scholarly journals Schizophrenia and Human Self-Domestication: An Evolutionary Linguistics Approach

2017 ◽  
Vol 89 (3) ◽  
pp. 162-184 ◽  
Author(s):  
Antonio Benítez-Burraco ◽  
Lorena Di Pietro ◽  
Marta Barba ◽  
Wanda Lattanzi
Keyword(s):  
Neural Crest ◽  
Language Processing ◽  
Expression Profiles ◽  
Neurodevelopmental Disorder ◽  
Human Populations ◽  
Altered Expression ◽  
Domestication Syndrome ◽  
Evolutionary Linguistics ◽  
Genetic And Environmental Factors ◽  
And Function

Schizophrenia (SZ) is a pervasive neurodevelopmental disorder that entails social and cognitive deficits, including marked language problems. Its complex multifactorial etiopathogenesis, including genetic and environmental factors, is still widely uncertain. SZ incidence has always been high and quite stable in human populations, across time and regardless of cultural implications, for unclear reasons. It has been hypothesized that SZ pathophysiology may involve the biological components that changed during the recent human evolutionary history, and led to our distinctive mode of cognition, which includes language skills. In this paper we explore this hypothesis, focusing on the self-domestication of the human species. This has been claimed to account for many human-specific distinctive traits, including aspects of our behavior and cognition, and to favor the emergence of complex languages through cultural evolution. The “domestication syndrome” in mammals comprises the constellation of traits exhibited by domesticated strains, seemingly resulting from the hypofunction of the neural crest. It is our intention to show that people with SZ exhibit more marked domesticated traits at the morphological, physiological, and behavioral levels. We also show that genes involved in domestication and neural crest development and function comprise nearly 20% of SZ candidates, most of which exhibit altered expression profiles in the brain of SZ patients, specifically in areas involved in language processing. Based on these observations, we conclude that SZ may represent an abnormal ontogenetic itinerary for the human faculty of language, resulting, at least in part, from changes in genes important for the domestication syndrome and primarily involving the neural crest.

scholarly journals Schizophrenia and human self-domestication: an evolutionary linguistics approach

2016 ◽  
Author(s):  
Antonio Benítez-Burraco ◽  
Lorena Di Pietro ◽  
Marta Barba ◽  
Wanda Lattanzi
Keyword(s):  
Neural Crest ◽  
Language Processing ◽  
Expression Profiles ◽  
Neurodevelopmental Disorder ◽  
Human Populations ◽  
Altered Expression ◽  
Domestication Syndrome ◽  
Evolutionary Linguistics ◽  
Genetic And Environmental Factors ◽  
And Function

AbstractSchizophrenia (SZ) is a pervasive neurodevelopmental disorder entailing social and cognitive deficits, including marked problems with language. Its complex multifactorial etiopathogenesis, including genetic and environmental factors, is still widely uncertain. SZ incidence has always been high and quite stable in human populations, across time and regardless of cultural implications, due to unclear reasons. It has been hypothesised that SZ pathophysiology may involve the biological components that changed during the recent human evolutionary history and led to our distinctive mode of cognition, which includes language skills. In this paper we explore this possibility, focusing on the self-domestication of the human species. This has been claimed to account for many human-specific distinctive traits, including aspects of our behaviour and cognition, and to favour the emergence of complex languages through cultural evolution. The “domestication syndrome” in mammals comprises the constellation of traits exhibited by domesticated strains, seemingly resulting from the hypofunction of the neural crest. It is our intention to show that people with SZ exhibit more marked domesticated traits at the morphological, physiological, and behavioural levels. We also show that genes involved in domestication and neural crest development and function comprise nearly 20% SZ candidates, most of which exhibit altered expression profiles in the brain of SZ patients, specifically in areas involved in language processing. Based on these observations, we conclude that SZ may represent an abnormal ontogenetic itinerary for the human faculty of language, resulting, at least in part, from changes in genes important for the “domestication syndrome” and, primarily involving the neural crest.

scholarly journals Language impairments in ASD resulting from a failed domestication of the human brain

2016 ◽  
Author(s):  
Antonio Benítez-Burraco ◽  
Wanda Lattanzi ◽  
Elliot Murphy
Keyword(s):  
Human Brain ◽  
Neural Crest ◽  
Language Processing ◽  
Expression Profiles ◽  
Autism Spectrum ◽  
Human Populations ◽  
Altered Expression ◽  
Domestication Syndrome ◽  
High Prevalence ◽  
The Brain

