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1.
J Exp Bot ; 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39225376

RESUMO

Cannabis sativa L. is one of the oldest domesticated crops. Hemp-type cultivars, which predominantly produce non-intoxicating cannabidiol (CBD), have been selected for their fast growth, seed, and fibre production, while drug-type chemovars were bred for high accumulation of tetrahydrocannabinol (THC). We investigated how the generation of CBD-dominant chemovars by introgression of hemp- into drug-type Cannabis impacted plant performance. The THC-dominant chemovar showed superior sink strength, higher flower biomass and demand-driven control of nutrient uptake. By contrast, the CBD-dominant chemovar hyperaccumulated phosphate in sink organs leading to reduced carbon and nitrogen assimilation in leaves, which limited flower biomass and cannabinoid yield. RNA-seq analyses determined organ- and chemovar-specific differences in expression of genes associated with nitrate and phosphate homeostasis as well as growth-regulating transcription factors that were correlated with measured traits. Among these were genes positively selected for during Cannabis domestication encoding an inhibitor of the phosphate starvation response SPX DOMAIN GENE3, nitrate reductase and two nitrate transporters. Altered nutrient sensing, acquisition or distribution are likely a consequence of adaption to growth on marginal, low-nutrient input lands in hemp. Our data provide evidence that such ancestral traits may become detrimental for female flower development and consequently overall CBD yield in protected cropping environments.

2.
Pol J Radiol ; 89: e336-e344, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39139255

RESUMO

Purpose: To evaluate the prevalence of vascular contact of the facial nerve in patients without hemifacial spasm or facial palsy using magnetic resonance imaging (MRI). Material and methods: Our radiology database was accessed to find a series of consecutive adult patients who underwent MRI of the brain during the study period, excluding those with a history of hemifacial spasm (HFS), facial palsy, traumatic brain injury, intracranial tumour, intracranial surgery, trigeminal neuro-vascular compression, brain radiation therapy, and studies with poor image quality. A total of 112 (224 sides) MRIs of the posterior fossa were independently reviewed by 2 radiologists for neurovascular contact involving the facial nerve. The presence of neuro-vascular contact, the number of points of contact, the location of contact along the intracranial course of the facial nerve, the culprit vessel, and the severity of compression were recorded in the CISS MRI sequence in the cohort of patients without HFS and facial palsy. Results: The prevalence of neurovascular contact involving the facial nerve can be as high as 51% in patients asymptomatic for HFS and facial palsy. It is frequently caused by the anterior inferior cerebellar artery and commonly involves the cisternal portion with mild to moderate severity. Conclusions: In asymptomatic patients, the pulsatile neurovascular contact of the intracranial segment of the facial nerve typically occurs at one point, involving the distal portion with milder severity in contrast to patients with HFS. These results in the asymptomatic cohort should be considered when evaluating the candidacy of HFS patients for microvascular decompression.

4.
Nanotechnology ; 35(39)2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38861969

RESUMO

A novel two-dimensional (2D) half-HeuslerZrNiSn nanosheetfor thermoelectric applications was designed from bulk half-Heusler ZrNiSn through first-principles calculation. Investigation of bulk half-Heusler and 2D nanosheet ZrNiSn was performed with the Quantum Espresso code based on a density functional theory plane wave basis set. Electronic band structure and density of states calculations were used to study the confinement effects. On moving from bulk to 2D a change of structure is observed from face-centered cubic to trigonal due to confinement effects. The semiconducting nature of bulk ZrNiSn is undisturbed while moving to a 2D nanosheet; however, the band gap is widened from 0.46 to 1.3 eV due to the restricted motion of electrons in one direction. Compared with bulk ZrNiSn, 2D nanosheets were found to have a higher Seebeck coefficient a lower thermal conductivity and higher figure of merit, which makes 2D ZrNiSn nanosheets suitable for thermoelectric applications. Atomically thin 2D structures with a flat surface have the potential to form van der Waals heterojunctions, paving the way for device fabrication at the nanoscale level.

