Regulation of Cell Fate Determination by Single-Repeat R3 MYB Transcription Factors in Arabidopsis

MYB transcription factors regulate multiple aspects of plant growth and development. Among the large family of MYB transcription factors, single-repeat R3 MYB are characterized by their short sequence (< 120 amino acids) consisting largely of the single MYB DNA-binding repeat. In the model plant Arabidopsis, R3 MYBs mediate lateral inhibition during epidermal patterning and are best characterized for their regulatory roles in trichome and root hair development. R3 MYBs act as negative regulators for trichome formation but as positive regulators for root hair development. In this article, we provide a comprehensive review on the role of R3 MYBs in the regulation of cell type specification in the model plant Arabidopsis

The small ethylene response factor ERF96 is involved in the regulation of the abscisic acid response in Arabidopsis

Ethylene regulates many aspects of plant growth and development including seed germination, leaf senescence, and fruit ripening, and of plant responses to environmental stimuli including both biotic and abiotic stresses. Ethylene Response Factors (ERFs) are plant-specific transcription factors and are a subfamily of the AP2 (APETALA2)/ERF transcription factor family. The function of many members in this large gene family remains largely unknown. ERF96, a member of the Group IX ERF family transcription factors, has recently been shown to be a transcriptional activator that is involved in plant defense response in Arabidopsis. Here we provide evidence that ERF96 is a positive regulator of abscisic acid (ABA) responses. Bioinformatics analysis indicated that there are a total four small ERFs in Arabidopsis including ERF95, ERF96, ERF97 and ERF98, and that ERF96 forms a cluster with ERF95 and ERF97. By using quantitative RT-PCR, we found that ERF96 is expressed in all tissues and organs examined except roots, with relatively high expression in flowers and seeds. Results from the protoplast transfection assay results indicated that the EDLL motif-containing C-terminal domain is responsible for ERF96’s transcriptional activity. Although loss-of-function mutant of ERF96 was morphologically similar to wild type plants, transgenic plants overexpressing ERF96 had smaller rosette size and were delayed in flowering time. In ABA sensitivity assays, we found that ERF96 overexpression plants were hypersensitive to ABA in terms of ABA inhibition of seed germination, early seedling development and root elongation. Consistent with these observations, elevated transcript levels of some ABA-responsive genes including RD29A, ABI5, ABF3, ABF4, P5CS and COR15A were observed in the transgenic plants in the presence of ABA. However, in the absence of ABA treatment, the transcript levels of these ABA-responsive genes remained largely unchanged. Our experiments also showed that water loss in ERF96 overexpression plants was slower than that in Col wild type plants. Stomatal closure assays indicated that ERF96 overexpression plants had reduced stomatal aperture in the presence of ABA. Taken together, our results suggest that AtERF96 positively regulates ABA responses in Arabidopsis

Neurons in the barrel cortex turn into processing whisker and odor signals: a cellular mechanism for the storage and retrieval of associative signals

Associative learning and memory are essential to logical thinking and cognition. How the neurons are recruited as associative memory cells to encode multiple input signals for their associated storage and distinguishable retrieval remains unclear. We studied this issue in the barrel cortex by in vivo two-photon calcium imaging, electrophysiology and neural tracing in our mouse model that the simultaneous whisker and olfaction stimulations led to odorant-induced whisker motion. After this cross-modal reflex arose, the barrel and piriform cortices connected. More than 40% of barrel cortical neurons became to encode odor signal alongside whisker signal. Some of these neurons expressed distinct activity patterns in response to acquired odor signal and innate whisker signal, and others encoded similar pattern in response to these signals. In the meantime, certain barrel cortical astrocytes encoded odorant and whisker signals. After associative learning, the neurons and astrocytes in the sensory cortices are able to store the newly learnt signal (cross-modal memory) besides the innate signal (native-modal memory). Such associative memory cells distinguish the differences of these signals by programming different codes and signify the historical associations of these signals by similar codes in information retrievals

TyrR, the regulator of aromatic amino acid metabolism, is required for mice infection of Yersinia pestis

