The dorsal hippocampal CA3 regulates spatial reference memory through the CtBP2/GluR2 pathway.

The dorsal hippocampus plays a pivotal role in spatial memory. However, the role of subregion-specific molecular pathways in spatial cognition remains unclear. We observed that the transcriptional coregulator C-terminal binding protein 2 (CtBP2) presented CA3-specific enrichment in expression. RNAi interference of CtBP2 in the dorsal CA3 (dCA3) neurons, but not the ventral CA3 (vCA3), specifically impaired spatial reference memory and reduced the expression of GluR2, the calcium permeability determinant subunit of AMPA receptors. Application of an antagonist for GluR2-absent calcium permeable AMPA receptors rescued spatial memory deficits in dCA3 CtBP2 knockdown animals. Transcriptomic analysis suggest that CtBP2 may regulate GluR2 protein level through post-translational mechanisms, especially by the endocytosis pathway which regulates AMPA receptor sorting. Consistently, CtBP2 deficiency altered the mRNA expression of multiple endocytosis-regulatory genes, and CtBP2 knockdown in primary hippocampal neurons enhanced GluR2-containing AMPA receptor endocytosis. Together, our results provide evidence that the dCA3 regulates spatial reference memory by the CtBP2/GluR2 pathway through the modulation of calcium permeable AMPA receptors.

Oxidative Dehydrogenation of Alkanes through Homogeneous Base Metal Catalysis.

Preparing valuable olefins from cheap and abundant alkane resources has long been a challenging task in organic synthesis, which mainly suffers from harsh reaction conditions and narrow scopes. Homogeneous transition metals catalyzed dehydrogenation of alkanes has attracted much attention for its excellent catalytic activities under relatively milder conditions. Among them, base metal catalyzed oxidative alkane dehydrogenation has emerged as a viable strategy for olefin synthesis for its usage of cheap catalysts, compatibility with various functional groups, and low reaction temperature. In this review, we discuss recent development of base metal catalyzed alkane dehydrogenation under oxidative conditions and their application in constructing complex molecules.

Fimbrins 4 and 5 Act Synergistically During Polarized Pollen Tube Growth to Ensure Fertility in Arabidopsis.

The germination and polar growth of pollen are prerequisite for double fertilization in plants. The actin cytoskeleton and its binding proteins play pivotal roles in pollen germination and pollen tube growth. Two homologs of the actin-bundling protein fimbrin, AtFIM4 and AtFIM5, are highly expressed in pollen in Arabidopsis and can form distinct actin architectures in vitro, but how they co-operatively regulate pollen germination and pollen tube growth in vivo is largely unknown. In this study, we explored their functions during pollen germination and polar growth. Histochemical analysis demonstrated that AtFIM4 was expressed only after pollen grain hydration and, in the early stage of pollen tube growth, the expression level of AtFIM4 was low, indicating that it functions mainly during polarized tube growth, whereas AtFIM5 had high expression levels in both pollen grains and pollen tubes. Atfim4/atfim5 double mutant plants had fertility defects including reduced silique length and seed number, which were caused by severe defects in pollen germination and pollen tube growth. When the atfim4/atfim5 double mutant was complemented with the AtFIM5 protein, the polar growth of pollen tubes was fully rescued; however, AtFIM4 could only partially restore these defects. Fluorescence labeling showed that loss of function of both AtFIM4 and AtFIM5 decreased the extent of actin filament bundling throughout pollen tubes. Collectively, our results revealed that AtFIM4 acts co-ordinately with AtFIM5 to organize and maintain normal actin architecture in pollen grains and pollen tubes to fulfill double fertilization in plants.

Targeted Protein Degradation: Principles, Strategies, and Applications.

Protein degradation is a general process to maintain cell homeostasis. The intracellular protein quality control system mainly includes the ubiquitin-proteasome system and the lysosome pathway. Inspired by the physiological process, strategies to degrade specific proteins have developed, which emerge as potent and effective tools in biological research and drug discovery. This review focuses on recent advances in targeted protein degradation techniques, summarizing the principles, advantages, and challenges. Moreover, the potential applications and future direction in biological science and clinics are also discussed.

The Curved Openspace Algorithm and a Spike-Latency Model for Sonar-Based Obstacle Avoidance.

