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Adriana Schatton, Ezequiel Mendoza, Kathrin Grube, Constance Scharff
Mutations in the transcription factors FOXP1, FOXP2 and FOXP4 affect human cognition, including language. The FoxP gene locus is evolutionarily ancient and highly conserved in its DNA-binding domain. In Drosophila melanogaster FoxP has been implicated in courtship behavior, decision making and specific types of motor-learning. Because honeybees (Apis mellifera, Am) excel at navigation and symbolic dance communication, they are a particularly suitable insect species to investigate a potential link between neural FoxP expression and cognition...
March 14, 2018: Journal of Comparative Neurology
Anna Kovalchuk, Yaroslav Ilnytskyy, Rafal Woycicki, Rocio Rodriguez-Juarez, Gerlinde A S Metz, Olga Kovalchuk
Recent advances in cancer treatments have led to significant increases in cure rates. Most cancer patients are treated with various cytotoxic chemotherapy regimens. These treatment modalities are mutagenic and genotoxic and cause a wide array of late-occurring health problems, and even exert a deleterious influence on future offspring. The adverse effects from exposed parents on offspring are referred to as transgenerational effects, and currently little is known about chemotherapy-induced transgenerational effects...
February 9, 2018: Oncotarget
Martin Becker, Paolo Devanna, Simon E Fisher, Sonja C Vernes
Mutations of the FOXP2 gene cause a severe speech and language disorder, providing a molecular window into the neurobiology of language. Individuals with FOXP2 mutations have structural and functional alterations affecting brain circuits that overlap with sites of FOXP2 expression, including regions of the cortex, striatum, and cerebellum. FOXP2 displays complex patterns of expression in the brain, as well as in non-neuronal tissues, suggesting that sophisticated regulatory mechanisms control its spatio-temporal expression...
2018: Frontiers in Molecular Neuroscience
Lei Zhang, Zhimin Geng, Xiankui Meng, Fandi Meng, Lin Wang
The present study aimed to investigate key long non-coding RNAs (lncRNAs) and genes, and to obtain insights into their roles in the progression of gallbladder cancer (GBC). The gene expression profile and non‑coding RNA profile of GSE62335, which included five separate GBC tissue samples and five matched adjacent gallbladder normal tissue samples, was downloaded from the Gene Expression Omnibus database. The differentially expressed lncRNAs and mRNAs in the GBC tissues were identified, following which RNA binding protein analysis was performed using starBase v2...
March 1, 2018: Molecular Medicine Reports
Qianru He, Lini Zhao, Yunhui Liu, Xiaobai Liu, Jian Zheng, Hai Yu, Heng Cai, Jun Ma, Libo Liu, Ping Wang, Zhen Li, Yixue Xue
Circular RNAs (circRNAs) are a type of endogenous non-coding RNAs, which have been considered to mediate diverse tumorigenesis including angiogenesis. The present study aims to elucidate the potential role and molecular mechanism of circ-SHKBP1 in regulating the angiogenesis of U87 glioma-exposed endothelial cells (GECs). The expression of circ-SHKBP1, but not linear SHKBP1, was significantly upregulated in GECs compared with astrocyte-exposed endothelial cells (AECs). circ-SHKBP1 knockdown inhibited the viability, migration, and tube formation of GECs dramatically...
March 2, 2018: Molecular Therapy. Nucleic Acids
Jiali Wu, Peng Liu, Hailin Tang, Zeyu Shuang, Qingsheng Qiu, Cailu Song, Lingrui Liu, Xiaoming Xie, Xiangsheng Xiao
The forkhead box (FOX) proteins constitute a superfamily of evolutionarily conserved transcriptional regulators with critical roles in various biological processes, including tumor development and progression. FOXP2, a member of the forkhead box P (FOXP) family, has been reported to be important in breast cancer pathogenesis and the regulation of breast cancer metastasis. However, its exact mechanisms and pathways remain unclear. This study therefore investigated the regulatory effects of FOXP2 on tumor proliferation and metastasis in triple-negative breast cancer (TNBC) and its underlying molecular mechanisms...
January 30, 2018: Current Cancer Drug Targets
Else Eising, Amaia Carrion-Castillo, Arianna Vino, Edythe A Strand, Kathy J Jakielski, Thomas S Scerri, Michael S Hildebrand, Richard Webster, Alan Ma, Bernard Mazoyer, Clyde Francks, Melanie Bahlo, Ingrid E Scheffer, Angela T Morgan, Lawrence D Shriberg, Simon E Fisher
Genetic investigations of people with impaired development of spoken language provide windows into key aspects of human biology. Over 15 years after FOXP2 was identified, most speech and language impairments remain unexplained at the molecular level. We sequenced whole genomes of nineteen unrelated individuals diagnosed with childhood apraxia of speech, a rare disorder enriched for causative mutations of large effect. Where DNA was available from unaffected parents, we discovered de novo mutations, implicating genes, including CHD3, SETD1A and WDR5...
