Diffraction (X‐ray, neutron and electron) and electron cryo‐microscopy are powerful methods to determine three‐dimensional macromolecular structures, which are required to understand biological ...processes and to develop new therapeutics against diseases. The overall structure‐solution workflow is similar for these techniques, but nuances exist because the properties of the reduced experimental data are different. Software tools for structure determination should therefore be tailored for each method. Phenix is a comprehensive software package for macromolecular structure determination that handles data from any of these techniques. Tasks performed with Phenix include data‐quality assessment, map improvement, model building, the validation/rebuilding/refinement cycle and deposition. Each tool caters to the type of experimental data. The design of Phenix emphasizes the automation of procedures, where possible, to minimize repetitive and time‐consuming manual tasks, while default parameters are chosen to encourage best practice. A graphical user interface provides access to many command‐line features of Phenix and streamlines the transition between programs, project tracking and re‐running of previous tasks.
Recent developments in the Phenix software package are described in the context of macromolecular structure determination using X‐rays, neutrons and electrons.
The Asian citrus psyllid (ACP), Diaphorina citri Kuwayama (Hemiptera: Psyllidae), is an important pest of citrus because it transmits phloem-limited bacteria Candidatus Liberibacter spp., notably Ca. ...L. asiaticus (LAS) associated with huanglongbing (HLB; citrus greening disease), currently considered the world's most serious disease of citrus. Asian citrus psyllid transmits LAS in a persistent manner and, although the rate of LAS transmission by ACP individuals usually is low, HLB can spread rapidly in a citrus grove and the geographic range of the disease is expanding, threatening citrus industries in new areas. Intensive chemical control of ACP is the primary management strategy currently advocated for HLB, but this strategy is costly, unsustainable, and generally ineffective. The scientific community is searching aggressively for solutions to HLB on many fronts, but it could still be years before solutions are found and implemented. Plant resistance to LAS is one area of research being pursued, whereby traits that confer resistance are identified and incorporated into citrus germplasm through conventional or transgenic methods. It remains to be seen if a solution to HLB can be found that specifically targets ACP, but research on ACP has been stepped up in a number of areas, notably on ACP-LAS-plant interactions, on host plant resistance to ACP, and on molecular methods of silencing ACP genes to induce mortality or to block its ability to transmit HLB-causing bacteria. Advancements in these and other research areas may depend greatly on a better understanding of basic ACP biology and vector-pathogen-host plant interactions at the molecular, cellular, and community levels. Here we present an updated review of ACP and HLB with an emphasis on the problem in Florida.
Increased pro‐inflammatory cytokine levels and proliferation of activated microglia have been found in Parkinson's disease (PD) patients and animal models of PD, suggesting that targeting of the ...microglial inflammatory response may result in neuroprotection in PD. Microglial proliferation is regulated by many factors, but colony stimulating factor‐1 receptor (CSF1R) has emerged as a primary factor. Using data mining techniques on existing microarray data, we found that mRNA expression of the CSF1R ligand, CSF‐1, is increased in the brain of PD patients compared to controls. In two different neurotoxic mouse models of PD, acute MPTP and sub‐chronic LPS treatment, mRNA and protein levels of CSF1R and CSF‐1 were significantly increased. Treatment with the CSF1R inhibitor GW2580 significantly attenuated MPTP‐induced CSF1R activation and Iba1‐positive cell proliferation, without a reduction of the basal Iba1‐positive population in the substantia nigra. GW2580 treatment also significantly decreased mRNA levels of pro‐inflammatory factors, without alteration of anti‐inflammatory mediators, and significantly attenuated the MPTP‐induced loss of dopamine neurons and motor behavioral deficits. Importantly, these effects were observed in the absence of overt microglial depletion, suggesting that targeting CSF1R signaling may be a viable neuroprotective strategy in PD that disrupts pro‐inflammatory signaling, but maintains the beneficial effects of microglia.
Neuroinflammation is one of the hallmarks of neurodegenerative diseases, such as Parkinson's disease (PD). Activation of glial cells, including microglia and astrocytes, is a characteristic of the ...inflammatory response. Glycoprotein non-metastatic melanoma protein B (GPNMB) is a transmembrane glycoprotein that releases a soluble signaling peptide when cleaved by ADAM10 or other extracellular proteases. GPNMB has demonstrated a neuroprotective role in animal models of ALS and ischemia. However, the mechanism of this protection has not been well established. CD44 is a receptor expressed on astrocytes that can bind GPNMB, and CD44 activation has been demonstrated to reduce NFκB activation and subsequent inflammatory responses in macrophages. GPNMB signaling has not been investigated in models of PD or specifically in astrocytes. More recently, genetic studies have linked polymorphisms in GPNMB with risk for PD. Therefore, it is important to understand the role this signaling protein plays in PD.
