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1.
Cureus ; 16(3): e55679, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38586806

ABSTRACT

Anton-Babinski syndrome is a rare extension of cortical blindness following injury to the occipital lobe. The patient behaves as sighted but has visual function derangements. The posterior cerebral artery (PCA) stroke represents 5% to 10% of total strokes. The COVID-19 pandemic has shown a rise in stroke cases. We present a case of this rare PCA stroke, first diagnosed by an ophthalmologist. This case had an inconsistent initial presentation, but subsequent computed tomography of the brain and other neurological investigations confirmed the diagnosis. If such cases are diagnosed early, they could have better management. Timely intervention can decrease morbidity as well as mortality.

2.
bioRxiv ; 2024 Jan 04.
Article in English | MEDLINE | ID: mdl-38260331

ABSTRACT

Brain development is highly dynamic and asynchronous, marked by the sequential maturation of functional circuits across the brain. The timing and mechanisms driving circuit maturation remain elusive due to an inability to identify and map maturing neuronal populations. Here we create DevATLAS (Developmental Activation Timing-based Longitudinal Acquisition System) to overcome this obstacle. We develop whole-brain mapping methods to construct the first longitudinal, spatiotemporal map of circuit maturation in early postnatal mouse brains. Moreover, we uncover dramatic impairments within the deep cortical layers in a neurodevelopmental disorders (NDDs) model, demonstrating the utility of this resource to pinpoint when and where circuit maturation is disrupted. Using DevATLAS, we reveal that early experiences accelerate the development of hippocampus-dependent learning by increasing the synaptically mature granule cell population in the dentate gyrus. Finally, DevATLAS enables the discovery of molecular mechanisms driving activity-dependent circuit maturation.

3.
Genome Biol Evol ; 16(1)2024 01 05.
Article in English | MEDLINE | ID: mdl-38159044

ABSTRACT

High-quality genome assemblies across a range of nontraditional model organisms can accelerate the discovery of novel aspects of genome evolution. The Drosophila virilis group has several attributes that distinguish it from more highly studied species in the Drosophila genus, such as an unusual abundance of repetitive elements and extensive karyotype evolution, in addition to being an attractive model for speciation genetics. Here, we used long-read sequencing to assemble five genomes of three virilis group species and characterized sequence and structural divergence and repetitive DNA evolution. We find that our contiguous genome assemblies allow characterization of chromosomal arrangements with ease and can facilitate analysis of inversion breakpoints. We also leverage a small panel of resequenced strains to explore the genomic pattern of divergence and polymorphism in this species and show that known demographic histories largely predicts the extent of genome-wide segregating polymorphism. We further find that a neo-X chromosome in Drosophila americana displays X-like levels of nucleotide diversity. We also found that unusual repetitive elements were responsible for much of the divergence in genome composition among species. Helitron-derived tandem repeats tripled in abundance on the Y chromosome in D. americana compared to Drosophila novamexicana, accounting for most of the difference in repeat content between these sister species. Repeats with characteristics of both transposable elements and satellite DNAs expanded by 3-fold, mostly in euchromatin, in both D. americana and D. novamexicana compared to D. virilis. Our results represent a major advance in our understanding of genome biology in this emerging model clade.


Subject(s)
DNA Transposable Elements , Drosophila , Animals , Drosophila/genetics , DNA, Satellite , Genomics/methods , Y Chromosome
4.
Cureus ; 15(9): e45914, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37885531

