A puzzling property of the transcriptional activators encoded by several animal viruses is their ability to function promiscuously. The adenovirus E1a protein, for example, stimulates transcription of adenoviral genes as well as a wide variety of other viral and cellular genes. We show that E1a can interact with several classes of cellular DNA-binding domains and thereby be recruited to diverse promoters. Our results explain how a single protein can regulate transcription of multiple genes that lack a common promoter element.

SUMMARY α-Synuclein (α-syn) is a small lipid-binding protein involved in vesicle trafficking whose function is poorly characterized. It is of great interest to human biology and medicine because α-syn dysfunction is associated with several neurodegenerative disorders, including Parkinson’s disease (PD). We previously created a yeast model of α-syn pathobiology, which established vesicle trafficking as a process that is particularly sensitive to α-syn expression. We also uncovered a core group of proteins with diverse activities related to α-syn toxicity that is conserved from yeast to mammalian neurons. Here, we report that a yeast strain expressing a somewhat higher level of α-syn also exhibits strong defects in mitochondrial function. Unlike our previous strain, genetic suppression of endoplasmic reticulum (ER)-to-Golgi trafficking alone does not suppress α-syn toxicity in this strain. In an effort to identify individual compounds that could simultaneously rescue these apparently disparate pathological effects of α-syn, we screened a library of 115,000 compounds. We identified a class of small molecules that reduced α-syn toxicity at micromolar concentrations in this higher toxicity strain. These compounds reduced the formation of α-syn foci, re-established ER-to-Golgi trafficking and ameliorated α-syn-mediated damage to mitochondria. They also corrected the toxicity of α-syn in nematode neurons and in primary rat neuronal midbrain cultures. Remarkably, the compounds also protected neurons against rotenone-induced toxicity, which has been used to model the mitochondrial defects associated with PD in humans. That single compounds are capable of rescuing the diverse toxicities of α-syn in yeast and neurons suggests that they are acting on deeply rooted biological processes that connect these toxicities and have been conserved for a billion years of eukaryotic evolution. Thus, it seems possible to develop novel therapeutic strategies to simultaneously target the multiple pathological features of PD.

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These authors contributed equally to this work. SUMMARYAuxin and cadmium (Cd) stress play critical roles during root development. There are only a few reports on the mechanisms by which Cd stress influences auxin homeostasis and affects primary root (PR) and lateral root (LR) development, and almost nothing is known about how auxin and Cd interfere with root hair (RH) development. Here, we characterize rice osaux1 mutants that have a longer PR and shorter RHs in hydroponic culture, and that are more sensitive to Cd stress compared to wild-type (Dongjin). OsAUX1 expression in root hair cells is different from that of its paralogous gene, AtAUX1, which is expressed in non-hair cells. However, OsAUX1, like AtAUX1, localizes at the plasma membrane and appears to function as an auxin tranporter. Decreased auxin distribution and contents in the osaux1 mutant result in reduction of OsCyCB1;1 expression and shortened PRs, LRs and RHs under Cd stress, but may be rescued by treatment with the membrane-permeable auxin 1-naphthalene acetic acid. Treatment with the auxin transport inhibitors 1-naphthoxyacetic acid and N-1-naphthylphthalamic acid increased the Cd sensitivity of WT rice. Cd contents in the osaux1 mutant were not altered, but reactive oxygen species-mediated damage was enhanced, further increasing the sensitivity of the osaux1 mutant to Cd stress. Taken together, our results indicate that OsAUX1 plays an important role in root development and in responses to Cd stress.

Messenger RNA (mRNA) turnover in eukaryotic cells begins with shortening of the poly (A) tail at the 3′ end, a process called deadenylation. In yeast, the deadenylation reaction is predominantly mediated by CCR4 and CCR4-associated factor 1 (CAF1), two components of the well-characterised protein complex named CCR4-NOT. We report here that AtCAF1a and AtCAF1b, putative Arabidopsis homologs of the yeast CAF1 gene, partially complement the growth defect of the yeast caf1 mutant in the presence of caffeine or at high temperatures. The expression of AtCAF1a and AtCAF1b is induced by multiple stress-related hormones and stimuli. Both AtCAF1a and AtCAF1b show deadenylation activity in vitro and point mutations in the predicted active sites disrupt this activity. T-DNA insertion mutants disrupting the expression of AtCAF1a and/or AtCAF1b are defective in deadenylation of stress-related mRNAs, indicating that the two AtCAF1 proteins are involved in regulated mRNA deadenylation in vivo. Interestingly, the single and double mutants of AtCAF1a and AtCAF1b show reduced expression of pathogenesis-related (PR) genes PR1 and PR2 and are more susceptible to Pseudomonas syringae pv tomato DC3000 (Pst DC3000) infection, whereas transgenic plants over-expressing AtCAF1a show elevated expression of PR1 and PR2 and increased resistance to the same pathogen. Our results suggest roles of the AtCAF1 proteins in regulated mRNA deadenylation and defence responses to pathogen infections.

