Stable MOB1 interaction with Hippo/MST is not essential for development and tissue growth control.

The Hippo tumor suppressor pathway is essential for development and tissue growth control, encompassing a core cassette consisting of the Hippo (MST1/2), Warts (LATS1/2), and Tricornered (NDR1/2) kinases together with MOB1 as an important signaling adaptor. However, it remains unclear which regulatory interactions between MOB1 and the different Hippo core kinases coordinate development, tissue growth, and tumor suppression. Here, we report the crystal structure of the MOB1/NDR2 complex and define key MOB1 residues mediating MOB1's differential binding to Hippo core kinases, thereby establishing MOB1 variants with selective loss-of-interaction. By studying these variants in human cancer cells and Drosophila, we uncovered that MOB1/Warts binding is essential for tumor suppression, tissue growth control, and development, while stable MOB1/Hippo binding is dispensable and MOB1/Trc binding alone is insufficient. Collectively, we decrypt molecularly, cell biologically, and genetically the importance of the diverse interactions of Hippo core kinases with the pivotal MOB1 signal transducer.The Hippo tumor suppressor pathway is essential for development and tissue growth control. Here the authors employ a multi-disciplinary approach to characterize the interactions of the three Hippo kinases with the signaling adaptor MOB1 and show how they differently affect development, tissue growth and tumor suppression

Baculovirus Infection Triggers a Shift from Amino Acid Starvation-Induced Autophagy to Apoptosis

Autophagy plays a central role in regulating important cellular functions such as cell survival during starvation and control of infectious pathogens. On the other hand, many pathogens have evolved mechanisms of inhibition of autophagy such as blockage of the formation of autophagosomes or the fusion of autophagosomes with lysosomes. Baculoviruses are important insect pathogens for pest control, and autophagy activity increases significantly during insect metamorphosis. However, it is not clear whether baculovirus infection has effects on the increased autophagy. In the present study, we investigated the effects of the Autographa californica nucleopolyhedrovirus (AcMNPV) infection on autophagy in SL-HP cell line from Spodoptera litura induced under amino acid deprivation. The results revealed that AcMNPV infection did not inhibit autophagy but triggered apoptosis under starvation pressure. In the early stage of infection under starvation, mitochondrial dysfunction was detected, suggesting the organelles might be involved in cell apoptosis. The semi-quantitative PCR assay revealed that the expression of both p35 and ie-1 genes of AcMNPV had no significant difference between the starved and unstarved SL-HP cells. The western blot analysis showed that no cleavage of endogenous Atg6 occurred during the process of apoptosis in SL-HP cells. These data demonstrated that some permissive insect cells may defend baculovirus infection via apoptosis under starvation and apoptosis is independent of the cleavage of Atg6 in SL-HP cells

RETRACTED ARTICLE: Engineering Bacillus licheniformis as a thermophilic platform for the production of l-lactic acid from lignocellulose-derived sugars

Abstract Background Bacillus licheniformis MW3 as a GRAS and thermophilic strain is a promising microorganism for chemical and biofuel production. However, its capacity to co-utilize glucose and xylose, the major sugars found in lignocellulosic biomass, is severely impaired by glucose-mediated carbon catabolite repression (CCR). In this study, a “dual-channel” process was implemented to engineer strain MW3 for simultaneous utilization of glucose and xylose, using l-lactic acid as a target product. Results A non-phosphotransferase system (PTS) glucose uptake route was activated via deletion of the glucose transporter gene ptsG and introduction of the galactose permease gene galP. After replacing the promoter of glucokinase gene glck with the strong promoter P als, the engineered strain recovered glucose consumption and utilized glucose and xylose simultaneously. Meanwhile, to improve the consumption rate of xylose in this strain, several measures were undertaken, such as relieving the regulation of the xylose repressor XylR, reducing the catabolite-responsive element, and optimizing the rate-limiting step. Knockout of ethanol and acetic acid pathway genes further increased lactic acid yield by 6.2%. The resultant strain, RH15, was capable of producing 121.9 g/L l-lactic acid at high yield (95.3%) after 40 h of fermentation from a mixture of glucose and xylose. When a lignocellulosic hydrolysate was used as the substrate, 99.3 g/L l-lactic acid was produced within 40 h, with a specific productivity of 2.48 g/[L h] and a yield of 94.6%. Conclusions Our engineered strain B. licheniformis RH15 could thermophilically produced l-lactic acid from lignocellulosic hydrolysate with relatively high concentration and productivity at levels that were competitive with most reported cases of l-lactic acid-producers. Thus, the engineered strain might be used as a platform for the production of other chemicals. In addition to engineering the B. licheniformis strain, the “dual-channel” process might serve as an alternative method for engineering a variety of other strains

Retraction Note to: Engineering Bacillus licheniformis as a thermophilic platform for the production of l-lactic acid from lignocellulose-derived sugars

Abstract The authors are retracting this article because the biological materials were used and the experiments were conducted without proper authorization from the laboratory where these data were obtained [1]

Whole genome level analysis of the DEATH protein superfamily in sheep (Ovis aries) and their coordination relationship in regulating lactation

