bluuebunny/crossref_metadata_2025 huggingface dataset:
Electroencephalographic Biomarkers, Cerebral Oximetry, and Postoperative Cognitive Function in Adult Noncardiac Surgical Patients: A Prospective Cohort Study
Authors: Vlisides Phillip E. , Li Duan , Maywood Michael , Zierau Mackenzie , Lapointe Andrew P. , Brooks Joseph , McKinney Amy M. , Leis Aleda M. , Mentz Graciela , Mashour George A.
Published: June 2023

Background

Perioperative neurocognitive disorders are a major public health issue, although there are no validated neurophysiologic biomarkers that predict cognitive function after surgery. This study tested the hypothesis that preoperative posterior electroencephalographic alpha power, alpha frontal-parietal connectivity, and cerebral oximetry would each correlate with postoperative neurocognitive function.

Methods

This was a single-center, prospective, observational study of adult (older than 18 yr) male and female noncardiac surgery patients. Whole-scalp, 16-channel electroencephalography and cerebral oximetry were recorded in the preoperative, intraoperative, and immediate postoperative settings. The primary outcome was the mean postoperative T-score of three National Institutes of Health Toolbox Cognition tests—Flanker Inhibitory Control and Attention, List Sorting Working Memory, and Pattern Comparison Processing Speed. These tests were obtained at preoperative baseline and on the first two postoperative mornings. The lowest average score from the first two postoperative days was used for the primary analysis. Delirium was a secondary outcome (via 3-min Confusion Assessment Method) measured in the postanesthesia care unit and twice daily for the first 3 postoperative days. Last, patient-reported outcomes related to cognition and overall well-being were collected 3 months postdischarge.

Results

Sixty-four participants were recruited with a median (interquartile range) age of 59 (48 to 66) yr. After adjustment for baseline cognitive function scores, no significant partial correlation (ρ) was detected between postoperative cognition scores and preoperative relative posterior alpha power (%; ρ = –0.03, P = 0.854), alpha frontal-parietal connectivity (via weight phase lag index; ρ = –0.10, P = 0.570, respectively), or preoperative cerebral oximetry (%; ρ = 0.21, P = 0.246). Only intraoperative frontal-parietal theta connectivity was associated with postoperative delirium (F[1,6,291] = 4.53, P = 0.034). No electroencephalographic or oximetry biomarkers were associated with cognitive or functional outcomes 3 months postdischarge.

Conclusions

Preoperative posterior alpha power, frontal-parietal connectivity, and cerebral oximetry were not associated with cognitive function after noncardiac surgery.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
Perioperative continuous body weight measurements with load cells under the bed legs in patients undergoing abdominal surgery
Authors: Son Kyongsuk , Tarao Kentaroh , Hateruma Yuki , Nozaki-Taguchi Natsuko , Sato Yasunori , Isono Shiroh
Published: June 2023

BACKGROUND

Both excessive positive fluid balance and body weight increase after surgery are risk factors for poor postoperative outcomes. The use in clinical practice and the value of perioperative body weight measurements are unclear at present, possibly due to difficulty in measuring body weight in patients lying on the bed and insufficient clinical research.

OBJECTIVES

To investigate the relationship between intraoperative fluid balance and body weight change and perioperative nightly body weight change pattern throughout the hospital stay with contact-free unconstraint load cells placed under the bed legs.

DESIGN

Observational and exploratory study.

SETTING

A single university hospital.

PATIENTS

Twenty adult patients were undergoing elective abdominal surgery under general anaesthesia.

MAIN OUTCOME MEASURES

Body weight.

RESULTS

Immediately after surgery, body weight increased significantly by 2.7 ± 1.3 kg, equivalent to a 5% increase from the preoperative body weight. This increase was not correlated with (P = 0.178) the intraoperative fluid balance and was significantly greater than the intraoperative fluid balance 1.5 ± 0.4 kg (P < 0.001). The body weight returned to the preoperative level on postoperative day (POD)3 and further significantly decreased to 97% of the preoperative body weight at POD6 (P < 0.001). This physiological nocturnal weight loss pattern was maintained throughout hospitalisation except when fluid was infused. Compared with their preoperative status, patients stayed in bed longer with smaller body movements and left the bed less frequently during the daytime until POD3. Conversely, the patients had greater body movements in bed during the night leading to smaller diurnal variation in the body movements in bed after POD4.

CONCLUSION

Both perioperative fluid balance calculation and body weight measurement may have different but mutually complementary roles in perioperative managements. Postoperative fluid and nutrition management strategies are potentially new directions for treatment through continuous weight monitoring during the perioperative period.

Trial registration

: UMIN Clinical Trials Registry (UMIN000040164).
Pelvic ring injuries: recent advances in diagnosis and treatment
Authors: de Ridder Victor A. , Whiting Paul S. , Balogh Zsolt J. , Mir Hassan R. , Schultz Blake J. , Routt Milton “Chip”
Published: June 2023

Pelvic ring injuries typically occur from high-energy trauma and are often associated with multisystem injuries. Prompt diagnosis of pelvic ring injuries is essential, and timely initial management is critical in the early resuscitation of polytraumatized patients. Definitive management of pelvic ring injuries continues to be a topic of much debate in the trauma community. Recent studies continue to inform our understanding of static and dynamic pelvic ring stability. Furthermore, literature investigating radiographic and clinical outcomes after nonoperative and operative management will help guide trauma surgeons select the most appropriate treatment of patients with these injuries.
Strategic predatory pursuit of the stealthy, highly manoeuvrable, slow flying bat
Corynorhinus townsendii
Authors: Bortoni Alberto , Swartz Sharon M. , Vejdani Hamid , Corcoran Aaron J.
Published: June 2023

