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1.
PeerJ ; 12: e17978, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39285925

RESUMEN

There is growing concern that some managed and wild insect pollinator populations are in decline, potentially threatening biodiversity and sustainable food production on a global scale. In recent years, there has been increasing evidence that sub-lethal exposure to neurotoxic, neonicotinoid pesticides can negatively affect pollinator immunocompetence and could amplify the effects of diseases, likely contributing to pollinator declines. However, a direct pathway connecting neonicotinoids and immune functions remains elusive. In this study we show that haemocytes and non-neural tissues of the honeybee Apis mellifera express the building blocks of the nicotinic acetylcholine receptors that are the target of neonicotinoids. In addition, we demonstrate that the haemocytes, which form the cellular arm of the innate immune system, actively express choline acetyltransferase, a key enzyme necessary to synthesize acetylcholine. In a last step, we show that the expression of this key enzyme is affected by field-realistic doses of clothianidin, a widely used neonicotinoid. These results support a potential mechanistic framework to explain the effects of sub-lethal doses of neonicotinoids on the immune function of pollinators.


Asunto(s)
Acetilcolina , Guanidinas , Hemocitos , Insecticidas , Neonicotinoides , Animales , Abejas/efectos de los fármacos , Abejas/inmunología , Insecticidas/toxicidad , Neonicotinoides/toxicidad , Acetilcolina/metabolismo , Hemocitos/efectos de los fármacos , Hemocitos/inmunología , Hemocitos/metabolismo , Guanidinas/toxicidad , Tiazoles , Receptores Nicotínicos/metabolismo , Receptores Nicotínicos/efectos de los fármacos , Colina O-Acetiltransferasa/metabolismo
2.
Cell Commun Signal ; 22(1): 450, 2024 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-39327600

RESUMEN

Mitochondrial activity directs neuronal differentiation dynamics during brain development. In this context, the long-established metabolic coupling of mitochondria and the eukaryotic host falls short of a satisfactory mechanistic explanation, hinting at an undisclosed facet of mitochondrial function. Here, we reveal an RNA-based inter-organellar communication mode that complements metabolic coupling of host-mitochondria and underpins neuronal differentiation. We show that within minutes of exposure to differentiation cues and activation of the electron transport chain, the mitochondrial outer membrane transiently fuses with the nuclear membrane of neural progenitors, leading to efflux of nuclear-encoded RNAs (neRNA) into the positively charged mitochondrial intermembrane space. Subsequent degradation of mitochondrial neRNAs by Polynucleotide phosphorylase 1 (PNPase) located in the intermembrane space curbs the transcriptomic memory of progenitor cells. Further, acquisition of neRNA by mitochondria leads to a collapse of proton motive force, suppression of ATP production, and a resultant amplification of autophagic flux that attenuates proteomic memory. Collectively, these events force the progenitor cells towards a "tipping point" characterised by emergence of a competing neuronal differentiation program. It appears that neuronal differentiation is a consequence of reprogrammed coupling of metabolomic and transcriptomic landscapes of progenitor cells, with mitochondria emerging as key "reprogrammers" that operate by acquiring and metabolising neRNAs. However, the documented role of mitochondria as "reprogrammers" of differentiation remains to be validated in other neuronal lineages and in vivo.


Asunto(s)
Diferenciación Celular , Mitocondrias , Neuronas , ARN Nuclear , Mitocondrias/metabolismo , Neuronas/metabolismo , Neuronas/citología , Animales , ARN Nuclear/metabolismo , ARN Nuclear/genética , Humanos , Ratones , Células-Madre Neurales/metabolismo , Células-Madre Neurales/citología , Neurogénesis/genética
3.
ACS Nano ; 18(33): 22369-22377, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39109416

