The membrane trafficking of cation-independent mannose 6-phosphate receptor(CI-M6PR) between the transGolgi network(TGN) and endosomal compartments is not only critical for maintaining lysosomal function but also ...The membrane trafficking of cation-independent mannose 6-phosphate receptor(CI-M6PR) between the transGolgi network(TGN) and endosomal compartments is not only critical for maintaining lysosomal function but also a well-known event for understanding molecular and cellular mechanisms in retrograde endosome-to-TGN trafficking.Although it has been well established in literature that the C-terminus of bovine CI-M6PR determines its retrograde trafficking,it remains unclear whether the luminal domain of the protein plays a role on these sorting events.In this study,we found that partial deletion of luminal domain of human CI-M6PR mistargeted the mutant protein to nonTGN compartments.Moreover,replacing the luminal domain of both bovine and human CI-M6PR with that from irrelevant membrane proteins such as CD8 or Tac also altered the TGN targeting of the chimeric proteins.On the other hand,only short sequence from HA fused with the transmembrane domain and C-terminus of the receptor,HA-hCIM6PR-tail,resulted in its preferential targeting to TGN as for the full length receptor,strongly suggesting that sorting of the receptor may be influenced by luminal sequence.Furthermore,using this luminal truncated form of HA-hCIM6 PR as a model cargo,we found that the trafficking of the chimeric protein was regulated by the retromer complex through interacting with SNX5.In conclusion,our study strongly suggested that the disrupted luminal domain from hCI-M6PR or other irrelevant membrane proteins interfere with the process of membrane trafficking and TGN targeting of CI-M6PR.展开更多
The aim of this study is to identify and analyze the pattern of visibility of the main actors in the photographic coverage of drug trafficking in six of Mexico’s national newspapers. The study was based on a sample o...The aim of this study is to identify and analyze the pattern of visibility of the main actors in the photographic coverage of drug trafficking in six of Mexico’s national newspapers. The study was based on a sample of 12,962,000 photographs published from 2006 to 2010. The images were processed by generating a codebook of key categories extracted from the informational context of drug trafficking and the war against drug trafficking. The technique used to explain the newspapers’ photographic coverage was the content analysis proposed by Johan Galtung in 1965, in its updated version of 2006. The limitations of the research are time constraints (only four years of President Felipe Calderón’s six-year term were analyzed) and information platforms (with the omission of online newspapers, supplements, and additional publications). The study offers an original analysis of the photographic coverage of drug trafficking in the Mexican press. The use of the Galtung Model reveals strong biases and imbalances in the coverage, with a clear tendency to defend the government’s position in the analyzed sample.展开更多
The theme of trafficking of human beings treats one of the most severe and dangerous criminal phenomena of the organized crime in Albania. The objects of this paper are: human trafficking; ways of trafficking; risk o...The theme of trafficking of human beings treats one of the most severe and dangerous criminal phenomena of the organized crime in Albania. The objects of this paper are: human trafficking; ways of trafficking; risk of Albanian society; and investment of the criminal benefits deriving from trafficking in legal economic activities, it is of great importance for the treatment of proactive investigations to the trafficking of human beings. Another important aspect of the trafficking investigations is the investigation of criminal assets and the way how they are used in the economy of the country. In this paper, we stress that the investigation of criminal assets benefited by the crime of trafficking human beings as well as other wealth financed by these assets is important as the investigation of the criminal activity of trafficking itself. Also, we aim to evaluate the necessity of acting of all law enforcement agencies and other state institutions in order to be successful in the fight against the crime of trafficking of human beings. At the end of this paper, we do treat the necessity and the ways of collaboration of law enforcement agencies, NGOs, and structures of local government for rehabilitation of the victims of trafficking and their integration in the social life.展开更多
This paper presents a comprehensive analysis of global human trafficking trends over a twenty-year period, leveraging a robust dataset from the Counter Trafficking Data Collaborative (CTDC). The study unfolds in a sys...This paper presents a comprehensive analysis of global human trafficking trends over a twenty-year period, leveraging a robust dataset from the Counter Trafficking Data Collaborative (CTDC). The study unfolds in a systematic manner, beginning with a detailed data collection phase, where ethical and legal standards for data usage and privacy are strictly observed. Following collection, the data undergoes a rigorous preprocessing stage, involving cleaning, integration, transformation, and normalization to ensure accuracy and consistency for analysis. The analytical phase employs time-series analysis to delineate historical trends and utilizes predictive modeling to forecast future trajectories of human trafficking using the advanced analytical capabilities of Power BI. A comparative analysis across regions—Africa, the Americas, Asia, and Europe—is conducted to identify and visualize the distribution of human trafficking, dissecting the data by victim demographics, types of exploitation, and duration of victimization. The findings of this study not only offer a descriptive and predictive outlook on trafficking patterns but also provide insights into the regional nuances that influence these trends. The article underscores the prevalence and persistence of human trafficking, identifies factors contributing to its evolution, and discusses the implications for policy and law enforcement. By integrating a methodological approach with quantitative analysis, this research contributes to the strategic planning and resource allocation for combating human trafficking. It highlights the necessity for continued research and international cooperation to effectively address and mitigate this global issue. The implications of this research are significant, offering actionable insights for policymakers, law enforcement, and advocates in the ongoing battle against human trafficking.展开更多
Arabidopsis plastid antiporters KEA1 and KEA2are critical for plastid development, photosynthetic efficiency, and plant development.Here, we show that KEA1 and KEA2 are involved in vacuolar protein trafficking. Geneti...Arabidopsis plastid antiporters KEA1 and KEA2are critical for plastid development, photosynthetic efficiency, and plant development.Here, we show that KEA1 and KEA2 are involved in vacuolar protein trafficking. Genetic analyses found that the kea1 kea2 mutants had short siliques, small seeds, and short seedlings. Molecular and biochemical assays showed that seed storage proteins were missorted out of the cell and the precursor proteins were accumulated in kea1 kea2. Protein storage vacuoles(PSVs) were smaller in kea1 kea2. Further analyses showed that endosomal trafficking in kea1 kea2 was compromised. Vacuolar sorting receptor 1(VSR1) subcellular localizations, VSR–cargo interactions, and p24 distribution on the endoplasmic reticulum(ER) and Golgi apparatus were affected in kea1 kea2. Moreover, plastid stromule growth was reduced and plastid association with the endomembrane compartments was disrupted in kea1 kea2. Stromule growth was regulated by the cellular pH and K+homeostasis maintained by KEA1 and KEA2. The organellar pH along the trafficking pathway was altered in kea1 kea2. Overall, KEA1 and KEA2 regulate vacuolar trafficking by controlling the function of plastid stromules via adjusting pH and K+homeostasis.展开更多
