Light-sensing phytochromes feel the heat

Plant phytochrome activity is governed not just by light, but also by prevailing temperature</jats:p

PIF7 controls leaf cell proliferation through an AN3 substitution-39 repression mechanism

Plants are agile, plastic organisms able to adapt to everchanging circumstances. Responding to far-red (FR) wavelengths from nearby vegetation, shade-intolerant species elicit the adaptive shade-avoidance syndrome (SAS), characterized by elongated petioles, leaf hyponasty, and smaller leaves. We utilized end-of-day FR (EODFR) treatments to interrogate molecular processes that underlie the SAS leaf response. Genetic analysis established that PHYTOCHROME-INTERACTING FACTOR 7 (PIF7) is required for EODFR-mediated constraint of leaf blade cell division, while EODFR messenger RNA sequencing data identified ANGUSTIFOLIA3 (AN3) as a potential PIF7 target. We show that PIF7 can suppress AN3 transcription by directly interacting with and sequestering AN3. We also establish that PIF7 and AN3 impose antagonistic control of gene expression via common cis-acting promoter motifs in several cell-cycle regulator genes. EODFR triggers the molecular substitution of AN3 to PIF7 at G-box/PBE-box promoter regions and a switch from promotion to repression of gene expression

Influence of Soybean Oil or Non-Soybean Oil Based Lipid Emulsions on Parenteral Nutrition Associated Liver Disease in Late Preterm and Term Infants

Background: Total parenteral nutrition (TPN) is a life-saving therapy given to neonates with intestinal failure. However, infants on long-term TPN may experience Parenteral Nutrition-Associated Liver Disease (PNALD). New formulations for lipid emulsions are purportedly better than the traditional soy-based lipid emulsions (SLE). Our primary objective was to determine the prevalence of PNALD in infants who received non-soybean-based lipid emulsions (NSLE) or SLE. Methods: In this retrospective study, medical records of all infants admitted to a tertiary neonatal intensive care unitfrom 2004 to 2013 were reviewed. Late preterm (34 -36 weeks of gestation) and term infants who were on TPN for more than two weeks were included. Their demographic data and clinical variables were collected. Results: 208 infants received SLE for more than two weeks. The prevalence rate of PNALD in those who received SLE was 21% while that of those who received the NSLE was 17%. No significant difference was found between the ‘Soy’ or ‘NonSoy’ subgroups (p = 0.315). Seventy infants received TPN for more than four weeks. The prevalence rate of PNALD in infants who received SLE and NSLE was 35% and 25% respectively. No significant statistical difference was found between the ‘Soy’ or ‘NonSoy’ subgroups (p = 0.132). Conclusions: The type of lipid emulsion does not significantly influence the rate of PNALD in late preterm and term infants on long-term TPN

Macroautophagy in sporadic and the genetic form of Parkinson’s disease with the A53T a-synuclein mutation

The A53T mutation in the a-synuclein gene causes autosomal-dominant Lewy body Parkinson’s disease (PD). Cultured cell models have linked this mutation to increased cell macroautophagy, although evidence of enhanced macroautophagy in patients with this mutation has not been assessed. Objective: To determine whether macroautophagy is increased by the A53T a-synuclein gene mutation in PD patients and cell models. Methods: Formalin-fixed paraffin-embedded 10 μm-thick tissue sections from the substantia nigra and anterior cingulate cortex of two PD patients with the A53T a-synuclein gene mutation were compared with four sporadic PD cases and four controls obtained from the Sydney Brain Bank. Lewy bodies were isolated from frontal cortex of a case with late stage PD (recruited from South Australian Brain Bank). Immunohistochemistry was performed for a-synuclein and the macroautophagy markers autophagy-specific gene (ATG) 5, ATG6/Beclin1 and ATG8/LC3. SHSY5Y cells were transfected with wild type or A53T mutant a-synuclein plasmids and observable changes in macroautophagy marker protein levels assessed using Western blotting. Results: a-Synuclein immunoreactive neurites and dots were more numerous in patients with A53T mutations compared with late stage sporadic PD patients, and perinuclear cytoplasmic a-synuclein aggregates were observed in the a-synuclein A53T gene transfected SH-SY5Y cells compared to wild type transfections. All PD patients (with or without A53T mutations) had increased immunohistochemical evidence for macroautophagy compared with controls, and the levels of the ATG5 complex were equally increased in wild type and A53T a-synuclein gene transfected cells compared to controls. Conclusion: Despite increased a-synuclein accumulation with A53T mutations, macroautophagy is not increased above that observed in sporadic patients with PD or in cells transfected with wild type a-synuclein, suggesting that mutated a-synuclein protein is not removed by macroautophagy

PIF7 controls leaf cell proliferation through an AN3 substitution repression mechanism

Plants are agile, plastic organisms able to adapt to everchanging circumstances. Responding to far-red (FR) wavelengths from nearby vegetation, shade-intolerant species elicit the adaptive shade-avoidance syndrome (SAS), characterized by elongated petioles, leaf hyponasty, and smaller leaves. We utilized end-of-day FR (EODFR) treatments to interrogate molecular processes that underlie the SAS leaf response. Genetic analysis established that PHYTOCHROME-INTERACTING FACTOR 7 (PIF7) is required for EODFR-mediated constraint of leaf blade cell division, while EODFR messenger RNA sequencing data identified ANGUSTIFOLIA3 (AN3) as a potential PIF7 target. We show that PIF7 can suppress AN3 transcription by directly interacting with and sequestering AN3. We also establish that PIF7 and AN3 impose antagonistic control of gene expression via common cis-acting promoter motifs in several cell-cycle regulator genes. EODFR triggers the molecular substitution of AN3 to PIF7 at G-box/PBE-box promoter regions and a switch from promotion to repression of gene expression

