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1.
PLoS Biol ; 21(8): e3002263, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37647291

RESUMEN

The target of rapamycin (TOR) signalling pathway plays a key role in the coordination between cellular growth and the cell cycle machinery in eukaryotes. The underlying molecular mechanisms by which TOR might regulate events after anaphase remain unknown. We show for the first time that one of the 2 TOR complexes in budding yeast, TORC1, blocks the separation of cells following cytokinesis by phosphorylation of a member of the NDR (nuclear Dbf2-related) protein-kinase family, the protein Cbk1. We observe that TORC1 alters the phosphorylation pattern of Cbk1 and we identify a residue within Cbk1 activation loop, T574, for which a phosphomimetic substitution makes Cbk1 catalytically inactive and, indeed, reproduces TORC1 control over cell separation. In addition, we identify the exocyst component Sec3 as a key substrate of Cbk1, since Sec3 activates the SNARE complex to promote membrane fusion. TORC1 activity ultimately compromises the interaction between Sec3 and a t-SNARE component. Our data indicate that TORC1 negatively regulates cell separation in budding yeast by participating in Cbk1 phosphorylation, which in turn controls the fusion of secretory vesicles transporting hydrolase at the site of division.


Asunto(s)
Saccharomycetales , Fosforilación , Anafase , Separación Celular , Diana Mecanicista del Complejo 1 de la Rapamicina
2.
Artículo en Inglés | MEDLINE | ID: mdl-38195840

RESUMEN

BACKGROUND: Ocular trauma is one of the most important causes of ocular morbidity and inadequate visual acuity in developed and developing countries. In some countries, eye trauma is the leading cause of monocular blindness. Studies conducted in developing countries like Colombia suggest that there is a lack of awareness of preventive measures. In Colombia, there is no countrywide ocular trauma registry. The purpose of the present study is to describe and analyse characteristics of ocular trauma at a tertiary ophthalmology emergency department in Colombia. PATIENTS/METHODS AND MATERIAL: Patients who consulted or were referred to the ophthalmologic emergency department of FOSCAL due to eye injuries between March 1, 2022, and January 10, 2023, were included in this cross-sectional study. RESULTS: Of 1 957 patients, 2 088 eyes were included. Men comprised 78.5% of the patients, the median age was 36 years, and 75.0% lived in urban areas. The median latency between trauma and ophthalmology consultation was 21.8 hours. Of the eyes, 1 805 (88.4%) had suffered mechanical or mixed (mechanical plus burn) trauma. Of the injuries, 87.5% were unilateral. In terms of the circumstances, 45.9% of injuries occurred during working or educational activities (in 85.6% of these cases, without eye protection), 28.2% in home accidents, and 14.0% in transportation situations. According to the Birmingham Eye Trauma Terminology System (BETT), 1 735 eyes (91.1%) were closed globe injuries, and 49 eyes (2.7%) were open globe injuries. Fifty eyes (2.8%) could not be categorised according to BETT at the initial consultation and were classified as "still to be determined". In the Ocular Trauma Score (OTS), 85.8% were category 5. Of the ocular burn cases, 93.0% were categorised as grade I according to the Roper Hall classification. CONCLUSIONS: In line with global literature, a much higher proportion of men than women sought consultation for ocular trauma. The findings suggest a need for improvement in the referral process from institutions with the lowest level of care. Lack of awareness about eye protection is an issue. Surgical exploration or additional tests may be necessary for precise injury classification. We therefore propose adding a "still to be determined" category to the BETT initial classification. These cases may be reclassified later, thus improving the accuracy of OTS calculation.