AbstractAutism spectrum disorders (ASD) are pervasive neurodevelopmental disorders entailing social and cognitive deficits, including marked problems with language. Numerous genes have been associated with ASD, but it is unclear how language deficits arise from gene mutation or dysregulation. It is also unclear why ASD shows such high prevalence within human populations. Interestingly, the emergence of a modern faculty of language has been hypothesised to be linked to changes in the human brain/skull, but also to the process of self-domestication of the human species. It is our intention to show that people with ASD exhibit less marked domesticated traits at the morphological, physiological, and behavioural levels. We also discuss many ASD candidates represented among the genes known to be involved in the domestication syndrome (the constellation of traits exhibited by domesticated mammals, which seemingly results from the hypofunction of the neural crest) and among the set of genes involved in language function closely connected to them. Moreover, many of these genes show altered expression profiles in the brain of autists. In addition, some candidates for domestication and language-readiness show the same expression profile in people with ASD and chimps in different brain areas involved in language processing. Similarities regarding the brain oscillatory behaviour of these areas can be expected too. We conclude that ASD may represent an abnormal ontogenetic itinerary for the human faculty of language resulting in part from changes in genes important for the domestication syndrome and, ultimately, from the normal functioning of the neural crest.

The Oral Intake of Organic Germanium, Ge-132, Elevates α-Tocopherol Levels in the Plas-ma and Modulates Hepatic Gene Expression Profiles to Promote Immune Activation in Mice

2014 ◽  
Vol 84 (3-4) ◽  
pp. 0183-0195 ◽  
Author(s):  
Takashi Nakamura ◽  
Tomoya Takeda ◽  
Yoshihiko Tokuji
Keyword(s):  
Gene Expression ◽  
Immune Activation ◽  
Expression Profiles ◽  
Water Soluble ◽  
Alpha Tocopherol ◽  
Hepatic Gene Expression ◽  
Tocopherol Concentration ◽  
Altered Expression ◽  
Atp Production ◽  
Transfer Protein

The common water-soluble organic germanium compound poly-trans-[(2-carboxyethyl) germasesquioxane] (Ge-132) exhibits activities related to immune responses and antioxidant induction. In this study, we evaluated the antioxidative effect of dietary Ge-132 in the plasma of mice. Male ICR mice (seven mice per group) received an AIN-76 diet with 0.05 % Ge-132; three groups received the Ge-132-containing diet for 0, 1 or 4 days. The plasma alpha-tocopherol (α-tocopherol) concentration increased from 6.85 to 9.60 μg/ml after 4 days of Ge-132 intake (p < 0.05). We evaluated the changes in hepatic gene expression related to antioxidative activity as well as in the entire expression profile after one day of Ge-132 intake, using DNA microarray technology. We identified 1,220 genes with altered expression levels greater than 1.5-fold (increased or decreased) as a result of Ge-132 intake, and α-tocopherol transfer protein (Ttpa) gene expression was increased 1.62-fold. Immune activation was identified as the category with the most changes (containing 60 Gene Ontology (GO) term biological processes (BPs), 41 genes) via functional clustering analysis of altered gene expression. Ge-132 affected genes in clusters related to ATP production (22 GO term BPs, 21 genes), lipid metabolism (4 GO term BPs, 38 genes) and apoptosis (5 GO term BPs). Many GO term BPs containing these categories were significantly affected by the Ge-132 intake. Oral Ge-132 intake may therefore have increased plasma α-tocopherol levels by up-regulating α-tocopherol transfer protein (Ttpa) gene expression.

scholarly journals The circular RNA circSlc7a11 promotes bone cancer pain pathogenesis in rats by modulating LLC-WRC 256 cell proliferation and apoptosis

2021 ◽  
Author(s):  
Han-Wen Chen ◽  
Xiao-Xia Zhang ◽  
Zhu-Ding Peng ◽  
Zu-Min Xing ◽  
Yi-Wen Zhang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cancer Pain ◽  
Expression Profiles ◽  
Bone Cancer ◽  
Circular Rna ◽  
Differentially Expressed ◽  
Bone Cancer Pain ◽  
Circular Rnas ◽  
Altered Expression ◽  
Proliferation And Apoptosis