ABSTRACT

Introduction Physical inactivity is a highly prevalent modifiable risk factor for many diseases, including cardiovascular and cerebrovascular diseases, the leading causes of death. Many health institutes have issued and adopted guidelines and recommendations on physical activity. This study aims to study the knowledge, practice, and barriers of medical students enrolled at the University of Khartoum, Sudan, regarding physical activity. It aimed to assess the students' knowledge about physical activity, to determine the levels of physical activity and compare it with the WHO recommended levels and data from other countries, to compare the activity and sedentary levels between males and females, and to take a look on the barriers to physical activity. Methods An observational, descriptive, cross-sectional study was conducted at the Faculty of Medicine, University of Khartoum in December 2022. A total of 336 students were included using systematic random sampling. Data were collected using an online questionnaire that included the Global Physical Activity Questionnaire (GPAQ). Levels of physical activity were described and compared between males and females. Results Around 40.5% of the students achieved the recommended level of physical activity. The mean level of vigorous-intensity physical activity was 50.9 minutes/week (SD= 125.7), the mean level of moderate-intensity physical activity was 156.5 minutes/week (SD= 316.1), the mean level of total physical activity was 207 minutes/week (SD= 356). Between males and females, there was a significant mean difference in the level of vigorous-intensity physical activity and total physical activity. The mean level of sedentary behavior was 7.61 hours/day (SD= 4.62) with no significant difference between males and females (p=0.127). Students showed good knowledge about the cardiovascular and mental benefits of physical activity but not about its protective benefits against cancer. Only 19.4% knew the WHO-recommended levels of physical activity. The most common major barriers toward physical activity reported by the students were lack of time (43.8%), and lack of suitable facilities (31.3%) among others. Conclusion More than half (59.5%) of the students were insufficiently active. Levels of physical activity were significantly associated with the participants' sex but not their knowledge of the recommended levels of physical activity. Males showed higher levels of physical activity. Lack of time was the most common barrier to exercise. More knowledge and education about physical activity should be provided as well as suitable facilities.

5.
bioRxiv ; 2023 Aug 14.
Article in English | MEDLINE | ID: mdl-37645834

ABSTRACT

High-quality genome assemblies across a range of non-traditional model organisms can accelerate the discovery of novel aspects of genome evolution. The Drosophila virilis group has several attributes that distinguish it from more highly studied species in the Drosophila genus, such as an unusual abundance of repetitive elements and extensive karyotype evolution, in addition to being an attractive model for speciation genetics. Here we used long-read sequencing to assemble five genomes of three virilis group species and characterized sequence and structural divergence and repetitive DNA evolution. We find that our contiguous genome assemblies allow characterization of chromosomal arrangements with ease and can facilitate analysis of inversion breakpoints. We also leverage a small panel of resequenced strains to explore the genomic pattern of divergence and polymorphism in this species and show that known demographic histories largely predicts the extent of genome-wide segregating polymorphism. We further find that a neo-X chromosome in D. americana displays X-like levels of nucleotide diversity. We also found that unusual repetitive elements were responsible for much of the divergence in genome composition among species. Helitron-derived tandem repeats tripled in abundance on the Y chromosome in D. americana compared to D. novamexicana, accounting for most of the difference in repeat content between these sister species. Repeats with characteristics of both transposable elements and satellite DNAs expanded by three-fold, mostly in euchromatin, in both D. americana and D. novamexicana compared to D. virilis. Our results represent a major advance in our understanding of genome biology in this emerging model clade.

6.
Cureus ; 15(7): e42243, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37605665

ABSTRACT

Objective The objective is to determine the impact of a health education intervention on self-rated health knowledge, levels of stress and anxiety, and ability to find and access school resources for international students studying at a Canadian University and College. Participants and setting This is a pre- and post-intervention survey. Undergraduate and graduate international students on the shared campus of Durham College and Ontario Tech University in Oshawa, Ontario were included. Interventions  International students participating in this study received two structured visits, scheduled two weeks apart. At the start of the first visit, students completed a baseline survey which included questions on self-rated health knowledge, stress levels, and ability to access school resources. At this visit, students received 30 minutes of structured health education from a registered nurse on the topics of sexual health and adult immunizations.  At the second visit, students received 30 minutes of structured teaching from the registered nurse on the topics of mental health, COVID-19, and campus resources. Upon the completion of this teaching, students completed a post-intervention survey with the same questions as the pre-survey, to gauge for changes related to the intervention. Results T-values were calculated for each survey item from the pre and post-survey. These t-values were used as the outcome measure to determine changes in health knowledge, stress levels, and ability to access resources following the intervention. In total, there were 202 participants. Statistical analysis showed significant t-values for all survey items in the pre- and post-analysis. Following the education intervention, the highest t-values were noted in self-rated sexual health knowledge (t-value 16.80, p < 0.001), ability to find and access school resources (t-value 16.14, p < 0.001), and current level of stress/anxiety in regard to being in a new country (t-value 14.04, p < 0.001). Conclusion Following a structured health education intervention, international students reported significant increases in self-rated health knowledge for specific topics, ability to find and access school resources, ability to get help for a mental health issue, and significant decreases in self-rated stress/anxiety. These results can support further exploration of health education in international student populations to ensure these students are adequately informed and supported when arriving in a new country.

