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1.
Pestic Biochem Physiol ; 201: 105881, 2024 May.
Article in English | MEDLINE | ID: mdl-38685247

ABSTRACT

Insect pests cause immense agronomic losses worldwide. One of the most destructive of major crops is the Fall Armyworm (Spodoptera frugiperda, FAW). The ability to migrate long distances, a prodigious appetite, and a demonstrated ability to develop resistance to insecticides, make it a difficult target to control. Insecticidal proteins, for example those produced by the bacterium Bacillus thuringiensis, are among the safest and most effective insect control agents. Genetically modified (GM) crops expressing such proteins are a key part of a successful integrated pest management (IPM) program for FAW. However, due to the development of populations resistant to commercialized GM products, new GM traits are desperately needed. Herein, we describe a further characterization of the newly engineered trait protein eCry1Gb.1Ig. Similar to other well characterized Cry proteins, eCry1Gb.1Ig is shown to bind FAW midgut cells and induce cell-death. Binding competition assays using trait proteins from other FAW-active events show a lack of competition when binding FAW brush border membrane vesicles (BBMVs) and when utilizing non-pore-forming versions as competitors in in vivo bioassays. Similarly, insect cell lines expressing SfABCC2 and SfABCC3 (well characterized receptors of existing commercial Cry proteins) are insensitive to eCry1Gb.1Ig. These findings are consistent with results from our previous work showing that eCry1Gb.1Ig is effective in controlling insects with resistance to existing traits. This underscores the value of eCry1Gb.1Ig as a new GM trait protein with a unique site-of-action and its potential positive impact to global food production.


Subject(s)
Bacterial Proteins , Spodoptera , Animals , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Hemolysin Proteins/pharmacology , Hemolysin Proteins/metabolism , Hemolysin Proteins/genetics , Endotoxins/pharmacology , Endotoxins/metabolism , Bacillus thuringiensis Toxins/pharmacology , Bacillus thuringiensis/genetics , Bacillus thuringiensis/metabolism , Insecticides/pharmacology , Plants, Genetically Modified , Pest Control, Biological/methods
2.
Curr Surg Rep ; 12(4): 45-51, 2024.
Article in English | MEDLINE | ID: mdl-38523630

ABSTRACT

Purpose of Review: Oral squamous cell carcinoma (OSCC) survival rates have remained stagnant due to a lack of targeted therapies and diagnostic tools. Patient risk is currently determined solely through clinicopathologic features, primarily tumor staging, which lacks the necessary precision to stratify patients by risk and accurately dictate adjuvant treatment. Similarly, conventional OSCC therapies have well-established toxicities and limited efficacy. Recent Findings: Recent studies show that patient risk can now be assessed using non-invasive techniques, at earlier time points, and with greater accuracy using molecular biomarker panels. Additionally, novel immunotherapies not only utilize the host's immune response to combat disease but also have the potential to form immunological memory to prevent future recurrence. Localized controlled-release formulas have further served to reduce toxicity and allow the de-escalation of other treatment modalities. Summary: We review the latest advances in head and neck cancer diagnosis and treatment, including novel molecular biomarkers and immunotherapies.

3.
BMC Genomics ; 24(1): 684, 2023 Nov 14.
Article in English | MEDLINE | ID: mdl-37964194

ABSTRACT

BACKGROUND: Aspergillus fumigatus is a major fungal pathogen that causes severe problems due to its increasing resistance to many therapeutic agents. Fludioxonil is a compound that triggers a lethal activation of the fungal-specific High Osmolarity Glycerol pathway. Its pronounced antifungal activity against A. fumigatus and other pathogenic molds renders this agent an attractive lead substance for the development of new therapeutics. The group III hydride histidine kinase TcsC and its downstream target Skn7 are key elements of the multistep phosphorelay that represents the initial section of the High Osmolarity Glycerol pathway. Loss of tcsC results in resistance to fludioxonil, whereas a Δskn7 mutant is partially, but not completely resistant. RESULTS: In this study, we compared the fludioxonil-induced transcriptional responses in the ΔtcsC and Δskn7 mutant and their parental A. fumigatus strain. The number of differentially expressed genes correlates well with the susceptibility level of the individual strains. The wild type and, to a lesser extend also the Δskn7 mutant, showed a multi-faceted stress response involving genes linked to ribosomal and peroxisomal function, iron homeostasis and oxidative stress. A marked difference between the sensitive wild type and the largely resistant Δskn7 mutant was evident for many cell wall-related genes and in particular those involved in the biosynthesis of chitin. Biochemical data corroborate this differential gene expression that does not occur in response to hyperosmotic stress. CONCLUSIONS: Our data reveal that fludioxonil induces a strong and TcsC-dependent stress that affects many aspects of the cellular machinery. The data also demonstrate a link between Skn7 and the cell wall reorganizations that foster the characteristic ballooning and the subsequent lysis of fludioxonil-treated cells.