AbstractTreatment of bone cancer pain (BCP) caused by bone metastasis in advanced cancers remains a challenge in clinical oncology, and the underlying mechanisms of BCP are poorly understood. This study aimed to investigate the pathogenic roles of circular RNAs (circRNAs) in regulating cancer cell proliferation and BCP development. Eight differentially expressed circRNAs in the rat spinal cord were validated by agarose gel electrophoresis and Sanger sequencing. Expression of circRNAs and mRNAs was detected by quantitative RT-PCR. MTS assay and flow cytometry were performed to analyze cell proliferation and apoptosis, respectively. Differentially expressed mRNA profiles were characterized by deep RNA sequencing, hierarchical clustering, and functional categorization. The interactions among circRNAs, microRNAs (miRNAs), and mRNAs were predicted using TargetScan. Additionally, western blot was performed to determine the protein levels of Pax8, Isg15, and Cxcl10. Multiple circRNAs were differentially expressed in the spinal cords of BCP model rats; of these, circSlc7a11 showed the greatest increase in expression. The overexpression of circSlc7a11 significantly promoted cell proliferation and repressed apoptosis of LLC-WRC 256 and UMR-106 cells, whereas circSlc7a11 silencing produced the opposite effects. Altered expression of circSlc7a11 also induced substantial changes in the mRNA expression profiles of LLC-WRC 256 cells; these changes were linked to multiple apoptotic processes and signaling pathways, such as the chemokine signaling pathway, and formed a complex circRNA/miRNA/mRNA network. Additionally, Pax8, Isg15, and Cxc110 protein level in LLC-WRC 256 cells was consistent with the mRNA results. The circRNA circSlc7a11 regulates rat BCP development by modulating LLC-WRC 256 cell proliferation and apoptosis through multiple-signaling mechanisms.

scholarly journals Inhibitors of Chemoresistance Pathways in Combination with Ara-C to Overcome Multidrug Resistance in AML. A Mini Review

2021 ◽  
Vol 22 (9) ◽  
pp. 4955
Author(s):  
Guadalupe Rosario Fajardo-Orduña ◽  
Edgar Ledesma-Martínez ◽  
Itzen Aguiñiga-Sánchez ◽  
María de Lourdes Mora-García ◽  
Benny Weiss-Steider ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Hematopoietic Cell Transplantation ◽  
Acquired Resistance ◽  
Clonal Expansion ◽  
Leukemic Cells ◽  
Hematopoietic Progenitor ◽  
Primary Resistance ◽  
Altered Expression ◽  
Synergistic Cytotoxicity ◽  
And Function

Acute myeloid leukemia (AML), the most common type of leukemia in older adults, is a heterogeneous disease that originates from the clonal expansion of undifferentiated hematopoietic progenitor cells. These cells present a remarkable variety of genes and proteins with altered expression and function. Despite significant advances in understanding the molecular panorama of AML and the development of therapies that target mutations, survival has not improved significantly, and the therapy standard is still based on highly toxic chemotherapy, which includes cytarabine (Ara-C) and allogeneic hematopoietic cell transplantation. Approximately 60% of AML patients respond favorably to these treatments and go into complete remission; however, most eventually relapse, develop refractory disease or chemoresistance, and do not survive for more than five years. Therefore, drug resistance that initially occurs in leukemic cells (primary resistance) or that develops during or after treatment (acquired resistance) has become the main obstacle to AML treatment. In this work, the main molecules responsible for generating chemoresistance to Ara-C in AML are discussed, as well as some of the newer strategies to overcome it, such as the inclusion of molecules that can induce synergistic cytotoxicity with Ara-C (MNKI-8e, emodin, metformin and niclosamide), subtoxic concentrations of chemotherapy (PD0332991), and potently antineoplastic treatments that do not damage nonmalignant cells (heteronemin or hydroxyurea + azidothymidine).

scholarly journals Targeting Senescent Cells to Counter Aging and Aging-Related Conditions

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 818-818
Author(s):  
Nathan LeBrasseur
Keyword(s):  
Human Populations ◽  
Geriatric Syndromes ◽  
Preclinical Models ◽  
Pharmacological Agents ◽  
New Class ◽  
Age Related ◽  
Selective Elimination ◽  
Early Phase Clinical Trials ◽  
And Function ◽  
State Of The Science

Abstract In response to various forms of age-associated damage, cells can enter a state of senescence. Senescent cells can compromise the health and function of a tissue, and their accumulation with advancing age is believed to contribute to age-related diseases and geriatric syndromes. In preclinical models (i.e., mice), selective elimination of senescent cells through either genetic approaches or a new class of pharmacological agents, termed “senolytics”, has been show to effectively delay, prevent, or reverse the onset and/or progression of pulmonary disease, osteoporosis, atherosclerosis, diabetes, cognitive decline, and several other conditions. Thus, considerable efforts are underway to optimize pharmacological strategies and test their effectiveness in human populations. This seminar will highlight the state-of-the-science of senolytic drugs, and the opportunities and challenges for early phase clinical trials in humans.

