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1.
Microbiol Resour Announc ; : e0059824, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38990025

ABSTRACT

We report the circularized 6,427,509-bp genome of Pseudomonas aeruginosa isolated from the inner ear of a laboratory mouse (Mus musculus) diagnosed with otitis media. The genome of P. aeruginosa NCTR 501 has a circular chromosome of 6,420,288 bp and two plasmids of 4,042 and 3,179 bp, respectively.

2.
Biol Aujourdhui ; 218(1-2): 63-72, 2024.
Article in French | MEDLINE | ID: mdl-39007778

ABSTRACT

Our taxonomic study from March 2014 to November 2015 along the atlantic coast between Casablanca and El Jadida revealed that phytoplanktonic structure is mainly represented by Diatoms (Bacillariophyceae), Dinoflagellates (Dinophyceae), Silicoflagellates (Dictyophyceae) and Euglenophyceae with a clear dominance of Diatoms and Dinoflagellates. A total of 101 taxa of planktonic algae have been identified revealing a relatively diversified taxocenosis. In terms of respective diversity, the Diatoms are represented by 62 taxa (61.4%), the Dinoflagellates by 36 taxa (35.6%) whereas the other two groups of Silicoflagellates and Euglenophyceae are only represented by 3 species (3.0%). Regarding potentially toxic species, more than fifteen taxa have been identified, most of which were Dinoflagellates and Diatoms (Pseudo-nitzschia australis and Pseudo-nitzschia cuspidata). The total phytoplankton densities exhibited great spatial and temporal variations as shown by analyses of diversity (H') and equitability (E) indices at the different coast sites investigated throughout the 2014-2015 years. Massive proliferation of some toxic species (e.g. Pseudo-nitzschia australis and Pseudo-nitzschia cuspidata, Lingulodinium polyedrum, Karenia mikimotoi) was also noticed. In addition, our study revealed the presence of opportunistic species (e.g. Eutreptiella, Thalassiosira, Prorocentrum scutellum) and of the new ectoparasite Dinoflagellate Amyloodinium ocellatum for the first time in Morocco. The detection of such diversity of toxic species, sometimes with alarming concentrations, should prompt the competent authorities to broaden the spectrum and frequency of biomonitoring to uncontrolled seafood harvesting sites.


Title: Dynamique du peuplement phytoplanctonique le long de l'axe côtier Casablanca ­ El Jadida. Abstract: Notre étude taxonomique entre mars 2014 et novembre 2015 le long de la côte atlantique entre Casablanca et El Jadida a permis de déceler une flore phytoplanctonique représentée par les Diatomées, Dinoflagellés, Silicoflagellés et Euglenophycées avec une nette dominance des Diatomées et des Dinoflagellés. Au total, 101 taxons d'algues planctoniques ont été identifiés, témoignant d'une taxocénose relativement diversifiée. Dans cet ensemble, les Diatomées sont représentées par 62 taxons (61,4 %), les Dinoflagellés par 36 taxa (35,6 %) et les deux autres groupes (Silicoflagellés et Euglénophycées) ne sont représentés que par 3 espèces seulement (3,0 %). En ce qui concerne les espèces potentiellement toxiques, plus d'une quinzaine de taxons ont été identifiés dont la plupart sont des Dinoflagellés et des Diatomées (Pseudo-nitzschia australis et Pseudo-nitzschia cuspidata). L'analyse de l'évolution spatiotemporelle des indices de diversité (H') et d'équitabilité (E) révèle des fluctuations saisonnières prononcées sans montrer, pour autant, une grande analogie entre les différents sites prospectés. Par ailleurs, les densités phytoplanctoniques totales présentent de grandes variations à la fois spatiales et temporelles (sur les deux cycles annuels). La présence de proliférations massives de certaines espèces potentiellement toxiques (Pseudo-nitzschia australis et Pseudo-nitzschia cuspidata, Lingulodinium polyedrum, Karenia mikimotoi), d'une nouvelle espèce de Dinoflagellé ectoparasite pour le Maroc (Amyloodinium ocellatum) et d'autres espèces opportunistes (Eutreptiella, Thalassiosira, Prorocentrum scutellum) a été notée au cours de cette étude. La détection des espèces potentiellement toxiques, parfois à des concentrations alarmantes, devrait inciter les autorités compétentes à élargir le spectre et la fréquence de biosurveillance aux sites non contrôlés.