The endosomal trafficking of signaling membrane proteins, such as receptors, transporters and channels, is mediated by the retromer-mediated sorting machinery, composed of a cargo-selective vacuolar protein sorting tr...The endosomal trafficking of signaling membrane proteins, such as receptors, transporters and channels, is mediated by the retromer-mediated sorting machinery, composed of a cargo-selective vacuolar protein sorting trimer and a membrane-deforming subunit of sorting nexin proteins. Recent studies have shown that the isoforms, sorting nexin 5 (SNX5) and SNX6, have played distinctive regulatory roles in retrograde membrane trafficking. However, the molecular insight determined functional differences within the proteins remains unclear. We reported that SNX5 and SNX6 had distinct binding affinity to the cargo protein vesicular monoamine transporter 2 (VMAT2). SNX5, but not SNX6, specifically interacted with VMAT2 through the Phox domain, which contains an alpha-helix binding motif. Using chimeric mutagenesis, we identified that several key residues within this domain were unique in SNX5, but not SNX6, and played an auxiliary role in its binding to VMAT2. Importantly, we generated a set of mutant SNX6, in which the corresponding key residues were mutated to those in SNX5. In addition to the gain in binding affinity to VMAT2, their overexpression functionally rescued the altered retrograde trafficking of VMAT2 induced by siRNA-mediated depletion of SNX5. These data strongly suggest that SNX5 and SNX6 have different functions in retrograde membrane trafficking, which is determined by the different structural elements within the Phox domain of two proteins. Our work provides a new information on the role of SNX5 and SNX6 in the molecular regulation of retrograde membrane trafficking and vesicular membrane targeting in monoamine neurotransmission and neurological diseases.展开更多
In 2006,a large quantity of clandestine sensitive radioactive materials surfaced at an abandoned scrap metal and lead recovery facility in the city Gaziemir,Izmir,Türkiye.In April,2007 the TAEK(Turkish Atomic Ene...In 2006,a large quantity of clandestine sensitive radioactive materials surfaced at an abandoned scrap metal and lead recovery facility in the city Gaziemir,Izmir,Türkiye.In April,2007 the TAEK(Turkish Atomic Energy Agency)official experts surveyed the 70,000 m^(2)site including the storage buildings.They reported that 20-300 microRad/h of radiation was detected throughout the site,especially high readings of more than 300 micRad/h were recorded inside the storage building containing about 1,100 tons of commercially valuable waste.About 15 tons of waste were taken from the storage building and sent to TAEK’s lab in Ankara to be analyzed.In April,2008 TAEK issued a press release(No:04/2012)on its official website confirming that their analysis of samples taken from the Aslan facility showed that,there is a scattered radioactive contamination in the Aslan lead-recovering factory.The radioactive isotopes of Europium-152 and Europium-154 were found in the landfilled area,additionally,these isotopes were more concentrated(higher readings)in the commercially valuable waste(approx.1,100 tons)which was kept in the storage building,a clear indication of the fact that at the Aslan facility,sensitive nuclear reactor parts,including but not limited to nuclear reactors control rods were being melted.展开更多
Plants employ sophisticated mechanisms to interact with pathogenic as well as beneficial microbes. Of those, membrane trafficking is key in establishing a rapid and precise response. Upon interaction with pathogenic m...Plants employ sophisticated mechanisms to interact with pathogenic as well as beneficial microbes. Of those, membrane trafficking is key in establishing a rapid and precise response. Upon interaction with pathogenic microbes, surface-localized immune receptors undergo endocytosis for signal transduction and activity regulation while cell wall components, antimicrobial compounds, and defense proteins are delivered to pathogen invasion sites through polarized secretion. To sustain mutualistic associations, host cells also reprogram the membrane trafficking system to accommodate invasive structures of symbi- otic microbes. Here, we provide an analysis of recent advances in understanding the roles of secretory and endocytic membrane trafficking pathways in plant immune activation. We also discuss strategies deployed by adapted microbes to manipulate these pathways to subvert or inhibit plant defense.展开更多
Inositol polyphosphate 5-phosphatases (5PTases) are enzymes of phosphatidylinositol metabolism that affect various aspects of plant growth and development. Arabidopsis 5PTasel3 regulates auxin homeostasis and hormon...Inositol polyphosphate 5-phosphatases (5PTases) are enzymes of phosphatidylinositol metabolism that affect various aspects of plant growth and development. Arabidopsis 5PTasel3 regulates auxin homeostasis and hormonerelated cotyledon vein development, and here we demonstrate that its knockout mutant 5pt13 has elevated sensitivity to gravistimulation in root gravitropic responses. The altered responses of 5pt13 mutants to 1-N-naphthylphthalamic acid (an auxin transport inhibitor) indicate that 5PTase13 might be involved in the regulation of auxin transport. Indeed, the auxin efflux carrier PIN2 is expressed more broadly under 5PTasel3 deficiency, and observations of the internalization of the membrane-selective dye FM4-64 reveal altered vesicle trafficking in 5pt13 mutants. Compared with wild-type, 5pt13 mutant seedlings are less sensitive to the inhibition by brefeldin A of vesicle cycling, seedling growth, and the intracellular cycling of the PIN1 and PIN2 proteins. Further, auxin redistribution upon gravitropic stimulation is stimulated under 5PTasel3 deficiency. These results suggest that 5PTasel3 may modulate auxin transport by regulating vesicle trafficking and thereby play a role in root gravitropism.展开更多
Activity-dependent postsynaptic receptor trafficking is critical for long-term synaptic plasticity in the brain, but it is unclear whether this mechanism actually mediates the spinal cord dorsal hom central sensitizat...Activity-dependent postsynaptic receptor trafficking is critical for long-term synaptic plasticity in the brain, but it is unclear whether this mechanism actually mediates the spinal cord dorsal hom central sensitization (a specific form of synaptic plasticity) that is associated with persistent pain. Recent studies have shown that peripheral inflammation drives changes in ct-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunit trafficking in the dorsal horn and that such changes contribute to the hypersensitivity that underlies persistent pain. Here, we review current evi- dence to illustrate how spinal cord AMPARs participate in the dorsal hom central sensitization associated with persistent pain. Understanding these mechanisms may allow the development of novel therapeutic strategies for treating persistent pain.展开更多
Inhibitory neurotransmission ensures normal brain function by counteracting and integrating excitatory activity.-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the mammalian central nervous system...Inhibitory neurotransmission ensures normal brain function by counteracting and integrating excitatory activity.-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the mammalian central nervous system,and mediates its effects via two classes of receptors:the GABA A and GABA B receptors.GABA A receptors are heteropentameric GABA-gated chloride channels and responsible for fast inhibitory neurotransmission.GABA B receptors are heterodimeric G protein coupled receptors (GPCR) that mediate slow and prolonged inhibitory transmission.The extent of inhibitory neurotransmission is determined by a variety of factors,such as the degree of transmitter release and changes in receptor activity by posttranslational modifications (e.g.,phosphorylation),as well as by the number of receptors present in the plasma membrane available for signal transduction.The level of GABA B receptors at the cell surface critically depends on the residence time at the cell surface and finally the rates of endocytosis and degradation.In this review we focus primarily on recent advances in the understanding of trafficking mechanisms that determine the expression level of GABA B receptors in the plasma membrane,and thereby signaling strength.展开更多
