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Article: Intermittent Hypoxia and Diet-Induced Obesity on the Intestinal Wall Morphology in a Murine Model of Sleep Apnea.

Valverde-Pérez, Esther / Olea, Elena / Obeso, Ana / Prieto-Lloret, Jesús / Rocher, Asunción / Gonzalez-Obeso, Elvira

Advances in experimental medicine and biology

2023 Volume 1427, Page(s) 89–97

Abstract: This work analyzes the impact of two conditions, intermittent hypoxia exposure and high-fat diet in rats as models of sleep apnea. We studied the autonomic activity and histological structure of the rat jejunum and whether the overlapping of both ... ...

Abstract	This work analyzes the impact of two conditions, intermittent hypoxia exposure and high-fat diet in rats as models of sleep apnea. We studied the autonomic activity and histological structure of the rat jejunum and whether the overlapping of both conditions, as often observed in patients, induces more deleterious effects on the intestinal barrier. We found alterations in jejunum wall histology, predominantly in HF rats, based on increased crypt depth and submucosal thickness, as well as decreased muscularis propria thickness. These alterations were maintained with the IH and HF overlap. An increase in the number and size of goblet cells in the villi and crypts and the infiltration of eosinophils and lymphocytes in the lamina propria suggest an inflammatory status, confirmed by the increase in plasma CRP levels in all experimental groups. Regarding the CAs analysis, IH, alone or combined with HF, causes a preferential accumulation of NE in the catecholaminergic nerve fibers of the jejunum. In contrast, serotonin increases in all three experimental conditions, with the highest level in the HF group. It remains to be elucidated whether the alterations found in the present work could affect the permeability of the intestinal barrier, promoting sleep apnea-induced morbidities.
MeSH term(s)	Mice ; Rats ; Animals ; Disease Models, Animal ; Obesity/complications ; Sleep Apnea Syndromes ; Diet, High-Fat/adverse effects ; Hypoxia/complications
Language	English
Publishing date	2023-06-15
Publishing country	United States
Document type	Journal Article
ISSN	2214-8019 ; 0065-2598
ISSN (online)	2214-8019
ISSN	0065-2598
DOI	10.1007/978-3-031-32371-3_10
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Article ; Online: Noninvasive modulation of human corticostriatal activity.

Caballero-Insaurriaga, Jaime / Pineda-Pardo, José A / Obeso, Ignacio / Oliviero, Antonio / Foffani, Guglielmo

Proceedings of the National Academy of Sciences of the United States of America

2023 Volume 120, Issue 15, Page(s) e2219693120

Abstract: Corticostriatal activity is an appealing target for nonpharmacological treatments of brain disorders. In humans, corticostriatal activity may be modulated with noninvasive brain stimulation (NIBS). However, a NIBS protocol with a sound neuroimaging ... ...

Abstract	Corticostriatal activity is an appealing target for nonpharmacological treatments of brain disorders. In humans, corticostriatal activity may be modulated with noninvasive brain stimulation (NIBS). However, a NIBS protocol with a sound neuroimaging measure demonstrating a change in corticostriatal activity is currently lacking. Here, we combine transcranial static magnetic field stimulation (tSMS) with resting-state functional MRI (fMRI). We first present and validate the ISAAC analysis, a well-principled framework that disambiguates functional connectivity between regions from local activity within regions. All measures of the framework suggested that the region along the medial cortex displaying greater functional connectivity with the striatum is the supplementary motor area (SMA), where we applied tSMS. We then use a data-driven version of the framework to show that tSMS of the SMA modulates the local activity in the SMA proper, in the adjacent sensorimotor cortex, and in the motor striatum. We finally use a model-driven version of the framework to clarify that the tSMS-induced modulation of striatal activity can be primarily explained by a change in the shared activity between the modulated motor cortical areas and the motor striatum. These results suggest that corticostriatal activity can be targeted, monitored, and modulated noninvasively in humans.
MeSH term(s)	Humans ; Corpus Striatum/diagnostic imaging ; Sensorimotor Cortex ; Neostriatum ; Motor Cortex/diagnostic imaging ; Motor Cortex/physiology ; Transcranial Magnetic Stimulation/methods ; Magnetic Resonance Imaging
Language	English
Publishing date	2023-04-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2219693120
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Article ; Online: Chylothorax and Central Venous Thrombosis: A Difficult and Challenging Relationship.

Obeso, Andrés / Romero Vázquez, Laura / Fernández Noya, Jorge

JACC. Case reports

2021 Volume 3, Issue 14, Page(s) 1576–1578

Language	English
Publishing date	2021-10-20
Publishing country	Netherlands
Document type	Editorial
ISSN	2666-0849
ISSN (online)	2666-0849
DOI	10.1016/j.jaccas.2021.07.026
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Article ; Online: Oxidase enzyme genes are differentially expressed during Acanthamoeba castellanii encystment.

