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1.
Curr Psychiatry Rep ; 23(10): 68, 2021 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-34648081

RESUMEN

PURPOSE OF REVIEW: We present biological and psychological factors implicated in psychiatric manifestations of SARS-CoV-2, as well as its neuroinvasive capability and immune pathophysiology. RECENT FINDINGS: Preexisting mental illness leads to worse clinical outcomes in COVID-19. The presence of the virus was reported in the cerebrospinal fluid (CSF) and brain tissue post-mortem. Most common psychiatric manifestations include delirium, mood disorders, anxiety disorders, and posttraumatic stress disorder. "Long-COVID" non-syndromal presentations include "brain-fogginess," autonomic instability, fatigue, and insomnia. SARS-CoV-2 infection can trigger prior vulnerabilities based on the priming of microglia and other cells, induced or perpetuated by aging and mental and physical illnesses. COVID-19 could further induce priming of neuroimmunological substrates leading to exacerbated immune response and autoimmunity targeting structures in the central nervous system (CNS), in response to minor immune activating environmental exposures, including stress, minor infections, allergens, pollutants, and traumatic brain injury.


Asunto(s)
COVID-19 , Trastornos por Estrés Postraumático , Encéfalo , Sistema Nervioso Central , Humanos , SARS-CoV-2
2.
Neuroepidemiology ; 54(5): 392-397, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32739915

RESUMEN

INTRODUCTION: Previous research has suggested that the Amish may experience a relatively high prevalence of Parkinson's disease (PD) and/or parkinsonian motor signs. METHODS: In a large sample from the Amish community in Lancaster County, Pennsylvania, age ≥18 years, we assessed the prevalence of self-reported PD diagnosis. For those without self-reported PD diagnosis, we assessed the frequency of PD-related motor symptoms using a 9-item questionnaire that was designed by the PD Epidemiology Research Group. Lastly, we queried study participants for the presence of 2 nonmotor symptoms that have been commonly linked to PD: bowel movement frequency and daytime sleepiness. RESULTS: Among 2,025 subjects who answered the PD questionnaire, 430 were older than 60 years. Of 430 participants ≥60 years, 5 (1.2%) reported a PD diagnosis. Of those without a PD diagnosis, 10.5% reported ≥1 and 1.2% ≥ 4 motor symptoms for the 9-item PD screening questionnaire. Of the 3,789 subjects who answered the question about bowel movement frequency, 0.7% reported ≤3 bowel movements per week. Among 1,710 subjects who answered the question about daytime sleepiness, 8.1% of the participants reported "always" sleepy during the day. DISCUSSION: These data neither support a markedly higher PD prevalence in the older Lancaster Amish nor do they show dramatically higher motor and/or selected nonmotor symptoms than the general population. Future studies that employ more rigorous procedures for case identification and PD-specific preclinical symptoms/tests are needed to determine the potential differences and similarities among different Amish populations and between Amish and non-Amish populations.


Asunto(s)
Amish , Enfermedad de Parkinson/etnología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estreñimiento/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/epidemiología , Pennsylvania , Proyectos Piloto , Prevalencia , Somnolencia , Encuestas y Cuestionarios , Adulto Joven
3.
Proc Natl Acad Sci U S A ; 114(31): E6361-E6370, 2017 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-28716924

RESUMEN

Porphyra umbilicalis (laver) belongs to an ancient group of red algae (Bangiophyceae), is harvested for human food, and thrives in the harsh conditions of the upper intertidal zone. Here we present the 87.7-Mbp haploid Porphyra genome (65.8% G + C content, 13,125 gene loci) and elucidate traits that inform our understanding of the biology of red algae as one of the few multicellular eukaryotic lineages. Novel features of the Porphyra genome shared by other red algae relate to the cytoskeleton, calcium signaling, the cell cycle, and stress-tolerance mechanisms including photoprotection. Cytoskeletal motor proteins in Porphyra are restricted to a small set of kinesins that appear to be the only universal cytoskeletal motors within the red algae. Dynein motors are absent, and most red algae, including Porphyra, lack myosin. This surprisingly minimal cytoskeleton offers a potential explanation for why red algal cells and multicellular structures are more limited in size than in most multicellular lineages. Additional discoveries further relating to the stress tolerance of bangiophytes include ancestral enzymes for sulfation of the hydrophilic galactan-rich cell wall, evidence for mannan synthesis that originated before the divergence of green and red algae, and a high capacity for nutrient uptake. Our analyses provide a comprehensive understanding of the red algae, which are both commercially important and have played a major role in the evolution of other algal groups through secondary endosymbioses.