Subject(s)
Dinoflagellida , Phytoplankton , Population Dynamics , Phytoplankton/physiology , Atlantic Ocean , Morocco/epidemiology , Dinoflagellida/physiology , Diatoms , Biodiversity
3.
ISME J ; 18(1)2024 Jan 08.
Article in English | MEDLINE | ID: mdl-38896583

ABSTRACT

Probiotics have gained significant attention as a potential strategy to improve health by modulating host-microbe interactions, particularly in situations where the normal microbiota has been disrupted. However, evidence regarding their efficacy has been inconsistent, with considerable interindividual variability in response. We aimed to explore whether a common genetic variant that affects the production of mucosal α(1,2)-fucosylated glycans, present in around 20% of the population, could explain the observed interpersonal differences in the persistence of commonly used probiotics. Using a mouse model with varying α(1,2)-fucosylated glycans secretion (Fut2WT or Fut2KO), we examined the abundance and persistence of Bifidobacterium strains (infantis, breve, and bifidum). We observed significant differences in baseline gut microbiota characteristics between Fut2WT and Fut2KO littermates, with Fut2WT mice exhibiting enrichment of species able to utilize α(1,2)-fucosylated glycans. Following antibiotic exposure, only Fut2WT animals showed persistent engraftment of Bifidobacterium infantis, a strain able to internalize α(1,2)-fucosylated glycans, whereas B. breve and B. bifidum, which cannot internalize α(1,2)-fucosylated glycans, did not exhibit this difference. In mice with an intact commensal microbiota, the relationship between secretor status and B. infantis persistence was reversed, with Fut2KO animals showing greater persistence compared to Fut2WT. Our findings suggest that the interplay between a common genetic variation and antibiotic exposure plays a crucial role in determining the dynamics of B. infantis in the recipient gut, which could potentially contribute to the observed variation in response to this commonly used probiotic species.


Subject(s)
Anti-Bacterial Agents , Fucosyltransferases , Galactoside 2-alpha-L-fucosyltransferase , Gastrointestinal Microbiome , Probiotics , Animals , Mice , Fucosyltransferases/genetics , Fucosyltransferases/metabolism , Probiotics/administration & dosage , Anti-Bacterial Agents/pharmacology , Bifidobacterium longum subspecies infantis/genetics , Bifidobacterium longum subspecies infantis/metabolism , Polysaccharides/metabolism , Host Microbial Interactions , Mice, Inbred C57BL , Mice, Knockout , Bifidobacterium/genetics , Bifidobacterium/metabolism
5.
Age Ageing ; 53(5)2024 05 01.
Article in English | MEDLINE | ID: mdl-38773946

ABSTRACT

OBJECTIVE: Moving into a long-term care facility (LTCF) requires substantial personal, societal and financial investment. Identifying those at high risk of short-term mortality after LTCF entry can help with care planning and risk factor management. This study aimed to: (i) examine individual-, facility-, medication-, system- and healthcare-related predictors for 90-day mortality at entry into an LTCF and (ii) create risk profiles for this outcome. DESIGN: Retrospective cohort study using data from the Registry of Senior Australians. SUBJECTS: Individuals aged ≥ 65 years old with first-time permanent entry into an LTCF in three Australian states between 01 January 2013 and 31 December 2016. METHODS: A prediction model for 90-day mortality was developed using Cox regression with the purposeful variable selection approach. Individual-, medication-, system- and healthcare-related factors known at entry into an LTCF were examined as predictors. Harrell's C-index assessed the predictive ability of our risk models. RESULTS: 116,192 individuals who entered 1,967 facilities, of which 9.4% (N = 10,910) died within 90 days, were studied. We identified 51 predictors of mortality, five of which were effect modifiers. The strongest predictors included activities of daily living category (hazard ratio [HR] = 5.41, 95% confidence interval [CI] = 4.99-5.88 for high vs low), high level of complex health conditions (HR = 1.67, 95% CI = 1.58-1.77 for high vs low), several medication classes and male sex (HR = 1.59, 95% CI = 1.53-1.65). The model out-of-sample Harrell's C-index was 0.773. CONCLUSIONS: Our mortality prediction model, which includes several strongly associated factors, can moderately well identify individuals at high risk of mortality upon LTCF entry.


