Is there a common water-activity limit for the three domains of life?

Archaea and Bacteria constitute a majority of life systems on Earth but have long been considered inferior to Eukarya in terms of solute tolerance. Whereas the most halophilic prokaryotes are known for an ability to multiply at saturated NaCl (water activity (a w) 0.755) some xerophilic fungi can germinate, usually at high-sugar concentrations, at values as low as 0.650-0.605 a w. Here, we present evidence that halophilic prokayotes can grow down to water activities of <0.755 for Halanaerobium lacusrosei (0.748), Halobacterium strain 004.1 (0.728), Halobacterium sp. NRC-1 and Halococcus morrhuae (0.717), Haloquadratum walsbyi (0.709), Halococcus salifodinae (0.693), Halobacterium noricense (0.687), Natrinema pallidum (0.681) and haloarchaeal strains GN-2 and GN-5 (0.635 a w). Furthermore, extrapolation of growth curves (prone to giving conservative estimates) indicated theoretical minima down to 0.611 a w for extreme, obligately halophilic Archaea and Bacteria. These were compared with minima for the most solute-tolerant Bacteria in high-sugar (or other non-saline) media (Mycobacterium spp., Tetragenococcus halophilus, Saccharibacter floricola, Staphylococcus aureus and so on) and eukaryotic microbes in saline (Wallemia spp., Basipetospora halophila, Dunaliella spp. and so on) and high-sugar substrates (for example, Xeromyces bisporus, Zygosaccharomyces rouxii, Aspergillus and Eurotium spp.). We also manipulated the balance of chaotropic and kosmotropic stressors for the extreme, xerophilic fungi Aspergillus penicilloides and X. bisporus and, via this approach, their established water-activity limits for mycelial growth (∼0.65) were reduced to 0.640. Furthermore, extrapolations indicated theoretical limits of 0.632 and 0.636 a w for A. penicilloides and X. bisporus, respectively. Collectively, these findings suggest that there is a common water-activity limit that is determined by physicochemical constraints for the three domains of life

Adjunctive raloxifene treatment improves attention and memory in men and women with schizophrenia

There is increasing clinical and molecular evidence for the role of hormones and specifically estrogen and its receptor in schizophrenia. A selective estrogen receptor modulator, raloxifene, stimulates estrogen-like activity in brain and can improve cognition in older adults. The present study tested the extent to which adjunctive raloxifene treatment improved cognition and reduced symptoms in young to middle-age men and women with schizophrenia. Ninety-eight patients with a diagnosis of schizophrenia or schizoaffective disorder were recruited into a dual-site, thirteen-week, randomized, double-blind, placebocontrolled, crossover trial of adjunctive raloxifene treatment in addition to their usual antipsychotic medications. Symptom severity and cognition in the domains of working memory, attention/processing speed, language and verbal memory were assessed at baseline, 6 and 13 weeks. Analyses of the initial 6-week phase of the study using a parallel groups design (with 39 patients receiving placebo and 40 receiving raloxifene) revealed that participants receiving adjunctive raloxifene treatment showed significant improvement relative to placebo in memory and attention/processing speed. There was no reduction in symptom severity with treatment compared with placebo. There were significant carryover effects, suggesting some cognitive benefits are sustained even after raloxifene withdrawal. Analysis of the 13-week crossover data revealed significant improvement with raloxifene only in attention/processing speed. This is the first study to show that daily, oral adjunctive raloxifene treatment at 120 mg per day has beneficial effects on attention/processing speed and memory for both men and women with schizophrenia. Thus, raloxifene may be useful as an adjunctive treatment for cognitive deficits associated with schizophrenia.TW Weickert, D Weinberg, R Lenroot, SV Catts, R Wells, A Vercammen, M O, Donnell, C Galletly, D Liu, R Balzan, B Short, D Pellen, J Curtis, VJ Carr, J Kulkarni, PR Schofield and CS Weicker

