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1.
Nutrients ; 13(11)2021 Nov 15.
Article in English | MEDLINE | ID: mdl-34836328

ABSTRACT

There are limited data on the fluid balance characteristics and fluid replenishment behaviors of high-performance adolescent athletes. The heterogeneity of hydration status and practices of adolescent athletes warrant efficient approaches to individualizing hydration strategies. This study aimed to evaluate and characterize the hydration status and fluid balance characteristics of high-performance adolescent athletes and examine the differences in fluid consumption behaviors during training. In total, 105 high-performance adolescent athletes (male: 66, female: 39; age 14.1 ± 1.0 y) across 11 sports had their hydration status assessed on three separate occasions-upon rising and before a low and a high-intensity training session (pre-training). The results showed that 20-44% of athletes were identified as hypohydrated, with 21-44% and 15-34% of athletes commencing low- and high-intensity training in a hypohydrated state, respectively. Linear mixed model (LMM) analyses revealed that athletes who were hypohydrated consumed more fluid (F (1.183.85)) = 5.91, (p = 0.016). Additional K-means cluster analyses performed highlighted three clusters: "Heavy sweaters with sufficient compensatory hydration habits," "Heavy sweaters with insufficient compensatory hydration habits" and "Light sweaters with sufficient compensatory hydration habits". Our results highlight that high-performance adolescent athletes with ad libitum drinking have compensatory mechanisms to replenish fluids lost from training. The approach to distinguish athletes by hydration characteristics could assist practitioners in prioritizing future hydration intervention protocols.


Subject(s)
Athletes/statistics & numerical data , Drinking Behavior , Machine Learning , Organism Hydration Status , Sports/statistics & numerical data , Adolescent , Athletic Performance , Cluster Analysis , Dehydration/diagnosis , Dehydration/epidemiology , Dehydration/etiology , Drinking , Female , Humans , Male , Singapore/epidemiology , Sports/physiology , Water-Electrolyte Balance
2.
J Hazard Mater ; 409: 124606, 2021 05 05.
Article in English | MEDLINE | ID: mdl-33246819

ABSTRACT

The impact of microplastic pollution on terrestrial biota is an emerging research area, and this is particularly so for soil biota. In this study, we addressed this knowledge gap by examining the impact of aged low-density polyethylene (LDPE) and polyester fibres (i.e. polyethylene terephthalate, PET) on a forest microbiome composition and activity. We also measured the corresponding physicochemical changes in the soil. We observed that bacteria community composition diverged in PET and LDPE treated soils from that of the control by day 42. These changes occurred at 0.2% and 0.4% (w/w) of PET and at 3% LDPE. Additionally, soil respiration was 8-fold higher in soil that received 3% LDPE compared to other treatments and control. There were no clear patterns linking these biological changes to physicochemical changes measured. Taken together, we concluded that microplastics aging in the environment may have evolutionary consequences for forest soil microbiome and there is immediate implication for climate change if the observed increase in soil respiration is reproducible in multiple ecosystems.


Subject(s)
Microbiota , Soil Pollutants , Ecosystem , Forests , Microplastics , Plastics/toxicity , Soil , Soil Pollutants/analysis , Soil Pollutants/toxicity
3.
J Environ Manage ; 269: 110821, 2020 Sep 01.
Article in English | MEDLINE | ID: mdl-32561018

ABSTRACT

Recent studies demonstrated that lignite application in feedlot can mitigate ammonia (NH3) emission from intensive livestock production, which is an important source of environmental pollution. However, the use of lignite on feedlot requires mining and transport of lignite, which are themselves sources of greenhouse gas and other gaseous pollutants. There is a need for an integrated assessment on the gas emissions to determine the potential impact of those additions to the production chain. Using a case study in Victoria, Australia, carbon dioxide (CO2) and NH3 were identified as key emission changes compared to business as usual (BAU). Social costs and benefits analysis indicated that these changes in emissions translate to social benefits of AUD$11 - $151 and $18 - $256 per cattle per year at lignite application rate of 3 and 6 kg m-2 respectively, while the corresponding social costs of the additional gaseous emissions are AUD$2 - $19 and $3 - $28 per cattle per year per 200 km. Our results indicate that the use of lignite in feedlot to mitigate NH3 can be targeted at feedlots located in proximity to lignite source, population centre and/or vulnerable ecosystems to maximise social benefits and minimise social costs. More broadly, estimating the social costs and benefits of changing manure management practice to mitigate NH3 emission generates information that can be used to evaluate alternative policies for N management.


