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Article ; Online: Investigating a Novel Neurodegenerative Disease Toxic Mechanism Involving Lipid Binding Specificity of Amyloid Oligomers.

Hirschbeck, Sarah S / Lindberg, Edward T / Jang, Joshua H / Jacob, MaKenna R / Lazar Cantrell, Kristi L / Do, Thanh D

ACS chemical neuroscience

2024 Volume 15, Issue 7, Page(s) 1523–1532

Abstract: Exploring the mechanisms underlying the toxicity of amyloid oligomers (AOs) presents a significant opportunity for discovering cures and developing treatments for neurodegenerative diseases. Recently, using a combination of ion mobility spectrometry-mass ...

Abstract	Exploring the mechanisms underlying the toxicity of amyloid oligomers (AOs) presents a significant opportunity for discovering cures and developing treatments for neurodegenerative diseases. Recently, using a combination of ion mobility spectrometry-mass spectrometry (IMS-MS) and X-ray crystallography (XRC), we showed that the peptide KVKVLWDVIEV, which is the G95W mutant of αB-Crystallin (90-100) and abbreviated as G6W, self-assembles up to a dodecamer that structurally resembles lipid transport proteins. The glycine to tryptophan mutation promotes not only larger oligomers and enhanced cytotoxicity in brain slices than the wild type but also a narrow hydrophobic cavity suitable for fatty acid or phospholipid binding. Here, we determine the plausibility of a novel cytotoxic mechanism where the G6W's structural motif could perturb lipid homeostasis by determining its lipid binding selectivity and specificity. We show that the G6W oligomers have a strong affinity toward unsaturated phospholipids with a preference toward phospholipids containing 16-C alkyl chains. Molecular dynamics simulations demonstrate how an unsaturated, 16-C phospholipid fits tightly inside and outside G6W's hydrophobic cavity. This binding is exclusive to the G6W peptide, as other amyloid oligomers with different atomic structures, including its wildtype αB-Crystallin (90-100) and several superoxide dismutase 1 (SOD1) peptides that are known to self-assemble into amyloid oligomers (SOD1
MeSH term(s)	Humans ; Neurodegenerative Diseases ; Superoxide Dismutase-1 ; Amyloid/metabolism ; Peptides ; Amyloidogenic Proteins ; Phospholipids ; Crystallins ; Amyloid beta-Peptides/metabolism
Chemical Substances	Superoxide Dismutase-1 (EC 1.15.1.1) ; Amyloid ; Peptides ; Amyloidogenic Proteins ; Phospholipids ; Crystallins ; Amyloid beta-Peptides
Language	English
Publishing date	2024-03-15
Publishing country	United States
Document type	Journal Article
ISSN	1948-7193
ISSN (online)	1948-7193
DOI	10.1021/acschemneuro.3c00830
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Plants cope with fluctuating light by frequency-dependent nonphotochemical quenching and cyclic electron transport.

Niu, Yuxi / Lazár, Dušan / Holzwarth, Alfred R / Kramer, David M / Matsubara, Shizue / Fiorani, Fabio / Poorter, Hendrik / Schrey, Silvia D / Nedbal, Ladislav

The New phytologist

2023 Volume 239, Issue 5, Page(s) 1869–1886

Abstract: In natural environments, plants are exposed to rapidly changing light. Maintaining photosynthetic efficiency while avoiding photodamage requires equally rapid regulation of photoprotective mechanisms. We asked what the operation frequency range of ... ...