scholarly journals Molecular Factors and Biochemical Pathways Induced by Febrile Temperature in Intraerythrocytic Plasmodium falciparum Parasites

2007 ◽  
Vol 75 (4) ◽  
pp. 2012-2025 ◽  
Author(s):  
Miranda S. M. Oakley ◽  
Sanjai Kumar ◽  
Vivek Anantharaman ◽  
Hong Zheng ◽  
Babita Mahajan ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Elevated Temperature ◽  
Profile Analysis ◽  
Expression Profiles ◽  
Febrile Illness ◽  
Dependent Manner ◽  
Sequence Profile ◽  
Host Cell Membrane ◽  
Altered Expression ◽  
Parasite Survival

ABSTRACT Intermittent episodes of febrile illness are the most benign and recognized symptom of infection with malaria parasites, although the effects on parasite survival and virulence remain unclear. In this study, we identified the molecular factors altered in response to febrile temperature by measuring differential expression levels of individual genes using high-density oligonucleotide microarray technology and by performing biological assays in asexual-stage Plasmodium falciparum parasite cultures incubated at 37°C and 41°C (an elevated temperature that is equivalent to malaria-induced febrile illness in the host). Elevated temperature had a profound influence on expression of individual genes; 336 of approximately 5,300 genes (6.3% of the genome) had altered expression profiles. Of these, 163 genes (49%) were upregulated by twofold or greater, and 173 genes (51%) were downregulated by twofold or greater. In-depth sensitive sequence profile analysis revealed that febrile temperature-induced responses caused significant alterations in the major parasite biologic networks and pathways and that these changes are well coordinated and intricately linked. One of the most notable transcriptional changes occurs in genes encoding proteins containing the predicted Pexel motifs that are exported into the host cytoplasm or inserted into the host cell membrane and are likely to be associated with erythrocyte remodeling and parasite sequestration functions. Using our sensitive computational analysis, we were also able to assign biochemical or biologic functional predictions for at least 100 distinct genes previously annotated as “hypothetical.” We find that cultivation of P. falciparum parasites at 41°C leads to parasite death in a time-dependent manner. The presence of the “crisis forms” and the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling-positive parasites following heat treatment strongly support the notion that an apoptosis-like cell death mechanism might be induced in response to febrile temperatures. These studies enhance the possibility of designing vaccines and drugs on the basis of disruption in molecules and pathways of parasite survival and virulence activated in response to febrile temperatures.

GAMYB TF modulates bHLH142 and is homeostatically regulated by TDR TF during rice anther tapetal and pollen development

2021 ◽  
Author(s):  
Swee-Suak Ko ◽  
Min-Jeng Li ◽  
Yi-Cheng Ho ◽  
Chun-Ping Yu ◽  
Ting-Ting Yang ◽  
...  
Keyword(s):  
Pollen Development ◽  
Molecular Mechanisms ◽  
Early Stage ◽  
Specific Binding ◽  
Biological Functions ◽  
Altered Expression ◽  
Regulatory Pathways ◽  
E Box ◽  
And Function ◽  
Different Tissues

Abstract GAMYB, UDT1, TIP2/bHLH142, TDR, and EAT1/DTD are important transcription factors (TFs) that play a crucial role during rice pollen development. This study demonstrates that bHLH142 acts downstream of UDT1 and GAMYB and works as a “hub” in these two pollen pathways. We show that GAMYB modulates bHLH142 expression through specific binding to the MYB motif of bHLH142 promoter during early stage of pollen development; while TDR acts as a transcriptional repressor of the GAMYB modulation of bHLH142 by binding to the E-box close to the MYB motif on the promoter. The altered expression of TFs highlights the importance that a tight, precise, and coordinated regulation among these TFs is essential for normal pollen development. Most notably, this study illustrates the regulatory pathways of GAMYB and UDT1 that rely on bHLH142 in a direct and an indirect manner, respectively, and function in different tissues with distinct biological functions during pollen development. This study advances our understanding of the molecular mechanisms of rice pollen development.

