Cyanobacterial α-carboxysome carbonic anhydrase is allosterically regulated by the Rubisco substrate RuBP.

Cyanobacterial CO2 concentrating mechanisms (CCMs) sequester a globally consequential proportion of carbon into the biosphere. Proteinaceous microcompartments, called carboxysomes, play a critical role in CCM function, housing two enzymes to enhance CO2 fixation: carbonic anhydrase (CA) and Rubisco. Despite its importance, our current understanding of the carboxysomal CAs found in α-cyanobacteria, CsoSCA, remains limited, particularly regarding the regulation of its activity. Here, we present a structural and biochemical study of CsoSCA from the cyanobacterium Cyanobium sp. PCC7001. Our results show that the Cyanobium CsoSCA is allosterically activated by the Rubisco substrate ribulose-1,5-bisphosphate and forms a hexameric trimer of dimers. Comprehensive phylogenetic and mutational analyses are consistent with this regulation appearing exclusively in cyanobacterial α-carboxysome CAs. These findings clarify the biologically relevant oligomeric state of α-carboxysomal CAs and advance our understanding of the regulation of photosynthesis in this globally dominant lineage.

The contribution of cannabis use to the increased psychosis risk among minority ethnic groups in Europe.

BACKGROUND: We examined whether cannabis use contributes to the increased risk of psychotic disorder for non-western minorities in Europe. METHODS: We used data from the EU-GEI study (collected at sites in Spain, Italy, France, the United Kingdom, and the Netherlands) on 825 first-episode patients and 1026 controls. We estimated the odds ratio (OR) of psychotic disorder for several groups of migrants compared with the local reference population, without and with adjustment for measures of cannabis use. RESULTS: The OR of psychotic disorder for non-western minorities, adjusted for age, sex, and recruitment area, was 1.80 (95% CI 1.39-2.33). Further adjustment of this OR for frequency of cannabis use had a minimal effect: OR = 1.81 (95% CI 1.38-2.37). The same applied to adjustment for frequency of use of high-potency cannabis. Likewise, adjustments of ORs for most sub-groups of non-western countries had a minimal effect. There were two exceptions. For the Black Caribbean group in London, after adjustment for frequency of use of high-potency cannabis the OR decreased from 2.45 (95% CI 1.25-4.79) to 1.61 (95% CI 0.74-3.51). Similarly, the OR for Surinamese and Dutch Antillean individuals in Amsterdam decreased after adjustment for daily use: from 2.57 (95% CI 1.07-6.15) to 1.67 (95% CI 0.62-4.53). CONCLUSIONS: The contribution of cannabis use to the excess risk of psychotic disorder for non-western minorities was small. However, some evidence of an effect was found for people of Black Caribbean heritage in London and for those of Surinamese and Dutch Antillean heritage in Amsterdam.

MIR137 polygenic risk for schizophrenia and ephrin-regulated pathway: Role in lateral ventricles and corpus callosum volume.

Background/Objective. Enlarged lateral ventricle (LV) volume and decreased volume in the corpus callosum (CC) are hallmarks of schizophrenia (SZ). We previously showed an inverse correlation between LV and CC volumes in SZ, with global functioning decreasing with increased LV volume. This study investigates the relationship between LV volume, CC abnormalities, and the microRNA MIR137 and its regulated genes in SZ, because of MIR137's essential role in neurodevelopment. Methods. Participants were 1224 SZ probands and 1466 unaffected controls from the GENUS Consortium. Brain MRI scans, genotype, and clinical data were harmonized across cohorts and employed in the analyses. Results. Increased LV volumes and decreased CC central, mid-anterior, and mid-posterior volumes were observed in SZ probands. The MIR137-regulated ephrin pathway was significantly associated with CC:LV ratio, explaining a significant proportion (3.42 %) of CC:LV variance, and more than for LV and CC separately. Other pathways explained variance in either CC or LV, but not both. CC:LV ratio was also positively correlated with Global Assessment of Functioning, supporting previous subsample findings. SNP-based heritability estimates were higher for CC central:LV ratio (0.79) compared to CC or LV separately. Discussion. Our results indicate that the CC:LV ratio is highly heritable, influenced in part by variation in the MIR137-regulated ephrin pathway. Findings suggest that the CC:LV ratio may be a risk indicator in SZ that correlates with global functioning.