Asunto(s)
Citoesqueleto/genética , Evolución Molecular , Genoma de Planta/genética , Porphyra/citología , Porphyra/genética , Actinas/genética , Señalización del Calcio/genética , Ciclo Celular/genética , Pared Celular/genética , Pared Celular/metabolismo , Cromatina/genética , Cinesinas/genética , Filogenia
4.
Br J Sports Med ; 53(6): 328-333, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30049779

RESUMEN

Various organisations and experts have published numerous statements and recommendations regarding different aspects of sports-related concussion including definition, presentation, treatment, management and return to play guidelines. 1-7 To date, there have been no written consensus statements specific for combat sports regarding management of combatants who have suffered a concussion or for return to competition after a concussion. In combat sports, head contact is an objective of the sport itself. Accordingly, management and treatment of concussion in combat sports should, and must, be more stringent than for non-combat sports counterparts.The Association of Ringside Physicians (an international, non-profit organisation dedicated to the health and safety of the combat sports athlete) sets forth this consensus statement to establish management guidelines that ringside physicians, fighters, referees, trainers, promoters, sanctioning bodies and other healthcare professionals can use in the ringside setting. We also provide guidelines for the return of a combat sports athlete to competition after sustaining a concussion. This consensus statement does not address the management of moderate to severe forms of traumatic brain injury, such as intracranial bleeds, nor does it address the return to competition for combat sports athletes who have suffered such an injury. These more severe forms of brain injuries are beyond the scope of this statement. This consensus statement does not address neuroimaging guidelines in combat sports.


Asunto(s)
Traumatismos en Atletas/terapia , Conmoción Encefálica/terapia , Medicina Deportiva/métodos , Atletas , Consenso , Humanos , Médicos , Volver al Deporte , Sociedades Médicas
5.
Pteridines ; 30(1): 133-141, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31631951

RESUMEN

BACKGROUND: Summer/spring-type seasonal affective disorder (S-SAD) is the less common subtype of seasonal affective disorder and evidence regarding potential triggers of S-SAD is scarce. Recent reports support association of airborne-pollen with seasonal exacerbation of depression (mood seasonality) and timing of suicidal behavior. Therefore, we hypothesized that Old Order Amish (OOA) with summer/spring pattern of seasonality (abbreviated as summer pattern) and S-SAD will have significant mood worsening on high pollen days. METHODS: A seasonal pattern of mood worsening and SAD parameters were estimated using Seasonal Pattern Assessment Questionnaire (SPAQ). Age- and gender-adjusted ANCOVAs and post hoc analyses were conducted to compare mood worsening on days with high pollen counts between summer-pattern vs no-summer-pattern of mood worsening, S-SAD vs no-S-SAD, winter-pattern vs no-winter-pattern of mood worsening, and W-SAD vs no-W-SAD groups. RESULTS: The prevalence of S-SAD was 0.4%, while 4.5% of individuals had a summer pattern of mood seasonality. A statistically significant difference for mood worsening on high pollen days was observed between summer-pattern vs no-summer-pattern of mood worsening (p = 0.006). The significant association between S-SAD vs no-SAD groups (p = 0.032) for mood worsening on high pollen days did not withstand Bonferroni adjustment for multiple comparisons. No significant association was found for winter-pattern vs no-winter-pattern of mood worsening (p = 0.61) and for W-SAD vs no-W-SAD (p = 0.19) groups. CONCLUSION: Our results are consistent with previous studies implicating links between aeroallergen exposure and summer pattern of seasonality, but not the winter pattern of seasonality.

