Association of Basal Forebrain Volume with Amyloid, Tau, and Cognition in Alzheimer's Disease.

Background: Degeneration of cholinergic basal forebrain (BF) neurons characterizes Alzheimer's disease (AD). However, what role the BF plays in the dynamics of AD pathophysiology has not been investigated precisely. Objective: To investigate the baseline and longitudinal roles of BF along with core neuropathologies in AD. Methods: In this retrospective cohort study, we enrolled 113 subjects (38 amyloid [Aß]-negative cognitively unimpaired, 6 Aß-positive cognitively unimpaired, 39 with prodromal AD, and 30 with AD dementia) who performed brain MRI for BF volume and cortical thickness, 18F-florbetaben PET for Aß, 18F-flortaucipir PET for tau, and detailed cognitive testing longitudinally. We investigated the baseline and longitudinal association of BF volume with Aß and tau standardized uptake value ratio and cognition. Results: Cross-sectionally, lower BF volume was not independently associated with higher cortical Aß, but it was associated with tau burden. Tau burden in the orbitofrontal, insular, lateral temporal, inferior temporo-occipital, and anterior cingulate cortices were associated with progressive BF atrophy. Lower BF volume was associated with faster Aß accumulation, mainly in the prefrontal, anterior temporal, cingulate, and medial occipital cortices. BF volume was associated with progressive decline in language and memory functions regardless of baseline Aß and tau burden. Conclusions: Tau deposition affected progressive BF atrophy, which in turn accelerated amyloid deposition, leading to a vicious cycle. Also, lower baseline BF volume independently predicted deterioration in cognitive function.

Computed tomography scanning revealed macropore-controlled N2O emissions under long-term tillage and cover cropping practices.

Microscale alterations in soil physical characteristics resulting from long-term soil health practices can contribute to changes in soil nitrous oxide (N2O) emissions. In this study, we investigated soil N2O emissions in relation to pore characteristics influencing soil gas diffusivity under long-term tillage and cover cropping practices. Intact soil cores from tillage (conventional tillage, Conv. T versus no tillage, NT) and cover crop (hairy vetch, HV versus no cover crop, NC) treatments were used for N2O measurements and computed tomography (CT) scanning. Using X-ray CT technique with a resolution of 59 µm, pore structure parameters including macroporosity, number of macropores, anisotropy, fractal dimension, tortuosity, and connectivity were determined. The results showed that Conv. T and HV emitted significantly higher N2O than NT and NC, respectively. A similar trend was observed for macroporosity, Conv. T soils had 27.4 % higher CT-derived macroporosity than the NT soils and HV increased macroporosity by 31.1 % over the NC treatment. The number of macropores and fractal dimension were significantly higher whereas degree of anisotropy was significantly lower under HV compared to NC. In the upper 3 cm of soil, HV had a connected porosity, whereas the pores were disconnected and isolated in NC. These CT-derived properties; however, were not impacted by tillage treatments. N2O emissions were positively and significantly correlated to relative soil gas diffusivity, CT-derived macroporosity, number of macropores, and fractal dimension. Our results demonstrated that soil macroporosity and relative gas diffusivity could lead to improved understanding and predictability of N2O emissions under high soil moisture conditions.

Methods to Isolate Muscle Stem Cells for Cell-Based Cultured Meat Production: A Review.

Cultured meat production relies on various cell types, including muscle stem cells (MuSCs), embryonic stem cell lines, induced pluripotent cell lines, and naturally immortalized cell lines. MuSCs possess superior muscle differentiation capabilities compared to the other three cell lines, making them key for cultured meat development. Therefore, to produce cultured meat using MuSCs, they must first be effectively separated from muscles. At present, the methods used to isolate MuSCs from muscles include (1) the pre-plating method, using the ability of cells to adhere differently, which is a biological characteristic of MuSCs; (2) the density gradient centrifugation method, using the intrinsic density difference of cells, which is a physical characteristic of MuSCs; and (3) fluorescence- and magnetic-activated cell sorting methods, using the surface marker protein on the cell surface of MuSCs, which is a molecular characteristic of MuSCs. Further efficient and valuable methods for separating MuSCs are expected to be required as the cell-based cultured meat industry develops. Thus, we take a closer look at the four methods currently in use and discuss future development directions in this review.

