Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.020
Filtrar
1.
Inorg Chem ; 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39018429

RESUMEN

One of the major challenges in processing rare-earth element (REE) materials arises from the large amounts of radioactive thorium (Th) that are often found within REE minerals, encouraging enhanced metal separation procedures. We report here a study aimed at developing improved systems for REE processing with the goal of efficient extraction of Th(IV) from acidic solution. A tripodal ligand, TRPN-CMPO-Ph, was prepared that utilizes carbamoylmethylphosphine oxide (CMPO) chelators tethered to a tris(3-aminopropyl)amine (TRPN) capping scaffold. The ligand and its metal complexes were characterized by using elemental analysis, NMR, Fourier transform infrared spectroscopy, mass spectrometry, and luminescence spectroscopy. Using a liquid-liquid metal extraction protocol, TRPN-CMPO-Ph selectively extracts Th(IV) at an efficiency of 79% from a mixture of Th(IV), UO22+, and all rare-earth metal cations (except promethium) dissolved in nitric acid into an organic solvent. Th(IV) extraction selectivity is maintained upon extraction from a mixture that approximates a typical monazite leach solution containing several relevant lanthanide ions, including two ions at higher concentration relative to Th(IV). Comparative studies with a tris(2-aminoethyl)amine (TREN)-capped derivative are presented and support the need for a larger TRPN capping scaffold in achieving Th(IV) extraction selectivity.

2.
Eur J Neurosci ; 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38858126

RESUMEN

Mild-moderate traumatic brain injuries (TBIs) are prevalent, and while many individuals recover, there is evidence that a significant number experience long-term health impacts, including increased vulnerability to neurodegenerative diseases. These effects are influenced by other risk factors, such as cardiovascular disease. Our study tested the hypothesis that a pre-injury reduction in cerebral blood flow (CBF), mimicking cardiovascular disease, worsens TBI recovery. We induced bilateral carotid artery stenosis (BCAS) and a mild-moderate closed-head TBI in male and female mice, either alone or in combination, and analyzed CBF, spatial learning, memory, axonal damage, and gene expression. Findings showed that BCAS and TBI independently caused a ~10% decrease in CBF. Mice subjected to both BCAS and TBI experienced more significant CBF reductions, notably affecting spatial learning and memory, particularly in males. Additionally, male mice showed increased axonal damage with both BCAS and TBI compared to either condition alone. Females exhibited spatial memory deficits due to BCAS, but these were not worsened by subsequent TBI. Gene expression analysis in male mice highlighted that TBI and BCAS individually altered neuronal and glial profiles. However, the combination of BCAS and TBI resulted in markedly different transcriptional patterns. Our results suggest that mild cerebrovascular impairments, serving as a stand-in for preexisting cardiovascular conditions, can significantly worsen TBI outcomes in males. This highlights the potential for mild comorbidities to modify TBI outcomes and increase the risk of secondary diseases.

3.
J Arthroplasty ; 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38821429

RESUMEN

BACKGROUND: Total knee arthroplasty (TKA) is an excellent surgical option for patients who have end-stage knee osteoarthritis. While rates of major postoperative complications have steadily decreased with modern implants and operative techniques, contemporary outcome data for patients who have Ehlers-Danlos syndrome (EDS) are scarce. The goal of this study was to compare complication rates after primary TKA in patients who have EDS versus matched controls. METHODS: A large administrative database was used to identify patients who underwent primary TKA from 2009 to 2020. Patients who had a diagnosis of EDS were identified by International Classification of Diseases Coding. Propensity scores were utilized to match these patients with controls at a 1:4 ratio based on age, sex, and various comorbidities. Multivariable logistic regression analysis was used to compare the rates of medical and surgical complications at 90 days and 2 years. A total of 188 patients who had EDS and 752 controls were included in this study. RESULTS: After univariate analysis, Ehlers-Danlos patients exhibited significantly higher rates of wound complications (4.8 versus 0.9%, P = .001) at 90 days. When adjusted for comorbidities, Ehlers-Danlos patients still exhibited significantly increased odds of developing wound complications (odds ratio: 7.06; P < .001). CONCLUSIONS: Patients who have EDS undergoing TKA exhibited significantly higher rates of wound complications within 90 days postoperatively compared to matched controls. Rates of instability, manipulation under anesthesia, periprosthetic joint infection, aseptic loosening, and aseptic revision arthroplasty did not significantly differ between the cohorts. This study found generally favorable short-term outcomes of TKA in this population; however, the inability to control for implant type and other confounding variables may have influenced the lack of difference in complication rates at 2 years. Surgeons should monitor for the potentially increased risk of wound complications and consider the possible need for increased constraint in this population during preoperative planning.