February 20, 2018: Molecular Psychiatry
Davor Stanić, Rishi R Dhingra, Mathias Dutschmann
Expression of the transcription factor FOXP2 is linked to brain circuits that control motor function and speech. Investigation of FOXP2 protein expression in respiratory areas of the ponto-medullary brainstem of adult rat revealed distinct rostro-caudal expression gradients. A high density of FOXP2 immunoreactive nuclei was observed within the rostral pontine Kölliker-Fuse nucleus, compared to low densities in caudal pontine and rostral medullary respiratory nuclei, including the: (i) noradrenergic A5 and parafacial respiratory groups; (ii) Bötzinger and pre-Bötzinger complex and; (iii) rostral ventral respiratory group...
January 31, 2018: Respiratory Physiology & Neurobiology
Sara B Estruch, Sarah A Graham, Martí Quevedo, Arianna Vino, Dick H W Dekkers, Pelagia Deriziotis, Elliot Sollis, Jeroen Demmers, Raymond A Poot, Simon E Fisher
FOXP transcription factors play important roles in neurodevelopment, but little is known about how their transcriptional activity is regulated. FOXP proteins cooperatively regulate gene expression by forming homo- and hetero-dimers with each other. Physical associations with other transcription factors might also modulate the functions of FOXP proteins. However, few FOXP-interacting transcription factors have been identified so far. Therefore, we sought to discover additional transcription factors that interact with the brain-expressed FOXP proteins, FOXP1, FOXP2 and FOXP4, through affinity-purifications of protein complexes followed by mass spectrometry...
January 22, 2018: Human Molecular Genetics
Zachary Daniel Burkett, Nancy F Day, Todd Haswell Kimball, Caitlin M Aamodt, Jonathan B Heston, Austin T Hilliard, Xinshu Xiao, Stephanie A White
Human speech is one of the few examples of vocal learning among mammals yet ~half of avian species exhibit this ability. Its neurogenetic basis is largely unknown beyond a shared requirement for FoxP2 in both humans and zebra finches. We manipulated FoxP2 isoforms in Area X, a song-specific region of the avian striatopallidum analogous to human anterior striatum, during a critical period for song development. We delineate, for the first time, unique contributions of each isoform to vocal learning. Weighted gene coexpression network analysis of RNA-seq data revealed gene modules correlated to singing, learning, or vocal variability...
January 23, 2018: ELife
Jiajun Yin, Ningren Jia, Yansong Liu, Chunhui Jin, Fuquan Zhang, Shui Yu, Jun Wang, Jianmin Yuan
BACKGROUND: Schizophrenia (SCZ) is a severe and heritable psychiatric disorder, and previous studies have shown that regulation of the forkhead-box P2 gene (FOXP2) may play a role in schizophrenia. Moreover, just a few studies have identified a single nucleotide polymorphism (SNP) rs10447760 within the gene that was a risk variant for SCZ in the Chinese Han population. METHODS: To examine whether the variant in the FOXP2 gene contributes toward SCZ susceptibility, we carried out an association analysis of the SNP rs10447760 of the FOXP2 gene in a case-control study (1405 cases, 1137 controls) from China...
January 17, 2018: Psychiatric Genetics
Zhimin Shi, Zoe Piccus, Xiaofang Zhang, Huidi Yang, Hannah Jarrell, Yan Ding, Zhaoqian Teng, Ofer Tchernichovski, XiaoChing Li
miR-9 is an evolutionarily conserved miRNA that is abundantly expressed in Area X, a basal ganglia nucleus required for vocal learning in songbirds. Here, we report that overexpression of miR-9 in Area X of juvenile zebra finches impairs developmental vocal learning, resulting in a song with syllable omission, reduced similarity to the tutor song, and altered acoustic features. miR-9 overexpression in juveniles also leads to more variable song performance in adulthood, and abolishes social context-dependent modulation of song variability...
January 18, 2018: ELife
Pedro M Rodenas-Cuadrado, Janine Mengede, Laura Baas, Paolo Devanna, Tobias A Schmid, Michael Yartsev, Uwe Firzlaff, Sonja C Vernes
Genes including FOXP2, FOXP1 and CNTNAP2, have been implicated in human speech and language phenotypes, pointing to a role in the development of normal language-related circuitry in the brain. Although speech and language are unique human phenotypes, a comparative approach is possible by addressing language-relevant traits in animal model systems. One such trait, vocal learning, represents an essential component of human spoken language, and is shared by cetaceans, pinnipeds, elephants, some birds and bats...