Oral-diadochokinesis between Parkinson's disease and neurotypical elderly among Malaysian-Malay speakers.

BACKGROUND: Parkinson's disease (PD) has an impact on speech production, manifesting in various ways including alterations in voice quality, challenges in articulating sounds and a decrease in speech rate. Numerous investigations have been conducted to ascertain the oral-diadochokinesis (O-DDK) rate in individuals with PD. However, the existing literature lacks exploration of such O-DDK rates in Malaysia and does not provide consistent evidence regarding the advantage of real-word repetition. AIMS: To explore the effect of gender, stimuli type and PD status and their interactions on the O-DDK rates among Malaysian-Malay speakers. METHODS & PROCEDURES: O-DDK performance of 62 participants (29 individuals with PD and 33 healthy elderly) using a non-word ('pataka'), a Malay real-word ('patahkan') and an English real-word ('buttercake') was audio recorded. The number of syllables produced in 8 s was counted. A hierarchical linear modelling was performed to investigate the effects of stimuli type (non-word, Malay real-word, English real-word), PD status (yes, no), gender (male, female) and their interactions on the O-DDK rate. The model accounted for participants' age as well as the nesting of repeated measurements within participants, thereby providing unbiased estimates of the effects. OUTCOMES & RESULTS: The stimuli effect was significant (p < 0.0001). Malay real-word showed the lowest O-DDK rate (5.03 ± 0.11 syllables/s), followed by English real-word (5.25 ± 0.11 syllables/s) and non-word (5.42 ± 0.11 syllables/s). Individuals with PD showed a significantly lower O-DDK rate compared to healthy elderly (4.73 ± 0.15 syllables/s vs. 5.74 ± 0.14 syllables/s, adjusted p < 0.001). A subsequent analysis indicated that the O-DDK rate declined in a quadratic pattern. However, neither gender nor age effects were observed. Additionally, no significant two-way interactions were found between stimuli type, PD status and gender (all p > 0.05). Therefore, the choice of stimuli type has no or only limited effect considering the use of O-DDK tests in clinical practice for diagnostic purposes. CONCLUSIONS & IMPLICATIONS: The observed slowness in O-DDK among individuals with PD can be attributed to the impact of the movement disorder, specifically bradykinesia, on the physiological aspects of speech production. Speech-language pathologists can gain insights into the impact of PD on speech production and tailor appropriate intervention strategies to address the specific needs of individuals with PD according to disease stages. WHAT THIS PAPER ADDS: What is already known on this subject The observed slowness in O-DDK rates among individuals with PD may stem from the movement disorder's effects on the physiological aspects of speech production, particularly bradykinesia. However, there is a lack of consistent evidence regarding the influence of real-word repetition and how O-DDK rates vary across different PD stages. What this study adds to existing knowledge The O-DDK rates decline in a quadratic pattern as the PD progresses. The research provides insights into the advantage of real-word repetition in assessing O-DDK rates, with Malay real-word showing the lowest O-DDK rate, followed by English real-word and non-word. What are the potential or actual clinical implications of this work? Speech-language pathologists can better understand the evolving nature of speech motor impairments as PD progresses. This insight enables them to design targeted intervention strategies that are sensitive to the specific needs and challenges associated with each PD stage. This finding can guide clinicians in selecting appropriate assessment tools for evaluating speech motor function in PD patients.

Effect of Crude Polysaccharides from Ecklonia cava Hydrolysate on Cell Proliferation and Differentiation of Hanwoo Muscle Stem Cells for Cultured Meat Production.

