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1.
Plant J ; 113(4): 851-865, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36597651

RESUMO

Auxin Response Factor 8 plays a key role in late stamen development: its splice variants ARF8.4 and ARF8.2 control stamen elongation and anther dehiscence. Here, we characterized the role of ARF8 isoforms in pollen fertility. By phenotypic and ultrastructural analysis of arf8-7 mutant stamens, we found defects in pollen germination and viability caused by alterations in exine structure and pollen coat deposition. Furthermore, tapetum degeneration, a prerequisite for proper pollen wall formation, is delayed in arf8-7 anthers. In agreement, the genes encoding the transcription factors TDF1, AMS, MS188 and MS1, required for exine and pollen coat formation, and tapetum development, are downregulated in arf8-7 stamens. Consistently, the sporopollenin content is decreased, and the expression of sporopollenin synthesis/transport and pollen coat protein biosynthetic genes, regulated by AMS and MS188, is reduced. Inducible expression of the full-length isoform ARF8.1 in arf8-7 inflorescences complements the pollen (and tapetum) phenotype and restores the expression of the above transcription factors. Chromatin immunoprecipitation-quantitative polymerase chain reaction assay revealed that ARF8.1 directly targets the promoters of TDF1, AMS and MS188. In conclusion, the ARF8.1 isoform controls pollen and tapetum development acting directly on the expression of TDF1, AMS and MS188, which belong to the pollen/tapetum genetic pathway.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Parede Celular/metabolismo , Fator VIII/genética , Fator VIII/metabolismo , Flores/genética , Regulação da Expressão Gênica de Plantas , Ácidos Indolacéticos/metabolismo , Pólen , Isoformas de Proteínas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
2.
Environ Sci Technol ; 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38332486

RESUMO

Plastic debris, including nanoplastic particles (NPPs), has emerged as an important global environmental issue due to its detrimental effects on human health, ecosystems, and climate. Atmospheric processes play an important role in the transportation and fate of plastic particles in the environment. In this study, a high-resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS) was employed to establish the first online approach for identification and quantification of airborne submicrometer polystyrene (PS) NPPs from laboratory-generated and ambient aerosols. The fragmentation ion C8H8+ is identified as the major tracer ion for PS nanoplastic particles, achieving an 1-h detection limit of 4.96 ng/m3. Ambient PS NPPs measured at an urban location in Texas are quantified to be 30 ± 20 ng/m3 by applying the AMS data with a constrained positive matrix factorization (PMF) method using the multilinear engine (ME-2). Careful analysis of ambient data reveals that atmospheric PS NPPs were enhanced as air mass passed through a waste incinerator plant, suggesting that incineration of waste may serve as a source of ambient NPPs. The online quantification of NPPs achieved through this study can significantly improve our understanding of the source, transport, fate, and climate effects of atmospheric NPPs to mitigate this emerging global environmental issue.

3.
Philos Trans A Math Phys Eng Sci ; 382(2273): 20230197, 2024 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-38736334

RESUMO

The origin of micrometeorites (MMs) from asteroids and comets is well-established, but the relative contribution from these two classes remains poorly resolved. Likewise, determining the precise origin of individual MMs is an open challenge. Here, cosmic-ray exposure ages are used to resolve the spatial origins of 12 MMs collected from urban areas and Antarctica. Their 26Al and 10Be concentration, produced during cosmic-ray irradiation in space, were measured by accelerator mass spectrometry. These data are compared to results from a model simulating the transport and irradiation of the MM precursors in space. This model, for the first time, considers a variety of orbits, precursor particle sizes, compositions and densities and incorporates non-isotropic solar and galactic cosmic-ray flux profiles, depth-dependent production rates, as well as spherical evaporation during atmospheric entry. While the origin for six MMs remains ambiguous, two MMs show a preferential tendency towards an origin in the Inner Solar System (Near Earth Objects to the Asteroid Belt) and four towards an origin in the Outer Solar System (Jupiter Family Comets to the Kuiper Belt). These findings challenge the notion that dust originating from the Outer Solar System is unlikely to survive long-term transport and delivery to the terrestrial planets. This article is part of the theme issue 'Dust in the Solar System and beyond'.