Subject(s)
Air Pollutants , Ammonia , Animal Husbandry , Animals , Cattle , Coal , Cost-Benefit Analysis , Ecosystem , Manure , Victoria
4.
Glob Chang Biol ; 26(6): 3356-3367, 2020 06.
Article in English | MEDLINE | ID: mdl-32281177

ABSTRACT

Plastic pollution is a global concern given its prevalence in aquatic and terrestrial ecosystems. Studies have been conducted on the distribution and impact of plastic pollution in marine ecosystems, but little is known on terrestrial ecosystems. Plastic mulch has been widely used to increase crop yields worldwide, yet the impact of plastic residues in cropland soils to soil health and crop production in the long term remained unclear. In this paper, using a global meta-analysis, we found that the use of plastic mulch can indeed increase crop yields on average by 25%-42% in the immediate season due to the increase of soil temperature (+8%) and moisture (+17%). However, the unabated accumulation of film residues in the field negatively impacts its physicochemical properties linked to healthy soil and threatens food production in the long term. It has multiple negative impacts on plant growth including crop yield (at the mean rate of -3% for every additional 100 kg/ha of film residue), plant height (-2%) and root weight (-5%), and soil properties including soil water evaporation capacity (-2%), soil water infiltration rate (-8%), soil organic matter (-0.8%) and soil available phosphorus (-5%) based on meta-regression. Using a nationwide field survey of China, the largest user of plastic mulch worldwide, we found that plastic residue accumulation in cropland soils has reached 550,800 tonnes, with an estimated 6%-10% reduction in cotton yield in some polluted sites based on current level of plastic residue content. Immediate actions should be taken to ensure the recovery of plastic film mulch and limit further increase in film residue loading to maintain the sustainability of these croplands.


Subject(s)
Agriculture , Plastics , China , Crops, Agricultural , Ecosystem , Food Supply , Soil
5.
Sci Total Environ ; 627: 1377-1388, 2018 Jun 15.
Article in English | MEDLINE | ID: mdl-30857101

ABSTRACT

Microplastics and nanoplastics are emerging pollutants of global importance. They are small enough to be ingested by a wide range of organisms and at nano-scale, they may cross some biological barriers. However, our understanding of their ecological impact on the terrestrial environment is limited. Plastic particle loading in agroecosystems could be high due to inputs of some recycled organic waste and plastic film mulching, so it is vital that we develop a greater understanding of any potentially harmful or adverse impacts of these pollutants to agroecosystems. In this article, we discuss the sources of plastic particles in agroecosystems, the mechanisms, constraints and dynamic behaviour of plastic during aging on land, and explore the responses of soil organisms and plants at different levels of biological organisation to plastic particles of micro and nano-scale. Based on limited evidence at this point and understanding that the lack of evidence of ecological impact from microplastic and nanoplastic in agroecosystems does not equate to the evidence of absence, we propose considerations for addressing the gaps in knowledge so that we can adequately safeguard world food supply.


Subject(s)
Agriculture , Ecosystem , Environmental Monitoring , Plastics/analysis , Soil Pollutants/analysis
6.
J Microbiol Immunol Infect ; 50(3): 314-320, 2017 Jun.
Article in English | MEDLINE | ID: mdl-26338309