Abstract Background Sheep milk is a nutritional and health-promoting food source for humans. The DEATH superfamily is a conserved protein family, and some of its members are closely related to lactation. Systematic studies of the members of the DEATH superfamily are important for further understanding its functions in the mammary gland during lactation; however, there studies are currently lacking. Results Herein, 74 members of the DEATH superfamily were identified in sheep, and phylogenetic analyses indicated that four subfamilies were strongly correlated in evolution. The Ka/Ks calculations demonstrated that negative selection was the primary pressure acting on DEATH members; however, the immune-related gene IFI203 was undergoing strong positive selection in sheep. Furthermore, in the late pregnancy and lactation period, these DEATH genes exhibited similar expression patterns under different nutritional conditions in the mammary gland, and four subfamilies were positively correlated in expression patterns. Additionally, half or more DEATH genes were upregulated in the lactation period, which implied their crucial roles in the lactation of sheep. Conclusions The current research contributes to a better understanding of the evolutionary characteristics of the DEATH superfamily and their roles in sheep lactation, and it also provides potential target genes for the molecular breeding of dairy sheep. Graphical Abstrac

MOESM1 of Engineering Bacillus licheniformis as a thermophilic platform for the production of l-lactic acid from lignocellulose-derived sugars

Additional file 1: Figure S1. The construction of gene knockout plasmids. Figure S2. The analysis of the stereoisomers of lactic acid produced by strain RH02. Table S1. Primers used in this study. Text 1. The codon-optimized sequences of xylAs

The role of cytochrome c on apoptosis induced by Anagrapha falcifera multiple nuclear polyhedrosis virus in insect Spodoptera litura cells.

There are conflicting reports on the role of cytochrome c during insect apoptosis. Our previous studies have showed that cytochrome c released from the mitochondria was an early event by western blot analysis and caspase-3 activation was closely related to cytochrome c release during apoptosis induced by baculovirus in Spodoptera litura cells (Sl-1 cell line). In the present study, alteration in mitochondrial morphology was observed by transmission electron microscopy, and cytochrome c release from mitochondria in apoptotic Sl-1 cells induced with Anagrapha falcifera multiple nuclear polyhedrosis virus (AfMNPV) has further been confirmed by immunofluoresence staining protocol, suggesting that structural disruption of mitochondria and the release of cytochrome c are important events during Lepidoptera insect cell apoptosis. We also used Sl-1 cell-free extract system and the technique of RNA interference to further investigate the role of cytochrome c in apoptotic Sl-1 cells induced by AfMNPV. Caspase-3 activity in cell-free extracts supplemented with exogenous cytochrome c was determined and showed an increase with the extension of incubation time. DsRNA-mediated silencing of cytochrome c resulted in the inhibition of apoptosis and protected the cells from AfMNPV-induced cell death. Silencing of expression of cytochrome c had a remarkable effect on pro-caspase-3 and pro-caspase-9 activation and resulted in the reduction of caspase-3 and caspase-9 activity in Sl-1 cells undergoing apoptosis. Caspase-9 inhibitor could inhibit activation of pro-caspase-3, and the inhibition of the function of Apaf-1 with FSBA blocked apoptosis, hinting that Apaf-1 could be involved in Sl-1 cell apoptosis induced by AfMNPV. Taken together, these results strongly demonstrate that cytochrome c plays an important role in apoptotic signaling pathways in Lepidopteran insect cells

Stable MOB1 interaction with Hippo/MST is not essential for development and tissue growth control.

The Hippo tumor suppressor pathway is essential for development and tissue growth control, encompassing a core cassette consisting of the Hippo (MST1/2), Warts (LATS1/2), and Tricornered (NDR1/2) kinases together with MOB1 as an important signaling adaptor. However, it remains unclear which regulatory interactions between MOB1 and the different Hippo core kinases coordinate development, tissue growth, and tumor suppression. Here, we report the crystal structure of the MOB1/NDR2 complex and define key MOB1 residues mediating MOB1's differential binding to Hippo core kinases, thereby establishing MOB1 variants with selective loss-of-interaction. By studying these variants in human cancer cells and Drosophila, we uncovered that MOB1/Warts binding is essential for tumor suppression, tissue growth control, and development, while stable MOB1/Hippo binding is dispensable and MOB1/Trc binding alone is insufficient. Collectively, we decrypt molecularly, cell biologically, and genetically the importance of the diverse interactions of Hippo core kinases with the pivotal MOB1 signal transducer.The Hippo tumor suppressor pathway is essential for development and tissue growth control. Here the authors employ a multi-disciplinary approach to characterize the interactions of the three Hippo kinases with the signaling adaptor MOB1 and show how they differently affect development, tissue growth and tumor suppression

Simple Synthesis of 3D Ground-Moss-Shaped MnO@N-C Composite as Superior Anode Material for Lithium-Ion Batteries

A MnO@N-doped carbon (MnO@N-C) composite, with a three-dimensional (3D) ground-moss-like structure, was synthesized through hydrothermal treatment, polydopamine coating, and calcination, all without the use of surfactants. In lithium-ion batteries, the MnO@N-C sample, when used as an anode, achieved a performance of 563 mAh g−1 at 1.0 A g−1 across 300 cycles and boasted an initial Coulombic efficiency of 73.2%. In contrast, the MnO electrode had a discharge capacity of 258 mAh g−1 and an efficiency of 53.3% under the same conditions. The improved performance stems from the 3D carbon networks hosting MnO. These networks enhance MnO’s electron transfer ability and offer space to offset volume changes during the charge–discharge cycle