Differences in the carcinogenic evaluation of glyphosate between the International Agency for Research on Cancer (IARC) and the European Food Safety Authority (EFSA)

The International Agency for Research on Cancer (IARC) Monographs Programme identifies chemicals, drugs, mixtures, occupational exposures, lifestyles and personal habits, and physical and biological agents that cause cancer in humans and has evaluated about 1000 agents since 1971. Monographs are written by ad hoc Working Groups (WGs) of international scientific experts over a period of about 12 months ending in an eight-day meeting. The WG evaluates all of the publicly available scientific information on each substance and, through a transparent and rigorous process,1 decides on the degree to which the scientific evidence supports that substance's potential to cause or not cause cancer in humans. For Monograph 112,2 17 expert scientists evaluated the carcinogenic hazard for four insecticides and the herbicide glyphosate.3 The WG concluded that the data for glyphosate meet the criteria for classification as a probable human carcinogen. The European Food Safety Authority (EFSA) is the primary agency of the European Union for risk assessments regarding food safety. In October 2015, EFSA reported4 on their evaluation of the Renewal Assessment Report5 (RAR) for glyphosate that was prepared by the Rapporteur Member State, the German Federal Institute for Risk Assessment (BfR). EFSA concluded that ?glyphosate is unlikely to pose a carcinogenic hazard to humans and the evidence does not support classification with regard to its carcinogenic potential?. Addendum 1 (the BfR Addendum) of the RAR5 discusses the scientific rationale for differing from the IARC WG conclusion. Serious flaws in the scientific evaluation in the RAR incorrectly characterise the potential for a carcinogenic hazard from exposure to glyphosate. Since the RAR is the basis for the European Food Safety Agency (EFSA) conclusion,4 it is critical that these shortcomings are corrected

Balloon catheters versus vaginal prostaglandins for labour induction (CPI Collaborative): an individual participant data meta-analysis of randomised controlled trials

Background: Induction of labour is one of the most common obstetric interventions globally. Balloon catheters and vaginal prostaglandins are widely used to ripen the cervix in labour induction. We aimed to compare the effectiveness and safety profiles of these two induction methods. Methods: We did an individual participant data meta-analysis comparing balloon catheters and vaginal prostaglandins for cervical ripening before labour induction. We systematically identified published and unpublished randomised controlled trials that completed data collection between March 19, 2019, and May 1, 2021, by searching the Cochrane Library, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, and PubMed. Further trials done before March 19, 2019, were identified through a recent Cochrane review. Data relating to the combined use of the two methods were not included, only data from women with a viable, singleton pregnancy were analysed, and no exclusion was made based on parity or membrane status. We contacted authors of individuals trials and participant-level data were harmonised and recoded according to predefined definitions of variables. Risk of bias was assessed with the ROB2 tool. The primary outcomes were caesarean delivery, indication for caesarean delivery, a composite adverse perinatal outcome, and a composite adverse maternal outcome. We followed the intention-to-treat principle for the main analysis. The primary meta-analysis used two-stage random-effects models and the sensitivity analysis used one-stage mixed models. All models were adjusted for maternal age and parity. This meta-analysis is registered with PROSPERO (CRD42020179924). Findings: Individual participant data were available from 12 studies with a total of 5460 participants. Balloon catheters, compared with vaginal prostaglandins, did not lead to a significantly different rate of caesarean delivery (12 trials, 5414 women; crude incidence 27·0%; adjusted OR [aOR] 1·09, 95% CI 0·95–1·24; I2=0%), caesarean delivery for failure to progress (11 trials, 4601 women; aOR 1·20, 95% CI 0·91–1·58; I2=39%), or caesarean delivery for fetal distress (10 trials, 4441 women; aOR 0·86, 95% CI 0·71–1·04; I2=0%). The composite adverse perinatal outcome was lower in women who were allocated to balloon catheters than in those allocated to vaginal prostaglandins (ten trials, 4452 neonates, crude incidence 13·6%; aOR 0·80, 95% CI 0·70–0·92; I2=0%). There was no significant difference in the composite adverse maternal outcome (ten trials, 4326 women, crude incidence 22·7%; aOR 1·02, 95% CI 0·89–1·18; I2=0%). Interpretation: In induction of labour, balloon catheters and vaginal prostaglandins have comparable caesarean delivery rates and maternal safety profiles, but balloon catheters lead to fewer adverse perinatal events. Funding: Australian National Health and Medical Research Council and Monash Health Emerging Researcher Fellowship

