Purpose: Strawberries are a high-value crop in the United States due to their increasing demand and nutritional benefits. However, strawberry plants are delicate and sensitive to abiotic and biotic factors and prone to gray mold caused by Botrytis cinerea during harvest and post-harvest operations, leading to significant economic losses. Fungicides are effective but raise concerns about residues and the evolution of fungal resistance, limiting their use. Hence, developing alternative approaches is critical for improving the strawberry plant's resilience and solutions to combat gray mold fungus. Methods: To assess the potassium silicate efficacy on agronomic traits, two strawberry cultivars (Flavorfest and Rutgers ScarletTM) growing under high tunnel conditions were foliar sprayed with different doses (0, 2, 3, and 4mL per gallon of water) in five applications in the fall of 2018 as well as in the spring of 2019. Silica accumulation in the plant samples was determined using Scanning Electron Microscope images coupled with an Energy Dispersive Spectrometer (SEM-EDS) analysis and spectrophotometer method. An in-vitro experiment was used to determine antifungal activity against B. cinerea. Results: Strawberry leaf samples treated with 2 mL per gallon had higher silica concentrations and phytolith production, which strengthened the aerial parts, reduced translocation to roots, and significantly boosted plant width and marketable yield compared to other treatments. Furthermore, treatment with 2 mL potassium silicate significantly reduced the growth of the B. cinerea. Conclusion: Our findings suggest that potassium silicate provides potential options to improve the agronomic traits in strawberries and preventative measures against B. cinerea.

Parkinson’s disease (PD) is a progressive neurodegenerative motor disorder without an available therapeutic to halt the formation of Lewy bodies for preventing dopaminergic neuronal loss in the nigrostriatal pathway. Since oxidative-stress-mediated damage has been commonly reported as one of the main pathological mechanisms in PD, we assessed the efficacy of a novel NOX inhibitor from AptaBio Therapeutics (C-6) in dopaminergic cells and PD mouse models. The compound reduced the cytotoxicity and enhanced the cell viability at various concentrations against MPP+ and α-synuclein preformed fibrils (PFFs). Further, the levels of ROS and protein aggregation were significantly reduced at the optimal concentration (1 µM). Using two different mouse models, we gavaged C-6 at two different doses to the PD sign-displaying transgenic mice for 2 weeks and stereotaxically PFF-injected mice for 5 weeks. Our results demonstrated that both C-6-treated mouse models showed alleviated motor deficits in pole test, hindlimb clasping, crossbeam, rotarod, grooming, and nesting analyses. We also confirmed that the compound treatment reduced the levels of protein aggregation, along with phosphorylated-α-synuclein, in the striatum and ventral midbrain and further dopaminergic neuronal loss. Taken together, our results strongly suggest that NOX inhibition can be a potential therapeutic target for PD.

Organ-on-a-chip devices that mimic in vivo physiology have the potential to identify effects of chemical and drug exposure in early preclinical stages of drug development while relying less heavily on animal models. We designed a hydrogel rat nerve-on-a-chip (RNoaC) construct that promotes axon growth analogous to mature nerve anatomy and is the first 3D in vitro model to collect electrophysiological and histomorphic metrics to assess in vivo pathophysiology. Here we culture embryonic rat dorsal root ganglia (DRG) in the construct to demonstrate its potential to screen for implications of nerve dysfunction in chemotherapy-induced peripheral neuropathy (CIPN). RNoaC constructs containing DRG explants from E15 rat pups were exposed to the chemotherapeutics bortezomib, oxaliplatin, paclitaxel or vincristine for 7 days. Then, axons were electrically stimulated to collect nerve conduction velocity (NCV) and peak amplitude (AMP), which are clinical electrophysiological metrics indicative of healthy or diseased populations. All chemotherapeutics decreased NCV and AMP in a concentration-dependent manner. At high drug concentrations, NCV and AMP were 10-60% lower than control values. Histopathological analysis revealed hallmarks of peripheral neuropathy. IC50 values calculated from concentration-response curves indicate that the significant decrease in function occurred before a decrease in viability. Our data suggest that electrophysiology recordings collected from our RNoaC platform can closely track subtle pathological changes in nerve function. The ability to collect clinically relevant data from RNoaC suggests it can be an effective tool for in vitro preclinical screening for peripheral neuropathy.

