Dec 2016, Volume 11 Issue 6

    

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• REVIEW

  Cellular, physiological and pathological aspects of the long non-coding RNA NEAT1

  Pang-Kuo Lo,Benjamin Wolfson,Qun Zhou

  2016, 11(6): 413-426. https://doi.org/10.1007/s11515-016-1433-z

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  BACKGROUND: The majority of mammalian genomes have been found to be transcribed into non-coding RNAs. One category of non-coding RNAs is classified as long non-coding RNAs (lncRNAs) based on their transcript sizes larger than 200 nucleotides. Growing evidence has shown that lncRNAs are not junk transcripts and play regulatory roles in multiple aspects of biological processes. Dysregulation of lncRNA expression has also been linked to diseases, in particular cancer. Therefore, studies of lncRNAs have attracted significant interest in the field of medical research. Nuclear enriched abundant transcript 1 (NEAT1), a nuclear lncRNA, has recently emerged as a key regulator involved in various cellular processes, physiological responses, developmental processes, and disease development and progression.

  OBJECTIVE: This review will summarize and discuss the most recent findings with regard to the roles of NEAT1 in the function of the nuclear paraspeckle, cellular pathways, and physiological responses and processes. Particularly, the most recently reported studies regarding the pathological roles of deregulated NEAT1 in cancer are highlighted in this review.

  METHODS: We performed a systematic literature search using the Pubmed search engine. Studies published over the past 8 years (between January 2009 and August 2016) were the sources of literature review. The following keywords were used: “Nuclear enriched abundant transcript 1,” “NEAT1,” and “paraspeckles.”

  RESULTS: The Pubmed search identified 34 articles related to the topic of the review. Among the identified literature, 13 articles report findings related to cellular functions of NEAT1 and eight articles are the investigations of physiological functions of NEAT1. The remaining 13 articles are studies of the roles of NEAT1 in cancers.

  CONCLUSION: Recent advances in NEAT1 studies reveal the multifunctional roles of NEAT1 in various biological processes, which are beyond its role in nuclear paraspeckles. Recent studies also indicate that dysregulation of NEAT1 function contributes to the development and progression of various cancers. More investigations will be needed to address the detailed mechanisms regarding how NEAT1 executes its cellular and physiological functions and how NEAT1 dysregulation results in tumorigenesis, and to explore the potential of NEAT1 as a target in cancer diagnosis, prognosis and therapy.

• REVIEW

  Transcription factor Pitx3 mutant mice as a model for Parkinson’s disease

  Fu-Ming Zhou,Li Li,Juming Yue,John A. Dani

  2016, 11(6): 427-438. https://doi.org/10.1007/s11515-016-1429-8

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  BACKGROUND: Parkinson?s disease (PD) is a common, age-dependent degenerative neurological disorder impairing motor control function and cognition. A key pathology of PD is a degeneration of the nigrostriatal dopamine system, leading to a severe dopamine denervation in the striatum and dynsfunction of the striatal neural circuits.

  OBJECTIVE: To better understand the pathophysiology of the nigrostriatal dopamine denervation and to discover better treatments, animal PD models are needed.

  METHODS: The authors’ original research on the transcription factor Pitx3 null mutant mice and the relevant literature were reviewed.

  RESULTS: An important feature of an animal PD model is the severe, PD-like nigrostriatal dopamine denervation. This feature is provided in the transcription factor Pitx3 null mutant mice. These mice have a severe and bilateral nigral dopamine neuron loss and dopamine denervation in the dorsal striatum, while the dopamine neuron loss in the ventral tegmental area and dopamine denervation in the ventral striatum are moderate, creating a dorsal-ventral dopamine loss gradient and mimicking the dopamine denervation pattern in PD. Pitx3 null mice show motor function deficits in the balance beam and pole tests and these deficits are reversed by L-3,4-dihydroxyphenylalanine (L-dopa). These mice also show impaired cognitive functions as indicated by reduced motor learning and avoidance memory. L-dopa, D1 agonists and, to a lesser extent, D2 agonists, induce normal horizontal movements (walking) and also dyskinesia-like movements consisting of vertical body trunk movements and waving paw movements.

  CONCLUSIONS: The easy-to-maintain Pitx3 null mice with an autogenic, consistent and gradient dopamine denervation are a convenient and suitable mouse model to study the consequences of dopamine loss in PD and to test dopaminergic replacement therapies for PD.