3.
BMC Bioinformatics ; 24(1): 144, 2023 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-37046202

RESUMEN

Extraction of associations of singular nucleotide polymorphism (SNP) and phenotypes from biomedical literature is a vital task in BioNLP. Recently, some methods have been developed to extract mutation-diseases affiliations. However, no accessible method of extracting associations of SNP-phenotype from content considers their degree of certainty. In this paper, several machine learning methods were developed to extract ranked SNP-phenotype associations from biomedical abstracts and then were compared to each other. In addition, shallow machine learning methods, including random forest, logistic regression, and decision tree and two kernel-based methods like subtree and local context, a rule-based and a deep CNN-LSTM-based and two BERT-based methods were developed in this study to extract associations. Furthermore, the experiments indicated that although the used linguist features could be employed to implement a superior association extraction method outperforming the kernel-based counterparts, the used deep learning and BERT-based methods exhibited the best performance. However, the used PubMedBERT-LSTM outperformed the other developed methods among the used methods. Moreover, similar experiments were conducted to estimate the degree of certainty of the extracted association, which can be used to assess the strength of the reported association. The experiments revealed that our proposed PubMedBERT-CNN-LSTM method outperformed the sophisticated methods on the task.


Asunto(s)
Aprendizaje Automático , Polimorfismo de Nucleótido Simple , Fenotipo , Bosques Aleatorios , Mutación
4.
Cell Mol Life Sci ; 79(3): 165, 2022 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-35230542

RESUMEN

Eukaryotic cells divide and separate all their components after chromosome segregation by a process called cytokinesis to complete cell division. Cytokinesis is highly regulated by the recruitment of the components to the division site and through post-translational modifications such as phosphorylations. The budding yeast mitotic kinases Cdc28-Clb2, Cdc5, and Dbf2-Mob1 phosphorylate several cytokinetic proteins contributing to the regulation of cytokinesis. The PP2A-Cdc55 phosphatase regulates mitosis counteracting Cdk1- and Cdc5-dependent phosphorylation. This prompted us to propose that PP2A-Cdc55 could also be counteracting the mitotic kinases during cytokinesis. Here we show that in the absence of Cdc55, AMR contraction and the primary septum formation occur asymmetrically to one side of the bud neck supporting a role for PP2A-Cdc55 in cytokinesis regulation. In addition, by in vivo and in vitro assays, we show that PP2A-Cdc55 dephosphorylates the chitin synthase II (Chs2 in budding yeast) a component of the Ingression Progression Complexes (IPCs) involved in cytokinesis. Interestingly, the non-phosphorylable version of Chs2 rescues the asymmetric AMR contraction and the defective septa formation observed in cdc55∆ mutant cells. Therefore, timely dephosphorylation of the Chs2 by PP2A-Cdc55 is crucial for proper actomyosin ring contraction. These findings reveal a new mechanism of cytokinesis regulation by the PP2A-Cdc55 phosphatase and extend our knowledge of the involvement of multiple phosphatases during cytokinesis.


Asunto(s)
Actomiosina/metabolismo , Citocinesis/fisiología , Quitina Sintasa/metabolismo , Segregación Cromosómica/fisiología , Fosforilación/fisiología , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomycetales/metabolismo
5.
Int J Mol Sci ; 24(21)2023 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-37958727

RESUMEN

The highly conserved TOR signaling pathway is crucial for coordinating cellular growth with the cell cycle machinery in eukaryotes. One of the two TOR complexes in budding yeast, TORC1, integrates environmental cues and promotes cell growth. While cells grow, they need to copy their chromosomes, segregate them in mitosis, divide all their components during cytokinesis, and finally physically separate mother and daughter cells to start a new cell cycle apart from each other. To maintain cell size homeostasis and chromosome stability, it is crucial that mechanisms that control growth are connected and coordinated with the cell cycle. Successive periods of high and low TORC1 activity would participate in the adequate cell cycle progression. Here, we review the known molecular mechanisms through which TORC1 regulates the cell cycle in the budding yeast Saccharomyces cerevisiae that have been extensively used as a model organism to understand the role of its mammalian ortholog, mTORC1.


