Lipidated DNA Nanostructures Target and Rupture Bacterial Membranes.

Chemistry has the power to endow supramolecular nanostructures with new biomedically relevant functions. Here it is reported that DNA nanostructures modified with cholesterol tags disrupt bacterial membranes to cause microbial cell death. The lipidated DNA nanostructures bind more readily to cholesterol-free bacterial membranes than to cholesterol-rich, eukaryotic membranes. These highly negatively charged, lipidated DNA nanostructures cause bacterial cell death by rupturing membranes. Strikingly, killing is mediated by clusters of barrel-shaped nanostructures that adhere to the membrane without the involvement of expected bilayer-puncturing barrels. These DNA nanomaterials may inspire the development of polymeric or small-molecule antibacterial agents that mimic the principles of selective binding and rupturing to help combat antimicrobial resistance.

Urbanicity and rates of untreated psychotic disorders in three diverse settings in the Global South.

BACKGROUND: Extensive evidence indicates that rates of psychotic disorder are elevated in more urban compared with less urban areas, but this evidence largely originates from Northern Europe. It is unclear whether the same association holds globally. This study examined the association between urban residence and rates of psychotic disorder in catchment areas in India (Kancheepuram, Tamil Nadu), Nigeria (Ibadan, Oyo), and Northern Trinidad. METHODS: Comprehensive case detection systems were developed based on extensive pilot work to identify individuals aged 18-64 with previously untreated psychotic disorders residing in each catchment area (May 2018-April/May/July 2020). Area of residence and basic demographic details were collected for eligible cases. We compared rates of psychotic disorder in the more v. less urban administrative areas within each catchment area, based on all cases detected, and repeated these analyses while restricting to recent onset cases (<2 years/<5 years). RESULTS: We found evidence of higher overall rates of psychosis in more urban areas within the Trinidadian catchment area (IRR: 3.24, 95% CI 2.68-3.91), an inverse association in the Nigerian catchment area (IRR: 0.68, 95% CI 0.51-0.91) and no association in the Indian catchment area (IRR: 1.18, 95% CI 0.93-1.52). When restricting to recent onset cases, we found a modest positive association in the Indian catchment area. CONCLUSIONS: This study suggests that urbanicity is associated with higher rates of psychotic disorder in some but not all contexts outside of Northern Europe. Future studies should test candidate mechanisms that may underlie the associations observed, such as exposure to violence.

Cannabis use and psychotic disorders in diverse settings in the Global South: findings from INTREPID II.

BACKGROUND: Cannabis use has been linked to psychotic disorders but this association has been primarily observed in the Global North. This study investigates patterns of cannabis use and associations with psychoses in three Global South (regions within Latin America, Asia, Africa and Oceania) settings. METHODS: Case-control study within the International Programme of Research on Psychotic Disorders (INTREPID) II conducted between May 2018 and September 2020. In each setting, we recruited over 200 individuals with an untreated psychosis and individually-matched controls (Kancheepuram India; Ibadan, Nigeria; northern Trinidad). Controls, with no past or current psychotic disorder, were individually-matched to cases by 5-year age group, sex and neighbourhood. Presence of psychotic disorder assessed using the Schedules for Clinical Assessment in Neuropsychiatry and cannabis exposure measured by the World Health Organisation Alcohol, Smoking and Substance Involvement Screening Test (ASSIST). RESULTS: Cases reported higher lifetime and frequent cannabis use than controls in each setting. In Trinidad, cannabis use was associated with increased odds of psychotic disorder: lifetime cannabis use (adj. OR 1.58, 95% CI 0.99-2.53); frequent cannabis use (adj. OR 1.99, 95% CI 1.10-3.60); cannabis dependency (as measured by high ASSIST score) (adj. OR 4.70, 95% CI 1.77-12.47), early age of first use (adj. OR 1.83, 95% CI 1.03-3.27). Cannabis use in the other two settings was too rare to examine associations. CONCLUSIONS: In line with previous studies, we found associations between cannabis use and the occurrence and age of onset of psychoses in Trinidad. These findings have implications for strategies for prevention of psychosis.

