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1.
Proc Natl Acad Sci U S A ; 121(31): e2402755121, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39042673

RESUMO

The precise assembly of a functional nervous system relies on axon guidance cues. Beyond engaging their cognate receptors and initiating signaling cascades that modulate cytoskeletal dynamics, guidance cues also bind components of the extracellular matrix, notably proteoglycans, yet the role and mechanisms of these interactions remain poorly understood. We found that Drosophila secreted semaphorins bind specifically to glycosaminoglycan (GAG) chains of proteoglycans, showing a preference based on the degree of sulfation. Structural analysis of Sema2b unveiled multiple GAG-binding sites positioned outside canonical plexin-binding site, with the highest affinity binding site located at the C-terminal tail, characterized by a lysine-rich helical arrangement that appears to be conserved across secreted semaphorins. In vivo studies revealed a crucial role of the Sema2b C-terminal tail in specifying the trajectory of olfactory receptor neurons. We propose that secreted semaphorins tether to the cell surface through interactions with GAG chains of proteoglycans, facilitating their presentation to cognate receptors on passing axons.


Assuntos
Orientação de Axônios , Proteínas de Drosophila , Proteoglicanas , Semaforinas , Transdução de Sinais , Animais , Semaforinas/metabolismo , Semaforinas/genética , Proteoglicanas/metabolismo , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Axônios/metabolismo , Drosophila melanogaster/metabolismo , Glicosaminoglicanos/metabolismo , Sítios de Ligação , Ligação Proteica , Neurônios Receptores Olfatórios/metabolismo
2.
Plant Biotechnol J ; 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38923713

RESUMO

Developing early maturing lentil has the potential to minimize yield losses, mainly during terminal drought. Whole-genome resequencing (WGRS) based QTL-seq identified the loci governing earliness in lentil. The genetic analysis for maturity duration provided a good fit to 3:1 segregation (F2), indicating earliness as a recessive trait. WGRS of Globe Mutant (late parent), late-flowering, and early-flowering bulks (from RILs) has generated 1124.57, 1052.24 million raw and clean reads, respectively. The QTL-Seq identified three QTLs (LcqDTF3.1, LcqDTF3.2, and LcqDTF3.3) on chromosome 3 having 246244 SNPs and 15577 insertions/deletions (InDels) and 13 flowering pathway genes. Of these, 11 exhibited sequence variations between bulks and validation (qPCR) revealed a significant difference in the expression of nine candidate genes (LcGA20oxG, LcFRI, LcLFY, LcSPL13a, Lcu.2RBY.3g060720, Lcu.2RBY.3g062540, Lcu.2RBY.3g062760, LcELF3a, and LcEMF1). Interestingly, the LcELF3a gene showed significantly higher expression in late-flowering genotype and exhibited substantial involvement in promoting lateness. Subsequently, an InDel marker (I-SP-383.9; LcELF3a gene) developed from LcqDTF3.2 QTL region showed 82.35% PVE (phenotypic variation explained) for earliness. The cloning, sequencing, and comparative analysis of the LcELF3a gene from both parents revealed 23 SNPs and InDels. Interestingly, a 52 bp deletion was recorded in the LcELF3a gene of L4775, predicted to cause premature termination of protein synthesis after 4 missense amino acids beyond the 351st amino acid due to the frameshift during translation. The identified InDel marker holds significant potential for breeding early maturing lentil varieties.

3.
J Org Chem ; 89(5): 2873-2884, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38354303

RESUMO

We have developed the first I2/base-catalyzed regio- and stereoselective intermolecular ß-amidosulfonylation of terminal alkynes using sodium sulfinates and quinoxalinone derivatives. The present methodology is compatible with a broad spectrum of various heterocyclic amides, terminal alkynes, and sodium sulfinates. It provides rapid access to valuable (Z)-ß-amidovinyl sulfones at mild conditions. Moreover, the synthetic application of this methodology was demonstrated by the late-stage functionalization of numerous bioactive molecules.