Asunto(s)
Proteínas de Saccharomyces cerevisiae , Transducción de Señal , Animales , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Nutrientes , Ciclo Celular/genética , Mamíferos/metabolismo
6.
Microsurgery ; 42(8): 749-756, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36102527

RESUMEN

BACKGROUND: Maxillary reconstructive surgery with fibula free flaps (FFFs) is a challenging procedure for head and neck surgeons. However, virtual surgical planning (VSP) and three-dimensional (3D) printing technologies have contributed to improved functional and aesthetic outcomes. The objective of this report is to demonstrate VSP/3D application in reconstruction of maxillary defects using the FFF by describing the different configurations available. We reviewed a series of consecutive cases operated at our institution and considered the management strategy of in-house planning in VSP/3D application. METHODS: In total, 11 cases were included from November 2016 to December 2021. Eight male and three female were included, with a mean age of 55.4 years old (range: 34-74 years old). Maxillary defects were classified according to Brown's Classification: two cases with IIB, one case with IIC, four cases with IID, three cases with III, and one case with IV. Preoperatively, facial computed tomography (CT) and lower extremity computed tomography angiogram (CTA) were performed in all patients. Osteocutaneous FFFs were planned, harvested, and customized according to the VSP/3D guide configuration. VSP and 3D printed cutting guides were performed by an external company in nine cases and were self-planned in three of them. Titanium 3D-printed fixation plates were used in four cases. RESULTS: All flaps survived, and the main reconstructive goals were achieved in 9 cases out of 11. Mean FFF length before osteotomy was 20.0 cm (17.5-22.5 cm). None of the cases experienced flap ischemia or venous congestion. At least one complication occurred in four cases: Prefabricated titanium plate exposure (two cases), loss of donor site skin grafts (one case), and ectropion (one case). One patient underwent a second FFF reconstruction. Two titanium printed plates became exposed after radiotherapy and needed to be removed. Mean follow-up time was 23.5 months (range 6-63 months). Dental rehabilitation was completed in eight of the 11 cases. Regarding functional recovery, five cases underwent delayed osseo-integrated dental implants (ODI), and two cases had immediate ODI procedures. One case was treated with removal dentition. CONCLUSION: VSP/3D printing technology is a new and helpful tool to successful restoration of craniofacial function and aesthetics. It can be used in the broad range of configurations offered by FFFs considering our suggested management strategy.


Asunto(s)
Colgajos Tisulares Libres , Reconstrucción Mandibular , Procedimientos de Cirugía Plástica , Cirugía Asistida por Computador , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Peroné/trasplante , Colgajos Tisulares Libres/trasplante , Reconstrucción Mandibular/métodos , Procedimientos de Cirugía Plástica/métodos , Cirugía Asistida por Computador/métodos , Titanio
7.
Pituitary ; 24(1): 117-129, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32785833

RESUMEN

PURPOSE AND METHODS: Sarcomas of the sellar region are uncommon and unexpected tumors. Here, we review the cases reported in literature via a systematic search. RESULTS: Ninety-four patients, 58.5% male with mean age of 39.2 ± 17.2 years were included. Fifty-seven (62%) had soft tissue sarcomas (STS) and 35 (38%) bone sarcomas (BS). Sarcoma was a primary tumor in 66%, developed after radiotherapy in 31.9% and 7.4% were metastatic. Median time between radiotherapy and sarcoma development was 10.5 (11) years. Main presentation symptoms were visual disorders (87.9%), headache (61.5%) and III cranial nerve palsy (24.1%). After surgery, sarcoma persisted or recurred in 82.3% and overall mortality reported was 44.6% with 6.5 (14) months of median survival. Tumor appeared earlier in BS compared to STS (34.4 ± 15.1 vs. 42.6 ± 17.6 years), p = 0.034 and complete tumor resection was achieved more often (41.3% vs. 4.4%), p = < 0.001. Condrosarcoma and rhabdomyosarcoma were more frequent subtypes among primary tumors while fibrosarcoma was among post-radiation sarcomas. Tumor size was larger in radiation associated sarcomas (mean maximum diameter 46.3 ± 9.3 vs. 29.1 ± 8.0 mm, p = 0.004) and persistency/recurrence was similar in both groups (70.1 vs. 73.3%, p = 0.259). CONCLUSION: Sarcomas appear as mass effect symptoms in the middle aged population, mainly as primary tumors, but one third is associated with radiotherapy. Surgery is commonly not curative, mortality rate is high and death ensues shortly after diagnosis.


