Dependent Pattern Research Articles

An extended substrate spectrum of the proton organic cation antiporter and relation to other cation transporters.

Most central nervous system (CNS) active drugs are organic cations, which need carrier proteins for efficient transfer through the blood-brain barrier (BBB). A genetically still unidentified proton organic cation (H+/OC) antiporter is found in several tissues, including endothelial cells of the BBB. We characterized the substrate spectrum of the H+/OC antiporter and the overlap in substrate spectrum with OCTN1, OCTN2 or OCT3 by screening 87 potential substrates for transport activity. Based on high antiport rates, 45 of the tested substances were substrates of the H+/OC antiporter. They included antidepressants (like tranylcypromine or nortriptyline), antipsychotics (like levomepromazine) and local anaesthetics. Concentration-dependent transport was confirmed for 38 of the substrates. Transport uptake depending on a pH gradient across the cell membrane confirmed that 43 drugs were indeed substrates of the H+/OC antiporter. However, the patterns of pH dependence differed between the substrates, possibly indicating different modes of transport or the existence of multiple antiporter proteins. The substrate overlap between the H+/OC antiporter and OCTN1, OCTN2 or OCT3 was minimal, indicating that the latter three are not the proteins underlying the H+/OC antiporter activity. Overall, about 50% of positively charged drugs may be substrates of the antiporter, which may be the most important membrane transport protein for many drugs.

Hydrolytically Degradable Zwitterionic Polyphosphazene Containing HEPES Moieties as Side Groups.

Zwitterionic polymers, ampholytic macromolecules containing ionic moieties of opposite sign on the same pendant groups, exhibit strong protein-repulsive properties and an inherent biological inertness. For that reason, these highly hydrated inner salt macromolecules have emerged as some of the most viable alternatives to poly(ethylene glycol) (PEG), a gold standard in enabling stealth behavior in life science applications. However, the structural diversity of polymer zwitterions remains limited, and currently available macromolecules do not possess an intrinsic ability to undergo hydrolytical degradation, an important prerequisite for use in drug delivery applications. The present paper reports on the synthesis of a zwitterionic polymer, a multimerized form (two thousand copies), of a biologically benign buffering agent, HEPES, which is covalently assembled on a polyphosphazene backbone. The polymer exhibits typical polyzwitterionic solution behavior, an environmentally dependent hydrolytic degradation pattern, and excellent in vitro compatibility, features that highlight its potential utility for life science applications.

Drinking refusal self-efficacy- a positive effect of attending de-addiction clinic -survey report of South Indian Union territory hospital.

Introduction: Alcoholism is the most common psychiatric disorder that causes impairment in physical health, mental health,and social functioning. “Alcohol dependence syndrome (ADS) is characterized by a state, psychic, and usually also physical,resulting from drinking alcohol. Self-efficacy is an individual’s belief in his/her innate ability to achieve goals. The prevalenceof current alcohol use in Pondicherry is 9.5% for males and 20 % in total. However, more than 40% of alcohol users drinkalcohol in a dependent pattern in Pondicherry. The current study aimed to assess the self-efficacy of clients to quit alcohol.Methodology: In this descriptive cross-sectional study 97 participants were selected by a convenient sampling technique atde addiction clinic, JIPMER, Puducherry. The tools used for the study include socio-demographic variables, modified versionof drinking refusal self-efficacy questionnaire, which consists of 19 questions to assess their belief about the ability to resistalcohol in the various situation on a six-point Likert scale ranged from 1( I am very sure I would drink) to 6 (I am sure I wouldnot drink)The primary objective was analysed using descriptive and inferential statistics and the secondary objectives were analysedusing the chi-square test and Pearson correlation.Results: The result showed that among 97 study participants, the majority of them could resist (58.8%) alcohol during theirde-addiction follow up visit.Conclusion: Our study concluded that patients who regularly attend de-addiction clinic could resist alcohol consumption.There is still a need for health education and counseling to quit Alcohol.