6.
Pteridines ; 30(1): 1-9, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30918422

RESUMEN

BACKGROUND: Evidence links Toxoplasmagondii (T. gondii), a neurotropic parasite, with schizophrenia, mood disorders and suicidal behavior, all of which are associated and exacerbated by disrupted sleep. Moreover, low-grade immune activation and dopaminergic overstimulation, which are consequences of T. gondii infection, could alter sleep patterns and duration. METHODS: Sleep data on 833 Amish participants [mean age (SD) = 44.28 (16.99) years; 59.06% women] were obtained via self-reported questionnaires that assessed sleep problems, duration and timing. T. gondii IgG was measured with ELISA. Data were analyzed using multivariable logistic regressions and linear mixed models, with adjustment for age, sex and family structure. RESULTS: T. gondii seropositives reported less sleep problems (p < 0.005) and less daytime problems due to poor sleep (p < 0.005). Higher T. gondii titers were associated with longer sleep duration (p < 0.05), earlier bedtime (p< 0.005) earlier mid-sleep time (p < 0.05). CONCLUSIONS: It seems unlikely that sleep mediates the previously reported associations between T. gondii and mental illness. Future longitudinal studies with objective measures are necessary to replicate our findings.

7.
J Phycol ; 54(6): 879-887, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30288746

RESUMEN

Red algae are the oldest identifiable multicellular eukaryotes, with a fossil record dating back more than a billion years. During that time two major rhodophyte lineages, bangiophytes and florideophytes, have evolved varied levels of morphological complexity. These two groups are distinguished, in part, by different patterns of multicellular development, with florideophytes exhibiting a far greater diversity of morphologies. Interestingly, during their long evolutionary history, there is no record of a rhodophyte achieving the kinds of cellular and tissue-specific differentiation present in other multicellular algal lineages. To date, the genetic underpinnings of unique aspects of red algal development are largely unexplored; however, they must reflect the complements and patterns of expression of key regulatory genes. Here we report comparative evolutionary and gene expression analyses of core subunits of the SWI/SNF chromatin-remodeling complex, which is implicated in cell differentiation and developmental regulation in more well studied multicellular groups. Our results suggest that a single, canonical SWI/SNF complex was present in the rhodophyte ancestor, with gene duplications and evolutionary diversification of SWI/SNF subunits accompanying the evolution of multicellularity in the common ancestor of bangiophytes and florideophytes. Differences in how SWI/SNF chromatin remodeling evolved subsequently, in particular gene losses and more rapid divergence of SWI3 and SNF5 in bangiophytes, could help to explain why they exhibit a more limited range of morphological complexity than their florideophyte cousins.


Asunto(s)
Proteínas Algáceas/genética , Ensamble y Desensamble de Cromatina , Rhodophyta/genética , Transcripción Genética , Proteínas Algáceas/metabolismo , Genoma , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Rhodophyta/metabolismo , Transcriptoma
8.
Proc Natl Acad Sci U S A ; 111(16): 5920-5, 2014 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-24711388

RESUMEN

In model eukaryotes, the C-terminal domain (CTD) of the largest subunit of DNA-dependent RNA polymerase II (RNAP II) is composed of tandemly repeated heptads with the consensus sequence YSPTSPS. The core motif and tandem structure generally are conserved across model taxa, including animals, yeasts and higher plants. Broader investigations revealed that CTDs of many organisms deviate substantially from this canonical structure; however, limited sampling made it difficult to determine whether disordered sequences reflect the CTD's ancestral state or degeneration from ancestral repetitive structures. Therefore, we undertook, to our knowledge, the broadest investigation to date of the evolution of the RNAP II CTD across eukaryotic diversity. Our results indicate that a tandemly repeated CTD existed in the ancestors of each major taxon, and that degeneration and reinvention of this ordered structure are common features of CTD evolution. Lineage-specific CTD modifications appear to be associated with greater developmental complexity in multicellular organisms, a pattern taken to an extreme in fungi and red algae, in which the CTD has undergone dramatic to complete alteration during the transition from unicellular to developmentally complex forms. Overall, loss and reinvention of repeats have punctuated CTD evolution, occurring independently and sometimes repeatedly in various groups.