Ecklonia cava, a brown seaweed native to the East Asian coast, is known for its unique composition, including polysaccharides, polyphenols, and phlorotannins. Fucoidan is a sulfated polysaccharide widely used as a functional ingredient in foods. This study obtained crude polysaccharides (ECC_CPS) from E. cava celluclast enzymatic hydrolysate using ethanol precipitation. ECC_CPS increased cell viability during the proliferation of Hanwoo muscle satellite cells (HMSCs). The effect of ECC_CPS on the expression of proliferation-related markers was confirmed as MYF5 and MYOD expression significantly increased, whereas PAX7 expression was maintained. The evaluation of cell migration activity has a major impact on cell proliferation and differentiation, and the cell migration index significantly increased with ECC_CPS treatment (p < 0.01). This was related to the HGF/MET pathway and FAK pathway. Treatment with ECC_CPS promoted differentiation at the cell differentiation stage, thereby increasing the expression of differentiation markers, such as MYH2, MYH7, and MYOG (p < 0.001 or p < 0.01). Therefore, our findings imply that crude polysaccharide obtained from E. cava can be an additive ingredient that enhances the proliferation and differentiation of muscle satellite cells used in the manufacture of cultured meat products.

Attitudes of Malaysian Speech-Language Pathologists and Speech-Language Pathology Students Toward Stuttering.

INTRODUCTION: Attitudes of speech-language pathologists (SLPs) toward stuttering play an important role in managing stuttering cases. Yet, such studies had not been studied in Malaysia, a country that is still developing the profession of speech-language pathology. This study aimed to explore the attitudes of Malaysian SLPs and speech-language pathology students toward stuttering. METHODS: A total of 50 SLPs and 67 speech-language pathology students completed the Clinician Attitudes Towards Stuttering (CATS) inventory. There were eight domains of attitudes toward stuttering: (a) etiology, (b) early intervention, (c) therapeutic efficacy, (d) personalities of PWS, (e) clinician expertise and roles, (f) teacher/counsellor roles and client/public reactions, (g) therapy strategies, and (h) parent attitudes. Descriptive data were presented and Multivariate Analysis of Variance was conducted to examine the effects of clinical certification on the eight domains of attitudes toward stuttering. RESULTS: Participants who possessed a clinical certification were more accepting toward the personalities of people who stutter (PWS) and therapy strategies. On the other hand, participants without a clinical certification were more accepting toward clinician expertise and roles. CONCLUSIONS: Current curriculum and professional training should be re-evaluated to remediate less accepting stereotypes held by SLPs and students toward PWS and to enhance essential skills such as counselling.

Awareness and Knowledge of Stuttering Among Malaysian School-Aged Children: An Exploratory Study.

INTRODUCTION: Knowledge and awareness of stuttering are closely associated with attitudes toward stuttering. Few studies have been conducted on the knowledge and awareness of school-aged children, and none have been conducted in Malaysia. This study aimed to: (a) determine knowledge and awareness of stuttering among Malaysian school-aged children, and (b) determine whether there are differences between age group, gender and PWS exposure groups. METHODS: A cross-sectional study was conducted among 192 Malay school-aged children (mean age = 9.47, SD = 1.781) recruited via email and social media platforms. They completed a Malay version of the questionnaire devised by van Borsel et al. (1999) on various aspects of stuttering, including prevalence, onset, gender distribution, occurrence in different cultures, cause, treatment, intelligence, and heredity of stuttering. The chi-square test of independence was performed to compare the distributions of survey responses by age group, gender and PWS exposure group. RESULTS: Around half of the school-age children had met a person who stutters, but certain aspects of their knowledge were limited. Knowledge also differed according to age and gender. Girls were more knowledgeable about stuttering than boys. Regarding stuttering treatment, younger children had more positive attitudes than older children. Participants who did not know a PWS were more likely to consult their family doctor rather than a speech-language pathologist in relation to stuttering. CONCLUSIONS: Knowledge and awareness of stuttering among Malaysian school-aged children were limited. Findings of this study could be used to develop a stuttering awareness program specific to children to increase their knowledge and awareness about stuttering.

Intravenous dexamethasone does not prolong the duration of pudendal nerve block in infants and children undergoing hypospadias surgery: A randomized clinical trial.