Scheckhuber, Christian Q / Damián Ferrara, Rebeca / Gómez-Montalvo, Jesús / Maciver, Sutherland K / de Obeso Fernández Del Valle, Alvaro

Parasitology research

2024 Volume 123, Issue 2, Page(s) 116

Abstract: Acanthamoeba castellanii, a ubiquitous protozoan, is responsible for significant diseases such as Acanthamoeba keratitis and granulomatous amoebic encephalitis. A crucial survival strategy of A. castellanii involves the formation of highly resistant ... ...

Abstract	Acanthamoeba castellanii, a ubiquitous protozoan, is responsible for significant diseases such as Acanthamoeba keratitis and granulomatous amoebic encephalitis. A crucial survival strategy of A. castellanii involves the formation of highly resistant cysts during adverse conditions. This study delves into the cellular processes underpinning encystment, focusing on gene expression changes related to reactive oxygen species (ROS) balance, with a particular emphasis on mitochondrial processes. Our findings reveal a dynamic response within the mitochondria during encystment, with the downregulation of key enzymes involved in oxidative phosphorylation (COX, AOX, and NADHalt) during the initial 48 h, followed by their overexpression at 72 h. This orchestrated response likely creates a pro-oxidative environment, facilitating encystment. Analysis of other ROS processing enzymes across the cell reveals differential expression patterns. Notably, antioxidant enzymes, such as catalases, glutaredoxins, glutathione S-transferases, peroxiredoxins, and thioredoxins, mirror the mitochondrial trend of downregulation followed by upregulation. Additionally, glycolysis and gluconeogenesis are downregulated during the early stages in order to potentially balance the metabolic requirement of the cyst. Our study underscores the importance of ROS regulation in Acanthamoeba encystment. Understanding these mechanisms offers insights into infection control and identifies potential therapeutic targets. This work contributes to unraveling the complex biology of A. castellanii and may aid in combatting Acanthamoeba-related infections. Further research into ROS and oxidase enzymes is warranted, given the organism's remarkable respiratory versatility.
MeSH term(s)	Humans ; Acanthamoeba castellanii/genetics ; Reactive Oxygen Species ; Catalase ; Acanthamoeba Keratitis ; Amebiasis ; Cysts
Chemical Substances	Reactive Oxygen Species ; Catalase (EC 1.11.1.6)
Language	English
Publishing date	2024-01-30
Publishing country	Germany
Document type	Journal Article
ZDB-ID	284966-5
ISSN	1432-1955 ; 0932-0113 ; 0044-3255
ISSN (online)	1432-1955
ISSN	0932-0113 ; 0044-3255
DOI	10.1007/s00436-024-08138-9
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Article ; Online: CollagenTransformer: End-to-End Transformer Model to Predict Thermal Stability of Collagen Triple Helices Using an NLP Approach.

Khare, Eesha / Gonzalez-Obeso, Constancio / Kaplan, David L / Buehler, Markus J

ACS biomaterials science & engineering

2022 Volume 8, Issue 10, Page(s) 4301–4310

Abstract: Collagen is one of the most important structural proteins in biology, and its structural hierarchy plays a crucial role in many mechanically important biomaterials. Here, we demonstrate how transformer models can be used to predict, directly from the ... ...

Abstract	Collagen is one of the most important structural proteins in biology, and its structural hierarchy plays a crucial role in many mechanically important biomaterials. Here, we demonstrate how transformer models can be used to predict, directly from the primary amino acid sequence, the thermal stability of collagen triple helices, measured via the melting temperature T<sub>m</sub>. We report two distinct transformer architectures to compare performance. First, we train a small transformer model from scratch, using our collagen data set featuring only 633 sequence-to-T<sub>m</sub> pairings. Second, we use a large pretrained transformer model, ProtBERT, and fine-tune it for a particular downstream task by utilizing sequence-to-T<sub>m</sub> pairings, using a deep convolutional network to translate natural language processing BERT embeddings into required features. Both the small transformer model and the fine-tuned ProtBERT model have similar R<sup>2</sup> values of test data (R<sup>2</sup> = 0.84 vs 0.79, respectively), but the ProtBERT is a much larger pretrained model that may not always be applicable for other biological or biomaterials questions. Specifically, we show that the small transformer model requires only 0.026% of the number of parameters compared to the much larger model but reaches almost the same accuracy for the test set. We compare the performance of both models against 71 newly published sequences for which T<sub>m</sub> has been obtained as a validation set and find reasonable agreement, with ProtBERT outperforming the small transformer model. The results presented here are, to our best knowledge, the first demonstration of the use of transformer models for relatively small data sets and for the prediction of specific biophysical properties of interest. We anticipate that the work presented here serves as a starting point for transformer models to be applied to other biophysical problems.
MeSH term(s)	Biocompatible Materials ; Collagen/chemistry ; Natural Language Processing
Chemical Substances	Biocompatible Materials ; Collagen (9007-34-5)
Language	English
Publishing date	2022-09-23
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
ISSN	2373-9878
ISSN (online)	2373-9878
DOI	10.1021/acsbiomaterials.2c00737
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Article: Effects of Gestational Intermittent Hypoxia on Placental Morphology and Fetal Development in a Murine Model of Sleep Apnea.