Subject(s)
Long-Term Care , Humans , Male , Female , Aged , Retrospective Studies , Aged, 80 and over , Long-Term Care/statistics & numerical data , Risk Factors , Risk Assessment , Australia/epidemiology , Registries , Activities of Daily Living , Nursing Homes/statistics & numerical data , Time Factors , Homes for the Aged/statistics & numerical data , Proportional Hazards Models
6.
Regul Toxicol Pharmacol ; 150: 105629, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38657894

ABSTRACT

The world's hunger for novel food ingredients drives the development of safe, sustainable, and nutritious novel food products. For foods containing novel proteins, potential allergenicity of the proteins is a key safety consideration. One such product is a fungal biomass obtained from the fermentation of Rhizomucor pusillus. The annotated whole genome sequence of this strain was subjected to sequence homology searches against the AllergenOnline database (sliding 80-amino acid windows and full sequence searches). In a stepwise manner, proteins were designated as potentially allergenic and were further compared to proteins from commonly consumed foods and from humans. From the sliding 80-mer searches, 356 proteins met the conservative >35% Codex Alimentarius threshold, 72 of which shared ≥50% identity over the full sequence. Although matches were identified between R. pusillus proteins and proteins from allergenic food sources, the matches were limited to minor allergens from these sources, and they shared a greater degree of sequence homology with those from commonly consumed foods and human proteins. Based on the in silico analysis and a literature review for the source organism, the risk of allergenic cross-reactivity of R. pusillus is low.


Subject(s)
Allergens , Biomass , Rhizomucor , Allergens/immunology , Rhizomucor/immunology , Humans , Food Ingredients , Computer Simulation , Food Hypersensitivity/immunology , Fungal Proteins/immunology
7.
Sci Rep ; 14(1): 6939, 2024 03 23.
Article in English | MEDLINE | ID: mdl-38521833

ABSTRACT

Chronic enteropathies (CE) are common disorders in cats and the differentiation between the two main underlying diseases, inflammatory bowel disease (IBD) and low-grade intestinal T-cell lymphoma (LGITL), can be challenging. Characterization of the serum metabolome could provide further information on alterations of disease-associated metabolic pathways and may identify diagnostic or therapeutic targets. Unbiased metabolomics analysis of serum from 28 cats with CE (14 cats with IBD, 14 cats with LGITL) and 14 healthy controls identified 1,007 named metabolites, of which 129 were significantly different in cats with CE compared to healthy controls at baseline. Random Forest analysis revealed a predictive accuracy of 90% for differentiating controls from cats with chronic enteropathy. Metabolic pathways found to be significantly altered included phospholipids, amino acids, thiamine, and tryptophan metabolism. Several metabolites were found to be significantly different between cats with IBD versus LGITL, including several sphingolipids, phosphatidylcholine 40:7, uridine, pinitol, 3,4-dihydroxybenzoic acid, and glucuronic acid. However, random forest analysis revealed a poor group predictive accuracy of 60% for the differentiation of IBD from LGITL. Of 129 compounds found to be significantly different between healthy cats and cats with CE at baseline, 58 remained different following treatment.