ABSTRACT

BACKGROUND/PURPOSE: Bacteremia in dengue may occur with common exposure to pathogens in association with severe organ impairment or severe dengue, which may result in death. Cohort studies identifying risk factors for concurrent bacteremia among patients with dengue are rare. METHODS: We conducted a retrospective case-control study of adult patients with dengue who were admitted to the Department of Infectious Diseases at Tan Tock Seng Hospital, Singapore from 2004 to 2008. For each case of dengue with concurrent bacteremia (within the first 72 hours of admission), we selected four controls without bacteremia, who were matched on year of infection and dengue confirmation method. Conditional logistic regression was performed to identify risk factors for concurrent bacteremia. RESULTS: Among 9,553 patients with dengue, 29 (0.3%) had bacteremia. Eighteen of these patients (62.1%) had concurrent bacteremia. The predominant bacteria were Staphylococcus aureus, one of which was a methicillin-resistant strain. Dengue shock syndrome occurred more frequently and hospital stay was longer among cases than among controls. Three cases did not survive, whereas none of the controls died. In multivariate analysis, being critically ill at hospital presentation was independently associated with 15 times the likelihood of a patient with dengue having concurrent bacteremia. CONCLUSION: Concurrent bacteremia in adult patients with dengue is uncommon but presents atypically and results in more deaths and longer hospital stay. Given the associated mortality, collection of blood cultures and empiric antibiotic therapy may be considered in patients who are critically ill.


Subject(s)
Bacteremia/epidemiology , Dengue/complications , Adolescent , Adult , Aged , Aged, 80 and over , Bacteremia/mortality , Case-Control Studies , Female , Hospitals , Humans , Male , Middle Aged , Retrospective Studies , Risk Factors , Singapore/epidemiology , Survival Analysis , Young Adult
7.
PLoS Negl Trop Dis ; 10(3): e0004576, 2016 Mar.
Article in English | MEDLINE | ID: mdl-27015272

ABSTRACT

BACKGROUND: Thrombocytopenia is a hallmark of dengue infection, and bleeding is a dreaded complication of dengue fever. Prophylactic platelet transfusion has been used to prevent bleeding in the management of dengue fever, although the evidence for its benefit is lacking. In adult dengue patients with platelet count <20,000/mm3 without bleeding, we aimed to assess if prophylactic platelet transfusion was effective in reducing clinical bleeding and other outcomes. METHOD: We conducted a retrospective non-randomised observational study of dengue patients with platelet count < 20,000/mm3 without bleeding (except petechiae) admitted to Tan Tock Seng Hospital from January 2005 to December 2008. Baseline characteristics and clinical outcomes were compared between the non-transfused vs. transfused groups. Outcomes studied were clinical bleeding, platelet increment, hospital length of stay, intensive care unit admission and death. RESULTS: Of the 788 patients included, 486 received prophylactic platelet transfusion. There was no significant difference in the presence of clinical bleeding in the two groups (18.2% in non-transfused group vs. 23.5% in transfused group; P = 0.08). Patients in the transfused group took a median of 1 day longer than the non-transfused group to increase their platelet count to 50,000/mm3 or more (3 days vs. 2 days, P <0.0001). The median duration of hospital stay in the non-transfused group was 5 days vs. 6 days in the transfused group (P< 0.0001). There was no significant difference in the proportion requiring ICU admission (non-transfused 0.66% vs. transfused 1.23%, P = 0.44) and death (non-transfused 0% vs. transfused 0.2%, P = 0.43). CONCLUSION: Platelet transfusion in absence of bleeding in adult dengue with platelet count <20,000/mm3 did not reduce bleeding or expedite platelet recovery. There was potential harm by slowing recovery of platelet count to >50,000/mm3 and increasing length of hospitalization.


Subject(s)
Dengue/complications , Platelet Transfusion/adverse effects , Thrombocytopenia/etiology , Thrombocytopenia/prevention & control , Adult , Aged , Female , Humans , Male , Middle Aged , Retrospective Studies , Young Adult
8.
Ecotoxicology ; 25(1): 213-24, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26547875