Unveiling the boson peaks in amorphous phase-change materials

The Boson peak is a universal phenomenon in amorphous solids. It can be observed as an anomalous contribution to the low-temperature heat capacity over the Debye model. Amorphous phase-change materials (PCMs) such as Ge-Sb-Te are a family of poor glass formers with fast crystallization kinetics, being of interest for phase-change memory applications. So far, whether Boson peaks exist in PCMs is unknown and, if they do, their relevance to PCM properties is unclear. Here, we investigate the thermodynamic properties of the pseudo-binary compositions on the tie-line between Ge15Te85and Ge15Sb85from a few Kelvins to the liquidus temperatures. Our results demonstrate the evidence of the pronounced Boson peaks in heat capacity below 10 K in the amorphous phase of all compositions. By fitting the data using the Debye model combined with a modification of the Einstein model, we can extract the characteristic parameters of the Boson peaks and attribute their origin to the excess vibrational modes of dynamic defects in the amorphous solids. We find that these parameters correlate almost linearly with the Sb-content of the alloys, despite the nonmonotonic behaviors in glass forming abilities and thermal stabilities. In a broader context, we show that the correlations of the characteristic parameters of the Boson peaks with Tg and kinetic fragility, vary according to the type of bonding. Specifically, metallic glasses and conventional covalent glasses exhibit distinct patterns of dependence, whereas PCMs manifest characteristics that lie in between. A deeper understanding of the Boson peaks in PCMs holds the promise to enable predictions of material properties at higher temperatures based on features observed in low-temperature heat capacity.

Acute Toxicity and IN VIVO Antischistosomal Effects of Entada africana Guill & Perott (Fabaceae) Methanol Stem Bark Extract in Albino Mice

The study was aimed at determining the acute toxicity and schistosomicidal effects of methanol extract (ME) of Entada africana (E. africana), in albino mice. Fresh stem bark of E. africana was shade-dried and extracted by Soxhlet extraction. Acute toxicity was carried out on 6 groups of mice (n=3) of 6-week-old, sizes 27-30g; to determine the therapeutic index, piloerection signs and possible mortality (LD50) in 24h exposure period. Cercaria from B. globosus snails were shed under a 100W bulb for 2 hours. In vivo antischistosomal assays was by used of 6-weeks old (27-30g) mice. Set I (n=10) involved investigation on schistosomules infection in the mice, 3-7 days post infection (PI). Set II (n=10) was infected and treated with E. africana ME extract, at concentrations 10-100mg/l, 35th day, PI for 5 consecutive days. Set III (n=10), were infected and treated with praziquantel– PZQ (positive control). While set IV (n=10) were infected and untreated (negative control). All were sacrificed, 75th day of PI. Data were analyzed by GraphPad® prism 8.4, version 2020. Findings revealed that E. africana ME did not generate any harmful or clinical effect within 24h, post administration; and there were no obvious reactions such as paw licking, stooling, piloerection or immediate death, except at phase II, 5000mg/kg bwt, (1⁄3) being the highest dosage. Worm burden decreased with increase in concentrations, especially at 70-100mg/l. Lower concentrations (10mg/l), had high worm population (76.00±21.28). Infected and untreated group had highest worm population (189.67±32.52). E. africana ME stem bark extract, showed antischistosomal effect and worm reduction in a dose- dependent pattern.

Technological Features of Filler Wire Melting for Arc Welding and Surfacing with the Introduction of SF6 into Protective Gas Atmosphere