5.
Mol Microbiol ; 121(6): 1245-1261, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38750617

RESUMO

Linear, unbranched (1,3;1,4)-ß-glucans (mixed-linkage glucans or MLGs) are commonly found in the cell walls of grasses, but have also been detected in basal land plants, algae, fungi and bacteria. Here we show that two family GT2 glycosyltransferases from the Gram-positive bacterium Sarcina ventriculi are capable of synthesizing MLGs. Immunotransmission electron microscopy demonstrates that MLG is secreted as an exopolysaccharide, where it may play a role in organizing individual cells into packets that are characteristic of Sarcina species. Heterologous expression of these two genes shows that they are capable of producing MLGs in planta, including an MLG that is chemically identical to the MLG secreted from S. ventriculi cells but which has regularly spaced (1,3)-ß-linkages in a structure not reported previously for MLGs. The tandemly arranged, paralogous pair of genes are designated SvBmlgs1 and SvBmlgs2. The data indicate that MLG synthases have evolved different enzymic mechanisms for the incorporation of (1,3)-ß- and (1,4)-ß-glucosyl residues into a single polysaccharide chain. Amino acid variants associated with the evolutionary switch from (1,4)-ß-glucan (cellulose) to MLG synthesis have been identified in the active site regions of the enzymes. The presence of MLG synthesis in bacteria could prove valuable for large-scale production of MLG for medical, food and beverage applications.


Assuntos
Glicosiltransferases , beta-Glucanas , Glicosiltransferases/metabolismo , Glicosiltransferases/genética , beta-Glucanas/metabolismo , Parede Celular/metabolismo , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Polissacarídeos Bacterianos/biossíntese , Polissacarídeos Bacterianos/metabolismo
6.
J Biochem Mol Toxicol ; 38(6): e23745, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38769715

RESUMO

Extensive use of heavy metals has posed a serious concern for ecosystem and human too. Heavy metals are toxic in nature and their accumulation in human body causes serious disorders such as neurological disease, cardiac disease, gastrointestinal problems, skin disorders, reproductive disease, lungs diseases, and so on. Furthermore, heavy metals not only affect the human health but also have a negative impact on the economy. In the current review, we have elaborated the impact of heavy metal exposure on human health and socioeconomics. We have discussed the molecular mechanism involved in the heavy metal-induced human disorders such as oxidative stress, neuroinflammation, and protein misfolding. Finally, we discussed the preventive measure and treatment strategy that could counter the negative effects of heavy metal intoxications. In conclusion, there is a substantial correlation between heavy metals and the onset and advancement of several health issues. Chelation treatment could be a useful tactic to lessen the toxic metal load and the difficulties that come with it.


Assuntos
Metais Pesados , Humanos , Metais Pesados/toxicidade , Exposição Ambiental/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Animais , Intoxicação por Metais Pesados/diagnóstico , Intoxicação por Metais Pesados/prevenção & controle , Intoxicação por Metais Pesados/terapia
7.
J Exp Bot ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38652155

RESUMO

Medicinal plants are integral to traditional medicine systems world-wide, being pivotal for human health. Harvesting plant material from natural environments, however, has led to species scarcity, prompting action to develop cultivation solutions that also aid conservation efforts. Biotechnological tools, specifically plant tissue culture and genetic transformation, offer solutions for sustainable, large-scale production and enhanced yield of valuable biomolecules. While these techniques are instrumental to the development of the medicinal plant industry, the challenge of inherent regeneration recalcitrance in some species to in vitro cultivation hampers these efforts. This review examines the strategies for overcoming recalcitrance in medicinal plants using a holistic approach, emphasising the meticulous choice of explants, e.g. embryonic/meristematic tissues; plant growth regulators, e.g. synthetic cytokinins; and use of novel regeneration-enabling methods to deliver morphogenic genes e.g. GRF/GIF chimeras and nanoparticles, which have been shown to contribute to overcoming recalcitrance barriers in agriculture crops. Furthermore, it highlights the benefit of cost-effective genomic technologies that enable precise genome editing and the value of integrating data-driven models to address genotype-specific challenges in medicinal plant research. These advances mark a progressive step towards a future where medicinal plant cultivation is not only more efficient and predictable but also inherently sustainable, ensuring the continued availability and exploitation of these important plants for current and future generations.