Asunto(s)
Neoplasias de los Tejidos Blandos/epidemiología , Adulto , Animales , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Sarcoma/epidemiología
8.
PLoS Genet ; 14(3): e1007299, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29601579

RESUMEN

Deposition of additional plasma membrane and cargoes during cytokinesis in eukaryotic cells must be coordinated with actomyosin ring contraction, plasma membrane ingression and extracellular matrix remodelling. The process by which the secretory pathway promotes specific incorporation of key factors into the cytokinetic machinery is poorly understood. Here, we show that cell polarity protein Spa2 interacts with actomyosin ring components during cytokinesis. Spa2 directly binds to cytokinetic factors Cyk3 and Hof1. The lethal effects of deleting the SPA2 gene in the absence of either Cyk3 or Hof1 can be suppressed by expression of the hypermorphic allele of the essential chitin synthase II (Chs2), a transmembrane protein transported on secretory vesicles that makes the primary septum during cytokinesis. Spa2 also interacts directly with the chitin synthase Chs2. Interestingly, artificial incorporation of Chs2 into the cytokinetic machinery allows the localisation of Spa2 at the site of division. In addition, increased Spa2 protein levels promote Chs2 incorporation at the site of division and primary septum formation. Our data indicate that Spa2 is recruited to the cleavage site to co-operate with the secretory vesicle system and particular actomyosin ring components to promote the incorporation of Chs2 into the so-called 'ingression progression complexes' during cytokinesis in budding yeast.


Asunto(s)
Polaridad Celular , Quitina Sintasa/metabolismo , Citocinesis , Proteínas del Citoesqueleto/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/citología
9.
Vertex ; XXXII(153): 29-39, 2021 09.
Artículo en Español | MEDLINE | ID: mdl-34783784

RESUMEN

INTRODUCTION: The impact of the COVID-19 pandemic on health workers has been studied on an international level. However, mental health workers, who are also called upon to address such ailments both in the general population as well as in the health personnel, have not been asked about their experiences. METHODS: Seventy mental health workers in five regions of Argentina were interviewed between May and June 2020 regarding the subjective impact of changes in their work due to the pandemic. The responses were analyzed quantitatively and qualitatively. RESULTS: The results indicate emotions and experiences associated with a negative impact, in connection to feelings of tiresome, uncertainty, fear, anguish and anxiety and, to a lesser extent, some positive impacts are also described. More than a third of participants mentioned mixed feelings (i.e., being surprised, ambivalent, alert and sensitive). CONCLUSIONS: The personnel who are supposed to support the rest of the health workers are affected and experience having been relegated one more time to other aspects within the health care system. Focusing on learnings, having management roles, counting on colleagues, and agreeing with macro policies could be protective factors against the difficulties associated with the changes in work that the pandemic has imposed.


Asunto(s)
COVID-19 , Servicios de Salud Mental , Ansiedad , Argentina/epidemiología , Personal de Salud , Humanos , Pandemias , SARS-CoV-2
10.
Int J Clin Pharmacol Ther ; 58(6): 316-331, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32324130

RESUMEN

OBJECTIVE: Naproxen sodium (NAPSO) is commonly used in a variety of pain conditions. There are several strengths of NAPSO available over the counter (OTC). Most published data are based on single or multiple doses using 220 mg, hence there is a need to assess the analgesic efficacy of other strengths of NAPSO used in the OTC setting. MATERIALS AND METHODS: We reviewed published and unpublished studies of naproxen (NAP) and NAPSO to establish the pharmacokinetic relationship between dosage, plasma concentration, and efficacy, and to compare the analgesic efficacy of NAPSO 220, 440, and 550 mg or NAP 500 mg versus placebo and active comparators. RESULTS: Increasing OTC doses of NAP are associated with linear pharmacokinetics, i.e., plasma levels of NAP increase proportionately with dosage. Accordingly, the therapeutic efficacy of higher doses of NAP or NAPSO is greater than lower doses. All OTC doses of NAP and NAPSO are significantly more effective than placebo. Higher strengths are as effective or more effective than lower strengths, and at least comparable to other active treatments. CONCLUSION: The pharmacokinetic linearity associated with NAP means that data on efficacy for the lower OTC doses of NAPSO can be extrapolated to the higher OTC doses. Thus, it is given that NAPSO 275 and 550 mg will be at least as effective as or superior to the lower doses of 220 and 440 mg.