Subject(s)
Cat Diseases , Inflammatory Bowel Diseases , Cats , Animals , Metabolomics , Metabolome , Cat Diseases/diagnosis
8.
Aging Clin Exp Res ; 36(1): 83, 2024 Mar 29.
Article in English | MEDLINE | ID: mdl-38551712

ABSTRACT

OBJECTIVES: To examine changes in primary, allied health, selected specialists, and mental health service utilisation by older people in the year before and after accessing home care package (HCP) services. METHODS: A retrospective cohort study using the Registry of Senior Australians Historical National Cohort (≥ 65 years old), including individuals accessing HCP services between 2017 and 2019 (N = 109,558), was conducted. The utilisation of general practice (GP) attendances, health assessments, chronic disease management plans, allied health services, geriatric, pain, palliative, and mental health services, subsidised by the Australian Government Medicare Benefits Schedule, was assessed in the 12 months before and after HCP access, stratified by HCP level (1-2 vs. 3-4, i.e., lower vs. higher care needs). Relative changes in service utilisation 12 months before and after HCP access were estimated using adjusted risk ratios (aRR) from Generalised Estimating Equation Poisson models. RESULTS: Utilisation of health assessments (7-10.2%), chronic disease management plans (19.7-28.2%), and geriatric, pain, palliative, and mental health services (all ≤ 2.5%) remained low, before and after HCP access. Compared to 12 months prior to HCP access, 12 months after, GP after-hours attendances increased (HCP 1-2 from 6.95 to 7.5%, aRR = 1.07, 95% CI 1.03-1.11; HCP 3-4 from 7.76 to 9.32%, aRR = 1.20, 95%CI 1.13-1.28) and allied health services decreased (HCP 1-2 from 34.8 to 30.7%, aRR = 0.88, 95%CI 0.87-0.90; HCP levels 3-4 from 30.5 to 24.3%, aRR = 0.80, 95%CI 0.77-0.82). CONCLUSIONS: Most MBS subsidised preventive, management and specialist services are underutilised by older people, both before and after HCP access and small changes are observed after they access HCP.


Subject(s)
Australasian People , Home Care Services , Mental Health Services , Humans , Aged , Australia , Retrospective Studies , National Health Programs , Pain
9.
Biochemistry ; 63(6): 725-732, 2024 Mar 19.
Article in English | MEDLINE | ID: mdl-38450612

ABSTRACT

Schwann cells (SCs) undergo phenotypic transformation and then orchestrate nerve repair following a peripheral nervous system injury. The low-density lipoprotein receptor-related protein-1 (LRP1) is significantly upregulated in SCs in response to acute injury, activating cJun and promoting SC survival. Matrix-metalloproteinase-9 (MMP-9) is an LRP1 ligand that binds LRP1 through its hemopexin domain (PEX) and activates SC survival signaling and migration. To identify novel peptide mimetics within the hemopexin domain of MMP-9, we examined the crystal structure of PEX, synthesized four peptides, and examined their potential to bind and activate LRP1. We demonstrate that a 22 amino acid peptide, peptide 2, was the only peptide that activated Akt and ERK1/2 signaling in SCs, similar to a glutathione s-transferase (GST)-fused holoprotein, GST-PEX. Intraneural injection of peptide 2, but not vehicle, into crush-injured sciatic nerves activated cJun greater than 2.5-fold in wild-type mice, supporting that peptide 2 can activate the SC repair signaling in vivo. Peptide 2 also bound to Fc-fusion proteins containing the ligand-binding motifs of LRP1, clusters of complement-like repeats (CCRII and CCRIV). Pulldown and computational studies of alanine mutants of peptide 2 showed that positively charged lysine and arginine amino acids within the peptide are critical for stability and binding to CCRII. Collectively, these studies demonstrate that a novel peptide derived from PEX can serve as an LRP1 agonist and possesses qualities previously associated with LRP1 binding and SC signaling in vitro and in vivo.