EISAs (n = 20), showed a significant reduction of BPD (29.0 vs. 70.0%, p = 0.004) and PDA (29.0 vs. 65.0%, p = 0.011). In the subgroup analysis of blood gas, arterial oxygen saturation (SaO 2) value at 1 and 12 h and partial pressure of arterial oxygen (PaO 2) at 12 h were all higher in the EISA group compared to the MISA group. Conclusion : MISA had no clear benefit on the incidence of BPD, but it was related to a reduction in PDA. It is an appropriate therapy for spontaneous breathing in infants with extremely low birth weight and NRDS.

Plants have developed a number of survival strategies which are significant for enhancing their adaptation to various biotic and abiotic stress factors. At the transcriptome level, G-protein-coupled receptors (GPCRs) are of great significance, enabling the plants to detect a wide range of endogenous and exogenous signals which are employed by the plants in regulating various responses in development and adaptation. In this research work, we carried out genome-wide analysis of target of Myb1 (TOM1), a member of the GPCR gene family. The functional role of TOM1 in salt stress tolerance was studied using a transgenic Arabidopsis plants over-expressing the gene. By the use of the functional domain PF06454, we obtained 16 TOM genes members in Gossypium hirsutum, 9 in Gossypium arboreum, and 11 in Gossypium raimondii. The genes had varying physiochemical properties, and it is significant to note that all the grand average of hydropathy (GRAVY) values were less than one, indicating that all are hydrophobic in nature. In all the genes analysed here, both the exonic and intronic regions were found. The expression level of Gh_A07G0747 (GhTOM) was significantly high in the transgenic lines as compared to the wild type; a similar trend in expression was observed in all the salt-related genes tested in this study. The study in epidermal cells confirmed the localization of the protein coded by the gene TOM1 in the plasma membrane. Analysis of anti-oxidant enzymes showed higher concentrations of antioxidants in transgenic lines and relatively lower levels of oxidant substances such as H2O2. The low malondialdehyde (MDA) level in transgenic lines indicated that the transgenic lines had relatively low level of oxidative damage compared to the wild types. The results obtained indicate that Gh_A07G0747 (GhTOM) can be a putative target gene for enhancing salt stress tolerance in plants and could be exploited in the future for the development of salt stress-tolerant cotton cultivars.

Background & Aims The outbreak of coronavirus disease 2019 (COVID‐19) has been declared a pandemic. Although COVID‐19 is caused by infection in the respiratory tract, extrapulmonary manifestations including dysregulation of the immune system and hepatic injury have been observed. Given the high prevalence of hepatitis B virus (HBV) infection in China, we sought to study the impact of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and HBV coinfection in patients. Methods Blood samples of 50 SARS‐CoV‐2 and HBV coinfected patients, 56 SARS‐CoV‐2 mono‐infected patients, 57 HBeAg‐negative chronic HBV patient controls and 57 healthy controls admitted to Renmin Hospital of Wuhan University were collected in this study. Complete blood count and serum biochemistry panels including markers indicative of liver functions were performed. Cytokines including IFN‐γ, TNF‐α, IL‐2, IL‐4, IL‐6 and IL‐10 were evaluated. T cell, B cell and NK cell counts were measured using flow cytometry. Results SARS‐CoV‐2 and HBV coinfection did not significantly affect the outcome of the COVID‐19. However, at the onset of COVID‐19, SARS‐CoV‐2 and HBV coinfected patients showed more severe monocytopenia and thrombocytopenia as well as more disturbed hepatic function in albumin production and lipid metabolism. Most of the disarrangement could be reversed after recovery from COVID‐19. Conclusions While chronic HBV infection did not predispose COVID‐19 patients to more severe outcomes, our data suggest SARS‐CoV‐2 and HBV coinfection poses a higher extent of dysregulation of host functions at the onset of COVID‐19. Thus, caution needs to be taken with the management of SARS‐CoV‐2 and HBV coinfected patients.