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1.
PLoS One ; 19(4): e0298817, 2024.
Article in English | MEDLINE | ID: mdl-38687760

ABSTRACT

Previous research demonstrating that positive episodic simulation enhances future expectancies has relied on explicit expectancy measures. The current study investigated the effects of episodic simulation on implicit expectancies. Using the Future Thinking Implicit Relational Assessment Procedure (FT-IRAP), participants made true/false decisions to indicate whether or not they expected positive/negative outcomes after adopting orientations consistent or inconsistent with an optimistic disposition. The outcome measure, DIRAP, was based on response time differences between consistent and inconsistent blocks. Participants then engaged in either positive simulation training, in which they imagined positive future events, or a neutral visualisation task before repeating the FT-IRAP twice following 10-minute intervals. Positive simulation training increased DIRAP scores for don't-expect-negative trials-boosting participants' readiness to affirm that negative events were unlikely to happen to them. Although findings did not generalise across all trial types, they show potential for positive simulation training to enhance implicit future expectancies.


Subject(s)
Thinking , Humans , Female , Male , Thinking/physiology , Young Adult , Adult , Reaction Time/physiology , Imagination , Adolescent
2.
Microbiologyopen ; 13(2): e1404, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38515236

ABSTRACT

The interplay between diet and fecal microbiota composition is garnering increased interest across various host species, including domestic dogs. While the influence of dietary macronutrients and their associated microbial communities have been extensively reviewed, these reviews are descriptive and do not account for differences in microbial community analysis, nor do they standardize macronutrient content across studies. To address this, a meta-analysis was performed to assess the impact of dietary crude protein ("protein") and dietary crude fat ("fat") on the fecal microbiota composition in healthy dogs. Sixteen publications met the eligibility criteria for the meta-analysis, yielding a final data set of 314 dogs. Diets were classed as low, moderate, high, or supra in terms of protein or fat content. Sequence data from each publication were retrieved from public databases and reanalyzed using consistent bioinformatic pipelines. Analysis of community diversity indices and unsupervised clustering of the data with principal coordinate analysis revealed a small effect size and complete overlap between protein and fat levels at the overall community level. Supervised clustering through random forest analysis and partial least squares-discriminant analysis indicated alterations in the fecal microbiota composition at a more individual taxonomic level, corresponding to the levels of protein or fat. The Prevotellaceae Ga6A1 group and Enterococcus were associated with increasing levels of protein, while Allobaculum and Clostridium sensu stricto 13 were associated with increasing levels of fat. Interestingly, the random forest analyses revealed that Sharpea, despite its low relative abundance in the dog's fecal microbiome, was primarily responsible for the separation of the microbiome for both protein and fat. Future research should focus on validating and understanding the functional roles of these relatively low-abundant genera.


Subject(s)
Microbiota , Wolves , Dogs , Animals , Pilot Projects , Wolves/metabolism , Diet/veterinary , Dietary Proteins/metabolism , Feces
3.
Memory ; 32(4): 476-483, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38547354

ABSTRACT

Two experiments investigated the role of visual imagery in prospective memory (PM). In experiment 1, 140 participants completed a general knowledge quiz which included a PM task of writing a letter "X" next to any questions that referred to space. Participants either visualised themselves performing this task, verbalised an implementation intention about the task, did both, or did neither. Performance on the PM task was enhanced in both conditions involving visual imagery but not by implementation intentions alone. In experiment 2, 120 participants imagined themselves writing a letter "X" next to questions about space, or in a bizarre imagery condition imagined themselves drawing an alien next to those questions. Relative to the control condition, PM was significantly enhanced when participants imagined writing a letter "X" next to the target questions, but not by the bizarre imagery task. The findings indicate that the robust effects of imagery observed in retrospective memory also extend to PM.


