NgCAM and VAMP2 Reveal that Direct Delivery and Dendritic Degradation Maintain Axonal Polarity

2021 ◽  
Author(s):  
Alec T. Nabb ◽  
Marvin Bentley
Keyword(s):  
Membrane Proteins ◽  
Molecular Mechanisms ◽  
Minor Role ◽  
Axonal Membrane ◽  
Quantitative Analyses ◽  
Direct Delivery ◽  
Novel Strategy ◽  
Extreme Scale ◽  
A Minor

Neurons are polarized cells of extreme scale and compartmentalization. To fulfill their role in electrochemical signaling, axons must maintain a specific complement of membrane proteins. Despite being subject of considerable attention, the trafficking pathway of axonal membrane proteins is not well understood. Two pathways, direct delivery and transcytosis, have been proposed. Previous studies reached contradictory conclusions about which of these mediates delivery of axonal membrane proteins to their destination, in part because they evaluated long-term distribution changes and not vesicle transport. We developed a novel strategy to selectively label vesicles in different trafficking pathways and determined the trafficking of two canonical axonal membrane proteins, NgCAM and VAMP2. Results from detailed quantitative analyses of transporting vesicles differed substantially from previous studies and found that axonal membrane proteins overwhelmingly undergo direct delivery. Transcytosis plays only a minor role in axonal delivery of these proteins. In addition, we identified a novel pathway by which wayward axonal proteins that reach the dendritic plasma membrane are targeted to lysosomes. These results redefine how axonal proteins achieve their polarized distribution, a crucial requirement for elucidating the underlying molecular mechanisms. [Media: see text] [Media: see text] [Media: see text] [Media: see text]

The role of heredity in cancer.

1989 ◽  
Vol 7 (4) ◽  
pp. 527-540 ◽  
Author(s):  
E G Levine ◽  
R A King ◽  
C D Bloomfield
Keyword(s):  
Molecular Mechanisms ◽  
Familial Cancer ◽  
Tumor Development ◽  
Future Research ◽  
Minor Role ◽  
Research Activity ◽  
Environmental Interactions ◽  
Future Research Directions ◽  
A Minor

Heredity is generally felt to play a minor role in the development of cancer. This review critically examines this assumption. Topics discussed include evidence for heritable predisposition in animals and humans; the potential importance of genetic-environmental interactions; approaches that are being used to successfully locate genes responsible for heritable predisposition; comparability of genetic findings among heritable and corresponding sporadic malignancies; and future research directions. Breast, colon, and lung cancer are used to exemplify clinical and research activity in familial cancer; clinical phenotypes, segregation and linkage analyses, models for environmental interactions with inherited traits, and molecular mechanisms of tumor development are discussed. We conclude that the contribution of heredity to the cancer burden is greater than generally accepted, and that study of heritable predisposition will continue to reveal carcinogenic mechanisms important to the development of all cancers.

scholarly journals Occurrence of L1014F and L1014S mutations in insecticide resistant Culex quinquefasciatus from filariasis endemic districts of West Bengal, India

2022 ◽  
Vol 16 (1) ◽  
pp. e0010000
Author(s):  
Priyanka Rai ◽  
Dhiraj Saha
Keyword(s):  
Culex Quinquefasciatus ◽  
West Bengal ◽  
Economic Status ◽  
Minor Role ◽  
Resistance Development ◽  
Vector Population ◽  
A Minor ◽  
First Time

Introduction Lymphatic filariasis causes long term morbidity and hampers the socio-economic status. Apart from the available treatments and medication, control of vector population Culex quinquefasciatus Say through the use of chemical insecticides is a widely applied strategy. However, the unrestrained application of these insecticides over many decades has led to resistance development in the vectors. Methods In order to determine the insecticide susceptibility/resistance status of Cx. quinquefasciatus from two filariasis endemic districts of West Bengal, India, wild mosquito populations were collected and assayed against six different insecticides and presence of L1014F; L1014S kdr mutations in the voltage-gated sodium channel gene was also screened along with the use of synergists to evaluate the role of major detoxifying enzymes in resistance development. Results The collected mosquito populations showed severe resistance to insecticides and the two synergists used–PBO (piperonyl butoxide) and TPP (triphenyl phosphate), were unable to restore the susceptibility status of the vector thereupon pointing towards a minor role of metabolic enzymes. kdr mutations were present in the studied populations in varying percent with higher L1014F frequency indicating its association with the observed resistance to pyrethroids and DDT. This study reports L1014S mutation in Cx. quinquefasciatus for the first time.