Water, sanitation and depression in rural communities: evidence from nationally representative study data in South Africa.

Clean water and sanitation provisions are essential for good hygiene and health, with rural South Africa facing a simultaneous access crisis of both, the direct health effect of restricted access to both on mental health remaining scarce and largely overlooked. This study investigated the association between access to clean water and sanitation on depression in rural South Africa utilizing the most recent data (year 2017) from the South African National Income Dynamics Study. Our study outcome was depression, based on the 10-item abridged version of the Center for Epidemiologic Studies Depression Scale (data available in SA-NIDS), the main exposures being access to clean water and adequate sanitation facilities (i.e. flushing toilets). Two types of analyses were conducted: first, adjusted logistic regression models were fitted to assess the relationship between lack of access to clean water and adequate sanitation to depression. Second, we conducted mediation analysis to investigate whether access to clean water mediated the relationship between lack of access to toilets and depression. A high proportion of rural participants lacked access to clean water (n = 6,188, 47.6%) and adequate toilets (n = 9,797, 81.6%). The regression analyses indicated that lack of access to both clean water (OR = 1.21, 95% CI: 1.06-1.39) and adequate sanitation (OR = 1.36, 95% CI: 1.10-1.69) were significantly associated with greater odds of depression. The mediation analysis indicated that access to clean water partially mediated the relationship between lack of access to adequate sanitation and depression, the total mediated effect being 18.2% (95% CI: 11.0%-51.0%). Most rural communities in South Africa lack access to basic services that are essential for human dignity and a decent quality of life, leading to opportunities for poor mental health, with its various consequences for socio-economic development and personal wellbeing, including avoidable depression.

Complexation of Astatine(III) with Ketones: Roles of NO3- Counterion and Exploration of Possible Binding Modes.

Ketones have been proven effective in extracting astatine(III) from aqueous solvents. Previous theoretical studies suggested a mechanism where the "sp2" lone pair on the carbonyl oxygen donates electron density into the π system of the AtO+ molecular cation to form a dative-type bond. In this study, co-extraction of NO3- as AtO(NO3)·(O═CR1R2) species into the organic phase appears to be a key factor. Adjusting the electronic properties of the ketone, by having an aryl group instead of an alkyl group in the alpha position of the ketone, increased the electron density on C═O, increased the bond strength between the ketone and AtO+, and in turn increased the extraction of 211At into the organic phase. Extraction with diketones shows dependence on the bridging distance between the two carbonyl moieties, where a C3 or longer bridge results in a 10-fold increase in extraction into the organic phase. DFT calculations show the longer bridge allows for the chelation of AtO(NO3) by either the second carbonyl or the phenyl ring.

Hydrophobic Interactions between DNA Duplexes and Synthetic and Biological Membranes.

Equipping DNA with hydrophobic anchors enables targeted interaction with lipid bilayers for applications in biophysics, cell biology, and synthetic biology. Understanding DNA-membrane interactions is crucial for rationally designing functional DNA. Here we study the interactions of hydrophobically tagged DNA with synthetic and cell membranes using a combination of experiments and atomistic molecular dynamics (MD) simulations. The DNA duplexes are rendered hydrophobic by conjugation to a terminal cholesterol anchor or by chemical synthesis of a charge-neutralized alkyl-phosphorothioate (PPT) belt. Cholesterol-DNA tethers to lipid vesicles of different lipid compositions and charges, while PPT DNA binding strongly depends on alkyl length, belt position, and headgroup charge. Divalent cations in the buffer can also influence binding. Our MD simulations directly reveal the complex structure and energetics of PPT DNA within a lipid membrane, demonstrating that longer alkyl-PPT chains provide the most stable membrane anchoring but may disrupt DNA base paring in solution. When tested on cells, cholesterol-DNA is homogeneously distributed on the cell surface, while alkyl-PPT DNA accumulates in clustered structures on the plasma membrane. DNA tethered to the outside of the cell membrane is distinguished from DNA spanning the membrane by nuclease and sphingomyelinase digestion assays. The gained fundamental insight on DNA-bilayer interactions will guide the rational design of membrane-targeting nanostructures.

