Phospholipase C-beta 1 Hypofunction in the Pathogenesis of Schizophrenia

Schizophrenia is a mental disorder that is characterized by various abnormal symptoms. Previous studies indicate decreased expression of phospholipase c-beta 1 (PLc-beta 1) in the brains of patients with schizophrenia. PLC-beta 1 -null (PLC-beta 1) mice exhibit multiple endophenotypes of schizophrenia. Furthermore, a study of PLC beta 1 knockdown in the medial prefrontal cortex of mice has shown a specific behavioral deficit, impaired working memory. These results support the notion that disruption of PLC-beta 1-linked signaling in the brain is strongly involved in the pathogenesis of schizophrenia. In this review, we broadly investigate recent studies regarding schizophrenia-related behaviors as well as their various clinical and biological correlates in PLC-beta 1- and knockdown mouse models. This will provide a better understanding of the pathological relevance of the altered expression of PLC p1 in the brains of patients with schizophrenia. Evidence accumulated will shed light on future in-depth studies, possibly in human subjects.1341scopu

Tomato Leaf Curl New Delhi Virus Found Associated with Eggplant Yellowing Disease in Italy

Tomato leaf curl New Delhi virus (ToLCNDV), a bipartite begomovirus (genus Begomovirus, family Geminiviridae), was originally described in tomato in India in 1995 (Padidam et al. 1995). The virus apparently remained confined to the Asian continent for about 20 years and has only recently been discovered in Europe. In Italy, ToLCNDV was detected for the first time in 2015 in zucchini squash in Sicily (Panno et al. 2016) and later on in other regions of continental Italy (Panno et al. 2019). Recently, epiphytotics of ToLCNDV were reported in central and south Italy, associated with yellowing and leaf curling symptoms in pepper crops (Luigi et al. 2019). In 2016, a large-scale survey was conducted to assess the distribution and the genetic diversity of the viral isolates spreading in Italy. Samples collected at that time included cucurbits and solanaceous plants, including five leaf samples from five distinct eggplant (Solanum melongena L.) plants of cultivar Violetta di Napoli that showed yellowing and light curling of the apical leaves and noticed in a cultivation located in Campania region (Castel Volturno municipality). A few Bemisia tabaci individuals were noticed associated to the cultivation. All five leaf samples tested positive for ToLCNDV with ImmunoStrip (Agdia, Elkhart, IN). These results were confirmed by PCR using ToLCNDV-specific primers TLCNDVCP1/TLCNDVCP2 (Parrella et al. 2018) on the total DNA extracted from each sample using an E.Z.N.A. Plant DNA kit (Omega Bio-tek, Norcross, GA). Amplicons of the expected size (∼1.0 kb) were obtained only from the five symptomatic plants, and the nucleotide sequences of these isolates were identical. One representative sample (Som-166/16) was selected for full-length amplification of the genome (DNA-A and DNA-B-like sequences) using the rolling circle amplification (RCA) method with an Illustra TempliPhi amplification kit (GE Healthcare, Piscataway, NJ), in accordance with the manufacturer's instructions. RCA products were digested with different restriction endonucleases to obtain a 2.8-kb linear DNA fragment. Among the different enzymes tested, BamHI resulted in a maximum DNA fragment length of 2.8 kb, which was cloned into a BamHI-linearized pUC19 plasmid. The ligated products were transformed into a competent DH5α strain of Escherichia coli, and the positive clones were sequenced in both orientations at Microsynth Seqlab (Gottingen, Germany). The obtained full-length DNA-A (2,738 nt; GenBank MN782303) and DNA-B (2,686 nt; GenBank MN782304) sequences showed the highest percentage of nucleotide identity with the ToLCNDV Italian isolates Caa-164/16 (GenBank MK732932) for the DNA-A (99.82%) and Cum-45/16 (GenBank MF688671) for the DNA-B (99.48%). Eggplant leaf yellowing caused by a ToLCNDV variant has been previously described in India (HQ264185 for DNA-A and HQ264186 for DNA-B) (Pratap et al. 2011), but the Italian and the Indian isolates exhibited only 90.20 and 79.00% nucleotide identity with respect to the nucleotide sequences of DNA-A and DNA-B. The Som-166/16 isolate was very similar at the molecular level to previously reported isolates from Mediterranean countries and belonged to the European strain ToLCNDV-ES, because the percentage of nucleotide identity was 98.83% for DNA-A with the ToLCNDV-ES strain A-MU.13.ME/4.3 (GenBank MH577751) and 97.88% for DNA-B with the ToLCNDV-ES strain B-AL.15.ZU/2.1 (GenBank MH577658) (Moriones et al. 2017; Panno et al. 2019). The ToLCNDV-ES strain evolved from ToLCNDV isolates of Asian origin and adapted to infect cucurbits (Moriones et al. 2017). Nevertheless, this report presents further evidence, in addition to a previous report (Luigi et al. 2019), that ToLCNDV-ES isolates can potentially pose a threat not only to cucurbits but also to solanaceous crops as well, because this is the first finding of ToLCNDV in eggplant in Italy. Control measures against ToLCNDV are limited and mainly based on vector control, cultivation in protected environments, and the prompt elimination of infected materials