4.
Xenobiotica ; 54(8): 521-532, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39329287

RESUMO

Antibody-drug conjugates (ADCs) are a class of biopharmaceuticals that combine the specificity of monoclonal antibodies (mAbs) with the cytotoxicity of small molecule drugs. 15 ADCs have been approved by regulatory authorities up to now, mainly for indications in oncology, however, this review paper will only focus on the 13 ADCs that have been approved by either the FDA or EMA.ADME (Absorption, Distribution, Metabolism, and Excretion) studies are essential for the development of small molecule drugs to evaluate their disposition properties. These studies help to select drug candidates, determine the optimal dosing regimen and help to identify potential safety concerns for the drug of interest in human. Tissue distribution studies are also important as they facilitate the understanding of the efficacy and safety for parent drug and its metabolites in preclinical and clinical studies.For biologics, ADME studies are usually not required. In this paper, we review the existing approval packages and literature for approved ADCs to determine the extent of ADME studies performed as part of ADC registration packages.We conclude that ADME studies are recommended for the development of ADCs if new linkers and payloads are used that have never been used in humans before as these studies provide valuable information on the pharmacokinetic properties, optimal dosing regimen, and potential safety concerns. However, for the development of ADCs with established linker payload combinations, radiolabelled ADME studies may not be necessary if the distribution, metabolism and excretion properties have been described before. Clinical radiolabelled ADME studies are not recommended where patients are treated for life threating diseases like for indications in oncology.


Assuntos
Imunoconjugados , Imunoconjugados/farmacocinética , Humanos , Distribuição Tecidual , Anticorpos Monoclonais/farmacocinética
5.
Xenobiotica ; 54(5): 257-262, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38178690

RESUMO

1. Challenges, strategies and new technologies in the field of biotransformation were presented and discussed at the fourth European Biotransformation Workshop which was held in collaboration with the joint ISSX/DMDG meeting on June 15, 2023 at the University of Hertfordshire in Hatfield, UK.2. In this meeting report we summarise the presentations and discussions from this workshop.3. The topics covered are listed below: Unusual biotransformation reactionsBiotransformation Workflows in Discovery utilising various softwares for structure elucidationBiotransformation software for the identification of peptide metabolitesAccelerator Mass Spectrometry (AMS) for endogenous and xenobiotic metabolite profilingMetabolite profiling using quantitative Nuclear magnetic resonance (NMR) and liquid chromatography coupled to inductively coupled plasma-mass spectrometry (LC-ICP-MS).


Assuntos
Biotransformação , Xenobióticos , Humanos , Cromatografia Líquida , Europa (Continente) , Espectrometria de Massas , Metabolômica , Xenobióticos/metabolismo
6.
Xenobiotica ; 54(9): 770-775, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39225512

RESUMO

Challenges, strategies and new technologies in the field of biotransformation were presented and discussed at the 5th European Biotransformation Workshop, which was held on March 14, 2024 on the Novartis Campus in Basel, Switzerland.In this meeting report we summarise the presentations and discussions from this workshop.The topics covered are listed below:Advances in understanding drug induced liver injury (DILI) risks of carboxylic acids and targeted covalent inhibitors.Biotransformation of oligonucleotide-based therapeutics including automated software tools for metabolite identification.Recent advances in metabolite synthesisQualification and validation of a new compact Low Energy Accelerator Mass Spectrometry (LEA) system for metabolite profiling.