RESUMEN

DNA-based Points Accumulation for Imaging in Nanoscale Topography (DNA-PAINT) is an effective super resolution microscopy technique, and its optimization is key to improve nanoscale detection. The state-of-the-art improvements that are at the base of this optimization have been first routinely validated on DNA nanostructure devices before being tested on biological samples. This allows researchers to finely tune DNA-PAINT imaging features in a more controllable in vitro environment. Dye-labeled oligonucleotide probes with short hybridization domains can expand DNA-PAINT's detection by targeting short nucleotide sequences and improving resolution, speed, and multiplexing. However, developing these probes is challenging as their brief bound state makes them difficult to capture under routine imaging conditions. To extend dwell binding times and promote duplex stability, we introduced structural and chemical modifications to our imager probes. The modifications included mini-hairpins and/or Bridged Nucleic Acids (BNA); both of which increase the thermomechanical stability of a DNA duplex. Using this approach we demonstrate DNA-PAINT imaging with approximately 5 nm resolution using a 4-nucleotide hybridization domain that is 43% shorter than previously reported probes. Imager probes with such short hybridization domains are key for improving detection on DNA nanostructure devices because they have the capability to target a larger number of binding domains per localization unit. This is essential for metrology applications such as Nucleic Acid Memory (NAM) where the information density is dependent on the binding site length. The selected imager probes reported here present imaging resolution equivalent to current state-of-the-art DNA-PAINT probes, creating a strategy to image shorter DNA domains for nanoscience and nanotechnology alike.


Asunto(s)
ADN , ADN/química , Sondas de ADN/química , Nanoestructuras/química , Hibridación de Ácido Nucleico
4.
PeerJ ; 12: e17781, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39076777

RESUMEN

The fitness effects of overt parasites, and host resistance to them, are well documented. Most symbionts, however, are more covert and their interactions with their hosts are less well understood. Wolbachia, an intracellular symbiont of insects, is particularly interesting because it is thought to be unaffected by the host immune response and to have fitness effects mostly focussed on sex ratio manipulation. Here, we use quantitative PCR to investigate whether host genotype affects Wolbachia infection density in the leaf-cutting ant Acromyrmex echinatior, and whether Wolbachia infection density may affect host morphology or caste determination. We found significant differences between host colonies in the density of Wolbachia infections, and also smaller intracolonial differences in infection density between host patrilines. However, the density of Wolbachia infections did not appear to affect the morphology of adult queens or likelihood of ants developing as queens. The results suggest that both host genotype and environment influence the host-Wolbachia relationship, but that Wolbachia infections carry little or no physiological effect on the development of larvae in this system.


Asunto(s)
Hormigas , Genotipo , Fenotipo , Simbiosis , Wolbachia , Animales , Wolbachia/fisiología , Wolbachia/genética , Simbiosis/genética , Hormigas/microbiología , Hormigas/genética , Femenino , Masculino
5.
Chem Sci ; 15(25): 9582-9590, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38939159

RESUMEN

Amines are centrally important motifs in medicinal chemistry and biochemistry, and indispensable intermediates and linchpins in organic synthesis. Despite their cross-disciplinary prominence, synthetic access to amine continues to rely on two-electron approaches based on reductions and additions of organometallic reagents, limiting their accessible chemical space and necessitating stepwise preassembly of synthetic precursors. We report herein a homogeneous photocatalytic tricomponent decarboxylative radical-mediated amine construction that enables modular access to α-branched secondary amines directly from the broad and structurally diverse chemical space of carboxylic acids in a tricomponent reaction with aldehydes and aromatic amines. Our studies reveal the key role of acridine photocatalysis acting in concert with copper and Brønsted acid catalytic processes in facilitating the previously inaccessible homogeneous photocatalytic reaction and provide a streamlined segue to a wide range of amines and nonproteinogenic α-amino acids.

6.
ACS Catal ; 14(9): 6973-6980, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38737399

RESUMEN

Development of photocatalytic systems that facilitate mechanistically divergent steps in complex catalytic manifolds by distinct activation modes can enable previously inaccessible synthetic transformations. However, multimodal photocatalytic systems remain understudied, impeding their implementation in catalytic methodology. We report herein a photocatalytic access to thiols that directly merges the structural diversity of carboxylic acids with the ready availability of elemental sulfur without substrate preactivation. The photocatalytic transformation provides a direct radical-mediated segue to one of the most biologically important and synthetically versatile organosulfur functionalities, whose synthetic accessibility remains largely dominated by two-electron-mediated processes based on toxic and uneconomical reagents and precursors. The two-phase radical process is facilitated by a multimodal catalytic reactivity of acridine photocatalysis that enables both the singlet excited state PCET-mediated decarboxylative carbon-sulfur bond formation and the previously unknown radical reductive disulfur bond cleavage by a photoinduced HAT process in the silane-triplet acridine system. The study points to a significant potential of multimodal photocatalytic systems in providing unexplored directions to previously inaccessible transformations.