We used data mining techniques to evaluate mRNA expression of GPNMB and its receptor CD44 in the substantia nigra of PD and control brains. Immunofluorescence and qPCR techniques were used to assess GPNMB and CD44 levels in mice treated with MPTP. In vitro experiments utilized the immortalized mouse astrocyte cell line IMA2.1 and purified primary mouse astrocytes. The effects of recombinant GPNMB on cytokine-induced astrocyte activation was determined by qPCR, immunofluorescence, and measurement of nitric oxide and reactive oxygen production.
Increased GPNMB and CD44 expression was observed in the substantia nigra of human PD brains and in GFAP-positive astrocytes in an animal model of PD. GPNMB treatment attenuated cytokine-induced levels of inducible nitric oxide synthase, nitric oxide, reactive oxygen species, and the inflammatory cytokine IL-6 in an astrocyte cell line and primary mouse astrocytes. Using primary mouse astrocytes from CD44 knockout mice, we found that the anti-inflammatory effects of GPNMB are CD44-mediated.
These results demonstrate that GPNMB may exert its neuroprotective effect through reducing astrocyte-mediated neuroinflammation in a CD44-dependent manner, providing novel mechanistic insight into the neuroprotective properties of GPNMB.
Hibiscus species (Family: Malvaceae) have long been used in traditional medicine to treat a variety of maladies such as abscesses, bilious conditions, cancer, cough, fatigue, gastrointestinal ...discomfort, fever, veisalgia, cardiovascular disorders, neurosis, scurvy, and urinary tract disorders. Its antioxidants have the capacity to destroy free radicals that damage cells and increase risk of inflammatory conditions such as metabolic syndrome, cancer, and cardiovascular disease.
This review synthesizes findings from animal studies and clinical trials to assess effectiveness of hibiscus for treating biomarkers of metabolic syndrome including hyperglycemia, hypertriglyceridemia, low high-density lipoprotein, obesity, and hypertension.
We searched for 12 edible species of hibiscus in the Google Scholar database. Each scientific name of these species, their common names and their edible plant parts were searched in conjunction with fourteen key words associated with metabolic syndrome. A total of 68 articles met all inclusion criteria for this review, including 18 that tested human subjects, 48 that tested other animals, one that tested humans and other animals, and one that did not specify.
Hibiscus often improved blood glucose, total cholesterol, high-density lipoprotein cholesterol, triglycerides, blood pressure, weight, lipid absorption and oxidation of fatty acids within vital organs around the abdominal cavity. Higher doses led to greater benefits in some cases, especially for body mass of animals, but lower doses were often equally effective. Hibiscus was often equally or more effective than pharmaceuticals in improving some biomarkers of metabolic syndrome, especially blood glucose and insulin sensitivity.
Hibiscus shows great promise for improving biomarkers of metabolic syndrome, but there are limitations that need to be addressed by future work, including increasing the number and size of human clinical trials, expanding human trials to include people from a greater diversity of ethnicities, taking into account the health and physical activity of human participants, investigating the influence of growing conditions and extraction/preparation techniques on nutrients in hibiscus, comparing the efficacy of several plant parts and plant products of hibiscus to a reference control group within the same experiment, incorporating rigorous statistical analysis of treatments and investigating the influence of dosage.
Display omitted
COVID-19 has taken its toll on citizens in all 50 states of the United States. The United States (U.S.) leads the world with 30,291,863 confirmed reported cases and 549,664 deaths as of March 29, ...2021 compared to globally confirmed cases at 127,442,926 and 2,787,915 deaths as of March 29, 2021. The U.S. federal government primarily left the response to the virus to individual states, and each implemented varying measures designed to protect health of citizens and the state's economic well-being. Unintended consequences of the virus and measures to stop its spread may include decreased physical activity and exercise, shifting access and consumption of food, and lower quality-of-life. Therefore, our primary goal was to quantify the impact of COVID-19 on health and well-being by measuring changes in physical activity, mental health-quality of life, food security and nutrition in adults ages 40 and older. We believed shifts in health behaviors would be more prevalent in minorities, less educated, lower socio-economic status, older adults, and those with underlying health conditions, so a secondary goal was to determine the impact of COVID-19 on these sub-populations.