Asunto(s)
Antiinflamatorios no Esteroideos/farmacocinética , Naproxeno/farmacocinética , Humanos , Medicamentos sin Prescripción/farmacocinética
11.
Am J Dent ; 33(2): 106-112, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32259416

RESUMEN

PURPOSE: Two studies evaluated the efficacy and safety of a single dose of naproxen sodium 440 mg (NS) compared to the combination of acetaminophen 600 mg and codeine phosphate 60 mg (AC) in subjects with postoperative dental pain. METHODS: The two studies were single center, randomized, double-blind and double-dummy trials. In both studies, subjects were randomized into one of the following three treatments in a 2:2:1 ratio, respectively: NS, AC, or placebo (PBO). Subjects were administered study medication when they had at least moderate pain following the surgical removal of three or four impacted molars, at least one of which was a mandibular partial or complete bony impaction. Efficacy assessments were completed over an 8-hour evaluation period. The co-primary efficacy assessments in both studies were time-weighted sum of categorical pain intensity differences over 4 hours (SPID4) and time-weighted sum of pain relief scores over 4 hours (TOTPAR4). Other efficacy assessments such as summed scores over 8 hours, time to onset of relief, time to rescue medication and global rating of medication were also assessed. RESULTS: In Study 1, there were 225 subjects evaluated for efficacy, and 228 evaluated for safety. In Study 2, there were 230 subjects evaluated for efficacy and safety. In both studies, NS and AC were significantly better than placebo for almost all efficacy measures. In Study 1, NS was significantly superior to AC for all summed efficacy scores over 4 and 8 hours except for SPID4. NS was also superior to AC for most individual time point scores from 3 through 8 hours, as well as for the time to taking rescue medication. Both actives had a similar onset of effect. The incidence of adverse events (AEs) was significantly higher in the AC group compared to NS and PBO. The most frequently reported AEs with AC were gastrointestinal (GI) and nervous system events. In Study 2, there were no statistically significant differences between the two active treatments for any summed efficacy score, except for TOTPAR8, where NS was significantly better than AC. NS was significantly better than AC for individual pain relief time point scores from 3 through 8 hours and significantly better for individual pain intensity difference scores from 5 through 8 hours. AC had a significantly faster onset of effect compared to NS, but NS had a significantly longer time to rescue compared to AC. Nervous system AEs (dizziness and somnolence) were reported significantly more frequently with AC compared to NS. In conclusion, Both NS and AC are effective in the relief of postoperative dental pain. NS provided comparable to superior relief vs. AC and its analgesic effects lasted significantly longer. NS was well tolerated and resulted in a lower rate of AEs than AC. CLINICAL SIGNIFICANCE: In 2017, the US Department of Human Health Services declared a public health emergency to address the national opioid crisis. Since dentists are among the most common specialty groups prescribing opioids, these studies show that NSAIDs (such as naproxen sodium) are effective analgesics for relieving postoperative pain.


Asunto(s)
Acetaminofén , Codeína , Dolor Postoperatorio , Atención Odontológica , Método Doble Ciego , Humanos , Naproxeno
12.
PLoS Genet ; 12(2): e1005864, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26891268