8.
J Am Psychiatr Nurses Assoc ; 30(3): 456-464, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38581184

RESUMO

BACKGROUND: Substance use disorder (SUD) is a chronic illness impacting more than 59 million Americans last year. Opioid use disorder (OUD) is a subset of SUD. The literature supports that healthcare providers frequently stigmatize patients with OUD. Individuals with OUD often feel shame associated with their disorder. Shame has been associated with maladaptive and avoidant behaviors. AIM: The aim of this qualitative descriptive study was to examine and describe the experiences of shame and health-seeking behaviors in individuals with OUD. METHODS: A qualitative exploratory design using focus groups with individuals in treatment for OUD was used to identify the issue of shame and its relationship to health-seeking behaviors. RESULTS: A systematic content analysis of discussions with 11 participants in four focus groups revealed four major themes and associated subthemes: Avoidance of Preventive Care (belief providers are judgmental); the Hidden Disorder (keeping secrets); Constraints of Shame (justification for the continuation of drug usage); and Trust in MOUD (Medication for Opioid Use Disorder) Providers. The feeling of shame leads to a reluctance to engage in health-promoting actions, such as scheduling appointments with primary care providers and dentists. CONCLUSION: Healthcare practitioners must prioritize providing a safe, nonstigmatizing environment for patients with SUD/OUD. This includes establishing trust and rapport, providing education, collaboration with psychiatric mental health specialists and other healthcare providers, and the offering support and resources to help patients manage their condition to achieve optimal health outcomes.


Assuntos
Grupos Focais , Transtornos Relacionados ao Uso de Opioides , Aceitação pelo Paciente de Cuidados de Saúde , Pesquisa Qualitativa , Vergonha , Humanos , Transtornos Relacionados ao Uso de Opioides/psicologia , Masculino , Feminino , Adulto , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Pessoa de Meia-Idade , Estigma Social
9.
Cureus ; 16(3): e56073, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38618418

RESUMO

BACKGROUND: The success of any dental prosthesis depends on aesthetics and function. A proper shade selection is a prime requisite for providing aesthetics to dental patients. PURPOSE: This study aims to compare the photographic method of shade selection with that of a digital spectrophotometer. MATERIALS AND METHODS: The study included 50 participants. The primary inclusion criterion was the presence of the maxillary left central incisor without a history of restorative or endodontic procedures. The shade of the left maxillary central incisor was determined using the VITA Easyshade V spectrophotometer (VITA Zahnfabrik, BadSäckingen, Germany) and the digital photography method for all the selected participants. The CIELAB colour space utilizes three values (L*, a*, and b*) to objectively measure colour. While the digital photography approach used Adobe Photoshop software (Adobe Systems Incorporated, San Jose, CA) to report solely the L*, a*, and b* values, the spectrophotometer reported the L*, a*, and b* values along with the actual shade. After obtaining the values of L*, a*, and b*, ΔE, which is their difference, was calculated using a standard formula. Statistical analysis was carried out by using Student's t-test and proportion z-test. RESULTS: When the comparison of the L*a*b* values was done, Student's t-test showed similar (P>0.05) L(t=0.16, P=0.872), a (t=0.52, P=0.607), and b (t=0.23, P=0.820) values between the two groups; that is, they did not differ significantly or showed perfect matching. There was agreement (ΔE≤2) in 42 (84.0%) cases and disagreement (ΔE>2) in eight (16.0%) cases. The proportion z-test showed an agreement of 84.0%, which was statistically highly significant (z=20.44, P<0.001). CONCLUSION: The true shade of the teeth can be depicted using standardized digital images.

