , Huesos/anatomía & histología , Preescolar , Evolución Cultural/historia , Dentición , Historia Antigua , Hominidae/anatomía & histología , Hominidae/clasificación , Humanos , Kenia
3.
Proc Natl Acad Sci U S A ; 121(19): e2319163121, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38696472

RESUMEN

DELLA proteins are negative regulators of the gibberellin response pathway in angiosperms, acting as central hubs that interact with hundreds of transcription factors (TFs) and regulators to modulate their activities. While the mechanism of TF sequestration by DELLAs to prevent DNA binding to downstream targets has been extensively documented, the mechanism that allows them to act as coactivators remains to be understood. Here, we demonstrate that DELLAs directly recruit the Mediator complex to specific loci in Arabidopsis, facilitating transcription. This recruitment involves DELLA amino-terminal domain and the conserved MED15 KIX domain. Accordingly, partial loss of MED15 function mainly disrupted processes known to rely on DELLA coactivation capacity, including cytokinin-dependent regulation of meristem function and skotomorphogenic response, gibberellin metabolism feedback, and flavonol production. We have also found that the single DELLA protein in the liverwort Marchantia polymorpha is capable of recruiting MpMED15 subunits, contributing to transcriptional coactivation. The conservation of Mediator-dependent transcriptional coactivation by DELLA between Arabidopsis and Marchantia implies that this mechanism is intrinsic to the emergence of DELLA in the last common ancestor of land plants.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Regulación de la Expresión Génica de las Plantas , Marchantia , Complejo Mediador , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Complejo Mediador/metabolismo , Complejo Mediador/genética , Marchantia/genética , Marchantia/metabolismo , Giberelinas/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Transcripción Genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética
4.
N Engl J Med ; 386(24): 2283-2294, 2022 06 16.
Artículo en Inglés | MEDLINE | ID: mdl-35704480

RESUMEN

BACKGROUND: In June 2019, the Bolivian Ministry of Health reported a cluster of cases of hemorrhagic fever that started in the municipality of Caranavi and expanded to La Paz. The cause of these cases was unknown. METHODS: We obtained samples for next-generation sequencing and virus isolation. Human and rodent specimens were tested by means of virus-specific real-time quantitative reverse-transcriptase-polymerase-chain-reaction assays, next-generation sequencing, and virus isolation. RESULTS: Nine cases of hemorrhagic fever were identified; four of the patients with this illness died. The etiologic agent was identified as Mammarenavirus Chapare mammarenavirus, or Chapare virus (CHAPV), which causes Chapare hemorrhagic fever (CHHF). Probable nosocomial transmission among health care workers was identified. Some patients with CHHF had neurologic manifestations, and those who survived had a prolonged recovery period. CHAPV RNA was detected in a variety of human body fluids (including blood; urine; nasopharyngeal, oropharyngeal, and bronchoalveolar-lavage fluid; conjunctiva; and semen) and in specimens obtained from captured small-eared pygmy rice rats (Oligoryzomys microtis). In survivors of CHHF, viral RNA was detected up to 170 days after symptom onset; CHAPV was isolated from a semen sample obtained 86 days after symptom onset. CONCLUSIONS: M. Chapare mammarenavirus was identified as the etiologic agent of CHHF. Both spillover from a zoonotic reservoir and possible person-to-person transmission were identified. This virus was detected in a rodent species, O. microtis. (Funded by the Bolivian Ministry of Health and others.).


