Plants generate effective responses to infection by recognizing both conserved and variable pathogen-encoded molecules. Pathogens deploy virulence effector proteins into host cells, where they ...interact physically with host proteins to modulate defense. We generated an interaction network of plant-pathogen effectors from two pathogens spanning the eukaryote-eubacteria divergence, three classes of "Arabidopsis" immune system proteins, and ∼8000 other "Arabidopsis" proteins. We noted convergence of effectors onto highly interconnected host proteins and indirect, rather than direct, connections between effectors and plant immune receptors. We demonstrated plant immune system functions for 15 of 17 tested host proteins that interact with effectors from both pathogens. Thus, pathogens from different kingdoms deploy independently evolved virulence proteins that interact with a limited set of highly connected cellular hubs to facilitate their diverse life-cycle strategies.
The role of orexin in Parkinson's disease Braun, Alisha; Manavis, Jim; Yamanaka, Akihiro ...
Journal of neuroscience research,
March 2024, 2024-Mar, 2024-03-00, 20240301, Letnik:
102, Številka:
3
Journal Article
Recenzirano
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Emerging evidence has implicated the orexin system in non‐motor pathogenesis of Parkinson's disease. It has also been suggested the orexin system is involved in the modulation of motor control, ...further implicating the orexin system in Parkinson's disease. Parkinson's disease is the second most common neurodegenerative disease with millions of people suffering worldwide with motor and non‐motor symptoms, significantly affecting their quality of life. Treatments are based solely on symptomatic management and no cure currently exists. The orexin system has the potential to be a treatment target in Parkinson's disease, particularly in the non‐motor stage. In this review, the most current evidence on the orexin system in Parkinson's disease and its potential role in motor and non‐motor symptoms of the disease is summarized. This review begins with a brief overview of Parkinson's disease, animal models of the disease, and the orexin system. This leads into discussion of the possible roles of orexin neurons in Parkinson's disease and levels of orexin in the cerebral spinal fluid and plasma in Parkinson's disease and animal models of the disease. The role of orexin is then discussed in relation to symptoms of the disease including motor control, sleep, cognitive impairment, psychological behaviors, and the gastrointestinal system. The neuroprotective effects of orexin are also summarized in preclinical models of the disease.
This review discusses the role of the orexin system in Parkinson's disease. It covers the role of orexin neurons, levels of orexin in the disease, neuroprotective properties of orexin, and the role of orexin in motor and non‐motor symptoms of the disease.
Innovation, creativity, and entrepreneurship are becoming key focus areas for employers looking for the 21st century employee. This means the academic side of the create-a-better-employee ...relationship should adapt the curricula to address this need by including problem-solving and creativity; and, this introduction should occur as early as possible in a student's course of study. This article relates the development and implementation of a problem-based learning (PBL)-modeled class in a business-oriented curriculum designed to help freshman and sophomore students learn about problem-solving and creativity techniques. One learning goal of the class is to have students be able to describe at least five problem-solving methods or activities. Results showed a clear majority-88% of the students satisfied this short-term, course goal. Additional results show observable changes that indicate more long-term learning concerning creativity and problem-solving occurred. Finally, some implications for upper division business curricula are discussed.