ABSTRACT

Today's ecosystems are influenced by different factors that could evolve into stressors. Effects of pesticides, especially in agricultural areas, may interact with environmental factors, such as soil moisture fluctuation caused by global climate change. In this contribution, two semi-field studies conducted in Germany and Portugal with terrestrial model ecosystems are presented. Their aim was to assess the effects of the fungicide pyrimethanil under different soil moisture levels on Enchytraeidae. In Portugal a no observed effect concentration design was chosen, using two concentration levels: the maximum application rate (MAR) according to the safe use registration within the European Union and five times the MAR (1.82 and 9.09 mg/kg dry soil, respectively). Both concentrations did neither affect the total enchytraeid abundance nor single populations. In Germany an ECx design (effect concentration) was conducted, using 11 concentrations. In general, 14 EC50 values for different combinations of single species, moisture level and sampling date were determined. The strongest effects were found in dry soil, particularly for Fridericia connata (EC50: 3.48 mg/kg dry soil after 8 weeks of exposure). The advantages and challenges of these test designs are discussed with regard to the registration process of pesticides in the European Union. In any case, enchytraeids are suitable test organisms in such higher tier studies for the combined evaluation of chemical and climatic stressors due to their usually high diversity and abundances and their close contact with the soil solution.


Subject(s)
Fungicides, Industrial/toxicity , Oligochaeta/drug effects , Pyrimidines/toxicity , Soil Pollutants/toxicity , Animals , Germany , Portugal , Soil/chemistry
9.
PLoS One ; 9(5): e96514, 2014.
Article in English | MEDLINE | ID: mdl-24788828

ABSTRACT

BACKGROUND: Pain is a prominent feature of acute dengue as well as a clinical criterion in World Health Organization guidelines in diagnosing dengue. We conducted a prospective cohort study to compare levels of pain during acute dengue between different ethnicities and dengue severity. METHODS: Demographic, clinical and laboratory data were collected. Data on self-reported pain was collected using the 11-point Numerical Rating Scale. Generalized structural equation models were built to predict progression to severe disease. RESULTS: A total of 499 laboratory confirmed dengue patients were recruited in the Prospective Adult Dengue Study at Tan Tock Seng Hospital, Singapore. We found no statistically significant differences between pain score with age, gender, ethnicity or the presence of co-morbidity. Pain score was not predictive of dengue severity but highly correlated to patients' day of illness. Prevalence of abdominal pain in our cohort was 19%. There was no difference in abdominal pain score between grades of dengue severity. CONCLUSION: Dengue is a painful disease. Patients suffer more pain at the earlier phase of illness. However, pain score cannot be used to predict a patient's progression to severe disease.


Subject(s)
Abdominal Pain/epidemiology , Dengue/pathology , Pain Measurement/methods , Abdominal Pain/ethnology , Adult , Dengue/epidemiology , Dengue/ethnology , Female , Humans , Male , Middle Aged , Prospective Studies , Self Report , Singapore/epidemiology , Singapore/ethnology , Young Adult
10.
BMC Infect Dis ; 13: 498, 2013 Oct 24.
Article in English | MEDLINE | ID: mdl-24152678

ABSTRACT

BACKGROUND: The recommendation from the 2009 World Health Organization guidelines for managing dengue suggests that patients with any warning sign can be hospitalized for observation and management. We evaluated the utility of using warning signs to guide hospital admission and predict disease progression in adults. METHODS: We conducted a prospective cohort study from January 2010 to September 2012. Daily demographic, clinical and laboratory data were collected from adult dengue patients. Warning signs were recorded. The proportion of admitted patients using current admission criteria and warning signs was compared. The sensitivity, specificity, positive and negative predictive values of warning signs in predicting disease progression were also evaluated. RESULTS: Four hundred and ninety-nine patients with confirmed dengue were analyzed. Using warning signs instead of the current admission criteria will lead to a 44% and 31% increase in admission for DHF II-IV and SD cases respectively. The proportion of non-severe dengue cases which were admitted also increased by 32% for non DHF II-IV and 33% for non-SD cases. Absence of any warning signs had a NPV of 91%, 100% and 100% for DHF I-IV, DHF II-IV and SD. Of those who progressed to severe illness, 16.3% had warning signs on the same day while 51.3% had warning signs the day before developing severe illness, respectively. CONCLUSIONS: Our findings demonstrated that patients without any warning signs can be managed safely with ambulatory care to reduce hospital resource burden. No single warning sign can independently predict disease progression. The window from onset of warning sign to severe illness in most cases was within one day.