January 3, 2018: Journal of Comparative Neurology
Lea J Hachigian, Vitor Carmona, Robert J Fenster, Ruth Kulicke, Adrian Heilbut, Annie Sittler, Luís Pereira de Almeida, Jill P Mesirov, Fan Gao, Eric D Kolaczyk, Myriam Heiman
Alteration of corticostriatal glutamatergic function is an early pathophysiological change associated with Huntington's disease (HD). The factors that regulate the maintenance of corticostriatal glutamatergic synapses post-developmentally are not well understood. Recently, the striatum-enriched transcription factor Foxp2 was implicated in the development of these synapses. Here, we show that, in mice, overexpression of Foxp2 in the adult striatum of two models of HD leads to rescue of HD-associated behaviors, while knockdown of Foxp2 in wild-type mice leads to development of HD-associated behaviors...
December 5, 2017: Cell Reports
Zhaoxiang Yu, Xiaobo Lin, Ming Tian, Weiping Chang
Accumulating evidence indicates that microRNAs (miRNAs) play important roles in tumorigenesis and metastasis. Recent research has shown that miR‑196b is implicated in metastasis by regulating the migration and invasion of cancer cells. However, the clinical significance of miR‑196b and its role as well as the underlying mechanisms in hepatocellular carcinoma (HCC) remain largely unknown. Here, we detected miR‑196b expression in HCC and matched non-tumor tissues with qRT‑PCR. We found that miR‑196b displayed higher expression in HCC patient tissues and cells...
February 2018: Oncology Reports
Nicky Staes, Chet C Sherwood, Katharine Wright, Marc de Manuel, Elaine E Guevara, Tomas Marques-Bonet, Michael Krützen, Michael Massiah, William D Hopkins, John J Ely, Brenda J Bradley
The gene coding for the forkhead box protein P2 (FOXP2) is associated with human language disorders. Evolutionary changes in this gene are hypothesized to have contributed to the emergence of speech and language in the human lineage. Although FOXP2 is highly conserved across most mammals, humans differ at two functional amino acid substitutions from chimpanzees, bonobos and gorillas, with an additional fixed substitution found in orangutans. However, FOXP2 has been characterized in only a small number of apes and no publication to date has examined the degree of natural variation in large samples of unrelated great apes...
December 4, 2017: Scientific Reports
Katrin Schulze, Faraneh Vargha-Khadem, Mortimer Mishkin
The discovery and description of the affected members of the KE family (aKE) initiated research on how genes enable the unique human trait of speech and language. Many aspects of this genetic influence on speech-related cognitive mechanisms are still elusive, e.g. if and how cognitive processes not directly involved in speech production are affected. In the current study we investigated the effect of the FOXP2 mutation on Working Memory (WM). Half the members of the multigenerational KE family have an inherited speech-language disorder, characterised as a verbal and orofacial dyspraxia caused by a mutation of the FOXP2 gene...
January 8, 2018: Neuropsychologia
Hongliang Diao, Zhou Ye, Renyi Qin
MicroRNAs have been reported to play an important role in tumor development and progression by targeting oncogenes and tumor suppressors. miR-23a has been described as significantly upregulated in multiple cancers and involved in tumorigenesis. The aim of this study was to evaluate the potential roles of miR-23a in pancreatic ductal adenocarcinoma (PDAC). We found that miR-23a level was significantly increased in tissues of PDAC compared with that in the control by real-time PCR. FOXP2 expression was downregulated and inversely correlated with miR-23a...
November 14, 2017: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
Serge Nataf
In the last decades, increasingly robust experimental approaches have formally demonstrated that autoimmunity is a physiological process involved in a large range of functions including cognition. On this basis, the recently enunciated "brain superautoantigens" theory proposes that autoimmunity has been a driving force of cognitive evolution. It is notably suggested that the immune and nervous systems have somehow co-evolved and exerted a mutual selection pressure benefiting to both systems. In this two-way process, the evolutionary-determined emergence of neurons expressing specific immunogenic antigens (brain superautoantigens) has exerted a selection pressure on immune genes shaping the T-cell repertoire...
2017: Frontiers in Neuroscience
Chunan Zhong, Jijun Liu, Yuzhe Zhang, Jianping Luo, Jia Zheng
AIMS: Osteosarcoma (OS) is the most common primary bone malignancy that affects adolescents. Although great attention has been paid to the diagnosis of and therapy for OS, the 5-year survival rate of patients with this disease remains poor. MicroRNAs are small non-coding RNAs involved in pathogenesis and progression of human malignancies. MiR-139 has been implicated in several human cancers. However, the role played by miR-139 in pathogenesis of human OS has remained largely unknown. MAIN METHODS: Realtime PCR was used to detect the expression of miR-139...
December 15, 2017: Life Sciences
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