12.
ISME J ; 18(1)2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38366029

RESUMO

Wildfires affect soils in multiple ways, leading to numerous challenges for colonizing microorganisms. Although it is thought that fire-adapted microorganisms lie at the forefront of postfire ecosystem recovery, the specific strategies that these organisms use to thrive in burned soils remain largely unknown. Through bioactivity screening of bacterial isolates from burned soils, we discovered that several Paraburkholderia spp. isolates produced a set of unusual rhamnolipid surfactants with a natural methyl ester modification. These rhamnolipid methyl esters (RLMEs) exhibited enhanced antimicrobial activity against other postfire microbial isolates, including pyrophilous Pyronema fungi and Amycolatopsis bacteria, compared to the typical rhamnolipids made by organisms such as Pseudomonas spp. RLMEs also showed enhanced surfactant properties and facilitated bacterial motility on agar surfaces. In vitro assays further demonstrated that RLMEs improved aqueous solubilization of polycyclic aromatic hydrocarbons, which are potential carbon sources found in char. Identification of the rhamnolipid biosynthesis genes in the postfire isolate, Paraburkholderia kirstenboschensis str. F3, led to the discovery of rhlM, whose gene product is responsible for the unique methylation of rhamnolipid substrates. RhlM is the first characterized bacterial representative of a large class of integral membrane methyltransferases that are widespread in bacteria. These results indicate multiple roles for RLMEs in the postfire lifestyle of Paraburkholderia isolates, including enhanced dispersal, solubilization of potential nutrients, and inhibition of competitors. Our findings shed new light on the chemical adaptations that bacteria employ to navigate, grow, and outcompete other soil community members in postfire environments.


Assuntos
Antibacterianos , Incêndios , Glicolipídeos , Microbiologia do Solo , Tensoativos , Tensoativos/metabolismo , Glicolipídeos/metabolismo , Antibacterianos/farmacologia , Antibacterianos/metabolismo , Burkholderiales/metabolismo , Burkholderiales/genética , Adaptação Fisiológica , Hidrocarbonetos Policíclicos Aromáticos/metabolismo
13.
J Perinatol ; 44(8): 1087-1097, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38245657

RESUMO

Evidence on effectiveness and safety of sirolimus in congenital vascular anomalies in infancy is lacking. We aim to systematically review the efficacy and safety of sirolimus in treating congenital VA in infancy. We searched for and included all studies evaluating sirolimus for VA in the first year of life. The primary outcome was effectiveness. The secondary outcome was safety. We included 84 case series and reports (172 participants). Sirolimus decreased the size of the VA in >50% of participants, most of whom had minor transient side effects, and 27% had no adverse effects at all. When categorized by age (<1 month, 1-5 months and 6-12 months), the effectiveness was similar in all age groups. Available evidence suggests that sirolimus is effective and well tolerated. The effectiveness of sirolimus should be evaluated in a well-designed randomized controlled or observational studies.


Assuntos
Sirolimo , Malformações Vasculares , Humanos , Sirolimo/uso terapêutico , Sirolimo/efeitos adversos , Lactente , Malformações Vasculares/tratamento farmacológico , Recém-Nascido
14.
Nurse Educ ; 49(2): E80-E82, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37537710

RESUMO

BACKGROUND: Engaging in scholarship is a critical component of being an effective nurse educator and can have a significant impact on the nursing profession as a whole. PROBLEM: Nurse educators are expected to teach and simultaneously engage in scholarship. Barriers include heavy workloads and lack of resources including faculty mentors. Evidence supports that organized work groups support success. APPROACH: Members of the Quality and Safety Education for Nurses (QSEN) Academic Task force were queried about scholarly activity as a result of engagement with fellow task force members. OUTCOMES: Scholarly outcomes included numerous peer-reviewed publications, teaching tips, presentations, and grants. CONCLUSION: Participating in national work groups can serve as a platform for fostering a community of scholars to make meaningful contributions to the profession.