Subject(s)
Imagination , Memory, Episodic , Humans , Male , Female , Young Adult , Adult , Visual Perception/physiology , Adolescent
4.
medRxiv ; 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38352442

ABSTRACT

Objective: Identifying microbial targets in irritable bowel syndrome (IBS) is challenged by dynamic microbiota-metabolite-host interactions. We aimed to assess microbial features associated with short chain fatty acids (SCFA) and determine if features were related to IBS symptoms, subtypes, and endophenotypes. Design: We performed an observational study of stool microbial metagenomes, stool SCFA, and IBS traits (stool form, stool bile acids, and colonic transit) in patients with IBS (IBS with constipation [IBS-C] IBS with diarrhea [IBS-D]) and healthy controls. We analyzed associations of microbiome composition with stool SCFA to identify microbe-SCFA relationships that were shared and distinct across groups. We compared gut microbiome-encoded potential for substrate utilization across groups and within a subset of participants selected by stool characteristics. In IBS-D, we compared stool microbiomes of patients with and without bile acid malabsorption (BAM). Results: Overall stool microbiome composition and abundances of individual taxa differed between groups. Increased abundances of several bacterial species were observed in IBS-D including Dorea sp. CAG:317.. Microbes-SCFA relationships varied across groups after accounting for transit and bile acids. Significant microbe-SCFA were common in IBS-D and several SCFA-producing species were inversely correlated with SCFA. Among participants selected by stool form characteristics, functional profiling demonstrated differential abundances of microbial genes/pathways for SCFA metabolism and degradation of carbohydrates and mucin across groups. SCFA-producing taxa were reduced in IBS-D with BAM. Conclusion: Microbe-SCFA associations differ across IBS subtypes and traits. Altered substrate preferences offer insights into functional microbiome traits and could be used as novel microbial IBS biomarkers. KEY MESSAGES: What is already known on this topic: The intestinal microbiota and its metabolites (e.g., short chain fatty acids [SCFA]) modulate irritable bowel syndrome (IBS) pathophysiology. What this study adds: We studied microbe-SCFA associations across IBS subtypes and endophenotypes to demonstrate (1) the intestinal microbiome plays distinct roles across IBS subtypes, (2) microbial substrate preferences vary between IBS subtypes and influences stool form, and (3) microbe-SCFA patterns may reveal key taxa that underlie shared and distinct microbial mechanisms across the IBS spectrum. How this study might affect research, practice or policy: Findings demonstrate that structural and functional features of the intestinal microbiome may represent unbiased microbial biomarkers for clinical and mechanistic IBS subtypes. Further study of these putative microbial targets as well as their interactions with diet- and host-specific traits should be pursued to develop individualized microbiome-based approached to IBS management.

5.
Mol Cell ; 84(4): 702-714.e10, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38295802

ABSTRACT

Expansions of CAG trinucleotide repeats cause several rare neurodegenerative diseases. The disease-causing repeats are translated in multiple reading frames and without an identifiable initiation codon. The molecular mechanism of this repeat-associated non-AUG (RAN) translation is not known. We find that expanded CAG repeats create new splice acceptor sites. Splicing of proximal donors to the repeats produces unexpected repeat-containing transcripts. Upon splicing, depending on the sequences surrounding the donor, CAG repeats may become embedded in AUG-initiated open reading frames. Canonical AUG-initiated translation of these aberrant RNAs may account for proteins that have been attributed to RAN translation. Disruption of the relevant splice donors or the in-frame AUG initiation codons is sufficient to abrogate RAN translation. Our findings provide a molecular explanation for the abnormal translation products observed in CAG trinucleotide repeat expansion disorders and add to the repertoire of mechanisms by which repeat expansion mutations disrupt cellular functions.


Subject(s)
Neurodegenerative Diseases , RNA Splice Sites , Humans , RNA Splice Sites/genetics , Neurodegenerative Diseases/genetics , Codon, Initiator , Trinucleotide Repeat Expansion/genetics
6.
bioRxiv ; 2023 Oct 16.
Article in English | MEDLINE | ID: mdl-37904984

ABSTRACT

Expansions of CAG trinucleotide repeats cause several rare neurodegenerative diseases. The disease-causing repeats are translated in multiple reading frames, without an identifiable initiation codon. The molecular mechanism of this repeat-associated non-AUG (RAN) translation is not known. We find that expanded CAG repeats create new splice acceptor sites. Splicing of proximal donors to the repeats produces unexpected repeat-containing transcripts. Upon splicing, depending on the sequences surrounding the donor, CAG repeats may become embedded in AUG-initiated open reading frames. Canonical AUG-initiated translation of these aberrant RNAs accounts for proteins that are attributed to RAN translation. Disruption of the relevant splice donors or the in-frame AUG initiation codons is sufficient to abrogate RAN translation. Our findings provide a molecular explanation for the abnormal translation products observed in CAG trinucleotide repeat expansion disorders and add to the repertoire of mechanisms by which repeat expansion mutations disrupt cellular functions.