BACKGROUND: The administration of intravenous dexamethasone increases the duration of neuraxial block and improves the quality of analgesia. However, little is known about these effects of dexamethasone on peripheral nerve blocks in children. AIMS: In this study, we aimed to investigate the benefit of intravenous dexamethasone for enhancing the effect of pudendal block on postoperative analgesia in children who underwent hypospadias surgery. METHODS: In total, 46 children aged 6-36 months who underwent hypospadias surgery were randomly allocated to either a control group (normal saline, group C) or dexamethasone group (0.5 mg/kg, group D). Pudendal block was performed before the surgery using 0.3 mL/kg of 0.225% ropivacaine on both sides. Parents were instructed to press the patient-controlled analgesia bolus button when their children's pain score was >4 points. The primary outcome measure was the time at which the first patient-controlled analgesia by proxy bolus dose was administered. The secondary outcome measures were pain score, number of patient-controlled analgesia administration by proxy bolus attempts, number of rescue analgesics required, total amount of fentanyl administered, and overall parental satisfaction. RESULTS: The time of first patient-controlled analgesia bolus administration by proxy was not different between the control and dexamethasone groups (5.6 [5.2, 8.8] h versus 6.5 [5.4, 8.1] h, hazard ratio 0.8, 95% confidence intervals 0.43 to 1.47, p = .46). There were no statistically significant differences among the secondary outcomes. CONCLUSIONS: Administration of intravenous dexamethasone did not enhance the duration of pudendal nerve block in infants and children aged 6-36 months who underwent hypospadias surgery.

Enhancing poly(3-hydroxybutyrate) production in halophilic bacteria through improved salt tolerance.

Polyhydroxyalkanoates (PHA) have emerged as a promising bio-compound in the industrial application due to their potential to replace conventional petroleum-based plastics with sustainable bioplastics. This study focuses on Halomonas sp. YJPS3-3, a halophilic bacterium, and presents a novel approach to enhance PHA production by exploiting its salt tolerance toward PHA biosynthesis. Through gamma irradiation-induced mutants with enhanced salt tolerance from 15% NaCl to 20% NaCl, mutant halo6 showing a significant 11% increase in PHA yield, was achieved. Moreover, the mutants displayed not only higher PHA content but also remarkable cell morphology with elongation. In addition, this research unravels the genetic determinants behind the elevated PHA content and identifies a corresponding shift in fatty acid composition favoring PHA accumulation. This novel mutant obtained from gamma irradiation with enhanced salt tolerance in halophilic bacteria opens up new avenues not only for the bioplastic industry but also for applications in the production of high-value metabolites.

Anti-suicidal effects of IV ketamine in a real-world setting.

The current study evaluated the effectiveness of intravenous ketamine treatment for suicidality in a community-based clinical sample of 295 outpatients (mean age=  40.37; 58.6 % male). We conducted growth mixture modeling to estimate latent classes of changes in symptoms of suicidality measured by the Concise Health Risk Tracking - Self-Report (CHRT-SR) across five infusions in a two-week course of treatment. Best-fit indices indicated three trajectory groups demonstrating non-linear, quadratic changes in CHRT-SR scores during ketamine treatment. The largest group of patients (n=  170, 57.6 %) had moderate CHRT-SR scores at baseline and showed gradual improvement during treatment. The other two groups of patients had severe CHRT-SR scores at baseline and diverged into one group with no improvement throughout treatment (n = 63, 21  %) and one group with rapid improvement (n = 62, 21 %). Of the clinical and demographic variables available and tested, only higher scores pertaining to active thoughts of death and/or plan were found to predict which of the patients with severe CHRT-SR scores at baseline would not benefit from treatment. The present study provides an important contribution to the knowledge of ketamine's effects on symptoms related to suicide over time. providing support for the possible effectiveness of ketamine in a proportion of patients.

Recent advances of additively manufactured noninvasive kinematic biosensors.

The necessity of reliable measurement data assessment in the realm of human life has experienced exponential growth due to its extensive utilization in health monitoring, rehabilitation, surgery, and long-term treatment. As a result, the significance of kinematic biosensors has substantially increased across various domains, including wearable devices, human-machine interaction, and bioengineering. Traditionally, the fabrication of skin-mounted biosensors involved complex and costly processes such as lithography and deposition, which required extensive preparation. However, the advent of additive manufacturing has revolutionized biosensor production by facilitating customized manufacturing, expedited processes, and streamlined fabrication. AM technology enables the development of highly sensitive biosensors capable of measuring a wide range of kinematic signals while maintaining a low-cost aspect. This paper provides a comprehensive overview of state-of-the-art noninvasive kinematic biosensors created using diverse AM technologies. The detailed development process and the specifics of different types of kinematic biosensors are also discussed. Unlike previous review articles that primarily focused on the applications of additively manufactured sensors based on their sensing data, this article adopts a unique approach by categorizing and describing their applications according to their sensing frequencies. Although AM technology has opened new possibilities for biosensor fabrication, the field still faces several challenges that need to be addressed. Consequently, this paper also outlines these challenges and provides an overview of future applications in the field. This review article offers researchers in academia and industry a comprehensive overview of the innovative opportunities presented by kinematic biosensors fabricated through additive manufacturing technologies.