Assuntos
Sucesso Acadêmico , Humanos , Pesquisa em Educação em Enfermagem , Docentes de Enfermagem , Bolsas de Estudo , Mentores
15.
Stem Cell Reports ; 18(12): 2418-2433, 2023 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-37995703

RESUMO

Although adult subependymal zone (SEZ) neural stem cells mostly generate GABAergic interneurons, a small progenitor population expresses the proneural gene Neurog2 and produces glutamatergic neurons. Here, we determined whether Neurog2 could respecify SEZ neural stem cells and their progeny toward a glutamatergic fate. Retrovirus-mediated expression of Neurog2 induced the glutamatergic lineage markers TBR2 and TBR1 in cultured SEZ progenitors, which differentiated into functional glutamatergic neurons. Likewise, Neurog2-transduced SEZ progenitors acquired glutamatergic neuron hallmarks in vivo. Intriguingly, they failed to migrate toward the olfactory bulb and instead differentiated within the SEZ or the adjacent striatum, where they received connections from local neurons, as indicated by rabies virus-mediated monosynaptic tracing. In contrast, lentivirus-mediated expression of Neurog2 failed to reprogram early SEZ neurons, which maintained GABAergic identity and migrated to the olfactory bulb. Our data show that NEUROG2 can program SEZ progenitors toward a glutamatergic identity but fails to reprogram their neuronal progeny.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos , Células-Tronco Neurais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Neurônios/metabolismo , Células-Tronco Neurais/metabolismo , Diferenciação Celular , Bulbo Olfatório/metabolismo , Neurogênese/fisiologia
16.
Plant Physiol ; 194(1): 168-189, 2023 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-37862163

RESUMO

Oat (Avena sativa) is a cereal crop whose grains are rich in (1,3;1,4)-ß-D-glucan (mixed-linkage glucan or MLG), a soluble dietary fiber. In our study, we analyzed oat endosperm development in 2 Canadian varieties with differing MLG content and nutritional value. We confirmed that oat undergoes a nuclear type of endosperm development but with a shorter cellularization phase than barley (Hordeum vulgare). Callose and cellulose were the first polysaccharides to be detected in the early anticlinal cell walls at 11 days postemergence (DPE) of the panicle. Other polysaccharides such as heteromannan and homogalacturonan were deposited early in cellularization around 12 DPE after the first periclinal walls are laid down. In contrast to barley, heteroxylan deposition coincided with completion of cellularization and was detected from 14 DPE but was only detectable after demasking. Notably, MLG was the last polysaccharide to be laid down at 18 DPE within the differentiation phase, rather than during cellularization. In addition, differences in the spatiotemporal patterning of MLG were also observed between the 2 varieties. The lower MLG-containing cultivar AC Morgan (3.5% w/w groats) was marked by the presence of a discontinuous pattern of MLG labeling, while labeling in the same walls in CDC Morrison (5.6% w/w groats) was mostly even and continuous. RNA-sequencing analysis revealed higher transcript levels of multiple MLG biosynthetic cellulose synthase-like F (CSLF) and CSLH genes during grain development in CDC Morrison compared with AC Morgan that likely contributes to the increased abundance of MLG at maturity in CDC Morrison. CDC Morrison was also observed to have smaller endosperm cells with thicker walls than AC Morgan from cellularization onwards, suggesting the processes controlling cell size and shape are established early in development. This study has highlighted that the molecular processes influencing MLG content and deposition are more complex than previously imagined.


Assuntos
Endosperma , Hordeum , Endosperma/metabolismo , Avena , Grão Comestível/genética , Grão Comestível/metabolismo , Canadá , Polissacarídeos/metabolismo , Glucanos/metabolismo , Hordeum/genética , Hordeum/metabolismo , Parede Celular/metabolismo
17.
Dev Cell ; 58(23): 2641-2651.e6, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-37890489

RESUMO

Choroid plexuses (ChPs) produce cerebrospinal fluid and sense non-cell-autonomous stimuli to control the homeostasis of the central nervous system. They are mainly composed of epithelial multiciliated cells, whose development and function are still controversial. We have thus characterized the stepwise order of mammalian ChP epithelia cilia formation using a combination of super-resolution-microscopy approaches and mouse genetics. We show that ChP ciliated cells are built embryonically on a treadmill of spatiotemporally regulated events, starting with atypical centriole amplification and ending with the construction of nodal-like 9+0 cilia, characterized by both primary and motile features. ChP cilia undergo axoneme resorption at early postnatal stages through a microtubule destabilization process controlled by the microtubule-severing enzyme spastin and mitigated by polyglutamylation levels. Notably, this phenotype is preserved in humans, suggesting a conserved ciliary resorption mechanism in mammals.