Introducing Bacteria and Synthetic Biomolecules along Engineered DNA Fibers.

Deoxyribonucleic acid (DNA) nanotechnology enables user-defined structures to be built with unrivalled control. The approach is currently restricted across the nanoscale, yet the ability to generate macroscopic DNA structures has enormous potential with applications spanning material, physical, and biological science. To address this need, I employed DNA nanotechnology and developed a new macromolecular nanoarchitectonic assembly method to produce DNA fibers with customizable properties. The process involves coalescing DNA nanotubes under high salt conditions to yield filament superstructures. Using this strategy, fibers over 100 microns long, with stiffnesses 10 times greater than cytoskeletal actin filaments can be fabricated. The DNA framework enables fibers to be functionalized with advanced synthetic molecules, including, aptamers, origami, nanoparticles, and vesicles. In addition, the fibers can act as bacterial extracellular scaffolds and adhere Escherichia coli cells in a controllable fashion. These results showcase the opportunities offered from DNA nanotechnology across the macroscopic scale. The new biophysical approach should find widespread use, from the generation of hybrid-fabric materials, smart analytical devices in biomedicine, and platforms to study cell-cell interactions.

Spectroscopic characterization of neptunium(VI), plutonium(VI), americium(VI) and neptunium(V) encapsulated in uranyl nitrate hexahydrate.

The coordination of crystalline products resulting from the co-crystallization of Np(vi), Pu(vi), Am(vi), and Np(v) with uranyl nitrate hexahydrate (UNH) has been revealed through solid-state spectroscopic characterization via diffuse reflectance UV-Vis-NIR spectroscopy, SEM-EDS, and extended X-ray absorption fine structure (EXAFS) spectroscopy. Density functional and multireference wavefunction calculations were performed to analyze the An(vi/v)O2(NO3)2·2H2O electronic structures and to help assign the observed transitions in the absorption spectra. EXAFS show a similar coordination between the U(VI) in UNH and Np(vi) and Pu(vi); while Am resulted in a similar coordination to Am(iii), as reduction of Am(vi) occurred prior to EXAFS data being obtained. The co-crystallization of the oxidized transuranic species-penta- and hexavalent-with UNH, represents a significant advance from not only a practical standpoint in providing an elegant solution for used nuclear fuel recycle, but also as an avenue to expand the fundamental understanding of the 5f electronic behavior in the solid-state.

Convolutional Neural Networks for Challenges in Automated Nuclide Identification.

Improvements in Radio-Isotope IDentification (RIID) algorithms have seen a resurgence in interest with the increased accessibility of machine learning models. Convolutional Neural Network (CNN)-based models have been developed to identify arbitrary mixtures of unstable nuclides from gamma spectra. In service of this, methods for the simulation and pre-processing of training data were also developed. The implementation of 1D multi-class, multi-label CNNs demonstrated good generalisation to real spectra with poor statistics and significant gain shifts. It is also shown that even basic CNN architectures prove reliable for RIID under the challenging conditions of heavy shielding and close source geometries, and may be extended to generalised solutions for pragmatic RIID.

Neurocognitive functioning in MDR-TB patients with and without HIV in KwaZulu-Natal, South Africa.

OBJECTIVES: Optimising medication adherence is one of the essential factors in reversing the tide of a TB-HIV syndemic in sub-Saharan Africa, especially South Africa. Impairment in key neurocognitive domains may impair patients' ability to maintain adherence to treatment, but the level of cognition and its relationship to HIV status has not been examined in individuals with drug-resistant TB. We therefore investigated performance on several key neurocognitive domains in relationship to HIV status in a multidrug-resistant tuberculosis patients (MDR-TB) sample. METHODS: We enrolled microbiologically confirmed MDR-TB inpatients at a TB-specialist referral hospital in KwaZulu-Natal province, South Africa. We collected cross-sectional data on sociodemographic, clinical and neurocognitive function (e.g. attention, memory, executive functioning, language fluency, visual-spatial, eye-hand coordination). For the primary analysis, we excluded participants with major depressive episode/substance use disorder (MDE/SUD). We fitted adjusted Poisson regression models to explore the association between HIV and neurocognitive function. RESULTS: We enrolled 200 people with MDR-TB; 33 had MDE/SUD, and data of 167 were analysed (151 HIV+, 16 HIV-). The mean age of participants was 34.2 years; the majority were female (83%), and 53% had not completed secondary school. There was evidence of impaired neurocognitive functioning across all domains in both HIV+/- study participants. Based on the regression analyses, individuals with co-infection (MDR-TB/HIV+), as well as those who had longer duration of hospital stays experienced significantly lower cognitive performance in several domains. Poor cognitive performance was significantly related to older age and lower educational attainment. The presence of major depression or substance use disorders did not influence the significance of the findings. CONCLUSIONS: Adults with MDR-TB have significant neurocognitive impairment, especially if HIV positive. An integrated approach is necessary in the management of MDR-TB as cognitive health influences the ability to adhere to chronic treatment, clinical outcomes and functionality.