Abstract	In natural environments, plants are exposed to rapidly changing light. Maintaining photosynthetic efficiency while avoiding photodamage requires equally rapid regulation of photoprotective mechanisms. We asked what the operation frequency range of regulation is in which plants can efficiently respond to varying light. Chlorophyll fluorescence, P700, plastocyanin, and ferredoxin responses of wild-types Arabidopsis thaliana were measured in oscillating light of various frequencies. We also investigated the npq1 mutant lacking violaxanthin de-epoxidase, the npq4 mutant lacking PsbS protein, and the mutants crr2-2, and pgrl1ab impaired in different pathways of the cyclic electron transport. The fastest was the PsbS-regulation responding to oscillation periods longer than 10 s. Processes involving violaxanthin de-epoxidase dampened changes in chlorophyll fluorescence in oscillation periods of 2 min or longer. Knocking out the PGR5/PGRL1 pathway strongly reduced variations of all monitored parameters, probably due to congestion in the electron transport. Incapacitating the NDH-like pathway only slightly changed the photosynthetic dynamics. Our observations are consistent with the hypothesis that nonphotochemical quenching in slow light oscillations involves violaxanthin de-epoxidase to produce, presumably, a largely stationary level of zeaxanthin. We interpret the observed dynamics of photosystem I components as being formed in slow light oscillations partially by thylakoid remodeling that modulates the redox rates.
MeSH term(s)	Electron Transport ; Photosystem II Protein Complex/metabolism ; Light ; Photosynthesis/physiology ; Arabidopsis/metabolism ; Chlorophyll/metabolism ; Light-Harvesting Protein Complexes/metabolism ; Mutation/genetics ; Arabidopsis Proteins/genetics ; Arabidopsis Proteins/metabolism ; Photosynthetic Reaction Center Complex Proteins/genetics ; Membrane Proteins/metabolism
Chemical Substances	Photosystem II Protein Complex ; Chlorophyll (1406-65-1) ; Light-Harvesting Protein Complexes ; PGR5 protein, Arabidopsis ; Arabidopsis Proteins ; Photosynthetic Reaction Center Complex Proteins ; PGRL1 protein, Arabidopsis ; Membrane Proteins
Language	English
Publishing date	2023-07-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	208885-x
ISSN	1469-8137 ; 0028-646X
ISSN (online)	1469-8137
ISSN	0028-646X
DOI	10.1111/nph.19083
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Article: Anthracycline's Effects on Heart Rate Variability in Children with Acute Lymphoblastic Leukemia: Early Toxicity Signs-Pilot Study.

Lazar, Diana R / Cainap, Simona / Maniu, Dana / Blag, Cristina / Bota, Madalina / Lazar, Florin-Leontin / Achim, Alexandru / Colceriu, Marius C / Zdrenghea, Mihnea

Journal of clinical medicine

2023 Volume 12, Issue 22

Abstract: ... of a 24 h Holter ECG, at baseline and after reaching half the total cumulative dose of doxorubicin ...

Abstract	Anthracycline treatments are known to cause cardiotoxic long-term side effects in cancer survivors. Recently, a decrease in heart rate variability (HRV) has been identified in these patients, signaling autonomic dysfunction and altered cardiac fitness. This study aimed at evaluating changes in HRV in children treated with anthracyclines. A total of 35 pediatric patients with acute lymphoblastic leukemia were evaluated by means of a 24 h Holter ECG, at baseline and after reaching half the total cumulative dose of doxorubicin equivalent (120 mg/m
Language	English
Publishing date	2023-11-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm12227052
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Article ; Online: Long-Term Pulmonary Damage in Surviving Antitoxin-Treated Mice following a Lethal Ricin Intoxication.

Gal, Yoav / Sapoznikov, Anita / Lazar, Shlomi / Shoseyov, David / Aftalion, Moshe / Gutman, Hila / Evgy, Yentl / Gez, Rellie / Nevo, Reinat / Falach, Reut

Toxins

2024 Volume 16, Issue 2

Abstract: Ricin, a highly potent plant-derived toxin, is considered a potential bioterrorism weapon due to its pronounced toxicity, high availability, and ease of preparation. Acute damage following pulmonary ricinosis is characterized by local cytokine storm, ... ...