Subject(s)
Hemopexin , Matrix Metalloproteinase 9 , Mice , Animals , Hemopexin/metabolism , Matrix Metalloproteinase 9/metabolism , Ligands , Signal Transduction/physiology , Peptides/pharmacology , Peptides/metabolism , Schwann Cells/metabolism , Low Density Lipoprotein Receptor-Related Protein-1/metabolism
10.
Proc Natl Acad Sci U S A ; 121(10): e2318615121, 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38416685

ABSTRACT

The late stages of Golgi maturation involve a series of sequential trafficking events in which cargo-laden vesicles are produced and targeted to multiple distinct subcellular destinations. Each of these vesicle biogenesis events requires activation of an Arf GTPase by the Sec7/BIG guanine nucleotide exchange factor (GEF). Sec7 localization and activity is regulated by autoinhibition, positive feedback, and interaction with other GTPases. Although these mechanisms have been characterized biochemically, we lack a clear picture of how GEF localization and activity is modulated by these signals. Here, we report the cryogenic electron microscopy structure of full-length Sec7 in its autoinhibited form, revealing the architecture of its multiple regulatory domains. We use functional experiments to determine the basis for autoinhibition and use structural predictions to produce a model for an active conformation of the GEF that is supported empirically. This study therefore elucidates the conformational transition that Sec7 undergoes to become active on the organelle membrane surface.


Subject(s)
GTP Phosphohydrolases , Golgi Apparatus , Golgi Apparatus/metabolism , ADP-Ribosylation Factors/metabolism
11.
J Mol Biol ; 436(8): 168499, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38401625

ABSTRACT

Small heat shock proteins (sHSPs) are ATP-independent chaperones vital to cellular proteostasis, preventing protein aggregation events linked to various human diseases including cataract. The α-crystallins, αA-crystallin (αAc) and αB-crystallin (αBc), represent archetypal sHSPs that exhibit complex polydispersed oligomeric assemblies and rapid subunit exchange dynamics. Yet, our understanding of how this plasticity contributes to chaperone function remains poorly understood. Using biochemical and biophysical analyses combined with single-particle electron microscopy (EM), we examined structural changes in αAc, αBc and native heteromeric lens α-crystallins (αLc) in their apo-states and at varying degree of chaperone saturation leading to co-aggregation, using lysozyme and insulin as model clients. Quantitative single-particle analysis unveiled a continuous spectrum of oligomeric states formed during the co-aggregation process, marked by significant client-triggered expansion and quasi-ordered elongation of the sHSP oligomeric scaffold, whereby the native cage-like sHSP assembly displays a directional growth to accommodate saturating conditions of client sequestration. These structural modifications culminated in an apparent amorphous collapse of chaperone-client complexes, resulting in the creation of co-aggregates capable of scattering visible light. Intriguingly, these co-aggregates maintain internal morphological features of highly elongated sHSP oligomers with striking resemblance to polymeric α-crystallin species isolated from aged lens tissue. This mechanism appears consistent across αAc, αBc and αLc, albeit with varying degrees of susceptibility to client-induced co-aggregation. Importantly, our findings suggest that client-induced co-aggregation follows a distinctive mechanistic and quasi-ordered trajectory, distinct from a purely amorphous process. These insights reshape our understanding of the physiological and pathophysiological co-aggregation processes of α-crystallins, carrying potential implications for a pathway toward cataract formation.


Subject(s)
Cataract , Crystallins , Heat-Shock Proteins, Small , alpha-Crystallins , Humans , Aged , alpha-Crystallins/metabolism , Molecular Chaperones/metabolism , Crystallins/metabolism , Cataract/metabolism
12.
Adv Sci (Weinh) ; 11(21): e2304748, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38342628