Optimal Positioning of Inertial Measurement Units in a Smart Shirt for Determining Respiratory Volume.

Tidal volume can be estimated using the surface motions of the upper body induced by respiration. However, the precision and instrumentation of such estimation must be improved to allow widespread application. In this study, respiration induced changes in parameters that can be recorded with inertial measurement units are examined to determine tidal volumes. Based on the data of an optical motion capture system, the optimal positions of inertial measurement units (IMU) in a smart shirt for sets of 4, 5 or 6 sensors were determined. The errors observed indicate the potential to determine tidal volumes using IMUs in a smart shirt.Clinical Relevance- The measurement of respiratory volumes via a low-cost and unobtrusive smart shirt would be a major advance in clinical diagnostics. In particular, conventional methods are expensive, and uncomfortable for conscious patients if measurement is desired over an extended period. A smart-shirt based on inertial sensors would allow a comfortable measurement and could be used in many clinical scenarios - from sleep apnoea monitoring to homecare and respiratory monitoring of comatose patients.

Effect of speed and water depth on limb and back kinematics in Thoroughbred horses walking on a water treadmill.

Water treadmill (WT) exercise may induce limb and back kinematics that meet specific training and rehabilitation goals. The study aimed to investigate the effects of walk speed, at different water depths (WDs), on limb and back kinematics of six Thoroughbreds exercising on a WT. Horses walked at 2.8/4.3/5.5/6.0 km/h (i.e. 0.8/1.2/1.5/1.7 m/s) at dry, metacarpophalangeal and carpal WD. Videography captured limb movement in the sagittal plane. Motion-capture measured thoracolumbosacral flexion-extension (FE), and lateral bend (LB) ranges of movement (ROM) using skin surface markers on the sixth, tenth, thirteenth, eighteenth thoracic, third and fifth lumbar, and third sacral spinous processes. Inertial-motion-sensors measured poll, withers and pelvic displacements. Following preliminary univariable analyses, multivariable mixed-effects linear-regression analyses were used to examine the relationship between speed, WD and each outcome variable (P < 0.05). Peak metacarpophalangeal, carpal and tarsal joint flexion increased with speed (P ≤ 0.002) and depth combined (P 0.001) while peak metatarsophalangeal flexion increased with WD only (P 0.001). Thoracolumbar FE-ROM between T10 and L3 and hindlimb retraction was increased by speed and WD combined (P 0.001). Hindlimb protraction was increased by speed (P 0.001) while hindlimb retraction was increased by speed and WD combined (P 0.001). Dorsoventral poll displacement was increased by speed (P 0.001) and carpal WD (P = 0.013), craniocaudal poll displacement was increased by speed and WD combined (P 0.001). Pelvic (tubera coxae and sacrum) dorsoventral displacements increased with speed and WD combined (P 0.001). Understanding the effects of speed and WD on limb, back and pelvic kinematics will improve decision making relating to dry and WT exercise within training.

Higher Polynomial Identities for Mutations of Associative Algebras.

We study polynomial identities satisfied by the mutation product xpy-yqx on the underlying vector space of an associative algebra A, where p, q are fixed elements of A. We simplify known results for identities in degree 4, proving that only two identities are necessary and sufficient to generate them all; in degree 5, we show that adding one new identity suffices; in degree 6, we demonstrate the existence of a significant number of new identities, which induce us to conjecture that the variety generated by mutation algebras of associative algebras is not finitely based.

Have yourself a 'merry' little Christmas: Alcohol adverts and alcohol content within adverts in the run-up to Christmas.

Exposure to alcohol adverts or other audio-visual content (AVC) in the media is associated with alcohol initiation and subsequent use by adolescents and adults, especially those with or at risk of an alcohol use disorder. The Christmas period is characterised by increased alcohol consumption and there may be an increase in alcohol advertisements during this period. The current study explored the number of alcohol advertisements shown on UK television in a sample of days in the run-up to Christmas 2022 and found that alcohol advertisements were commonly shown but alcohol was also seen in advertisements for other things such as supermarkets. The amount of alcohol shown is likely to encourage drinking and make Christmas a difficult time for people with alcohol use disorders or who are in recovery.