4.
Childs Nerv Syst ; 40(1): 213-218, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37428253

RESUMO

OBJECTIVE: The fibroneural stalk of an LDM has variable thickness, complexity, and length, which can span 5 to 6 vertebral segments from its skin attachment to its "merge point" with the dorsal spinal cord. Therefore, complete resection may require extensive multi-level laminotomies. In this technical note, a modification of the procedure is presented that avoids long segment laminectomies while ensuring complete excision of long LDM stalks. RESULTS: An illustrative case of resection of LDM is presented using skip laminectomies. The technique ensures complete removal of the stalk, thus reducing the risk of future intradural dermoid development, while at the same time minimizes the risk for delayed kyphotic deformity. CONCLUSIONS: A technique of "skip-hop" proximal and distal short segment laminectomies in cases of LDM optimizes the objectives of complete stalk resection with preservation of spinal integrity.


Assuntos
Laminectomia , Medula Espinal , Humanos , Medula Espinal/cirurgia , Pele , Coluna Vertebral/cirurgia
5.
Proc Natl Acad Sci U S A ; 118(15)2021 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-33876743

RESUMO

Chemotherapy-induced peripheral neuropathy (CIPN) is a major side effect from cancer treatment with no known method for prevention or cure in clinics. CIPN often affects unmyelinated nociceptive sensory terminals. Despite the high prevalence, molecular and cellular mechanisms that lead to CIPN are still poorly understood. Here, we used a genetically tractable Drosophila model and primary sensory neurons isolated from adult mouse to examine the mechanisms underlying CIPN and identify protective pathways. We found that chronic treatment of Drosophila larvae with paclitaxel caused degeneration and altered the branching pattern of nociceptive neurons, and reduced thermal nociceptive responses. We further found that nociceptive neuron-specific overexpression of integrins, which are known to support neuronal maintenance in several systems, conferred protection from paclitaxel-induced cellular and behavioral phenotypes. Live imaging and superresolution approaches provide evidence that paclitaxel treatment causes cellular changes that are consistent with alterations in endosome-mediated trafficking of integrins. Paclitaxel-induced changes in recycling endosomes precede morphological degeneration of nociceptive neuron arbors, which could be prevented by integrin overexpression. We used primary dorsal root ganglia (DRG) neuron cultures to test conservation of integrin-mediated protection. We show that transduction of a human integrin ß-subunit 1 also prevented degeneration following paclitaxel treatment. Furthermore, endogenous levels of surface integrins were decreased in paclitaxel-treated mouse DRG neurons, suggesting that paclitaxel disrupts recycling in vertebrate sensory neurons. Altogether, our study supports conserved mechanisms of paclitaxel-induced perturbation of integrin trafficking and a therapeutic potential of restoring neuronal interactions with the extracellular environment to antagonize paclitaxel-induced toxicity in sensory neurons.


Assuntos
Integrinas/metabolismo , Nociceptores/metabolismo , Doenças do Sistema Nervoso Periférico/metabolismo , Animais , Antineoplásicos/toxicidade , Células Cultivadas , Drosophila melanogaster , Endossomos/metabolismo , Feminino , Gânglios Espinais/citologia , Integrinas/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Nociceptores/fisiologia , Paclitaxel/toxicidade , Doenças do Sistema Nervoso Periférico/etiologia
6.
Proc Natl Acad Sci U S A ; 118(4)2021 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-33468672

RESUMO

The pathogenesis of chemotherapy-induced peripheral neuropathy (CIPN) is poorly understood. Here, we report that the CIPN-causing drug bortezomib (Bort) promotes delta 2 tubulin (D2) accumulation while affecting microtubule stability and dynamics in sensory neurons in vitro and in vivo and that the accumulation of D2 is predominant in unmyelinated fibers and a hallmark of bortezomib-induced peripheral neuropathy (BIPN) in humans. Furthermore, while D2 overexpression was sufficient to cause axonopathy and inhibit mitochondria motility, reduction of D2 levels alleviated both axonal degeneration and the loss of mitochondria motility induced by Bort. Together, our data demonstrate that Bort, a compound structurally unrelated to tubulin poisons, affects the tubulin cytoskeleton in sensory neurons in vitro, in vivo, and in human tissue, indicating that the pathogenic mechanisms of seemingly unrelated CIPN drugs may converge on tubulin damage. The results reveal a previously unrecognized pathogenic role for D2 in BIPN that may occur through altered regulation of mitochondria motility.