The internalization of essential nutrients,lipids and receptors is a crucial process for all eukaryotic cells.Accordingly,endocytosis is highly conserved across cell types and species.Once internalized,small cargocont...The internalization of essential nutrients,lipids and receptors is a crucial process for all eukaryotic cells.Accordingly,endocytosis is highly conserved across cell types and species.Once internalized,small cargocontaining vesicles fuse with early endosomes(also known as sorting endosomes),where they undergo segregation to distinct membrane regions and are sorted and transported on through the endocytic pathway.Although the mechanisms that regulate this sorting are still poorly understood,some receptors are directed to late endosomes and lysosomes for degradation,whereas other receptors are recycled back to the plasma membrane;either directly or through recycling endosomes.The Rab family of small GTP-binding proteins plays crucial roles in regulating these trafficking pathways.Rabs cycle from inactive GDP-bound cytoplasmic proteins to active GTP-bound membraneassociated proteins,as a consequence of the activity of multiple specific GTPase-activating proteins(GAPs) and GTP exchange factors(GEFs).Once bound to GTP,Rabs interact with a multitude of effector proteins that carry out Rab-specific functions.Recent studies have shown that some of these effectors are also interaction partners for the C-terminal Eps15 homology(EHD) proteins,which are also intimately involved in endocytic regulation.A particularly interesting example of common Rab-EHD interaction partners is the MICALlike protein,MICAL-L1.MICAL-L1 and its homolog,MICAL-L2,belong to the larger MICAL family of proteins,and both have been directly implicated in regulating endocytic recycling of cell surface receptors and junctional proteins,as well as controlling cytoskeletal rearrangement and neurite outgrowth.In this review,we summarize the functional roles of MICAL and Rab proteins,and focus on the significance of their interactions and the implications for endocytic transport.展开更多
Eukaryotic cells are confined by membranes that create hydrophobic barriers for substance and information exchange between the inside and outside of the cell.These barriers are formed by assembly of lipids and protein...Eukaryotic cells are confined by membranes that create hydrophobic barriers for substance and information exchange between the inside and outside of the cell.These barriers are formed by assembly of lipids and protein in aqueous environments.Lipids not only serve as building blocks for membrane construction,but also possess regulatory functions in cellular activities.These regulatory lipids are non-uniformly distributed in membrane systems;their temporal and spatial accumulation in specific membranes decodes environmental cues and changes cellular activity accordingly.Phosphoinositides(PIs)are phospholipids that exert regulatory effects.In recent years,research on PIs roles in regulating plant growth,development,and responses to environmental stress is increasing.Several reviews have been published on the composition of PIs,intermolecular transferring of PIs by lipid kinases(phosphatases)or PI-PLCs,subcellular localization,and specially their functions in plant developments.Herein,we review the crucial regulatory functions of PIs in plant stress responses,with a particular focus on PIs involved in membrane trafficking.展开更多
Increasing evidence suggests that the impaired neuroprotection of vesicular monoamine transporter 2(VMAT2)contributes to the pathogenesis of Parkinson's disease.That has been linked to aberrant subcellular retrogra...Increasing evidence suggests that the impaired neuroprotection of vesicular monoamine transporter 2(VMAT2)contributes to the pathogenesis of Parkinson's disease.That has been linked to aberrant subcellular retrograde trafficking as strongly indicated by recent genomic studies on familial Parkinson's diseases.However,whether VMAT2 function is regulated by retrograde trafficking is unknown.By using biochemistry and cell biology approaches,we have shown that VMAT2 was stringently localized to the trans-Golgi network and underwent retrograde trafficking in non-neuronal cells.The transporter also interacted with the key component of retromer,Vps35,biochemically and subcellularly.Using specific siRNA,we further showed that Vps35 depletion altered subcellular localization of VMAT2.Moreover,siRNA-mediated Vps35 knockdown also decreased the stability of VMAT2 as demonstrated by the reduced half-life.Thus,our work suggested that altered vesicular trafficking of VMAT2 may play a vital role in neuroprotection of the transporter as well as in the pathogenesis of Parkinson's disease.展开更多
Parkinson's disease(PD) associated leucine-rich repeat kinase 2(LRRK2) mutants have shown pathogenic effects on a variety of subcellular processes. Two small GTPases Rac1 and Rab29 have been indicated as possible...Parkinson's disease(PD) associated leucine-rich repeat kinase 2(LRRK2) mutants have shown pathogenic effects on a variety of subcellular processes. Two small GTPases Rac1 and Rab29 have been indicated as possible downstream effectors participating in LRRK2 signaling but their detail mechanisms remain unclear. In this study, we have used biochemical and cell biology approaches to address whether two GTPases interact with LRRK2 and hence function differently in LRRK2 mediated pathogenesis. Here we show that Rac1 and Rab29 specifically interact with LRRK2 with higher affinity for Rab29 and with different preference in functional domain binding. Mutant Rab29 but not Racl alters the endosome-to-TGN retrograde trafficking of a cargo protein cation-independent mannose-6-phosphate receptor(CI-M6 PR) and its stability. On the other hand, overexpressed wild type Rab29 but not Racl rescued the altered retrograde membrane trafficking induced by the pathogenic mutant LRRK2^(G2019 S). Furthermore,both Rac1 and Rab29 rescued neurite shortening in differentiated SH-SY5 Y cells induced by LRRK2^(G2019 S). Our study strongly suggests that Rac1 and Rab29 are involved in distinct functions as downstream effectors in LRRK2 signaling pathways.展开更多
Axonal regeneration in the central nervous system is an energy-intensive process.In contrast to mammals,adult zebrafish can functionally recover from neuronal injury.This raises the question of how zebrafish can cope ...Axonal regeneration in the central nervous system is an energy-intensive process.In contrast to mammals,adult zebrafish can functionally recover from neuronal injury.This raises the question of how zebrafish can cope with this high energy demand.We previously showed that in adult zebrafish,subjected to an optic nerve crush,an antagonistic axon-dendrite interplay exists wherein the retraction of retinal ganglion cell dendrites is a prerequisite for effective axonal repair.We postulate a‘dendrites for regeneration’paradigm that might be linked to intraneuronal mitochondrial reshuffling,as ganglion cells likely have insufficient resources to maintain dendrites and restore axons simultaneously.Here,we characterized both mitochondrial distribution and mitochondrial dynamics within the different ganglion cell compartments(dendrites,somas,and axons)during the regenerative process.Optic nerve crush resulted in a reduction of mitochondria in the dendrites during dendritic retraction,whereafter enlarged mitochondria appeared in the optic nerve/tract during axonal regrowth.Upon dendritic regrowth in the retina,mitochondrial density inside the retinal dendrites returned to baseline levels.Moreover,a transient increase in mitochondrial fission and biogenesis was observed in retinal ganglion cell somas after optic nerve damage.Taken together,these findings suggest that during optic nerve injury-induced regeneration,mitochondria shift from the dendrites to the axons and back again and that temporary changes in mitochondrial dynamics support axonal and dendritic regrowth after optic nerve crush.展开更多
Neuroligins (Nlgs) are transmembrane cell adhesion molecules playing essential roles in synapse development and function. Genetic mutations in neuroUgin genes have been linked with some neurodevelopmental disorders ...Neuroligins (Nlgs) are transmembrane cell adhesion molecules playing essential roles in synapse development and function. Genetic mutations in neuroUgin genes have been linked with some neurodevelopmental disorders such as autism. These mutated Nlgs are mostly retained in the endoplasmic reticulum (ER). However, the mechanisms underlying normal Nlg maturation and trafficking have remained largely unknown. Here, we found that Drosophila neuroligin 2 (DNlg2) undergoes proteolytic cleavage in the ER in a variety of Drosophila tissues throughout developmental stages. A region encompassing Y642-T698 is required for this process. The immature non-cleavable DNtg2 is retained in the ER and non-functionaL The C-terminal fragment of DNlg2 instead of the full-length or non-cleavable DNIg2 is able to rescue neuromuscular junction defects and GluRIIB reduction induced by dnlg2 deletion. Intriguingly, the autism-associated R598C mutation in DNIg2 leads to similar marked defects in DNIg2 proteo- lytic process and ER export, revealing a potential role of the improper Nlg cleavage in autism pathogenesis. Collectively, our find- ings uncover a specific mechanism that controls DNIg2 maturation and trafficking via proteolytic cleavage in the ER, suggesting that the perturbed proteolytic cleavage of Nlgs likely contributes to autism disorder.展开更多