Valverde-Pérez, Esther / Prieto-Lloret, Jesús / Gonzalez-Obeso, Elvira / Cabero, María I / Nieto, Maria L / Pablos, Marta I / Obeso, Ana / Gomez-Niño, Angela / Cárdaba-García, Rosa M / Rocher, Asunción / Olea, Elena

Advances in experimental medicine and biology

2023 Volume 1427, Page(s) 73–81

Abstract: Obstructive sleep apnea (OSA) during pregnancy is characterized by episodes of intermittent hypoxia (IH) during sleep, resulting in adverse health outcomes for mother and offspring. Despite a prevalence of 8-20% in pregnant women, this disorder is often ... ...

Abstract	Obstructive sleep apnea (OSA) during pregnancy is characterized by episodes of intermittent hypoxia (IH) during sleep, resulting in adverse health outcomes for mother and offspring. Despite a prevalence of 8-20% in pregnant women, this disorder is often underdiagnosed.We have developed a murine model of gestational OSA to study IH effects on pregnant mothers, placentas, fetuses, and offspring. One group of pregnant rats was exposed to IH during the last 2 weeks of gestation (GIH). One day before the delivery date, a cesarean section was performed. Other group of pregnant rats was allowed to give birth at term to study offspring's evolution.Preliminary results showed no significant weight differences in mothers and fetuses. However, the weight of GIH male offspring was significantly lower than the controls at 14 days (p < 0.01). The morphological study of the placentas showed an increase in fetal capillary branching, expansion of maternal blood spaces, and number of cells of the external trophectoderm in the tissues from GIH-exposed mothers. Additionally, the placentas from the experimental males were enlarged (p < 0.05). Further studies are needed to follow the long-term evolution of these changes to relate the histological findings of the placentas with functional development of the offspring in adulthood.
MeSH term(s)	Mice ; Animals ; Pregnancy ; Female ; Rats ; Male ; Humans ; Placenta ; Disease Models, Animal ; Cesarean Section ; Hypoxia ; Fetal Development ; Sleep Apnea, Obstructive ; Parturition
Language	English
Publishing date	2023-06-15
Publishing country	United States
Document type	Journal Article
ISSN	2214-8019 ; 0065-2598
ISSN (online)	2214-8019
ISSN	0065-2598
DOI	10.1007/978-3-031-32371-3_8
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Article ; Online: Conclusions.

Obeso, Jose / Stoessl, A Jon

Movement disorders : official journal of the Movement Disorder Society

2018 Volume 33, Issue 5, Page(s) 701

Language	English
Publishing date	2018-07-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	607633-6
ISSN	1531-8257 ; 0885-3185
ISSN (online)	1531-8257
ISSN	0885-3185
DOI	10.1002/mds.27432
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Article ; Online: Heterogeneous and Cooperative Rupture of Histidine-Ni

Khare, Eesha / Gonzalez Obeso, Constancio / Martín-Moldes, Zaira / Talib, Ayesha / Kaplan, David L / Holten-Andersen, Niels / Blank, Kerstin G / Buehler, Markus J

ACS biomaterials science & engineering

2024

Abstract: Metal-coordination bonds, a highly tunable class of dynamic noncovalent interactions, are pivotal to the function of a variety of protein-based natural materials and have emerged as binding motifs to produce strong, tough, and self-healing bioinspired ... ...

Abstract	Metal-coordination bonds, a highly tunable class of dynamic noncovalent interactions, are pivotal to the function of a variety of protein-based natural materials and have emerged as binding motifs to produce strong, tough, and self-healing bioinspired materials. While natural proteins use clusters of metal-coordination bonds, synthetic materials frequently employ individual bonds, resulting in mechanically weak materials. To overcome this current limitation, we rationally designed a series of elastin-like polypeptide templates with the capability of forming an increasing number of intermolecular histidine-Ni
Language	English
Publishing date	2024-04-26
Publishing country	United States
Document type	Journal Article
ISSN	2373-9878
ISSN (online)	2373-9878
DOI	10.1021/acsbiomaterials.3c01819
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Article ; Online: Acanthamoeba castellanii exhibits intron retention during encystment.

de Obeso Fernández Del Valle, Alvaro / Gómez-Montalvo, Jesús / Maciver, Sutherland K

Parasitology research

2022 Volume 121, Issue 9, Page(s) 2615–2622

Abstract: Intron retention (IR) refers to the mechanism of alternative splicing in which an intron is not excised from the mature transcript. IR in the cosmopolitan free-living amoeba Acanthamoeba castellanii has not been studied. We performed an analysis of RNA ... ...