Asunto(s)
Evolución Molecular , Variación Genética , Filogenia , ARN Polimerasa II/química , ARN Polimerasa II/genética , Animales , Hongos/metabolismo , Plantas/metabolismo , Estructura Terciaria de Proteína , ARN Polimerasa II/metabolismo , Secuencias Repetitivas de Aminoácido , Rhodophyta/metabolismo
9.
Pteridines ; 28(3-4): 185-194, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29657363

RESUMEN

Toxoplasma gondii (T. gondii) IgG seropositivity and serointensity have been previously associated with suicidal self-directed violence (SSDV). Although associations with unipolar depression have also been investigated, the results have been inconsistent, possibly as a consequence of high heterogeneity. We have now studied this association in a more homogeneous population, [that is (i.e.) Old Order Amish (OOA)] with previously reported high T. gondii seroprevalence. In 306 OOA with a mean age of 46.1 ± 16.7 years, including 191 (62.4%) women in the Amish Wellness Study, we obtained both T. gondii IgG titers (by enzyme-linked immunosorbent assay [ELISA]), and depression screening questionnaires (Patient Health Questionnaire [PHQ-9] [n = 280] and PHQ-2 [n = 26]). Associations between T. gondii IgG and dysphoria/hopelessness and anhedonia scores on depression screening questionnaires were analyzed using multivariable linear methods with adjustment for age and sex. Serointensity was associated with both current dysphoria/hopelessness (p = 0.045) and current combined anhedonia and dysphoria/hopelessness (p = 0.043), while associations with simple anhedonia and past/lifelong (rather than current) phenotypes were not significant. These results indicate the need for larger longitudinal studies to corroborate the association between dysphoria/hopelessness and T. gondii IgG-titers. Current hopelessness is a known risk factor for SSDV which responds particularly well to cognitive behavioral therapy, and may be a focused treatment target for T. gondii-positive individuals at high-risk for SSDV.

10.
Pteridines ; 28(3-4): 195-204, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29657364

RESUMEN

Toxoplasma gondii (T. gondii) infects central nervous tissue and is kept in relative dormancy by a healthy immune system. Sleep disturbances have been found to precipitate mental illness, suicidal behavior and car accidents, which have been previously linked to T. gondii as well. We speculated that if sleep disruption, particularly insomnia, would mediate, at least partly, the link between T. gondii infection and related behavioral dysregulation, then we would be able to identify significant associations between sleep disruption and T. gondii. The mechanisms for such an association may involve dopamine (DA) production by T. gondii, or collateral effects of immune activation necessary to keep T. gondii in check. Sleep questionnaires from 2031 Old Order Amish were analyzed in relationship to T. gondii-IgG antibodies measured by enzyme-linked immunosorbent assay (ELISA). Toxoplasma gondii seropositivity and serointensity were not associated with any of the sleep latency variables or Epworth Sleepiness Scale (ESS). A secondary analysis identified, after adjustment for age group, a statistical trend toward shorter sleep duration in seropositive men (p = 0.07). In conclusion, it is unlikely that sleep disruption mediates links between T. gondii and mental illness or behavioral dysregulation. Trending gender differences in associations between T. gondii and shorter sleep need further investigation.