Subject(s)
Antifungal Agents , Aspergillus fumigatus , Dioxoles , Pyrroles , Aspergillus fumigatus/genetics , Aspergillus fumigatus/metabolism , Antifungal Agents/pharmacology , Antifungal Agents/metabolism , Fungal Proteins/genetics , Fungal Proteins/metabolism , Glycerol/metabolism , Cell Wall/metabolism
4.
PLoS Pathog ; 19(11): e1011841, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38033163

ABSTRACT

Macrophages play a key role in disseminated cryptococcosis, a deadly fungal disease caused by Cryptococcus neoformans. This opportunistic infection can arise following the reactivation of a poorly characterized latent infection attributed to dormant C. neoformans. Here, we investigated the mechanisms underlying reactivation of dormant C. neoformans using an in vitro co-culture model of viable but non-culturable (VBNC; equivalent of dormant) yeast cells with bone marrow-derived murine macrophages (BMDMs). Comparative transcriptome analysis of BMDMs incubated with log, stationary phase or VBNC cells of C. neoformans showed that VBNC cells elicited a reduced transcriptional modification of the macrophage but retaining the ability to regulate genes important for immune response, such as NLRP3 inflammasome-related genes. We further confirmed the maintenance of the low immunostimulatory capacity of VBNC cells using multiplex cytokine profiling, and analysis of cell wall composition and dectin-1 ligands exposure. In addition, we evaluated the effects of classic (M1) or alternative (M2) macrophage polarization on VBNC cells. We observed that intracellular residence sustained dormancy, regardless of the polarization state of macrophages and despite indirect detection of pantothenic acid (or its derivatives), a known reactivator for VBNC cells, in the C. neoformans-containing phagolysosome. Notably, M0 and M2, but not M1 macrophages, induced extracellular reactivation of VBNC cells by the secretion of extracellular vesicles and non-lytic exocytosis. Our results indicate that VBNC cells retain the low immunostimulatory profile required for persistence of C. neoformans in the host. We also describe a pro-pathogen role of macrophage-derived extracellular vesicles in C. neoformans infection and reinforce the impact of non-lytic exocytosis and the macrophage profile on the pathophysiology of cryptococcosis.


Subject(s)
Cryptococcosis , Cryptococcus neoformans , Extracellular Vesicles , Animals , Mice , Cryptococcus neoformans/genetics , Cryptococcosis/microbiology , Macrophages , Exocytosis
5.
BMC Womens Health ; 23(1): 524, 2023 10 04.
Article in English | MEDLINE | ID: mdl-37794374

ABSTRACT

BACKGROUND: Yoga is a popular training practice that enhances women's physical activity level and modifies the major risk factors contributing to noncommunicable diseases. This study aimed to compare general health and cardiovascular health, musculoskeletal health, psychological health, and health-related quality of life between aged women with and without long-term yoga practice. METHODS: Thirty-two female yoga practitioners (mean age 56 years) with ≥ 2 years experience in regular yoga practice and 32 age-matched women without yoga experience participated in the study. Between-group comparisons was performed to explore the differences in various health outcomes, including body build indices, exercise endurance, blood pressure, and heart rate variability; hamstring flexibility, upper-limb muscle strength, shoulder range of motion, and upper-limb function; and the symptoms of anxiety and depression, sleep quality, and fatigue. RESULTS: Our findings revealed that yoga practitioners demonstrated greater hamstring flexibility, shoulder ROM on the non-dominant side, and hand-grip strength; a higher heart rate variability parameter value (RMSSD); and shorter sleep latency than those who did not practice yoga. CONCLUSIONS: In view of the encouraging results of the long-term benefits of yoga practice, it warrants being promoted among aged women to enhance their physical and mental well-being.