Variation in the recruitment behaviour of seagrass seeds: implications for population dynamics and resource management

1999 ◽  
Vol 5 (4) ◽  
pp. 251 ◽  
Author(s):  
Graeme J. Inglis
Keyword(s):  
Field Studies ◽  
Clonal Plants ◽  
Minor Role ◽  
Spatial And Temporal Scales ◽  
Local Populations ◽  
Seed Supply ◽  
Seed Reserves ◽  
A Minor ◽  
Effective Conservation

Effective conservation of marine organisms requires an understanding of the processes that affect the establishment, persistence and extinction of local populations. Our knowledge of the recruitment of seagrasses comes largely from studies done at small spatial and temporal scales within extant meadows. Descriptions of the demography of local populations, therefore, typically emphasize prolific ramet production and only a minor role for sexual propagules. Recent genetic and field studies, however, have shown greater variation in recruitment behaviour than previously suspected. In this paper, I review what is known about the seeds of seagrasses ? including their dormancy, dispersability and requirements for germination and establishment ? and examine the utility of recent conceptual models, developed for terrestrial clonal plants, to explain the long-term dynamics of seagrass populations. Sizable variation among species in seed size and dispersal strategy appears to be related predictably to variation in life-history and rates of recruitment. Species with small, poorly-dispersed fruits (e.g., Halophila, Halodule) are more likely to form persistent seed reserves and be rapid colonizers of disturbances within established meadows. Genera with large, buoyant fruits, capable of moderate dispersal (e.g., Thalassia, Posidonia), in contrast, appear to recruit rarely within existing meadows of conspecifics. Our ability to model long-term changes in demography and community structure is likely to benefit from a better knowledge of the importance of seed supply and microsite availability to recruitment.

scholarly journals Seasonal Changes of the Airborne Microbiome in a Large Urban Area

2020 ◽  
Author(s):  
Andrés Núñez ◽  
Diego A Moreno ◽  
Ana M García ◽  
Raul Guantes
Keyword(s):  
Disease Outbreaks ◽  
Urban Environments ◽  
Minor Role ◽  
Near Surface ◽  
Surface Atmosphere ◽  
Ecological Importance ◽  
Bacteria And Fungi ◽  
A Minor

Abstract Background Compared to soil or aquatic ecosystems, the atmosphere is still an underexplored environment for microbial diversity. Besides its ecological importance, the spatial and temporal characterization of aerosolized microorganisms is relevant for understanding allergy and disease outbreaks, especially in highly populated cities. Results In this study, we surveyed the composition, variability and sources of microbes (bacteria and fungi) in the near surface atmosphere of a highly populated area, spanning ~ 4,000 Km 2 around the city center of Madrid (Spain), in different seasonal periods along two years. We found a core of abundant bacterial genera robust across space and time, most of soil origin, while fungi were more sensitive to environmental conditions. Microbial communities showed clear seasonal patterns driven by variability of environmental factors, mainly temperature and accumulated rain, while local sources played a minor role. We also identified taxa in both kingdoms characteristic of seasonal periods, but not of specific sampling sites or plant coverage. Conclusions The present study suggests that the near surface atmosphere of urban environments constitutes a stable ecosystem, with a relatively homogenous composition, modulated by climatic variations. As such, it contributes to our understanding of the long-term changes associated to the human exposome in the air of highly populated areas.

Identification of Escherichia coli O157 : H7 genes influencing colonization of the bovine gastrointestinal tract using signature-tagged mutagenesis

Microbiology ◽  
2004 ◽  
Vol 150 (11) ◽  
pp. 3631-3645 ◽  
Author(s):  
Francis Dziva ◽  
Pauline M. van Diemen ◽  
Mark P. Stevens ◽  
Amanda J. Smith ◽  
Timothy S. Wallis
Keyword(s):  
Escherichia Coli ◽  
Molecular Mechanisms ◽  
Minor Role ◽  
Intestinal Colonization ◽  
E Coli ◽  
Type Iii ◽  
Fimbrial Subunit ◽  
Type Iii Protein Secretion ◽  
The Uk ◽  
A Minor

Enterohaemorrhagic Escherichia coli (EHEC) cause acute gastroenteritis in humans that may be complicated by life-threatening systemic sequelae. The predominant EHEC serotype affecting humans in the UK and North America is O157 : H7 and infections are frequently associated with contact with ruminant faeces. Strategies to reduce the carriage of EHEC in ruminants are expected to lower the incidence of human EHEC infections; however, the molecular mechanisms underlying persistence of EHEC in ruminants are poorly understood. This paper reports the first comprehensive survey for EHEC factors mediating colonization of the bovine intestines by using signature-tagged transposon mutagenesis. Seventy-nine E. coli O157 : H7 mutants impaired in their ability to colonize calves were isolated and 59 different genes required for intestinal colonization were identified by cloning and sequencing of the transposon insertion sites. Thirteen transposon insertions were clustered in the locus of enterocyte effacement (LEE), which encodes a type III protein secretion system required for the formation of attaching and effacing lesions on intestinal epithelia. A putative structural component of the apparatus (EscN) is essential for intestinal colonization; however, the type III secreted effector protein Map plays only a minor role. Other Type III secretion-associated genes were implicated in colonization of calves by E. coli O157 : H7, including z0990 (ecs0850), which encodes the non-LEE-encoded type III secreted effector NleD and the closely related z3023 (ecs2672) and z3026 (ecs2674) genes which encode homologues of Shigella IpaH proteins. We also identified a novel fimbrial locus required for intestinal colonization in calves by E. coli O157 : H7 (z2199-z2206; ecs2114-ecs2107/locus 8) and demonstrated that a mutant harbouring a deletion of the putative major fimbrial subunit gene is rapidly out-competed by the parent strain in co-infection studies. Our data provide valuable new information for the development of intervention strategies.