OBJECTIVE Investigate the effects of diazepam(DZP) on γ2 subunit containing GABA type A receptor(GABA A R) trafficking.METHODS Immunofluorescence microscopy measured surface GABA A Rs and gephyrin in rat cortical neu...OBJECTIVE Investigate the effects of diazepam(DZP) on γ2 subunit containing GABA type A receptor(GABA A R) trafficking.METHODS Immunofluorescence microscopy measured surface GABA A Rs and gephyrin in rat cortical neurons after 24 h exposure of 1.0 μmol·L^(-1) DZP.Biochemical studies of mice injected with 10 mg·kg^(-1) DZP vs vehicle were assessed for γ2 subunit and total gephyrin cortical levels 12 h post-injection.Ubiquitination of the γ2 subunit was studied by immunoprecipitation after 12 h of 1.0 μmol·L^(-1) DZP exposure.A γ2 subunit encoding an N terminal fluorogen-activating peptide and pH-sensitive green fluorescent protein(γ2 pH FAP) measured lysosomal targeting of γ2 containing GABA A Rs.RFP-gephyrin and γ2 pH FAP synaptic diffusion rates were examined using fluorescence recovery after photobleaching(FRAP).RESULTS Extrasynaptic levels of γ2 GABA A Rs decreased by 12.2%,while synaptic gephyrin S270 phosphorylation increased by 18.3% in DZP-treated neurons after 24 h compared to control(P<0.05).Dendritic levels of gephyrin were also reduced to 74.1% of control,while S270 phosphorylation was elevated by 25.2%(P<0.05;P<0.01).Mice 12 h post-DZP injection demonstrated a 12.7% and 26.1% decrease in total γ2 and gephyrin levels,respectively(P<0.05;P<0.01).12 h DZP treatment enhanced γ2 subunit ubiquitination 1.13-fold relative to control(P<0.05).Internalized γ2 pH FAP GABA A Rs associated with lysosomes was 8.0% higher in neurons treated with 12-16 h DZP compared to control.Pilot FRAP experiments suggest gephyrin and γ2 have increased mobility and turnover at synapses following DZP.CONCLUSION DZP treatment decreases γ2 GABA A R levels and gephyrin scaffolding function after one day of exposure,which may contribute to the formation of DZP tolerance.展开更多
Trafficking in persons, especially women and girls has been on for long and is still going on. Persons in the female group constitute the mostly trafficked humans. This study was conducted to determine the effects of ...Trafficking in persons, especially women and girls has been on for long and is still going on. Persons in the female group constitute the mostly trafficked humans. This study was conducted to determine the effects of human trafficking on household farm labor needs available among farming households. Arable farming households involved in human trafficking were identified and purposively selected for this study with the aid of key informants in purposively selected communities. This led to the selection of 60 arable farming household heads in Delta North Agricultural zone, 65 farming household heads in Delta Central Agricultural Zone, and 36 arable farming household heads in Delta south agricultural zone to give a total of 151 respondents. Data for the study were collected with the utilization of questionnaire and interview schedule. The collected data were subjected to statistical analysis with the application of frequency counts, percentages and means derived from 4-point likert-type scale. The hypothesis was tested using Tobit regression analysis. Human trafficking was found to be age and sex selective and the causes of human trafficking included both push and pull factors, such as high income in destination countries poverty, low risk profit, nature of trafficking in persons, ease in control and manipulation of vulnerable women and girls, low risk involved in working in destination countries, lacking of legitimate and fulfilling employment, sex selective migration policies, less access to information and peer pressure. Shortage of household farm labor was experienced by farming households in clearing and brushing of farm land, sowing, weeding, harvesting and processing/storage. Human trafficking was found to affect household labor availability in clearing/brushing of farm land, sowing, weeding, harvesting and processing/storage of farm produce. It is recommended that poverty alleviation programs should be specially organized for poor women, government and NGOs and international agencies should develop strategies to mitigate human trafficking. The government needs to collaborate with community based organizations and law enforcement agencies to create anti-trafficking committee in fanning communities. Community education should be created for the farming communities to emphasize anti-human trafficking with the use of change agents; extension agents should integrate anti-trafficking messages in their interaction with farmers.展开更多
The overriding objective of this research was to assess the status,major origins and contributing factors of cross-border migration and human trafficking in Ethiopia with the intention of identifying key policy lesson...The overriding objective of this research was to assess the status,major origins and contributing factors of cross-border migration and human trafficking in Ethiopia with the intention of identifying key policy lessons to address the problem.To meet the intended objectives,desk review and key informant interview data gathering techniques were employed.The results of the assessment disclosed that Ethiopia is one of the largest origins(transit and destination as well)of the trafficked persons from Africa.The most common drivers are found to be an amalgam of socioeconomic,political and environmental factors.It was also found that the journey is often dangerous leading to physical assault,sexual abuse,abduction,robbery,drug/alcohol trafficking and even death.In most destination areas,illegal migrants face restricted mobility,exploitative working conditions and harassment of different kinds.The ultimate mechanism to address the problem was found to be adequate job creation and poverty reduction through intensified development efforts involving governmental and non-governmental organizations and the private sector.Furthermore,enhanced democratization of the government system,political tolerance,good governance,improved access to legal travel authorization(visa)for safe migration,awareness creation campaigns,improved monitoring of the private employment agencies and increased cooperation among stakeholders were found to be vital solutions to minimize and halt illicit cross-border human trafficking from Ethiopia.展开更多
基金supported by the National Nature Science Foundation of China to Y.Liu(Grant No.31371436 and No.8157051134)Y.Huang(Grant No.81500678)the laboratory start-up grant from Nanjing Medical University to Y.Liu
文摘The membrane trafficking of cation-independent mannose 6-phosphate receptor(CI-M6PR) between the transGolgi network(TGN) and endosomal compartments is not only critical for maintaining lysosomal function but also a well-known event for understanding molecular and cellular mechanisms in retrograde endosome-to-TGN trafficking.Although it has been well established in literature that the C-terminus of bovine CI-M6PR determines its retrograde trafficking,it remains unclear whether the luminal domain of the protein plays a role on these sorting events.In this study,we found that partial deletion of luminal domain of human CI-M6PR mistargeted the mutant protein to nonTGN compartments.Moreover,replacing the luminal domain of both bovine and human CI-M6PR with that from irrelevant membrane proteins such as CD8 or Tac also altered the TGN targeting of the chimeric proteins.On the other hand,only short sequence from HA fused with the transmembrane domain and C-terminus of the receptor,HA-hCIM6PR-tail,resulted in its preferential targeting to TGN as for the full length receptor,strongly suggesting that sorting of the receptor may be influenced by luminal sequence.Furthermore,using this luminal truncated form of HA-hCIM6 PR as a model cargo,we found that the trafficking of the chimeric protein was regulated by the retromer complex through interacting with SNX5.In conclusion,our study strongly suggested that the disrupted luminal domain from hCI-M6PR or other irrelevant membrane proteins interfere with the process of membrane trafficking and TGN targeting of CI-M6PR.