After several years of steady decline, syphilis is reemerging globally as a public health hazard, especially among people living with human immunodeficiency virus (HIV). Syphilis resurgence is ...observed mainly in men who have sex with men (MSM), yet other transmission groups are affected too. In this manuscript, we study the factors associated with syphilis incidence in the Swiss HIV cohort study in the era of highly effective antiretrovirals. Using parametric interval censored models with fixed and time-varying covariates, we studied the immunological, behavioral, and treatment-related elements associated with syphilis incidence in 3 transmission groups: MSM, heterosexuals, and intravenous drug users. Syphilis incidence has been increasing annually since 2005, with up to 74 incident cases per 1000 person-years in 2013, with MSM being the population with the highest burden (92% of cases). While antiretroviral treatment (ART) in general did not affect syphilis incidence, nevirapine (NVP) was associated with a lower hazard of syphilis incidence (multivariable hazard ratio 0.5, 95% confidence interval 0.2-1.0). We observed that condomless sex and younger age were associated with higher syphilis incidence. Moreover, time-updated CD4, nadir CD4, and CD8 cell counts were not associated with syphilis incidence. Finally, testing frequency higher than the recommended once a year routine testing was associated with a 2-fold higher risk of acquiring syphilis. Condomless sex is the main driver of syphilis resurgence in the Swiss HIV Cohort study; ART and immune reconstitution provide no protection against syphilis. This entails targeted interventions and frequent screening of high-risk populations. There is no known effect of NVP on syphilis; therefore, further clinical, epidemiological, and microbiological investigation is necessary to validate our observation.
The Patch-seq approach is a powerful variation of the patch-clamp technique that allows for the combined electrophysiological, morphological, and transcriptomic characterization of individual ...neurons. To generate Patch-seq datasets at scale, we identified and refined key factors that contribute to the efficient collection of high-quality data. We developed patch-clamp electrophysiology software with analysis functions specifically designed to automate acquisition with online quality control. We recognized the importance of extracting the nucleus for transcriptomic success and maximizing membrane integrity during nucleus extraction for morphology success. The protocol is generalizable to different species and brain regions, as demonstrated by capturing multimodal data from human and macaque brain slices. The protocol, analysis and acquisition software are compiled at https://githubcom/AllenInstitute/patchseqtools. This resource can be used by individual labs to generate data across diverse mammalian species and that is compatible with large publicly available Patch-seq datasets.
Four pilot-scale treatment process streams (Stream 1 – Conventional treatment (coagulation/flocculation/dual media filtration); Stream 2 – Magnetic ion exchange (MIEX)/Conventional treatment; Stream ...3 – MIEX/Conventional treatment/granular activated carbon (GAC) filtration; Stream 4 – Microfiltration/nanofiltration) were commissioned to compare their effectiveness in producing high quality potable water prior to disinfection. Despite receiving highly variable source water quality throughout the investigation, each stream consistently reduced colour and turbidity to below Australian Drinking Water Guideline levels, with the exception of Stream 1 which was difficult to manage due to the reactive nature of coagulation control. Of particular interest was the bacteriological quality of the treated waters where flow cytometry was shown to be the superior monitoring tool in comparison to the traditional heterotrophic plate count method. Based on removal of total and active bacteria, the treatment process streams were ranked in the order: Stream 4 (average log removal of 2.7) > Stream 2 (average log removal of 2.3) > Stream 3 (average log removal of 1.5) > Stream 1 (average log removal of 1.0). The lower removals in Stream 3 were attributed to bacteria detaching from the GAC filter. Bacterial community analysis revealed that the treatments affected the bacteria present, with the communities in streams incorporating conventional treatment clustering with each other, while the community composition of Stream 4 was very different to those of Streams 1, 2 and 3. MIEX treatment was shown to enhance removal of bacteria due to more efficient flocculation which was validated through the novel application of the photometric dispersion analyser.
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► Removal of bacteria varied between the process streams with log removal values of between 0.9 and 2.7. ► Based on removal of bacteria, the streams were ranked: Stream 4 > Stream 2 > Stream 3 > Stream 1. ► FCM was superior to the HPC method with more definitive comparisons made between the streams. ► DGGE analysis revealed that the community of Stream 4 was very different to those of Streams 1, 2 and 3. ► MIEX enhanced bacterial removal through more efficient coagulation as determined by PDA indices.