scholarly journals Towards the Understanding of Hydrogeochemical Seismic Responses in Karst Aquifers: A Retrospective Meta-Analysis Focused on the Apennines (Italy)

Minerals ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1058
Author(s):  
Gilberto Binda ◽  
Andrea Pozzi ◽  
Alessandro M. Michetti ◽  
Paula J. Noble ◽  
Michael R. Rosen
Keyword(s):  
Meta Analysis ◽  
Monitoring Network ◽  
Solute Concentration ◽  
Minor Role ◽  
Published Data ◽  
Permeability Enhancement ◽  
Set Up ◽  
Different Response ◽  
A Minor

Earthquakes are known to affect groundwater properties, yet the mechanisms causing chemical and physical aquifer changes are still unclear. The Apennines mountain belt in Italy presents a rich literature of case studies documenting hydrogeochemical response to seismicity, due to the high frequency of seismic events and the presence of different regional aquifers in the area. In this study, we synthesize published data from the last 30 years in the Apennine region in order to shed light on the main mechanisms causing earthquake induced water changes. The results suggest the geologic and hydrologic setting specific to a given spring play an important role in spring response, as well as the timing of the observed response. In contrast to setting, the main focal mechanisms of earthquake and the distance between epicenter and the analyzed springs seems to present a minor role in defining the response. The analysis of different response variables, moreover, indicates that an important driver of change is the degassing of CO2, especially in thermal springs, whereas a rapid increase in solute concentration due to permeability enhancement is observable in different cold and shallow springs. These findings also leave open the debate regarding whether earthquake precursors can be recognized beyond site-specific responses. Such responses can be understood more comprehensively through the establishment of a regional long-term monitoring system and continuous harmonization of data and sampling strategies, achievable in the Apennine region through the set-up of a monitoring network.

scholarly journals CO2 fertilization plays a minor role in long-term carbon accumulation patterns in temperate pine forests in the southwestern Pyrenees

2019 ◽  
Vol 407 ◽  
pp. 108737 ◽  
Author(s):  
Yueh-Hsin Lo ◽  
Juan A. Blanco ◽  
Ester González de Andrés ◽  
J. Bosco Imbert ◽  
Federico J. Castillo
Keyword(s):  
Carbon Accumulation ◽  
Pine Forests ◽  
Minor Role ◽  
Co2 Fertilization ◽  
A Minor

scholarly journals Natural Competence Is a Major Mechanism for Horizontal DNA Transfer in the Oral Pathogen Porphyromonas gingivalis

mBio ◽  
2012 ◽  
Vol 3 (1) ◽  
Author(s):  
Gena D. Tribble ◽  
Todd W. Rigney ◽  
Doan-Hieu V. Dao ◽  
Cindy T. Wong ◽  
Jennifer E. Kerr ◽  
...  
Keyword(s):  
Porphyromonas Gingivalis ◽  
Dna Transfer ◽  
Extracellular Dna ◽  
Minor Role ◽  
Chromosomal Dna ◽  
Natural Competence ◽  
Content Type ◽  
A Minor ◽  
First Time