Asunto(s)
Arenavirus del Nuevo Mundo , Fiebre Hemorrágica Americana , ARN Viral , Roedores , Animales , Arenavirus del Nuevo Mundo/genética , Arenavirus del Nuevo Mundo/aislamiento & purificación , Bolivia/epidemiología , Infección Hospitalaria/transmisión , Infección Hospitalaria/virología , Transmisión de Enfermedad Infecciosa , Fiebre Hemorrágica Americana/complicaciones , Fiebre Hemorrágica Americana/genética , Fiebre Hemorrágica Americana/transmisión , Fiebre Hemorrágica Americana/virología , Fiebres Hemorrágicas Virales/genética , Fiebres Hemorrágicas Virales/transmisión , Fiebres Hemorrágicas Virales/virología , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Reacción en Cadena de la Polimerasa , ARN Viral/genética , ARN Viral/aislamiento & purificación , Ratas/virología , Roedores/virología , Zoonosis Virales/transmisión , Zoonosis Virales/virología
5.
Yeast ; 41(7): 458-472, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38874348

RESUMEN

The yeast Saccharomyces cerevisiae and most eukaryotes carry two 5' → 3' exoribonuclease paralogs. In yeast, they are called Xrn1, which shuttles between the nucleus and the cytoplasm, and executes major cytoplasmic messenger RNA (mRNA) decay, and Rat1, which carries a strong nuclear localization sequence (NLS) and localizes to the nucleus. Xrn1 is 30% identical to Rat1 but has an extra ~500 amino acids C-terminal extension. In the cytoplasm, Xrn1 can degrade decapped mRNAs during the last round of translation by ribosomes, a process referred to as "cotranslational mRNA decay." The division of labor between the two enzymes is still enigmatic and serves as a paradigm for the subfunctionalization of many other paralogs. Here we show that Rat1 is capable of functioning in cytoplasmic mRNA decay, provided that Rat1 remains cytoplasmic due to its NLS disruption (cRat1). This indicates that the physical segregation of the two paralogs plays roles in their specific functions. However, reversing segregation is not sufficient to fully complement the Xrn1 function. Specifically, cRat1 can partially restore the cell volume, mRNA stability, the proliferation rate, and 5' → 3' decay alterations that characterize xrn1Δ cells. Nevertheless, cotranslational decay is only slightly complemented by cRat1. The use of the AlphaFold prediction for cRat1 and its subsequent docking with the ribosome complex and the sequence conservation between cRat1 and Xrn1 suggest that the tight interaction with the ribosome observed for Xrn1 is not maintained in cRat1. Adding the Xrn1 C-terminal domain to Rat1 does not improve phenotypes, which indicates that lack of the C-terminal is not responsible for partial complementation. Overall, during evolution, it appears that the two paralogs have acquired specific characteristics to make functional partitioning beneficial.


Asunto(s)
Exorribonucleasas , Estabilidad del ARN , ARN Mensajero , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Exorribonucleasas/metabolismo , Exorribonucleasas/genética , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/enzimología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Citoplasma/metabolismo , Biosíntesis de Proteínas
6.
Appl Environ Microbiol ; 90(7): e0039724, 2024 07 24.
Artículo en Inglés | MEDLINE | ID: mdl-38975758

RESUMEN

Beer brewing is a well-known process that still faces great challenges, such as the total consumption of sugars present in the fermentation media. Lager-style beer, a major worldwide beer type, is elaborated by Saccharomyces pastorianus (Sp) yeast, which must ferment high maltotriose content worts, but its consumption represents a notable problem, especially among Sp strains belonging to group I. Factors, such as fermentation conditions, presence of maltotriose transporters, transporter copy number variation, and genetic regulation variations contribute to this issue. We assess the factors affecting fermentation in two Sp yeast strains: SpIB1, with limited maltotriose uptake, and SpIB2, known for efficient maltotriose transport. Here, SpIB2 transported significantly more maltose (28%) and maltotriose (32%) compared with SpIB1. Furthermore, SpIB2 expressed all MAL transporters (ScMALx1, SeMALx1, ScAGT1, SeAGT1, MTT1, and MPHx) on the first day of fermentation, whereas SpIB1 only exhibited ScMalx1, ScAGT1, and MPH2/3 genes. Some SpIB2 transporters had polymorphic transmembrane domains (TMD) resembling MTT1, accompanied by higher expression of these transporters and its positive regulator genes, such as MAL63. These findings suggest that, in addition to the factors mentioned above, positive regulators of Mal transporters contribute significantly to phenotypic diversity in maltose and maltotriose consumption among the studied lager yeast strains.IMPORTANCEBeer, the third most popular beverage globally with a 90% market share in the alcoholic beverage industry, relies on Saccharomyces pastorianus (Sp) strains for lager beer production. These strains exhibit phenotypic diversity in maltotriose consumption, a crucial process for the acceptable organoleptic profile in lager beer. This diversity ranges from Sp group II strains with a notable maltotriose-consuming ability to Sp group I strains with limited capacity. Our study highlights that differential gene expression of maltose and maltotriose transporters and its upstream trans-elements, such as MAL gene-positive regulators, adds complexity to this variation. This insight can contribute to a more comprehensive analysis needed to the development of controlled and efficient biotechnological processes in the beer brewing industry.