Assuntos
Biotransformação , Humanos , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Espectrometria de Massas
7.
J Dairy Sci ; 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-39004130

RESUMO

Antimicrobial use (AMU) data are essential for monitoring usage over time, facilitating reduction strategies to combat the threat of antimicrobial resistance (AMR) to both human and animal health. The objective of this study was to measure and describe AMU over a 12-mo period in Irish dairy herds and compare 3 different recording methods to a reference method. A sample of 33 Irish dairy herds were randomly selected from 6 private veterinary practices across Ireland. The herds were followed for a 12-mo period and their AMU was monitored using 3 recording methods: 1. Veterinary prescription data (VET), 2. The inventory of medicine bins on the farms (BIN), and 3. Farmer treatment records from herd recording software (APP). Each recording method was compared with a previously developed reference method for AMU. The reference method used was based on pre- and poststudy medicine stock on the farms combined with veterinary prescription data. Antimicrobial use was analyzed using both mass- and dosed-based metrics, including mass (mg) of antimicrobial active ingredient per population correction unit (mg/PCU), defined daily doses for animals (DDDVET) and defined course doses for animals (DCDVET). Median AMU was 16.24, 10.47, 8.87 and 15.55 mg/PCU by mass, and 2.43, 1.55, 1.19 and 2.26 DDDVET by dose for VET, BIN, APP, and reference method data, respectively. Reliability of the agreement between each pair of methods was quantified using the concordance correlation coefficient (CCC). When compared with the reference method, VET data had excellent reliability [95% confidence interval (CI) of CCC: 0.992-0.998]. The BIN data had good to excellent reliability [95% CI of CCC: 0.776-0.936]. The APP data had poor reliability when compared with the reference method [95% CI of CCC: -0.167-0.156]. Our results highlight that a small number of herds were contributing most to overall use and farmers showed varying levels of consistency in recording AMU. Veterinary data were the most reliable approach for assessing AMU when compared with a reference method of AMU. This is an important finding for the future monitoring of AMU at a national level.

8.
J Formos Med Assoc ; 123(11): 1161-1166, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38331638

RESUMO

Acute mountain sickness (AMS) is initiated in response to a hypoxic and hypobaric environment at a high altitude. The precise prevalence of AMS in Jade Mountain climbers remained largely unknown, particularly data obtained from real medical consultations. An overnight stay at the Pai-Yun Lodge (3402 m) is usually required before an ascent of the Jade Mountain. Since 2004, a Pai-Yun Clinic has been established in the Pai-Yun Lodge. The Pai-Yun Clinic provided regular and emergency medical service every weekend. We conducted a retrospective study by using medical records from the Pai-Yun Clinic between 2018 and 2019. A total of 1021 patients were enrolled, with 56.2 % males. Different age groups were 3.2 %, 54.5 %, 37.9 %, and 4.4 % in <20, 20-39, 40-59, and ≥60 years, respectively. There were 582 (57.0 %) patients diagnosed to have AMS (230 [39.5 %] were mild type and 352 [60.5 %] were severe type). The factors associated with AMS development included young age, absence of climbing history (>3000 m) within the last 3 months, first climbing (>3000 m) experience, taking preventive medication, low oxygen saturation, and a high Lake Louise AMS score (LLAMSS). The factors associated with AMS severity included absence of taking preventive medication, low oxygen saturation, and a high LLAMSS. Approximately 15 % of Jade Mountain climbers needed medical service, of which 60 % had AMS. 60 % of patients with AMS must require oxygen supply or medication prescription. Oxygen saturation measure and LLAMSS evaluation are reasonable tools to predict the occurrence and severity of AMS on Jade Mountain.


Assuntos
Doença da Altitude , Montanhismo , Humanos , Doença da Altitude/epidemiologia , Estudos Retrospectivos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Taiwan/epidemiologia , Doença Aguda , Idoso , Índice de Gravidade de Doença , Prevalência , Modelos Logísticos , Fatores de Risco
9.
Int J Mol Sci ; 25(20)2024 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-39457093

RESUMO

A high-altitude, low-pressure hypoxic environment has severe effects on the health and work efficiency of its residents, and inadequate preventive measures and adaptive training may lead to the occurrence of AMS. Acute exposure to hypoxia conditions can have a less-favorable physiological effect on the human immune system. However, the regulation of the immune system in high-altitude environments is extremely complex and remains elusive. This study integrated system bioinformatics methods to screen for changes in immune cell subtypes and their associated targets. It also sought potential therapeutically effective natural compound candidates. The present study observed that monocytes, M1 macrophages and NK cells play a crucial role in the inflammatory response in AMS. IL15RA, CD5, TNFSF13B, IL21R, JAK2 and CXCR3 were identified as hub genes, and JAK2 was positively correlated with monocytes; TNFSF13B was positively correlated with NK cells. The natural compound monomers of jasminoidin and isoliquiritigenin exhibited good binding affinity with JAK2, while dicumarol and artemotil exhibited good binding affinity with TNFSF13B, and all are expected to become a potential therapeutic agents.