A predator's capacity to catch prey depends on its ability to navigate its environment in response to prey movements or escape behaviour. In predator–prey interactions that involve an active chase, pursuit behaviour can be studied as the collection of rules that dictate how a predator should steer to capture prey. It remains unclear how variable this behaviour is within and across species since most studies have detailed the pursuit behaviour of high-speed, open-area foragers. In this study, we analyse the pursuit behaviour in 44 successful captures by
Corynorhinus townsendii
, Townsend's big-eared bat (
n
= 4). This species forages close to vegetation using slow and highly manoeuvrable flight, which contrasts with the locomotor capabilities and feeding ecologies of other taxa studied to date. Our results indicate that this species relies on an initial stealthy approach, which is generally sufficient to capture prey (32 out of 44 trials). In cases where the initial approach is not sufficient to perform a capture attempt (12 out of 44 trials),
C. townsendii
continues its pursuit by reacting to prey movements in a manner best modelled with a combination of pure pursuit, or following prey directly, and proportional navigation, or moving to an interception point.
Why are biting flies attracted to blue objects?
Authors: Santer Roger D. , Akanyeti Otar , Endler John A. , Galván Ismael , Okal Michael N.
Published: June 2023

Diurnal biting flies are strongly attracted to blue objects. This behaviour is widely exploited for fly control, but its functional significance is debated. It is hypothesized that blue objects resemble animal hosts; blue surfaces resemble shaded resting places; and blue attraction is a by-product of attraction to polarized light. We computed the fly photoreceptor signals elicited by a large sample of leaf and animal integument reflectance spectra, viewed under open/cloudy illumination and under woodland shade. We then trained artificial neural networks (ANNs) to distinguish animals from leaf backgrounds, and shaded from unshaded surfaces, in order to find the optimal means of doing so based upon the sensory information available to a fly. After training, we challenged ANNs to classify blue objects used in fly control. Trained ANNs could make both discriminations with high accuracy. They discriminated animals from leaves based upon blue–green photoreceptor opponency and commonly misclassified blue objects as animals. Meanwhile, they discriminated shaded from unshaded stimuli using achromatic cues and never misclassified blue objects as shaded. We conclude that blue–green opponency is the most effective means of discriminating animals from leaf backgrounds using a fly's sensory information, and that blue objects resemble animal hosts through such mechanisms.
Soil moisture incidentally selects for microbes that facilitate locally adaptive plant response
Authors: Ricks Kevin D. , Yannarell Anthony C.
Published: June 2023

While a plant's microbiome can facilitate adaptive phenotypes, the plant's role in selecting for these microbes is unclear. Do plants actively recruit microbes beneficial to their current environment, or are beneficial microbes only an incidental by-product of microbial adaptation? We addressed these questions through a multigeneration greenhouse experiment, selecting for either dry- or wet-adapted soil microbial communities, either with or without plants. After three plant generations, we conducted a full reciprocal transplant of each soil community onto wet- and dry-treated plants. We found that plants generally benefited from soil microbes, and this benefit was greater whenever their current watering conditions matched the microbes' historical watering conditions. Principally, the plant's presence was not necessary in the historical treatments for this environmental matching benefit to emerge. Moreover, we found microbes from droughted soils could better tolerate drought stress. Taken together, these results suggest that the moisture environment selects for microbes that benefit plants under those specific moisture conditions, and that these beneficial properties arise as a by-product of microbial adaptation to the watering environment and not as a co-adapting plant–microbe system. This work highlights that understanding the selective agents on these plant-associated microbes will lead to a better understanding of plant adaptation.
Metagenomics analysis of mice gut to unravel the role of metal exposure and piperine
Authors: Kaur Ravidarshdeep , Rawal Rakesh
Published: June 2023

The gut and intestinal microbiota, consisting of trillions of microorganisms inhabiting the human gastrointestinal tract. It plays a crucial role in human health leading to understanding the dynamic crosstalk of host-microbe interaction in the gut and has become necessary for the detection, prevention, or therapy of diseases. Gut microbiota deviations are linked with many diseases, suggesting that various pathways involved in immunity, energy, lipid, and glucose metabolism are affected. Further, it is also altered by external insults such as metal toxicity, antibiotics and pesticides. Heavy metals like arsenic, mercury, cadmium and chromium are one of the well-studied classes of environmental pollutants. Mouse models have become the model of choice for most studies in this emerging field, as they allow perturbations in the gut microbiota to be studied in a controlled experimental setup. Here, we investigate the composition and diversity of intestinal microbes utilizing cecal samples from different intervention groups: arsenic exposure (As(III)), arsenic and piperine co-administration (As+Pp), piperine perse and control group. We obtained DNA samples from these groups and performed PCR amplification and sequencing of the 16S V3-V4 region. The sequencing data were analyzed utilizing bioinformatics tools and taxonomically categorized. The findings showed shift in microbial composition and abundance among different intervention groups, revealing taxa that may contribute to the microbial diversity.
Closed-loop Control of Functional Electrical Stimulation Using a Selectively Recording and Bidirectional Nerve Cuff Interface
Authors: Hwang Y. E. , Long L. , Filho J. Sales , Genov R. , Zariffa J.
Published: June 2023

Background

Discriminating recorded afferent neural information can provide sensory feedback for closed-loop control of functional electrical stimulation, which restores movement to paralyzed limbs. Previous work achieved state-of-the-art off-line classification of electrical activity in different neural pathways recorded by a multi-contact nerve cuff electrode, by applying deep learning to spatiotemporal neural patterns.