The mitochondrial ATP synthase is a negative regulator of the mitochondrial permeability transition pore.

The mitochondrial permeability transition pore (mPTP) is a channel in the inner mitochondrial membrane whose sustained opening in response to elevated mitochondrial matrix Ca2+ concentrations triggers necrotic cell death. The molecular identity of mPTP is unknown. One proposed candidate is the mitochondrial ATP synthase, whose canonical function is to generate most ATP in multicellular organisms. Here, we present mitochondrial, cellular, and in vivo evidence that, rather than serving as mPTP, the mitochondrial ATP synthase inhibits this pore. Our studies confirm previous work showing persistence of mPTP in HAP1 cell lines lacking an assembled mitochondrial ATP synthase. Unexpectedly, however, we observe that Ca2+-induced pore opening is markedly sensitized by loss of the mitochondrial ATP synthase. Further, mPTP opening in cells lacking the mitochondrial ATP synthase is desensitized by pharmacological inhibition and genetic depletion of the mitochondrial cis-trans prolyl isomerase cyclophilin D as in wild-type cells, indicating that cyclophilin D can modulate mPTP through substrates other than subunits in the assembled mitochondrial ATP synthase. Mitoplast patch clamping studies showed that mPTP channel conductance was unaffected by loss of the mitochondrial ATP synthase but still blocked by cyclophilin D inhibition. Cardiac mitochondria from mice whose heart muscle cells we engineered deficient in the mitochondrial ATP synthase also demonstrate sensitization of Ca2+-induced mPTP opening and desensitization by cyclophilin D inhibition. Further, these mice exhibit strikingly larger myocardial infarctions when challenged with ischemia/reperfusion in vivo. We conclude that the mitochondrial ATP synthase does not function as mPTP and instead negatively regulates this pore.

Feasibility and limitations of deep learning-based coronary calcium scoring in PET-CT: a comparison with coronary calcium score CT.

OBJECTIVE: This study aimed to determine the feasibility and limitations of deep learning-based coronary calcium scoring using positron emission tomography-computed tomography (PET-CT) in comparison with coronary calcium scoring using ECG-gated non-contrast-enhanced cardiac computed tomography (CaCT). MATERIALS AND METHODS: A total of 215 individuals who underwent both CaCT and PET-CT were enrolled in this retrospective study. The Agatston method was used to calculate the coronary artery calcium scores (CACS) from CaCT, PET-CT(reader), and PET-CT(AI) to analyse the effect of using different modalities and AI-based software on CACS measurement. The total CACS and CACS classified according to the CAC-DRS guidelines were compared between the three sets of CACS. The differences, correlation coefficients, intraclass coefficients (ICC), and concordance rates were analysed. Statistical significance was set at p < 0.05. RESULTS: The correlation coefficient of the total CACS from CaCT and PET-CT(reader) was 0.837, PET-CT(reader) and PET-CT(AI) was 0.894, and CaCT and PET-CT(AI) was 0.768. The ICC of CACS from CaCT and PET-CT(reader) was 0.911, PET-CT(reader) and PET-CT(AI) was 0.958, and CaCT and PET-CT(AI) was 0.842. The concordance rate between CaCT and PET-CT(AI) was 73.8%, with a false-negative rate of 37.3% and a false-positive rate of 4.4%. Age and male sex were associated with an increased misclassification rate. CONCLUSIONS: Artificial intelligence-assisted CACS measurements in PET-CT showed comparable results to CACS in coronary calcium CT. However, the relatively high false-negative results and tendency to underestimate should be of concern. CLINICAL RELEVANCE STATEMENT: Application of automated calcium scoring to PET-CT studies could potentially select patients at high risk of coronary artery disease from among cancer patients known to be susceptible to coronary artery disease and undergoing routine PET-CT scans. KEY POINTS: • Cancer patients are susceptible to coronary disease, and PET-CT could be potentially used to calculate coronary artery calcium score (CACS). • Calcium scoring using artificial intelligence in PET-CT automatically provides CACS with high ICC to CACS in coronary calcium CT. • However, underestimation and false negatives of CACS calculation in PET-CT should be considered.