11.
J Phycol ; 50(3): 462-71, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26988319

RESUMEN

The idea that evolutionary models should minimize plastid endosymbioses has dominated thinking about the history of eukaryotic photosynthesis. Although a reasonable starting point, this framework has not gained support from observed patterns of algal and plant evolution, and can be an obstacle to fully understanding the modern distribution of plastids. Empirical data indicate that plastid losses are extremely uncommon, that major changes in plastid biochemistry/architecture are evidence of an endosymbiotic event, and that comparable selection pressures can lead to remarkable convergences in algae with different endosymbiotic origins. Such empirically based generalizations can provide a more realistic philosophical framework for interpreting complex and often contradictory results from phylogenomic investigations of algal evolution.

12.
BMC Evol Biol ; 13: 37, 2013 Feb 11.
Artículo en Inglés | MEDLINE | ID: mdl-23398820

RESUMEN

BACKGROUND: The acquisition of complex transcriptional regulatory abilities and epigenetic machinery facilitated the transition of the ancestor of apicomplexans from a free-living organism to an obligate parasite. The ability to control sophisticated gene expression patterns enabled these ancient organisms to evolve several differentiated forms, invade multiple hosts and evade host immunity. How these abilities were acquired remains an outstanding question in protistan biology. RESULTS: In this work, we study SET domain bearing genes that are implicated in mediating immune evasion, invasion and cytoadhesion pathways of modern apicomplexans, including malaria parasites. We provide the first conclusive evidence of a horizontal gene transfer of a Histone H4 Lysine 20 (H4K20) modifier, Set8, from an animal host to the ancestor of apicomplexans. Set8 is known to contribute to the coordinated expression of genes involved in immune evasion in modern apicomplexans. We also show the likely transfer of a H3K36 methyltransferase (Ashr3 from plants), possibly derived from algal endosymbionts. These transfers appear to date to the transition from free-living organisms to parasitism and coincide with the proposed horizontal acquisition of cytoadhesion domains, the O-glycosyltransferase that modifies these domains, and the primary family of transcription factors found in apicomplexan parasites. Notably, phylogenetic support for these conclusions is robust and the genes clearly are dissimilar to SET sequences found in the closely related parasite Perkinsus marinus, and in ciliates, the nearest free-living organisms with complete genome sequences available. CONCLUSIONS: Animal and plant sources of epigenetic machinery provide new insights into the evolution of parasitism in apicomplexans. Along with the horizontal transfer of cytoadhesive domains, O-linked glycosylation and key transcription factors, the acquisition of SET domain methyltransferases marks a key transitional event in the evolution to parasitism in this important protozoan lineage.


Asunto(s)
Apicomplexa/genética , Evolución Biológica , Transferencia de Gen Horizontal , Plasmodium falciparum/genética , Secuencia de Aminoácidos , Animales , Teorema de Bayes , ADN Protozoario/genética , Dictyostelium/genética , Histona Metiltransferasas , N-Metiltransferasa de Histona-Lisina/genética , Funciones de Verosimilitud , Nematodos/genética , Parásitos/genética , Filogenia , Análisis de Secuencia de ADN
13.
J Affect Disord ; 339: 933-942, 2023 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-37481129

RESUMEN

BACKGROUND: Increasing evidence suggests that conditions with decreased morning and increased evening light exposure, including shift work, daylight-saving time, and eveningness, are associated with elevated mortality and suicide risk. Given that the alignment between the astronomical, biological, and social time varies across a time zone, with later-shifted daylight exposure in the western partition, we hypothesized that western time zone partitions would have higher suicide rates than eastern partitions. METHODS: United States (U.S.) county-level suicide and demographic data, from 2010 to 2018, were obtained from a Centers for Disease Control database. Using longitude and latitude, counties were sorted into the western, middle, or eastern partition of their respective time zones, as well as the northern and southern halves of the U.S. Linear regressions were used to estimate the associations between suicide rates and time zone partitions, adjusting for gender, race, ethnicity, age group, and unemployment rates. RESULTS: Data were available for 2872 counties. Across the U.S., western partitions had statistically significantly higher rates of suicide compared to eastern partitions and averaged up to two additional yearly deaths per 100,000 people (p < .001). LIMITATIONS: Ecological design and limited adjustment for socioeconomic factors. CONCLUSIONS: To our knowledge, this is the first study of the relationship between longitude-based time zone partitions and suicide. The results were consistent with the hypothesized elevated suicide rates in the western partitions, and concordant with previous reports on cancer mortality and transportation fatalities. The next step is to retest the hypothesis with individual-level data, accounting for latitude, photoperiodic changes, daylight-saving time, geoclimatic variables, physical and mental health indicators, as well as socioeconomic adversity and protection.