Disturbances in Body Ownership in Schizophrenia: Evidence from the Rubber Hand Illusion and Case Study of a Spontaneous Out-of-Body Experience

A weakened sense of self may contribute to psychotic experiences. Body ownership, one component of self-awareness, can be studied with the rubber hand illusion (RHI). Watching a rubber hand being stroked while one's unseen hand is stroked synchronously can lead to a sense of ownership over the rubber hand, a shift in perceived position of the real hand, and a limb-specific drop in stimulated hand temperature. We aimed to assess the RHI in schizophrenia using quantifiable measures: proprioceptive drift and stimulation-dependent changes in hand temperature.The RHI was elicited in 24 schizophrenia patients and 21 matched controls by placing their unseen hand adjacent to a visible rubber hand and brushing real and rubber hands synchronously or asynchronously. Perceived finger location was measured before and after stimulation. Hand temperature was taken before and during stimulation. Subjective strength of the illusion was assessed by a questionnaire.Across groups, the RHI was stronger during synchronous stimulation, indicated by self-report and proprioceptive drift. Patients reported a stronger RHI than controls. Self-reported strength of RHI was associated with schizotypy in controls Proprioceptive drift was larger in patients, but only following synchronous stimulation. Further, we observed stimulation-dependent changes in skin temperature. During right hand stimulation, temperature dropped in the stimulated hand and rose in the unstimulated hand. Interestingly, induction of RHI led to an out-of-body experience in one patient, linking body disownership and psychotic experiences.The RHI is quantitatively and qualitatively stronger in schizophrenia. These findings suggest that patients have a more flexible body representation and weakened sense of self, and potentially indicate abnormalities in temporo-parietal networks implicated in body ownership. Further, results suggest that these body ownership disturbances might be at the heart of a subset of the pathognomonic delusions of passivity

Comprehensive analysis of temporal alterations in cellular proteome of bacillus subtilis under curcumin treatment

Curcumin is a natural dietary compound with antimicrobial activity against various gram positive and negative bacteria. This study aims to investigate the proteome level alterations in Bacillus subtilis due to curcumin treatment and identification of its molecular/cellular targets to understand the mechanism of action. We have performed a comprehensive proteomic analysis of B. subtilis AH75 strain at different time intervals of curcumin treatment (20, 60 and 120 min after the drug exposure, three replicates) to compare the protein expression profiles using two complementary quantitative proteomic techniques, 2D-DIGE and iTRAQ. To the best of our knowledge, this is the first comprehensive longitudinal investigation describing the effect of curcumin treatment on B. subtilis proteome. The proteomics analysis revealed several interesting targets such UDP-N-acetylglucosamine 1-carboxyvinyltransferase 1, putative septation protein SpoVG and ATP-dependent Clp protease proteolytic subunit. Further, in silico pathway analysis using DAVID and KOBAS has revealed modulation of pathways related to the fatty acid metabolism and cell wall synthesis, which are crucial for cell viability. Our findings revealed that curcumin treatment lead to inhibition of the cell wall and fatty acid synthesis in addition to differential expression of many crucial proteins involved in modulation of bacterial metabolism. Findings obtained from proteomics analysis were further validated using 5-cyano-2,3-ditolyl tetrazolium chloride (CTC) assay for respiratory activity, resazurin assay for metabolic activity and membrane integrity assay by potassium and inorganic phosphate leakage measurement. The gene expression analysis of selected cell wall biosynthesis enzymes has strengthened the proteomics findings and indicated the major effect of curcumin on cell division