Tobacco use in first-episode psychosis, a multinational EU-GEI study.

BACKGROUND: Tobacco is a highly prevalent substance of abuse in patients with psychosis. Previous studies have reported an association between tobacco use and schizophrenia. The aim of this study was to analyze the relationship between tobacco use and first-episode psychosis (FEP), age at onset of psychosis, and specific diagnosis of psychosis. METHODS: The sample consisted of 1105 FEP patients and 1355 controls from the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. We assessed substance use with the Tobacco and Alcohol Questionnaire and performed a series of regression analyses using case-control status, age of onset of psychosis, and diagnosis as outcomes and tobacco use and frequency of tobacco use as predictors. Analyses were adjusted for sociodemographic characteristics, alcohol, and cannabis use. RESULTS: After controlling for cannabis use, FEP patients were 2.6 times more likely to use tobacco [p ⩽ 0.001; adjusted odds ratio (AOR) 2.6; 95% confidence interval (CI) [2.1-3.2]] and 1.7 times more likely to smoke 20 or more cigarettes a day (p = 0.003; AOR 1.7; 95% CI [1.2-2.4]) than controls. Tobacco use was associated with an earlier age at psychosis onset (ß = -2.3; p ⩽ 0.001; 95% CI [-3.7 to -0.9]) and was 1.3 times more frequent in FEP patients with a diagnosis of schizophrenia than in other diagnoses of psychosis (AOR 1.3; 95% CI [1.0-1.8]); however, these results were no longer significant after controlling for cannabis use. CONCLUSIONS: Tobacco and heavy-tobacco use are associated with increased odds of FEP. These findings further support the relevance of tobacco prevention in young populations.

Dynamic changes of the Prf/Pto tomato resistance complex following effector recognition.

In both plants and animals, nucleotide-binding leucine-rich repeat (NLR) immune receptors play critical roles in pathogen recognition and activation of innate immunity. In plants, NLRs recognise pathogen-derived effector proteins and initiate effector-triggered immunity (ETI). However, the molecular mechanisms that link NLR-mediated effector recognition and downstream signalling are not fully understood. By exploiting the well-characterised tomato Prf/Pto NLR resistance complex, we identified the 14-3-3 proteins TFT1 and TFT3 as interacting partners of both the NLR complex and the protein kinase MAPKKKα. Moreover, we identified the helper NRC proteins (NLR-required for cell death) as integral components of the Prf /Pto NLR recognition complex. Notably our studies revealed that TFTs and NRCs interact with distinct modules of the NLR complex and, following effector recognition, dissociate facilitating downstream signalling. Thus, our data provide a mechanistic link between activation of immune receptors and initiation of downstream signalling cascades.

Integrating the patients' voice in designing and delivering a research study: The Yorkshire Cancer Research funded PREHABS study's experience.

INTRODUCTION: Engaging with patients when designing a clinical or research project is beneficial; feedback from the intended audience provides invaluable insight form the patients' perspective. Working with patients can result in developing successful research grants and interventions. The benefit of including the voice of the patient in the Yorkshire Cancer Research funded PREHABS study is described in this article. METHODS: Patients were included in the PREHABS study from inception to completion. The Theory of Change methodology was used to provide a framework to implement patient feedback to refine the study intervention. RESULTS: In total, 69 patients engaged with the PREHABS project. Two patients were recruited as co-applicants on the grant and were members on the Trial Management Group. Six patients attended the pre application workshop and provided feedback on their lived experiences of being a lung cancer patient. Commentary from the patients influenced the interventions selected and the design of the prehabs study. Following ethical approval (21/EE/0048) and informed written consent, 61 patients were recruited into the PREHABS study between October 2021 and November 2022. The breakdown of recruited patients was 19 males: mean age 69.1 years (SD 8.91) and 41 females; mean age 74.9 years (SD 8.9). CONCLUSION: It is practicable and beneficial to include patients at all stages of designing and delivering a research study. Patient feedback can help refine the study interventions to allow for maximum acceptance, recruitment and retention. IMPLICATIONS FOR PRACTICE: Including patients in the design of radiotherapy research studies can provide invaluable insight that can support the selection and delivery of interventions that are acceptable to the patient cohort.