Objective

To incorporate this approach into closed-loop stimulation.

Methods

Acutein vivoexperiments were conducted on 11 Long Evans rats to demonstrate closed-loop stimulation. A 64-channel (8 × 8) nerve cuff electrode was implanted on each rat’s sciatic nerve for recording and stimulation. A convolutional neural network (CNN) was trained with spatiotemporal signal recordings associated with 3 different states of the hindpaw (dorsiflexion, plantarflexion, and pricking of the heel). After training, firing rates were reconstructed from the classifier outputs for each of the three target classes. A rule-based closed-loop controller was implemented to produce ankle movement trajectories using neural stimulation, based on the classified nerve recordings. Closed-loop stimulation was initiated by the detection of a heel prick, and induced dorsiflexion. The detection of dorsiflexion triggered stimulation to induce plantarflexion, and vice versa. A single trial began with a heel prick and ended when an incorrect state transition occurred or when a second heel prick was detected.

Results

Closed-loop stimulation was successfully demonstrated in 6 subjects. Number of successful trials per subject ranged from 1-17 and number of correct state transitions per trial ranged from 3-53.

Conclusion

This work demonstrates that a CNN applied to multi-contact nerve cuff recordings can be used for closed-loop control of functional electrical stimulation.
Dysregulation of Neuroprotective Lipoxin Pathway in Astrocytes in Response to Cytokines and Ocular Hypertension
Authors: Karnam Shruthi , Maurya Shubham , Ng Elainna , Choudhary Amodini , Thobani Arzin , Flanagan John G , Gronert Karsten
Published: June 2023

Glaucoma leads to vision loss due to retinal ganglion cell death. Astrocyte reactivity contributes to neurodegeneration. Our recent study found that lipoxin B4(LXB4), produced by retinal astrocytes, has direct neuroprotective actions on retinal ganglion cells. In this study, we aimed to investigate how the autacoid LXB4influences astrocyte activity in the retina under inflammatory cytokine-induced activation and during ocular hypertension. The protective activity of LXB4was investigatedin vivousing the mouse silicone-oil model of chronic ocular hypertension (n=40). By employing a range of analytical techniques, including bulk RNA-seq, RNAscope in-situ hybridization, qPCR, and lipidomic analyses, we discovered the formation of lipoxins and expression of the lipoxin pathway in rodents (including the retina and optic nerve), primates (optic nerve), and human brain astrocytes, indicating the presence of this neuroprotective pathway across various species. Findings in the mouse retina identified significant dysregulation of the lipoxin pathway in response to chronic ocular hypertension, leading to an increase in 5- lipoxygenase (5-LOX) activity and a decrease in 15-LOX activity. This dysregulation was coincident with a marked upregulation of astrocyte reactivity. Reactive human brain astrocytes also showed a significant increase in 5-LOX. Treatment with LXB4amplified the lipoxin biosynthetic pathway by restoring and amplifying the generation of another member of the lipoxin family, LXA4, and mitigated astrocyte reactivity in mouse retinas and human brain astrocytes. In conclusion, the lipoxin pathway is functionally expressed in rodents, primates, and human astrocytes, and is a resident neuroprotective pathway that is downregulated in reactive astrocytes. Novel cellular targets for LXB4’s neuroprotective action are inhibition of astrocyte reactivity and restoration of lipoxin generation. Amplifying the lipoxin pathway is a potential target to disrupt or prevent astrocyte reactivity in neurodegenerative diseases, including retinal ganglion cell death in glaucoma.
Cellular-resolution gene expression mapping reveals organization in the head ganglia of the gastropod,Berghia stephanieae
Authors: Ramirez M. Desmond , Bui Thi N. , Katz Paul S.
Published: June 2023

Gastropod molluscs such asAplysia,Lymnaea, andTritoniahave been important for determining fundamental rules of motor control, learning, and memory because of their large, individually identifiable neurons. Yet for the vast majority of gastropod neurons, as well as glia, there are no established molecular markers, limiting the ability to establish brain-wide structure-function relations. Here we combine high-throughput, single-cell RNA sequencing (scRNAseq) within-situhybridization chain reaction (HCR) in the nudibranchBerghia stephanieaeto identify and visualize the expression of markers for cell types. Broad neuronal classes were characterized by genes associated with neurotransmitters, like acetylcholine, glutamate, serotonin, and GABA, as well as neuropeptides. These classes were subdivided by other genes including transcriptional regulators and unannotated genes. Marker genes expressed by neurons and glia formed discrete, previously unrecognized regions within and between ganglia. This study provides the foundation for understanding the fundamental cellular organization of gastropod nervous systems.
A fast, reproducible, high-throughput variant calling workflow for evolutionary, ecological, and conservation genomics
Authors: Mirchandani Cade D. , Shultz Allison J. , Thomas Gregg W.C. , Smith Sara J. , Baylis Mara , Arnold Brian , Corbett-Detig Russ , Enbody Erik , Sackton Timothy B.
Published: June 2023