7.
Chemistry ; 30(39): e202401407, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38699860

RESUMEN

Semiochemicals can be used to manipulate insect behaviour for sustainable pest management strategies, but their high volatility is a major issue for their practical implementation. Inclusion of these molecules within porous materials is a potential solution to this issue, as it can allow for a slower and more controlled release. In this work, we demonstrate that a series of Zr(IV) and Al(III) metal-organic frameworks (MOFs) with channel-type pores enable controlled release of three semiochemicals over 100 days by pore size design, with the uptake and rate of release highly dependent on the pore size. Insight from grand canonical Monte Carlo simulations indicates that this is due to weaker MOF-guest interactions per guest molecule as the pore size increases. These MOFs are all stable post-release and can be reloaded to show near-identical re-release profiles. These results provide valuable insight on the diffusion behaviour of volatile guests in MOFs, and for the further development of porous materials for sustainable agriculture applications.

8.
Heart Lung Circ ; 33(8): 1221-1226, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38719696

RESUMEN

BACKGROUND: Socio-economic status (SES) has a large impact on health through a complex interplay of upstream, midstream and downstream factors. However, little is known about the predictive role of SES on long-term major adverse cardiovascular, cerebrovascular events, and mortality (MACCE). AIM: To determine the long-term relationship between SES and MACCE for men and women. The secondary endpoint was to determine the relationship between SES and all-cause mortality. METHOD: A total of 3,034 participants (1,494 women and 1,540 men) were assessed at baseline in the Geelong Osteoporosis Study, a large regional Australian population cohort study. Area-based SES was assessed, utilising the Index of Relative Socio-Economic Disadvantage (IRSD) and grouped into quintiles. The primary endpoint, MACCE, was defined as a composite of myocardial infarction, heart failure hospitalisation, malignant arrhythmias, stroke, and all-cause mortality. The secondary endpoint was all-cause mortality. Baseline data including age, sex, smoking status and alcohol use, and comorbidities were collected between 1993-1997 for women, and 2001-2006 for men, with follow-up over 30 and 22 years, respectively. Logistic regression was utilised to assess MACCE and all-cause mortality outcomes across the SES quintiles. RESULTS: Participants lost to follow-up or with incomplete data collection were excluded leaving 2,173 participants eligible for analysis. SES was associated with MACCE outcomes. Compared with Quintile I (lowest SES stratum), the odds of MACCE for each IRSD stratum were: Quintile II, odds ratio (OR) 0.85 (95% confidence interval [CI] 0.65-1.13); Quintile III, OR 0.69 (95% CI 0.51-0.91); Quintile IV, OR 0.66 (95% CI 0.50-0.88); and, Quintile V, OR 0.55 (95% CI 0.41-0.72). In the adjusted model, an inverse trend was noted, with reducing MACCE outcomes with an increasing SES status; IRSD Quintile II, OR 0.85 (95% CI 0.62-1.17); Quintile III, OR 0.70 (95% CI 0.50-0.97); Quintile IV, OR 0.73 (95% CI 0.52-1.02); and, Quintile V, OR 0.54 (95% CI 0.39-0.74). SES was inversely associated with all-cause mortality; IRSD Quintile II (OR 0.87, 95% CI 0.66-1.16) failed to achieve significance however IRSD Quintile III (OR 0.65, 95% CI 0.48-0.88), Quintile IV (OR 0.59, 95% CI 0.44-0.80) and Quintile V (OR 0.46, 95% CI 0.34-0.62) had a lower risk of mortality compared with Quintile I. In the adjusted model, an inversely proportional trend was noted between SES and all-cause mortality; IRSD Quintile II (OR 0.82, 95% CI 0.59-1.15), IRSD Quintile III (OR 0.63, 95% CI 0.49-0.95), Quintile IV (OR 0.59, 95% CI 0.45-0.90) and Quintile V (OR 0.44, 95% CI 0.31-0.61) had fewer mortality events compared with IRSD Quintile I. CONCLUSIONS: Our research indicates that being part of a lower socio-economic stratum is linked to a higher likelihood of experiencing negative cardiovascular and cerebrovascular events, along with an increased risk of overall mortality. SES is an important risk stratification marker for long-term prognosis of cardiovascular diseases and stroke, and warrants further investigation.