Subject(s)
Yoga , Humans , Female , Aged , Middle Aged , Yoga/psychology , Quality of Life , Health Status , Exercise , Blood Pressure/physiology
6.
Eur J Oncol Nurs ; 66: 102399, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37689046

ABSTRACT

PURPOSE: To compare the physical performance, including upper-limb motor and cardiovascular functions, and psychological functions, including anxiety and depression, sleep, and fatigue, between women with and without breast cancer. METHODS: Thirty-two women with breast cancer and 32 healthy counterparts were recruited for the study. Upper-limb muscle strength, shoulder range of motion, and upper-limb function were assessed using a handheld dynamometer, a goniometer, and the short form of the Disabilities of Arm-Shoulder-Hand Questionnaire, respectively. Exercise endurance and cardiovascular functions were assessed using the 6-min walk test and blood pressure and heart rate variability, respectively. The Hospital Anxiety and Depression Scale, the Pittsburgh Sleep Quality Index, and the Fatigue Assessment Scale were used to assess the symptoms of anxiety and depression, sleep quality, and fatigue, respectively. RESULTS: Breast cancer participants' body-weight-adjusted upper-limb strength of both the affected and unaffected sides (0.11-0.14) was only 61.1-77.8% of those of the healthy participants (0.18). Their shoulder mobility of the affected side (flexion: 161.64°; abduction: 157.01°) were 94.2% (flexion) and 92.5% (abduction) of those of the healthy participants (flexion: 171.56°; abduction: 169.68°), respectively. Breast cancer participants had higher quickDASH mean score (19.53), HADS-A mean score (6.78), HADS-D mean score (4.72), global PSQI mean score (7.22) and FAS mean score (25.97) as well as shorter mean distance covered by 6 MWT (496.66 m) than those of the healthy participants. CONCLUSIONS: Rehabilitative interventions, such as mind-body interventions and exercise training, target physical fitness and promote the psychological health of women with breast cancer are necessary.

7.
Front Oncol ; 13: 1132178, 2023.
Article in English | MEDLINE | ID: mdl-37576891

ABSTRACT

Introduction: Dose perturbation of spot-scanning proton beams passing through a dislocated metallic port (MP) of a breast tissue expander may degrade target dose coverage or deliver excess dose to the ipsilateral lung and heart. The feasibility of utilizing daily cone-beam computed tomography (CBCT)-based synthetic CTs (synCTs) for dose reconstruction was evaluated, and the fractional and cumulative dosimetric impact due to daily MP dislocation is reported. Methods: The synCT was generated by deforming the simulation CT to daily CBCT. The MP structure template was mapped onto all CTs on the basis of daily MP position. Proton treatment plans were generated with two and three fields on the planned CT (pCT, Plan A) and the first verification CT (vCT, Plan B), respectively, for a fractional dose of 1.8 Gy(RBE). Plan A and Plan B were used alternatively, as determined by the daily MP position. The reconstructed fractional doses were calculated with corresponding plans and synCTs, and the cumulative doses were summed with the rigid or deformed fractional doses on pCT and vCT. Results: The planned and reconstructed fractional dose demonstrated a low-dose socket around the planned MP position due to the use of field-specific targets (FSTs). Dose hot spots with >120% of the prescription due to MP dislocation were found behind the planned MP position on most reconstructed fractional doses. The reconstructed cumulative dose shows two low-dose sockets around the two planned MP positions reflecting the two plans used. The doses at the hot spots behind the planned MPs averaged out to 114% of the prescription. The cumulative D95% of the CTV_Chest Wall decreased by up to 2.4% and 4.0%, and the cumulative V20Gy(RBE) of the left lung decreased to 16.1% and 16.8% on pCT and vCT, respectively. The cumulative Dmean of the heart decreased to as low as 0.7 Gy(RBE) on pCT but increased to as high as 1.6 Gy(RBE) on vCT. Conclusion: The robustness of proton plans using FSTs around the magnet in the MP of the tissue expander can be improved by applying multiple fields and plans, which provides forgiveness of dose heterogeneity incurred from dislocation of high-Z materials in this single case.