The increasing availability of genomic resequencing datasets and high quality reference genomes across the tree of life present exciting opportunities for comparative population genomic studies. However, substantial challenges prevent the simple reuse of data across different studies and species, arising from variability in variant calling pipelines, data quality, and the need for computationally intensive reanalysis. Here, we present snpArcher, a flexible and highly efficient workflow designed for the analysis of genomic resequencing data in non-model organisms. snpArcher provides a standardized variant calling pipeline and includes modules for variant quality control, data visualization, variant filtering, and other downstream analysis.Implemented in Snakemake, snpArcher is user-friendly, reproducible, and designed to be compatible with HPC clusters and cloud environments. To demonstrate the flexibility of this pipeline, we applied snpArcher to 26 public resequencing datasets from non-mammalian vertebrates. These variant datasets are hosted publicly to enable future comparative population genomic analyses. With its extensibility and the availability of public datasets, snpArcher will contribute to a broader understanding of genetic variation across species by facilitating rapid use and reuse of large genomic datasets.
High performers demonstrate greater neural synchrony than low performers across behavioral domains
Authors: Chamberlain Taylor A. , Corriveau Anna , Song Hayoung , Kwon Young Hye , Yoo Kwangsun , Chun Marvin M. , Rosenberg Monica D.
Published: June 2023

Heterogeneity in brain activity gives rise to heterogeneity in behavior, which in turn comprises our distinctive characteristics as individuals. Studying the path from brain to behavior, however, often requires making assumptions about how similarity in behavior scales with similarity in brain activity. Here, we expand upon recent work which proposes a theoretical framework for testing the validity of such assumptions. Using intersubject representational similarity analysis in two independent movie-watching fMRI datasets, we probe how brain-behavior relationships vary as a function of behavioral domain and participant sample. We find evidence that, in some cases, the neural similarity of two individuals is not correlated with behavioral similarity. Rather, individuals with higher behavioral scores are more similar to other high scorers whereas individuals with lower behavioral scores are dissimilar from everyone else. Ultimately, our findings motivate a more extensive investigation of both the structure of brain-behavior relationships and the tacit assumption that people who behave similarly will demonstrate shared patterns of brain activity.
Tessellation of artificial touch via microstimulation of human somatosensory cortex
Authors: Greenspon Charles M. , Shelchkova Natalya D. , Valle Giacomo , Hobbs Taylor G. , Berger-Wolf Ev I. , Hutchison Brianna C. , Dogruoz Efe , Verbarschott Ceci , Callier Thierri , Sobinov Anton R. , Okorokova Elizaveta V. , Jordan Patrick M. , Prasad Dillan , He Qinpu , Liu Fang , Kirsch Robert F. , Miller Jonathan P. , Lee Ray C. , Satzer David , Gonzalez-Martinez Jorge , Warnke Peter C. , Miller Lee E. , Boninger Michael L. , Ajiboye Abidemi B. , Graczyk Emily L. , Downey John E. , Collinger Jennifer L. , Hatsopoulos Nicholas G. , Gaunt Robert A. , Bensmaia Sliman J.
Published: June 2023

When we interact with objects, we rely on signals from the hand that convey information about the object and our interaction with it. A basic feature of these interactions, the locations of contacts between the hand and object, is often only available via the sense of touch. Information about locations of contact between a brain-controlled bionic hand and an object can be signaled via intracortical microstimulation (ICMS) of somatosensory cortex (S1), which evokes touch sensations that are localized to a specific patch of skin. To provide intuitive location information, tactile sensors on the robotic hand drive ICMS through electrodes that evoke sensations at skin locations matching sensor locations. This approach requires that ICMS-evoked sensations be focal, stable, and distributed over the hand. To systematically investigate the localization of ICMS-evoked sensations, we analyzed the projected fields (PFs) of ICMS-evoked sensations – their location and spatial extent – from reports obtained over multiple years from three participants implanted with microelectrode arrays in S1. First, we found that PFs vary widely in their size across electrodes, are highly stable within electrode, are distributed over large swaths of each participant’s hand, and increase in size as the amplitude or frequency of ICMS increases. Second, while PF locations match the locations of the receptive fields (RFs) of the neurons near the stimulating electrode, PFs tend to be subsumed by the corresponding RFs. Third, multi-channel stimulation gives rise to a PF that reflects the conjunction of the PFs of the component channels. By stimulating through electrodes with largely overlapping PFs, then, we can evoke a sensation that is experienced primarily at the intersection of the component PFs. To assess the functional consequence of this phenomenon, we implemented multi-channel ICMS-based feedback in a bionic hand and demonstrated that the resulting sensations are more localizable than are those evoked via single-channel ICMS.
Mechanistic basis for nigericin-induced NLRP1 inflammasome activation in human epithelial cells
Authors: Rozario Pritisha , Pinilla Miriam , Vind Anna Constance , Robinson Kim S. , Ann Toh Gee , Firdaus Muhammad Jasrie , Martínez José Francisco , Zhewang Lin , Bekker-Jensen Simon , Meunier Etienne , Zhong Franklin
Published: June 2023