7.
Psychol Sport Exerc ; 68: 102475, 2023 09.
Article in English | MEDLINE | ID: mdl-37665896

ABSTRACT

Despite widespread awareness of the physiological and psychological benefits of physical activity, many individuals do not meet recommended guidelines. The current research investigated whether episodic memories of physical activity experiences and the emotions elicited by such memories differ between active and inactive individuals. A total of 40 active individuals (36 females, 4 males; Age X‾ = 20.40) and 36 inactive individuals (31 females, 5 males Age X‾ = 22.67) were asked to retrieve positive and negative memories of physical activity experiences and to rate them for phenomenological characteristics such as vividness, coherence, remembered emotion, and the emotions elicited when recalling those experiences. There was no difference between the active and inactive individuals in the remembered emotion of negative physical activity memories, but the positive memories recalled by active individuals were rated as more positive than those recalled by inactive individuals. The memories recalled by active individuals also elicited 'in the moment' emotions that were more positive for positive memories, and less negative for negative memories, compared to those recalled by inactive individuals. The findings are in line with hedonistic theories of physical activity engagement and suggest that futher research exploring the role of physical activity memories, and their associated affective processing, is warranted.


Subject(s)
Memory, Episodic , Female , Male , Humans , Emotions , Exercise , Mental Recall , Sedentary Behavior
8.
Int J Mol Sci ; 24(13)2023 Jun 21.
Article in English | MEDLINE | ID: mdl-37445611

ABSTRACT

Brain signalling pathways involved in subclinical anxiety and depressed mood can be modulated via the gut brain axis (GBA), providing the potential for diet and dietary components to affect mood. We investigated behavioural, physiological and gut microbiome responses to the Lacticaseibacillus rhamnosus strain HN001 (LactoB HN001™), which has been shown to reduce postpartum anxiety and depression, and a milk fat globule membrane-enriched product, Lipid 70 (SurestartTM MFGM Lipid 70), which has been implicated in memory in stress-susceptible Wistar Kyoto rats. We examined behaviour in the open field, elevated plus maze and novel object recognition tests in conjunction with the expression of host genes in neuro-signalling pathways, and we also assessed brain lipidomics. Treatment-induced alterations in the caecal microbiome and short-chain fatty acid (SCFA) profiles were also assessed. Neither ingredient induced behavioural changes or altered the brain lipidome (separately or when combined). However, with regard to brain gene expression, the L. rhamnosus HN001 + Lipid 70 combination produced a synergistic effect, reducing GABAA subunit expression in the amygdala (Gabre, Gat3, Gabrg1) and hippocampus (Gabrd). Treatment with L. rhamnosus HN001 alone altered expression of the metabotropic glutamate receptor (Grm4) in the amygdala but produced only minor changes in gut microbiota composition. In contrast, Lipid 70 alone did not alter brain gene expression but produced a significant shift in the gut microbiota profile. Under the conditions used, there was no observed effect on rat behaviour for the ingredient combination. However, the enhancement of brain gene expression by L. rhamnosus HN001 + Lipid 70 implicates synergistic actions on region-specific neural pathways associated with fear, anxiety, depression and memory. A significant shift in the gut microbiota profile also occurred that was mainly attributable to Lipid 70.