Subject(s)
Dengue/diagnosis , Adult , Cohort Studies , Disease Progression , Female , Hospitalization , Humans , Male , Middle Aged , Prospective Studies , Sensitivity and Specificity , Young Adult
11.
Cell Biochem Funct ; 30(6): 515-23, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22473705

ABSTRACT

Lysosomes serve key degradative functions for the turnover of membrane lipids and protein components. Its biogenesis is principally dependent on exocytic traffic from the late endosome via the trans-Golgi network, and it also receives cargo to be degraded from the endocytic pathway. Membrane trafficking to the late endosome-lysosome is tightly regulated to maintain the amplitude of signalling events and cellular homeostasis. Key coordinators of lysosomal traffic include members of the Rab small GTPase family. Amongst these, Rab7, Rab9 and the more recently studied Rab22B/31 have all been reported to regulate membrane trafficking processed at the late endosome-lysosome system. We discuss what is known about the roles of these Rab proteins and their interacting partners on the regulation of traffic of important receptor proteins such as the epidermal growth factor receptor (EGFR) and the mannose 6-phosphate receptor (M6PR), in association with the late endosome-lysosome system. Better knowledge of EGFR and M6PR traffic in this regard may aid in understanding the pathological processes, such as oncogenic transformations associated with these receptors.


Subject(s)
Endosomes/metabolism , ErbB Receptors/metabolism , Intracellular Membranes/metabolism , Lysosomes/metabolism , Receptor, IGF Type 2/metabolism , rab GTP-Binding Proteins/metabolism , Animals , Humans , Protein Transport
12.
J Cell Physiol ; 221(3): 716-28, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19725050

ABSTRACT

The expression profile and functions of the brain-enriched Rab22B/Rab31 small GTPase had remained uncharacterized. Using specific antibodies against Rab22B, we found the protein to be exceptionally enriched in nestin and RC2-positive radial glia of the embryonic mouse brain. In the adult brain, Rab22B is rather specifically expressed in glial fibrillary acidic protein (GFAP)-positive mature astrocytes, but is not clearly detectable in either 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase)-positive mature oligodendrocytes or betaIII-tubulin (TuJ)-positive neurons. In probing for specific functions of Rab22B, we found that Rab22B silencing in A431 cells resulted in abnormal trafficking of the epidermal growth factor receptor (EGFR), Texas-red-labeled EGF, and the cation-independent mannose 6-phosphate receptor (M6PR). Affinity pull-down assays and co-immunoprecipitation analysis indicated that Rab22B could associate with EGFR in a GTP-dependent manner. Rab22B is thus a Rab protein specifically expressed in the astroglia lineage and may have a role in regulating EGFR trafficking in some cell types. Given that EGFR signaling modulates astrocyte development and oncogenesis of multiple cell types, Rab22B may thus have specific developmental or pathophysiological roles in cell types which it is enriched in.


Subject(s)
Astrocytes/metabolism , ErbB Receptors/metabolism , Protein Transport/physiology , rab GTP-Binding Proteins/metabolism , Animals , Brain/cytology , Brain/metabolism , Cell Line, Tumor , Cell Membrane/metabolism , Cell Proliferation , Embryo, Mammalian/metabolism , Endosomes/metabolism , Epidermal Growth Factor/metabolism , Epidermal Growth Factor/pharmacology , Glial Fibrillary Acidic Protein , Humans , Mice , Mice, Inbred C57BL , Nerve Tissue Proteins/metabolism , Neuroglia/metabolism , Protein Binding/physiology , RNA, Small Interfering/genetics , Rats , Rats, Sprague-Dawley , Receptor, IGF Type 2 , Receptors, Cytoplasmic and Nuclear/metabolism , Vesicular Transport Proteins/metabolism
13.
Cell Motil Cytoskeleton ; 66(7): 365-70, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19418559