Yersinia pestis, the causative agent of plague, poses a serious health threat to rodents and human beings. TyrR is a transcriptional regulator that controls the metabolism of aromatic amino acids in Escherichia coli. In this paper, TyrR played an important role in Y. pestis virulence. Inactivation of tyrR did not seem to affect the in vitro growth of this organism, but resulted in at least 10,000-fold attenuation compared with the wild-type (WT) strain upon subcutaneous infection to mice. In addition, loads of tyrR mutant within mice livers and spleens significantly decreased compared with the WT strain. Transcriptome analysis revealed that TyrR, directly or indirectly, regulated 29 genes encoded on Y. pestis chromosome or plasmids under in vitro growth condition. Similar to the regulatory function of this protein in E. coli, five aromatic-pathway genes (aroF-tyrA, aroP, aroL, and tyrP) were significantly reduced upon deletion of the tyrR gene. Two genes (glnL and glnG) that encode sensory histidine kinase and regulator in a two-component regulatory system involved in nitrogen assimilation were downregulated in the tyrR mutant. Several genes encoding type III secretion proteins were transcribed by 2.0- to 4.2-fold in a tyrR mutant relative to the WT strain. Interestingly, the acid-stressed genes, hdeB and hdeD, were downregulated, and such downregulation partly accounted for the decrease in tolerance of the tyrR mutant under acidic conditions. In conclusion, regulation of TyrR in Y. pestis is similar to, but distinct from, that in E. coli. TyrR is a metabolic virulence determinant in Y. pestis that is important for extracellular survival and/or proliferation

Mycobacterium marinum mmar_2318 and mmar_2319 are Responsible for Lipooligosaccharide Biosynthesis and Virulence towards Dictyostelium

Resistance to phagocyte killing is an important virulence factor in mycobacteria. Dictyostelium has been used to study the interaction between phagocytes and bacteria, given its similarity to the mammalian macrophage. Here, we investigated the genes responsible for virulence to Dictyostelium by screening 1728 transposon mutants of the Mycobacterium marinum NTUH-M6094 strain. A total of 30 mutants that permissive for Dictyostelium growth were identified. These mutants revealed interruptions in 20 distinct loci. Of the 20 loci, six genes (losA, mmar_2318, mmar_2319, wecE, mmar_2323 and mmar_2353) were located in the lipooligosaccharide (LOS) synthesis cluster. LOS are antigenic glycolipids and the core LOS structure from LOS-I to LOS-IV have been reported to exist in M. marinum. Two-dimensional thin-layer chromatography (2D-TLC) glycolipid profiles revealed that deletion of mmar_2318 or mmar_2319 resulted in the accumulation of LOS-III and deficiency of LOS-IV. Deletion and complementation of mmar_2318 or mmar_2319 confirmed that these genes both contributed to virulence towards Dictyostelium but not entry and replication inside Dictyostelium. Co-incubation with a murine macrophage cell line J774a.1 or PMA-induced human monocytic cell line THP-1 demonstrated that mmar_2318 or mmar_2319 deletion mutant could grow in macrophages, and their initial entry rate was not affected in J774a.1 but significantly increased in THP-1. In conclusion, although mmar_2319 has been reported to involve LOS biosynthesis in a previous study, we identified a new gene, mmar_2318 that is also involved in the biosynthesis of LOS. Deletion of mmar_2318 or mmar_2319 both exhibits reduction of virulence towards Dictyostelium and increased entry into THP-1 cells

Painful faces-induced attentional blink modulated by top-down and bottom-up mechanisms

Pain-related stimuli can capture attention in an automatic (bottom-up) or intentional (top-down) fashion. Previous studies have examined attentional capture by pain-related information using spatial attention paradigms that involve mainly a bottom-up mechanism. In the current study, we investigated the pain information–induced attentional blink (AB) using a rapid serial visual presentation (RSVP) task, and compared the effects of task-irrelevant and task-relevant pain distractors. Relationships between accuracy of target identification and individual traits (i.e., empathy and catastrophizing thinking about pain) were also examined. The results demonstrated that task-relevant painful faces had a significant pain information–induced AB effect, whereas task-irrelevant faces a near-significant trend of this effect, supporting the notion that pain-related stimuli can influence the temporal dynamics of attention. Furthermore, we found a significant negative correlation between response accuracy and pain catastrophizing score in task-relevant trials. These findings suggest that active scanning of environmental information related to pain produces greater deficits in cognition than does unintentional attention toward pain, which may represent the different ways in which healthy individuals and patients with chronic pain process pain-relevant information. These results may provide insight into the understanding of maladaptive attentional processing in patients with chronic pain