• REVIEW

  Neuroprotective strategies for NMDAR-mediated excitotoxicity in Huntington’s Disease

  Kimberly D. Girling,Yu Tian Wang

  2016, 11(6): 439-458. https://doi.org/10.1007/s11515-016-1425-z

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  BACKGROUND: Huntington’s Disease (HD) is an autosomal dominant neurodegenerative disease causing severe neurodegeneration of the striatum as well as marked cognitive and motor disabilities. Excitotoxicity, caused by overstimulation of NMDA receptors (NMDARs) has been shown to have a key role in the neuropathogenesis of HD, suggesting that targeting NMDAR-dependent signaling may be an effective clinical approach for HD. However, broad NMDAR antagonists are generally poor therapeutics in clinical practice. It has been suggested that GluN2A-containing, synaptically located NMDARs activate cell survival signaling pathways, while GluN2B-containing, primarily extrasynaptic NMDARs trigger cell death signaling. A better approach to development of effective therapeutics for HD may be to target, specifically, the cell-death specific pathways associated with extrasynaptic GluN2B NMDAR activation, while maintaining or potentiating the cell-survival activity of GluN2A-NMDARs.

  OBJECTIVE: This review outlines the role of NMDAR-mediated excitotoxicity in HD and overviews current efforts to develop better therapeutics for HD where NMDAR excitotoxicity is the target.

  METHODS: A systematic review process was conducted using the PubMed search engine focusing on research conducted in the past 5-10 years. 235 articles were consulted for the review, with key search terms including “Huntington’s Disease,” “excitotoxicity,” “NMDAR” and “therapeutics.”

  RESULTS: A wide range of NMDAR excitotoxicity-based targets for HD were identified and reviewed, including targeting NMDARs directly by blocking GluN2B, extrasynaptic NMDARs and/or potentiating GluN2A, synaptic NMDARs, targeting glutamate release or uptake, or targeting specific downstream cell-death signaling of NMDARs.

  CONCLUSION: The current review identifies NMDAR-mediated excitotoxicity as a key player in HD pathogenesis and points to various excitotoxicity-focused targets as potential future preventative therapeutics for HD.

• REVIEW

  Neuronal activity controls the development of interneurons in the somatosensory cortex

  Rachel Babij,Natalia De Marco Garcia

  2016, 11(6): 459-470. https://doi.org/10.1007/s11515-016-1427-x

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  BACKGROUND: Neuronal activity in cortical areas regulates neurodevelopment by interacting with defined genetic programs to shape the mature central nervous system. Electrical activity is conveyed to sensory cortical areas via intracortical and thalamocortical neurons, and includes oscillatory patterns that have been measured across cortical regions.

  OBJECTIVE: In this work, we review the most recent findings about how electrical activity shapes the developmental assembly of functional circuitry in the somatosensory cortex, with an emphasis on interneuron maturation and integration. We include studies on the effect of various neurotransmitters and on the influence of thalamocortical afferent activity on circuit development. We additionally reviewed studies describing network activity patterns.

  METHODS: We conducted an extensive literature search using both the PubMed and Google Scholar search engines. The following keywords were used in various iterations: “interneuron”, “somatosensory”, “development”, “activity”, “network patterns”, “thalamocortical”, “NMDA receptor”, “plasticity”. We additionally selected papers known to us from past reading, and those recommended to us by reviewers and members of our lab.

  RESULTS: We reviewed a total of 132 articles that focused on the role of activity in interneuronal migration, maturation, and circuit development, as well as the source of electrical inputs and patterns of cortical activity in the somatosensory cortex. 79 of these papers included in this timely review were written between 2007 and 2016.

  CONCLUSIONS: Neuronal activity shapes the developmental assembly of functional circuitry in the somatosensory cortical interneurons. This activity impacts nearly every aspect of development and acquisition of mature neuronal characteristics, and may contribute to changing phenotypes, altered transmitter expression, and plasticity in the adult. Progressively changing oscillatory network patterns contribute to this activity in the early postnatal period, although a direct requirement for specific patterns and origins of activity remains to be demonstrated.

• RESEARCH ARTICLE

  Factor XIII Val34Leu polymorphism and risk of recurrent pregnancy loss in Iranian population: a case control study

  Seyed Mehdi Sajjadi,Abbas Khosravi,Jalil Pakravesh,Zahra-soheila Soheili,Shahram Samiei,Saeed Mohammadi,Mohammad Ali Jalali far

  2016, 11(6): 471-475. https://doi.org/10.1007/s11515-016-1419-x

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  BACKGROUND: Recurrent pregnancy loss (RPL) is a heterogeneous condition and thrombophilias have been considered as a probable cause.