OBJECTIFS: L'optimisation de l'adhésion au traitement est l'un des facteurs essentiels pour inverser la tendance d'un syndrome TB-VIH en Afrique subsaharienne, en particulier en Afrique du Sud. Des déficiences dans des domaines neurocognitifs clés peuvent entraver la capacité des patients à maintenir l'adhésion au traitement, mais le niveau de cognition et sa relation avec le statut VIH n'ont pas été examinés chez les personnes atteintes de TB résistante aux médicaments. Nous avons donc étudié les performances de plusieurs domaines neurocognitifs clés en relation avec le statut VIH dans un échantillon de tuberculose multirésistante (TB-MDR). MÉTHODES: Nous avons recruté des patients hospitalisés pour une TB-MDR confirmée microbiologiquement dans un hôpital de référence spécialisé dans la TB dans la province du KwaZulu-Natal, en Afrique du Sud. Nous avons recueilli des données transversales sur les fonctions sociodémographiques, cliniques et neurocognitives (par exemple l'attention, la mémoire, le fonctionnement exécutif, la maîtrise du langage, la coordination visuelle-spatiale et œil-main). Pour l'analyse primaire, nous avons exclu les participants souffrant d'un épisode dépressif majeur ou d'un trouble lié à la consommation de substances (EDM/TCS). Nous avons appliqué des modèles de régression de Poisson ajustés pour explorer l'association entre le VIH et la fonction neurocognitive. RÉSULTATS: Nous avons recruté 200 personnes atteintes de TB-MDR, 33 d'entre elles étaient atteintes de EDM/TCS, les données des 167 autres ont été analysées (151 VIH-positives, 16 VIH-négatives). L'âge moyen des participants était de 34,2 ans; la majorité étaient des femmes (83%) et 53% n'avaient pas terminé leurs études secondaires. Les participants à l'étude VIH+ et VIH- présentaient des signes de dysfonctionnement neurocognitif dans tous les domaines. D'après les analyses de régression, les personnes coinfectées (TB-MDR/VIH), ainsi que celles qui ont été hospitalisées pendant une longue période, présentent des performances cognitives nettement inférieures dans plusieurs domaines. Les mauvaises performances cognitives étaient significativement liées à l'âge plus élevé et à un niveau d'éducation plus faible. La présence d'une dépression majeure ou de troubles liés à la consommation de substances n'a pas influencé la signification des résultats. CONCLUSIONS: Les adultes atteints de TB-MDR présentent une importante déficience neurocognitive, surtout s'ils sont VIH-positifs. Une approche intégrée est nécessaire dans la prise en charge de la TB-MDR car la santé cognitive influence la capacité d'adhésion à un traitement chronique, les résultats cliniques et la fonctionnalité.

Risk of invasive fungal infections in patients with high-risk MDS and AML receiving hypomethylating agents.