Asunto(s)
Suicidio , Humanos , Estados Unidos/epidemiología , Factores Socioeconómicos , Etnicidad , Salud Mental
14.
Gen Comp Endocrinol ; 176(1): 52-61, 2012 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-22226730

RESUMEN

Somatolactin (SL) and SL receptor (SLR) belong to the growth hormone and cytokine type I receptor superfamilies, respectively. However, further research is required to define the duplications and functions of SL and its receptors in basal vertebrates including environmental background color adaptation in fish. In the present study, we cloned and sequenced SL and its putative receptor (SLR), classified and compared the sequences phylogenetically, and determined SL and SLR mRNA expression levels during long-term background color exposure in Cichlasoma dimerus, a freshwater South American cichlid. Our results show that C. dimerus SL and SLR share high sequence similarity with homologous from other perciform fish. Phylogenetic analysis indicates that C. dimerus SL belongs to the SLα clade sub-group. C. dimerus SLR is clearly a member of the GHR1 receptor subgroup, which includes the experimentally validated SLR from salmonids. Higher transcript levels of SLα in the pituitary and SLR in the epidermis and dermis cells of fish scales were observed in fish following long-term black background color exposure compared to those exposed to a white background. A higher number of melanophores was also observed in fish exposed for 10days to a black background compared to those exposed to a white background. These changes were concomitant to differences in SL or SLR transcript levels found in fish exposed to these two different background colors. Our results suggest, for the first time, that SLR is expressed in fish scales, and that there is an increase in SL in the pituitary and the putative SLR in likely target cells, i.e., melanophores, in long-term black background exposure in C. dimerus.


Asunto(s)
Aclimatación/genética , Cíclidos/genética , Proteínas de Peces/genética , Glicoproteínas/genética , Hormonas Hipofisarias/genética , Receptores de la Hormona Hipofisaria/genética , Receptores de Somatotropina/genética , Pigmentación de la Piel/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Cíclidos/fisiología , Clonación Molecular , Color , Ambiente , Proteínas de Peces/fisiología , Glicoproteínas/fisiología , Melanóforos/fisiología , Datos de Secuencia Molecular , Filogenia , Hormonas Hipofisarias/fisiología , ARN Mensajero/metabolismo , Receptores de la Hormona Hipofisaria/fisiología , Receptores de Somatotropina/fisiología
15.
Front Plant Sci ; 13: 840439, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35371140

RESUMEN

Genetic reprogramming of differentiated cells is studied broadly in multicellular Viridiplantae as an adaptation to herbivory or damage; however, mechanisms underlying cell development and redifferentiation are largely unknown in red algae, their nearest multicellular relatives. Here we investgate cell reprogramming in the widely cultivated, edible seaweed Neopyropia yezoesis ("nori"), where vegetative cells in wounded blades differentiate and release as large numbers of asexual spores. Based upon physiological changes and transcriptomic dynamics after wound stress in N. yezoensis and its congener Neoporphyra haitanensis, another cultivar that does not differentiate spores after wounding, we propose a three-phase model of wound-induced spore development in N. yezoensis. In Phase I, propagation of ROS by RBOH and SOD elicites systematic transduction of the wound signal, while Ca2+ dependent signaling induces cell reprogramming. In Phase II, a TOR signaling pathway and regulation of cyclin and CDK genes result in cell divisions that spread inward from the wound edge. Once sporangia form, Phase III involves expression of proteins required for spore maturation and cell wall softening. Our analyses not only provide the first model for core molecular processes controlling cellular reprogramming in rhodophytes, but also have practical implications for achieving greater control over seeding in commercial nori farming.