4.
Musculoskeletal Care ; 22(1): e1876, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38511963

RESUMEN

INTRODUCTION: Globally, back pain is the leading cause of years of disability. In the United Kingdom, over 20 million people live with musculoskeletal (MSK) pain, with low back pain being one of the most common causes. National strategies promote self-management and the use of digital technologies to empower populations. AIMS: To evaluate the uptake and impact of providing the SelfSTart approach (STarT Back and SelfBACK App) when delivered by a First Contact Physiotherapist (FCP) to people presenting with low back pain in primary care. METHODS: Patients presenting with a new episode of low back pain underwent routine assessment and completion of a STarT Back questionnaire. Patients with low/medium scores were offered the SelfBACK App. A control population was provided by the MIDAS-GP study. Patient Experience, outcome measures, healthcare utilisation and retention were captured through the app and clinical systems (EMIS). Interviews with five FCPs explored the experiences of using the SelfSTart approach. RESULTS: SelfSTarT was taken up by almost half (48%) of those to whom it was offered. Compared to MIDAS-GP, users were more likely to be younger, male, in work, and with higher health literacy. SelfSTarT users reported significant improved experiences relating to receiving an agreed care plan and receiving sufficient information. There were no significant differences in treatments offered. FCPs were positive about the app and felt it had value but wanted feedback on patient progress. They recognised that a digital solution would not be suitable for all. CONCLUSION: This approach offers an opportunity to empower and support self-management, using robustly evaluated digital technology.


Asunto(s)
Dolor de la Región Lumbar , Dolor Musculoesquelético , Fisioterapeutas , Humanos , Masculino , Dolor de la Región Lumbar/terapia , Dolor de Espalda/terapia , Encuestas y Cuestionarios , Evaluación de Resultado en la Atención de Salud
5.
Mucosal Immunol ; 17(2): 303-313, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38428738

RESUMEN

The mammalian gastrointestinal tract hosts a diverse community of trillions of microorganisms, collectively termed the microbiota, which play a fundamental role in regulating tissue physiology and immunity. Recent studies have sought to dissect the cellular and molecular mechanisms mediating communication between the microbiota and host immune system. Epithelial cells line the intestine and form an initial barrier separating the microbiota from underlying immune cells, and disruption of epithelial function has been associated with various conditions ranging from infection to inflammatory bowel diseases and cancer. From several studies, it is now clear that epithelial cells integrate signals from commensal microbes. Importantly, these non-hematopoietic cells also direct regulatory mechanisms that instruct the recruitment and function of microbiota-sensitive immune cells. In this review, we discuss the central role that has emerged for epithelial cells in orchestrating intestinal immunity and highlight epithelial pathways through which the microbiota can calibrate tissue-intrinsic immune responses.


Asunto(s)
Enfermedades Inflamatorias del Intestino , Microbiota , Animales , Humanos , Intestinos , Enfermedades Inflamatorias del Intestino/metabolismo , Sistema Inmunológico , Mucosa Intestinal , Mamíferos
6.
Colorectal Dis ; 26(2): 309-316, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38173125