On the basis of the results of experimental studies the paper establishes important patterns of dependence of the frequency of short circuits of the arc gap and the coefficient of loss of electrode metal due to spatter from the voltage on the arc and the feed rate of the filler wire during welding and surfacing with the introduction of gaseous SF6 into the Ar + CO2 protective mixture. It is proposed to introduce fluorine-containing components of SF6 directly into the protective gas mixture of 82 % Ar + 18 % CO2 in quantities not exceeding 2 %. The technology makes it possible to reduce the amount of diffusion hydrogen in the deposited metal, which is an urgent task when welding high-strength steels and materials sensitive to hydrogen embrittlement. Previously, we resolved a number of issues related to the obstacle to increasing the concentration of S in the deposited metal, which made it possible to determine the most effective concentrations of SF6 in the protective gas environment, limited to 1.5 % by volume of the total composition (Ar + CO2) + SF6. At the same time, modification of the protective gas atmosphere with the halide compound SF6 has a significant effect on the melting characteristics of the electrode wire and temperature indicators in the arc combustion zone. This is due to the high ionization potential of fluorine as a product of the high-temperature dissociation reaction of SF6. The results obtained have made it possible to determine the most effective relationships between the values of the mode parameters, as well as to study the specifics of melting the filler wire in a protective atmosphere modified with SF6. Important regularities have been established that reveal the technological features of welding and surfacing with modification of the protective atmosphere with halide compounds.

A copula-based approach for multi-modal demand dependence modeling: Temporal correlation between demand of subway and bike-sharing

As a representative mode of shared mobility, bike-sharing serves not only as a convenient way to conduct short-distance trips in urban areas, but also as a feeder mode to public transit, forming the Bike and Ride (BnR) system. Conducting management for such a hybrid multi-modal system faces various challenges, including the complex interactions between bike-sharing and other modes, highly dynamic passenger demand, and the difficulty of accessing direct transfer data. To overcome such difficulties, our study proposes a framework for assessing the dependency between the two usage modes. Firstly, a Dynamic-Time-Warping-based (DTW) method is utilized to determine the catchment area (CA) between the two modes, allowing the BnR-related tendency similarity under a given time scale to be considered. Then, the patterns of probabilistic dependence between travel demand of the two modes are obtained by a copula-based approach, which separates correlations under specific usage levels from single modal demands. A case study on the multi-modal system formed by docked bike-sharing and subway in New York is conducted to validate the proposed framework. The tendency similarity is found to be most pronounced within 500 m on average under a 4-hour interval. For each formed station group (SG), the best-fitted copula type is selected, capturing the strong tail correlations present only at specific usage levels. The results show a variety of different correlation patterns within SGs, despite the close geographic locations they may share. Areas of potential transfer resistance between the two modes are identified, which is more evident in first-mile-related (FMR) activities. In contrast, the two modes display more weak connections in last-mile-related (LMR) activities. The obtained results can be utilized by bike-sharing service providers to analyze demand distributions and conduct efficient station-level rebalancing. Compared to previous methods, our proposed framework is computationally inexpensive since no direct transfer of data or complex inference network is required. It incorporates statistically significant spatial–temporal information, allowing for a more accurate determination of the bi-modal assessment range. Moreover, considering that single-mode influences are mathematically removed, the resulting correlation in principle links to the strength of the connections between the two modes. Therefore, it can be assessed as an indicator of the reliability of the multi-modal system.

Addressing India’s alcohol misuse crisis: The urgent need for screening and brief intervention to bridge the healthcare gap

India faces a significant challenge with alcohol misuse, as evidenced by the national survey revealing that 57 million out of 160 million persons with alcohol use exhibit harmful or dependent patterns, necessitating professional assistance. The Global Status Report on Alcohol and Health (2018) indicates a rising per capita alcohol consumption in the Southeast Asian Region, with India contributing substantially. To address this, implementing policies and programs to curb hazardous alcohol use is crucial. Despite a shortage of mental health professionals in India, they remain the primary caregivers for those with alcohol-related issues. Only one in five individuals with problematic alcohol use can access professional help. I argue for adopting Screening and Brief Intervention (SBI) to bridge this healthcare gap. SBI is a concise, structured counseling approach that proves effective and scalable. It can be delivered by various healthcare providers, including doctors, nurses, counselors, and paramedics. Hence, it can be seamlessly integrated into primary care, emergency, and nonclinical settings. The efficacy of SBI extends to electronic formats, providing a scope of expansion through telehealth. The WHO advocates SBI by its SAFER initiative aimed at reducing negative alcohol-associated health and social consequences. SBI is effective across age groups, including adolescents and young adults, constituting most of India’s population. Emerging evidence suggests that SBI is acceptable, feasible, and effective in the Indian context. Universal or targeted SBI can be a pivotal tool in achieving the Sustainable Development Goals (2030) and global commitments for noncommunicable diseases, fortifying efforts to prevent and treat alcohol misuse.