RESUMEN

Eukaryotic cells must coordinate contraction of the actomyosin ring at the division site together with ingression of the plasma membrane and remodelling of the extracellular matrix (ECM) to support cytokinesis, but the underlying mechanisms are still poorly understood. In eukaryotes, glycosyltransferases that synthesise ECM polysaccharides are emerging as key factors during cytokinesis. The budding yeast chitin synthase Chs2 makes the primary septum, a special layer of the ECM, which is an essential process during cell division. Here we isolated a group of actomyosin ring components that form complexes together with Chs2 at the cleavage site at the end of the cell cycle, which we named 'ingression progression complexes' (IPCs). In addition to type II myosin, the IQGAP protein Iqg1 and Chs2, IPCs contain the F-BAR protein Hof1, and the cytokinesis regulators Inn1 and Cyk3. We describe the molecular mechanism by which chitin synthase is activated by direct association of the C2 domain of Inn1, and the transglutaminase-like domain of Cyk3, with the catalytic domain of Chs2. We used an experimental system to find a previously unanticipated role for the C-terminus of Inn1 in preventing the untimely activation of Chs2 at the cleavage site until Cyk3 releases the block on Chs2 activity during late mitosis. These findings support a model for the co-ordinated regulation of cell division in budding yeast, in which IPCs play a central role.


Asunto(s)
Citocinesis , Matriz Extracelular/metabolismo , Saccharomycetales/citología , Saccharomycetales/metabolismo , Actomiosina/metabolismo , Biocatálisis , Dominio Catalítico , División Celular , Quitina/biosíntesis , Modelos Biológicos , Unión Proteica , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/metabolismo
13.
Vertex ; XXIX(142): 255-262, 2018 Nov.
Artículo en Español | MEDLINE | ID: mdl-30785967

RESUMEN

Eight years after the enactment of the National Mental Health Law (26.657), we consider it necessary to build spaces for debate on the potentialities and challenges in its practical implementation. This research addresses the mental health practices in the general public hospitals of the city of Rosario and Gran Rosario, Argentina, from the workers' perspective. Through a qualitative and exploratory / descriptive approach, semi-structured interviews were conducted with 23 mental health workers (nurses, psychiatrists, psychologists, social workers and therapeutic companions). The analysis of the results allowed to stablish that the sanction of the law legitimized and strengthened already existing conceptions and practices, making possible its extension and the creation of new devices. Political, management, building, training and human resources limitations were analyzed. The scarcity of substitute devices to the psychiatric hospital, in addition to previously mentioned limitations, points to the importance of a Mental Health Plan, with clear resources, objectives and guidelines that may enable changes in the paradigm of care.


Asunto(s)
Hospitales Generales , Salud Mental , Psiquiatría , Argentina , Hospitales Psiquiátricos , Humanos , Servicios de Salud Mental
14.
EMBO J ; 31(17): 3620-34, 2012 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-22872148

RESUMEN

Polarisation of the actin cytoskeleton must cease during cytokinesis, to support efficient assembly and contraction of the actomyosin ring at the site of cell division, but the underlying mechanisms are still understood poorly in most species. In budding yeast, the Mitotic Exit Network (MEN) releases Cdc14 phosphatase from the nucleolus during anaphase, leading to the inactivation of mitotic forms of cyclin-dependent kinase (CDK) and the onset of septation, before G1-CDK can be reactivated and drive re-polarisation of the actin cytoskeleton to a new bud. Here, we show that premature inactivation of mitotic CDK, before release of Cdc14, allows G1-CDK to divert the actin cytoskeleton away from the actomyosin ring to a new site of polarised growth, thereby delaying progression through cytokinesis. Our data indicate that cells normally avoid this problem via the MEN-dependent release of Cdc14, which counteracts all classes of CDK-mediated phosphorylations during cytokinesis and blocks polarised growth. The dephosphorylation of CDK targets is therefore central to the mechanism by which the MEN and Cdc14 initiate cytokinesis and block polarised growth during late mitosis.