The Antioxidant Activity of Undaria pinnatifida Sporophyll Extract Obtained Using Ultrasonication: A Focus on Crude Polysaccharide Extraction Using Ethanol Precipitation.

Undaria pinnatifida, a marine biological resource from which antioxidants such as polysaccharides can be obtained, is primarily distributed in the coastal areas of East Asia. Reactive oxygen species (ROS) are essential for physiological processes; however, excess ROS levels in the body result in cellular oxidative damage. Several extraction methods exist; however, factors such as long extraction times and high temperatures degrade polysaccharides. Therefore, this study aimed to increase the yield of U. pinnatifida sporophyll extract (UPE), a U. pinnatifida byproduct, using ultrasonication, an environmentally friendly extraction method, and identify UPE components with antioxidant activity. UPE_2, 4, 6, and 8 extracts were obtained at extraction times of 2, 4, 6, and 8 h, respectively. UPE_8 had the highest yield (31.91%) and polysaccharide (69.22%), polyphenol, (8.59 GAE µg/mg), and fucoxanthin contents (2.3 µg/g). UPE_8 showed the greatest protective and inhibitory effects on ROS generation in H2O2-damaged Vero cells. Ethanol precipitation of UPE_8 confirmed that UPE_8P (precipitate) had superior antioxidant activity in Vero cells compared to UPE_8S (supernatant). UPE_8P contained a large amount of polysaccharides, a major contributor to the antioxidant activity of UPE_8. This study shows that UPE_8 obtained using ultrasonication can be a functional food ingredient with excellent antioxidant activity.

H2A.X promotes endosperm-specific DNA methylation in Arabidopsis thaliana.

BACKGROUND: H2A.X is an H2A variant histone in eukaryotes, unique for its ability to respond to DNA damage, initiating the DNA repair pathway. H2A.X replacement within the histone octamer is mediated by the FAcilitates Chromatin Transactions (FACT) complex, a key chromatin remodeler. FACT is required for DEMETER (DME)-mediated DNA demethylation at certain loci in Arabidopsis thaliana female gametophytes during reproduction. Here, we sought to investigate whether H2A.X is involved in DME- and FACT-mediated DNA demethylation during reproduction. RESULTS: H2A.X is encoded by two genes in Arabidopsis genome, HTA3 and HTA5. We generated h2a.x double mutants, which displayed a normal growth profile, whereby flowering time, seed development, and root tip organization, S-phase progression and proliferation were all normal. However, h2a.x mutants were more sensitive to genotoxic stress, consistent with previous reports. H2A.X fused to Green Fluorescent Protein (GFP) under the H2A.X promoter was highly expressed especially in newly developing Arabidopsis tissues, including in male and female gametophytes, where DME is also expressed. We examined DNA methylation in h2a.x developing seeds and seedlings using whole genome bisulfite sequencing, and found that CG DNA methylation is decreased genome-wide in h2a.x mutant endosperm. Hypomethylation was most striking in transposon bodies, and occurred on both parental alleles in the developing endosperm, but not the embryo or seedling. h2a.x-mediated hypomethylated sites overlapped DME targets, but also included other loci, predominately located in heterochromatic transposons and intergenic DNA. CONCLUSIONS: Our genome-wide methylation analyses suggest that H2A.X could function in preventing access of the DME demethylase to non-canonical sites. Overall, our data suggest that H2A.X is required to maintain DNA methylation homeostasis in the unique chromatin environment of the Arabidopsis endosperm.

Flavobacterium sp. strain GJW24 ameliorates drought resistance in Arabidopsis and Brassica.