Invasive fungal infections (IFI) are a significant source of morbidity and mortality for patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Given the heterogeneity of the population receiving hypomethylating agents (HMA), it is difficult for clinicians to accurately assess their patients' risk of infection. Literature on the incidence of IFI following HMA is limited to several studies of azacitidine. The primary objective of this retrospective study was to establish the incidence of IFI in HMA treated AML/MDS patients at a large U.S. comprehensive cancer center. Secondary objectives included comparing incidence of IFI among pre-specified subgroups to identify potential risk factors for IFI. Two hundred three patients with AML, intermediate to very high risk MDS or chronic myelomonocytic leukemia who received at least two cycles of HMA were included. The incidence of IFI, as defined by the European Organization for Research and Treatment of Cancer / Invasive Fungal Infections Cooperative Group criteria, was 9.6%, with 20 IFI diagnosed following HMA (three proven, four probable, 13 possible). Among the proven cases of IFI, molds included Scedosporium and Fusarium spp. Eleven patients who developed IFIs were neutropenic upon initiating HMA. The majority (17/20) of infections occurred during the first four cycles. Given this incidence, mold-active prophylaxis can be considered in patients who are neutropenic at the start of therapy.

Neurocognitive Impairment Risk Among Individuals With Multiple Drug-Resistant Tuberculosis and Human Immunodeficiency Virus Coinfection: Implications for Systematic Linkage to and Retention of Care in Tuberculosis/Human Immunodeficiency Virus Treatment.

Although neurocognitive impairment (NCI) is a well-recognized challenge in human immunodeficiency virus (HIV), there is little evidence regarding it among individuals with multiple drug-resistant tuberculosis (MDR-TB) within HIV endemic sub-Saharan Africa. The extent of NCI risk, particularly HIV-associated neurocognitive disorders (HAND) risk, was investigated in 200 microbiologically confirmed inpatients with MDR-TB at a TB-specialist hospital in KwaZulu-Natal Province, South Africa. Within this population, the prevalence of HIV coinfection, major depressive episode, and substance use disorder was 89.50%, 10.50%, and 7.00%, respectively. After excluding individuals with major depressive episode/substance use disorder and monoinfection (i.e., MDR-TB without HIV), the prevalence of HAND risk was 43.5%. Older and low-income individuals had significantly greater odds of HAND risk, whereas those with family members/relatives who work(ed) in the health services had lower odds. The role of timely linkage to and retention of care in TB/HIV treatment to offset cognitive decline in MDR-TB/HIV coinfected individuals needs to be investigated further.

Major depression and household food insecurity among individuals with multidrug-resistant tuberculosis (MDR-TB) in South Africa.

PURPOSE: Household food insecurity in South Africa is a pervasive public health challenge. Although its link to chronic health conditions is well established, its relationship to mental illness, particularly major depression, is not well-understood. Despite KwaZulu-Natal Province being the epicenter of the drug-resistant tuberculosis (MDR-TB) epidemic, and having the largest share of poverty in South Africa, this relationship remains unexamined. This study investigated the association between major depressive episode (MDE) and household food insecurity among individuals with MDR-TB. METHODS: We enrolled and interviewed 141 newly admitted microbiologically confirmed MDR-TB inpatients at a specialized TB hospital in KwaZulu-Natal Province, South Africa. Logistic regression models were fitted to assess the relationship between MDE and household food insecurity, while accounting for socio-demographic status (e.g., age, gender, education, marital status, social grant status, income, and preference for living in one's community). RESULTS: The prevalence of MDE and household food insecurity was 11.35% and 21.01%, respectively. MDE was significantly associated with household food insecurity (aOR 4.63, 95% CI 1.17-18.38). Individuals who are female (aOR 6.29, 95% CI 1.13-35.03), young (aOR 8.86, 95% CI 1.69-46.34), have low educational attainment (aOR 6.19, 95% CI 1.70-22.59) and receive social grants (aOR 7.60, 95% CI 2.36-24.48) were most at risk of household food insecurity. CONCLUSIONS: MDE in individuals with MDR-TB was significantly associated with household food insecurity, independent of socio-economic status. Although MDR-TB is not exclusively a disease of the poor, individuals from socio-economically disadvantaged backgrounds (e.g., female, young adults, low education, and social grant recipients) were more likely to experience household food insecurity. Our study underscores the need to address the co-occurring cycles of food insecurity and untreated MDE in South Africa.

Solubility and Complexation of the Bismuthate Ion in Nitric Acid Systems.