Nigericin, an ionophore derived fromStreptomyces hygroscopicus, is arguably the most commonly used tool compound to study the NLRP3 inflammasome. Recent findings, however, showed that nigericin also activates the NLRP1 inflammasome in human keratinocytes. In this study, we resolve the mechanistic basis of nigericin-driven NLRP1 inflammasome activation. In multiple non-hematopoietic cell types, nigericin rapidly and specifically inhibits the elongation stage of the ribosome cycle by depleting cytosolic potassium ions. This activates the ribotoxic stress response (RSR) sensor kinase ZAKɑ, p38 and JNK, as well as the hyperphosphorylation of the NLRP1 linker domain. As a result, nigericin-induced pyroptosis in human keratinocytes is blocked by extracellular potassium supplementation, ZAKɑ knockout or pharmacologic inhibitors of ZAKɑ and p38 kinase activities. By surveying a diverse panel of ionophores, we show that the electroneutrality of potassium efflux is essential to activate ZAKɑ-driven RSR, likely because a greater extent of K+ depletion is necessary to activate ZAKɑ-NLRP1 than NLRP3. These findings resolve the mechanism by which nigericin activates NLRP1 in nonhematopoietic cell types and demonstrate an unexpected connection between RSR, perturbations of potassium ion flux and innate immunity.

GRAPHICAL ABSTRACT

SIGNIFICANCE

Nigericin is familiar to the inflammasome field as the most robust and commonly used NLRP3 inducer. It has enabled numerous breakthroughs in the field linking NLRP3 activation to potassium efflux. In this manuscript, we report that nigericin activates an alternate inflammasome sensor, NLRP1 in primary human skin, nasal and corneal epithelial cells. NLRP1 activation by nigericin requires K+ efflux-driven ribosome stalling and the ribotoxic stress response (RSR) sensor MAP3K, ZAKɑ. We further identify the key biophysical principles that explain why only a subset of K+ ionophores, exemplified by nigericin, function as ‘super’ inflammasome agonists that can activate either NLRP1 or NLRP3, depending on cell type. These results reveal an unexpected connection between RSR, potassium ion flux and innate immunity.
Deficiency of IQCH causes male infertility in humans and mice
Authors: Ruan Tiechao , Zhou Ruixi , Yang Yihong , Guo Junchen , Jiang Chuan , Wang Xiang , Shen Gan , Dai Siyu , Chen Suren , Shen Ying
Published: June 2023

IQ motif-containing proteins can be recognized by calmodulin (CaM) and are essential for many biological processes. However, the role of IQ motif-containing proteins in spermatogenesis is largely unknown. In this study, we identified a loss-of-function mutation in the novel gene IQ motif-containing H (IQCH) in a Chinese family with male infertility characterized by a cracked flagellar axoneme and abnormal mitochondrial structure. To verify the function of IQCH,Iqchknockout (KO) mice were generated via CRISPR-Cas9 technology. As expected, theIqchKO male mice exhibited impaired fertility, which was related to deficient acrosome activity and abnormal structures of the axoneme and mitochondria, mirroring the patient phenotypes. Mechanistically, IQCH can bind to CaM and subsequently regulate the expression of RNA-binding proteins (especially HNRPAB), which are indispensable for spermatogenesis. Overall, this study revealed the function of IQCH, expanded the role of IQ motif-containing proteins in reproductive processes, and provided important guidance for genetic counseling and genetic diagnosis of male infertility.
Novel mouse model of Weaver syndrome displays overgrowth and excess osteogenesis reversible with KDM6A/6B inhibition
Authors: Gao Christine W , Lin WanYing , Riddle Ryan C , Kushwaha Priyanka , Boukas Leandros , Björnsson Hans T , Hansen Kasper D , Fahrner Jill A
Published: June 2023

Weaver syndrome is a Mendelian disorder of the epigenetic machinery (MDEM) caused by germline pathogenic variants inEZH2, which encodes the predominant H3K27 methyltransferase and key enzymatic component of Polycomb repressive complex 2 (PRC2). Weaver syndrome is characterized by striking overgrowth and advanced bone age, intellectual disability, and distinctive facies. We generated a mouse model for the most common Weaver syndrome missense variant,EZH2p.R684C.Ezh2R684C/R684Cmouse embryonic fibroblasts (MEFs) showed global depletion of H3K27me3.Ezh2R684C/+mice had abnormal bone parameters indicative of skeletal overgrowth, andEzh2R684C/+osteoblasts showed increased osteogenic activity. RNA-seq comparing osteoblasts differentiated fromEzh2R684C/+andEzh2+/+bone marrow mesenchymal stem cells (BM-MSCs) indicated collective dysregulation of the BMP pathway and osteoblast differentiation. Inhibition of the opposing H3K27 demethylases Kdm6a/6b substantially reversed the excessive osteogenesis inEzh2R684C/+cells both at the transcriptional and phenotypic levels. This supports both the ideas that writers and erasers of histone marks exist in a fine balance to maintain epigenome state, and that epigenetic modulating agents have therapeutic potential for the treatment of MDEMs.
Multi-night naturalistic cortico-basal recordings reveal mechanisms of NREM slow wave suppression and spontaneous awakenings in Parkinson’s disease
Authors: Anjum Md Fahim , Smyth Clay , Dijk Derk-Jan , Starr Philip , Denison Timothy , Little Simon
Published: June 2023

Background

Sleep disturbance is a prevalent and highly disabling comorbidity in individuals with Parkinson’s disease (PD) that leads to worsening of daytime symptoms, accelerated disease progression and reduced quality of life.

Objectives

We aimed to investigate changes in sleep neurophysiology in PD particularly during non-rapid eye movement (NREM) sleep, both in the presence and absence of deep brain stimulation (DBS).