TAIL DEPENDENCE OF COMMODITY FUTURES RETURNS IN THE AGRICULTURAL AND ENERGY SECTORS

The goal of this research was to examine tail dependence structures between selected commodity futures returns. Tail dependence, called also extremal dependence, was evaluated for the pairs of commodities coming from the same sector (energy or agricultural). The study covers the years 2018-2023, embracing the COVID-19 pandemic and the outbreak of the Russia-Ukraine war. To achieve the goal, bivariate dynamic models were applied to percentage log returns of commodity futures. Marginal distributions were described using the ARMA-GARCH models. Joint distributions were constructed using the symmetrized Joe-Clayton copula, which allowed to model asymmetric dependence in the tails of a distribution. Time variation of the copula parameters, here equal to tail dependence coefficients, was described using the evolution equations [Patton 2006]. In the energy sector, the dependence in both tails of analyzed distributions was relatively strong, dynamic and higher in the lower tail than in the upper tail. On the contrary, the agricultural sector lacks common patterns of tail dependency. This feature of the agricultural sector creates an opportunity for investors or risk managers to build well-diversified portfolios.

Establishing a Marine Protected Area network using a Marine Spatial Planning approach: A reflection on practical challenges and opportunities for social–ecological integration

AbstractIntegrative social–ecological approaches are crucial for addressing sustainability challenges in coastal and marine systems. Among these, Marine Spatial Planning (MSP) emerges as a pivotal approach for integrated management. Often, the establishment of Marine Protected Areas (MPAs) and the application of MSP occur in parallel. Given the potential synergies, there is a need to better understand and address barriers to the adoption of MSP approaches for integrative conservation mechanisms. Using São Tomé and Príncipe as a case study, we illustrate how MSP was employed as an operational framework for establishing an MPA network. Drawing on the experiences of people directly involved in this co‐design process, we reflect on the main challenges and opportunities in achieving social–ecological integration, and highlight recommendations for conservation practitioners and planners. Applying MSP was perceived to contribute substantially to multiple project goals, with some (e.g., incorporating perspectives and needs of vulnerable groups) more challenging to achieve. While MSP enhanced conceptual, disciplinary, methodological and functional integration, practical challenges in implementation hindered the extent to which each of these was achieved. Given international commitments to Blue Growth, high fisheries dependence and current patterns of change, developing effective integrative MSP approaches is essential for social–ecological resilience.

Artificial intelligence-based analysis of behavior and brain images in cocaine-self-administered marmosets

BackgroundThe sophisticated behavioral and cognitive repertoires of non-human primates (NHPs) make them suitable subjects for studies involving cocaine self-administration (SA) schedules. However, ethical considerations, adherence to the 3Rs principle (replacement, reduction and refinement), and other factors make it challenging to obtain NHPs individuals for research. Consequently, there is a need for methods that can comprehensively analyze small datasets using artificial intelligence (AI). New methodsWe employed AI to identify cocaine dependence patterns from collected data. First, we collected behavioral data from cocaine SA marmosets (Callithrix jacchus) to develop a dependence prediction model. SHapley Additive exPlanations (SHAP) values were used to demonstrate the importance of various variables. Additionally, we collected positron emission tomographic (PET) images showing dopamine transporter (DAT) binding potential and developed an algorithm for PET image segmentation. ResultsThe prediction model indicated that the Random Forest (RF) algorithm performed best, with an area under the curve (AUC) of 0.92. The top five variables influencing the model were identified using SHAP values. The PET image segmentation model achieved an accuracy of 0.97, a mean squared error of 0.02, an intersection over union (IoU) of 0.845, and a Dice coefficient of 0.913. Comparison with existing methods and conclusionUtilizing data from the marmoset SA experiment, we developed an ML-based dependence prediction model and analyzed variable importance rankings using SHAP. AI-based imaging segmentation methods offer a valuable tool for evaluating DAT availability in NHPs following chronic cocaine administration.