ABSTRACT

The Rab family of small GTPases functions in regulating vesicular transport in all eukaryotes. In the past few years, several important reports have linked some members of the Rab family to intriguing mechanistic aspects of cancer cell migration and invasiveness. Rab5 and Rab21 associate with alpha-integrin subunits and modulate their endosomal traffic and subcellular localization. Expression of the latter enhances adhesion and migration of certain cancer cell types. Rab25 has been functionally linked to tumor progression and the invasiveness of some epithelial cancers. Rab25 promotes invasive migration of cells in three-dimensional microenvironments by associating with alpha5beta1 integrin, and directing its recycling to dynamic ruffling protrusions at the migrating cell front. Acting directly, or through its effector, the Rab-coupling protein, Rab25 could potentially engage both integrin and epidermal growth factor receptor and enhance their oncogenic recycling and signaling. Tumor invasiveness may also be modulated by Rab8-mediated exocytic traffic of MT1-matrix metalloproteinase, with the latter's activity likely influenced by interaction with the mammalian suppressor of Sec4 (Mss4), a Rab8 guanine nucleotide exchange factor, and integrin. We discuss highlights in the recent literature that point towards a role for Rab-mediated membrane traffic in cancer cell migration and invasion.


Subject(s)
Cell Movement , Neoplasms/enzymology , Neoplasms/pathology , Transport Vesicles/physiology , rab GTP-Binding Proteins/metabolism , Animals , Cell Adhesion/physiology , Endocytosis/physiology , ErbB Receptors/metabolism , Humans , Integrin alpha5beta1/metabolism , Matrix Metalloproteinase 14/metabolism , Neoplasm Invasiveness/pathology
14.
Brain Res Rev ; 58(1): 236-46, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18485483

ABSTRACT

The Rab family of small GTPases serves as cellular regulators of vesicular transport in all eukaryotes. Higher organisms have a vastly expanded number of Rabs. Some of these would presumably perform cell-type or tissue-specific functions. Roles for Rab proteins in several aspects of cellular physiology that are peculiar to neurons have been revealed. Rabs, in conjunction with their effectors and regulators, participate in central nervous system development (Rab23), polarized neurite growth (Rab8 and Rab11), endocytosis and axonal retrograde transport (Rab5 and Rab7). At chemical synapses, Rabs perform specific functions in synaptic vesicle exocytosis (Rab3) and postsynaptic compartment dynamics of glutamate receptors (Rab8). Much less is known about the role of Rabs in astroglia/oligodendroglia-specific processes, although Rab family members that are glia-enriched (Rab22B, Rab40C) have been reported. We summarized and discussed recent findings on the roles played by Rabs in neurons and glia in the central nervous system, and speculate on future directions.


Subject(s)
Neuroglia/physiology , Neurons/physiology , rab GTP-Binding Proteins/metabolism , Animals , Brain/enzymology , Brain/physiology , Humans , Models, Biological , Neuroglia/cytology , Neuroglia/enzymology , Neurons/cytology , Neurons/enzymology , Signal Transduction/physiology , Synapses/metabolism , Synapses/physiology
15.
Biochem Biophys Res Commun ; 361(3): 751-7, 2007 Sep 28.
Article in English | MEDLINE | ID: mdl-17678623

ABSTRACT

The small GTPase Rab22B (or Rab31) has been suspected to be involved in trafficking at trans-Golgi network. However, its exact cellular localization, tissue expression profile, and functions have not been uncharacterized. Specific antibody raised against Rab22B's protein revealed that Rab22B is brain-enriched, but is also present in substantial levels in spleen and intestine. In HeLa cells, endogenous Rab22B is largely associated with the trans-Golgi network (TGN). Over-expression of a GDP-binding mutant (Rab22BSN), but not wild-type Rab22B, specifically disrupts the TGN localization of TGN46, a dynamic marker which cycles between the TGN and the plasma membrane. The TGN resident membrane protein syntaxin 16, cis-Golgi markers such as GM130 and syntaxin 5, as well as the TGN/late endosome marker mannose 6-phosphate receptor (M6PR) are not affected by Rab22BSN, neither was endosomal-TGN transport of the Shiga toxin B subunit. The disruption of TGN46 staining by Rab22BSN could be specifically attributed to a domain at the C-terminal portion of Rab22B, where its sequence deviates the most from Rab22A. Over-expression of Rab22BSN inhibits the cell surface transport of the vesicular stomatitis virus G protein. Thus, Rab22B may have a role in anterograde exit from the TGN.