The dissolution rate and solubility of NaBiO3 have been investigated in nitric acid systems ranging from 4 to 6 M HNO3 and were found to be 58-76 µg/cm2·d and 490-830 mM, respectively. The presence of 50 mM U(VI) drastically increased the solubility to 540-1200 mM, while rates of dissolution were relatively unchanged. The solubility of NaBiO3 increased with an increase in U(VI) concentrations at 4 M HNO3, with log-log analysis indicating a one-to-one complex between Bi and U and infrared spectroscopic evidence monitoring uranyl stretching, suggesting complex formation. Absorbance spectra were obtained experimentally and computationally with an absorbance band in the range of 450-600 nm that has been attributed to Bi(V). The ingrowth and decay of Bi(V) in solution was also studied as a function of mass of solid NaBiO3 present, acidity, and temperature. The activation energies of dissolution and decomposition were calculated to be 39 ± 4 and 61 ± 6 kJ/mol, respectively. These results indicate that dissolution of NaBiO3 into the respective Na+ and BiO3-occurs prior to undergoing reduction, a process which conventionally has been believed to occur in the reverse order.

: a database of ciliate genome rearrangements.

Ciliated protists exhibit nuclear dimorphism through the presence of somatic macronuclei (MAC) and germline micronuclei (MIC). In some ciliates, DNA from precursor segments in the MIC genome rearranges to form transcriptionally active genes in the mature MAC genome, making these ciliates model organisms to study the process of somatic genome rearrangement. Similar broad scale, somatic rearrangement events occur in many eukaryotic cells and tumors. The (http://oxytricha.princeton.edu/mds_ies_db) is a database of genome recombination and rearrangement annotations, and it provides tools for visualization and comparative analysis of precursor and product genomes. The database currently contains annotations for two completely sequenced ciliate genomes: Oxytricha trifallax and Tetrahymena thermophila.

Proximity to healthcare clinic and depression risk in South Africa: geospatial evidence from a nationally representative longitudinal study.

Proximity to primary healthcare facilities may be a serious barrier to accessing mental health services in resource-limited settings. In this study, we examined whether the distance to the primary healthcare clinic (PHCC) was associated with risk of depression in KwaZulu-Natal Province, South Africa. Depressive symptoms and household coordinates data were accessed from the nationally representative South African National Income Dynamics Study. Distances between households and their nearest PHCCs were calculated and mixed-effects logistic regression models fitted to the data. Participants residing <6 km from a PHCC (aOR = 0.608, 95% CI 0.42-0.87) or 6-14.9 km (aOR = 0. 612, 95% CI 0.44-0.86) had a lower depression risk compared to those residing ≥15 km from the nearest PHCC. Distance to the PHCC was independently associated with increased depression risk, even after controlling for key socioeconomic determinants. Minimizing the distance to PHCC through mobile health clinics and technology could improve mental health.

Substance use in adolescents with mental illness in Durban, South Africa.

Comorbid substance use in adolescents with mental illness is often an indicator of poor treatment outcome. This study aims to determine the prevalence of, and associated risk factors for, substance use in adolescents with mental illness attending a mental health service. Data was collected from hospital records of 162 adolescents, using a structured data sheet, over a two-year period. Substance use was more significant in older adolescents and those with severe mental illness. Sixty-two (38.3%) adolescents used substances. Thirty-seven (38.1%) male adolescents reported substance use compared to 25 (38.5%) female adolescents. Alcohol was the most commonly used substance (n = 48; 29.6%), followed by cannabis (n = 32; 19.8%). There were significant direct associations between substance use and history of abuse or neglect, forensic history, educational setting, admission status, and the psychiatric diagnoses of schizophrenia, other psychotic disorders, and bipolar mood disorder. Inverse associations were found between substance use and adjustment disorders, attention deficit hyperactivity disorder, and intellectual disability. The results of this study indicate an urgent need for substance misuse programmes for at risk youth, and the introduction of dual diagnosis intervention programmes in this age group.

The clinical impact of a positive family history of psychosis or mental illness in psychotic and non-psychotic mentally ill adolescents.