RESUMEN

AIM: The aim of this work was to evaluate colorectal cancer (CRC) outcomes after 'low' (sub-threshold) faecal immunochemical test (FIT) results in symptomatic patients tested in primary care. METHOD: This work comprised a retrospective audit of 35 289 patients with FIT results who had consulted their general practitioner with lower gastrointestinal symptoms and had subsequent CRC diagnoses. The Rapid Colorectal Cancer Diagnosis pathway was introduced in November 2017 to allow incorporation of FIT into clinical practice. The local '4F' protocol combined FIT results with blood tests and digital rectal examination (DRE): FIT, full blood count, ferritin and finger [DRE]. The outcome used was detection rates of CRC, missed CRC and time to diagnosis in local 4F protocols for patients with a subthreshold faecal haemoglobin (fHb) result compared with thresholds of 10 and 20 µg Hb/g faeces. RESULTS: A single threshold of 10 µg Hb/g faeces identifies a population in whom the risk of CRC is 0.2%, but this would have missed 63 (10.5%) of 599 CRCs in this population. The Nottingham 4F protocol would have missed fewer CRCs [42 of 599 (7%)] despite using a threshold of 20 µg Hb/g faeces for patients with normal blood tests. Subthreshold FIT results in patients subsequently diagnosed with a palpable rectal tumour yielded the longest delays in diagnosis. CONCLUSION: A combination of FIT with blood results and DRE (the 4F protocol) reduced the risk of missed or delayed diagnosis. Further studies on the impact of such protocols on the diagnostic accuracy of FIT are expected. The value of adding blood tests to FIT may be restricted to specific parts of the fHb results spectrum.


Asunto(s)
Neoplasias Colorrectales , Neoplasias del Recto , Humanos , Neoplasias Colorrectales/patología , Sensibilidad y Especificidad , Estudios Retrospectivos , Hemoglobinas/análisis , Colonoscopía , Heces/química , Sangre Oculta , Detección Precoz del Cáncer/métodos
7.
Curr Res Toxicol ; 6: 100146, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38223505

RESUMEN

Recently, oxyfluorfen, a pre- and post-emergent diphenyl ether herbicide, was identified in our laboratory as an inhibitor of iodide uptake by the sodium iodide symporter (NIS), the first key step in the synthesis of thyroid hormones (THs). This inhibition was observed in vitro, using both a human NIS engineered cell line (hNIS-HEK293T-EPA) and a rat thyroid follicular cell line (FRTL-5). Oxyfluorfen was found to be a potent inhibitor of NIS activity with an EC50 of approximately 2 µM in both cell lines with no observed cytotoxicity at any concentration tested up to 100 µM. The current research tested the hypothesis that oxyfluorfen alters circulating concentrations of THs. This hypothesis was first tested in a pilot study with both juvenile male and female rats exposed to oxyfluorfen for 4 days at 0, 125, 250 and 500 mg/kg/day. Once we identified that this short-term 4-day oxyfluorfen exposure suppressed both total serum thyroxine (T4) and triiodothyronine (T3) at all doses, we tested seven lower concentrations of oxyfluorfen (0.8125 to 62.5 mg/kg day) in an 8-day exposure paradigm to more closely evaluate the dose-response. We found that oxyfluorfen suppressed serum T4 with a LOEL of 3.25 mg/kg/day and T3 with a LOEL 62.5 mg/kg/day. Analytical chemistry of the serum showed an accumulation over time following oral exposure to oxyfluorfen in both the 4- and 8-day groups. Analytical chemistry of the thyroid glands in the 8-day study revealed higher accumulation in the thyroid as compared to the serum (2 to 3- fold at 62.5 mg/kg). No changes in thyroid weight or serum TSH were observed following the 8-day exposure. This study is the first to demonstrate an effect of oxyfluorfen on serum thyroid hormones in the rat. Additional studies are needed to further evaluate the effects on thyroid homeostasis with extended exposures and the potential implications of the observed effects.