Cell cycle regulatory functions of the KSHV oncoprotein LANA

Manipulation of cell cycle is a commonly employed strategy of viruses for achieving a favorable cellular environment during infection. Kaposi’s sarcoma-associated herpesvirus (KSHV), the primary etiological agent of several human malignancies including Kaposi’s sarcoma (KS) and primary effusion lymphoma (PEL), encodes several oncoproteins that deregulate normal physiology of cell cycle machinery to persist with endothelial cells and B cells and subsequently establish a latent infection. During latency, only a small subset of viral proteins is expressed. LANA (Latency-associated nuclear antigen) is one of the latent antigens shown to be essential for transformation of endothelial cells in vitro. It has been well demonstrated that LANA is critical for the maintenance of latency, episome DNA replication, segregation and gene transcription. In this review, we summarize recent studies and address how LANA functions as an oncoprotein to steer host cell cycle-related events including proliferation and apoptosis by interacting with various cellular and viral factors, and highlight the potential therapeutic strategy of disrupting LANA-dependent signaling as targets in KSHV-associated cancers

D-galactan II is an immunodominant antigen in O1 lipopolysaccharide and affects virulence in Klebsiella pneumoniae: implication in vaccine design

In the O1 strain of Klebsiella, the lipopolysaccharide (LPS) O-antigen is composed of D-galactan I and D-galactan II. Although the composition of the O1 antigen of Klebsiella was resolved more than two decades, the genetic locus involved in the biosynthesis of D-galactan II and the role of D-galactan II in bacterial pathogenesis remain unclear. Here, we report the identification of the D-galactan II-synthesizing genes by screening a transposon mutant library of an acapsulated Klebsiella pneumoniae O1 strain with bacteriophage. K. pneumoniae strain deleted for wbbY exhibited abrogated D-galactan II production; altered serum resistance and attenuation of virulence. Serologic analysis of K. pneumoniae clinical isolates demonstrated that D-galactan II was more prevalent in community-acquired pyogenic liver abscess (PLA) -causing strains than in non-tissue-invasive strains. WbbY homologs, WbbZ homologs, and lipopolysaccharide structures based on D-galactan II also were present in several Gram-negative bacteria. Immunization of mice with the magA-mutant (K1- O1) (that is, with a LPS D-galactan II-producing strain) provided protection against infection with an O1:K2 PLA strain. Our findings indicate that both WbbY and WbbZ homologs are sufficient for the synthesis of D-galactan II. D-galactan II represents an immunodominant antigen; is conserved among multiple species of Gram-negative bacteria and could be a useful vaccine candidate

MicroRNA Machinery Genes as Novel Biomarkers for Cancer

MicroRNAs (miRNAs) directly and indirectly affect tumorigenesis. To be able to perform their myriad roles, miRNA machinery genes, such as Drosha, DGCR8, Dicer1, XPO5, TRBP, and AGO2, must generate precise miRNAs. These genes have specific expression patterns, protein-binding partners, and biochemical capabilities in different cancers. Our preliminary analysis of data from The Cancer Genome Atlas consortium on multiple types of cancer revealed significant alterations in these miRNA machinery genes. Here, we review their biological structures and functions with an eye towards understanding how they could serve as cancer biomarkers

Combining Self-Organizing Mapping and Supervised Affinity Propagation Clustering Approach to Investigate Functional Brain Networks Involved in Motor Imagery and Execution with fMRI Measurements

AbstractClustering analysis methods have been widely applied to identifying the functional brain networks of a multitask paradigm. However, the previously used clustering analysis techniques are computationally expensive and thus impractical for clinical applications. In this study a novel method, called SOM-SAPC that combines self-organizing mapping (SOM) and supervised affinity propagation clustering (SAPC), is proposed and implemented to identify the motor execution (ME) and motor imagery (MI) networks. In SOM-SAPC, SOM was first performed to process fMRI data and SAPC is further utilized for clustering the patterns of functional networks. As a result, SOM-SAPC is able to significantly reduce the computational cost for brain network analysis. Simulation and clinical tests involving ME and MI were conducted based on SOM-SAPC, and the analysis results indicated that functional brain networks were clearly identified with different response patterns and reduced computational cost. In particular, three activation clusters were clearly revealed, which include parts of the visual, ME and MI functional networks. These findings validated that SOM-SAPC is an effective and robust method to analyze the fMRI data with multitasks