We conducted an online survey with 9969 adults 40 years and older between 9 August and 15 September 2020 in urban areas across the four U.S. census regions. The survey included questions about demographic variables, pre-existing health conditions, physical activity, access to food, quality-of-life, and nutritional food status and asked participants to respond with information from pre-pandemic and pandemic conditions. We used paired-sample t-tests to detect changes in variables after the start of the pandemic and Cohen's d to determine effect sizes.
Our main findings showed a decrease in physical activity since the onset of COVID-19 for minorities and non-minorities. Food security also slightly increased for minorities during the pandemic, but we found no other changes in food security, quality-of-life indicators, or nutritional status of those who responded to this survey.
It is concerning that physical activity declined. Such activity helps maintain physical and mental health, and it is also an important time to socialize for many older adults. In many ways, our data indicate that the older adult population in U.S. cities may be more resilient than expected during the pandemic. However, the pandemic could have negative impacts that we did not detect, either due to the survey instrument or the timing of our survey, so the health and well-being of older adults should continue to be monitored in order to mitigate potential negative impacts.
Electrically evoked frequency-following responses (eFFRs) provide insight in the phase-locking ability of brainstem of cochlear-implant (CI) users. eFFRs can potentially be used to gain insight in ...the individual differences in the biological limitation on temporal encoding of the electrically stimulated auditory pathway, which can be inherent to the electrical stimulation itself and/or the degenerative processes associated with hearing loss. One of the major challenge of measuring eFFRs in CI users is the process of isolating the stimulation artifact from the neural response, as both the response and the artifact overlap in time and have similar frequency characteristics. Here we introduce a new artifact removal method based on template subtraction that successfully removes the stimulation artifacts from the recordings when CI users are stimulated with pulse trains from 128 to 300 pulses per second in a monopolar configuration. Our results show that, although artifact removal was successful in all CI users, the phase-locking ability of the brainstem to the different pulse rates, as assessed with the eFFR differed substantially across participants. These results show that the eFFR can be measured, free from artifacts, in CI users and that they can be used to gain insight in individual differences in temporal processing of the electrically stimulated auditory pathway.
Urban agriculture is increasingly valued as a strategy for improving quality of life in cities, but urban growers face challenges and often lack coordinated support from governments and the ...agricultural industry. We surveyed urban growers through an online survey, primarily in the Northeastern United States, to develop a profile of growers and associated organizations, assess the current state of urban agriculture, and determine how universities could help meet their needs. A total of 394 respondents completed the survey and most urban growers were white (non-Hispanic) and younger than 45 years old. Women and men were in almost equal proportion. Urban growers were well-educated, but most did not receive a degree in agriculture. Urban agriculture in our study area was dominated by relatively small non-profit organizations and home and community gardens were the most common types of organizations. Urban agricultural organizations want to improve environmental sustainability and socio-cultural conditions through food access and security, regardless of their tax status. Urban growers face diverse barriers and challenges and the most ubiquitous barriers and challenges reported by respondents were related to availability of land and long-term access in urban areas. Many respondents received low revenue or were operating at a net loss even though they reported diverse income streams. Respondents need a wide range of training, including in traditional agricultural topics as well as financial management and business trainings. Universities can play a key role in promoting urban agriculture by offering training and research. Workforce development is a large priority among universities, so urban growers should regularly be consulted, and the results shared with career and workforce development professionals and researchers in urban areas to identify training and research that meets the needs of stakeholders.
We review the primary literature to document the incidence of cannibalism among insects that typically are not carnivorous. Most of the cannibalistic species were coleopterans and lepidopterans, and ...the cannibals often were juveniles that aggregate or that overlap in phenology with the egg stage. Cannibalism can be adaptive by improving growth rate, survivorship, vigor, longevity, and fecundity. It also can play an important role in regulating population density and suppressing population outbreaks, stabilizing host plant-insect relationships, and reducing parasitism rates. Cannibalism often was favored by density-dependent factors for herbivores that feed in concealed feeding situations (such as stem borers, leafminers), but also by density-independent factors (such as high ambient temperature) for herbivores that feed in exposed feeding situations.
PDF