7.
Cureus ; 15(7): e41620, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37565093

ABSTRACT

Background The discharge summary is a vital component of the modern health system. It is defined as a synopsis of information regarding events occurring during the inpatient care of a patient, to allow for a safe, quick, and effective patient-centered discharge process. It contains important information about the patient's hospital stay, including the reason for admission, treatment received, and follow-up needed. Low-quality discharge summaries pose a great risk to patient healthcare since the most frequent reason for error in clinical settings is poor communication. In the United Kingdom, the Professional Record Standards Body (PRSB) has adopted the Academy of Medical Royal Colleges (AoMRC) "Standards for the Clinical Structure and Content of Patient Records" and produced a standard discharge summary form. This study aimed to assess the quality of discharge summaries at Al-Shaab Hospital in Sudan in terms of information, filling adequacy, and adherence to international guidelines and evaluate the discharge interviews. Methods A cross-sectional institution-based study was conducted in the period of September to December 2022 at Al-Shaab Teaching Hospital in Khartoum, Sudan. Systematic random sampling was used to select the study participants from the discharged patients. A total of 70 patients were met in their wards over a period of two months, and the contents of their discharge cards were compared to items on an online checklist based on the Professional Record Standards Body (PRSB) and the Academy of Medical Royal Colleges (AoMRC) standard discharge summary. The patients were also interviewed to assess their knowledge regarding their discharge information. Results The hospital's discharge summary form contained only four headings: date, patient name, age, and ID number. The assessed cards were found to be missing valuable information, including date of admission (missing in 83%), filling doctor's name (missing in 71%), and medication changes (missing in 70%). Only half of the summaries were clearly readable. The majority of patients had poor knowledge regarding their medication side effects (89%) and how to act in an emergency (86%), while knowledge of medication doses and follow-up details was good in 80% and 66%, respectively. Conclusion The patients are discharged with inadequately filled discharge forms. This may be due to the poor design of the form, so a newly designed form will be proposed, based on international standards. The discharge interview is also in need of improvement, to make sure patients are fully aware of their condition.

8.
Mol Cell Proteomics ; 22(8): 100610, 2023 08.
Article in English | MEDLINE | ID: mdl-37391044

ABSTRACT

Reproductive traits often evolve rapidly between species. Understanding the causes and consequences of this rapid divergence requires characterization of female and male reproductive proteins and their effect on fertilization success. Species in the Drosophila virilis clade exhibit rampant interspecific reproductive incompatibilities, making them ideal for studies on diversification of reproductive proteins and their role in speciation. Importantly, the role of intraejaculate protein abundance and allocation in interspecific divergence is poorly understood. Here, we identify and quantify the transferred male ejaculate proteome using multiplexed isobaric labeling of the lower female reproductive tract before and immediately after mating using three species of the virilis group. We identified over 200 putative male ejaculate proteins, many of which show differential abundance between species, suggesting that males transfer a species-specific allocation of seminal fluid proteins during copulation. We also identified over 2000 female reproductive proteins, which contain female-specific serine-type endopeptidases that showed differential abundance between species and elevated rates of molecular evolution, similar to that of some male seminal fluid proteins. Our findings suggest that reproductive protein divergence can also manifest in terms of species-specific protein abundance patterns.