Methods

Multi-night (n=58) intracranial recordings were performed at-home, from chronic electrocorticography and subcortical electrodes, with sensing-enabled DBS pulse generators, paired with portable polysomnography. Four people with PD and one person with cervical dystonia were evaluated to determine the neural structures, signals and connections modulated during NREM sleep and prior to spontaneous awakenings. Recordings were performed both ON and OFF DBS in the presence of conventional dopaminergic replacement medications.

Results

We demonstrate an increase in cortico-basal slow wave activity in delta (1-4 Hz) and a decrease in beta (13-31 Hz) during NREM (N2 and N3) versus wakefulness in PD. Cortical-subcortical coherence was also found to be higher in the delta range and lower in the beta range during NREM versus wakefulness. DBS stimulation resulted in a further elevation in cortical delta and a decrease in alpha (8-13 Hz) and low beta (13-15 Hz) power compared to the OFF stimulation state. During NREM sleep, we observed a strong inverse interaction between subcortical beta and cortical slow wave activity and found that subcortical beta increases prior to spontaneous awakenings.

Conclusions

Chronic, multi-night recordings in PD reveal opposing sleep stage specific modulations of cortico-basal slow wave activity in delta and subcortical beta power and connectivity in NREM, effects that are enhanced in the presence of DBS. Within NREM specifically, subcortical beta and cortical delta are strongly inversely correlated and subcortical beta power is found to increase prior to and predict spontaneous awakenings. We find that DBS therapy appears to improve sleep in PD partially through direct modulation of cortico-basal beta and delta oscillations. Our findings help elucidate a contributory mechanism responsible for sleep disturbances in PD and highlight potential biomarkers for future precision neuromodulation therapies targeting sleep and spontaneous awakenings.
Field phenomics reveals genetic variation for transpiration response to vapor pressure deficit in sorghum
Authors: Raymundo Rubí , Wang Xu , Felderhoff Terry , Sexton-Bowser Sarah , Poland Jesse , Lipka Alexander E. , Morris Geoffrey P.
Published: June 2023

Drought adaptation for water-limited environments relies on traits that optimize plant water budgets. Limited transpiration (LT) reduces water demand under high vapor pressure deficit (VPD) (i.e., dry air condition), conserving water for efficient use during the reproductive stage. Although studies in controlled environments report genetic variation for LT, confirming its replicability in field conditions is critical for developing water-resilient crops. Here we test the existence of genetic variation for LT in sorghum in field trials and whether canopy temperature (TC) is a surrogate method to discriminate this trait. We phenotyped transpiration response to VPD (TR-VPD) via stomatal conductance (gs), canopy temperature (TC) from fixed IRT sensors (TCirt), and unoccupied aerial system thermal imagery (TCimg) in 11 genotypes. Replicability among phenomic approaches for three genotypes revealed genetic variability for TR-VPD. Genotypes BTx2752 and SC979 carry the LT trait, while genotype DKS54-00 has the non-LT trait. TCcan determine differences in TR-VPD. However, the broad sense heritability (H2) and correlations suggest that canopy architecture and stand count hampers TCirtand TCimgmeasurement. Unexpectedly, observations of gsand VPD showed non-linear patterns for genotypes with LT and non-LT traits. Our findings provide further insights into the genetics of plant water dynamics.
Assembly of tight junction belts by surface condensation and actin elongation
Authors: Sun Daxiao , Zhao Xueping , Wiegand Tina , Bartolucci Giacomo , Martin-Lemaitre Cecilie , Grill Stephan W. , Hyman Anthony A. , Weber Christoph , Honigmann Alf
Published: June 2023

Formation of biomolecular condensates via phase separation enables compartmentation of many cellular processes. However, how cells can control condensation at specific locations to create complex cellular structures remains poorly understood. Here, we investigated the mechanism of tight junction formation, which involves condensation of scaffold proteins at cell-cell contacts and elongation of the condensates into a belt around the cellular perimeter. Using cell biology, reconstitution, and thermodynamic theory, we discovered that cells use surface phase transitions to control local condensation at the membrane far below bulk saturation. Surface condensation of junctional ZO-scaffold proteins is mediated by receptor binding and regulated by the receptor’s oligomerization state. Functionally, ZO surface condensation is directly coupled to actin polymerization and bundling, which drives elongation of receptor-ZO-actin condensates similar to tight junction belt formation in cells. We conclude that surface phase transitions provide a robust mechanism to control the position and shape of protein condensates.

One-Sentence Summary

Local surface binding of cytosolic scaffold proteins provides spatial control of protein condensation to assemble adhesion junctions.
Rethinking simultaneous suppression in visual cortex via compressive spatiotemporal population receptive fields
Authors: Kupers Eline R , Kim Insub , Grill-Spector Kalanit
Published: June 2023