Subject(s)
Gastrointestinal Microbiome , Lacticaseibacillus rhamnosus , Probiotics , Female , Rats , Animals , Receptors, GABA-A , Lacticaseibacillus , Probiotics/pharmacology , Glycolipids/pharmacology , Diet
9.
J Air Waste Manag Assoc ; 73(8): 618-624, 2023 08.
Article in English | MEDLINE | ID: mdl-37389486

ABSTRACT

The COVID-19 pandemic impacted different aspects of human lifestyle, including waste generation and management. The landfilled and recycled waste volume from the City of Fargo's annual solid waste report between 2019 and 2021 was critically analyzed to understand these impacts. The analysis showed a 4.5% increase in the residential waste volume in 2020 compared to 2019 and 2021, suggesting a pandemic-induced lockdown effect. The monthly residential waste volume was approximately 5-15% greater during the mandatory quarantine period (April - November 2020) than in 2019 and 2021. Commercial waste volume decreased by 12% during 2020 and then sharply increased in 2021 as commercial facilities reopened. The total recycling volume increased slightly by 2.5% in 2020 compared to 2019 and 2021. Cardboard recycling showed a 5.8% increase in 2020 from 2019 and a 13% increase in 2021 compared to 2020. This was presumably caused by the reliance on online shopping during the pandemic and becoming habituated to online shopping. The COVID-19 pandemic did not significantly impact other classes of recycled waste volumes. In summary, COVID-19 affected landfilling and recycling in different capacities in the City of Fargo. The data will contribute to the global understanding of the impact of COVID-19 on solid waste management practices.Implications: The COVID-19 pandemic impacted waste generation and management. In Fargo, USA, the monthly residential waste volume increased by up to 15% during the mandatory quarantine period in 2020 compared to the same period in 2019 and 2021. Conversely, the monthly commercial waste volume decreased during the mandatory quarantine period in 2020. The commercial waste volume increased in 2021 as commercial activities became normal. The cardboard recycling increased significantly because people became used to online shopping during the lockdown, and the practice continues. The findings will contribute to the global understanding of the impact of COVID-19 on solid waste management practices.


Subject(s)
COVID-19 , Refuse Disposal , Triallate , Waste Management , Humans , COVID-19/epidemiology , Pandemics , North Dakota , Communicable Disease Control , Solid Waste/analysis , Recycling
10.
Materials (Basel) ; 16(10)2023 May 09.
Article in English | MEDLINE | ID: mdl-37241250

ABSTRACT

Water uptake by organic coating systems used for corrosion prevention on airframes is one of the principal contributors to the loss of barrier properties of the coating. We used equivalent circuit analyses of electrochemical impedance spectroscopy (EIS) data to track changes in coating layer capacitance for a two-layer coating system consisting of an epoxy primer and polyurethane topcoat immersed in NaCl solutions with different concentrations and temperatures. The capacitance curve exhibited two different response regions, consistent with the "two-stage kinetics" mechanisms for water uptake by the polymers. We tested several numerical diffusion models of water sorption and found the most successful to be one that varied the diffusion coefficient as a function of polymer type and immersion time and accounted for physical aging processes in the polymer. We employed the Brasher mixing law along with the water sorption model to estimate the coating capacitance as a function of water uptake. The predicted capacitance of the coating was found to be consistent with the capacitance obtained from the EIS data, which is consistent with theories that water uptake occurs via initial rapid transport followed by a much slower aging process. Thus, both these water uptake processes need to be considered when making EIS measurements to assess the state of a coating system.

11.
EJHaem ; 4(2): 339-349, 2023 May.
Article in English | MEDLINE | ID: mdl-37206270

ABSTRACT

Secondary immunodeficiency (SID), manifesting as increased susceptibility to infection, is an emergent clinical problem in haematoncology. Management of SID includes vaccination, prophylactic antibiotics (pAbx) and immunoglobulin replacement therapy (IgRT). We report clinical and laboratory parameters of 75 individuals, treated for haematological malignancy, who were referred for immunological assessment due to recurrent infections. Forty-five were managed with pAbx while thirty required IgRT after failing to improve on pAbx. Individuals requiring IgRT had significantly more bacterial, viral and fungal infections resulting in hospitalization at least 5 years after their original haemato-oncological diagnosis. Following immunological assessment and intervention, a 4.39-fold reduction in the frequency of hospital admissions to treat infection was observed in the IgRT cohort and a 2.30-fold reduction in the pAbx cohort. Significant reductions in outpatient antibiotic use were also observed in both cohorts following immunology input. Patients requiring IgRT were more hypogammaglobulinaemic and had lower titres of pathogen-specific antibodies and smaller memory B cell populations than those requiring pAbx. Test vaccination with pneumococcal conjugate vaccine discriminated poorly between the two groups. Patients requiring IgRT could be distinguished by combining wider pathogen-specific serology with a frequency of hospital admissions for infection. If validated in larger cohorts, this approach may circumvent the need for test vaccination and enhance patient selection for IgRT.