Subject(s)
Drosophila Proteins , Drosophila , Animals , Male , Female , Drosophila/metabolism , Proteomics , Reproduction , Biological Evolution , Drosophila Proteins/metabolism
9.
G3 (Bethesda) ; 13(6)2023 06 01.
Article in English | MEDLINE | ID: mdl-37094819

ABSTRACT

Capturing and sequencing small RNAs is standard practice; however, identification of a group of these small RNAs-small interfering RNAs (siRNAs)-has been more difficult. We present smalldisco, a command-line tool for small interfering RNA discovery and annotation from small RNA-seq datasets. smalldisco can distinguish short reads that map antisense to an annotated genomic feature (e.g. exons or mRNAs), annotate these siRNAs, and quantify their abundance. smalldisco also uses the program Tailor to quantify 3' nontemplated nucleotides of siRNAs or any small RNA species. smalldisco and supporting documentation are available for download from GitHub (https://github.com/ianvcaldas/smalldisco) and archived in Zenodo (https://doi.org/10.5281/zenodo.7799621).


Subject(s)
Genome , Genomics , RNA, Small Interfering/genetics , Sequence Analysis, RNA , RNA-Seq , Software
10.
J Biol Chem ; 299(5): 104644, 2023 05.
Article in English | MEDLINE | ID: mdl-36965617

ABSTRACT

The mechanistic target of rapamycin complex 1 (mTORC1) is a central regulator of mammalian cell growth that is dysregulated in a number of human diseases, including metabolic syndromes, aging, and cancer. Structural, biochemical, and pharmacological studies that have increased our understanding of how mTORC1 executes growth control often relied upon purified mTORC1 protein. However, current immunoaffinity-based purification methods are expensive, inefficient, and do not necessarily isolate endogenous mTORC1, hampering their overall utility in research. Here we present a simple tool to isolate endogenous mTORC1 from various cellular sources. By recombinantly expressing and isolating mTORC1-binding Rag GTPases from Escherichia coli and using them as affinity probes, we demonstrate that mTORC1 can be isolated from mouse, bovine, and human sources. Our results indicate that mTORC1 isolated by this relatively inexpensive method is catalytically active and amenable to scaling. Collectively, this tool may be utilized to isolate mTORC1 from various cellular sources, organs, and disease contexts, aiding mTORC1-related research.


Subject(s)
Biotechnology , Mechanistic Target of Rapamycin Complex 1 , Monomeric GTP-Binding Proteins , Recombinant Proteins , Animals , Cattle , Humans , Mice , Mammals/metabolism , Mechanistic Target of Rapamycin Complex 1/chemistry , Mechanistic Target of Rapamycin Complex 1/isolation & purification , Mechanistic Target of Rapamycin Complex 1/metabolism , Monomeric GTP-Binding Proteins/chemistry , Monomeric GTP-Binding Proteins/genetics , Monomeric GTP-Binding Proteins/metabolism , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Escherichia coli/genetics , Biotechnology/methods , Escherichia coli Proteins/genetics , Escherichia coli Proteins/metabolism , Models, Molecular
11.
Health Informatics J ; 29(1): 14604582231152790, 2023.
Article in English | MEDLINE | ID: mdl-36657139

ABSTRACT

INTRODUCTION: The introduction of information technology was one of the key priorities for policymakers in healthcare organisations over the last two decades, due to the potential benefits of this technology to improve healthcare services and quality. However, about 50% of those projects failed to achieve their intended aims. This was as a result of several factors and included the level of readiness to the new IT projects. AIM: The aim of the study was to assess the readiness of Saudi primary health care centres (PHCCs) readiness for the implementation of an electronic health record system (EHRS) from the project team perspective. METHODS: Explanatory mixed methods design was used with both qualitative and quantitative methods. Thirty-one members of project team at the ministry of health (MOH) participated in the online-based questionnaire, while 13 participants from the same population took part in the semi-structure interviews. Eight different readiness scales were quantitatively examined. These scales include resources, Knowledge, process, management structure and administrative support, end user, technology and values and goals. RESULT: Although, very high level of readiness has been recorded at the process, management structure and administrative support levels, readiness was average at the end user, technology and values and goals levels. Moreover, the study findings revealed that primary health care centres readiness for an electronic health record system must be considered in the early stages of implementation (pre-implementation phase), particularly readiness at a technical level, such as preparedness of the infrastructure. A positive significant correlation has been recorded between all readiness scales with centralization of management system and financial resources. CONCLUSION: Overall, the level of primary health care centres readiness recorded to be high, which indicates that primary health care centres are ready for implementation of the electronic health record system, and in this context, management structure, organizational process, financial recourses and administrative support play significant roles to increase the project success rate.