Assuntos
Bortezomib/efeitos adversos , Neoplasias/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/genética , Tubulina (Proteína)/genética , Animais , Antineoplásicos/efeitos adversos , Axônios/efeitos dos fármacos , Axônios/patologia , Modelos Animais de Doenças , Drosophila melanogaster/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HEK293 , Humanos , Larva/efeitos dos fármacos , Larva/genética , Microtúbulos/efeitos dos fármacos , Microtúbulos/genética , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/genética , Dinâmica Mitocondrial/efeitos dos fármacos , Dinâmica Mitocondrial/genética , Neoplasias/genética , Neoplasias/patologia , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/patologia , Células Receptoras Sensoriais/efeitos dos fármacos , Células Receptoras Sensoriais/patologia , Peixe-Zebra/genética
7.
Neurocrit Care ; 41(2): 576-582, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38580801

RESUMO

BACKGROUND: Hypoxemia is the main modifiable factor preventing lungs from being transplanted from organ donors after brain death. One major contributor to impaired oxygenation in patients with brain injury is atelectasis. Apnea testing, an integral component of brain death declaration, promotes atelectasis and can worsen hypoxemia. In this study, we tested whether performing a recruitment maneuver (RM) after apnea testing could mitigate hypoxemia and atelectasis. METHODS: During the study period, an RM (positive end-expiratory pressure of 15 cm H2O for 15 s then 30 cm H2O for 30 s) was performed immediately after apnea testing. We measured partial pressure of oxygen, arterial (PaO2) before and after RM. The primary outcomes were oxygenation (PaO2 to fraction of inspired oxygen [FiO2] ratio) and the severity of radiographic atelectasis (proportion of lung without aeration on computed tomography scans after brain death, quantified using an image analysis algorithm) in those who became organ donors. Outcomes in RM patients were compared with control patients undergoing apnea testing without RM in the previous 2 years. RESULTS: Recruitment maneuver was performed in 54 patients after apnea testing, with a median immediate increase in PaO2 of 63 mm Hg (interquartile range 0-109, p = 0.07). Eighteen RM cases resulted in hypotension, but none were life-threatening. Of this cohort, 37 patients became organ donors, compared with 37 donors who had apnea testing without RM. The PaO2:FiO2 ratio was higher in the RM group (355 ± 129 vs. 288 ± 127, p = 0.03), and fewer had hypoxemia (PaO2:FiO2 ratio < 300 mm Hg, 22% vs. 57%; p = 0.04) at the start of donor management. The RM group showed less radiographic atelectasis (median 6% vs. 13%, p = 0.045). Although there was no difference in lungs transplanted (35% vs. 24%, p = 0.44), both better oxygenation and less atelectasis were associated with a higher likelihood of lungs being transplanted. CONCLUSIONS: Recruitment maneuver after apnea testing reduces hypoxemia and atelectasis in organ donors after brain death. This effect may translate into more lungs being transplanted.


Assuntos
Apneia , Morte Encefálica , Atelectasia Pulmonar , Doadores de Tecidos , Humanos , Atelectasia Pulmonar/prevenção & controle , Atelectasia Pulmonar/etiologia , Atelectasia Pulmonar/diagnóstico por imagem , Morte Encefálica/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Hipóxia , Respiração com Pressão Positiva/métodos , Idoso , Oxigênio/metabolismo
8.
Neurocrit Care ; 40(1): 303-313, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37188885