12.
Proc Natl Acad Sci U S A ; 120(3): e2215071120, 2023 01 17.
Article in English | MEDLINE | ID: mdl-36623192

ABSTRACT

CAG trinucleotide repeat expansions cause several neurodegenerative diseases, including Huntington's disease and spinocerebellar ataxia. RNAs with expanded CAG repeats contribute to disease in two unusual ways. First, these repeat-containing RNAs may agglomerate in the nucleus as foci that sequester several RNA-binding proteins. Second, these RNAs may undergo aberrant repeat-associated non-AUG (RAN) translation in multiple frames and produce aggregation-prone proteins. The relationship between RAN translation and RNA foci, and their relative contributions to cellular dysfunction, are unclear. Here, we show that CAG repeat-containing RNAs that undergo RAN translation first accumulate at nuclear foci and, over time, are exported to the cytoplasm. In the cytoplasm, these RNAs are initially dispersed but, upon RAN translation, aggregate with the RAN translation products. These RNA-RAN protein agglomerates sequester various RNA-binding proteins and are associated with the disruption of nucleocytoplasmic transport and cell death. In contrast, RNA accumulation at nuclear foci alone does not produce discernable defects in nucleocytoplasmic transport or cell viability. Inhibition of RAN translation prevents cytoplasmic RNA aggregation and alleviates cell toxicity. Our findings demonstrate that RAN translation-induced RNA-protein aggregation correlates with the key pathological hallmarks observed in disease and suggest that cytoplasmic RNA aggregation may be an underappreciated phenomenon in CAG trinucleotide repeat expansion disorders.


Subject(s)
Huntington Disease , Spinocerebellar Ataxias , Humans , RNA/genetics , Trinucleotide Repeat Expansion/genetics , Spinocerebellar Ataxias/genetics , Huntington Disease/genetics
13.
Memory ; 31(4): 502-508, 2023 04.
Article in English | MEDLINE | ID: mdl-36705639

ABSTRACT

ABSTRACTTwo experiments investigated the effects of survival processing on memory for pictures of objects. In experiment 1, participants were presented with 32 pictures of common objects and rated them for their relevance to a survival scenario, a moving home scenario, or for pleasantness. In a surprise recall test, participants in the survival condition recalled more of the verbal labels of the objects than participants in the moving and pleasantness conditions. In experiment 2, participants rated 64 pictures of objects in survival, moving home, or pleasantness conditions. Memory for visual detail was assessed using a forced-choice recognition test in which participants had to decide which of two highly similar pictures was the one they rated at study. In contrast to the results of experiment 1, correct recognition scores were highest in the pleasantness condition and lowest in the survival condition. This pattern suggests that survival processing enhances memory for objects but not for precise visual detail. The findings are consistent with the view that rating objects for their survival value directs attention to the potential uses of the objects. They also emphasise the importance of the match between encoding and retrieval processes in the survival processing paradigm.


Subject(s)
Mental Recall , Recognition, Psychology , Humans , Emotions , Pattern Recognition, Visual
14.
Children (Basel) ; 11(1)2023 Dec 29.
Article in English | MEDLINE | ID: mdl-38255358