Subject(s)
Delivery of Health Care , Electronic Health Records , Humans , Surveys and Questionnaires , Health Facilities , Primary Health Care
12.
Cureus ; 14(9): e29459, 2022 Sep.
Article in English | MEDLINE | ID: mdl-36168652

ABSTRACT

Vaccine hesitancy during the COVID-19 pandemic has been a worldwide public health challenge. Organizational behaviour, the study of people's behaviours in organizational settings, can be used to identify the behavioural drivers contributing to vaccine hesitancy and to develop targeted strategies to combat those drivers and improve vaccine uptake. Some common behaviours driving vaccine hesitancy arise from individualism, motivation, attitude, perception, groupthink, heuristics and cognitive bias. Organizational behaviour strategies to combat vaccine hesitancy include fostering a collectivist attitude, overcoming personal barriers to communication such as individual beliefs and values, utilizing motivation theories to target the individualistic mindset, and overcoming attitudes and perceptions by addressing heuristics and cognitive biases.

13.
Cureus ; 14(7): e26786, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35967134

ABSTRACT

This case report depicts a 39-year-old male with no significant past medical history who was admitted for fever of unknown origin and sepsis. He was then found to have Streptococcus intermedius bacteremia and pyogenic liver abscess. The treatment course was complicated by pleural empyema leading to readmission. The case presented here adds to the medical literature, where a clear underrepresentation has been noted, and outlines a unique case of S. intermedius liver abscess complicated by pleural empyema in a patient without significant medical history, risk factors, or typical physical exam findings.

14.
Braz J Biol ; 84: e259351, 2022.
Article in English | MEDLINE | ID: mdl-35830130

ABSTRACT

Zinc oxide nanoparticles were synthesized from the leaf extract of Brassica oleracea L. Acephala group (collard green) followed by their characterization using Scanning Electron Microscope (SEM), and Energy Dispersive X-ray (EDX). The antibacterial properties of zinc nanoparticles were tested against Gram-negative bacteria, Pseudomonas aeruginosa (ATCC ® 9027™), Escherichia coli (ATCC ® 8739™), Klebsiella pneumoniae (ATCC® BAA-1705™) and Gram-positive bacteria, Staphylococcus aureus (ATCC ® 6538™) and Listeria monocytogenes (ATCC ® 13932™), at four different concentrations (50.00 µg/ml, 100.00 µg/ml, 500.00 µg/ml and 1 mg/ml) of zinc oxide nanoparticles suspension. Results revealed that the synthesized nanoparticles exhibit strong antibacterial effects against Pseudomonas aeruginosa, Listeria monocytogenes, Klebsiella pneumonia, Staphylococcus aureus and Escherichia coli at 500.00 µg/ml-1 mg/ml concentrations. An increase in efficacy of nanoparticles with the decrease of their size was also evident. This is a first ever report on Brassica oleracea, L. based nanoparticles which demonstrates that 500.00 µg-1 mg/ml conc. of zinc oxide nanoparticles have antibacterial activity against both Gram -ve and Gram +ve bacteria and have the potential to be considered as an antibacterial agent in future.