8.
Arch Sex Behav ; 53(1): 57-76, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38038854

RESUMEN

Persons who have renounced a prior transgender identification, often after some degree of social and medical transition, are increasingly visible. We recruited 78 US individuals ages 18-33 years who previously identified as transgender and had stopped identifying as transgender at least six months prior. On average, participants first identified as transgender at 17.1 years of age and had done so for 5.4 years at the time of their participation. Most (83%) participants had taken several steps toward social transition and 68% had taken at least one medical step. By retrospective reports, fewer than 17% of participants met DSM-5 diagnostic criteria for Gender Dysphoria in Childhood. In contrast, 53% of participants believed that "rapid-onset gender dysphoria" applied to them. Participants reported a high rate of psychiatric diagnoses, with many of these prior to trans-identification. Most participants (N = 71, 91%) were natal females. Females (43%) were more likely than males (0%) to be exclusively homosexual. Participants reported that their psychological health had improved dramatically since detransition/desistance, with marked decreases in self-harm and gender dysphoria and marked increases in flourishing. The most common reason given for initial trans-identification was confusing mental health issues or reactions to trauma for gender dysphoria. Reasons for detransition were more likely to reflect internal changes (e.g., the participants' own thought processes) than external pressures (e.g., pressure from family). Results suggest that, for some transgender individuals, detransition is both possible and beneficial.


Asunto(s)
Disforia de Género , Minorías Sexuales y de Género , Personas Transgénero , Transexualidad , Masculino , Femenino , Humanos , Adulto Joven , Estudios Retrospectivos , Transexualidad/psicología , Personas Transgénero/psicología , Salud Mental , Disforia de Género/diagnóstico , Disforia de Género/psicología , Identidad de Género
9.
Org Lett ; 26(14): 2778-2783, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-37883080

RESUMEN

The influence of added surfactant to aqueous reaction mixtures containing various IREDs has been determined. Just the presence of a nonionic surfactant tends to increase both rates and extent of conversion to the targeted amines. The latter can be as much as >40% relative to buffer alone. Several tandem sequences featuring several steps that combine use of an IRED together with various types of chemocatalysis are also presented, highlighting the opportunities for utilizing chemoenzymatic catalysis, all in water.

10.
Proc Natl Acad Sci U S A ; 120(48): e2301642120, 2023 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-37983511

RESUMEN

Science is among humanity's greatest achievements, yet scientific censorship is rarely studied empirically. We explore the social, psychological, and institutional causes and consequences of scientific censorship (defined as actions aimed at obstructing particular scientific ideas from reaching an audience for reasons other than low scientific quality). Popular narratives suggest that scientific censorship is driven by authoritarian officials with dark motives, such as dogmatism and intolerance. Our analysis suggests that scientific censorship is often driven by scientists, who are primarily motivated by self-protection, benevolence toward peer scholars, and prosocial concerns for the well-being of human social groups. This perspective helps explain both recent findings on scientific censorship and recent changes to scientific institutions, such as the use of harm-based criteria to evaluate research. We discuss unknowns surrounding the consequences of censorship and provide recommendations for improving transparency and accountability in scientific decision-making to enable the exploration of these unknowns. The benefits of censorship may sometimes outweigh costs. However, until costs and benefits are examined empirically, scholars on opposing sides of ongoing debates are left to quarrel based on competing values, assumptions, and intuitions.


Asunto(s)
Censura de la Investigación , Ciencia , Responsabilidad Social , Costos y Análisis de Costo
11.
Antimicrob Agents Chemother ; 67(12): e0110223, 2023 12 14.
Artículo en Inglés | MEDLINE | ID: mdl-37966228

RESUMEN

We describe a genome-scale approach to identify the essential biological process targeted by a new antibiotic. The procedure is based on the identification of essential genes whose inactivation sensitizes a Gram-negative bacterium (Acinetobacter baylyi) to a drug and employs recently developed transposon mutant screening and single-mutant validation procedures. The approach, based on measuring the rates of loss of newly generated knockout mutants in the presence of antibiotic, provides an alternative to traditional procedures for studying essential functions using conditional expression or activity alleles. As a proof of principle study, we evaluated whether mutations enhancing sensitivity to the ß-lactam antibiotic meropenem corresponded to the known essential target process of the antibiotic (septal peptidoglycan synthesis). We found that indeed mutations inactivating most genes needed for peptidoglycan synthesis and cell division strongly sensitized cells to meropenem. Additional classes of sensitizing mutations in essential genes were also identified, including those that inactivated capsule synthesis, DNA replication, or envelope stress response regulation. The essential capsule synthesis mutants appeared to enhance meropenem sensitivity by depleting a precursor needed for both capsule and peptidoglycan synthesis. The replication mutants may sensitize cells by impairing division. Nonessential gene mutations sensitizing cells to meropenem were also identified in the screen and largely corresponded to functions subordinately associated with the essential target process, such as in peptidoglycan recycling. Overall, these results help validate a new approach to identify the essential process targeted by an antibiotic and define the larger functional network determining sensitivity to it.