Asunto(s)
Clase Social , Humanos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Estudios de Seguimiento , Australia/epidemiología , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/epidemiología , Trastornos Cerebrovasculares/mortalidad , Trastornos Cerebrovasculares/epidemiología , Factores de Riesgo , Factores de Tiempo
9.
Breastfeed Med ; 19(6): 425-434, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38651604

RESUMEN

Introduction: Human milk is the preferred source of enteral nutrition for very low birthweight (VLBW) infants, and it possibly decreases dependence on parenteral nutrition (PN) and reduces incidence of late-onset sepsis (LOS). No systematic review to date has specifically addressed the value of early versus late introduction of human milk diet (HMD) on duration of PN and incidence of LOS among VLBW infants. Objective: To review the evidence for an early versus late introduction of HMD on duration of PN and incidence of LOS in VLBW infants. Method: Preferred reporting items for systematic reviews and meta-analysis-guided search of EMBASE and PubMed/Medline databases was conducted for this systematic review using phrases addressing population, intervention, comparator, and outcome framework to identify articles published over the past two decades without language restrictions. Full-text articles (both observational and randomized) that studied an early versus late initiation of HMD were included. Mean difference (MD) and relative risk (RR) with 95% confidence intervals (CIs) were calculated for PN and LOS. Quality of evidence was analyzed using UK National Service Framework and the risk-of-bias was assessed using Robvis®. Results: One randomized controlled trial (RCT) and two observational studies (two English and one Chinese) recruited 474 VLBW infants (455 analyzed). Among an intrauterine growth-restricted cohort enrolled in the RCT (n = 72), early HMD resulted in statistically significant reduction in PN dependence. However, no statistically significant difference was found in LOS. Two observational studies found similar reductions in PN duration and LOS incidence among the early HMD cohort. One observational study reported significant PN reduction; however, the incidence of LOS did not reach statistical significance in either case. Conclusion: An early HMD may reduce the duration of PN for a growth-restricted VLBW cohort. Observational studies suggesting reduced PN and LOS from early HMD endorse the need for bioactivity-focused human milk research. Variations in feeding guidelines among VLBW infants have the potential to influence neonatal outcomes significantly.


Asunto(s)
Recién Nacido de muy Bajo Peso , Leche Humana , Nutrición Parenteral , Humanos , Recién Nacido , Incidencia , Sepsis/epidemiología , Sepsis/prevención & control , Fenómenos Fisiológicos Nutricionales del Lactante , Factores de Tiempo , Recien Nacido Prematuro , Lactancia Materna/estadística & datos numéricos
10.
Chem Sci ; 15(14): 5277-5283, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38577370

RESUMEN

Chemodivergent construction of structurally distinct heterocycles from the same precursors by adjusting specific reaction parameters is an emergent area of organic synthesis; yet, understanding of the processes that underpin the reaction divergence is lacking, preventing the development of new synthetic methods by systematically harnessing key mechanistic effects. We describe herein cesium carbonate-promoted oxadiaza excision cross-coupling reactions of ß-ketoesters with 1,2,3-triazine 1-oxides that form pyridones in good to high yields, instead of the sole formation of pyridines when the same reaction is performed in the presence of other alkali metal carbonates or organic bases. The reaction can be further extended to the construction of synthetically challenging pyridylpyridones. A computational study comparing the effect of cesium and sodium ions in the oxadiaza excision cross-coupling reactions reveals that the cesium-coordinated species changes the reaction preference from attack at the ketone carbonyl to attack at the ester carbon due to metal ion-specific transition state conformational accommodation, revealing a previously unexplored role of cesium ions that may facilitate the development of chemodivergent approaches to other heterocyclic systems.