Linkage of alternative exon assembly in Drosophila TrpA1 transcripts

Drosophila TrpA1 (transient receptor potential ankyrin 1) transcripts are alternatively spliced at two distinct sites each with a choice of mutually exclusive exons. The first site determines exon1 encoding the amino terminus to produce either nucleophile-, electrophile- and noxious temperature-gated TRPA1(A) or electrophile- and innocuous warmth-gated TRPA1(B). The second site selects for exon10, resulting in TrpA1 variants with either exon10a or exon10b encoding a domain between the N-terminal ankyrin repeats and the transmembrane segments. Although unbiased assembly would generate TRPA1 with four different domain combinations, the functional impact of these alternative domains remains to be thoroughly examined. Here, we find that there is a relatively strong linkage in mRNA splicing between the two sites in case of TrpA1(B), but not TrpA1(A), transcripts. Our semi-quantitative assay, consisting of reverse transcription polymerase chain reaction (RT-PCR) and Sanger sequencing, revealed that exon10b is little coupled with TrpA1(B) transcripts, suggesting that only three isoforms, TRPA1(A)-exon10a [denoted as TRPA1(A)], TRPA1(A)-exon10b [TRPA1(A)10b] and TRPA1(B)-exon10a [TRPA1(B)], are present at detectable levels using our method. Interestingly, heterologously expressed TRPA1(A)10b showed elevated sensitivity to low concentrations of N-methyl maleimide (NMM), a cysteine-modifying electrophile, compared with other isoforms. Equivalent isoforms in malaria-transmitting Anopheles gambiae displayed a similar pattern of isoform-dependent NMM dose dependences, suggesting that the chemosensory regulation by selective domain assembly is conserved in insect TRPA1s. Thus, alternative RNA splicing of exon10 is coordinated in conjunction with the first exons, regulating chemical sensitivity of insect TRPA1s.

A land plant phylogenetic framework for GLABROUS INFLORESCENCE STEMS (GIS), SUPERMAN, JAGGED and allies plus their TOPLESS co-repressor

Members of the plant specific family of C1-1i zincfinger transcriptionfactors (ZF-TFs), such as SUPERMAN, JAGGED, KNUCKLES or GIS,regulatediversedevelopmental processes including sexual reproduction. C1-1is consist of one zinc-finger and one to two EAR domains, connected by large intrinsically disordered regions (IDR). While the role of C1-i1 ZF-TFs in development processes is well known for some genes in Arabidopsis, rice or tomatoa comprehensive and broadphylogenetic background is lacking, yet knowledge of orthology is a requirement for a better understanding of C1-1i-Zf-TFs diverse roles in plants. Here, we provide a fine-grained and land plant wide classification of C1-1i sub-families and their known co-repressors TOPLESS and TOPLESS RELATED. Our work combines the identification of orthologous groups with Maximum-Likelihood phylogeny reconstructions and digital gene expression analyses mining high quality land plant genomes and transcriptomes to generate a comprehensive framework of C1-1i ZF-TF evolution. We show that C1-1i’s are low to moderate copy genesand that orthologous genesonly partiallyhaveconserved sub-family and life cycle stage dependent expression pattern across land plants while others are highly diverged. Our workprovides the phylogenetic framework for C1-1i ZF-TFs, s and strengthen C1-1 ZF-TFs as a potential model for IDR-research in plants.

Rank-based correlation matrix estimation for high dimensional microbiome data

In recent years, the progress made in high-throughout sequencing techniques supports the analysis of microbial communities greatly. The fact that real-world microbiome data lie in a high-dimensional simplex makes conventional statistical analysis unreliable owing to the sum-to-one constraint. Motivated by the urgent requirements of directly inferring the dependence pattern and dependence intensity simultaneously among microbial taxa, we address the challenge of correlation matrix estimation for this kind of data. Assuming that the unobserved log-basis random vectors follow the elliptical distribution, a robust method built on the Kendall's tau statistic is developed to estimate the basis generalized correlation matrix. Regardless of the existence of the covariance, the basis generalized correlation matrix is always a reliable measure of dependence structure. Theoretically, we establish the convergence rate of the proposed estimator under the spectral norm. Support recovery is discussed as well. Empirically, simulation studies demonstrate the outstanding numerical performance of our method. We also apply our method to analyse a microbiome dataset from human gut. We provide all the codes at https://github.com/lwfwhunanhero/CRCE.