文摘The aim of this study is to identify and analyze the pattern of visibility of the main actors in the photographic coverage of drug trafficking in six of Mexico’s national newspapers. The study was based on a sample of 12,962,000 photographs published from 2006 to 2010. The images were processed by generating a codebook of key categories extracted from the informational context of drug trafficking and the war against drug trafficking. The technique used to explain the newspapers’ photographic coverage was the content analysis proposed by Johan Galtung in 1965, in its updated version of 2006. The limitations of the research are time constraints (only four years of President Felipe Calderón’s six-year term were analyzed) and information platforms (with the omission of online newspapers, supplements, and additional publications). The study offers an original analysis of the photographic coverage of drug trafficking in the Mexican press. The use of the Galtung Model reveals strong biases and imbalances in the coverage, with a clear tendency to defend the government’s position in the analyzed sample.
文摘The theme of trafficking of human beings treats one of the most severe and dangerous criminal phenomena of the organized crime in Albania. The objects of this paper are: human trafficking; ways of trafficking; risk of Albanian society; and investment of the criminal benefits deriving from trafficking in legal economic activities, it is of great importance for the treatment of proactive investigations to the trafficking of human beings. Another important aspect of the trafficking investigations is the investigation of criminal assets and the way how they are used in the economy of the country. In this paper, we stress that the investigation of criminal assets benefited by the crime of trafficking human beings as well as other wealth financed by these assets is important as the investigation of the criminal activity of trafficking itself. Also, we aim to evaluate the necessity of acting of all law enforcement agencies and other state institutions in order to be successful in the fight against the crime of trafficking of human beings. At the end of this paper, we do treat the necessity and the ways of collaboration of law enforcement agencies, NGOs, and structures of local government for rehabilitation of the victims of trafficking and their integration in the social life.
文摘This paper presents a comprehensive analysis of global human trafficking trends over a twenty-year period, leveraging a robust dataset from the Counter Trafficking Data Collaborative (CTDC). The study unfolds in a systematic manner, beginning with a detailed data collection phase, where ethical and legal standards for data usage and privacy are strictly observed. Following collection, the data undergoes a rigorous preprocessing stage, involving cleaning, integration, transformation, and normalization to ensure accuracy and consistency for analysis. The analytical phase employs time-series analysis to delineate historical trends and utilizes predictive modeling to forecast future trajectories of human trafficking using the advanced analytical capabilities of Power BI. A comparative analysis across regions—Africa, the Americas, Asia, and Europe—is conducted to identify and visualize the distribution of human trafficking, dissecting the data by victim demographics, types of exploitation, and duration of victimization. The findings of this study not only offer a descriptive and predictive outlook on trafficking patterns but also provide insights into the regional nuances that influence these trends. The article underscores the prevalence and persistence of human trafficking, identifies factors contributing to its evolution, and discusses the implications for policy and law enforcement. By integrating a methodological approach with quantitative analysis, this research contributes to the strategic planning and resource allocation for combating human trafficking. It highlights the necessity for continued research and international cooperation to effectively address and mitigate this global issue. The implications of this research are significant, offering actionable insights for policymakers, law enforcement, and advocates in the ongoing battle against human trafficking.
基金supported by the National Natural Science Foundation of China (NSFC)(31571464, 31371438, 31070222 to Quan-Sheng Qiu)the National Basic Research Program of China (973)project, 2013CB429904 to Quan-Sheng Qiu)+5 种基金the Research Fund for the Doctoral Program of Higher Education of China(RFDP)(20130211110001 to Quan-Sheng Qiu)Research Team of Stress Tolerance Mechanisms and Molecular Breeding of Plateau PlantsQinghai Province “Kunlun Talents·Advanced Innovative and Entrepreneurial Talents” Program (2022 to QuanSheng Qiu)the Qinghai Provincial Department of Science and Technology Qinghai basic research program (2022-ZJ-724 to Quan-Sheng Qiu)the Independent Research and Development Project of State Key Laboratory of Herbage Improvement and Grassland Agro-ecosystems (202202 to Quan-Sheng Qiu)the Core Facility of School of Life Sciences,Lanzhou University。
文摘Arabidopsis plastid antiporters KEA1 and KEA2are critical for plastid development, photosynthetic efficiency, and plant development.Here, we show that KEA1 and KEA2 are involved in vacuolar protein trafficking. Genetic analyses found that the kea1 kea2 mutants had short siliques, small seeds, and short seedlings. Molecular and biochemical assays showed that seed storage proteins were missorted out of the cell and the precursor proteins were accumulated in kea1 kea2. Protein storage vacuoles(PSVs) were smaller in kea1 kea2. Further analyses showed that endosomal trafficking in kea1 kea2 was compromised. Vacuolar sorting receptor 1(VSR1) subcellular localizations, VSR–cargo interactions, and p24 distribution on the endoplasmic reticulum(ER) and Golgi apparatus were affected in kea1 kea2. Moreover, plastid stromule growth was reduced and plastid association with the endomembrane compartments was disrupted in kea1 kea2. Stromule growth was regulated by the cellular pH and K+homeostasis maintained by KEA1 and KEA2. The organellar pH along the trafficking pathway was altered in kea1 kea2. Overall, KEA1 and KEA2 regulate vacuolar trafficking by controlling the function of plastid stromules via adjusting pH and K+homeostasis.