Abstract	Ricin, a highly potent plant-derived toxin, is considered a potential bioterrorism weapon due to its pronounced toxicity, high availability, and ease of preparation. Acute damage following pulmonary ricinosis is characterized by local cytokine storm, massive neutrophil infiltration, and edema formation, resulting in respiratory insufficiency and death. A designated equine polyclonal antibody-based (antitoxin) treatment was developed in our laboratory and proved efficacious in alleviating lung injury and increasing survival rates. Although short-term pathogenesis was thoroughly characterized in antitoxin-treated mice, the long-term damage in surviving mice was never determined. In this study, long-term consequences of ricin intoxication were evaluated 30 days post-exposure in mice that survived antitoxin treatment. Significant pulmonary sequelae were demonstrated in surviving antitoxin-treated mice, as reflected by prominent histopathological changes, moderate fibrosis, increased lung hyperpermeability, and decreased lung compliance. The presented data highlight, for the first time to our knowledge, the possibility of long-term damage development in mice that survived lethal-dose pulmonary exposure to ricin due to antitoxin treatment.
MeSH term(s)	Animals ; Horses ; Mice ; Antitoxins/therapeutic use ; Ricin/toxicity ; Lung/pathology ; Respiratory Insufficiency ; Lung Injury/drug therapy
Chemical Substances	Antitoxins ; Ricin (9009-86-3)
Language	English
Publishing date	2024-02-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2518395-3
ISSN	2072-6651 ; 2072-6651
ISSN (online)	2072-6651
ISSN	2072-6651
DOI	10.3390/toxins16020103
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Article ; Online: Somatosensory cortex of macaque monkeys is designed for opposable thumb.

Lazar, Leslee / Chand, Prem / Rajan, Radhika / Mohammed, Hisham / Jain, Neeraj

Cerebral cortex (New York, N.Y. : 1991)

2022 Volume 33, Issue 1, Page(s) 195–206

Abstract: The evolution of opposable thumb has enabled fine grasping ability and precision grip, therefore the ability to finely manipulate the objects and refined tool use. Since tactile inputs to an opposable thumb are often spatially and temporally out of sync ... ...

Abstract	The evolution of opposable thumb has enabled fine grasping ability and precision grip, therefore the ability to finely manipulate the objects and refined tool use. Since tactile inputs to an opposable thumb are often spatially and temporally out of sync with inputs from the fingers, we hypothesized that inputs from the opposable thumb would be processed in an independent module in the primary somatosensory cortex (area 3b). Here we show that in area 3b of macaque monkeys, most neurons in the thumb representation do not respond to tactile stimulation of other digits and receive few intrinsic cortical inputs from other digits. However, neurons in the representations of other 4 digits respond to touch on any of the 4 digits and interconnect significantly more. The thumb inputs are thus processed in an independent module, whereas there is a significantly more interdigital information exchange between the other digits. This cortical organization reflects behavioral use of a hand with an opposable thumb.
MeSH term(s)	Animals ; Somatosensory Cortex/physiology ; Thumb ; Macaca ; Haplorhini ; Brain Mapping
Language	English
Publishing date	2022-02-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1077450-6
ISSN	1460-2199 ; 1047-3211
ISSN (online)	1460-2199
ISSN	1047-3211
DOI	10.1093/cercor/bhac061
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Article ; Online: Topical Vancomycin for Sternal Wound Infection Prophylaxis: Reinventing the Wheel All Over Again.

Lazar, Harold / Suwalski, Piotr / Lorusso, Roberto / Meani, Paolo / Kowalewski, Mariusz

The Annals of thoracic surgery

2022 Volume 116, Issue 2, Page(s) 440–441

MeSH term(s)	Humans ; Vancomycin/therapeutic use ; Anti-Bacterial Agents/therapeutic use ; Sternum/surgery ; Wound Infection/drug therapy ; Surgical Wound Infection/prevention & control ; Antibiotic Prophylaxis ; Administration, Topical
Chemical Substances	Vancomycin (6Q205EH1VU) ; Anti-Bacterial Agents
Language	English
Publishing date	2022-12-06
Publishing country	Netherlands
Document type	Letter ; Comment
ZDB-ID	211007-6
ISSN	1552-6259 ; 0003-4975
ISSN (online)	1552-6259
ISSN	0003-4975
DOI	10.1016/j.athoracsur.2022.11.033
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Article ; Online: Attenuation of Anxiety-Potentiated Startle After Treatment With Escitalopram or Mindfulness Meditation in Anxiety Disorders.