8.
Cell Metab ; 35(7): 1179-1194.e5, 2023 07 11.
Article in English | MEDLINE | ID: mdl-37437544

ABSTRACT

Emerging new evidence highlights the importance of prolonged daily fasting periods for the health and survival benefits of calorie restriction (CR) and time-restricted feeding (TRF) in male mice; however, little is known about the impact of these feeding regimens in females. We placed 14-month-old female mice on five different dietary regimens, either CR or TRF with different feeding windows, and determined the effects of these regimens on physiological responses, progression of neoplasms and inflammatory diseases, serum metabolite levels, and lifespan. Compared with TRF feeding, CR elicited a robust systemic response, as it relates to energetics and healthspan metrics, a unique serum metabolomics signature in overnight fasted animals, and was associated with an increase in lifespan. These results indicate that daytime (rest-phase) feeding with prolonged fasting periods initiated late in life confer greater benefits when combined with imposed lower energy intake.


Subject(s)
Caloric Restriction , Fasting , Female , Male , Animals , Mice , Energy Intake , Intermittent Fasting , Longevity
9.
Sensors (Basel) ; 23(13)2023 Jun 26.
Article in English | MEDLINE | ID: mdl-37447780

ABSTRACT

Objective: We designed and validated a wireless, low-cost, easy-to-use, mobile, dry-electrode headset for scalp electroencephalography (EEG) recordings for closed-loop brain-computer (BCI) interface and internet-of-things (IoT) applications. Approach: The EEG-based BCI headset was designed from commercial off-the-shelf (COTS) components using a multi-pronged approach that balanced interoperability, cost, portability, usability, form factor, reliability, and closed-loop operation. Main Results: The adjustable headset was designed to accommodate 90% of the population. A patent-pending self-positioning dry electrode bracket allowed for vertical self-positioning while parting the user's hair to ensure contact of the electrode with the scalp. In the current prototype, five EEG electrodes were incorporated in the electrode bracket spanning the sensorimotor cortices bilaterally, and three skin sensors were included to measure eye movement and blinks. An inertial measurement unit (IMU) provides monitoring of head movements. The EEG amplifier operates with 24-bit resolution up to 500 Hz sampling frequency and can communicate with other devices using 802.11 b/g/n WiFi. It has high signal-to-noise ratio (SNR) and common-mode rejection ratio (CMRR) (121 dB and 110 dB, respectively) and low input noise. In closed-loop BCI mode, the system can operate at 40 Hz, including real-time adaptive noise cancellation and 512 MB of processor memory. It supports LabVIEW as a backend coding language and JavaScript (JS), Cascading Style Sheets (CSS), and HyperText Markup Language (HTML) as front-end coding languages and includes training and optimization of support vector machine (SVM) neural classifiers. Extensive bench testing supports the technical specifications and human-subject pilot testing of a closed-loop BCI application to support upper-limb rehabilitation and provides proof-of-concept validation for the device's use at both the clinic and at home. Significance: The usability, interoperability, portability, reliability, and programmability of the proposed wireless closed-loop BCI system provides a low-cost solution for BCI and neurorehabilitation research and IoT applications.


Subject(s)
Brain-Computer Interfaces , Humans , Reproducibility of Results , Electroencephalography , Brain , Eye Movements
10.
PLoS One ; 18(7): e0288650, 2023.
Article in English | MEDLINE | ID: mdl-37450481