Asunto(s)
Proteínas de Ciclo Celular/fisiología , Quinasas Ciclina-Dependientes/fisiología , Proteínas Fúngicas/fisiología , Proteínas Tirosina Fosfatasas/fisiología , Saccharomycetales/fisiología , Citocinesis , Mitosis , Fosforilación
15.
EMBO J ; 31(9): 2195-206, 2012 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-22433841

RESUMEN

Mcm10 is essential for chromosome replication in eukaryotic cells and was previously thought to link the Mcm2-7 DNA helicase at replication forks to DNA polymerase alpha. Here, we show that yeast Mcm10 interacts preferentially with the fraction of the Mcm2-7 helicase that is loaded in an inactive form at origins of DNA replication, suggesting a role for Mcm10 during the initiation of chromosome replication, but Mcm10 is not a stable component of the replisome subsequently. Studies with budding yeast and human cells indicated that Mcm10 chaperones the catalytic subunit of polymerase alpha and preserves its stability. We used a novel degron allele to inactivate Mcm10 efficiently and this blocked the initiation of chromosome replication without causing degradation of DNA polymerase alpha. Strikingly, the other essential helicase subunits Cdc45 and GINS were still recruited to Mcm2-7 when cells entered S-phase without Mcm10, but origin unwinding was blocked. These findings indicate that Mcm10 is required for a novel step during activation of the Cdc45-MCM-GINS helicase at DNA replication origins.


Asunto(s)
Proteínas de Ciclo Celular/metabolismo , Proteínas Cromosómicas no Histona/metabolismo , ADN Helicasas/metabolismo , Proteínas Fúngicas/metabolismo , Antígenos Comunes de Leucocito/metabolismo , Replicación del ADN , ADN de Hongos/metabolismo , Levaduras
16.
Sensors (Basel) ; 16(1)2016 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-26805839

RESUMEN

Inappropriate speed is a relevant concurrent factor in many traffic accidents. Moreover, in recent years, traffic accidents numbers in Spain have fallen sharply, but this reduction has not been so significant on single carriageway roads. These infrastructures have less equipment than high-capacity roads, therefore measures to reduce accidents on them should be implemented in vehicles. This article describes the development and analysis of the impact on the driver of a warning system for the safe speed on each road section in terms of geometry, the presence of traffic jams, weather conditions, type of vehicle and actual driving conditions. This system is based on an application for smartphones and includes knowledge of the vehicle position via Ground Positioning System (GPS), access to intravehicular information from onboard sensors through the Controller Area Network (CAN) bus, vehicle data entry by the driver, access to roadside information (short-range communications) and access to a centralized server with information about the road in the current and following sections of the route (long-range communications). Using this information, the system calculates the safe speed, recommends the appropriate speed in advance in the following sections and provides warnings to the driver. Finally, data are sent from vehicles to a server to generate new information to disseminate to other users or to supervise drivers' behaviour. Tests in a driving simulator have been used to define the system warnings and Human Machine Interface (HMI) and final tests have been performed on real roads in order to analyze the effect of the system on driver behavior.

17.
J Cell Sci ; 125(Pt 22): 5453-66, 2012 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-22956544

RESUMEN

The chitin synthase that makes the primary septum during cell division in budding yeasts is an important therapeutic target with an unknown activation mechanism. We previously found that the C2-domain of the Saccharomyces cerevisiae Inn1 protein plays an essential but uncharacterised role at the cleavage site during cytokinesis. By combining a novel degron allele of INN1 with a point mutation in the C2-domain, we screened for mutations in other genes that suppress the resulting defect in cell division. In this way, we identified 22 dominant mutations of CHS2 (chitin synthase II) that map to two neighbouring sites in the catalytic domain. Chs2 in isolated cell membranes is normally nearly inactive (unless protease treatment is used to bypass inhibition); however, the dominant suppressor allele Chs2-V377I has enhanced activity in vitro. We show that Inn1 associates with Chs2 in yeast cell extracts. It also interacts in a yeast two-hybrid assay with the N-terminal 65% of Chs2, which contains the catalytic domain. In addition to compensating for mutations in the Inn1 C2-domain, the dominant CHS2 alleles suppress cytokinesis defects produced by the lack of the Cyk3 protein. Our data support a model in which the C2-domain of Inn1 acts in conjunction with Cyk3 to regulate the catalytic domain of Chs2 during cytokinesis. These findings suggest novel approaches for developing future drugs against important fungal pathogens.