1

When multiple visual stimuli are presented simultaneously in the receptive field, the neural response is suppressed compared to presenting the same stimuli sequentially. The prevailing hypothesis suggests that this suppression is due to competition among multiple stimuli for limited resources within receptive fields, governed by task demands. However, it is unknown how stimulus-driven computations may give rise to simultaneous suppression. Using fMRI, we find simultaneous suppression in single voxels, which varies with both stimulus size and timing, and progressively increases up the visual hierarchy. Using population receptive field (pRF) models, we find that compressive spatiotemporal summation rather than compressive spatial summation predicts simultaneous suppression, and that increased simultaneous suppression is linked to larger pRF sizes and stronger compressive nonlinearities. These results necessitate a rethinking of simultaneous suppression as the outcome of stimulus-driven compressive spatiotemporal computations within pRFs, and open new opportunities to study visual processing capacity across space and time.
Antimicrobial Evaluation ofSalvadora persicaMethanolic Stem Extract andIn vivoModelling of its Identified Constituting Compounds Revealed Antibacterial Effect of 2-[(5-Iodosalicylidene)hydrazino]-4-morpholino-6-(1-pyrrolidinyl)-1,3,5-triazine in the Treatment of Dental Plague
Authors: Adigun Temidayo Olamide , Muhammed Maikarfi , Funmilayo Adisa Mofoluwaso , Alli Abdulhameed Oluwatomi , Olufunke Fagboro Oluwayemisi , Oluwatosin Oyebamiji Samson , Ayodeji Akinsehinwa Samuel , Oyebola Aina Kehinde
Published: June 2023

Challenges of resistance to synthetic antimicrobials have opened new vistas in the search for natural products. This research rigorously reviews plant used in oral health. The antimicrobial activities ofSalvadora persicacommonly used as chewing stick was investigated against 3 clinical strains ofEscherichia coli, Staphylococcus aureus, Aspergillus nigar. The antibacterial and antifungal activities of the extracts were determined using the agar well diffusion.Salvadora persica, was active against all the isolates especially on the bacteria with a MIC and MBC of 12.5mg/mL and 25mg/mL respectively. Phytochemical screening revealed the presence of alkaloids, tannins, flavonoids, saponins and traces of terpenoids.In silicomodelling of the compounds identified in the chewing stick extract reveals that the aromatic nitrogen-rich compound with PubChem ID: 135580681 is likely responsible for the mechanistic inhibition associated with antibacterial effect of the plant material against dental plagues
Proteasome condensate formation is driven by multivalent interactions with shuttle factors and K48-linked ubiquitin chains
Authors: Waite Kenrick A. , Vontz Gabrielle , Lee Stella Y. , Roelofs Jeroen
Published: June 2023

Stress conditions can cause the relocalization of proteasomes to condensates in yeast and mammalian cells. The interactions that facilitate the formation of proteasome condensates, however, are unclear. Here, we show that the formation of proteasome condensates in yeast depends on long K48-linked ubiquitin chains together with the proteasome shuttle factors Rad23 and Dsk2. These shuttle factors colocalize to these condensates. Strains deleted for the third shuttle factor gene,DDI1, show proteasome condensates in the absence of cellular stress, consistent with the accumulation of substrates with long K48-linked ubiquitin chains that accumulate in this mutant. We propose a model where the long K48-linked ubiquitin chains function as a scaffold for the ubiquitin binding domains of the shuttle factors and the proteasome, allowing for the multivalent interactions that further drive condensate formation. Indeed, we determined different intrinsic ubiquitin receptors of the proteasome (Rpn1, Rpn10, and Rpn13) are critical under different condensate inducing conditions. In all, our data support a model where the cellular accumulation of substrates with long ubiquitin chains, potentially due to reduced cellular energy, allows for proteasome condensate formation. This suggests that proteasome condensates are not simply for proteasome storage, but function to sequester soluble ubiquitinated substrates together with inactive proteasomes.

Significance

Stress conditions can cause the relocalization of proteasomes to condensates in yeast as well as mammalian cells. Our work shows that the formation of proteasome condensates in yeast depends on long K48-linked ubiquitin chains, the proteasome binding shuttle factors Rad23 and Dsk2 and proteasome intrinsic ubiquitin receptors. Here, different receptors are critical for different condensate inducers. These results indicate distinct condensates can form with specific functionality. Our identification of key factors involved in the process is crucial for understanding the function of proteasome relocalization to condensates. We propose that cellular accumulation of substrates with long ubiquitin chains results in the formation of condensates comprising those ubiquitinated substrates, proteasomes, and proteasome shuttle factors, where the ubiquitin chains serve as the scaffold for condensate formation.
Intrinsically Disordered Regions Promote Protein Refoldability and Facilitate Retrieval from Biomolecular Condensates
Authors: To Philip , Bhagwat Atharva M. , Tarbox Haley E. , Ecer Ayse , Wendorff Hannah , Jamieson Zanya , Trcek Tatjana , Fried Stephen D.
Published: June 2023

Many eukaryotic proteins contain intrinsically disordered regions (IDRs) that intersperse globular folded domains, in contrast with bacterial proteins which are typically highly globular1, 2. Recent years have seen great progress in identifying biological functions associated with these elusive protein sequence: in specific cases, they mediate liquid liquid phase separation3, perform molecular recognition4, or act as sensors to changes in the environment5. Nevertheless, only a small number of IDRs have annotated functions6despite their presence in 64% of yeast proteins,7stimulating some to question what ‘general purpose’ they may serve8, 9. Here, by interrogating the refoldability of two fungal proteomes (Saccharomyces cerevisiaeandNeurosporra crassa), we show that IDRs render their host proteins more refoldable from the denatured state, allowing them to cohere more closely to Anfinsen’s thermodynamic hypothesis10, 11. The data provide an exceptionally clear picture of which biophysical and topological characteristics enable refoldability. Moreover, we find that almost all yeast proteins that partition into stress granules during heat shock are refoldable, a finding that holds for other condensates such as P-bodies and the nucleolus. Finally, we find that the Hsp104 unfoldase12is the principal actor in mediating disassembly of heat stress granules and that the efficiency with which condensed proteins are returned to the soluble phase is also well explained by refoldability. Hence, these studies establish spontaneous refoldability as an adaptive trait that endows proteins with the capacity to reform their native soluble structures following their extraction from condensates. Altogether, our results provide an intuitive model for the function of IDRs in many multidomain proteins and clarifies their relationship to the phenomenon of biomolecular condensation.
Folate receptor overexpression shortensC. eleganslifespan by impeding adaptation to microbial metabolism
Authors: Shrestha Bideep , Tallila Milla , Matilainen Olli
Published: June 2023