  OBJECTIVE: The aim of this study was to investigate the prevalence of the coagulation factor XIII Val34Leu polymorphism among women with unexplained RPL.

  METHODS: A total of 140 women with a history of unexplained RPL and 100 age-matched healthy fertile women were recruited. The presence of FXIII Val34Leu polymorphism among the cases and controls was investigated using PCR-RFLP method.

  RESULTS: Genotype analyses of the subjects revealed that the patients had a significantly higher prevalence of V/L and L/L than the controls (P<0.05): 33.5% vs. 15%, and 9.2% vs. 2%, respectively.

  CONCLUSION: These results indicate a significant association between FXIII Val34Leu polymorphism and unexplained RPL in the Iranian patient.

• RESEARCH ARTICLE

  Exploring the bioactive potential of Serriatia marcescens VITAPI (Acc: 1933637) isolated from soil

  Aruna Muthukumar,Pallavi Pradeep,Isha Thigale,Mohanasrinivasan V.,Jemimah Naine S.,C. Subathra Devi

  2016, 11(6): 476-480. https://doi.org/10.1007/s11515-016-1430-2

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  BACKGROUND:Serratia is one of the most important groups of bacteria which produces proteolytic enzymes effectively and known to possess anti-inflammatory properties. The main focus of the current study was to extract the enzyme serratiopeptidase and pigment prodigiosin from Serratia mascescens. Prodigiosin is a red colored pigment produced by the bacterium Serratia marcescens. It is emerging as a valuable molecule because of its large applications. It has already been proved that pigmented strain of Serratia marcescens is less virulent than non-pigmented strains. Moreover the strain we have obtained is from farm soil which indicates that prodigiosin production can be carried safely using this strain.

  METHODS: In the present study, the isolate VITASP strain was confirmed by morphological, biochemical and molecular studies. The enzyme and pigment were analyzed for anti-oxidant, anti-inflammatory and cytotoxic properties.

  RESULTS: The isolate was further confirmed and identified as Serratia marcescens with 99% similarity. The extracted pigment showed potent radical scavenging effect with 86% and the enzyme was found to inhibit 83%, which was significant in comparison to ascorbic acid standard. The in vitro anti-inflammatory effect of pigment in controlled experimental conditions revealed its protection at 88% and the enzyme with 90%. Aspirin was used as the reference drug. The present findings exhibited a concentration dependent inhibition. The cytotoxic bioassay of pigment showed the IC₅₀ value as (50) µg/mL with 63% cytotoxicity which was statistically significant compared to positive control.

  CONCLUSIONS: Therefore, it appears to be an essential remedial and application research. It may turn out to be highly beneficial to mankind in solving many problems associated with human health.

• RESEARCH ARTICLE

  Rhizoplane microbiota of superior wheat varieties possess enhanced plant growth-promoting abilities

  Ayesha Siddiqa,Yasir Rehman,Shahida Hasnain

  2016, 11(6): 481-487. https://doi.org/10.1007/s11515-016-1426-y

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  BACKGROUND: Microbes affect the growth of plants. In this study, the diversity and plant growth-supporting activities of wheat rhizospheric bacteria were examined.

  METHODS: Sampling was performed thrice at different phases of plant growth. Microbes associated with the rhizoplane of three wheat varieties (Seher, Lasani, and Faisalabad) were cultured and assessed for their plant growth-promoting abilities based on auxin production, hydrogen cyanide production, phosphate solubilization, and nitrogen fixation.

  RESULTS: Bacterial load (CFU/mL) declined, and the succession of bacterial diversity occurred as the plants aged. Most auxin-producing bacteria and the highest concentrations of auxin (77 µg/mL) were observed during the second sampling point at the tillering stage. The Seher variety harbored the most auxin-producing as well as phosphate-solubilizing bacteria. Most of the bacteria belonged to Bacillus and Pseudomonas. Planomicrobium, Serratia, Rhizobium, Brevundimonas, Stenotrophomonas, and Exiguobacterium sp. were also found.

  CONCLUSIONS: These results suggest that the rhizoplane microbiota associated with higher-yield plant varieties have better plant growth-promoting abilities as compared to the microbiota associated with lower-yield plant varieties.