Assuntos
Doença da Altitude , Biomarcadores , Simulação de Acoplamento Molecular , Humanos , Doença da Altitude/genética , Doença da Altitude/tratamento farmacológico , Doença da Altitude/sangue , Perfilação da Expressão Gênica/métodos , Transcriptoma , Janus Quinase 2/genética , Janus Quinase 2/metabolismo , Monócitos/metabolismo , Monócitos/efeitos dos fármacos , Inflamação/sangue , Inflamação/genética
10.
Biol Sport ; 41(1): 3-15, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38188113

RESUMO

A rapidly emerging area of interest in high-pressure environments is that of pupillometry, where handheld quantitative infrared pupillometers (HQIPs) are able to track psycho-physiological fatigue in a fast, objective, valid, reliable, and non-invasive manner. However, the application of HQIPs in the context of athlete monitoring is yet to be determined. Therefore, the main aim of this pilot study was to examine the potential usefulness of a HQIP to monitor game-induced fatigue inside a professional female basketball setting by determining its (1) test-retest repeatability, (2) relationship with other biomarkers of game-induced fatigue, and (3) time-course from rested to fatigued states. A non-ophthalmologic practitioner performed a standardized Pupil Light Reflex (PLR) test using a medically graded HQIP among 9 professional female basketball players (2020-2021 Euro Cup) at baseline, 24-h pre-game (GD-1), 24-h post-game (GD+1) and 48-h post-game (GD+2). This was repeated over four subsequent games, equalling a total of 351 observations per eye. Two out of seven pupillometrics displayed good ICCs (0.95-0.99) (MinD and MaxD). Strong significant relationships were found between MaxD, MinD, and all registered biomarkers of game-induced fatigue (r = 0.69-0.82, p < 0.05), as well as between CV, MCV, and cognitive, lower-extremity muscle, and physiological fatigue markers (r = 0.74-0.76, p < 0.05). Three pupillometrics were able to detect a significant difference between rested and fatigued states. In particular, PC (right) (F = 5.173, η2 = 0.115 p = 0.028) and MCV (right) (F = 3.976, η2 = 0.090 p = 0.049) significantly decreased from baseline to GD+2, and LAT (left) (F = 4.023, η2 = 0.109 p = 0.009) significantly increased from GD-1 to GD+2. HQIPs have opened a new window of opportunity for monitoring game-induced fatigue in professional female basketball players. However, future research initiatives across larger and heterogenous samples, and longer investigation periods, are required to expand upon these preliminary findings.

11.
World J Urol ; 41(6): 1691-1696, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37055589

RESUMO

PURPOSE: Patients with artificial urinary eventually need surgical revision. Unfortunately, in women, this requires another invasive abdominal intervention. Robotic-assisted revision may provide a less invasive and more acceptable approach for sphincter revision in women. We wanted to determinate the continence status after robotic-assisted artificial urinary sphincter revision among women with stress incontinence. We also examined postoperative complications and the safety of the procedure. METHODS: The chart of the 31 women with stress urinary incontinence who underwent robotic-assisted AUS revision at our referral center from January 2015 to January 2022 were reviewed retrospectively. All patients underwent a robotic-assisted artificial urinary sphincter revision by one of our two expert surgeons. The primary outcome was to determinate the continence rate after revision and the secondary outcome aimed to evaluate the safety and feasibility of the procedure. RESULTS: Mean patients age was 65 years old, and the mean time between the sphincter revision and previous implantation was 98 months. After a mean follow-up of 35 months, 75% of the patients were fully continent (0-pad). Moreover, 71% of the women were back to the same continence status as with the previously functional sphincter, while 14% even have an improved continence status. Clavien-Dindo grade [Formula: see text] 3 and overall complications occurred in 9% and 20.5% of our patients, respectively. This study is mainly limited by its retrospective design. CONCLUSION: Robotic-assisted AUS revision carries satisfying outcome in terms of continence and safety.