RESUMO

BACKGROUND: Cerebral edema has primarily been studied using midline shift or clinical deterioration as end points, which only captures the severe and delayed manifestations of a process affecting many patients with stroke. Quantitative imaging biomarkers that measure edema severity across the entire spectrum could improve its early detection, as well as identify relevant mediators of this important stroke complication. METHODS: We applied an automated image analysis pipeline to measure the displacement of cerebrospinal fluid (ΔCSF) and the ratio of lesional versus contralateral hemispheric cerebrospinal fluid (CSF) volume (CSF ratio) in a cohort of 935 patients with hemispheric stroke with follow-up computed tomography scans taken a median of 26 h (interquartile range 24-31) after stroke onset. We determined diagnostic thresholds based on comparison to those without any visible edema. We modeled baseline clinical and radiographic variables against each edema biomarker and assessed how each biomarker was associated with stroke outcome (modified Rankin Scale at 90 days). RESULTS: The displacement of CSF and CSF ratio were correlated with midline shift (r = 0.52 and - 0.74, p < 0.0001) but exhibited broader ranges. A ΔCSF of greater than 14% or a CSF ratio below 0.90 identified those with visible edema: more than half of the patients with stroke met these criteria, compared with only 14% who had midline shift at 24 h. Predictors of edema across all biomarkers included a higher National Institutes of Health Stroke Scale score, a lower Alberta Stroke Program Early CT score, and lower baseline CSF volume. A history of hypertension and diabetes (but not acute hyperglycemia) predicted greater ΔCSF but not midline shift. Both ΔCSF and a lower CSF ratio were associated with worse outcome, adjusting for age, National Institutes of Health Stroke Scale score, and Alberta Stroke Program Early CT score (odds ratio 1.7, 95% confidence interval 1.3-2.2 per 21% ΔCSF). CONCLUSIONS: Cerebral edema can be measured in a majority of patients with stroke on follow-up computed tomography using volumetric biomarkers evaluating CSF shifts, including in many without visible midline shift. Edema formation is influenced by clinical and radiographic stroke severity but also by chronic vascular risk factors and contributes to worse stroke outcomes.


Assuntos
Edema Encefálico , Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , AVC Isquêmico/complicações , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/epidemiologia , Edema Encefálico/diagnóstico por imagem , Edema Encefálico/epidemiologia , Edema Encefálico/etiologia , Incidência , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/epidemiologia , Biomarcadores , Edema/complicações , Fatores de Risco , Resultado do Tratamento
9.
J Stroke Cerebrovasc Dis ; 33(10): 107913, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39098362

RESUMO

BACKGROUND: Hemorrhagic transformation (HT) and cerebral edema (CED) are both major complications following ischemic stroke, but few studies have evaluated their overlap. We evaluated the frequency and predictors of CED/HT overlap and whether their co-occurrence impacts functional outcome more than each in isolation. METHODS: 892 stroke patients enrolled in a prospective study had follow-up CT imaging evaluated for HT and CED; the latter was quantified using the ratio of hemispheric CSF volumes (with hemispheric CSF ratio < 0.90 used as the CED threshold). The interaction between HT and CED on functional outcome (using modified Rankin Scale at 3 months) was compared to that for each condition separately. RESULTS: Among the 275 (31%) who developed HT, 233 (85%) manifested hemispheric CSF ratio < 0.9 (CED/HT), with this overlap group representing half of the 475 with measurable CED. Higher baseline NIHSS scores and larger infarct volumes were observed in the CED/HT group compared with those with CED or HT alone. Functional outcome was worse in those with CED/HT [median mRS 3 (IQR 2-5)] than those with CED [median 2 (IQR 1-4)] or HT alone [median 1 (IQR 0-2), p < 0.0001]. Overlap of CED/HT independently predicted worse outcome [OR 1.89 (95% CI: 1.12-3.18), p = 0.02] while HT did not; however, CED/HT was no longer associated with worse outcome after adjusting for severity of CED [adjusted OR 0.35 (95% CI: 0.23, 0.51) per 0.21 lower hemispheric CSF ratio, p < 0.001]. CONCLUSIONS: Most stroke patients with HT also have measurable CED. The co-occurrence of CED and HT occurs in larger and more severe strokes and is associated with worse functional outcome, although this is driven by greater severity of stroke-related edema in those with HT.


Assuntos
Edema Encefálico , Avaliação da Deficiência , Estado Funcional , AVC Isquêmico , Recuperação de Função Fisiológica , Humanos , Masculino , Idoso , Feminino , Edema Encefálico/diagnóstico por imagem , Edema Encefálico/etiologia , Edema Encefálico/fisiopatologia , Edema Encefálico/líquido cefalorraquidiano , AVC Isquêmico/fisiopatologia , AVC Isquêmico/diagnóstico , AVC Isquêmico/diagnóstico por imagem , AVC Isquêmico/líquido cefalorraquidiano , AVC Isquêmico/complicações , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo , Hemorragia Cerebral/fisiopatologia , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/diagnóstico , Idoso de 80 Anos ou mais , Prognóstico , Tomografia Computadorizada por Raios X , Hemorragias Intracranianas/fisiopatologia , Hemorragias Intracranianas/etiologia
10.
Agron Sustain Dev ; 44(1): 2, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38161803