ABSTRACT

Spatial planning for marine areas of multi-species conservation concern requires in-depth assessment of the distribution of predators and their prey. Northern Gannets Morus bassanus are generalist predators that predate several different forage fishes depending on their availability. In the western North Atlantic, gannets employ different dive tactics while in pursuit of different prey types, performing deep, prolonged U-shaped dives when foraging on capelin (Mallotus villosus), and rapid, shallow, V-shaped dives when foraging on larger pelagic fishes. Therefore, much can be inferred about the distribution and abundance of key forage fishes by assessing the foraging behaviour and space-use of gannets. In this study, we aimed to quantify space-use and to determine areas of suitable foraging habitat for gannets in pursuit of different prey types using habitat suitability models and kernel density utilization distributions. We deployed 25 GPS/Time-depth recorder devices on parental Northern Gannets at Cape St. Mary's, Newfoundland, Canada from 2019 to 2021. To assess the influence of environmental variables on gannets foraging for different prey types, we constructed three different habitat suitability models: a U-shaped dive model, and two V-shaped dive models (early and late chick-rearing). Suitable foraging habitat for capelin, deduced by the U-shaped dive model, was defined by coastal, shallow waters with flat relief and sea surface temperatures (SST) of 11-15° C. Suitable habitat for early V-shaped dives was defined by shallow and coastal waters with steep slope and SST of 12-15°C and ~18°C, likely reflecting the variability in environmental preferences of different prey species captured when performing V-shaped dives. Suitable habitat for late V-shaped dives was defined by shallow coastal waters (<100m depth), as well as waters deeper than 200 m, and by SST greater than 16°C. We show that space-use by gannets can vary both within and between years depending on environmental conditions and the prey they are searching for, with consequences for the extent of potential interaction with anthropogenic activities. Further, we suggest regions defined as suitable for U-shaped dives are likely to be critical habitat of multi-species conservation concern, as these regions are likely to represent consistent capelin spawning habitat.


Subject(s)
Diving , Morus , Animals , Ecosystem , Fishes , Chickens
11.
Arch Psychiatr Nurs ; 44: 93-100, 2023 06.
Article in English | MEDLINE | ID: mdl-37197869

ABSTRACT

BACKGROUND: Stress is a crucial driver that affects hygiene behavior. The Hong Kong population lacks a COVID-19 or pandemic related stress measure investigating the COVID-19 related stress after one year of outbreak. DESIGN AND METHODS: The original COVID Stress Scale (CSS) was translated and culturally adapted into the Chinese (Cantonese) version (CSS-C). Six hundred and twenty-four participants were recruited from the general public to examine the internal consistency, and concurrent and convergent validity of the CSS-C. The test-retest reliability of CSS-C was examined using 39 university students. RESULTS: People with old age, women, single, low educational level and borderline and abnormal levels of anxiety and depression were likely to perceive high level of COVID-19 related stress. All CSS-C subscales demonstrated good internal consistency, moderate to good test-retest reliability, and weak to moderate correlations with various mental health-related measures. DISCUSSION: The CSS could help monitor the stress associated the current and potential future pandemics.


Subject(s)
COVID-19 , Pandemics , Stress, Psychological , Female , Humans , COVID-19/psychology , East Asian People , Hong Kong/epidemiology , Psychometrics , Reproducibility of Results , Surveys and Questionnaires , Stress, Psychological/epidemiology
12.
Open Forum Infect Dis ; 10(4): ofad159, 2023 Apr.
Article in English | MEDLINE | ID: mdl-37065989

ABSTRACT

Eculizumab, a recombinant humanized monoclonal antibody (mAb), is used for the treatment of patients (both adults and children) with paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome. This mAb binds to complement protein 5 (C5), thereby inhibiting its cleavage. On the other hand, one of the C5 cleavage products, C5a, is a potent anaphylatoxin with proinflammatory properties, involved in antimicrobial surveillance. Administration of eculizumab has been reported to make patients more susceptible to infection by encapsulated bacteria. Here, we are reporting an adult case of disseminated infection due to the encapsulated yeast Cryptococcus neoformans following eculizumab therapy and discuss its pathogenesis.