16.
BMC Evol Biol ; 11: 259, 2011 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-21923904

RESUMEN

A growing number of phylogenomic investigations from diverse eukaryotes are examining conflicts among gene trees as evidence of horizontal gene transfer. If multiple foreign genes from the same eukaryotic lineage are found in a given genome, it is increasingly interpreted as concerted gene transfers during a cryptic endosymbiosis in the organism's evolutionary past, also known as "endosymbiotic gene transfer" or EGT. A number of provocative hypotheses of lost or serially replaced endosymbionts have been advanced; to date, however, these inferences largely have been post-hoc interpretations of genomic-wide conflicts among gene trees. With data sets as large and complex as eukaryotic genome sequences, it is critical to examine alternative explanations for intra-genome phylogenetic conflicts, particularly how much conflicting signal is expected from directional biases and statistical noise. The availability of genome-level data both permits and necessitates phylogenomics that test explicit, a priori predictions of horizontal gene transfer, using rigorous statistical methods and clearly defined experimental controls.


Asunto(s)
Biología Computacional/métodos , Evolución Molecular , Transferencia de Gen Horizontal/genética , Genoma/genética , Modelos Genéticos , Filogenia , Simbiosis/genética , Genómica/métodos
17.
Mol Biol Evol ; 27(11): 2628-41, 2010 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-20558594

RESUMEN

With a simple tandem iterated sequence, the carboxyl terminal domain (CTD) of eukaryotic RNA polymerase II (RNAP II) serves as the central coordinator of mRNA synthesis by harmonizing a diversity of sequential interactions with transcription and processing factors. Despite intense research interest, many key questions regarding functional and evolutionary constraints on the CTD remain unanswered; for example, what selects for the canonical heptad sequence, its tandem array across organismal diversity, and constant CTD length within given species and finally and how a sequence-identical, repetitive structure can orchestrate a diversity of simultaneous and sequential, stage-dependent interactions with both modifying enzymes and binding partners? Here we examine comparative sequence evolution of 58 RNAP II CTDs from diverse taxa representing all six major eukaryotic supergroups and employ integrated evolutionary genetic, biochemical, and biophysical analyses of the yeast CTD to further clarify how this repetitive sequence must be organized for optimal RNAP II function. We find that the CTD is composed of indivisible and independent functional units that span diheptapeptides and not only a flexible conformation around each unit but also an elastic overall structure is required. More remarkably, optimal CTD function always is achieved at approximately wild-type CTD length rather than number of functional units, regardless of the characteristics of the sequence present. Our combined observations lead us to advance an updated CTD working model, in which functional, and therefore, evolutionary constraints require a flexible CTD conformation determined by the CTD sequence and tandem register to accommodate the diversity of CTD-protein interactions and a specific CTD length rather than number of functional units to correctly order and organize global CTD-protein interactions. Patterns of conservation of these features across evolutionary diversity have important implications for comparative RNAP II function in eukaryotes and can more clearly direct specific research on CTD function in currently understudied organisms.


Asunto(s)
Secuencia Conservada/genética , Evolución Molecular , ARN Polimerasa II/química , ARN Polimerasa II/genética , Secuencia de Aminoácidos , Dicroismo Circular , Variación Genética , Modelos Genéticos , Datos de Secuencia Molecular , Mutagénesis Insercional , Proteínas Mutantes/química , Proteínas Mutantes/metabolismo , Péptidos/química , Péptidos/genética , Péptidos/metabolismo , Fenotipo , Fosforilación , Docilidad , Estructura Terciaria de Proteína , Saccharomyces cerevisiae/enzimología , Saccharomyces cerevisiae/genética , Relación Estructura-Actividad
18.
Bioessays ; 31(11): 1219-32, 2009 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-19847819