Blueberries (Vaccinium spp.) are highly vulnerable to changing climatic conditions, especially increasing temperatures. To gain insight into mechanisms underpinning the response to heat stress, two blueberry species were subjected to heat stress for 6 and 9 h at 45 °C, and leaf samples were used to study the morpho-physiological and transcriptomic changes. As compared with Vaccinium corymbosum, Vaccinium darrowii exhibited thermal stress adaptation features such as small leaf size, parallel leaf orientation, waxy leaf coating, increased stomatal surface area, and stomatal closure. RNAseq analysis yielded ~135 million reads and identified 8305 differentially expressed genes (DEGs) during heat stress against the control samples. In V. corymbosum, 2861 and 4565 genes were differentially expressed at 6 and 9 h of heat stress, whereas in V. darrowii, 2516 and 3072 DEGs were differentially expressed at 6 and 9 h, respectively. Among the pathways, the protein processing in the endoplasmic reticulum (ER) was the highly enriched pathway in both the species: however, certain metabolic, fatty acid, photosynthesis-related, peroxisomal, and circadian rhythm pathways were enriched differently among the species. KEGG enrichment analysis of the DEGs revealed important biosynthesis and metabolic pathways crucial in response to heat stress. The GO terms enriched in both the species under heat stress were similar, but more DEGs were enriched for GO terms in V. darrowii than the V. corymbosum. Together, these results elucidate the differential response of morpho-physiological and molecular mechanisms used by both the blueberry species under heat stress, and help in understanding the complex mechanisms involved in heat stress tolerance.

Prostate cancer is the most common type of solid-organ cancer in men. Early detection and treatment with radical prostatectomy has improved cancer-specific survival but is associated with penile shortening and erectile dysfunction. Penile traction therapy (PTT) has been shown to increase penile length prior to penile prosthesis placement, and there is preliminary data suggesting that it improves erectile function in patients with Peyronie’s Disease.

Small ubiquitin-like modifier (SUMO) is a widespread regulatory mechanism of post-translational modification (PTM) that induces rapid and reversible changes in protein function and stability. Using SUMO conjugase Ubc9-overexpressing or knock-down cells in Parkinson's disease (PD) models, we demonstrate that SUMOylation protects dopaminergic cells against MPP+ or preformed fibrils (PFFs) of α-synuclein (α-syn)-induced toxicities in cell viability and cytotoxicity assays. In the mechanism of protection, Ubc9 overexpression significantly suppressed the MPP+ or PFF-induced reactive oxygen species (ROS) generation, while Ubc9-RNAi enhanced the toxicity-induced ROS production. Further, PFF-mediated protein aggregation was exacerbated by Ubc9-RNAi in thioflavin T staining, compared with NC1 controls. In cycloheximide (Chx)-based protein stability assays, higher protein level of α-syn was identified in Ubc9-enhanced green fluorescent protein (EGFP) than in EGFP cells. Since there was no difference in endogenous mRNA levels of α-syn between Ubc9 and EGFP cells in quantitative real-time PCR (qRT-PCR), we assessed the mechanisms of SUMO-mediated delayed α-syn degradation via MG132, proteasomal inhibitor, and PMA, lysosomal degradation inducer. Ubc9-mediated SUMOylated α-syn avoided PMA-induced lysosomal degradation because of its high solubility. Our results suggest that Ubc9 enhances the levels of SUMO1 and ubiquitin on α-syn and interrupts SUMO1 removal from α-syn. In immunohistochemistry, dopaminergic axon tips in the striatum and cell bodies in the substantia nigra from Ubc9-overexpressing transgenic mice were protected from MPTP toxicities compared with wild-type (WT) siblings. Our results support that SUMOylation can be a regulatory target to protect dopaminergic neurons from oxidative stress and protein aggregation, with the implication that high levels of SUMOylation in dopaminergic neurons can prevent the pathologic progression of PD.

Aim Marked neutrophilia and omphalitis in an infant resulted in the diagnosis of the first case of leukocyte adhesion deficiency type 1 (LAD1) in Ireland. Diagnosis LAD1 requires specific molecular diagnostics for its correct identification. Results Early identification of this disorder allowed for rapid referral for haemotopoeitic stem cell transplant which has resulted in an excellent outcome for this patient. Conclusion The identification of a previously unknown ITGB2 mutation resulting in LAD1 in Ireland should alert physicians to the diagnostic possibility of this extremely rare disorder.

We demonstrate that time-resolved second harmonic (SH) light scattering, when applied as an imaging modality, can be used to spatially resolve the adsorption and transport rates of molecules diffusing across the membrane in a living cell. As a representative example, we measure the passive transport of the amphiphilic ion, malachite green, across the plasma membrane in living human dermal fibroblast cells. Analysis of the time-resolved SH images reveals that membrane regions, which appear to be enduring higher stress, exhibit slower transport rates. It is proposed that this stress-transport relation may be a result of local enrichment of membrane rigidifiers as part of a response to maintain membrane integrity under strain.