BACKGROUND: A family history of psychosis is associated with negative clinical characteristics of psychosis. AIM: We aimed to determine the relationship between a family history (in first-degree relatives) of psychosis (FHP) or of any mental illness (FHM), and the clinical features (including cannabis use) of first episode early onset psychosis (EOP). METHOD: Forty-five adolescents with first episode EOP presenting to psychiatric services were assessed by clinical interview with the following tools: socio-demographic questionnaire, Positive and Negative Syndrome Scale (PANSS), Symptom Onset in Schizophrenia (SOS) inventory, and the World Health Organisation's (WHO) Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST) for cannabis misuse. Forty-five gender and age matched controls with incident non-psychotic mental illness were recruited from the same clinical sites. RESULTS: While there was evidence of trend associations, EOP adolescents and controls did not differ in terms of either FHP or FHM. However, adolescents with a non-psychotic mental illness (controls) were significantly more likely to have a family history of non-psychotic mental illness (EOP = 13%; controls = 47%, p = 0.001). In EOP adolescents, a positive FHP was associated with a significantly lower mean PANSS positive score (p = 0.009), but not with other clinical features. CONCLUSION: FHP may be a diagnostic clue in adolescents and is not necessarily associated with negative clinical characteristics at disease onset in EOP. However, this requires further research.

Co-Immobilization of Proteins and DNA Origami Nanoplates to Produce High-Contrast Biomolecular Nanoarrays.

The biofunctionalization of nanopatterned surfaces with DNA origami nanostructures is an important topic in nanobiotechnology. An unexplored challenge is, however, to co-immobilize proteins with DNA origami at pre-determined substrate sites in high contrast relative to the nontarget areas. The immobilization should, in addition, preferably be achieved on a transparent substrate to allow ultrasensitive optical detection. If successful, specific co-binding would be a step towards stoichiometrically defined arrays with few to individual protein molecules per site. Here, we successfully immobilize with high specificity positively charged avidin proteins and negatively charged DNA origami nanoplates on 100 nm-wide carbon nanoislands while suppressing undesired adsorption to surrounding nontarget areas. The arrays on glass slides achieve unprecedented selectivity factors of up to 4000 and allow ultrasensitive fluorescence read-out. The co-immobilization onto the nanoislands leads to layered biomolecular architectures, which are functional because bound DNA origami influences the number of capturing sites on the nanopatches for other proteins. The novel hybrid DNA origami-protein nanoarrays allow the fabrication of versatile research platforms for applications in biosensing, biophysics, and cell biology, and, in addition, represent an important step towards single-molecule protein arrays.

Recurring patterns among scrambled genes in the encrypted genome of the ciliate Oxytricha trifallax.

Some genera of ciliates, such as Oxytricha and Stylonychia, undergo massive genome reorganization during development and provide model organisms to study DNA rearrangement. A common feature of these ciliates is the presence of two types of nuclei: a germline micronucleus and a transcriptionally-active somatic macronucleus containing over 16,000 gene sized "nano-chromosomes". During conjugation the old parental macronucleus disintegrates and a new macronucleus forms from a copy of the zygotic micronucleus. During this process, macronuclear chromosomes assemble through DNA processing events that delete 90-98% of the DNA content of the micronucleus. This includes the deletion of noncoding DNA segments that interrupt precursor DNA regions in the micronucleus, as well as transposons and other germline-limited DNA. Each macronuclear locus may be present in the micronucleus as several nonconsecutive, permuted, and/or inverted DNA segments. Here we investigate the genome-wide range of scrambled gene architectures that describe all precursor-product relationships in Oxytricha trifallax, the first completely sequenced scrambled genome. We find that five general, recurrent patterns in the sets of scrambled micronuclear precursor pieces can describe over 80% of Oxytricha's scrambled genes. These include instances of translocations and inversions, and other specific patterns characterized by alternating stretches of consecutive odd and even DNA segments. Moreover, we find that iterating patterns of alternating odd-even segments up to four times can describe over 96% of the scrambled precursor loci. Recurrence of these highly structured genetic architectures within scrambled genes presumably reflects recurrent evolutionary events that gave rise to over 3000 of scrambled loci in the germline genome.