RESUMEN

Some nuclear-encoded proteins are imported into higher plant plastids via the endomembrane (EM) system. Compared with multi-protein Toc and Tic translocons required for most plastid protein import, the relatively uncomplicated nature of EM trafficking led to suggestions that it was the original transport mechanism for nuclear-encoded endosymbiont proteins, and critical for the early stages of plastid evolution. Its apparent simplicity disappears, however, when EM transport is considered in light of selective constraints likely encountered during the conversion of stable endosymbionts into fully integrated organelles. From this perspective it is more parsimonious to presume the early evolution of post-translational protein import via simpler, ancestral forms of modern Toc and Tic plastid translocons, with EM trafficking arising later to accommodate glycosylation and/or protein targeting to multiple cellular locations. This hypothesis is supported by both empirical and comparative data, and is consistent with the relative paucity of EM-based transport to modern primary plastids.


Asunto(s)
Anhidrasas Carbónicas/genética , Plastidios/genética , Arabidopsis/metabolismo , Evolución Biológica , Membrana Celular/metabolismo , Evolución Molecular , Glicosilación , Mitocondrias/metabolismo , Modelos Biológicos , Modelos Teóricos , Péptidos/química , Fosfatos/metabolismo , Plastidios/metabolismo , Procesamiento Proteico-Postraduccional , Transporte de Proteínas , Simbiosis
19.
J Alzheimers Dis ; 74(1): 1-28, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32176646

RESUMEN

There is an increasing evidence that inflammation contributes to clinical and functional outcomes in traumatic brain injury (TBI). Many successful target-engaging, lesion-reducing, symptom-alleviating, and function-improving interventions in animal models of TBI have failed to show efficacy in clinical trials. Timing and immunological context are paramount for the direction, quality, and intensity of immune responses to TBI and the resulting neuroanatomical, clinical, and functional course. We present components of the immune system implicated in TBI, potential immune targets, and target-engaging interventions. The main objective of our article is to point toward modifiable molecular and cellular mechanisms that may modify the outcomes in TBI, and contribute to increasing the translational value of interventions that have been identified in animal models of TBI.


Asunto(s)
Lesiones Traumáticas del Encéfalo/inmunología , Lesiones Traumáticas del Encéfalo/patología , Encefalitis/inmunología , Encefalitis/patología , Animales , Humanos
20.
J Psychiatr Res ; 125: 75-84, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32213352

RESUMEN

Vitamin D deficiency is associated with immune dysregulation, increased vulnerability to infections, depression, and suicidal behavior. One mediator of vitamin D-dependent immune regulation and antimicrobial defense is the cathelicidin antimicrobial peptide (LL-37), encoded by the cathelicidin-related antimicrobial peptide (CRAMP) gene. We compared the mRNA expression of the CRAMP gene, the vitamin D receptor (VDR) gene, as well as the CYP27B1 and CYP24A1 genes (involved in vitamin D metabolism) in the dorsolateral prefrontal cortex (dlPFC) and anterior cingulate cortex (ACC) between depressed individuals who died by suicide (n = 15) and matched (age, gender, and post-mortem interval) non-psychiatric controls (n = 15). Gene expression was measured through qRT-PCR with TaqMan® primers and probes, with GAPDH and ß-actin genes as endogenous controls. Statistical analyses included t-tests and Pearson correlations. CRAMP mRNA expression was downregulated and VDR mRNA expression was upregulated in both dlPFC and ACC in suicides relative to controls, with no significant differences in expression of CYP24A1 and CYP27B1. To our knowledge, this is the first study on brain cathelicidin expression in the human brain in relationship to suicide. Increased VDR and decreased CRAMP expression are consistent with previously reported associations between vitamin D deficiency, immune dysregulation, and suicidal behavior, and should lead to future studies uncovering novel interactive targets for suicide prevention.


Asunto(s)
Receptores de Calcitriol , Suicidio , Péptidos Catiónicos Antimicrobianos , Encéfalo/metabolismo , Expresión Génica , Humanos , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo , Catelicidinas
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