RESUMO

The UK Government has set an ambitious target of achieving a national "net-zero" greenhouse gas economy by 2050. Agriculture is arguably placed at the heart of achieving net zero, as it plays a unique role as both a producer of GHG emissions and a sector that has the capacity via land use to capture carbon (C) when managed appropriately, thus reducing the concentration of carbon dioxide (CO2) in the atmosphere. Agriculture's importance, particularly in a UK-specific perspective, which is also applicable to many other temperate climate nations globally, is that the majority of land use nationwide is allocated to farming. Here, we present a systematic review based on peer-reviewed literature and relevant "grey" reports to address the question "how can the agricultural sector in the UK reduce, or offset, its direct agricultural emissions at the farm level?" We considered the implications of mitigation measures in terms of food security and import reliance, energy, environmental degradation, and value for money. We identified 52 relevant studies covering major foods produced and consumed in the UK. Our findings indicate that many mitigation measures can indeed contribute to net zero through GHG emissions reduction, offsetting, and bioenergy production, pending their uptake by farmers. While the environmental impacts of mitigation measures were covered well within the reviewed literature, corresponding implications regarding energy, food security, and farmer attitudes towards adoption received scant attention. We also provide an open-access, informative, and comprehensive dataset for agri-environment stakeholders and policymakers to identify the most promising mitigation measures. This research is of critical value to researchers, land managers, and policymakers as an interim guideline resource while more quantitative evidence becomes available through the ongoing lab-, field-, and farm-scale trials which will improve the reliability of agricultural sustainability modelling in the future. Supplementary Information: The online version contains supplementary material available at 10.1007/s13593-023-00938-0.

11.
Planta ; 258(1): 3, 2023 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-37212904

RESUMO

MAIN CONCLUSION: The consortium inoculation with strains R1 and R4 modified the root system to boost seedling growth, increase the zinc content of French bean pods, and reduce salinity stress. The present study demonstrated the effect of two 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase-producing plant growth-promoting rhizobacteria (Pantoea agglomerans R1 and Pseudomonas fragi R4) alone and consortia on the root system development, French bean growth, and zinc content as well as salinity stress tolerance. Both the strains were characterized for ACC utilization activity (426.23 and 380.54 nmol α-ketobutyrate mg protein-1 h-1), indole acetic acid (IAA) production, phosphate solubilization, ammonia, hydrogen cyanide (HCN), and siderophore production. The strains exhibited zinc solubilization in both plate and broth assays with zinc oxide and zinc carbonate as zinc sources as validated by atomic absorption spectroscopy (AAS). Single or combined inoculations with the selected strains significantly modulated the architectural and morphological traits of the root system of French bean plants. Furthermore, the application of R1and R4 consortia has enhanced zinc content in roots (60.83 mg kg-1), shoots (15.41 mg kg-1), and pods (30.04 mg kg-1) of French bean plants grown in ZnCO3 amended soil. In another set of pot experiments, the consortium bacterization has significantly enhanced length as well as fresh and dry biomass of roots and shoots of the French bean plant under saline stress conditions. Additionally, inoculation with ACC-degrading rhizobacterial strains has increased chlorophyll and carotenoid contents, osmoprotectant content, and antioxidative enzyme (catalase and peroxidase) activity in comparison to their counterparts exposed to salt treatments only. Current findings suggested ACC deaminase-producing rhizobacterial strains hold the potential to improve root architecture which in turn promotes plant growth under salt-stressed conditions as well as enhances micronutrient concentration in host plants.


Assuntos
Phaseolus , Bactérias , Carbono-Carbono Liases , Cloreto de Sódio , Estresse Salino , Zinco , Microbiologia do Solo , Raízes de Plantas , Salinidade
12.
Acta Neuropathol ; 145(1): 29-48, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36357715