The rapid control of a sonar-guided vehicle to pursue a goal while avoiding obstacles has been a persistent research topic for decades. Taking into account the limited field-of-view of practical sonar systems and vehicle kinematics, we propose a neural model for obstacle avoidance that maps the 2-D sensory space into a 1-D motor space and evaluates motor actions while combining obstacles and goal information. A two-stage winner-take-all (WTA) mechanism is used to select the final steering action. To avoid excessive scanning of the environment, an attentional system is proposed to control the directions of sonar pings for efficient, task-driven, sensory data collection. A mobile robot was used to test the proposed model navigating through a cluttered environment using a narrow field-of-view sonar system. We further propose a spiking neural model using spike-timing representations, a spike-latency memory, and a "race-to-first-spike" WTA circuit.

Adoptive transfer of metabolically reprogrammed macrophages for atherosclerosis treatment in diabetic ApoE -/- mice.

Atherosclerosis is characterized by inflammation in the arterial wall, which is known to be exacerbated by diabetes. Therapeutic repression of inflammation is a promising strategy for treating atherosclerosis. In this study, we showed that diabetes aggravated atherosclerosis in apolipoproteinE knockout (ApoE -/-) mice, in which increased expression of long-chain acyl-CoA synthetase 1 (Acsl1) in macrophages played an important role. Knockdown of Acsl1 in macrophages (Mφ shAcsl1 ) reprogrammed macrophages to an anti-inflammatory phenotype, especially under hyperglycemic conditions. Injection of Mφ shAcsl1 reprogrammed macrophages into streptozotocin (STZ)-induced diabetic ApoE -/- mice (ApoE -/-+ STZ) alleviated inflammation locally in the plaque, liver and spleen. Consistent with the reduction in inflammation, plaques became smaller and more stable after the adoptive transfer of reprogrammed macrophages. Taken together, our findings indicate that increased Acsl1 expression in macrophages play a key role in aggravated atherosclerosis of diabetic mice, possibly by promoting inflammation. Adoptive transfer of Acsl1 silenced macrophages may serve as a potential therapeutic strategy for atherosclerosis.

ErbB4 regulate extracellular dopamine through the p38 MAPK signaling pathway.

ErbB4 loss-of-function in catecholaminergic neurons induces catecholamine dyshomeostasis. Despite ErbB4's significant role in neuropathology, the signaling pathways that regulate these changes are still widely unknown. In this study, we attempt to identify the downstream pathway of ErbB4 that regulates catecholamine homeostasis. The SH-SY5Y human neuroblastoma cell line was used as the in vitro model for catecholaminergic neurons. Western blotting, enzyme-linked immunosorbent assay, and pharmacological and genetic manipulations by agonist/antagonist or small interference RNA were used to investigate the relationship between ErbB4 and extracellular catecholamines. We confirmed that ErbB4 is abundantly expressed in undifferentiated and retinoic acid-differentiated catecholaminergic cells from the SH-SY5Y cell line. ErbB4 inhibition increase the ratio of phosphorylated p38 to total p38 in SH-SY5Y human neuroblastoma cells. Consistent with previous in vivo observations in mice, ErbB4 deficiency led to increases in extracellular dopamine and norepinephrine levels. However, the resulting increase in extracellular dopamine, but not norepinephrine, could be suppressed by p38 inhibitor SB202190. Our results suggest that both extracellular dopamine and norepinephrine homeostasis could be regulated by ErbB4 in human catecholaminergic cells, and ErbB4 may regulate extracellular dopamine, but not norepinephrine, through the p38 MAPK signaling pathway, thus indicating different regulatory pathways of dopamine and norepinephrine by ErbB4 in catecholaminergic neurons.

Nuclear dynamics and programmed cell death in Arabidopsis root hairs.

In this paper we demonstrate the coupling of nuclear migration to the base of Arabidopsis root hairs with programmed cell death (PCD). Nuclear migration and positioning are fundamental processes of eukaryotic cells. To date, no evidence for a direct connection between nucleus migration and PCD has been described in the literature. Based on the findings of our previous study, we hereby further establish the regulatory role of caspase-3-like/DEVDase in root hair death and demonstrate nuclear migration to a position close to the root hair basement during PCD. In addition, continuous observation and statistical analysis have revealed that the nucleus disengages from the root hair tip and moves back to the root after the root hair grows to a certain length. Finally, pharmacological studies have shown that the meshwork of actin filaments surrounding the nucleus plays a pivotal role in nuclear movement during root hair PCD, and the basipetal movement of the nucleus is markedly inhibited by the caspase-3 inhibitor, Ac-DEVD-CHO.