11.
Nephrology (Carlton) ; 29(8): 537-540, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38599614

RESUMEN

This report details the case of a 51-year-old man with a Tiger snake bite who developed systemic envenomation, coagulopathy and thrombotic microangiopathy (TMA) requiring renal replacement therapy. He received plasma exchange as additional therapy while awaiting confirmation of the cause of the TMA. We discuss clinical decision making in detection of systemic envenomation and management of the rare complication of TMA, as well as current Australian guidelines around antivenom administration. This is the fourth known documented case of TMA from a Tiger snake bite in Australia.


Asunto(s)
Elapidae , Mordeduras de Serpientes , Microangiopatías Trombóticas , Microangiopatías Trombóticas/etiología , Microangiopatías Trombóticas/terapia , Coagulación Intravascular Diseminada/etiología , Coagulación Intravascular Diseminada/terapia , Mordeduras de Serpientes/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Terapia de Reemplazo Renal , Intercambio Plasmático , Australia , Antivenenos/uso terapéutico , Resultado del Tratamiento , Anticoagulantes/uso terapéutico , Heparina/uso terapéutico
12.
J Strength Cond Res ; 38(6): 1072-1081, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38489587

RESUMEN

ABSTRACT: Hughes, W, Healy, R, Lyons, M, Higginbotham, C, Lane, A, and Beattie, K. The strength characteristics of elite and subelite female Gaelic football players. J Strength Cond Res 38(6): 1072-1081, 2024-There is currently an underrepresentation of sports science research focused on the female athlete, specifically in the context of Gaelic football. The aims of this study are to (a) compare the strength characteristics of elite and subelite players and (b) establish normative-based values and percentile scores for the strength characteristics of female Gaelic football players. Ninety-two female Gaelic football players were recruited for this study and subsequently categorized as elite (intercounty n = 30, age; 25.1 ± 5.3 years, stature; 1.69 ± 0.06 m, mass; 69.5 ± 5.9 kg) or subelite (club n = 62, age; 25.4 ± 6.8 years, stature; 1.66 ± 0.06 m, mass; 65.1 ± 8.9 kg). The physical strength characteristics of the subjects were assessed through the isometric midthigh pull (IMTP), countermovement jump (CMJ), and 10-5 repeated jump test. Statistically significant differences were found in the physical strength characteristics between the groups with elite players demonstrating greater peak force (large effect), relative peak force (moderate effect), and reactive strength index (large effect). Statistically significant differences were also observed for key CMJ phase characteristics with elite players producing greater RSI mod (moderate effect), jump height (large effect), and propulsion peak power (large effect) than subelite players. This study demonstrated that there are moderate to large differences between playing standards with elite players displaying superior reactive-, explosive-, and maximal-strength than their subelite counterparts. The strength characteristics evaluated in this study may be used in conjunction with other performance indices to distinguish between elite and subelite playing standards in female Gaelic football players.


Asunto(s)
Fuerza Muscular , Humanos , Femenino , Fuerza Muscular/fisiología , Adulto Joven , Adulto , Rendimiento Atlético/fisiología , Atletas , Prueba de Esfuerzo , Músculo Esquelético/fisiología
13.
Nanotechnology ; 35(27)2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38373400

RESUMEN

DNA Nanotechnology is being applied to multiple research fields. The functionality of DNA nanostructures is significantly enhanced by decorating them with nanoscale moieties including: proteins, metallic nanoparticles, quantum dots, and chromophores. Decoration is a complex process and developing protocols for reliable attachment routinely requires extensive trial and error. Additionally, the granular nature of scientific communication makes it difficult to discern general principles in DNA nanostructure decoration. This tutorial is a guidebook designed to minimize experimental bottlenecks and avoid dead-ends for those wishing to decorate DNA nanostructures. We supplement the reference material on available technical tools and procedures with a conceptual framework required to make efficient and effective decisions in the lab. Together these resources should aid both the novice and the expert to develop and execute a rapid, reliable decoration protocols.