RESUMO

Epitranscriptomic regulation adds a layer of post-transcriptional control to brain function during development and adulthood. The identification of RNA-modifying enzymes has opened the possibility of investigating the role epitranscriptomic changes play in the disease process. NOP2/Sun RNA methyltransferase 2 (NSun2) is one of the few known brain-enriched methyltransferases able to methylate mammalian non-coding RNAs. NSun2 loss of function due to autosomal-recessive mutations has been associated with neurological abnormalities in humans. Here, we show NSun2 is expressed in adult human neurons in the hippocampal formation and prefrontal cortex. Strikingly, we unravel decreased NSun2 protein expression and an increased ratio of pTau/NSun2 in the brains of patients with Alzheimer's disease (AD) as demonstrated by Western blotting and immunostaining, respectively. In a well-established Drosophila melanogaster model of tau-induced toxicity, reduction of NSun2 exacerbated tau toxicity, while overexpression of NSun2 partially abrogated the toxic effects. Conditional ablation of NSun2 in the mouse brain promoted a decrease in the miR-125b m6A levels and tau hyperphosphorylation. Utilizing human induced pluripotent stem cell (iPSC)-derived neuronal cultures, we confirmed NSun2 deficiency results in tau hyperphosphorylation. We also found that neuronal NSun2 levels decrease in response to amyloid-beta oligomers (AßO). Notably, AßO-induced tau phosphorylation and cell toxicity in human neurons could be rescued by overexpression of NSun2. Altogether, these results indicate that neuronal NSun2 deficiency promotes dysregulation of miR-125b and tau phosphorylation in AD and highlights a novel avenue for therapeutic targeting.


Assuntos
Doença de Alzheimer , Células-Tronco Pluripotentes Induzidas , MicroRNAs , Camundongos , Animais , Humanos , Adulto , Metiltransferases/genética , Fosforilação/genética , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , MicroRNAs/genética , Proteínas tau/metabolismo , Mamíferos/metabolismo
13.
J Org Chem ; 88(19): 13666-13677, 2023 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-37737722

RESUMO

The first multicomponent regio- and stereoselective difunctionalization of alkynes via concomitant C-O and C-S bond formation using 1,3-diketones and sodium sulfinate has been developed for the synthesis of various sulfonated enethers. The viability of this strategy is unveiled by gram-scale, various synthetic modifications and late-stage functionalization. This transformation does not require any prefunctionalization, metal catalysts, and oxidants. The present operationally simple, efficient, and sustainable approach provides various functionalized olefins in a one-pot protocol with high Z-selectivity.

14.
Brain ; 145(7): 2486-2506, 2022 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-35148384

RESUMO

Microtubules play fundamental roles in the maintenance of neuronal processes and in synaptic function and plasticity. While dynamic microtubules are mainly composed of tyrosinated tubulin, long-lived microtubules contain detyrosinated tubulin, suggesting that the tubulin tyrosination/detyrosination cycle is a key player in the maintenance of microtubule dynamics and neuronal homeostasis, conditions that go awry in neurodegenerative diseases. In the tyrosination/detyrosination cycle, the C-terminal tyrosine of α-tubulin is removed by tubulin carboxypeptidases and re-added by tubulin tyrosine ligase (TTL). Here we show that TTL heterozygous mice exhibit decreased tyrosinated microtubules, reduced dendritic spine density and both synaptic plasticity and memory deficits. We further report decreased TTL expression in sporadic and familial Alzheimer's disease, and reduced microtubule dynamics in human neurons harbouring the familial APP-V717I mutation. Finally, we show that synapses visited by dynamic microtubules are more resistant to oligomeric amyloid-ß peptide toxicity and that expression of TTL, by restoring microtubule entry into spines, suppresses the loss of synapses induced by amyloid-ß peptide. Together, our results demonstrate that a balanced tyrosination/detyrosination tubulin cycle is necessary for the maintenance of synaptic plasticity, is protective against amyloid-ß peptide-induced synaptic damage and that this balance is lost in Alzheimer's disease, providing evidence that defective tubulin retyrosination may contribute to circuit dysfunction during neurodegeneration in Alzheimer's disease.


Assuntos
Doença de Alzheimer , Tubulina (Proteína) , Doença de Alzheimer/metabolismo , Animais , Humanos , Camundongos , Microtúbulos , Peptídeos/metabolismo , Tubulina (Proteína)/metabolismo , Tirosina/metabolismo
15.
Phys Chem Chem Phys ; 25(42): 28784-28795, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37850482