Assuntos
Procedimentos Cirúrgicos Robóticos , Incontinência Urinária por Estresse , Esfíncter Urinário Artificial , Humanos , Feminino , Pré-Escolar , Esfíncter Urinário Artificial/efeitos adversos , Estudos Retrospectivos , Implantação de Prótese/métodos , Incontinência Urinária por Estresse/etiologia , Resultado do Tratamento
12.
Xenobiotica ; 53(2): 123-127, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36692101

RESUMO

Challenges, strategies and new technologies in the field of biotransformation were presented and discussed at the 3rd European Biotransformation Workshop which was held in collaboration with the DMDG on 5-6 October 2022 in Amsterdam. In this meeting report we summarise the presentations and discussions from this workshop. The topics covered are listed below:Accelerator mass spectrometry (AMS) for the support of microtracer studiesBiotransformation of the novel myeloperoxidase inhibitor AZD4831 in preclinical species and humansAMS in biotransformation studies: unusual case studiesDiscussion on new FDA draft guidance and AMSMultimodal molecular imaging and ion mobility applications in drug discovery and developmentMetabolites in Safety Testing considerations for large molecules.


Assuntos
Descoberta de Drogas , Humanos , Espectrometria de Massas/métodos , Biotransformação
13.
J Dairy Sci ; 106(12): 8835-8846, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37641339

RESUMO

Cow-calf contact (CCC) systems, although beneficial in many respects, introduce additional challenges to collect reliable data on milk production, which is important to assess individual cow efficiency and dairy farm profitability. Apart from weighing calves before and after each feeding, the amount of saleable milk lost due to calf suckling is practically impossible to measure. Here, we assess 2 indirect methods for estimating loss of saleable milk when housing cows and calves together in a robotic milking unit. In our study, treatment (CCC) cows and calves were kept together full time until the calves were 127 ± 6.6 d old (mean ± SD). Control cows were separated from their calves within 12 h of birth and then kept in the same unit as the treatment cows but with no access to either their own or treatment calves. Milk yield recording of both groups was performed from calving until pasture release at 233 ± 20 d in milk. The first estimation method relied on observed postseparation milk yield data, which were fed into a modified Wilmink regression model to determine the best-fitting lactation curve for the preseparation period. The second method was based on the cows' daily energy intake postseparation, calculated by measuring the daily feed intake and analyzing the energy content of the ration. The calculated energy intake was used to determine the average ratio between energy intake and the observed milk yield the following day for each individual cow, assuming constant rates of mobilization and deposition of body fat. The obtained ratio was then used to calculate the expected daily milk yield based on daily energy intake data during the preseparation period. In this paper, we analyzed data from 17 CCC cows kept together with their calves and 16 control cows; both groups calved from September to October 2020 and were followed up until release to pasture in May 2021. Saleable milk yield was lower in CCC cows than in control cows, both before and after separation. The 2 methods were used on data for control cows and showed milk yield loss using the lactation curve method (average of -3.4 ± 2.8 kg/d) and almost no loss using energy intake data (average of -1.4 ± 2.7 kg/d). Milk yield loss for CCC cows was estimated at average 11.3 ± 4.8 and 7.3 ± 6.6 kg milk/d, respectively. The proposed lactation curve estimation method tends to overestimate milk yield loss, whereas the method based on energy intake is more accurate. However, collecting detailed energy intake data per individual cow requires additional effort and equipment, which is not always feasible on commercial farms. Further research is needed to improve milk loss estimation and to better understand trade-offs in CCC systems.