High dose concentration administration of ascorbic acid inhibits tumor growth in BALB/C mice implanted with sarcoma 180 cancer cells via the restriction of angiogenesis

To test the carcinostatic effects of ascorbic acid, we challenged the mice of seven experimental groups with 1.7 × 10-4 mol high dose concentration ascorbic acid after intraperitoneal administrating them with sarcoma S-180 cells. The survival rate was increased by 20% in the group that received high dose concentration ascorbic acid, compared to the control. The highest survival rate was observed in the group in which 1.7 × 10-4 mol ascorbic acid had been continuously injected before and after the induction of cancer cells, rather than just after the induction of cancer cells. The expression of three angiogenesis-related genes was inhibited by 0.3 times in bFGF, 7 times in VEGF and 4 times in MMP2 of the groups with higher survival rates. Biopsy Results, gene expression studies, and wound healing analysis in vivo and in vitro suggested that the carcinostatic effect induced by high dose concentration ascorbic acid occurred through inhibition of angiogenesis

REPercussions: how geminiviruses recruit host factors for replication

Circular single-stranded DNA viruses of the family Geminiviridae encode replication-associated protein (Rep), which is a multifunctional protein involved in virus DNA replication, transcription of virus genes, and suppression of host defense responses. Geminivirus genomes are replicated through the interaction between virus Rep and several host proteins. The Rep also interacts with itself and the virus replication enhancer protein (REn), which is another essential component of the geminivirus replicase complex that interacts with host DNA polymerases α and δ. Recent studies revealed the structural and functional complexities of geminivirus Rep, which is believed to have evolved from plasmids containing a signature domain (HUH) for single-stranded DNA binding with nuclease activity. The Rep coding sequence encompasses the entire coding sequence for AC4, which is intricately embedded within it, and performs several overlapping functions like Rep, supporting virus infection. This review investigated the structural and functional diversity of the geminivirus Rep

Genome-wide identification of long non-coding RNAs in tomato plants irradiated by neutrons followed by infection with Tomato yellow leaf curl virus

Long non-coding RNAs (lncRNAs) play an important role in regulating many biological processes. In this study, tomato seeds were first irradiated by neutrons. Eight tomato mutants were then selected and infected by Tomato yellow leaf curl virus (TYLCV). RNA sequencing followed by bioinformatics analyses identified 1,563 tomato lncRNAs. About half of the lncRNAs were derived from intergenic regions, whereas antisense lncRNAs accounted for 35%. There were fewer lncRNAs identified in our study than in other studies identifying tomato lncRNAs. Functional classification of 794 lncRNAs associated with tomato genes showed that many lncRNAs were associated with binding functions required for interactions with other molecules and localized in the cytosol and membrane. In addition, we identified 19 up-regulated and 11 down-regulated tomato lncRNAs by comparing TYLCV infected plants to non-infected plants using previously published data. Based on these results, the lncRNAs identified in this study provide important resources for characterization of tomato lncRNAs in response to TYLCV infection

Avian influenza virus transmission is suppressed in chickens fed Lactobacillus paracasei expressing the 3D8 single-chain variable fragment protein

The 3D8 single-chain variable fragment (scFv) is a mini-antibody sequence with independent nuclease activity that shows antiviral effects against all types of viruses in chickens and mice. In this study, chickens were treated daily with an oral dose of 109 CFU Lactobacillus paracasei (L. paracasei) expressing either a secreted or anchored 3D8 scFv for three weeks. After L. paracasei administration, the chickens were challenged with avian influenza virus (AIV). From each experimental group, three chickens were directly infected with 100 µL of 107.5 EID50/mL H9N2 AIV and seven chickens were indirectly challenged through contact transmission. oropharyngeal and cloacal swab samples were collected at 3, 5, 7, and 9 days post-inoculation (dpi) from AIV-challenged chickens, AIV Shedding titres were measured by quantitative real-time PCR. Contact transmission in the chickens that were fed 3D8 scFv-secreting L. paracasei showed a significant reduction in viral shedding when compared with other groups. These results suggest that L. paracasei secreting 3D8 provides a basis for the development of ingestible antiviral probiotics with activity against AIV