RESUMO

Herein, the monoclinic phase of tungsten oxide (γ-WO3) was successfully obtained after annealing hydrothermally synthesised WO3 powder at 500 °C. As per the result obtained from the N2 adsorption-desorption isotherm, the material has been identified as mesoporous with a specific surface area of 3.71 m2 g-1 from BET (Brunauer-Emmett-Teller) analysis. Moreover, the average pore size (49.52 nm) and volume (0.050 cm3 g-1) were also determined by the BJH (Barrett-Joyner-Halenda) method. FE-SEM (field emission scanning electron microscopy) and HR-TEM (high resolution transmission electron microscopy) have confirmed the formation of nanoplates with an average diameter of approximately 274 nm. Raman spectroscopy has shown peaks at the lower wavenumber region (270 cm-1 and 326 cm-1) and the higher wavenumber region (713 cm-1 and 806 cm-1) for O-W-O bending modes and stretching modes, respectively. The combined effect of relative humidity (RH-11%-RH-95%-RH-11%) and NH3 (150 ppm, 300 ppm, 450 ppm, 600 ppm, 700 ppm, and 800 ppm) was investigated in this reported work. The synthesised γ-WO3 has shown highly responsive behaviour for humidity of 96.5% (RH-11%-95%) and NH3 sensing (under humidity) of 97.4% (RH-11%-95% with 800 ppm NH3). The response and recovery time were calculated as 15 s and 52 s, and 16 s and 54 s for humidity, and NH3 under humidity, respectively. The experimental findings demonstrated that the resistance of the sensor depends on the concentration of NH3 and humidity. Moreover, γ-WO3 has been investigated as a promising catalyst for the dye degradation of methylene blue (MB) with a degradation efficiency of 72.82% and methyl orange (MO) with a degradation efficiency of 53.84% under visible light exposure. This dye degradation occurred within 160 min in the presence of a catalyst under visible light irradiation.

16.
Environ Res ; 231(Pt 2): 116108, 2023 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-37187311

RESUMO

The present study is aimed to evaluate the environmental and economic burden associated with current waste collection practices in Dhanbad city, Jharkhand, India. In this study various alternatives were suggested to mitigate these impacts by optimizing resource utilization and maximizing material recovery using life cycle approach. The functional unit adapted is the daily collection service provided for 180 tonnes of municipal solid waste generated in the study area. GaBi 10.6.1 software was used for impact assessment and impacts were assessed for five scenarios in terms of five different impact categories. This study assessed the collection services and treatment options jointly. Baseline scenario (S1) representing the current collection system had the highest impacts on all the impact categories and landfilling contributed the highest (67%) to the overall impacts on the environment. Scenario S2 involved the provision of material recovery facility and considered recycling of plastic wastes having sorting efficiency of 75% which reduced the overall impacts significantly (∼971%) compared to the baseline scenario. Scenario S3 considered composting of food waste (80% food waste sent for composting) and offered further overall impacts reduction (∼1052%) compared to the baseline scenario. In scenario S4, use of electric tippers was accounted which did not offer any significant impacts reductions. Scenario S5 considered the future electricity mix at grid (2030) in India which increased the benefits of using electric tippers. S5 had the least environmental impacts providing overall reductions of ∼1063% compared to baseline scenario and provided maximum economic benefits. Sensitivity analysis results found that variation in recycling had significant change in the environmental impacts. Considering the decrease in recycling rate from 100% to 50%, the impacts on abiotic depletion fossil increased by 136%, acidification by 176%, global warming by 11%, human toxicity by 172% and terrestrial ecotoxicity by 56%.


Assuntos
Eliminação de Resíduos , Gerenciamento de Resíduos , Humanos , Eliminação de Resíduos/métodos , Alimentos , Resíduos Sólidos/análise , Meio Ambiente , Cidades , Gerenciamento de Resíduos/métodos
17.
Retina ; 43(11): 1922-1927, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37490757