13.
Pestic Biochem Physiol ; 192: 105385, 2023 May.
Article in English | MEDLINE | ID: mdl-37105627

ABSTRACT

MIR162, a maize event that expresses Vip3Aa20 (Vip3A) approved for commercial cultivation around 2010, has been excellent for control of major Lepidopteran pests. However, development of fall armyworm (FAW) resistance to Vip3A is a serious concern. Resistant colonies selected in the laboratory can serve as valuable tools not only for better understanding of Vip3A's mode of action (MOA) and mechanism of resistance (MOR) but also for screening novel leads of new MOA that will help control FAW in case resistance to Vip3A in the field becomes a reality. We selected a Vip3A-resistant FAW strain, FAWVip3AR, by subjecting a FAW founder population containing field genetics to Vip3A exposure. FAWVip3AR had >9800-fold resistance to Vip3A by diet surface overlay bioassays and resistance was stable. Feeding bioassays using detached leaf tissues or whole plants indicated that FAWVip3AR larvae readily fed and completed the full life cycle on Vip3A-expressing MIR162 maize plants and leaf tissues that killed 100% of susceptible larvae. Yet, FAWVip3AR faced at least two challenges. First, FAWVip3AR suffered an apparent disadvantage (incomplete resistance) when feeding on MIR162 in comparison to FAWVip3AR feeding on Vip3A-free isoline AX5707 maize; and second, FAWVip3AR showed a fitness costs in comparison to a Vip3A-susceptible strain when both fed on AX5707. We also demonstrated that, >10 years after commercialization, MIR162 and Vip3A remain highly efficacious against field populations of three major Lepidopteran pests from different geographic locations and FAW strains resistant to other Bacillus thuringiensis (Bt) toxins that are currently on the market.


Subject(s)
Bacillus thuringiensis , Animals , Bacillus thuringiensis/genetics , Zea mays/genetics , Plants, Genetically Modified , Bacterial Proteins/genetics , Bacterial Proteins/pharmacology , Larva/genetics , Bacillus thuringiensis Toxins , Endotoxins/pharmacology , Insecticide Resistance/genetics , Hemolysin Proteins/pharmacology
14.
Educ Psychol Rev ; 35(1): 16, 2023.
Article in English | MEDLINE | ID: mdl-36776579

ABSTRACT

Transfer of learning is a fundamental goal of education but is challenging to achieve, especially where far transfer to remote contexts is at stake. How can we improve learners' flexible application of knowledge to distant domains? In a counterintuitive phenomenon termed the derring effect, deliberately committing and correcting errors in low-stakes contexts enhances learning more than avoiding errors. Whereas this benefit has been demonstrated with tests in domains similar to those in the initial learning task, the present set of three experiments (N = 120) investigated whether deliberate erring boosts far transfer of conceptual knowledge to dissimilar domains. Undergraduates studied scientific expository texts either by generating conceptually correct responses or by deliberately generating conceptually erroneous responses then correcting them. Deliberate erring improved not only retention (Experiment 1), but also far transfer on inferential test questions that required applying the learned concepts to remote knowledge domains (e.g., from biology/vaccines to geography/forest management techniques; Experiment 2). This advantage held even over a control that further involved spotting and correcting the same errors that one's peers had deliberately made (Experiment 3). Yet, learners failed to predict or recognize the benefits of deliberate erring even after the test. Altogether, these results suggest that the derring effect is specific to generating incorrect, but not correct, elaborations. Neither does mere exposure to others' errors nor juxtaposing these errors with the correct responses suffice. Rather, guiding learners to personally commit and correct deliberate errors is vital for enhancing generalization and far transfer of learning to distant knowledge domains. Supplementary Information: The online version contains supplementary material available at 10.1007/s10648-023-09739-z.

15.
Horm Behav ; 148: 105297, 2023 02.
Article in English | MEDLINE | ID: mdl-36623432

ABSTRACT

Females show greater benefits of exercise on cognition in both humans and rodents, which may be related to brain-derived neurotrophic factor (BDNF). A single nucleotide polymorphism (SNP), the Val66Met polymorphism, within the human BDNF gene, causes impaired activity-dependent secretion of neuronal BDNF and impairments to some forms of memory. We evaluated whether sex and BDNF genotype (Val66Met polymorphism (Met/Met) versus wild-type (Val/Val)) influenced the ability of voluntary running to enhance cognition and hippocampal neurogenesis in mice. Middle-aged C57BL/6J (13 months) mice were randomly assigned to either a control or an aerobic training (AT) group (running disk access). Mice were trained on the visual discrimination and reversal paradigm in a touchscreen-based technology to evaluate cognitive flexibility. BDNF Met/Met mice had fewer correct responses compared to BDNF Val/Val mice on both cognitive tasks. Female BDNF Val/Val mice showed greater cognitive flexibility compared to male mice regardless of AT. Despite running less than BDNF Val/Val mice, AT improved performance in both cognitive tasks in BDNF Met/Met mice. AT increased neurogenesis in the ventral hippocampus of BDNF Val/Val mice of both sexes and increased the proportion of mature type 3 doublecortin-expressing cells in the dorsal hippocampus of female mice only. Our results indicate AT improved cognitive performance in BDNF Met/Met mice and increased hippocampal neurogenesis in BDNF Val/Val mice in middle age. Furthermore, middle-aged female mice may benefit more from AT than males in terms of neuroplasticity, an effect that was influenced by the BDNF Val66Met polymorphism.