Assuntos
Lactação , Leite , Feminino , Bovinos , Animais , Leite/metabolismo , Ingestão de Energia , Ingestão de Alimentos , Fazendas , Indústria de Laticínios/métodos
14.
Sensors (Basel) ; 23(10)2023 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-37430520

RESUMO

The magnetic spectrometer AMS-100, which includes a superconducting coil, is designed to measure cosmic rays and detect cosmic antimatter in space. This extreme environment requires a suitable sensing solution to monitor critical changes in the structure such as the beginning of a quench in the superconducting coil. Rayleigh-scattering-based distributed optical fibre sensors (DOFS) fulfil the high requirements for these extreme conditions but require precise calibration of the temperature and strain coefficients of the optical fibre. Therefore, the fibre-dependent strain and temperature coefficients KT and Kϵ for the temperature range from 77 K to 353 K were investigated in this study. The fibre was integrated into an aluminium tensile test sample with well-calibrated strain gauges to determine the fibre's Kϵ independently of its Young's modulus. Simulations were used to validate that the strain caused by changes in temperature or mechanical conditions was the same in the optical fibre as in the aluminium test sample. The results indicated a linear temperature dependence of Kϵ and a non-linear temperature dependence of KT. With the parameters presented in this work, it was possible to accurately determine the strain or temperature of an aluminium structure over the entire temperature range from 77 K to 353 K using the DOFS.

15.
Int J Mol Sci ; 24(14)2023 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-37511091

RESUMO

Yaks are often subject to long-term starvation and a high prevalence of respiratory diseases and mortality in the withered season, yet the mechanisms that cause this remain unclear. Research has demonstrated that ß-hydroxybutyrate (BHB) plays a significant role in regulating the immune system. Hence, we hypothesize that the low glucose and high BHB condition induced by severe starvation might have an effect on the pro-inflammatory response of the alveolar macrophages (AMs) in yaks. To validate our hypothesis, we isolated and identified primary AMs from freshly slaughtered yaks and cultured them in a medium with 5.5 mM of glucose or 2.8 mM of glucose plus 1-4 mM of BHB. Utilizing a real-time quantitative polymerase chain reaction (RT-qPCR), immunoblot assay, and enzyme-linked immunosorbent assay (ELISA), we evaluated the gene and protein expression levels of GPR109A (G-protein-coupled receptor 109A), NF-κB p65, p38, and PPARγ and the concentrations of pro-inflammatory cytokines interleukin (IL)-1ß and IL-6 and tumor necrosis factor (TNF)-α in the supernatant. The results demonstrated that AMs exposed to low glucose plus BHB had significantly higher levels of IL-1ß, IL-6, and TNF-α (p < 0.05) and higher activity of the GPR109A/NF-κB signaling pathway. A pretreatment of either pertussis toxin (PTX, inhibitor of GPR109A) or pyrrolidinedithiocarbamic (PDTC, inhibitor of NF-κB p65) was effective in preventing the elevated secretion of pro-inflammatory cytokines induced by low glucose plus BHB (p < 0.05). These results indicated that the low glucose plus BHB condition would induce an enhanced pro-inflammatory response through the activation of the GPR109A/NF-κB signaling pathway in primary yak AMs, which is probably the reason why yaks experience a higher rate of respiratory diseases and mortality. This study will offer new insight into the prevention and treatment of bovine respiratory diseases.


Assuntos
Macrófagos Alveolares , NF-kappa B , Bovinos , Animais , NF-kappa B/metabolismo , Ácido 3-Hidroxibutírico/farmacologia , Macrófagos Alveolares/metabolismo , Interleucina-6/farmacologia , Transdução de Sinais , Citocinas/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Glucose/farmacologia
16.
Int J Mol Sci ; 24(6)2023 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-36982413