Anemia in children aged 6-59 months was significantly associated with maternal anemia status in rural Zimbabwe.

Globally, anemia is a public health problem affecting mostly women of reproductive age (WRA, n = 452) and children aged 6-59 months (n = 452) from low- and lower-middle-income countries. This cross-sectional study assessed the prevalence and determinants of anemia in WRA and children aged 6-59 months in rural Zimbabwe. The venous blood sample was measured for hemoglobin utilizing a HemoCue machine. Anthropometric indices were assessed and classified based on World Health Organization standards. Socioeconomic characteristics were assessed. The median (±inter quartile range (IQR)) age of WRA was 29 ± 12 years and that for children was 29 ± 14 months. The prevalence of anemia was 29.6% and 17.9% in children and WRA, respectively, while the median (±IQR) hemoglobin levels were 13.4 ± 1.8 and 11.7 ± 1.5 g/dl among women and children, respectively. Multiple logistic regression analysis was used to assess determinants of anemia. Anemia in children was significantly associated with maternal anemia (odds ratio (OR) = 2.02; 95% CI 1.21-3.37; p = .007) and being a boy (OR = 0.63; 95% CI 0.41-0.95; p = .029), while anemia in WRA was significantly associated with the use of unimproved dug wells as a source of drinking water (OR = 0.36; 95% CI 0.20-0.66; p = .001) and lack of agricultural land ownership (OR = 0.51; 95% CI 0.31-0.85; p = .009). Anemia is a public health problem in the study setting. The positive association between maternal and child anemia reflects the possibility of cross-generational anemia. Therefore, interventions that focus on improving preconceptual and maternal nutritional status may help to reduce anemia in low-income settings.

The Chlamydomonas reinhardtii chloroplast envelope protein LCIA transports bicarbonate in planta.

LCIA (low CO2-inducible protein A) is a chloroplast envelope protein associated with the CO2-concentrating mechanism of the green alga Chlamydomonas reinhardtii. LCIA is postulated to be a HCO3- channel, but previous studies were unable to show that LCIA was actively transporting bicarbonate in planta. Therefore, LCIA activity was investigated more directly in two heterologous systems: an Escherichia coli mutant (DCAKO) lacking both native carbonic anhydrases and an Arabidopsis mutant (ßca5) missing the plastid carbonic anhydrase ßCA5. Neither DCAKO nor ßca5 can grow in ambient CO2 conditions, as they lack carbonic anhydrase-catalyzed production of the necessary HCO3- concentration for lipid and nucleic acid biosynthesis. Expression of LCIA restored growth in both systems in ambient CO2 conditions, which strongly suggests that LCIA is facilitating HCO3- uptake in each system. To our knowledge, this is the first direct evidence that LCIA moves HCO3- across membranes in bacteria and plants. Furthermore, the ßca5 plant bioassay used in this study is the first system for testing HCO3- transport activity in planta, an experimental breakthrough that will be valuable for future studies aimed at improving the photosynthetic efficiency of crop plants using components from algal CO2-concentrating mechanisms.

Broader functions of TIR domains in Arabidopsis immunity.