Hoge, Elizabeth A / Armstrong, Caroline H / Mete, Mihriye / Oliva, Isabelle / Lazar, Sara W / Lago, Tiffany R / Grillon, Christian

Biological psychiatry

2023 Volume 95, Issue 1, Page(s) 85–92

Abstract: Background: Biological markers for anxiety disorders may further understanding of disorder pathophysiology and suggest potential targeted treatments. The fear-potentiated startle (FPS) (a measure of startle to predictable threat) and anxiety-potentiated ...

Abstract	Background: Biological markers for anxiety disorders may further understanding of disorder pathophysiology and suggest potential targeted treatments. The fear-potentiated startle (FPS) (a measure of startle to predictable threat) and anxiety-potentiated startle (APS) (startle to unpredictable threat) laboratory paradigm has been used to detect physiological differences in individuals with anxiety disorders compared with nonanxious control individuals, and in pharmacological challenge studies in healthy adults. However, little is known about how startle may change with treatment for anxiety disorders, and no data are available regarding alterations due to mindfulness meditation training. Methods: Ninety-three individuals with anxiety disorders and 66 healthy individuals completed 2 sessions of the neutral, predictable, and unpredictable threat task, which employs a startle probe and the threat of shock to assess moment-by-moment fear and anxiety. Between the two testing sessions, patients received randomized 8-week treatment with either escitalopram or mindfulness-based stress reduction. Results: APS, but not FPS, was higher in participants with anxiety disorders compared with healthy control individuals at baseline. Further, there was a significantly greater decrease in APS for both treatment groups compared with the control group, with the patient groups showing reductions bringing them into the range of control individuals at the end of the treatment. Conclusions: Both anxiety treatments (escitalopram and mindfulness-based stress reduction) reduced startle potentiation during unpredictable (APS) but not predictable (FPS) threat. These findings further validate APS as a biological correlate of pathological anxiety and provide physiological evidence for the impact of mindfulness-based stress reduction on anxiety disorders, suggesting that there may be comparable effects of the two treatments on anxiety neurocircuitry.
MeSH term(s)	Adult ; Humans ; Anxiety ; Anxiety Disorders/therapy ; Escitalopram ; Meditation ; Mindfulness ; Reflex, Startle/physiology ; Case-Control Studies
Chemical Substances	Escitalopram (4O4S742ANY)
Language	English
Publishing date	2023-06-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	209434-4
ISSN	1873-2402 ; 0006-3223
ISSN (online)	1873-2402
ISSN	0006-3223
DOI	10.1016/j.biopsych.2023.06.003
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Article: Assessment of Frontal Hemispherical Lateralization in Plaque Psoriasis and Atopic Dermatitis.

Journal of clinical medicine

2023 Volume 12, Issue 13

Abstract: Background: Each brain hemisphere plays a specialized role in cognitive and behavioral processes, known as hemispheric lateralization. In chronic skin diseases, such as plaque psoriasis (Pso) and atopic dermatitis (AD), the degree of lateralization ... ...