ABSTRACT

Many cardiovascular problems stem from blockages that form within the vasculature and often treatment includes fitting a stent through percutaneous coronary intervention. This offers a minimally invasive therapy but re-occlusion through restenosis or thrombosis formation often occurs post-deployment. Research is ongoing into the creation of smart stents that can detect the occurrence of further problems. In this study, it is shown that selectively metalizing a non-conductive stent can create a set of electrodes that are capable of detecting a build-up of material around the stent. The associated increase in electrical impedance across the electrodes is measured, testing the stent with blood clot to mimic thrombosis. It is shown that the device is capable of sensing different amounts of occlusion. The stent can reproducibly sense the presence of clot showing a 16% +/-3% increase in impedance which is sufficient to reliably detect the clot when surrounded by explanted aorta (one sample t-test, p = 0.009, n = 9). It is demonstrated that this approach can be extended beyond the 3D printed prototypes by showing that it can be applied to a commercially available stent and it is believed that it can be further utilized by other types of medical implants.


Subject(s)
Biosensing Techniques , Stents , Thrombosis , Biosensing Techniques/methods , Biosensing Techniques/instrumentation , Thrombosis/diagnosis , Humans , Animals , Electric Impedance
13.
Public Health Rep ; 139(2): 230-240, 2024.
Article in English | MEDLINE | ID: mdl-38240243

ABSTRACT

OBJECTIVES: Effective health communication can increase intent to vaccinate. We compared 8 messages that may influence parents' intent to vaccinate their children against COVID-19. METHODS: In a cross-sectional survey of adults in the United States administered online in August 2021, 1837 parents and legal guardians were exposed to 8 messages (individual choice, gain/practical benefits, nonexpert, health care provider recommendation, altruism/community good, safety/effectiveness, safety, and effectiveness) to determine message reception and influence on intent to vaccinate their children. Parents responded to 10 questions using a Likert scale. We computed odds ratios (ORs) for each message, with an OR >1.0 indicating greater observed odds of participant agreement with the follow-up statement as compared with a reference message. We compared outcomes individually across messages with ordinal logistic regression fit using generalized estimating equations. RESULTS: The individual choice message had the highest odds of agreement for understanding intent (OR = 2.10; 95% CI, 1.94-2.27), followed by the health care provider recommendation message (OR = 1.58; 95% CI, 1.46-1.71). The individual choice message had the highest odds of memorability, relatability, and trustworthiness. The altruism/community good message was at or near second best. The altruism/community good message had the highest or near-highest odds of increasing parents' intent to vaccinate their children, asking friends and family for their thoughts, and searching for additional information. The message that most motivated parents to vaccinate their children depended on parental intent to vaccinate prior to being exposed to the tested messages. CONCLUSIONS: Messages with themes of individual choice, health care provider recommendation, and altruism/community good may be used in future message campaigns. Further research is needed to refine message concepts related to altruism/community good.


Subject(s)
COVID-19 , Vaccination , Humans , Adult , Child , United States , Cross-Sectional Studies , COVID-19/epidemiology , COVID-19/prevention & control , Parents , Intention , Health Knowledge, Attitudes, Practice
15.
Methods Mol Biol ; 2717: 143-157, 2024.
Article in English | MEDLINE | ID: mdl-37737982

ABSTRACT

Clinically, oral food challenges have value in the diagnosis and management of food allergy. Oral food challenges are used not only for diagnostic confirmation that ingestion of a specific food elicits an adverse reaction, but also for determining individual threshold doses, tracking the progress toward desensitization during immunotherapy, determining the effect of processing on the allergenicity of a specific food, assessing the allergenicity of an ingredient derived from an allergenic source, and tracking the progress toward development of age-related tolerance to a specific food. To eliminate bias in oral challenges, the food under investigation is masked in a matrix so that it is not sensorially detectable by the patient or the clinical observer. The preparation of oral challenge foods requires care in the selection of the allergenic components, the selection of the components of the matrix, the masking of the allergenic component, and the homogeneity of the allergen in the overall matrix.