TIR domains are NAD-degrading enzymes that function during immune signaling in prokaryotes, plants, and animals. In plants, most TIR domains are incorporated into intracellular immune receptors termed TNLs. In Arabidopsis, TIR-derived small molecules bind and activate EDS1 heterodimers, which in turn activate RNLs, a class of cation channel-forming immune receptors. RNL activation drives cytoplasmic Ca2+ influx, transcriptional reprogramming, pathogen resistance, and host cell death. We screened for mutants that suppress an RNL activation mimic allele and identified a TNL, SADR1. Despite being required for the function of an autoactivated RNL, SADR1 is not required for defense signaling triggered by other tested TNLs. SADR1 is required for defense signaling initiated by some transmembrane pattern recognition receptors and contributes to the unbridled spread of cell death in lesion simulating disease 1. Together with RNLs, SADR1 regulates defense gene expression at infection site borders, likely in a non-cell autonomous manner. RNL mutants that cannot sustain this pattern of gene expression are unable to prevent disease spread beyond localized infection sites, suggesting that this pattern corresponds to a pathogen containment mechanism. SADR1 potentiates RNL-driven immune signaling not only through the activation of EDS1 but also partially independently of EDS1. We studied EDS1-independent TIR function using nicotinamide, an NADase inhibitor. Nicotinamide decreased defense induction from transmembrane pattern recognition receptors and decreased calcium influx, pathogen growth restriction, and host cell death following intracellular immune receptor activation. We demonstrate that TIR domains can potentiate calcium influx and defense and are thus broadly required for Arabidopsis immunity.

Rubisco, the imperfect winner: it's all about the base.

Rubisco catalysis is complex and includes an activation step through the formation of a carbamate at the conserved active site lysine residue and the formation of a highly reactive enediol that is the key to its catalytic reaction. The formation of this enediol is both the basis of its success and its Achilles' heel, creating imperfections to its catalytic efficiency. While Rubisco originally evolved in an atmosphere of high CO2, the earth's multiple oxidation events provided challenges to Rubisco through the fixation of O2 that competes with CO2 at the active site. Numerous catalytic screens across the Rubisco superfamily have identified significant variation in catalytic properties that have been linked to large and small subunit sequences. Despite this, we still have a rudimentary understanding of Rubisco's catalytic mechanism and how the evolution of kinetic properties has occurred. This review identifies the lysine base that functions both as an activator and a proton abstractor to create the enediol as a key to understanding how Rubisco may optimize its kinetic properties. The ways in which Rubisco and its partners have overcome catalytic and activation imperfections and thrived in a world of high O2, low CO2, and variable climatic regimes is remarkable.

Negative patterning in the spatial domain.

In three experiments, animals were required to learn about the presence or absence of a hidden platform in a swimming pool. This was determined with reference to different patterned landmarks. In Experiment 1, the presence of a spotted or a striped cue indicated the position of the platform, while the combination of patterns, a half-spotted and half-striped cue, predicted the absence of the goal (i.e., negative patterning). In Experiment 2 the task was redesigned to better represent a locale navigation task. Rats received the same discrimination task, but it took place in an equilateral triangle with landmarks positioned on the walls of the arena. The hidden platform (if present) was located in one corner of the triangle. Experiment 3 used a more complex negative patterning discrimination in the triangular swimming pool to help dissociate between the unique cue and configural associative learning theories. Experiment 1 and 2 provides the first instance of negative patterning in a spatial task, while Experiment 3 provides initial evidence that some rats may represent compound stimuli in a way explained by the unique cue theory of associative learning. This begins to elucidate the underlying of associate principles that guide learning in the spatial domain.

Prehabilitation and Rehabilitation for Patients with Lung Cancer: A Review of Where we are Today.

Lung cancer is the third most common type of cancer in the UK, with nearly 50 000 new cases diagnosed a year. Treatments for lung cancer have improved in recent years with the advent of new surgical and radiotherapy techniques and the increased use of immunotherapies. These advances have resulted in increasing numbers of patients surviving beyond the completion of their treatment. Lung cancer patients are now not dying from their cancer diagnosis, but from other co-existing pathologies. Lung cancer patients commonly present with multiple comorbidities. Mitigating the effects of poor lifestyles and changing behaviours may improve the efficacy of treatments, reduce side-effects and improve the quality of life for lung cancer patients. Published evidence supports the use of interventions to manage behavioural habits, to optimise the health of patients. There is no consensus as to what, when or how to embed these into the patient pathway. Supporting patients before, during and after their cancer treatments to increase activity, eat well and stop smoking have been seen to decrease side-effects and improve patient outcomes and wellbeing. The challenge is to provide a package of interventions that is acceptable to patients and fits within the patient pathway so as not to conflict with diagnostic and therapeutic activities. This article reviews where we are today with providing behavioural support to optimise the health of lung cancer patients undergoing treatment.