The Arabidopsis thaliana Homeobox Gene ATHB12 Is Involved in Symptom Development Caused by Geminivirus Infection

BACKGROUND: Geminiviruses are single-stranded DNA viruses that infect a number of monocotyledonous and dicotyledonous plants. Arabidopsis is susceptible to infection with the Curtovirus, Beet severe curly top virus (BSCTV). Infection of Arabidopsis with BSCTV causes severe symptoms characterized by stunting, leaf curling, and the development of abnormal inflorescence and root structures. BSCTV-induced symptom development requires the virus-encoded C4 protein which is thought to interact with specific plant-host proteins and disrupt signaling pathways important for controlling cell division and development. Very little is known about the specific plant regulatory factors that participate in BSCTV-induced symptom development. This study was conducted to identify specific transcription factors that are induced by BSCTV infection. METHODOLOGY/PRINCIPAL FINDINGS: Arabidopsis plants were inoculated with BSCTV and the induction of specific transcription factors was monitored using quantitative real-time polymerase chain reaction assays. We found that the ATHB12 and ATHB7 genes, members of the homeodomain-leucine zipper family of transcription factors previously shown to be induced by abscisic acid and water stress, are induced in symptomatic tissues of Arabidopsis inoculated with BSCTV. ATHB12 expression is correlated with an array of morphological abnormalities including leaf curling, stunting, and callus-like structures in infected Arabidopsis. Inoculation of plants with a BSCTV mutant with a defective c4 gene failed to induce ATHB12. Transgenic plants expressing the BSCTV C4 gene exhibited increased ATHB12 expression whereas BSCTV-infected ATHB12 knock-down plants developed milder symptoms and had lower ATHB12 expression compared to the wild-type plants. Reporter gene studies demonstrated that the ATHB12 promoter was responsive to BSCTV infection and the highest expression levels were observed in symptomatic tissues where cell cycle genes also were induced. CONCLUSIONS/SIGNIFICANCE: These results suggest that ATHB7 and ATHB12 may play an important role in the activation of the abnormal cell division associated with symptom development during geminivirus infection

The role of mediodorsal thalamic nucleus in fear extinction

Understanding the neural mechanism underlying the formation and extinction of fear memory would guide the development of advanced strategies for treatment of post-traumatic stress disorder (PTSD), a generalized anxiety disorder. The mediodorsal thalamic nucleus (MD) is reciprocally connected with limbic circuitry including the prefrontal cortex and amygdala, key structures for fear formation, and extinction. In addition to the distinctive anatomical relationships, the MD participates in learning and memory process in fear extinction through thalamic dual firing modes: tonic and burst. This review will briefly describe neural mechanisms of fear extinction and highlight the role of MD in modulation of fear extinction. We suggest that excitability of the MD neurons may modulate fear circuits and can be a novel target for treatment of anxiety disorders.© 2016 Lee and Shin. Open Access1

Extrasynaptic GABAA Receptors in Mediodorsal Thalamic Nucleus Modulate Fear Extinction Learning

Background: The gamma-amino-butyric acid (GABA) system is a critical mediator of fear extinction process. GABA can induce “phasic” or “tonic” inhibition in neurons through synaptic or extrasynaptic GABAA receptors, respectively. However, role of the thalamic “tonic GABA inhibition” in cognition has not been explored. We addressed this issue in extinction of conditioned fear in mice. Results: Here, we show that GABAA receptors in the mediodorsal thalamic nucleus (MD) modulate fear extinction. Microinjection of gabazine, a GABAA receptor antagonist, into the MD decreased freezing behavior in response to the conditioned stimulus and thus facilitated fear extinction. Interestingly, microinjection of THIP (4,5,6,7-tetrahydroisoxazolo [5,4-c]pyridin-3-ol), a preferential agonist for the δ-subunit of extrasynaptic GABAA receptors, into the MD attenuated fear extinction. In the opposite direction, an MD-specific knock-out of the extrasynaptic GABAA receptors facilitated fear extinction. Conclusions: Our results suggest that “tonic GABA inhibition” mediated by extrasynaptic GABAA receptors in MD neurons, suppresses fear extinction learning. These results raise a possibility that pharmacological control of tonic mode of GABAA receptor activation may be a target for treatment of anxiety disorders like post-traumatic stress disorder.110111sciescopu