Subject(s)
Food Hypersensitivity , Immune Tolerance , Humans , Allergens , Immunotherapy , Food Hypersensitivity/diagnosis , Food Hypersensitivity/immunology
16.
bioRxiv ; 2023 Nov 22.
Article in English | MEDLINE | ID: mdl-38045260

ABSTRACT

The late stages of Golgi maturation involve a series of sequential trafficking events in which cargo-laden vesicles are produced and targeted to multiple distinct subcellular destinations. Each of these vesicle biogenesis events requires activation of an Arf GTPase by the Sec7/BIG guanine nucleotide exchange factor (GEF). Sec7 localization and activity is regulated by autoinhibition, positive feedback, and interaction with other GTPases. Although these mechanisms have been characterized biochemically, we lack a clear picture of how GEF localization and activity is modulated by these signals. Here we report the cryoEM structure of full-length Sec7 in its autoinhibited form, revealing the architecture of its multiple regulatory domains. We use functional experiments to determine the basis for autoinhibition and use structural predictions to produce a model for an active conformation of the GEF that is supported empirically. This study therefore elucidates the conformational transition that Sec7 undergoes to become active on the organelle membrane surface.

17.
New Phytol ; 240(5): 2050-2057, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37798874

ABSTRACT

Endophytic feeding behaviors, including stem borings and galling, have been observed in the fossil record from as early as the Devonian and involve the consumption of a variety of plant (and fungal) tissues. Historically, the exploitation of internal stem tissues through galling has been well documented as emerging during the Pennsylvanian (c. 323-299 million years ago (Ma)), replaced during the Permian by galling of foliar tissues. However, leaf mining, a foliar endophytic behavior that today is exhibited exclusively by members of the four hyperdiverse holometabolous insect orders, has been more sparsely documented, with confirmed examples dating back only to the Early Triassic (c. 252-250 Ma). Here, we describe a trace fossil on seed-fern foliage from the Rhode Island Formation of Massachusetts, USA, representing the earliest indication of a general, endophytic type of feeding damage and dating from the Middle Pennsylvanian (c. 312 Ma). Although lacking the full features of Mesozoic leaf mines, this specimen provides evidence of how endophytic mining behavior may have originated. It sheds light on the evolutionary transition to true foliar endophagy, contributes to our understanding of the behaviors of early holometabolous insects, and enhances our knowledge of macroevolutionary patterns of plant-insect interactions.


Subject(s)
Biological Evolution , Plants , Animals , Fossils , Insecta , Herbivory
18.
Animals (Basel) ; 13(17)2023 Aug 30.
Article in English | MEDLINE | ID: mdl-37685017

ABSTRACT

Chronic enteropathy (CE) in cats encompasses food-responsive enteropathy, chronic inflammatory enteropathy (or inflammatory bowel disease), and low-grade intestinal T-cell lymphoma. While alterations in the gut metabolome have been extensively studied in humans and dogs with gastrointestinal disorders, little is known about the specific metabolic profile of cats with CE. As lipids take part in energy storage, inflammation, and cellular structure, investigating the lipid profile in cats with CE is crucial. This study aimed to measure fecal concentrations of various fatty acids, sterols, and bile acids. Fecal samples from 56 cats with CE and 77 healthy control cats were analyzed using gas chromatography-mass spectrometry, targeting 12 fatty acids, 10 sterols, and 5 unconjugated bile acids. Fecal concentrations of nine targeted fatty acids and animal-derived sterols were significantly increased in cats with CE. However, fecal concentrations of plant-derived sterols were significantly decreased in cats with CE. Additionally, an increased percentage of primary bile acids was observed in a subset of cats with CE. These findings suggest the presence of lipid maldigestion, malabsorption, and inflammation in the gastrointestinal tract of cats with CE. Understanding the lipid alterations in cats with CE can provide insights into the disease mechanisms and potential future therapeutic strategies.