基金This work was supported by the National Natural Science Foundation of China(Grant Nos.31371436 and 8157051134 to Y.L.)by the laboratory start-up grant from Nanjing Medical University(to Y.L.).
文摘The endosomal trafficking of signaling membrane proteins, such as receptors, transporters and channels, is mediated by the retromer-mediated sorting machinery, composed of a cargo-selective vacuolar protein sorting trimer and a membrane-deforming subunit of sorting nexin proteins. Recent studies have shown that the isoforms, sorting nexin 5 (SNX5) and SNX6, have played distinctive regulatory roles in retrograde membrane trafficking. However, the molecular insight determined functional differences within the proteins remains unclear. We reported that SNX5 and SNX6 had distinct binding affinity to the cargo protein vesicular monoamine transporter 2 (VMAT2). SNX5, but not SNX6, specifically interacted with VMAT2 through the Phox domain, which contains an alpha-helix binding motif. Using chimeric mutagenesis, we identified that several key residues within this domain were unique in SNX5, but not SNX6, and played an auxiliary role in its binding to VMAT2. Importantly, we generated a set of mutant SNX6, in which the corresponding key residues were mutated to those in SNX5. In addition to the gain in binding affinity to VMAT2, their overexpression functionally rescued the altered retrograde trafficking of VMAT2 induced by siRNA-mediated depletion of SNX5. These data strongly suggest that SNX5 and SNX6 have different functions in retrograde membrane trafficking, which is determined by the different structural elements within the Phox domain of two proteins. Our work provides a new information on the role of SNX5 and SNX6 in the molecular regulation of retrograde membrane trafficking and vesicular membrane targeting in monoamine neurotransmission and neurological diseases.
文摘In 2006,a large quantity of clandestine sensitive radioactive materials surfaced at an abandoned scrap metal and lead recovery facility in the city Gaziemir,Izmir,Türkiye.In April,2007 the TAEK(Turkish Atomic Energy Agency)official experts surveyed the 70,000 m^(2)site including the storage buildings.They reported that 20-300 microRad/h of radiation was detected throughout the site,especially high readings of more than 300 micRad/h were recorded inside the storage building containing about 1,100 tons of commercially valuable waste.About 15 tons of waste were taken from the storage building and sent to TAEK’s lab in Ankara to be analyzed.In April,2008 TAEK issued a press release(No:04/2012)on its official website confirming that their analysis of samples taken from the Aslan facility showed that,there is a scattered radioactive contamination in the Aslan lead-recovering factory.The radioactive isotopes of Europium-152 and Europium-154 were found in the landfilled area,additionally,these isotopes were more concentrated(higher readings)in the commercially valuable waste(approx.1,100 tons)which was kept in the storage building,a clear indication of the fact that at the Aslan facility,sensitive nuclear reactor parts,including but not limited to nuclear reactors control rods were being melted.
文摘Plants employ sophisticated mechanisms to interact with pathogenic as well as beneficial microbes. Of those, membrane trafficking is key in establishing a rapid and precise response. Upon interaction with pathogenic microbes, surface-localized immune receptors undergo endocytosis for signal transduction and activity regulation while cell wall components, antimicrobial compounds, and defense proteins are delivered to pathogen invasion sites through polarized secretion. To sustain mutualistic associations, host cells also reprogram the membrane trafficking system to accommodate invasive structures of symbi- otic microbes. Here, we provide an analysis of recent advances in understanding the roles of secretory and endocytic membrane trafficking pathways in plant immune activation. We also discuss strategies deployed by adapted microbes to manipulate these pathways to subvert or inhibit plant defense.
文摘Inositol polyphosphate 5-phosphatases (5PTases) are enzymes of phosphatidylinositol metabolism that affect various aspects of plant growth and development. Arabidopsis 5PTasel3 regulates auxin homeostasis and hormonerelated cotyledon vein development, and here we demonstrate that its knockout mutant 5pt13 has elevated sensitivity to gravistimulation in root gravitropic responses. The altered responses of 5pt13 mutants to 1-N-naphthylphthalamic acid (an auxin transport inhibitor) indicate that 5PTase13 might be involved in the regulation of auxin transport. Indeed, the auxin efflux carrier PIN2 is expressed more broadly under 5PTasel3 deficiency, and observations of the internalization of the membrane-selective dye FM4-64 reveal altered vesicle trafficking in 5pt13 mutants. Compared with wild-type, 5pt13 mutant seedlings are less sensitive to the inhibition by brefeldin A of vesicle cycling, seedling growth, and the intracellular cycling of the PIN1 and PIN2 proteins. Further, auxin redistribution upon gravitropic stimulation is stimulated under 5PTasel3 deficiency. These results suggest that 5PTasel3 may modulate auxin transport by regulating vesicle trafficking and thereby play a role in root gravitropism.
基金supported by grants from the National Institutes of Health (NS058886 and NS072206)Rita Allen Foundation+1 种基金Mr. David Koch and the Patrick C. Walsh Prostate Cancer Research Fundthe Blaustein Pain Research Fund
文摘Activity-dependent postsynaptic receptor trafficking is critical for long-term synaptic plasticity in the brain, but it is unclear whether this mechanism actually mediates the spinal cord dorsal hom central sensitization (a specific form of synaptic plasticity) that is associated with persistent pain. Recent studies have shown that peripheral inflammation drives changes in ct-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunit trafficking in the dorsal horn and that such changes contribute to the hypersensitivity that underlies persistent pain. Here, we review current evi- dence to illustrate how spinal cord AMPARs participate in the dorsal hom central sensitization associated with persistent pain. Understanding these mechanisms may allow the development of novel therapeutic strategies for treating persistent pain.
基金Supported by The Swiss Science Foundation Grant,31003A_121963
文摘Inhibitory neurotransmission ensures normal brain function by counteracting and integrating excitatory activity.-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the mammalian central nervous system,and mediates its effects via two classes of receptors:the GABA A and GABA B receptors.GABA A receptors are heteropentameric GABA-gated chloride channels and responsible for fast inhibitory neurotransmission.GABA B receptors are heterodimeric G protein coupled receptors (GPCR) that mediate slow and prolonged inhibitory transmission.The extent of inhibitory neurotransmission is determined by a variety of factors,such as the degree of transmitter release and changes in receptor activity by posttranslational modifications (e.g.,phosphorylation),as well as by the number of receptors present in the plasma membrane available for signal transduction.The level of GABA B receptors at the cell surface critically depends on the residence time at the cell surface and finally the rates of endocytosis and degradation.In this review we focus primarily on recent advances in the understanding of trafficking mechanisms that determine the expression level of GABA B receptors in the plasma membrane,and thereby signaling strength.