Subject(s)
Anti-Bacterial Agents/pharmacology , Brassica , Metal Nanoparticles , Zinc Oxide , Bacteria/classification , Bacteria/drug effects , Bacterial Infections/drug therapy , Brassica/chemistry , Microbial Sensitivity Tests , Zinc Oxide/pharmacology
15.
Front Psychol ; 13: 914328, 2022.
Article in English | MEDLINE | ID: mdl-35859835

ABSTRACT

The current study aimed to investigate the mediating role of loneliness, ASMR, on the relationship between narcissism, Machiavellianism, and psychopathy and anxiety disorder. The population of the study was professionals working in public and private sector organizations. Non-probability snowball technique was used. Data was collected from 512 professionals. A total of 653 questionnaires were distributed and 512 were used in the analysis yielding a response rate of 78.4%. PLS-SEM was used to analyze the data. Measurement and structural models were developed to test the reliability, and validity of the scales as well as hypotheses. Findings of the measurement model revealed that scales were reliable and valid while results of the structural model revealed that narcissism, psychopathy, COVID loneliness, and ASMR have a significant direct impact on anxiety disorder but Machiavellianism does not have a significant effect on anxiety disorder. In addition, COVID loneliness and ASMR mediated between narcissism and psychopathy but do not significantly mediate between Machiavellianism and anxiety disorder. The current study has extended the body of knowledge by bridging the two theories theory of attachment and cognitive dissonance theory. The current study has provided the primary evidence that COVID loneliness increases anxiety while ASMR (audio-visual) tingling sensations help to reduce anxiety disorder.

16.
J Neurosci Rural Pract ; 13(2): 176-180, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35694070

ABSTRACT

Objectives Illicit opioid use is a major concern across the globe due to its adverse health consequences. Pharmacological intervention is regarded as the cornerstone of management of opioid dependence and the Opioid Agonist Treatment (OAT) is the most effective intervention for this chronic relapsing disorder. Since the pattern of use of illicit substances, like opioids, changes with the course of time, we studied the profile of patients registered in an OAT clinic of a tertiary care center in North India over last 8 years. Methods Retrospective chart review of patients registered in the OAT clinic was done. Comparisons were made among two periods (2012-2015 and 2016-2019). Results Total number of opioid dependent patients registered in OAT clinic has increased from 139 in 2012 to 2015 to 309 in 2016 to 2019. Mean age at the first use of opioids has reduced significantly from 20.2 (± 2.7) years in 2012 to 2015 to 18.3 (± 3.2) years in 2016 to 2019 ( p = 0.02). Parenteral route continues to remain as the dominant mode of use of opioids, though it has increased from 80.6 to 99% of users. There has been increased use of heroin over these years (12.2% in 2012-2015 to 72.5% in 2016-19) with concomitant decrease of pentazocine use (69.1-17.5%), respectively. Conclusion The changing demographic and opioid use pattern in the last couple of years among patients attending OAT clinic should alert the policy makers, so that an integrated approach is put into action for effective prevention and management of opioid use disorders.

17.
Cureus ; 14(6): e26246, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35754443

ABSTRACT

We present a novel case of de novo membranous nephropathy (DNMN) leading to transplant rejection in a 51-year-old female patient. The patient has a transplant history of two renal transplants for end-stage renal disease due to lupus nephritis. She had a prior unrelated, living donor kidney transplant that was subsequently replaced by a deceased donor kidney transplant due to graft failure. This patient's case is intriguing because DNMN is a rare cause of transplant rejection, and the literature demonstrates a scarcity of clinical examples. Interestingly, post-transplant DNMN has been suggested to be a separate disease from recurrent post-transplant MN and is associated with separate risk factors and diagnostic findings. As DNMN is considered a manifestation of antibody-mediated rejection, it should be treated with immunosuppressive therapy. As such, the presented case has received immunosuppressive therapy. In addition, DNMN is associated with humoral alloimmunity. Potentially other inflammatory processes (such as infection/potential UTI in our patient's case) could cause exposure to undetectable donor antigens on renal transplants leading to antibody-mediated rejection via DNMN.

18.
Mol Biol Cell ; 33(9): br14, 2022 08 01.
Article in English | MEDLINE | ID: mdl-35609215

ABSTRACT

Polo-like-kinase (PLK) 1 activity is associated with maintaining the functional and physical properties of the centrosome's pericentriolar matrix (PCM). In this study, we use a multimodal approach of human cells (HeLa), zebrafish embryos, and phylogenic analysis to test the role of a PLK1 binding protein, cenexin, in regulating the PCM. Our studies identify that cenexin is required for tempering microtubule nucleation by maintaining PCM cohesion in a PLK1-dependent manner. PCM architecture in cenexin-depleted zebrafish embryos was rescued with wild-type human cenexin, but not with a C-terminal cenexin mutant (S796A) deficient in PLK1 binding. We propose a model where cenexin's C terminus acts in a conserved manner in eukaryotes, excluding nematodes and arthropods, to sequester PLK1 that limits PCM substrate phosphorylation events required for PCM cohesion.