ABSTRACT

Based on available data that include approximately 20 lines of evidence from studies in laboratory animal models, observations in humans, correlations in time, and pharmacological/toxicological considerations, it has been concluded without reasonable doubt and with no evidence to the contrary that exposure of susceptible babies and children to acetaminophen (paracetamol) induces many, if not most, cases of autism spectrum disorder (ASD). However, the relative number of cases of ASD that might be induced by acetaminophen has not yet been estimated. Here, we examine a variety of evidence, including the acetaminophen-induced reduction of social awareness in adults, the prevalence of ASD through time, and crude estimates of the relative number of ASD cases induced by acetaminophen during various periods of neurodevelopment. We conclude that the very early postpartum period poses the greatest risk for acetaminophen-induced ASD, and that nearly ubiquitous use of acetaminophen during early development could conceivably be responsible for the induction in the vast majority, perhaps 90% or more, of all cases of ASD. Despite over a decade of accumulating evidence that acetaminophen is harmful for neurodevelopment, numerous studies demonstrate that acetaminophen is frequently administered to children in excess of currently approved amounts and under conditions in which it provides no benefit. Further, studies have failed to demonstrate long-term benefits of acetaminophen for the pediatric population, leaving no valid rationale for continued use of the drug in that population given its risks to neurodevelopment.

15.
JDS Commun ; 3(6): 387-392, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36465501

ABSTRACT

The human intestine plays an important role as a barrier against the ingress of pathogens and other harmful antigens. Accordingly, proper regulation of the intestinal barrier is essential for optimal health. Intestinal barrier function is regulated in part by the interactions between dietary compounds and the intestinal immune system. Bioactive whey proteins from bovine milk (such as lactoferrin, lactoperoxidase, and immunoglobulins) are known to exert a range of physiological functions, including modulation of the immune system, and thus have the potential to regulate intestinal barrier function. While the effects of individual whey proteins on intestinal barrier function have been studied to some extent, less is known about the potentially synergistic properties of whey protein mixtures. Here we investigated the effects of a bioactive bovine whey protein (BWP) extract containing all whey proteins with an isoelectric point >6.8 on intestinal barrier function in vitro. Intestinal epithelial cell (Caco-2) monolayers were treated with BWP before measuring the barrier integrity over 48 h by means of trans-epithelial electrical resistance (TEER). Treatment of epithelial monolayers with 1 mg/mL BWP resulted in an increase in TEER compared with untreated epithelial monolayers. To determine whether BWP could mitigate immune-mediated intestinal barrier dysfunction, we challenged differentiated Caco-2 cell monolayers with tumor necrosis factor α (TNFα) to obtain an in vitro model of a "leaky" intestinal epithelium. The TNFα challenge led to a decrease in TEER over time across untreated control monolayers, indicating a loss of barrier function. This loss of barrier function was mitigated in monolayers treated with 1 mg/mL BWP, but not monolayers treated with the equivalent amount of lactoferrin present in 1 mg/mL BWP. These data suggest that naturally co-occurring bioactive proteins together may enhance intestinal barrier integrity and protect against inflammation-induced barrier dysfunction to a greater extent than lactoferrin alone. Further work is required to determine the key proteins and protein combinations within BWP, and the mechanisms through which BWP modulates intestinal barrier function.

16.
Front Nutr ; 9: 1002369, 2022.
Article in English | MEDLINE | ID: mdl-36386940

ABSTRACT

The probiotic Lacticaseibacillus rhamnosus strain HN001 has been shown to have several beneficial health effects for both pediatric and maternal groups, including reduced risk of eczema in infants and gestational diabetes and postnatal depression in mothers. While L. rhamnosus HN001 appears to modify immune and gut barrier biomarkers, its mode of action remains to be fully elucidated. To gain insights into the role of HN001 on the infant microbiome, the impacts of L. rhamnosus HN001 supplementation was studied in 10-day old male piglets that were fed either infant formula, or infant formula with L. rhamnosus HN001 at a low (1.3 × 105 CFU/ml) or high dose (7.9 × 106 CFU/ml) daily for 24 days. The cecal and fecal microbial communities were assessed by shotgun metagenome sequencing and host gene expression in the cecum and colon tissue was assessed by RNA-seq. Piglet fecal samples showed only modest differences between controls and those receiving dietary L. rhamnosus HN001. However, striking differences between the three groups were observed for cecal samples. While total lactobacilli were significantly increased only in the high dose L. rhamnosus HN001 group, both high and low dose groups showed an up to twofold reduction across the Firmicutes phylum and up to fourfold increase in Prevotella compared to controls. Methanobrevibacter was also decreased in HN001 fed piglets. Microbial genes involved in carbohydrate and vitamin metabolism were among those that differed in relative abundance between those with and without L. rhamnosus HN001. Changes in the cecal microbiome were accompanied by increased expression of tight junction pathway genes and decreased autophagy pathway genes in the cecal tissue of piglets fed the higher dose of L. rhamnosus HN001. Our findings showed supplementation with L. rhamnosus HN001 caused substantial changes in the cecal microbiome with likely consequences for key microbial metabolic pathways. Host gene expression changes in the cecum support previous research showing L. rhamnosus HN001 beneficially impacts intestinal barrier function. We show that fecal samples may not adequately reflect microbiome composition higher in the gastrointestinal tract, with the implication that effects of probiotic consumption may be missed by examining only the fecal microbiome.