Asunto(s)
Antibacterianos , Genes Esenciales , Antibacterianos/farmacología , Meropenem/farmacología , Peptidoglicano/metabolismo , Elementos Transponibles de ADN
12.
Sci Adv ; 9(46): eadi9036, 2023 11 17.
Artículo en Inglés | MEDLINE | ID: mdl-37967186

RESUMEN

DNA methylation mediates silencing of transposable elements and genes in part via recruitment of the Arabidopsis MBD5/6 complex, which contains the methyl-CpG binding domain (MBD) proteins MBD5 and MBD6, and the J-domain containing protein SILENZIO (SLN). Here, we characterize two additional complex members: α-crystalline domain (ACD) containing proteins ACD15 and ACD21. We show that they are necessary for gene silencing, bridge SLN to the complex, and promote higher-order multimerization of MBD5/6 complexes within heterochromatin. These complexes are also highly dynamic, with the mobility of MBD5/6 complexes regulated by the activity of SLN. Using a dCas9 system, we demonstrate that tethering the ACDs to an ectopic site outside of heterochromatin can drive a massive accumulation of MBD5/6 complexes into large nuclear bodies. These results demonstrate that ACD15 and ACD21 are critical components of the gene-silencing MBD5/6 complex and act to drive the formation of higher-order, dynamic assemblies at CG methylation (meCG) sites.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Proteínas de Unión al ADN/metabolismo , Heterocromatina/genética , Heterocromatina/metabolismo , Elementos Transponibles de ADN/genética , Arabidopsis/genética , Arabidopsis/metabolismo , Metilación de ADN , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo
13.
Autism ; : 13623613231213283, 2023 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-38006211

RESUMEN

LAY ABSTRACT: Caregiver-mediated early interventions support caregivers' use of strategies to improve their young autistic child's communication. In the current clinical trial, we sought to isolate the most effective strategies to improve short-term and long-term child communication outcomes. Results demonstrated how children may benefit from caregiver prompts to facilitate long-term language outcomes. In conclusion, the current study improves our understanding of how early intervention facilitates child communication outcomes.

14.
bioRxiv ; 2023 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-38014173

RESUMEN

Human RAD52 1,2 is a multifunctional DNA repair protein involved in several cellular events that support genome stability including protection of stalled DNA replication forks from excessive degradation 3-7 . In its gatekeeper role, RAD52 binds to and stabilizes stalled replication forks during replication stress protecting them from reversal by SMARCAL1 5 . The structural and molecular mechanism of the RAD52-mediated fork protection remains elusive. Here, using P1 nuclease sensitivity, biochemical and single-molecule analyses we show that RAD52 dynamically remodels replication forks through its strand exchange activity. The presence of the ssDNA binding protein RPA at the fork modulates the kinetics of the strand exchange without impeding the reaction outcome. Mass photometry and single-particle cryo-electron microscopy show that the replication fork promotes a unique nucleoprotein structure containing head-to-head arrangement of two undecameric RAD52 rings with an extended positively charged surface that accommodates all three arms of the replication fork. We propose that the formation and continuity of this surface is important for the strand exchange reaction and for competition with SMARCAL1.