ABSTRACTPorphyromonas gingivalisis a Gram-negative anaerobe that resides exclusively in the human oral cavity. Long-term colonization byP. gingivalisrequires the bacteria to evade host immune responses while adapting to the changing host physiology and alterations in the composition of the oral microflora. The genetic diversity ofP. gingivalisappears to reflect the variability of its habitat; however, little is known about the molecular mechanisms generating this diversity. Previously, our research group established that chromosomal DNA transfer occurs betweenP. gingivalisstrains. In this study, we examine the role of putative DNA transfer genes in conjugation and transformation and demonstrate that natural competence mediated bycomFis the dominant form of chromosomal DNA transfer, with transfer by a conjugation-like mechanism playing a minor role. Our results reveal that natural competence mechanisms are present in multiple strains ofP. gingivalis, and DNA uptake is not sensitive to DNA source or modification status. Furthermore, extracellular DNA was observed for the first time inP. gingivalisbiofilms and is predicted to be the major DNA source for horizontal transfer and allelic exchange between strains. We propose that exchange of DNA in plaque biofilms by a transformation-like process is of major ecological importance in the survival and persistence ofP. gingivalisin the challenging oral environment.IMPORTANCEP. gingivaliscolonizes the oral cavities of humans worldwide. The long-term persistence of these bacteria can lead to the development of chronic periodontitis and host morbidity associated with tooth loss.P. gingivalisis a genetically diverse species, and this variability is believed to contribute to its successful colonization and survival in diverse human hosts, as well as evasion of host immune defenses and immunization strategies. We establish here that natural competence is the major driving force behindP. gingivalisDNA exchange and that conjugative DNA transfer plays a minor role. Furthermore, we reveal for the first time the presence of extracellular DNA inP. gingivalisbiofilms, which is most likely the source of DNA exchanged between strains within dental plaque. These studies expand our understanding of the mechanisms used by this important member of the human oral flora to transition its relationship with the host from a commensal to a pathogenic relationship.

scholarly journals Half a century of monitoring macrobenthic animals on tidal flats in the Dutch Wadden Sea

2020 ◽  
Vol 656 ◽  
pp. 1-18
Author(s):  
JJ Beukema ◽  
R Dekker
Keyword(s):  
Tidal Flat ◽  
Wadden Sea ◽  
Late Summer ◽  
Late Winter ◽  
Minor Role ◽  
Data Series ◽  
Shore Crabs ◽  
A Minor ◽  
Rates Of Growth

Macrobenthic animals living in a tidal-flat area in the westernmost part of the Wadden Sea were monitored for 50 yr (1970-2019) using consistent methods. About 100 papers were published on this project. We review a number of results and conclusions on observed changes and their possible underlying causal processes. The most significant changes in population sizes and growth rates of several species could be attributed to climate warming (by about 2°C), along with increasing trends in species richness and total late-winter zoobenthic biomass. In the initial years, eutrophication (doubling of nutrients and chlorophyll concentrations) resulted in a doubling of zoobenthic biomass. The subsequent de-eutrophication after the mid-1980s was reflected only in the biomass values observed in late summer. A long-term trend in food supply for birds was not observed. Disturbances from fisheries were intermittent and modest. In several bivalve species, magnitudes of production and biomass were determined primarily by recruitment variation, which was mainly caused by spring abundance of epibenthic predators (shore crabs and shrimps). Their abundance increased with temperatures in the preceding winter. In contrast to this top-down regulation, bottom-up processes apparently played only a minor role in the determination of bivalve biomass. Rarely occurring extremely high bivalve numbers resulted in reduced rates of growth and production. We conclude that the uniquely long monitoring of the tidal-flat macrozoobenthos yielded data series which not only indicated several long-term trends, but also contributed to our insight in processes underlying the observed trends. Most of the observed trends were related to climate change and eutrophication followed by de-eutrophication.

scholarly journals Vasopressin Receptor Antagonists (Vaptans) in Heart Failure

2019 ◽  
Vol 17 ◽  
Author(s):  
Piotr Lipiec ◽  
Marco Metra
Keyword(s):  
Volume Overload ◽  
Minor Role ◽  
Receptor Subtypes ◽  
Vasopressin Receptor ◽  
Receptor Antagonists ◽  
Attractive Therapeutic Target ◽  
The Usa ◽  
A Minor ◽  
Long Term Mortality

Arginine vasopressin (a peptide neuroendocrine hormone) levels are elevated in patients with HF. Acting through 3 receptor subtypes, it can cause vasoconstriction and cardiac remodelling (receptors V1a), adrenocorticotropic hormone release (receptors V1b) and water reabsorption (receptors V2), thereby increasing preload and afterload. Vasopressin-receptor antagonists (vaptans), induce hypotonic diuresis and have been proposed as a treatment option for hyponatraemia, a known complication of HF. Three vaptans have been so tested; tolvaptan, conivaptan and lixivaptan, and  two (tolvaptan and conivaptan) have been approved for clinical use in hyponatraemia (in the USA). The EVEREST trial studied tolvaptan in over 4100 patients hospitalized with an exacerbation of chronic HF with reduced LVEF. No effect was seen on long-term mortality or HF-related morbidity, but there was greater weight loss and better dyspnoea and oedema relief over the short-term.  Similar results were seen in the AQUAMARINE study. The 2016 European HF guidelines, therefore gave the limited recommendation: “Tolvaptan may be used to treat patients with volume overload and resistant hyponatraemia”. Despite targeting  an attractive  therapeutic target,  vasopressin receptor antagonists (vaptans) have to date played only a minor role in our management of HF.

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