Assuntos
Axonema , Cílios , Humanos , Camundongos , Animais , Cílios/fisiologia , Células Epiteliais/fisiologia , Epitélio , Corioide , Mamíferos
18.
Environ Microbiol ; 25(11): 2498-2515, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37553729

RESUMO

Prescribed fire is a critical strategy for mitigating the effects of catastrophic wildfires. While the above-ground response to fire has been well-documented, fewer studies have addressed the effect of prescribed fire on soil microorganisms. To understand how soil microbial communities respond to prescribed fire, we sampled four plots at a high temporal resolution (two burned, two controls), for 17 months, in a mixed conifer forest in northern California, USA. Using amplicon sequencing, we found that prescribed fire significantly altered both fungal and bacterial community structure. We found that most differentially abundant fungal taxa had a positive fold-change, while differentially abundant bacterial taxa generally had a negative fold-change. We tested the null hypothesis that these communities assembled due to neutral processes (i.e., drift and/or dispersal), finding that >90% of taxa fit this neutral prediction. However, a dynamic sub-community composed of burn-associated indicator taxa that were positively differentially abundant was enriched for non-neutral amplicon sequence variants, suggesting assembly via deterministic processes. In synthesizing these results, we identified 15 pyrophilous taxa with a significant and positive response to prescribed burns. Together, these results lay the foundation for building a process-driven understanding of microbial community assembly in the context of the classical disturbance regime of fire.


Assuntos
Incêndios , Traqueófitas , Solo , Florestas , California , Ecossistema
19.
Nurs Sci Q ; 36(3): 240-245, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37309146

RESUMO

There are many nursing scholars who have contributed to nursing knowledge. Dr. Monika Schuler started her career as a cranberry biologist and is now a nurse scholar and educator. Her contributions to nursing knowledge include two new models that contribute to our understanding of nursing professional growth: (1) the reflection, feedback, and restructuring model for role development in nursing and (2) the substance use disorder nursing attitude model. Dr. Schuler is working with colleagues toward developing an understanding of how nursing experiences inform their role development. In this scholarly dialogue, Dr. Schuler shares her path to nursing scholarship and her recent contributions to nursing knowledge development.


Assuntos
Vaccinium macrocarpon , Feminino , Humanos , Pessoal de Saúde , Modelos de Enfermagem
20.
Plants (Basel) ; 12(7)2023 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-37050054

RESUMO

Plant proteins that are secreted without a classical signal peptide leader sequence are termed leaderless secretory proteins (LSPs) and are implicated in both plant development and (a)biotic stress responses. In plant proteomics experimental workflows, identification of LSPs is hindered by the possibility of contamination from other subcellar compartments upon purification of the secretome. Applying machine learning algorithms to predict LSPs in plants is also challenging due to the rarity of experimentally validated examples for training purposes. This work attempts to address this issue by establishing criteria for identifying potential plant LSPs based on experimental observations and training random forest classifiers on the putative datasets. The resultant plant protein database LSPDB and bioinformatic prediction tools LSPpred and SPLpred are available at lsppred.lspdb.org. The LSPpred and SPLpred modules are internally validated on the training dataset, with false positives controlled at 5%, and are also able to classify the limited number of established plant LSPs (SPLpred (3/4, LSPpred 4/4). Until such time as a larger set of bona fide (independently experimentally validated) LSPs is established using imaging technologies (light/fluorescence/electron microscopy) to confirm sub-cellular location, these tools represent a bridging method for predicting and identifying plant putative LSPs for subsequent experimental validation.

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