Plants are resistant to most microbial species due to nonhost resistance (NHR), providing broad-spectrum and durable immunity. However, the molecular components contributing to NHR are poorly ...characterised. We address the question of whether failure of pathogen effectors to manipulate nonhost plants plays a critical role in NHR. RxLR (Arg-any amino acid-Leu-Arg) effectors from two oomycete pathogens,
, enhanced pathogen infection when expressed in host plants (
and Arabidopsis, respectively) but the same effectors performed poorly in distantly related nonhost pathosystems. Putative target proteins in the host plant potato were identified for 64
. infestans RxLR effectors using yeast 2-hybrid (Y2H) screens. Candidate orthologues of these target proteins in the distantly related non-host plant Arabidopsis were identified and screened using matrix Y2H for interaction with RxLR effectors from both
. infestans and
.
. Few
. infestans effector-target protein interactions were conserved from potato to candidate Arabidopsis target orthologues (cAtOrths). However, there was an enrichment of
.
RxLR effectors interacting with cAtOrths. We expressed the cAtOrth AtPUB33, which unlike its potato orthologue did not interact with
.
effector PiSFI3, in potato and Nicotiana benthamiana. Expression of AtPUB33 significantly reduced
.
colonization in both host plants. Our results provide evidence that failure of pathogen effectors to interact with and/or correctly manipulate target proteins in distantly related non-host plants contributes to NHR. Moreover, exploiting this breakdown in effector-nonhost target interaction, transferring effector target orthologues from non-host to host plants is a strategy to reduce disease.
Despite cancer being a leading comorbidity amongst individuals with HIV, there are limited data assessing cancer trends across different antiretroviral therapy (ART)-eras. We calculated ...age-standardised cancer incidence rates (IRs) from 2006-2021 in two international cohort collaborations (D:A:D and RESPOND). Poisson regression was used to assess temporal trends, adjusted for potential confounders. Amongst 64,937 individuals (31% ART-naïve at baseline) and 490,376 total person-years of follow-up (PYFU), there were 3763 incident cancers (IR 7.7/1000 PYFU 95% CI 7.4, 7.9): 950 AIDS-defining cancers (ADCs), 2813 non-ADCs, 1677 infection-related cancers, 1372 smoking-related cancers, and 719 BMI-related cancers (groups were not mutually exclusive). Age-standardised IRs for overall cancer remained fairly constant over time (8.22/1000 PYFU 7.52, 8.97 in 2006-2007, 7.54 6.59, 8.59 in 2020-2021). The incidence of ADCs (3.23 2.79, 3.72, 0.99 0.67, 1.42) and infection-related cancers (4.83 4.2, 5.41, 2.43 1.90, 3.05) decreased over time, whilst the incidence of non-ADCs (4.99 4.44, 5.58, 6.55 5.67, 7.53), smoking-related cancers (2.38 2.01, 2.79, 3.25 2.63-3.96), and BMI-related cancers (1.07 0.83, 1.37, 1.88 1.42, 2.44) increased. Trends were similar after adjusting for demographics, comorbidities, HIV-related factors, and ART use. These results highlight the need for better prevention strategies to reduce the incidence of NADCs, smoking-, and BMI-related cancers.
Four treatment processes; conventional coagulation, magnetic ion exchange (MIEX)/coagulation, with and without granular activated carbon (GAC), and membrane treatment combining microfiltration (MF) ...and nanofiltration (NF), were operated in parallel using the same source water from the Murray–Darling basin in South Australia. During the two year study, high levels of natural organic matter and turbidity arising from floods affecting the Murray–Darling basin in 2010–2012 challenged the four processes. The comparative study indicated that all four processes could effectively meet basic water quality guidelines of turbidity and colour despite challenging source water quality but that the more advanced treatments improved overall organic and bacterial removal. Interestingly, the high organics and turbidity arising from the floods resulted in improved treatment efficiency for all treatments incorporating coagulation to the extent that, despite flood conditions, treated water quality could remain comparatively constant provided that the process was operated and optimised effectively.
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•Four treatment processes operated in parallel using same source water over 2 years.•Floods in source water caused large variation in organics and turbidity.•All processes met basic water quality guidelines despite source water challenges.•More complex treatments improved overall organic and bacterial removal.•Efficiency of treatments incorporating coagulation improved during floods.
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