Alcohol Use Disorders in Patients Suffering from Obsessive–Compulsive Disorder: A Cross-sectional Study

Background: Comorbidity in obsessive–compulsive disorder (OCD) is known, especially alcohol use disorders (AUDs) in OCD. Data are lacking regarding the prevalence, the obsessions and compulsions in people with OCD with comorbid alcohol use. Aims and Objectives: The aim was to study the prevalence of AUDs in people with OCD. The primary objective was to study the prevalence of AUDs in 100 people with OCD. Secondary objective was to study the clinical characteristics, obsessions, and compulsions of people with OCD and comorbid alcohol use. Settings and Designs: The study design was a cross-sectional study. Materials and Methods: 100 patients of Asha Hospital diagnosed with OCD were screened and included in the study after a written informed consent. YBOCS checklist and scoring were done. People satisfying the criteria for AUD were further assessed with SADQ questionnaire. SPSS software was used for statistical analysis. Results and Conclusions: The lifetime prevalence of substance use disorders was found 18%. Point prevalence of any substance use was 13%, out of which 7% had AUDs. 2% had a dependence pattern and 5% had an abuse pattern. When comparing people with alcohol versus non-alcohol use, there was a significant difference in the proportion of males in the alcohol group (P = 0.0011). Nicotine was used in higher proportion in the alcohol group (P = 0.0001). Alcohol users were not regular with medications (P = 0.01). Miscellaneous obsessions are more common in them (P = 0.002). Alcohol users had a higher proportion of nil compulsions (P = 0.057) implying that obsessions were more prominent than compulsions in them. Mean scores of OCD in both groups were around moderate severity, with no significant difference between the two.

Patterns of childhood maltreatment and maternal substance use disorder on the development of emerging adult offspring substance use.

Exposure to child maltreatment and maternal substance use disorder represent two highly consequential and co-occurring experiences of family-level adversity for the development of concerning substance use behaviors among offspring. The present study uses latent class analysis to identify how characteristics of childhood maltreatment and maternal substance use disorder naturally cluster. Further, this study investigates how distinct patterns of maltreatment and maternal substance use differentially predict emerging adult substance use in offspring. Participants (N = 405) were drawn from a longitudinal follow-up study of emerging adults who participated in a research summer camp program as children. Wave 1 of the study included 674 school-aged children with and without maltreatment histories, all of whom experienced low socioeconomic status. Patterns of child maltreatment experiences, based on coded Child Protective Services record data, and maternal substance use behaviors, per a diagnostic interview, were used to predict Wave 2 (emerging adulthood) substance use. Results indicated that children who were exposed to a pattern of multitype maltreatment and multitype maternal substance dependence, relative to those exposed to multitype maltreatment alone, reported greater alcohol dependence symptoms during emerging adulthood. Additionally, these same individuals reported greater past-year hard liquor consumption relative to those who experienced chronic, multitype maltreatment and maternal alcohol dependence. These findings highlight how a pattern of maternal polysubstance use and multitype maltreatment is particularly consequential for the intergenerational transmission of substance use behaviors. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Different patterns of fine-root exudation rates along soil depth of Pinus densiflora, Chamaecyparis obtusa, and Cryptomeria japonica in coniferous forests