RESUMO

PURPOSE: To assess the characteristics of completed panretinal photocoagulation (PRP), using ultra-widefield imaging in proliferative diabetic retinopathy. METHODS: Quantitative assessment of ultra-widefield imaging images of 133 patients with proliferative diabetic retinopathy with completed PRP was made using ImageJ software. The parameters assessed included distance of laser spots from the optic disk, foveal center, superior and inferior arcades, and extent of the maximum width of laser. Areas assessed were total area of the image, area of the inner limit within which laser spots are restricted, minimum areas of unlasered patches, total area lasered, and ideal area to be covered by PRP. RESULTS: Two hundred one images were assessed for the final analysis. The mean distance of laser spots was 4.2 ± 2.4 mm from the optic disk (nasal) and 6.6 ± 2.5 mm from the foveal center (temporal). The mean distance of laser spots from the superior arcade vessel was 3.2 ± 1.9 mm and 6.2 ± 4.4 mm from the inferior arcade. The mean area of the retina that should have been ideally lasered was found to be 900 ± 267 mm 2 , and the actual area lasered was found to be 681 ± 254.4 mm 2 . CONCLUSION: Approximately one-quarter area of the retina continues to remain ischemic because of the lack of inadequate coverage of PRP. Further longitudinal studies are recommended, using ultra-widefield imaging to objectively assess the adequacy of PRP and its role in modulating the course of progression of the retinopathy.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Disco Óptico , Humanos , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/cirurgia , Retina/diagnóstico por imagem , Retina/cirurgia , Fotocoagulação a Laser/métodos , Tomografia de Coerência Óptica/métodos
18.
Appl Opt ; 62(10): 2501-2509, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37132798

RESUMO

In recent years, visible light communication (VLC) has emerged as a potential technique for beyond 5G communication networks. In this study, an angular diversity receiver (ADR) is used to propose a multiple-input multiple-output (MIMO) VLC system employing L-pulse position modulation (L-PPM). Repetition coding (RC) is used at the transmitter, while receiver diversity techniques such as maximum-ratio combining (MRC), selection best combining (SBC), and equal gain combining (EGC) are used at the receiver to improve performance. This study presents the exact probability of error expressions for the proposed system with and without channel estimation error (CEE). The analysis shows that the probability of error of the proposed system increases as the estimation error increases. Further, the study shows that the increase in signal-to-noise ratio is not enough to counter the impact of CEE, especially when the estimation error is large. The distribution of error probability of the proposed system using EGC, SBC, and MRC throughout the area of the room is presented. The simulation findings are compared to the analytical results.

19.
Appl Opt ; 62(25): 6639-6651, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37706796

RESUMO

Visible light communication (VLC) allows white LEDs to communicate while lighting, which improves resource consumption. Multiple relay approaches can be employed in conjunction with cooperative communications to achieve large gains in spatial diversity, expand the coverage, and possibly boost system capacity. In this paper, the nonorthogonal multiple access (NOMA) cooperative techniques for VLC systems using on-off keying (OOK) and L-pulse-position modulation (L-PPM) are proposed. The maximum ratio combining (MRC) schemes is adopted at the receiving node to combine the signals received from cooperative transmissions. Further, the decode-and-forward relaying protocol is considered for cooperation. The proposed system is analyzed for a multiuser scenario that is followed by a two- and three-user scenario for detailed analysis. This study calculates the bit error probability (BEP) of an OOK/L-PPM modulated NOMA cooperative VLC system under perfect and imperfect successive interference cancellation. Simulation results are presented to validate the produced analytical BEP results.

20.
Plant Dis ; 107(3): 896-898, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36265154

RESUMO

Ustilaginoidea virens is the fungal pathogen causing an emerging false smut disease that affects crop yield as well as deteriorates quality of the grains by producing mycotoxins. A high quality genome of U. virens isolate UV2_4G was sequenced using Nanopore and Illumina HiSeq 2,000 sequencing platforms. The total assembled genome of Indian isolate UV2_4G was 35.9 Mb, which comprised 89 scaffolds with N50 of 700,296 bp. A total of 358,697 variants were identified in the genome, out of which 355,173 were SNPs and 3,524 were INDELS. Further, 7,390 SSRs belonging to different repeat types were also identified in the genome. Out of 7,444 proteins predicted, 7,206 were functionally annotated. A total of 1,307 CAZymes, 501 signal peptides, 1,876 effectors, and 2,709 genes involved in host-pathogen interactions were identified. Comparative analysis revealed isolate UV2_4G is distinct with 31 unique clusters and placed distantly in phylogenetic analysis. Taken together, this high-quality genome assembly and sequence annotation resource can give an improved insight for characterizing the biological and pathogenic mechanisms of U. virens.


Assuntos
Hypocreales , Oryza , Ustilaginales , Oryza/microbiologia , Filogenia , Doenças das Plantas/microbiologia , Hypocreales/genética , Ustilaginales/genética
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