17.
Sci Rep ; 12(1): 16218, 2022 09 28.
Article in English | MEDLINE | ID: mdl-36171423

ABSTRACT

Single-cell assays have enriched our understanding of hematopoiesis and, more generally, stem and progenitor cell biology. However, these single-end-point approaches provide only a static snapshot of the state of a cell. To observe and measure dynamic changes that may instruct cell fate, we developed an approach for examining hematopoietic progenitor fate specification using long-term (> 7-day) single-cell time-lapse imaging for up to 13 generations with in situ fluorescence staining of primary human hematopoietic progenitors followed by algorithm-assisted lineage tracing. We analyzed progenitor cell dynamics, including the division rate, velocity, viability, and probability of lineage commitment at the single-cell level over time. We applied a Markov probabilistic model to predict progenitor division outcome over each generation in culture. We demonstrated the utility of this methodological pipeline by evaluating the effects of the cytokines thrombopoietin and erythropoietin on the dynamics of self-renewal and lineage specification in primary human bipotent megakaryocytic-erythroid progenitors (MEPs). Our data support the hypothesis that thrombopoietin and erythropoietin support the viability and self-renewal of MEPs, but do not affect fate specification. Thus, single-cell tracking of time-lapse imaged colony-forming unit assays provides a robust method for assessing the dynamics of progenitor self-renewal and lineage commitment.


Subject(s)
Erythropoietin , Thrombopoietin , Cell Differentiation , Cell Lineage , Erythropoietin/pharmacology , Humans , Megakaryocytes , Thrombopoietin/pharmacology
18.
Obstet Med ; 15(1): 45-49, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35444730

ABSTRACT

Aims: To report pregnancy outcomes and complications in women receiving eculizumab for the management of paroxysmal nocturnal haemoglobinuria. Methods: A service evaluation of routinely collected medical records across 49 pregnancies in 21 women. Results: Eculizumab was used in 37 pregnancies, 31 of which (83.8%) ended in live birth. Eight infants (25.8%) were born prematurely. Over half (54%) of women required increases in their dose of eculizumab to control their haemolysis. There were no reported cases of maternal thrombosis. Major ante/postpartum bleeding necessitating urgent intervention was reported in 10.8% of pregnancies. There were two cases of intrauterine death and three miscarriages. There were no maternal or neonatal deaths. Three newborns required prolonged hospital stays. Conclusions: Eculizumab appears to benefit pregnant women with paroxysmal nocturnal haemoglobinuria and pregnancy outcomes following its use are largely good.

20.
Front Chem ; 10: 820379, 2022.
Article in English | MEDLINE | ID: mdl-35321477

ABSTRACT

This work investigates the previously unexplored impact of tensile stress on oxygen reduction reaction (ORR) kinetics of a precipitation-hardened, stainless-steel fastener material, UNS S13800. ORR is known to drive localized and galvanic corrosion in aircraft assemblies and greater understanding of this reaction on structural alloys is important in forecasting component lifetime and service requirements. The mechano-electrochemical behavior of UNSS13800 was examined using amperometry to measure the reduction current response to tensile stress. Mechanical load cycles within the elastic regime demonstrated reversible electrochemical current shifts under chloride electrolyte droplets that exhibited a clear potential dependence. Strain ramping produced current peaks with a strain rate dependence, which was distinct from the chronoamperometric shifts during static tensile load conditions. Finally, mechanistic insight into the dynamic and static responses was obtained by deoxygenation, which demonstrated ORR contributions that were distinct from other reductive processes.

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