Tree fine-root exudation and organic carbon compounds in the soil affect physiological functions through degradation by microorganisms around the roots and the enhancement of allelopathic effects on invasion attempts by other plant species. However, the underlying mechanism of fine-root action in vertically heterogeneous resource-distribution patterns along the soil profile is little known. Here, we quantified root exudation and its morphological and chemical traits in the soil layers down to 100-cm depth for three conifer species, Pinus densiflora (ectomycorrhiza), Chamaecyparis obtusa, and Cryptomeria japonica (arbuscular mycorrhiza), in a cool temperate Japanese forest. By using glass filter-trap method, root exudation rates in all three species varied with soil depth in a species dependent pattern. Specifically, the root exudation rate of P. densiflora was significantly higher in the middle soil layer, and lower in the topsoil layer, whereas the exudation rates significantly decreased in C. japonica and did not vary in C. obtusa along soil depth. Exudation strongly correlated with variation in root traits in C. obtusa and C. japonica but not in P. densiflora. These findings suggest that differences in exudation patterns among tree species are likely compensated for by structural modifications in fine roots in response to soil depth. In addition, the traits with mycorrhizal types might be related to adequate root exudation and enhanced soil-nutrient acquisition. Distinct differences among species in exudation, associated with vertical root distribution, will increase our understanding of root survival strategies for nutrient acquisition and carbon sequestration in forest tree species.

Electroencephalographic Microstates During Sleep and Wake in Schizophrenia

BackgroundAberrant functional connectivity is a hallmark of schizophrenia. The precise nature and mechanism of dysconnectivity in schizophrenia remains unclear, but evidence suggests that dysconnectivity is different in wake versus sleep. Microstate analysis uses electroencephalography (EEG) to investigate large-scale patterns of coordinated brain activity by clustering EEG data into a small set of recurring spatial patterns, or microstates. We hypothesized that this technique would allow us to probe connectivity between brain networks at a fine temporal resolution and uncover previously unknown sleep-specific dysconnectivity. MethodsWe studied microstates during sleep in patients with schizophrenia by analyzing high-density EEG sleep data from 114 patients with schizophrenia and 79 control participants. We used a polarity-insensitive k-means analysis to extract a set of 6 microstate topographies. ResultsThese 6 states included 4 widely reported canonical microstates. In patients and control participants, falling asleep was characterized by a shift from microstates A, B, and C to microstates D, E, and F. Microstate F was decreased in patients during wake, and microstate E was decreased in patients during sleep. The complexity of microstate transitions was greater in patients than control participants during wake, but this reversed during sleep. ConclusionsOur findings reveal behavioral state–dependent patterns of cortical dysconnectivity in schizophrenia. Furthermore, these findings are largely unrelated to previous sleep-related EEG markers of schizophrenia such as decreased sleep spindles. Therefore, these findings are driven by previously undescribed sleep-related pathology in schizophrenia.

Sterolysin from a 1950s culture of Karlodinium veneficum (aka Gymnodinium veneficum Ballantine) forms lethal sterol dependent membrane pores

In 1957 Abbott and Ballantine described a highly toxic activity from a dinoflagellate isolated from the English Channel in 1949 by Mary Park. From a culture maintained at Plymouth Laboratory since 1950, we have been able to isolate two toxic molecules (abbotoxin and 59-E-Chloro-abbotoxin), determine the planar structures by analysis of HRMS and 1D and 2D NMR spectra, and found them to be karlotoxin (KmTx) congeners. Both toxins kill larval zebrafish with symptoms identical to those described by Abbot and Ballantine for gobies (Gobius virescens). Using surface plasma resonance the sterol binding specificity of karlotoxins is shown to require desmethyl sterols. Our results with black lipid membranes indicate that karlotoxin forms large-conductance channels in the lipid membrane, which are characterized by large ionic conductance, poor ionic selectivity, and a complex gating behavior that exhibits strong voltage dependence and multiple gating patterns. In addition, we show that KmTx 2 pore formation is a highly targeted mechanism involving sterol-specificity. This is the first report of the functional properties of the membrane pores formed by karlotoxins and is consistent with the initial observations of Abbott and Ballantine from 1957.

Heterospecific mating interference in ladybird beetles: age dependent patterns and consequences

Heterospecific mating interference in ladybird beetles: age dependent patterns and consequences