Abstract	Intron retention (IR) refers to the mechanism of alternative splicing in which an intron is not excised from the mature transcript. IR in the cosmopolitan free-living amoeba Acanthamoeba castellanii has not been studied. We performed an analysis of RNA sequencing data during encystment to identify genes that presented differentially retained introns during this process. We show that IR increases during cyst formation, indicating a potential mechanism of gene regulation that could help downregulate metabolism. We identify 69 introns from 67 genes that are differentially retained comparing the trophozoite stage and encystment after 24 and 48 h. These genes include several hypothetical proteins. We show different patterns of IR during encystment taking as examples a lipase, a peroxin-3 protein, an Fbox domain containing protein, a proteasome subunit, a polynucleotide adenylyltransferase, and a tetratricopeptide domain containing protein. A better understanding of IR in Acanthamoeba, and even other protists, could help elucidate changes in life cycle and combat disease such as Acanthamoeba keratitis in which the cyst is key for its persistence.
MeSH term(s)	Acanthamoeba Keratitis ; Acanthamoeba castellanii/genetics ; Animals ; Humans ; Introns ; Life Cycle Stages ; Trophozoites
Language	English
Publishing date	2022-07-01
Publishing country	Germany
Document type	Journal Article
ZDB-ID	284966-5
ISSN	1432-1955 ; 0932-0113 ; 0044-3255
ISSN (online)	1432-1955
ISSN	0932-0113 ; 0044-3255
DOI	10.1007/s00436-022-07578-5
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Article ; Online: Neuron types in the primate striatum: Stereological analysis of projection neurons and interneurons in control and parkinsonian monkeys.

Del Rey, Natalia López-González / Trigo-Damas, Inés / Obeso, José A / Cavada, Carmen / Blesa, Javier

Neuropathology and applied neurobiology

2022 Volume 48, Issue 5, Page(s) e12812

Abstract: Aims: The striatum is mainly composed of projection neurons. It also contains interneurons, which modulate and control striatal output. The aim of the present study was to assess the percentages of projection neurons and interneuron populations in the ... ...

Abstract	Aims: The striatum is mainly composed of projection neurons. It also contains interneurons, which modulate and control striatal output. The aim of the present study was to assess the percentages of projection neurons and interneuron populations in the striatum of control monkeys and of parkinsonian monkeys. Methods: Unbiased stereology was used to estimate the volume density of every neuron population in the caudate, putamen and ventral striatum of control monkeys and of monkeys treated with MPTP, which results in striatal dopamine depletion. The various neuron population phenotypes were identified by immunohistochemistry. All analyses were performed within the same subjects using similar processing and analysis parameters, thus allowing for reliable data comparisons. Results: In control monkeys, the projection neurons, which express the dopamine-and-cAMP-regulated-phosphoprotein, 32-KDa (DARPP-32), were the most abundant: ~86% of the total neurons counted. The interneurons accounted for the remaining 14%. Among the interneurons, those expressing calretinin were the most abundant (Cr+: ~57%; ~8% of the total striatal neurons counted), followed those expressing Parvalbumin (Pv+: ~18%; 2.6%), dinucleotide phosphate-diaphorase (NADPH+: ~13%; 1.8%), choline acetyltransferase (ChAT+: ~11%; 1.5%) and tyrosine hydroxylase (TH+: ~0.5%; 0.1%). No significant changes in volume densities occurred in any population following dopamine depletion, except for the TH+ interneurons, which increased in parkinsonian non-symptomatic monkeys and even more in symptomatic monkeys. Conclusions: These data are relevant for translational studies targeting specific neuron populations of the striatum. The fact that dopaminergic denervation does not cause neuron loss in any population has potential pathophysiological implications.
MeSH term(s)	Animals ; Corpus Striatum/cytology ; Corpus Striatum/pathology ; Dopamine ; Haplorhini ; Interneurons/cytology ; Neurons/cytology ; Parkinsonian Disorders/physiopathology
Chemical Substances	Dopamine (VTD58H1Z2X)
Language	English
Publishing date	2022-03-20
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80371-6
ISSN	1365-2990 ; 0305-1846
ISSN (online)	1365-2990
ISSN	0305-1846
DOI	10.1111/nan.12812
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