基金Supported by The National Institutes of Health grants R01GM074876 (Caplan S and Naslavsky N),R01GM087455 (Caplan S),the Nebraska Dept. of Health (Naslavsky N)P20 RR018759 from the National Center
文摘The internalization of essential nutrients,lipids and receptors is a crucial process for all eukaryotic cells.Accordingly,endocytosis is highly conserved across cell types and species.Once internalized,small cargocontaining vesicles fuse with early endosomes(also known as sorting endosomes),where they undergo segregation to distinct membrane regions and are sorted and transported on through the endocytic pathway.Although the mechanisms that regulate this sorting are still poorly understood,some receptors are directed to late endosomes and lysosomes for degradation,whereas other receptors are recycled back to the plasma membrane;either directly or through recycling endosomes.The Rab family of small GTP-binding proteins plays crucial roles in regulating these trafficking pathways.Rabs cycle from inactive GDP-bound cytoplasmic proteins to active GTP-bound membraneassociated proteins,as a consequence of the activity of multiple specific GTPase-activating proteins(GAPs) and GTP exchange factors(GEFs).Once bound to GTP,Rabs interact with a multitude of effector proteins that carry out Rab-specific functions.Recent studies have shown that some of these effectors are also interaction partners for the C-terminal Eps15 homology(EHD) proteins,which are also intimately involved in endocytic regulation.A particularly interesting example of common Rab-EHD interaction partners is the MICALlike protein,MICAL-L1.MICAL-L1 and its homolog,MICAL-L2,belong to the larger MICAL family of proteins,and both have been directly implicated in regulating endocytic recycling of cell surface receptors and junctional proteins,as well as controlling cytoskeletal rearrangement and neurite outgrowth.In this review,we summarize the functional roles of MICAL and Rab proteins,and focus on the significance of their interactions and the implications for endocytic transport.
基金the National Natural Science Foundation of China (32100553, 32171956, and 31770294)Natural Science Foundation of Jiangsu Province (BK20200555)the Fundamental Research Funds for the Central Universities, and a start-up fund for advanced talents from Nanjing Agricultural University (680-804016 to F.L.)
文摘Eukaryotic cells are confined by membranes that create hydrophobic barriers for substance and information exchange between the inside and outside of the cell.These barriers are formed by assembly of lipids and protein in aqueous environments.Lipids not only serve as building blocks for membrane construction,but also possess regulatory functions in cellular activities.These regulatory lipids are non-uniformly distributed in membrane systems;their temporal and spatial accumulation in specific membranes decodes environmental cues and changes cellular activity accordingly.Phosphoinositides(PIs)are phospholipids that exert regulatory effects.In recent years,research on PIs roles in regulating plant growth,development,and responses to environmental stress is increasing.Several reviews have been published on the composition of PIs,intermolecular transferring of PIs by lipid kinases(phosphatases)or PI-PLCs,subcellular localization,and specially their functions in plant developments.Herein,we review the crucial regulatory functions of PIs in plant stress responses,with a particular focus on PIs involved in membrane trafficking.
基金supported by the National Nature Science Foundation of China(Grant No.31371436 and No.8157051134)by the laboratory start-up grant from Nanjing Medical University to Y.Liu
文摘Increasing evidence suggests that the impaired neuroprotection of vesicular monoamine transporter 2(VMAT2)contributes to the pathogenesis of Parkinson's disease.That has been linked to aberrant subcellular retrograde trafficking as strongly indicated by recent genomic studies on familial Parkinson's diseases.However,whether VMAT2 function is regulated by retrograde trafficking is unknown.By using biochemistry and cell biology approaches,we have shown that VMAT2 was stringently localized to the trans-Golgi network and underwent retrograde trafficking in non-neuronal cells.The transporter also interacted with the key component of retromer,Vps35,biochemically and subcellularly.Using specific siRNA,we further showed that Vps35 depletion altered subcellular localization of VMAT2.Moreover,siRNA-mediated Vps35 knockdown also decreased the stability of VMAT2 as demonstrated by the reduced half-life.Thus,our work suggested that altered vesicular trafficking of VMAT2 may play a vital role in neuroprotection of the transporter as well as in the pathogenesis of Parkinson's disease.
基金supported by the National Nature Science Foundation of China (Grant No. 31371436 andNo. 8157051134)the laboratory start-up grant from Nanjing Medical University to Y.Liu
文摘Parkinson's disease(PD) associated leucine-rich repeat kinase 2(LRRK2) mutants have shown pathogenic effects on a variety of subcellular processes. Two small GTPases Rac1 and Rab29 have been indicated as possible downstream effectors participating in LRRK2 signaling but their detail mechanisms remain unclear. In this study, we have used biochemical and cell biology approaches to address whether two GTPases interact with LRRK2 and hence function differently in LRRK2 mediated pathogenesis. Here we show that Rac1 and Rab29 specifically interact with LRRK2 with higher affinity for Rab29 and with different preference in functional domain binding. Mutant Rab29 but not Racl alters the endosome-to-TGN retrograde trafficking of a cargo protein cation-independent mannose-6-phosphate receptor(CI-M6 PR) and its stability. On the other hand, overexpressed wild type Rab29 but not Racl rescued the altered retrograde membrane trafficking induced by the pathogenic mutant LRRK2^(G2019 S). Furthermore,both Rac1 and Rab29 rescued neurite shortening in differentiated SH-SY5 Y cells induced by LRRK2^(G2019 S). Our study strongly suggests that Rac1 and Rab29 are involved in distinct functions as downstream effectors in LRRK2 signaling pathways.
基金financially supported by the Katholieke Universiteit Leuven Research Council (C14/18/053)the research foundation Flanders (FWO) (G082221N)+1 种基金a personal L’Oréal/UNESCO (For Women in Science) fellowshipa personal FWO fellowship
文摘Axonal regeneration in the central nervous system is an energy-intensive process.In contrast to mammals,adult zebrafish can functionally recover from neuronal injury.This raises the question of how zebrafish can cope with this high energy demand.We previously showed that in adult zebrafish,subjected to an optic nerve crush,an antagonistic axon-dendrite interplay exists wherein the retraction of retinal ganglion cell dendrites is a prerequisite for effective axonal repair.We postulate a‘dendrites for regeneration’paradigm that might be linked to intraneuronal mitochondrial reshuffling,as ganglion cells likely have insufficient resources to maintain dendrites and restore axons simultaneously.Here,we characterized both mitochondrial distribution and mitochondrial dynamics within the different ganglion cell compartments(dendrites,somas,and axons)during the regenerative process.Optic nerve crush resulted in a reduction of mitochondria in the dendrites during dendritic retraction,whereafter enlarged mitochondria appeared in the optic nerve/tract during axonal regrowth.Upon dendritic regrowth in the retina,mitochondrial density inside the retinal dendrites returned to baseline levels.Moreover,a transient increase in mitochondrial fission and biogenesis was observed in retinal ganglion cell somas after optic nerve damage.Taken together,these findings suggest that during optic nerve injury-induced regeneration,mitochondria shift from the dendrites to the axons and back again and that temporary changes in mitochondrial dynamics support axonal and dendritic regrowth after optic nerve crush.