Asunto(s)
ADN , Nanoestructuras , Nanotecnología , ADN/química , Nanoestructuras/química , Nanotecnología/métodos , Puntos Cuánticos/química , Nanopartículas del Metal/química
14.
PeerJ ; 12: e16713, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38313023

RESUMEN

Fungi can have important beneficial and detrimental effects on animals, yet our understanding of the diversity and function of most bee-associated fungi is poor. Over 2 million bumblebee colonies are traded globally every year, but the presence and transport of viable fungi within them is unknown. Here, we explored whether any culturable fungi could be isolated from commercial bumblebee nests. We collected samples of various substrates from within 14 bumblebee colonies, including the honey, honey cup wall, egg cup wall, and frass then placed them on agar and recorded any growth. Fungal morphotypes were then subcultured and their ITS region sequenced for identification. Overall, we cultured 11 fungal species from the various nest substrates. These included both pathogenic and non-pathogenic fungi, such as Aspergillus sp., Penicillium sp., and Candida sp. Our results provide the first insights into the diversity of viable fungal communities in commercial bumblebee nests. Further research is needed to determine if these fungi are unique to commercial colonies or prevalent in wild bumblebee nests, and crucially to determine the ecological and evolutionary implications of these fungi in host colonies.


Asunto(s)
Aspergillus , Penicillium , Abejas , Animales , Agar
15.
J Trauma Acute Care Surg ; 96(1): 85-93, 2024 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-38098145

RESUMEN

BACKGROUND: Traumatic insults, infection, and surgical procedures can leave skin defects that are not amenable to primary closure. Split-thickness skin grafting (STSG) is frequently used to achieve closure of these wounds. Although effective, STSG can be associated with donor site morbidity, compounding the burden of illness in patients undergoing soft tissue reconstruction procedures. With an expansion ratio of 1:80, autologous skin cell suspension (ASCS) has been demonstrated to significantly decrease donor skin requirements compared with traditional STSG in burn injuries. We hypothesized that the clinical performance of ASCS would be similar for soft tissue reconstruction of nonburn wounds. METHODS: A multicenter, within-patient, evaluator-blinded, randomized-controlled trial was conducted of 65 patients with acute, nonthermal, full-thickness skin defects requiring autografting. For each patient, two treatment areas were randomly assigned to concurrently receive a predefined standard-of-care meshed STSG (control) or ASCS + more widely meshed STSG (ASCS+STSG). Coprimary endpoints were noninferiority of ASCS+STSG for complete treatment area closure by Week 8, and superiority for relative reduction in donor skin area. RESULTS: At 8 weeks, complete closure was observed for 58% of control areas compared with 65% of ASCS+STSG areas (p = 0.005), establishing noninferiority of ASCS+STSG. On average, 27.4% less donor skin was required with ASCS+ STSG, establishing superiority over control (p < 0.001). Clinical healing (≥95% reepithelialization) was achieved in 87% and 85% of Control and ASCS+STSG areas, respectively, at 8 weeks. The treatment approaches had similar long-term scarring outcomes and safety profiles, with no unanticipated events and no serious ASCS device-related events. CONCLUSION: ASCS+STSG represents a clinically effective and safe solution to reduce the amount of skin required to achieve definitive closure of full-thickness defects without compromising healing, scarring, or safety outcomes. This can lead to reduced donor site morbidity and potentially decreased cost associated with patient care.Clincaltrials.gov identifier: NCT04091672. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level I.


Asunto(s)
Quemaduras , Cicatriz , Humanos , Trasplante Autólogo/métodos , Autoinjertos/cirugía , Piel/patología , Cicatrización de Heridas , Trasplante de Piel/métodos , Quemaduras/cirugía , Quemaduras/patología
16.
Chem Sci ; 14(46): 13384-13391, 2023 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-38033883

RESUMEN

Sulfinamides are some of the most centrally important four-valent sulfur compounds that serve as critical entry points to an array of emergent medicinal functional groups, molecular tools for bioconjugation, and synthetic intermediates including sulfoximines, sulfonimidamides, and sulfonimidoyl halides, as well as a wide range of other S(iv) and S(vi) functionalities. Yet, the accessible chemical space of sulfinamides remains limited, and the approaches to sulfinamides are largely confined to two-electron nucleophilic substitution reactions. We report herein a direct radical-mediated decarboxylative sulfinamidation that for the first time enables access to sulfinamides from the broad and structurally diverse chemical space of carboxylic acids. Our studies show that the formation of sulfinamides prevails despite the inherent thermodynamic preference for the radical addition to the nitrogen atom, while a machine learning-derived model facilitates prediction of the reaction efficiency based on computationally generated descriptors of the underlying radical reactivity.