Subject(s)
Brain-Derived Neurotrophic Factor , Cognition , Middle Aged , Male , Humans , Female , Mice , Animals , Brain-Derived Neurotrophic Factor/genetics , Mice, Inbred C57BL , Cognition/physiology , Polymorphism, Single Nucleotide , Genotype , Neurogenesis/genetics
16.
Proc Natl Acad Sci U S A ; 120(6): e2212003120, 2023 02 07.
Article in English | MEDLINE | ID: mdl-36719915

ABSTRACT

While establishing an invasive infection, the dormant conidia of Aspergillus fumigatus transit through swollen and germinating stages, to form hyphae. During this morphotype transition, the conidial cell wall undergoes dynamic remodeling, which poses challenges to the host immune system and antifungal drugs. However, such cell wall reorganization during conidial germination has not been studied so far. Here, we explored the molecular rearrangement of Aspergillus fumigatus cell wall polysaccharides during different stages of germination. We took advantage of magic-angle spinning NMR to investigate the cell wall polysaccharides, without employing any destructive method for sample preparation. The breaking of dormancy was associated with a significant change in the molar ratio between the major polysaccharides ß-1,3-glucan and α-1,3-glucan, while chitin remained equally abundant. The use of various polarization transfers allowed the detection of rigid and mobile polysaccharides; the appearance of mobile galactosaminogalactan was a molecular hallmark of germinating conidia. We also report for the first time highly abundant triglyceride lipids in the mobile matrix of conidial cell walls. Water to polysaccharides polarization transfers revealed an increased surface exposure of glucans during germination, while chitin remained embedded deeper in the cell wall, suggesting a molecular compensation mechanism to keep the cell wall rigidity. We complement the NMR analysis with confocal and atomic force microscopies to explore the role of melanin and RodA hydrophobin on the dormant conidial surface. Exemplified here using Aspergillus fumigatus as a model, our approach provides a powerful tool to decipher the molecular remodeling of fungal cell walls during their morphotype switching.


Subject(s)
Aspergillus fumigatus , Fungal Proteins , Aspergillus fumigatus/metabolism , Spores, Fungal/metabolism , Fungal Proteins/metabolism , Polysaccharides/metabolism , Chitin/metabolism , Glucans/metabolism , Cell Wall/metabolism
17.
J Exp Psychol Appl ; 29(1): 124-135, 2023 Mar.
Article in English | MEDLINE | ID: mdl-34166036

ABSTRACT

In two experiments (N = 200), we compared the effects of longhand note-taking, photographing lecture materials with a smartphone camera, and not taking any notes on video-recorded lecture learning. Experiment 1 revealed a longhand-superiority effect: Longhand note-takers outperformed photo-takers and control learners on a recall test, notwithstanding an equal opportunity to review their learning material right before being tested, and even when photo-takers and control participants reviewed an exact transcript of the lecture slides via their photos or printouts, whereas longhand note-takers accessed only a fraction of the content as captured in their handwritten notes. Photo-takers performed comparably to learners who had not taken any notes at all. Experiment 2 further showed that mind-wandering mediates the mnemonic benefits of longhand note-taking: Relative to learners who took photos or did not take any notes, longhand note-takers mind-wandered less and, in turn, demonstrated superior retention of the lecture content. Yet, across both experiments, learners were not cognizant of the advantages of longhand note-taking, but misjudged all three techniques to be equally effective. These findings point to key attentional differences between longhand note-taking and photo-taking that impact learning-knowledge that is easily and conveniently acquired in a snap may not be better remembered. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Subject(s)
Learning , Memory , Humans , Mental Recall , Attention
18.
SN Soc Sci ; 2(12): 267, 2022.
Article in English | MEDLINE | ID: mdl-36531139