文摘Neuroligins (Nlgs) are transmembrane cell adhesion molecules playing essential roles in synapse development and function. Genetic mutations in neuroUgin genes have been linked with some neurodevelopmental disorders such as autism. These mutated Nlgs are mostly retained in the endoplasmic reticulum (ER). However, the mechanisms underlying normal Nlg maturation and trafficking have remained largely unknown. Here, we found that Drosophila neuroligin 2 (DNlg2) undergoes proteolytic cleavage in the ER in a variety of Drosophila tissues throughout developmental stages. A region encompassing Y642-T698 is required for this process. The immature non-cleavable DNtg2 is retained in the ER and non-functionaL The C-terminal fragment of DNlg2 instead of the full-length or non-cleavable DNIg2 is able to rescue neuromuscular junction defects and GluRIIB reduction induced by dnlg2 deletion. Intriguingly, the autism-associated R598C mutation in DNIg2 leads to similar marked defects in DNIg2 proteo- lytic process and ER export, revealing a potential role of the improper Nlg cleavage in autism pathogenesis. Collectively, our find- ings uncover a specific mechanism that controls DNIg2 maturation and trafficking via proteolytic cleavage in the ER, suggesting that the perturbed proteolytic cleavage of Nlgs likely contributes to autism disorder.
基金supported by National Institute of Health(T32GM008424)Whitehall Foundation+1 种基金William C DEGROAT Neuropharmacology Departmental FellowshipPharmacology and Chemical Biology Startup Funds
文摘OBJECTIVE Investigate the effects of diazepam(DZP) on γ2 subunit containing GABA type A receptor(GABA A R) trafficking.METHODS Immunofluorescence microscopy measured surface GABA A Rs and gephyrin in rat cortical neurons after 24 h exposure of 1.0 μmol·L^(-1) DZP.Biochemical studies of mice injected with 10 mg·kg^(-1) DZP vs vehicle were assessed for γ2 subunit and total gephyrin cortical levels 12 h post-injection.Ubiquitination of the γ2 subunit was studied by immunoprecipitation after 12 h of 1.0 μmol·L^(-1) DZP exposure.A γ2 subunit encoding an N terminal fluorogen-activating peptide and pH-sensitive green fluorescent protein(γ2 pH FAP) measured lysosomal targeting of γ2 containing GABA A Rs.RFP-gephyrin and γ2 pH FAP synaptic diffusion rates were examined using fluorescence recovery after photobleaching(FRAP).RESULTS Extrasynaptic levels of γ2 GABA A Rs decreased by 12.2%,while synaptic gephyrin S270 phosphorylation increased by 18.3% in DZP-treated neurons after 24 h compared to control(P<0.05).Dendritic levels of gephyrin were also reduced to 74.1% of control,while S270 phosphorylation was elevated by 25.2%(P<0.05;P<0.01).Mice 12 h post-DZP injection demonstrated a 12.7% and 26.1% decrease in total γ2 and gephyrin levels,respectively(P<0.05;P<0.01).12 h DZP treatment enhanced γ2 subunit ubiquitination 1.13-fold relative to control(P<0.05).Internalized γ2 pH FAP GABA A Rs associated with lysosomes was 8.0% higher in neurons treated with 12-16 h DZP compared to control.Pilot FRAP experiments suggest gephyrin and γ2 have increased mobility and turnover at synapses following DZP.CONCLUSION DZP treatment decreases γ2 GABA A R levels and gephyrin scaffolding function after one day of exposure,which may contribute to the formation of DZP tolerance.
文摘Trafficking in persons, especially women and girls has been on for long and is still going on. Persons in the female group constitute the mostly trafficked humans. This study was conducted to determine the effects of human trafficking on household farm labor needs available among farming households. Arable farming households involved in human trafficking were identified and purposively selected for this study with the aid of key informants in purposively selected communities. This led to the selection of 60 arable farming household heads in Delta North Agricultural zone, 65 farming household heads in Delta Central Agricultural Zone, and 36 arable farming household heads in Delta south agricultural zone to give a total of 151 respondents. Data for the study were collected with the utilization of questionnaire and interview schedule. The collected data were subjected to statistical analysis with the application of frequency counts, percentages and means derived from 4-point likert-type scale. The hypothesis was tested using Tobit regression analysis. Human trafficking was found to be age and sex selective and the causes of human trafficking included both push and pull factors, such as high income in destination countries poverty, low risk profit, nature of trafficking in persons, ease in control and manipulation of vulnerable women and girls, low risk involved in working in destination countries, lacking of legitimate and fulfilling employment, sex selective migration policies, less access to information and peer pressure. Shortage of household farm labor was experienced by farming households in clearing and brushing of farm land, sowing, weeding, harvesting and processing/storage. Human trafficking was found to affect household labor availability in clearing/brushing of farm land, sowing, weeding, harvesting and processing/storage of farm produce. It is recommended that poverty alleviation programs should be specially organized for poor women, government and NGOs and international agencies should develop strategies to mitigate human trafficking. The government needs to collaborate with community based organizations and law enforcement agencies to create anti-trafficking committee in fanning communities. Community education should be created for the farming communities to emphasize anti-human trafficking with the use of change agents; extension agents should integrate anti-trafficking messages in their interaction with farmers.
文摘The overriding objective of this research was to assess the status,major origins and contributing factors of cross-border migration and human trafficking in Ethiopia with the intention of identifying key policy lessons to address the problem.To meet the intended objectives,desk review and key informant interview data gathering techniques were employed.The results of the assessment disclosed that Ethiopia is one of the largest origins(transit and destination as well)of the trafficked persons from Africa.The most common drivers are found to be an amalgam of socioeconomic,political and environmental factors.It was also found that the journey is often dangerous leading to physical assault,sexual abuse,abduction,robbery,drug/alcohol trafficking and even death.In most destination areas,illegal migrants face restricted mobility,exploitative working conditions and harassment of different kinds.The ultimate mechanism to address the problem was found to be adequate job creation and poverty reduction through intensified development efforts involving governmental and non-governmental organizations and the private sector.Furthermore,enhanced democratization of the government system,political tolerance,good governance,improved access to legal travel authorization(visa)for safe migration,awareness creation campaigns,improved monitoring of the private employment agencies and increased cooperation among stakeholders were found to be vital solutions to minimize and halt illicit cross-border human trafficking from Ethiopia.