Subject(s)
Protein Transport/physiology , rab GTP-Binding Proteins/physiology , trans-Golgi Network/physiology , Animals , Antibodies/immunology , Antibody Specificity , Cell Membrane/metabolism , Cells, Cultured , HeLa Cells , Humans , Immunohistochemistry , Mice , Rabbits , Rats , Transfection , rab GTP-Binding Proteins/metabolism
16.
Traffic ; 7(6): 746-50, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16683919

ABSTRACT

Rab23 is the product of the gene mutated in the mouse open brain1 phenotype, which displays neural tube defects. It appears to antagonize sonic hedgehog (Shh)-mediated signaling during mouse development, presumably by regulating the intracellular trafficking of one or more of Shh's-signaling components. The Shh receptor Patched1 (Ptch1) and its downstream effector Smoothened (Smo) were initial prime suspects as they are membrane proteins whose cellular dynamics are modulated by the Shh signal. However, Rab23 mutants do not appear to affect the localization and dynamics of either protein. Genetic analyses have now shown that Rab23 functions downstream of Smo and affects the function of the Shh-regulated Gli family of transcription factors in a more direct manner than previously thought. A plethora of proteins that influence Shh signaling and whose cellular trafficking could potentially be regulated by Rab23 has also emerged. These include members of the intraflagellar transport complex, as well as motor proteins responsible for their assembly at the cilia. Rab23 is also expressed in adult mouse neurons and may thus have functions beyond embryonic developmental stages and Shh signaling. We discuss these new findings and explore the myriad of possibilities whereby Rab23 may function.


Subject(s)
rab GTP-Binding Proteins/metabolism , Animals , Cilia/metabolism , Embryonic Development/physiology , Hedgehog Proteins , Mice , Models, Biological , Mutation , Phenotype , Protein Transport , Receptors, G-Protein-Coupled/metabolism , Signal Transduction , Smoothened Receptor , Trans-Activators/metabolism , rab GTP-Binding Proteins/genetics
17.
J Neurosci Res ; 83(6): 1118-27, 2006 May 01.
Article in English | MEDLINE | ID: mdl-16463280

ABSTRACT

The gene mutated in the mouse open brain (opb) phenotype antagonizes sonic hedgehog-mediated signaling and encodes a small GTPase of the Rab family, Rab23. To date, the brain expression profile and exact mechanism of function of the Rab23 protein has remained unknown. Specific antibodies generated against Rab23 showed that the protein is highly enriched in the adult rodent brain and present in low levels in multiple tissues of the adult rodent. Rab23 is found in the cytosol as well as being associated with the plasma and endosomal membranes. In the adult mouse brain, Rab23 is found in betaIII tubulin (TuJ) positive neuronal cell bodies and are most prominent in the cortex, hypothalamus and the cerebellum. It is, however, absent from glial fibrillary acidic protein (GFAP) positive astrocytes or CNPase positive oligodendrocytes. Despite the plasma membrane/endosomal membrane localization of Rab23, neither overexpression of the GTP-restricted nor the GDP-bound mutant forms affect internalization of transferrin or epidermal growth factor. Exogenous overexpression of Rab23 or its mutants also did not affect the morphological differentiation of thalamic neurons in culture. Expression of Rab23 in the adult brain is suggestive, however, of having a postnatal function beyond its role in embryonic development.


Subject(s)
Brain/metabolism , Gene Expression Regulation, Developmental/physiology , Gene Expression/physiology , rab GTP-Binding Proteins/physiology , Age Factors , Animals , Blotting, Western/methods , Cells, Cultured , Embryo, Mammalian , Endocytosis/genetics , Humans , Immunohistochemistry/methods , Mice , Mutation/physiology , Neurites/physiology , Neuroglia/metabolism , Neurons/cytology , Subcellular Fractions/metabolism , Tissue Distribution/physiology , Transfection/methods , rab GTP-Binding Proteins/genetics , rab5 GTP-Binding Proteins/metabolism
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