15.
J Cardiopulm Rehabil Prev ; 43(6): 412-418, 2023 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-37890176

RESUMEN

PURPOSE: The objective of this report was to identify the main mechanisms of home-based remote monitoring programs for cardiac rehabilitation (RM CR) and examine how these mechanisms vary by context. METHODS: This was a systematic review using realist synthesis. To be included, articles had to be published in English between 2010 and November 2020 and contain specific data related to mechanisms of effect of programs. MEDLINE All (1946-) via Ovid, Embase (1974-) via Ovid, APA PsycINFO (1806-), CINAHL via EBSCO, Scopus databases, and gray literature were searched. RESULTS: From 13 747 citations, 91 focused on cardiac conditions, with 23 reports including patients in CR. Effective RM CR programs more successfully adapted to different patient home settings and broader lives, incorporated individualized patient health data, and had content designed specifically for patients in cardiac rehabilitation. Relatively minor but common technical issues could significantly reduce perceived benefits. Patients and families were highly receptive to the programs and viewed themselves as fortunate to receive such services. The RM CR programs could be improved via incorporating more connectivity to other patients. No clear negative effects on perceived utility or outcomes occurred by patient age, ethnicity, or sex. Overall, the programs were seen to best suit highly motivated patients and consolidated rather than harmed existing relationships with health care professionals and teams. CONCLUSIONS: Remote monitoring CR programs are perceived by patients to be beneficial and attractive. Future RM CR programs should consider adaptability to different home settings, incorporate individualized health data, and contain content specific to patient needs.


Asunto(s)
Rehabilitación Cardiaca , Cardiopatías , Humanos
16.
bioRxiv ; 2023 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-37662299

RESUMEN

DNA methylation mediates silencing of transposable elements and genes in part via recruitment of the Arabidopsis MBD5/6 complex, which contains the methyl-CpG-binding domain (MBD) proteins MBD5 and MBD6, and the J-domain containing protein SILENZIO (SLN). Here we characterize two additional complex members: α-crystalline domain containing proteins ACD15 and ACD21. We show that they are necessary for gene silencing, bridge SLN to the complex, and promote higher order multimerization of MBD5/6 complexes within heterochromatin. These complexes are also highly dynamic, with the mobility of complex components regulated by the activity of SLN. Using a dCas9 system, we demonstrate that tethering the ACDs to an ectopic site outside of heterochromatin can drive massive accumulation of MBD5/6 complexes into large nuclear bodies. These results demonstrate that ACD15 and ACD21 are critical components of gene silencing complexes that act to drive the formation of higher order, dynamic assemblies.

17.
J Speech Lang Hear Res ; 66(9): 3622-3632, 2023 09 13.
Artículo en Inglés | MEDLINE | ID: mdl-37536464

RESUMEN

PURPOSE: Child development milestones are a critical tool for pediatricians and caregivers to use for developmental surveillance. Following review and selection by a panel of subject matter experts, the Centers for Disease Control and Prevention (CDC) published a revised list of milestones across multiple domains of development. Using expressive vocabulary, a key indicator of language development, as an illustrative example, the purpose of this brief review is to evaluate the evidence used to establish the CDC developmental milestones and determine whether the samples used to establish these milestones are representative of U.S. children. METHOD: Authors reviewed the methods and evidence cited to determine the CDC milestones. First, authors identified each language/communication milestone that measured expressive vocabulary as number of words, followed by review of the sources cited in support of each extracted milestone. Then, data related to both milestones and sample characteristics were extracted and compiled as well as compared with data from a validated parent report measure of expressive vocabulary, the MacArthur-Bates Communication Development Inventories. RESULTS: Results indicated that evidence was conflicting, misaligned, or missing for the selected CDC expressive vocabulary milestones. This review also indicated that the samples used to determine the selected CDC expressive vocabulary milestones are not representative of U.S. children. CONCLUSION: The striking paucity of evidence supporting the new CDC milestones for expressive vocabulary illustrates the critical need for future research in this area to establish more accurate milestones for U.S. children, with a focus on culturally inclusive large-scale data.