RESUMO

The cytosolic carboxypeptidase (CCP) 1 protein, encoded by CCP1, is expressed in cerebellar Purkinje cells (PCs). The dysfunction of CCP1 protein (caused by CCP1 point mutation) and the deletion of CCP1 protein (caused by CCP1 gene knockout) all lead to the degeneration of cerebellar PCs, which leads to cerebellar ataxia. Thus, two CCP1 mutants (i.e., Ataxia and Male Sterility [AMS] mice and Nna1 knockout [KO] mice) are used as disease models. We investigated the cerebellar CCP1 distribution in wild-type (WT), AMS and Nna1 KO mice on postnatal days (P) 7-28 to investigate the differential effects of CCP protein deficiency and disorder on cerebellar development. Immunohistochemical and immunofluorescence studies revealed significant differences in the cerebellar CCP1 expression in WT and mutant mice of P7 and P15, but no significant difference between AMS and Nna1 KO mice. Electron microscopy showed slight abnormality in the nuclear membrane structure of PCs in the AMS and Nna1 KO mice at P15 and significant abnormality with depolymerization and fragmentation of microtubule structure at P21. Using two CCP1 mutant mice strains, we revealed the morphological changes of PCs at postnatal stages and indicated that CCP1 played an important role in cerebellar development, most likely via polyglutamylation.


Assuntos
Ataxia Cerebelar , D-Ala-D-Ala Carboxipeptidase Tipo Serina , Animais , Masculino , Camundongos , Ataxia/genética , Ataxia Cerebelar/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Camundongos Knockout , Processamento de Proteína Pós-Traducional , Células de Purkinje/metabolismo , D-Ala-D-Ala Carboxipeptidase Tipo Serina/genética , D-Ala-D-Ala Carboxipeptidase Tipo Serina/metabolismo , Tubulina (Proteína)/genética , Tubulina (Proteína)/metabolismo
17.
J Exp Bot ; 73(16): 5543-5558, 2022 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-35617147

RESUMO

Pollen development is dependent on the tapetum, a sporophytic anther cell layer surrounding the microspores that functions in pollen wall formation but is also essential for meiosis-associated development. There is clear evidence of crosstalk and co-regulation between the tapetum and microspores, but how this is achieved is currently not characterized. ABORTED MICROSPORES (AMS), a tapetum transcription factor, is important for pollen wall formation, but also has an undefined role in early pollen development. We conducted a detailed investigation of chromosome behaviour, cytokinesis, radial microtubule array (RMA) organization, and callose formation in the ams mutant. Early meiosis initiates normally in ams, shows delayed progression after the pachytene stage, and then fails during late meiosis, with disorganized RMA, defective cytokinesis, abnormal callose formation, and microspore degeneration, alongside abnormal tapetum development. Here, we show that selected meiosis-associated genes are directly repressed by AMS, and that AMS is essential for late meiosis progression. Our findings indicate that AMS has a dual function in tapetum-meiocyte crosstalk by playing an important regulatory role during late meiosis, in addition to its previously characterized role in pollen wall formation. AMS is critical for RMA organization, callose deposition, and therefore cytokinesis, and is involved in the crosstalk between the gametophyte and sporophytic tissues, which enables synchronous development of tapetum and microspores.


Assuntos
Regulação da Expressão Gênica de Plantas , Pólen , Células Germinativas Vegetais , Meiose , Pólen/metabolismo , Fatores de Transcrição/metabolismo
18.
Environ Sci Technol ; 56(9): 5421-5429, 2022 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-35413185

RESUMO

The chemical pathways for the production of secondary organic aerosols (SOA) are influenced by the concentration of nitrogen oxides (NOx), including the production of organonitrates (ON). Herein, a series of experiments conducted in an environmental chamber investigated the production and partitioning of total organonitrates from α-pinene photo-oxidation from <1 to 24 ppb NOx. Gas-phase and particle-phase organonitrates (gON and pON, respectively) were measured by laser-induced fluorescence (LIF). The composition of the particle phase and the particle mass concentration were simultaneously characterized by online aerosol mass spectrometry. The LIF and MS measurements of pON concentrations had a Pearson correlation coefficient of 0.91 from 0.3 to 1.1 µg m-3. For 1-6 ppb NOx, the yield of SOA particle mass concentration increased from 0.02 to 0.044 with NOx concentration. For >6 ppb NOx, the yield steadily dropped, reaching 0.034 at 24 ppb NOx. By comparison, the yield of pON steadily increased from 0.002 to 0.022 across the range of investigated NOx concentrations. The yield of gON likewise increased from 0.005 to 0.148. The gas-to-particle partitioning ratio (pON/(pON + gON)) depended strongly on the NOx concentration, changing from 0.27 to 0.13 as the NOx increased from <1 to 24 ppb. In the atmosphere, there is typically a cross-over point between clean and polluted conditions that strongly affects SOA production, and the results herein quantitatively identify 6 ppb NOx as that point for α-pinene photo-oxidation under these study conditions, including the production and partitioning of organonitrates. The trends in SOA yield and partitioning ratio as a function of NOx occur because of the changes in pON volatility.