Asunto(s)
Cerveza , Fermentación , Proteínas Fúngicas , Maltosa , Saccharomyces , Trisacáridos , Maltosa/metabolismo , Trisacáridos/metabolismo , Saccharomyces/genética , Saccharomyces/metabolismo , Cerveza/microbiología , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Transporte Biológico , Proteínas de Transporte de Monosacáridos/genética , Proteínas de Transporte de Monosacáridos/metabolismo , Regulación Fúngica de la Expresión Génica
7.
Osteoarthritis Cartilage ; 32(5): 526-534, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38190960

RESUMEN

OBJECTIVE: To investigate genetic interactions between mitochondrial deoxyribonucleic acid (mtDNA) haplogroups and nuclear single nucleotide polymorphisms (nSNPs) to analyze their impact on the development of the rapid progression of knee osteoarthritis (OA). DESIGN: A total of 1095 subjects from the Osteoarthritis Initiative, with a follow-up time of at least 48-months, were included. Appropriate statistical approaches were performed, including generalized estimating equations adjusting for age, gender, body mass index, contralateral knee OA, Western Ontario and McMaster Universities Osteoarthritis Index pain, previous injury in target knee and the presence of the mtDNA variant m.16519C. Additional genomic data consisted in the genotyping of Caucasian mtDNA haplogroups and eight nSNPs previously associated with the risk of knee OA in robust genome-wide association studies. RESULTS: The simultaneous presence of the G allele of rs12107036 at TP63 and the haplogroup Uk significantly increases the risk of a rapid progression of knee OA (odds ratio = 1.670; 95% confidence interval [CI]: 1.031-2.706; adjusted p-value = 0.027). The assessment of the population attributable fraction showed that the highest proportion of rapid progressors was under the simultaneous presence of the G allele of rs12107036 and the haplogroup Uk (23.4%) (95%CI: 7.89-38.9; p-value < 0.05). The area under the curve of the cross-validation model (0.730) was very similar to the obtained for the predictive model (0.735). A nomogram was constructed to help clinicians to perform clinical trials or epidemiologic studies. CONCLUSIONS: This study demonstrates the existence of a mitonuclear epistasis in OA, providing new mechanisms by which nuclear and mitochondrial variation influence the susceptibility to develop different OA phenotypes.


Asunto(s)
Osteoartritis de la Rodilla , Humanos , Osteoartritis de la Rodilla/genética , Osteoartritis de la Rodilla/epidemiología , Estudio de Asociación del Genoma Completo , Epistasis Genética , Articulación de la Rodilla , ADN Mitocondrial/genética , Progresión de la Enfermedad , Factores de Transcripción/genética , Proteínas Supresoras de Tumor/genética
8.
Eur J Clin Invest ; : e14313, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39239962