Subject(s)
Cell Cycle Proteins , Centrosome , Heat-Shock Proteins , Protein Serine-Threonine Kinases , Proto-Oncogene Proteins , Zebrafish Proteins , Zebrafish , Animals , Humans , Cell Cycle Proteins/metabolism , Centrosome/metabolism , Heat-Shock Proteins/genetics , Heat-Shock Proteins/metabolism , HeLa Cells , Microtubules/metabolism , Phosphorylation , Protein Binding , Protein Serine-Threonine Kinases/metabolism , Proto-Oncogene Proteins/metabolism , Zebrafish/embryology , Zebrafish/genetics , Zebrafish/metabolism , Zebrafish Proteins/deficiency , Zebrafish Proteins/genetics , Zebrafish Proteins/metabolism , Polo-Like Kinase 1
19.
Cell Rep ; 38(3): 110262, 2022 01 18.
Article in English | MEDLINE | ID: mdl-35045281

ABSTRACT

Disruption of retromer-dependent endosomal trafficking is considered pathogenic in late-onset Alzheimer's disease (AD). Here, to investigate this disruption in the intact brain, we turn to a genetic mouse model where the retromer core protein VPS35 is depleted in hippocampal neurons, and then we replete VPS35 using an optimized viral vector protocol. The VPS35 depletion-repletion studies strengthen the causal link between the neuronal retromer and AD-associated neuronal phenotypes, including the acceleration of amyloid precursor protein cleavage and the loss of synaptic glutamate receptors. Moreover, the studies show that the neuronal retromer can regulate a distinct, dystrophic, microglia morphology, phenotypic of hippocampal microglia in AD. Finally, the neuronal and, in part, the microglia responses to VPS35 depletion were found to occur independent of tau. Showing that the neuronal retromer can regulate AD-associated pathologies in two of AD's principal cell types strengthens the link, and clarifies the mechanism, between endosomal trafficking and late-onset sporadic AD.


Subject(s)
Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Microglia/pathology , Neurons/pathology , Vesicular Transport Proteins/metabolism , Animals , Endosomes/metabolism , Mice , Microglia/metabolism , Neurons/metabolism , Phenotype , Protein Transport/physiology
20.
BMC Genomics ; 22(1): 896, 2021 Dec 15.
Article in English | MEDLINE | ID: mdl-34906087

ABSTRACT

BACKGROUND: Mating induces behavioral and physiological changes in the arbovirus vector Aedes aegypti, including stimulation of egg development and oviposition, increased survival, and reluctance to re-mate with subsequent males. Transferred seminal fluid proteins and peptides derived from the male accessory glands induce these changes, though the mechanism by which they do this is not known. RESULTS: To determine transcriptome changes induced by seminal proteins, we injected extract from male accessory glands and seminal vesicles (MAG extract) into females and examined female lower reproductive tract (LRT) transcriptomes 24 h later, relative to non-injected controls. MAG extract induced 87 transcript-level changes, 31 of which were also seen in a previous study of the LRT 24 h after a natural mating, including 15 genes with transcript-level changes similarly observed in the spermathecae of mated females. The differentially-regulated genes are involved in diverse molecular processes, including immunity, proteolysis, neuronal function, transcription control, or contain predicted small-molecule binding and transport domains. CONCLUSIONS: Our results reveal that seminal fluid proteins, specifically, can induce gene expression responses after mating and identify gene targets to further investigate for roles in post-mating responses and potential use in vector control.


Subject(s)
Aedes , Aedes/genetics , Animals , Female , Male , Mosquito Vectors/genetics , Reproduction/genetics , Sexual Behavior, Animal , Transcriptome
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