Abstract	Background: Each brain hemisphere plays a specialized role in cognitive and behavioral processes, known as hemispheric lateralization. In chronic skin diseases, such as plaque psoriasis (Pso) and atopic dermatitis (AD), the degree of lateralization between the frontal hemispheres may provide insight into specific connections between skin diseases and the psyche. This study aims to analyze the hemispherical lateralization, neurovegetative responses, and psychometric characteristics of patients with Pso and AD. Methods: The study included 46 patients with Pso, 56 patients with AD, and 29 healthy control (Ctrl) subjects. The participants underwent frontal electroencephalogram (EEG) measurement, heart rate variability (HRV) assessment, and psychological tests. Statistical analyses were performed using ANOVA, with Bonferroni correction applied for multiple comparisons. Results: This study shows a significant right-lateralized prefrontal activity in both AD patients ( Conclusion: Psychophysiological and psychometric data suggest a shared prevalence of right-hemispheric dominance in both AD and Pso patient groups. However, the findings indicate distinct psychodermatological mechanisms in AD and Pso.
Language	English
Publishing date	2023-06-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm12134194
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Article ; Online: Reported sleep duration reveals segmentation of the adult life-course into three phases.

Coutrot, A / Lazar, A S / Richards, M / Manley, E / Wiener, J M / Dalton, R C / Hornberger, M / Spiers, H J

Nature communications

2022 Volume 13, Issue 1, Page(s) 7697

Abstract: Classically the human life-course is characterized by youth, middle age and old age. A wide range of biological, health and cognitive functions vary across this life-course. Here, using reported sleep duration from 730,187 participants across 63 ... ...

Abstract	Classically the human life-course is characterized by youth, middle age and old age. A wide range of biological, health and cognitive functions vary across this life-course. Here, using reported sleep duration from 730,187 participants across 63 countries, we find three distinct phases in the adult human life-course: early adulthood (19-33yrs), mid-adulthood (34-53yrs), and late adulthood (54+yrs). They appear stable across culture, gender, education and other demographics. During the third phase, where self-reported sleep duration increases with age, cognitive performance, as measured by spatial navigation, was found to have an inverted u-shape relationship with reported sleep duration: optimal performance peaks at 7 hours reported sleep. World-wide self-reported sleep duration patterns are geographically clustered, and are associated with economy, culture, and latitude.
MeSH term(s)	Middle Aged ; Adolescent ; Adult ; Humans ; Sleep Duration ; Time Factors ; Sleep ; Self Report ; Cognition
Language	English
Publishing date	2022-12-13
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-022-34624-8
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Article ; Online: Rational Design of Biological Crystals with Enhanced Physical Properties by Hydrogen Bonding Interactions.

Yuan, Hui / Xue, Bin / Yang, Dingyi / Rencus-Lazar, Sigal / Cao, Yi / Gazit, Ehud / Tan, Dan / Yang, Rusen

Research (Washington, D.C.)

2023 Volume 6, Page(s) 46

Abstract: ... between O and H atoms contributes to low mechanical strength that permits important ion displacement under ...

Abstract	Hydrogen bonds are non-covalent interactions and essential for assembling supermolecules into ordered structures in biological systems, endowing crystals with fascinating physical properties, and inspiring the construction of eco-friendly electromechanical devices. However, the interplay between hydrogen bonding and the physical properties is not fully understood at the molecular level. Herein, we demonstrate that the physical property of biological crystals with double-layer structures could be enhanced by rationally controlling hydrogen bonding interactions between amino and carboxyl groups. Different hydrogen bonding interactions result in various thermal, mechanical, electronic, and piezoelectric properties. In particular, the weak interaction between O and H atoms contributes to low mechanical strength that permits important ion displacement under stress, giving rise to a strong piezoelectric response. This study not only reveals the correlation between the hydrogen bonding and physical properties in double-layer structures of biological crystals but also demonstrates the potential of these crystals as functional biomaterials for high-performance energy-harvesting devices. Theoretical calculations and experimental verifications in this work provide new insights into the rational design of biomaterials with desirable physical properties for bioelectrical devices by modulating intermolecular interactions.
Language	English
Publishing date	2023-02-24
Publishing country	United States
Document type	Journal Article
ISSN	2639-5274
ISSN (online)	2639-5274
DOI	10.34133/research.0046
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