Candidate strains that contribute to drought resistance in plants have been previously screened using approximately 500 plant growth-promoting rhizobacteria (PGPR) obtained from Gotjawal, South Korea, to further understand PGPR associated with plant drought tolerance. In this study, a selected PGPR candidate, Flavobacterium sp. strain GJW24, was employed to enhance plant drought tolerance. GJW24 application to Arabidopsis increased its survival rate under drought stress and enhanced stomatal closure. Furthermore, GJW24 promoted Arabidopsis survival under salt stress, which is highly associated with drought stress. GJW24 ameliorated the drought/salt tolerance of Brassica as well as Arabidopsis, indicating that the drought-resistance characteristics of GJW24 could be applied to various plant species. Transcriptome sequencing revealed that GJW24 upregulated a large portion of drought- and drought-related stress-inducible genes in Arabidopsis. Moreover, Gene Ontology analysis revealed that GJW24-upregulated genes were highly related to the categories involved in root system architecture and development, which are connected to amelioration of plant drought resistance. The hyper-induction of many drought/salt-responsive genes by GJW24 in Arabidopsis and Brassica demonstrated that the drought/salt stress tolerance conferred by GJW24 might be achieved, at least in part, through regulating the expression of the corresponding genes. This study suggests that GJW24 can be utilized as a microbial agent to offset the detrimental effects of drought stress in plants.

Spectral features of non-nutritive suck dynamics in extremely preterm infants.

Background: Non-nutritive suck (NNS) is used to promote ororhythmic patterning and assess oral feeding readiness in preterm infants in the neonatal intensive care unit (NICU). While time domain measures of NNS are available in real time at cribside, our understanding of suck pattern generation in the frequency domain is limited. The aim of this study is to model the development of NNS in the frequency domain using Fourier and machine learning (ML) techniques in extremely preterm infants (EPIs). Methods: A total of 117 EPIs were randomized to a pulsed or sham orocutaneous intervention during tube feedings 3 times/day for 4 weeks, beginning at 30 weeks post-menstrual age (PMA). Infants were assessed 3 times/week for NNS dynamics until they attained 100% oral feeding or NICU discharge. Digitized NNS signals were processed in the frequency domain using two transforms, including the Welch power spectral density (PSD) method, and the Yule-Walker PSD method. Data analysis proceeded in two stages. Stage 1: ML longitudinal cluster analysis was conducted to identify groups (classes) of infants, each showing a unique pattern of change in Welch and Yule-Walker calculations during the interventions. Stage 2: linear mixed modeling (LMM) was performed for the Welch and Yule-Walker dependent variables to examine the effects of gestationally-aged (GA), PMA, sex (male, female), patient type [respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD)], treatment (NTrainer, Sham), intervention phase [1, 2, 3], cluster class, and phase-by-class interaction. Results: ML of Welch PSD method and Yule-Walker PSD method measures revealed three membership classes of NNS growth patterns. The dependent measures peak_Hz, PSD amplitude, and area under the curve (AUC) are highly dependent on PMA, but show little relation to respiratory status (RDS, BPD) or somatosensory intervention. Thus, neural regulation of NNS in the frequency domain is significantly different for each identified cluster (classes A, B, C) during this developmental period. Conclusions: Efforts to increase our knowledge of the evolution of the suck central pattern generator (sCPG) in preterm infants, including NNS rhythmogenesis will help us better understand the observed phenotypes of NNS production in both the frequency and time domains. Knowledge of those features of the NNS which are relatively invariant vs. other features which are modifiable by experience will likewise inform more effective treatment strategies in this fragile population.

Revisiting frequencies of phonological sound classes in speech input: Change over time in child-directed speech.

The purpose of the current study was to revisit a controversial topic: whether frequencies of phonological consonant and vowel classes differ in speech directed to children and to adults. In addition, the current study investigated whether the frequency of phonological consonant and vowel classes changes with children's increasing chronological and/or developmental age. This study analyzed speech input from 44 adults to four different age groups of listeners (i.e., three groups of children at 6, 18, and 36 months of age and one group of adult listeners) in terms of frequency of occurrence of consonant and vowel classes. Results revealed that consonant stop, nasal, fricative and glide manner classes as well as all four consonant place classes were significantly different in speech directed to the four different age groups. A perspective is discussed to better understand the nature of frequency input of phonological sound classes.