ABSTRACT

Respectful maternity care (RMC) is part of a global movement addressing the previous absence of human rights in global safe maternal care guidance. RMC is grounded in kindness, compassion, dignity and respectful working conditions. The decolonisation movement in healthcare seeks to dismantle structural biases set up from a historically white, male, heteronormative Eurocentric medical system. This article applies a decolonising lens to the RMC agenda and examines barriers to its implementation in UK healthcare systems. Searches of peer-reviewed journals about decolonising maternity care in the UK revealed little. Drawing from wider information bases, we examine power imbalances constructed throughout a history of various colonial biases yet lingering in maternity care. The overarching findings of our analysis revealed 3 areas of focus: professional structures and institutional biases; power imbalances between types of staff and stakeholders of care; and person-centred care through a decolonial lens. To uproot inequity and create fairer and more respectful maternity care for women, birthing people and staff, it is vital that contemporary maternity institutions understand the decolonial perspective. This novel enquiry offers a scaffolding to undertake this process. Due to significant differences in colonial history between Western colonising powers, it is important to decolonise with respect to these different territories, histories and challenges.

19.
Front Immunol ; 13: 978152, 2022.
Article in English | MEDLINE | ID: mdl-36211424

ABSTRACT

Invasive aspergillosis (IA) is a life-threatening fungal infection for immunocompromised hosts. It is, therefore, necessary to understand the immune pathways that control this infection. Although the primary infection site is the lungs, aspergillosis can disseminate to other organs through unknown mechanisms. Herein we have examined the in vivo role of various complement pathways as well as the complement receptors C3aR and C5aR1 during experimental systemic infection by Aspergillus fumigatus, the main species responsible for IA. We show that C3 knockout (C3-/-) mice are highly susceptible to systemic infection of A. fumigatus. Intriguingly, C4-/- and factor B (FB)-/- mice showed susceptibility similar to the wild-type mice, suggesting that either the complement pathways display functional redundancy during infection (i.e., one pathway compensates for the loss of the other), or complement is activated non-canonically by A. fumigatus protease. Our in vitro study substantiates the presence of C3 and C5 cleaving proteases in A. fumigatus. Examination of the importance of the terminal complement pathway employing C5-/- and C5aR1-/- mice reveals that it plays a vital role in the conidial clearance. This, in part, is due to the increased conidial uptake by phagocytes. Together, our data suggest that the complement deficiency enhances the susceptibility to systemic infection by A. fumigatus.


Subject(s)
Aspergillosis , Aspergillus fumigatus , Animals , Complement C5/genetics , Complement C5/metabolism , Complement Factor B/genetics , Lung , Mice , Spores, Fungal
20.
Geroscience ; 44(5): 2471-2490, 2022 10.
Article in English | MEDLINE | ID: mdl-35996062

ABSTRACT

Caloric restriction (CR) is the leading non-pharmacological intervention to delay induced and spontaneous tumors in pre-clinical models. These effects of CR are largely attributed to canonical inhibition of pro-growth pathways. However, our recent data suggest that CR impairs primary tumor growth and cancer progression in the murine 4T1 model of triple negative breast cancer (TNBC), at least in part, through reduced frequency of the myeloid-derived suppressor cells (MDSC). In the present study, we sought to determine whether injection of excess MDSCs could block regression in 4T1 tumor growth and metastatic spread in BALB/cJ female mice undergoing daily CR. Our findings show that MDSC injection impeded CR-mediated protection against tumor growth without increasing lung metastatic burden. Overall, these results reveal that CR can slow cancer progression by affecting immune suppressive cells.Impact statement: Inoculation of MDSCs from donor mice effectively impedes the ability of calorie restriction to protect against primary tumor growth without impacting lung metastatic burden in recipient animals.


Subject(s)
Myeloid-Derived Suppressor Cells , Triple Negative Breast Neoplasms , Humans , Female , Mice , Animals , Myeloid-Derived Suppressor Cells/metabolism , Myeloid-Derived Suppressor Cells/pathology , Triple Negative Breast Neoplasms/metabolism , Triple Negative Breast Neoplasms/pathology , Caloric Restriction , Disease Models, Animal , Cell Line, Tumor
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