19.
Endocrinology ; 164(11)2023 09 23.
Article in English | MEDLINE | ID: mdl-37776515

ABSTRACT

The current model for the synchronization of GnRH neural activity driving GnRH and LH pulses proposes that a set of arcuate (ARC) neurons that contain kisspeptin, neurokinin B, and dynorphin (KNDy neurons) is the GnRH pulse generator. This study tested the functional role of ovine KNDy neurons in pulse generation and explored the roles of nearby Kiss1 receptor (Kiss1R)-containing cells using lesions produced with saporin (SAP) conjugates. Injection of NK3-SAP ablated over 90% of the KNDy cells, while Kiss-SAP (saporin conjugated to kisspeptin-54) lesioned about two-thirds of the Kiss1R population without affecting KNDy or GnRH cell number. Both lesions produced a dramatic decrease in LH pulse amplitude but had different effects on LH pulse patterns. NK3-SAP increased interpulse interval, but Kiss-SAP did not. In contrast, Kiss-SAP disrupted the regular hourly occurrence of LH pulses, but NK3-SAP did not. Because Kiss1R is not expressed in KNDy cells, HiPlex RNAScope was used to assess the colocalization of 8 neurotransmitters and 3 receptors in ARC Kiss1R-containing cells. Kiss1R cells primarily contained transcript markers for GABA (68%), glutamate (28%), ESR1 (estrogen receptor-α) mRNA, and OPRK1 (kappa opioid receptor) mRNA. These data support the conclusion that KNDy neurons are essential for GnRH pulses in ewes, whereas ARC Kiss1R cells are not but do maintain the amplitude and regularity of GnRH pulses. We thus propose that in sheep, ARC Kiss1R neurons form part of a positive feedback circuit that reinforces the activity of the KNDy neural network, with GABA or glutamate likely being involved.


Subject(s)
Arcuate Nucleus of Hypothalamus , Kisspeptins , Luteinizing Hormone , Neurons , Animals , Female , Arcuate Nucleus of Hypothalamus/metabolism , Dynorphins/metabolism , gamma-Aminobutyric Acid , Glutamates , Gonadotropin-Releasing Hormone/metabolism , Kisspeptins/metabolism , Neurokinin B/metabolism , Neurons/metabolism , Receptors, Kisspeptin-1/genetics , RNA, Messenger , Saporins , Sheep , Luteinizing Hormone/metabolism
20.
bioRxiv ; 2023 Aug 17.
Article in English | MEDLINE | ID: mdl-37645910

ABSTRACT

Small heat shock proteins (sHSPs) are ATP-independent chaperones vital to cellular proteostasis, preventing protein aggregation events linked to various human diseases including cataract. The α-crystallins, αA-crystallin (αAc) and αB-crystallin (αBc), represent archetypal sHSPs that exhibit complex polydispersed oligomeric assemblies and rapid subunit exchange dynamics. Yet, our understanding of how this plasticity contributes to chaperone function remains poorly understood. This study investigates structural changes in αAc and αBc during client sequestration under varying degree of chaperone saturation. Using biochemical and biophysical analyses combined with single-particle electron microscopy (EM), we examined αAc and αBc in their apo-states and at various stages of client-induced co-aggregation, using lysozyme as a model client. Quantitative single-particle analysis unveiled a continuous spectrum of oligomeric states formed during the co-aggregation process, marked by significant client-triggered expansion and quasi-ordered elongation of the sHSP scaffold. These structural modifications culminated in an apparent amorphous collapse of chaperone-client complexes, resulting in the creation of co-aggregates capable of scattering visible light. Intriguingly, these co-aggregates maintain internal morphological features of highly elongated sHSP scaffolding with striking resemblance to polymeric α-crystallin species isolated from aged lens tissue. This mechanism appears consistent across both αAc and αBc, albeit with varying degrees of susceptibility to client-induced co-aggregation. Importantly, our findings suggest that client-induced co-aggregation follows a distinctive mechanistic and quasi-ordered trajectory, distinct from a purely amorphous process. These insights reshape our understanding of the physiological and pathophysiological co-aggregation processes of sHSPs, carrying potential implications for a pathway toward cataract formation.

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