Another role for melanocytes: their importance for normal stria vascularis development in the mammalian inner ear

Development ◽  
1989 ◽  
Vol 107 (3) ◽  
pp. 453-463 ◽  
Author(s):  
K.P. Steel ◽  
C. Barkway
Keyword(s):  
Neural Crest ◽  
Basal Cell ◽  
Stria Vascularis ◽  
Normal Adult ◽  
Basal Cells ◽  
Cochlear Duct ◽  
Cell Layers ◽  
Marginal Cells ◽  
Intermediate Cells ◽  
And Function

The stria vascularis of the mammalian cochlea is composed primarily of three types of cells. Marginal cells line the lumen of the cochlear duct and are of epithelial origin. Basal cells also form a continuous layer and they may be mesodermal or derived from the neural crest. Intermediate cells are melanocyte-like cells, presumably derived from the neural crest, and are scattered between the marginal and basal cell layers. The marginal cells form extensive interdigitations with the basal and intermediate cells in the normal adult stria. The stria also contains a rich supply of blood vessels. We investigated the role of melanocytes in the stria vascularis by studying its development in a mouse mutant, viable dominant spotting, which is known to have a primary neural crest defect leading to an absence of recognisable melanocytes in the skin. Melanocytes were not found in the stria of most of the mutants examined, and from about 6 days of age onwards a reduced amount of interdigitation amongst the cells of the stria was observed. These ultrastructural anomalies were associated with strial dysfunction. In the normal adult mammal, the stria produces an endocochlear potential (EP), a resting dc potential in the endolymph in the cochlear duct, which in mice is normally about +100 mV. In our control mice, EP rose to adult levels between 6 and 16 days after birth. In most of the mutants we studied, EP was close to zero at all ages from 6 to 20 days. Melanocyte-like cells appear to be vital for normal stria vascularis development and function. They may be necessary to facilitate the normal process of interdigitation between marginal and basal cell processes at a particular stage during development, and the lack of adequate interdigitation in the mutants may be the cause of their strial dysfunction. Alternatively, melanocytes may have some direct, essential role in the production of an EP by the stria. Melanocytes may be important both for normal strial development and for the production of the EP. We believe this is the clearest demonstration yet of a role for migratory melanocytes other than their role in pigmentation.

scholarly journals Salivary MicroRNAs for Early Detection of Head and Neck Squamous Cell Carcinoma: A Case-Control Study in the High Altitude Mestizo Ecuadorian Population

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Carolina Salazar-Ruales ◽  
Jessica-Viviana Arguello ◽  
Andrés López-Cortés ◽  
Alejandro Cabrera-Andrade ◽  
Jennyfer M. García-Cárdenas ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
High Altitude ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Expression Profiles ◽  
Neck Squamous Cell Carcinoma ◽  
Altered Expression ◽  
Mortality And Morbidity ◽  
Tumor Stages

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer with the highest incidence worldwide. HNSCC is often diagnosed at advanced stages, incurring significant high mortality and morbidity. The use of saliva, as a noninvasive tool for the diagnosis of cancer, has recently increased. Salivary microRNAs (miRNAs) have emerged as a promising molecular tool for early diagnosis of HNSCC. The aim was to identify the differential expression of salivary miRNAs associated with HNSCC in the high altitude mestizo Ecuadorian population. Using PCR Arrays, miR-122-5p, miR-92a-3p, miR-124-3p, miR-205-5p, and miR-146a-5p were found as the most representative ones. Subsequently, miRNAs expression was confirmed in saliva samples from 108 cases and 108 controls. miR-122-5p, miR-92a-3p, miR-124-3p, and miR-146a-5p showed significant statistical difference between cases and controls with areas under the curve (AUC) of 0.73 (p < 0.001), 0.70 (p < 0.001), 0.71 (p = 0.002), and 0.66 (p = 0.008), respectively. miRNAs were also deregulated in between HNSCC localizations. A differentiated expression of miR-122-5p between oral cancer and oropharynx cancer (AUC of 0.96 p = 0.01) was found: miR-124-3p between larynx and pharynx (AUC = 0.97, p < 0.01) and miR-146a-5p between larynx, oropharynx, and oral cavity (AUC = 0.96, p = 0.01). Moreover, miR-122-5p, miR-124-3p, miR-205-5p, and miR-146a-5p could differentiate between HPV+ and HPV- (p=0.004). Finally, the expression profiles of the five miRNAs were evaluated to discriminate HNSCC patient’s tumor stages (TNM 2-4). miR-122-5p differentiates TNM 2 and 3 (p = 0.002, AUC = 0.92), miR-124-3p TNM 2, 3, and 4 (p < 0.001, AUC = 98), miR-146a-5p TNM 2 and 3 (p < 0.001, AUC = 0.97), and miR-92a-3p TNM 3 (p < 0.001, AUC = 0.99). Taken together, these findings show that altered expression of miRNAs could be used as biomarkers for HNSCC diagnosis in the high altitude mestizo Ecuadorian population.

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