17.
Mol Ecol ; 32(21): 5709-5723, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37789741

RESUMEN

Insect pollination is fundamental for natural ecosystems and agricultural crops. The bumblebee species Bombus terrestris has become a popular choice for commercial crop pollination worldwide due to its effectiveness and ease of mass rearing. Bumblebee colonies are mass produced for the pollination of more than 20 crops and imported into over 50 countries including countries outside their native ranges, and the risk of invasion by commercial non-native bumblebees is considered an emerging issue for global conservation and biological diversity. Here, we use genome-wide data from seven wild populations close to and far from farms using commercial colonies, as well as commercial populations, to investigate the implications of utilizing commercial bumblebee subspecies in the UK. We find evidence for generally low levels of introgression between commercial and wild bees, with higher admixture proportions in the bees occurring close to farms. We identify genomic regions putatively involved in local and global adaptation, and genes in locally adaptive regions were found to be enriched for functions related to taste receptor activity, oxidoreductase activity, fatty acid and lipid biosynthetic processes. Despite more than 30 years of bumblebee colony importation into the UK, we observe low impact on the genetic integrity of local B. terrestris populations, but we highlight that even limited introgression might negatively affect locally adapted populations.


Asunto(s)
Ecosistema , Insectos , Abejas/genética , Animales , Polinización/genética , Biodiversidad
18.
Commun Chem ; 6(1): 226, 2023 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-37853171

RESUMEN

Networks of interacting DNA oligomers are useful for applications such as biomarker detection, targeted drug delivery, information storage, and photonic information processing. However, differences in the chemical kinetics of hybridization reactions, referred to as kinetic dispersion, can be problematic for some applications. Here, it is found that limiting unnecessary stretches of Watson-Crick base pairing, referred to as unnecessary duplexes, can yield exceptionally low kinetic dispersions. Hybridization kinetics can be affected by unnecessary intra-oligomer duplexes containing only 2 base-pairs, and such duplexes explain up to 94% of previously reported kinetic dispersion. As a general design rule, it is recommended that unnecessary intra-oligomer duplexes larger than 2 base-pairs and unnecessary inter-oligomer duplexes larger than 7 base-pairs be avoided. Unnecessary duplexes typically scale exponentially with network size, and nearly all networks contain unnecessary duplexes substantial enough to affect hybridization kinetics. A new method for generating networks which utilizes in-silico optimization to mitigate unnecessary duplexes is proposed and demonstrated to reduce in-vitro kinetic dispersions as much as 96%. The limitations of the new design rule and generation method are evaluated in-silico by creating new oligomers for several designs, including three previously programmed reactions and one previously engineered structure.

19.
Opt Express ; 31(20): 32619-32636, 2023 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-37859061

RESUMEN

We present a study on the optical losses of Fabry-Pérot cavities subject to realistic transverse mirror misalignment. We consider mirrors of the two most prevalent surface forms: idealised spherical depressions, and Gaussian profiles generated by laser ablation. We first describe the mode mixing phenomena seen in the spherical mirror case and compare to the frequently-used clipping model, observing close agreement in the predicted diffraction loss, but with the addition of protective mode mixing at transverse degeneracies. We then discuss the Gaussian mirror case, detailing how the varying surface curvature across the mirror leads to complex variations in round trip loss and mode profile. In light of the severe mode distortion and strongly elevated loss predicted for many cavity lengths and transverse alignments when using Gaussian mirrors, we suggest that the consequences of mirror surface profile are carefully considered when designing cavity experiments.

20.
BMC Bioinformatics ; 24(1): 160, 2023 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-37085766

RESUMEN

Deoxyribonucleic acid (DNA) is emerging as an alternative archival memory technology. Recent advancements in DNA synthesis and sequencing have both increased the capacity and decreased the cost of storing information in de novo synthesized DNA pools. In this survey, we review methods for translating digital data to and/or from DNA molecules. An emphasis is placed on methods which have been validated by storing and retrieving real-world data via in-vitro experiments.


Asunto(s)
ADN , ADN/genética , Análisis de Secuencia de ADN/métodos
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