Assuntos
Poluentes Atmosféricos , Aerossóis/química , Poluentes Atmosféricos/análise , Atmosfera , Monoterpenos Bicíclicos , Monoterpenos/química
19.
Environ Sci Technol ; 56(11): 6956-6967, 2022 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-34786936

RESUMO

The COVID-19 outbreak provides a "controlled experiment" to investigate the response of aerosol pollution to the reduction of anthropogenic activities. Here we explore the chemical characteristics, variations, and emission sources of organic aerosol (OA) based on the observation of air pollutants and combination of aerosol mass spectrometer (AMS) and positive matrix factorization (PMF) analysis in Beijing in early 2020. By eliminating the impacts of atmospheric boundary layer and the Spring Festival, we found that the lockdown effectively reduced cooking-related OA (COA) but influenced fossil fuel combustion OA (FFOA) very little. In contrast, both secondary OA (SOA) and O3 formation was enhanced significantly after lockdown: less-oxidized oxygenated OA (LO-OOA, 37% in OA) was probably an aged product from fossil fuel and biomass burning emission with aqueous chemistry being an important formation pathway, while more-oxidized oxygenated OA (MO-OOA, 41% in OA) was affected by regional transport of air pollutants and related with both aqueous and photochemical processes. Combining FFOA and LO-OOA, more than 50% of OA pollution was attributed to combustion activities during the whole observation period. Our findings highlight that fossil fuel/biomass combustion are still the largest sources of OA pollution, and only controlling traffic and cooking emissions cannot efficiently eliminate the heavy air pollution in winter Beijing.


Assuntos
Poluentes Atmosféricos , COVID-19 , Aerossóis/análise , Idoso , Poluentes Atmosféricos/análise , Efeitos Antropogênicos , Pequim , Controle de Doenças Transmissíveis , Monitoramento Ambiental , Combustíveis Fósseis/análise , Humanos , Material Particulado/análise
20.
Environ Sci Technol ; 56(6): 3645-3657, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35229595

RESUMO

Wildfire-influenced air masses under regional background conditions were characterized at the Mt. Bachelor Observatory (∼2800 m a.s.l.) in summer 2019 to provide a better understanding of the aging of biomass burning organic aerosols (BBOAs) and their impacts on the remote troposphere in the western United States. Submicron aerosol (PM1) concentrations were low (average ± 1σ = 2.2 ± 1.9 µg sm-3), but oxidized BBOAs (average O/C = 0.84) were constantly detected throughout the study. The BBOA correlated well with black carbon, furfural, and acetonitrile and comprised above 50% of PM1 during plume events when the peak PM1 concentration reached 18.0 µg sm-3. Wildfire plumes with estimated transport times varying from ∼10 h to >10 days were identified. The plumes showed ΔOA/ΔCO values ranging from 0.038 to 0.122 ppb ppb-1 with a significant negative relation to plume age, indicating BBOA loss relative to CO during long-range transport. Additionally, increases of average O/C and aerosol sizes were seen in more aged plumes. The mass-based size mode was approximately 700 nm (Dva) in the most oxidized plume that likely originated in Siberia, suggesting aqueous-phase processing during transport. This work highlights the widespread impacts that wildfire emissions have on aerosol concentration and properties, and thus climate, in the western United States.


Assuntos
Poluentes Atmosféricos , Incêndios Florestais , Aerossóis/análise , Poluentes Atmosféricos/análise , Biomassa , Monitoramento Ambiental , Material Particulado/análise , Estados Unidos
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