The dopamine transporter (DAT) is a plasma membrane protein responsible for the uptake of released dopamine back to the presynaptic terminal and ending dopamine neurotransmission. The DAT is the molecular target for cocaine and amphetamine as well as a number of pathological conditions including autism spectrum disorders, attention-deficit hyperactivity disorder (ADHD), dopamine transporter deficiency syndrome (DTDS), and Parkinson’s disease. The DAT uptake capacity is dependent on its level in the plasma membrane. In vitro studies show that DAT functional expression is regulated by a balance of endocytosis, recycling, and lysosomal degradation. However, recent reports suggest that DAT regulation by endocytosis in neurons is less significant than previously reported. Therefore, additional mechanisms appear to determine DAT steady-state level and functional expression in the neuronal plasma membrane. Here, we hypothesize that the ubiquitin-like protein small ubiquitin-like modifier 1 (SUMO1) increases the DAT steady-state level in the plasma membrane. In confocal microscopy, fluorescent resonance energy transfer (FRET), and Western blot analyses, we demonstrate that DAT is associated with SUMO1 in the rat dopaminergic N27 and DAT overexpressing Human Embryonic Kidney cells (HEK)-293 cells. The overexpression of SUMO1 and the Ubc9 SUMO-conjugase induces DAT SUMOylation, reduces DAT ubiquitination and degradation, enhancing DAT steady-state level. In addition, the Ubc9 knock-down by interference RNA (RNAi) increases DAT degradation and reduces DAT steady-state level. Remarkably, the Ubc9-mediated SUMOylation increases the expression of DAT in the plasma membrane and dopamine uptake capacity. Our results strongly suggest that SUMOylation is a novel mechanism that plays a central role in regulating DAT proteostasis, dopamine uptake, and dopamine signaling in neurons. For that reason, the SUMO pathway including SUMO1, SUMO2, Ubc9, and DAT SUMOylation, can be critical therapeutic targets in regulating DAT stability and dopamine clearance in health and pathological states.

Aims We report a case of bilateral neonatal suppurative sialadenitis (NSS) in an extremely low birth weight infant (ELBW). Methods The infant developed bilateral sub-mandibular swelling at 3 weeks of age. NSS with abscess was confirmed with ultrasound. Despite intravenous antibiotic therapy the masses increased in size and developed abscesses. Results Unilaterally the abscess discharged via Wharton’s duct necessitating intubation to protect the airway. The abscess remnant was incised and drained. Culture grew a methicillin sensitive staphyloccocus aureus. The NSS resolved following two weeks of antibiotics. Conclusion We wish to highlight the importance of early recognition of this rare condition in preterm neonates.

The study of phenotypic variation in plant pathogenesis provides fundamental information about the nature of disease resistance. Cellular mechanisms that alter pathogenesis can be elucidated with confocal microscopy; however, systematic phenotyping platforms-from sample processing to image analysis-to investigate this do not exist. We have developed a platform for 3D phenotyping of cellular features underlying variation in disease development by fluorescence-specific resolution of host and pathogen interactions across time (4D). A confocal microscopy phenotyping platform compatible with different maize-fungal pathosystems (fungi: Setosphaeria turcica, Cochliobolus heterostrophus, and Cercospora zeae-maydis) was developed. Protocols and techniques were standardized for sample fixation, optical clearing, species-specific combinatorial fluorescence staining, multisample imaging, and image processing for investigation at the macroscale. The sample preparation methods presented here overcome challenges to fluorescence imaging such as specimen thickness and topography as well as physiological characteristics of the samples such as tissue autofluorescence and presence of cuticle. The resulting imaging techniques provide interesting qualitative and quantitative information not possible with conventional light or electron 2D imaging. Microsc. Res. Tech., 81:141-152, 2018. © 2016 Wiley Periodicals, Inc.

We find that cusp densities of hyperbolic knots in the 3-sphere are dense in [0,0.6826...] and those of links are dense in [0,0.853...]. We define a new invariant associated with cusp volume, the cusp crossing density, as the ratio between the cusp volume and the crossing number of a link, and show that cusp crossing density for links is bounded above by 3.1263.... Moreover, there is a sequence of links with cusp crossing density approaching 3. The least upper bound for cusp crossing density remains an open question. For two-component hyperbolic links, cusp crossing density is shown to be dense in the interval [0,1.6923...] and for all hyperbolic links, cusp crossing density is shown to be dense in [0, 2.120...].

Aim: There is strong and consistent evidence from large scale randomised controlled trials that type 2 diabetes can be prevented or delayed through lifestyle modification which improves diet quality, increases physical activity and achieves weight loss in people at risk. Worldwide, the prevalence of type 2 diabetes is increasing in individuals of Chinese descent. Culturally tailored programs are required to address the risk in the Chinese population. This paper analyses effectiveness of a culturally tailored community-based lifestyle modification program (Sydney Diabetes Prevention Program (SDPP)) targeting Mandarin speakers.Aim: The SDPP was a 12 month translational study aiming to promote increased physical activity and dietary changes. Effectiveness was assessed through the improvement of anthropometric, metabolic, physical activity and dietary outcomes and number of goals met.Methods: Seventy-eight Mandarin-speaking participants at a high risk (Australian Diabetes Risk, AUSDRISK >= 15) of developing diabetes were recruited for this study. Results: In this cohort, waist circumference, total cholesterol and fat intake significantly improved at the 12-month review. In comparison to the English-speaking stream, the Mandarin-speaking stream achieved fewer improvements in outcomes and goals.Conclusion: The SDPP was not effective in reducing the risk factors associated with developing type 2 diabetes in this cohort of high risk Mandarin-speaking individuals living in Sydney. (C) 2017 Elsevier B.V. All rights reserved.