The pathogenesis of cingulate atrophy in behavioral variant frontotemporal dementia and Alzheimer’s disease

BACKGROUND: Early atrophy of the cingulate cortex is a feature of both behavioral variant frontotemporal dementia (bvFTD) and Alzheimer’s disease (AD), with degeneration of the anterior cingulate region increasingly recognized as a strong predictor of bvFTD. The total number of neurons in this region, rather than the density of neurons, is associated with mood disturbance in other dementias, although there are no data on the extent and magnitude of neuronal loss in patients with bvFTD. While the density of small populations of neurons in this region has been assessed, it is unlikely that the degree of atrophy of the cingulate cortex seen in bvFTD can be explained by the loss of these subpopulations. This suggests that there is more generalized degeneration of neurons in this region in bvFTD. The present study assesses total neuronal number, as well as characteristic pathologies, in the anterior and posterior cingulate cortices of pathologically confirmed bvFTD (N = 11) and AD (N = 9) patients compared with age-matched controls (N = 14). The bvFTD cohort comprised 5 cases with tau pathology (Pick’s disease), and 6 with TDP-43 pathology. RESULTS: At postmortem, atrophy was detected in the anterior and posterior cingulate cortices of bvFTD cases, but only in the posterior cingulate cortex of AD cases. As predicted, there was a significant reduction in both the density and total number of neurons in the anterior but not the posterior cingulate cortex of bvFTD cases with the opposite observed for the AD cases. Importantly, neuronal loss in the anterior cingulate cortex was only observed in cases with tau pathology. CONCLUSIONS: This study confirms significant neuronal loss in the posterior but not anterior cingulate cortex in AD, and demonstrates that significant neuron loss in bvFTD occurs only in the anterior cingulate cortex but only in cases with tau pathology compared with cases with TDP pathology. We propose that significant neurodegeneration in the anterior cingulate cortex may be useful in differentiating the pathological subtypes in vivo

Investigating the genetic control of plant development in spring barley under speed breeding conditions

Key message: This study found that the genes, PPD-H1 and ELF3, control the acceleration of plant development under speed breeding, with important implications for optimizing the delivery of climate-resilient crops. Abstract: Speed breeding is a tool to accelerate breeding and research programmes. Despite its success and growing popularity with breeders, the genetic basis of plant development under speed breeding remains unknown. This study explored the developmental advancements of barley genotypes under different photoperiod regimes. A subset of the HEB-25 Nested Association Mapping population was evaluated for days to heading and maturity under two contrasting photoperiod conditions: (1) Speed breeding (SB) consisting of 22 h of light and 2 h of darkness, and (2) normal breeding (NB) consisting of 16 h of light and 8 h of darkness. GWAS revealed that developmental responses under both conditions were largely controlled by two loci: PPDH-1 and ELF3. Allelic variants at these genes determine whether plants display early flowering and maturity under both conditions. At key QTL regions, domesticated alleles were associated with late flowering and maturity in NB and early flowering and maturity in SB, whereas wild alleles were associated with early flowering under both conditions. We hypothesize that this is related to the dark-dependent repression of PPD-H1 by ELF3 which might be more prominent in NB conditions. Furthermore, by comparing development under two photoperiod regimes, we derived an estimate of plasticity for the two traits. Interestingly, plasticity in development was largely attributed to allelic variation at ELF3. Our results have important implications for our understanding and optimization of speed breeding protocols particularly for introgression breeding and the design of breeding programmes to support the delivery of climate-resilient crops

Levetiracetam-loaded biodegradable polymer implants in the tetanus toxin model of temporal lobe epilepsy in rats

Approximately one-third of people with epilepsy receive insufficient benefit from currently available anticonvulsant medication, and some evidence suggests that this may be due to a lack of effective penetration into brain parenchyma. The current study investigated the ability of biodegradable polymer implants loaded with levetiracetam to ameliorate seizures following implantation above the motor cortex in the tetanus toxin model of temporal lobe epilepsy in rats. The implants led to significantly shorter seizures and a trend towards fewer seizures for up to 1 week. The results of this study indicate that drug-eluting polymer implants represent a promising evolving treatment option for intractable epilepsy. Future research is warranted to investigate issues of device longevity and implantation site

RVX-208, a BET-inhibitor for treating atherosclerotic cardiovascular disease, raises ApoA-I/HDL and represses pathways that contribute to cardiovascular disease

AbstractHigh density lipoproteins (HDL), through activity of the main protein component apolipoprotein A-I (ApoA-I), can reduce the risk of cardiovascular disease (CVD) by removing excess cholesterol from atherosclerotic plaque. In this study, we demonstrate that the bromodomain and extraterminal domain (BET) inhibitor RVX-208 increases ApoA-I gene transcription and protein production in human and primate primary hepatocytes. Accordingly, RVX-208 also significantly increases levels of ApoA-I, HDL-associated cholesterol, and HDL particle number in patients who received the compound in recently completed phase 2b trials SUSTAIN and ASSURE. Moreover, a post-hoc analysis showed lower instances of major adverse cardiac events in patients receiving RVX-208. To understand the effects of RVX-208 on biological processes underlying cardiovascular risk, we performed microarray analyses of human primary hepatocytes and whole blood treated ex vivo. Overall, data showed that RVX-208 raises ApoA-I/HDL and represses pro-inflammatory, pro-atherosclerotic and pro-thrombotic pathways that can contribute to CVD risk