Folate receptor (FR) alpha and beta (FRα and FRβ) are membrane-anchored transporters that mediate folate uptake through endocytosis. Unlike other folate transporters, FRs are expressed at low levels in normal tissues, while their expression is strongly increased in several cancers. In addition to its canonical role in folate transport, FRα, the most studied FR, also regulates signaling pathways unrelated to folate- or one-carbon metabolism. Nevertheless, it is not known how loss of folate receptors, or their overexpression, affects health- and lifespan. To elucidate this, we utilizedCaenorhabditis elegans, in which FOLR-1 is the sole homolog of folate receptors. Interestingly, loss of FOLR-1 does not affect reproduction, fitness, proteostasis or lifespan, indicating that it is not required for folate transport to maintain health. Strikingly, in contrast tofolr-1depletion,folr-1overexpression shortens lifespan in a coculturedE. colistrain-dependent manner. Furthermore, we found thatfolr-1overexpression blunts the lifespan extension upon treatment with sulfamethoxazole, a sulfonamide that promotes longevity by limiting folate inE. coli. These data suggest that animals overexpressingfolr-1are deficient in their ability to adapt to changes in microbial metabolism, thus revealing an intriguing and non-canonical role of FR in lifespan regulation. Therefore, this work could serve as a basis for further studies to elucidate the organismal effects of abnormal FR expression in diseases such as cancer.

Author Summary

Folate receptors (FRs) differ from other folate transporters based on, for example, these two things: their expression is strongly restricted, and they can regulate intracellular cellular processes independently of folate- and one-carbon metabolism (OCM). Interestingly, FRs have an essential role in embryonic development, but on the other hand, their overexpression in cancer have been shown to reduce patient survival. Apart from development and disease, the role of FRs in aging remains unknown. By utilizingC. elegans, we show that FOLR-1 (FR homolog inC. elegans) is not required to maintain normal physiology, whereas its overexpression shortens lifespan through a mechanism dependent on cocultured bacteria. Since cocultured bacteria constitute theC. elegansgut microbiota, this study places elevated FR expression as a link between gut commensal bacteria and organism’s lifespan, raising the intriguing question of whether the same mechanism applies in cancer.
The role of micropyle for grass pea germination
Authors: Wiraguna Edi
Published: June 2023

Purpose

This study aims to identify the location of the micropyle, the role of the micropyle in seed germination and the association between the micropyle size and seed weight of grass peas.

Design/methodology/approach

First, the micropyle was identified by cutting the seed in half and observing the seeds under the electron microscope. Second, the micropyle was covered by lanolin to block water imbibition. The rate of imbibition and germination was then observed. Lastly, micropyle sizes of various grass pea genotypes were identified by capturing seed images under a light microscope and converting the sizes to mm2 using computer software (ImageJ).

Findings

The location of micropyle was located nearby the hilum, similar to soybean seeds. Seed imbibition was significantly lower in lanolin application (<87%) than in the control (>124%) after 24 hours of submergence. Germination was a day delay for lanolin application on the micropyle compared to lanolin application on the non-micropyle. The germination delay resulted in a significantly lower germination percentage at <57% on the micropyle lanolin application than at >79% on the non-micropyle lanolin application after 10 days of sowing. There is no correlation between the micropyle size and seed weight.

Originality/value

These findings add information on the location and the role of the micropyle for grass pea seed germination.
The impact of board gender diversity on financial performance: a systematic review and agenda for future research
Authors: Hazaea Saddam A. , Al-Matari Ebrahim Mohammed , Farhan Najib H.S. , Zhu Jinyu
Published: June 2023

Purpose

In recent years, mandatory rules and regulations were issued to stress the importance of increasing gender diversity in companies, assuming that gender diversity would enhance financial performance. Thus, the purpose of this paper is to review recent research concerning board gender diversity and its impact on financial performance for the period of 2002 to 2022.

Design/methodology/approach

Using the Web of Science and Scopus databases, 152 studies were analyzed, out of 91 high-impact journals. The analysis focuses on discussing the moderating, mediating and controlling variables and exploring the theories and theoretical foundations that are most prevalent in the literature.

Findings

The findings indicated an incompatibility between the results of the studies on the impact of gender diversity on financial performance. In addition, results showed the majority of studies focused on discussing the controlling variables associated with the company compared to the variables related to employees or the surrounding environment. On the other hand, the results also showed widespread use of the theoretical basis with the development of new theories in the recent period in parallel with the increase in the literature.

Originality/value

The results of this study help to reconcile the findings of the different and conflicting literature by presenting the perception that the efficacy of the positive impact of gender diversity on financial performance is related to several organizational and environmental factors that companies have to consider.