RESUMEN

BACKGROUND: Physiotherapists encounter challenges in diagnosing myofascial trigger points (MTrPs), which are crucial for managing myofascial pain but difficult due to their complex referred pain patterns. We aimed to assess if an interactive software (MyofAPPcial) can enhance the ability of physical therapists specialized in musculoskeletal disorders (as clinicians and as researchers and educators) to identify referred pain patterns associated with specific MTrPs and to explore their opinion about incorporating this technology regularly into their professional setting. METHODS: After developing the app, a descriptive cross-sectional survey study was conducted. Participants were asked about their demographic characteristics, professional experience, two knowledge tests (first without and later with MyofAPPcial support) and the 18-item mHealth app usability questionnaire. RESULTS: Fifty-nine participants completed the survey (47.5% clinicians and 62.5% researchers/educators). Groups were comparable in terms of age, gender and professional experience (p > .05). However, clinicians coursed shorter specific MPS trainings (p = .007) and handle more cases a week (p < .001). In the first knowledge test, participants in both the groups were more accurate in identifying pain maps of highly prevalent MTrPs than those with a moderate or low prevalence (p < .001), with no differences between the groups for individual items (all, p > .05) nor the total score (p > .05). In the second knowledge test, perfect scores were obtained for all items in both the groups. Finally, MyofAPPcial scored high satisfaction and app usefulness, with no difference between clinicians and researchers/educators (except greater convenience of use for researchers/educators p = .02). CONCLUSIONS: MyofAPPcial enhances physiotherapists' ability to accurately identify MTrPs, with a good acceptation among clinicians and researchers/educators.

9.
Proteome Sci ; 22(1): 1, 2024 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-38195472

RESUMEN

BACKGROUND: Tepary bean (Phaseolus acutifolius A. Gray) is one of the five species domesticated from the genus Phaseolus with genetic resistance to biotic and abiotic stress. To understand the mechanisms underlying drought responses in seed storage proteins germinated on water and polyethylene glycol (PEG-6000) at -0.49 MPa, we used a proteomics approach to identify potential molecular target proteins associated with the low water potential stress response. METHODS: Storage proteins from cotyledons of Tepary bean seeds germinated at 24, 48 and 72 h on water and PEG-6000 at -0.49 MPa were analyzed by one-dimensional electrophoresis (DE) with 2-DE analysis and shotgun mass spectrometry. Using computational database searching and bioinformatics analyses, we performed Gene Ontology (GO) and protein interactome (functional protein association network) String analyses. RESULTS: Comparative analysis showed that the effect of PEG-6000 on root growth was parallel to that on germination. Based on the SDS‒PAGE protein banding patterns and 2-DE analysis, ten differentially abundant seed storage proteins showed changes in storage proteins, principally in the phaseolin and lectin fractions. We found many proteins that are recognized as drought stress-responsive proteins, and several of them are predicted to be intrinsically related to abiotic stress. The shotgun analysis searched against UniProt's legume database, and Gene Ontology (GO) analysis indicated that most of the seed proteins were cytosolic, with catalytic activity and associated with carbohydrate metabolism. The protein‒protein interaction networks from functional enrichment analysis showed that phytohemagglutinin interacts with proteins associated with the degradation of storage proteins in the cotyledons of common bean during germination. CONCLUSION: These findings suggest that Tepary bean seed proteins provide valuable information with the potential to be used in genetic improvement and are part of the drought stress response, making our approach a potentially useful strategy for discovering novel drought-responsive proteins in other plant models.

10.
Chemphyschem ; 25(19): e202400372, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39250431

RESUMEN

Why are DNA bases stacked in a double helix structure? We combined three theoretical approaches to demonstrate how one core concept derived from quantum mechanics (Pauli repulsion) annihilates the contribution of dispersion to the π-π stacking. The helical architecture is governed by a combination of exchange and electrostatic forces, a result that is interpreted from both a computational and a biological perspective.


Asunto(s)
ADN , Conformación de Ácido Nucleico , Teoría Cuántica , ADN/química , Electricidad Estática
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