Asunto(s)
Desarrollo Infantil , Vocabulario , Niño , Humanos , Desarrollo del Lenguaje , Comunicación
18.
J Am Chem Soc ; 145(29): 15981-15989, 2023 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-37433011

RESUMEN

Highly efficient chemical ligations that operate in water under mild conditions are the foundation of bioorthogonal chemistry. However, the toolbox of suitable reactions is limited. Conventional approaches to expand this toolbox aim at altering the inherent reactivity of functional groups to design new reactions that meet the required benchmarks. Inspired by controlled reaction environments that enzymes provide, we report a fundamentally different approach that makes inefficient reactions highly efficient within defined local environments. Contrasting enzymatically catalyzed reactions, the reactivity controlling self-assembled environment is brought about by the ligation targets themselves─avoiding the use of a catalyst. Targeting [2 + 2] photocycloadditions, which are inefficient at low concentrations and readily quenched by oxygen, short ß-sheet encoded peptide sequences are inserted between a hydrophobic photoreactive styrylpyrene unit and a hydrophilic polymer. In water, electrostatic repulsion of deprotonated amino acid residues governs the formation of small self-assembled structures, which enable a highly efficient photoligation of the polymer, reaching ∼90% ligation within 2 min (0.034 mM). Upon protonation at low pH, the self-assembly changes into 1D fibers, altering photophysical properties and shutting down the photocycloaddition reaction. Using the reversible morphology change, it is possible to switch the photoligation "ON" or "OFF" under constant irradiation simply by varying the pH. Importantly, in dimethylformamide, the photoligation reaction did not occur even at 10-fold higher concentrations (0.34 mM). The self-assembly into a specific architecture, encoded into the polymer ligation target, enables a highly efficient ligation that overcomes the concentration limitations and high oxygen sensitivity of [2 + 2] photocycloadditions.

19.
Arch Sex Behav ; 2023 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-37415028

RESUMEN

Some men sexually attracted to types of persons (e.g., women) or things (e.g., animals) also have internalized sexual attractions: sexual arousal by the idea of being the type of person or thing to whom they are attracted. Consequently, some of these men develop erotic target identity inversions, in which they imitate, yearn to be, or identify as an instance of their erotic target. Erotic Target Identity Inversion Theory predicts that for every external erotic target to which men are attracted, a subset of men will develop an internalized sexual attraction, which may cause an erotic target identity inversion. We examined these predictions in Internet surveys of three samples of men with paraphilic sexual interests: 322 men attracted to amputees, 1501 men attracted to animals, and 402 men attracted to severely obese persons. All samples included substantial minorities of men reporting internalized sexual attractions and erotic target identity inversions specific to their external sexual attractions (e.g., men attracted to amputees who are also aroused by the fantasy of being amputees and wish to become amputees). The correlation between degree of each internalized sexual attraction and degree of its corresponding erotic target identity inversion was approximately 1.0 after correction for attenuation. In each sample, participants' specific internalized sexual attraction was positively correlated with autogynephilia, likely the most common internalized sexual attraction in men. Erotic Target Identity Inversion Theory can potentially explain a variety of otherwise puzzling phenomena, including transgender identity among female-attracted natal males and men seeking amputations of healthy limbs.

20.
Nat Microbiol ; 8(7): 1318-1329, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37308592

RESUMEN

Bacterial cell envelope polymers are often modified with acyl esters that modulate physiology, enhance pathogenesis and provide antibiotic resistance. Here, using the D-alanylation of lipoteichoic acid (Dlt) pathway as a paradigm, we have identified a widespread strategy for how acylation of cell envelope polymers occurs. In this strategy, a membrane-bound O-acyltransferase (MBOAT) protein transfers an acyl group from an intracellular thioester onto the tyrosine of an extracytoplasmic C-terminal hexapeptide motif. This motif shuttles the acyl group to a serine on a separate transferase that moves the cargo to its destination. In the Dlt pathway, here studied in Staphylococcus aureus and Streptococcus thermophilus, the C-terminal 'acyl shuttle' motif that forms the crucial pathway intermediate is found on a transmembrane microprotein that holds the MBOAT protein and the other transferase together in a complex. In other systems, found in both Gram-negative and Gram-positive bacteria as well as some archaea, the motif is fused to the MBOAT protein, which interacts directly with the other transferase. The conserved chemistry uncovered here is widely used for acylation throughout the prokaryotic world.


Asunto(s)
Proteínas Bacterianas , Polímeros , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Ácidos Teicoicos/metabolismo , Alanina/metabolismo , Bacterias/metabolismo , Transferasas , Micropéptidos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...