Genetic and psychosocial stressors have independent effects on the level of subclinical psychosis: findings from the multinational EU-GEI study.

AIMS: Gene x environment (G×E) interactions, i.e. genetic modulation of the sensitivity to environmental factors and/or environmental control of the gene expression, have not been reliably established regarding aetiology of psychotic disorders. Moreover, recent studies have shown associations between the polygenic risk scores for schizophrenia (PRS-SZ) and some risk factors of psychotic disorders, challenging the traditional gene v. environment dichotomy. In the present article, we studied the role of GxE interaction between psychosocial stressors (childhood trauma, stressful life-events, self-reported discrimination experiences and low social capital) and the PRS-SZ on subclinical psychosis in a population-based sample. METHODS: Data were drawn from the EUropean network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) study, in which subjects without psychotic disorders were included in six countries. The sample was restricted to European descendant subjects (n = 706). Subclinical dimensions of psychosis (positive, negative, and depressive) were measured by the Community Assessment of Psychic Experiences (CAPE) scale. Associations between the PRS-SZ and the psychosocial stressors were tested. For each dimension, the interactions between genes and environment were assessed using linear models and comparing explained variances of 'Genetic' models (solely fitted with PRS-SZ), 'Environmental' models (solely fitted with each environmental stressor), 'Independent' models (with PRS-SZ and each environmental factor), and 'Interaction' models (Independent models plus an interaction term between the PRS-SZ and each environmental factor). Likelihood ration tests (LRT) compared the fit of the different models. RESULTS: There were no genes-environment associations. PRS-SZ was associated with positive dimensions (ß = 0.092, R2 = 7.50%), and most psychosocial stressors were associated with all three subclinical psychotic dimensions (except social capital and positive dimension). Concerning the positive dimension, Independent models fitted better than Environmental and Genetic models. No significant GxE interaction was observed for any dimension. CONCLUSIONS: This study in subjects without psychotic disorders suggests that (i) the aetiological continuum hypothesis could concern particularly the positive dimension of subclinical psychosis, (ii) genetic and environmental factors have independent effects on the level of this positive dimension, (iii) and that interactions between genetic and individual environmental factors could not be identified in this sample.

Early Diagnosis and Lung Cancer Screening.

Lung cancer remains the most significant cause of cancer death, accounting for about 20% of all cancer-related mortality. A significant reason for this is delayed diagnosis, either due to lack of symptoms in early-stage disease or presentation with non-specific symptoms common with a broad range of alternative diagnoses. More is needed in terms of increasing public awareness, providing adequate healthcare professional education and implementing clinical pathways that improve the earlier diagnosis of symptomatic lung cancer. Low-dose computed tomography screening of high-risk, asymptomatic populations has been shown to reduce lung cancer mortality, with focus now shifting towards how best to implement lung cancer screening on a wider scale in a safe, efficient and cost-effective manner. For maximum benefit, efforts must be made to optimise uptake, especially among high-risk populations with significant socioeconomic deprivation, as well as successfully incorporate tobacco-dependency treatment. Quality assured programme management will be critical to minimising screening-related harms and adequately managing incidental findings. By undertaking the above, there can be optimism that lung cancer outcomes can be improved significantly in the near future.

The effect of schizotypy on spatial learning in an environment with a distinctive shape.

In two experiments, participants completed the Oxford-Liverpool Inventory of Feelings and Experiences measuring schizotypal traits across four dimensions (unusual experiences, cognitive disorganization, introvertive anhedonia, and impulsive non-conformity). They then took part in a virtual navigation task where they were required to learn about the position of a hidden goal with reference to geometric cues of a rectangular arena or rely on colored wall panels to find the hidden goal in a square-shaped arena. Unusual experience and cognitive disorganization were significant predictors of the use of geometric cues, but no significant predictors were found for the use of wall panels. Implications to hippocampal function and the clinical domain are considered.