Asunto(s)
Proteínas de Ciclo Celular/metabolismo , Quitina Sintasa/metabolismo , Citocinesis , Proteínas Asociadas a Microtúbulos/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/citología , Saccharomyces cerevisiae/enzimología , Alelos , Secuencia de Aminoácidos , Biocatálisis , Proliferación Celular , Quitina Sintasa/química , Genes Dominantes/genética , Genes Fúngicos/genética , Genes Supresores , Datos de Secuencia Molecular , Proteínas Mutantes/metabolismo , Mutación/genética , Unión Proteica/genética , Estructura Secundaria de Proteína , Estructura Terciaria de Proteína , Proteínas de Saccharomyces cerevisiae/química , Supresión Genética
18.
Dalton Trans ; 53(16): 7081-7092, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38567490

RESUMEN

Semiconductor heterojunctions are an effective way to achieve efficient photocatalysts, as they can provide an adequate redox potential with visible light excitation. Several works have reported synergistic effects with nanoparticle semiconductor materials. The question is still open for thin film heterojunctions formed by stacked layers, as photocatalysis is considered a surface phenomenon. To investigate if the internal layer really affects or modifies the photocatalytic properties of the external material, we analyze the thin film heterojunction with ZnO and Bi2O3 semiconductors deposited by spray pyrolysis in two configurations: substrate/ZnO/Bi2O3 and substrate/Bi2O3/ZnO. Microstructural analysis was performed to verify the formation of the physical junction of the materials and discard new ternary phases. The photocatalytic activity was analyzed as a function of the thickness of the layers under blue light irradiation. We determined the conduction and valence bands positions, the carrier concentrations, mobilities, Fermi levels, etc. that allowed us to distinguish two reaction mechanisms depending on the configuration. There is a strong compromise between the order and thickness of the layers with the photocatalytic activity. The internal electric field produced in the interface defines the route of the photogenerated charges, and therefore the photocatalytic response. Thus, well-designed thin film heterojunctions can indeed improve the photocatalytic activity of the surface layer.

19.
Front Vet Sci ; 11: 1416365, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39170637

RESUMEN

Introduction: Feeding local forages to ruminants is a promising strategy for enhancing metabolic processes, promoting sustainable farming, and improving product quality. However, studies comparing the effects of different forages on rumen histology and meat attributes of heifers are limited and variable. Material and methods: This study evaluated the benefits of incorporating local forages into heifer diets by comparing barley straw (BS) and oat hay (OH) on heifer attributes focusing on meat quality (MQ) and rumen status (RS). Sixteen crossbred (Charolais x Limousin) female heifers (7 months of age, 263 ± 10.50 kg) were randomly assigned to two dietary treatments (BS or OH) over 120 days. Results and discussion: Heifers fed OH showed enhanced RS (p < 0.05), characterized by improved intestinal epithelial integrity and a lower percentage of hyperpigmented cells, suggesting a potential reduction in inflammatory processes compared to BS, which may indicate a lower risk of metabolic diseases. Despite this, no significant differences (p > 0.05) were found in animal performance, chemical composition, and technological properties of the meat between the dietary groups, while lower levels (p < 0.05) of certain saturated fatty acids (C12:0, C15:0, and C22:0) were found in the meat from heifers fed OH. Principal component analysis (PCA) reduced the variables and demonstrated that all variables assessed can be condensed into four new variables explaining 75.06% of the variability. Moreover, biplot analysis reveals that the OH diet could be discriminated from BS. Our findings suggest that OH is a valuable fiber source, positively influencing certain heifer attributes, and supporting sustainable animal agriculture practices.

20.
Digit Discov ; 3(8): 1509-1533, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39118978

RESUMEN

The Open Databases Integration for Materials Design (OPTIMADE) application programming interface (API) empowers users with holistic access to a growing federation of databases, enhancing the accessibility and discoverability of materials and chemical data. Since the first release of the OPTIMADE specification (v1.0), the API has undergone significant development, leading to the v1.2 release, and has underpinned multiple scientific studies. In this work, we highlight the latest features of the API format, accompanying software tools, and provide an update on the implementation of OPTIMADE in contributing materials databases. We end by providing several use cases that demonstrate the utility of the OPTIMADE API in materials research that continue to drive its ongoing development.

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