Association of Sleep Disturbances With Brain Amyloid and Tau Burden, Cortical Atrophy, and Cognitive Dysfunction Across the AD Continuum.

BACKGROUND AND OBJECTIVES: Patients with Alzheimer disease (AD) frequently suffer from various sleep disturbances. However, how sleep disturbance is associated with AD and its progression remains poorly investigated. We investigated the association of total sleep time with brain amyloid and tau burden, cortical atrophy, cognitive dysfunction, and their longitudinal changes in the AD spectrum. METHODS: In this retrospective cohort study, we enrolled participants on the AD spectrum who were positive on 18F-florbetaben (FBB) PET. All participants underwent the Pittsburgh Sleep Quality Index, brain MRI, FBB PET, 18F-flortaucipir (FTP) PET, and detailed neuropsychological testing. In addition, a subset of participants completed follow-up assessments. We analyzed the association of total sleep time with the baseline and longitudinal FBB-standardized uptake value ratio (SUVR), FTP-SUVR, cortical thickness, and cognitive domain composite scores. RESULTS: We examined 138 participants on the AD spectrum (15 with preclinical AD, 62 with prodromal AD, and 61 with AD dementia; mean age 73.4 ± 8.0 years; female 58.7%). Total sleep time was longer in the AD dementia group (7.4 ± 1.6 hours) compared with the preclinical (6.5 ± 1.4 hours; p = 0.026) and prodromal groups (6.6 ± 1.4 hours; p = 0.001), whereas other sleep parameters did not differ between groups. Longer total sleep time was not associated with amyloid accumulation but rather with tau accumulation, especially in the amygdala, hippocampus, basal forebrain, insular, cingulate, occipital, inferior temporal cortices, and precuneus. Longer total sleep time predicted faster tau accumulation in Braak regions V-VI (ß = 0.016, p = 0.007) and disease progression to mild cognitive impairment or dementia (hazard ratio = 1.554, p = 0.024). Longer total sleep time was also associated with memory deficit (ß = -0.19, p = 0.008). DISCUSSION: Prolonged total sleep time was associated with tau accumulation in sleep-related cortical and subcortical areas as well as memory dysfunction. It also predicted faster disease progression with tau accumulation. Our study highlights the clinical importance of assessing total sleep time as a marker for disease severity and prognosis in the AD spectrum.

BAK contributes critically to necrosis and infarct generation during reperfused myocardial infarction.

At least seven cell death programs are activated during myocardial infarction (MI), but which are most important in causing heart damage is not understood. Two of these programs are mitochondrial-dependent necrosis and apoptosis. The canonical function of the pro-cell death BCL-2 family proteins BAX and BAK is to mediate permeabilization of the outer mitochondrial membrane during apoptosis allowing apoptogen release. BAX has also been shown to sensitize cells to mitochondrial-dependent necrosis, although the underlying mechanisms remain ill-defined. Genetic deletion of Bax or both Bax and Bak in mice reduces infarct size following reperfused myocardial infarction (MI/R), but the contribution of BAK itself to cardiomyocyte apoptosis and necrosis and infarction has not been investigated. In this study, we use Bak-deficient mice and isolated adult cardiomyocytes to delineate the role of BAK in the pathogenesis of infarct generation and post-infarct remodeling during MI/R and non-reperfused MI. Generalized homozygous deletion of Bak reduced infarct size ∼50% in MI/R in vivo, which was attributable primarily to decreases in necrosis. Protection from necrosis was also observed in BAK-deficient isolated cardiomyocytes suggesting that the cardioprotection from BAK loss in vivo is at least partially cardiomyocyte-autonomous. Interestingly, heterozygous Bak deletion, in which the heart still retains ∼28% of wild type BAK levels, reduced infarct size to a similar extent as complete BAK absence. In contrast to MI/R, homozygous Bak deletion did not attenuate acute infarct size or long-term scar size, post-infarct remodeling, cardiac dysfunction, or mortality in non-reperfused MI. We conclude that BAK contributes significantly to cardiomyocyte necrosis and infarct generation during MI/R, while its absence does not appear to impact the pathogenesis of non-reperfused MI. These observations suggest BAK may be a therapeutic target for MI/R and that even partial pharmacological antagonism may provide benefit.