Perceived Social Support Network and Achievement : Mediation by Motivational Beliefs and Moderation by Gender

Research has shown that perceived social support (PSS) (from parents and teachers) influences achievement. However, little is known about how this relationship operates. This study examines the multiple mediational effects of students’ motivational beliefs in relationship to the association between PSS and mathematics achievement. The sample included the African countries that participated in the TIMSS 2011 (Ghana, Botswana, South Africa, Morocco, and Tunisia). A bootstrap analysis indicated a unique pattern of the role of motivational beliefs in mediating the relationships between PSS and achievement. Moreover, gender was found to moderate the indirect effect in some countries. The findings indicate that total mediation effect of students’ motivational belief on the relationship between PSS and achievement is “culture-fair but not culture-free”Research has shown that perceived social support (PSS) (from parents and teachers) influences achievement. However, little is known about how this relationship operates. This study examines the multiple mediational effects of students’ motivational beliefs in relationship to the association between PSS and mathematics achievement. The sample included the African countries that participated in the TIMSS 2011 (Ghana, Botswana, South Africa, Morocco, and Tunisia). A bootstrap analysis indicated a unique pattern of the role of motivational beliefs in mediating the relationships between PSS and achievement. Moreover, gender was found to moderate the indirect effect in some countries. The findings indicate that total mediation effect of students’ motivational belief on the relationship between PSS and achievement is “culture-fair but not culture-free”.Peer reviewe

Dissociation between the Activity of the Right Middle Frontal Gyrus and the Middle Temporal Gyrus in Processing Semantic Priming

The aim of this event-related functional magnetic resonance imaging (fMRI) study was to test whether the right middle frontal gyrus (MFG) and middle temporal gyrus (MTG) would show differential sensitivity to the effect of prime-target association strength on repetition priming. In the experimental condition (RP), the target occurred after repetitive presentation of the prime within an oddball design. In the control condition (CTR), the target followed a single presentation of the prime with equal probability of the target as in RP. To manipulate semantic overlap between the prime and the target both conditions (RP and CTR) employed either the onomatopoeia “oink” as the prime and the referent “pig” as the target (OP) or vice-versa (PO) since semantic overlap was previously shown to be greater in OP. The results showed that the left MTG was sensitive to release of adaptation while both the right MTG and MFG were sensitive to sequence regularity extraction and its verification. However, dissociated activity between OP and PO was revealed in RP only in the right MFG. Specifically, target “pig” (OP) and the physically equivalent target in CTR elicited comparable deactivations whereas target “oink” (PO) elicited less inhibited response in RP than in CTR. This interaction in the right MFG was explained by integrating these effects into a competition model between perceptual and conceptual effects in priming processing

Complement and the Alternative Pathway Play an Important Role in LPS/D-GalN-Induced Fulminant Hepatic Failure

Fulminant hepatic failure (FHF) is a clinically severe type of liver injury with an extremely high mortality rate. Although the pathological mechanisms of FHF are not well understood, evidence suggests that the complement system is involved in the pathogenesis of a variety of liver disorders. In the present study, to investigate the role of complement in FHF, we examined groups of mice following intraperitoneal injection of LPS/D-GalN: wild-type C57BL/6 mice, wild-type mice treated with a C3aR antagonist, C5aR monoclonal antibody (C5aRmAb) or CR2-Factor H (CR2-fH, an inhibitor of the alternative pathway), and C3 deficient mice (C3−/− mice). The animals were euthanized and samples analyzed at specific times after LPS/D-GalN injection. The results show that intraperitoneal administration of LPS/D-GalN activated the complement pathway, as evidenced by the hepatic deposition of C3 and C5b-9 and elevated serum levels of the complement activation product C3a, the level of which was associated with the severity of the liver damage. C3a receptor (C3aR) and C5a receptor (C5aR) expression was also upregulated. Compared with wild-type mice, C3−/− mice survived significantly longer and displayed reduced liver inflammation and attenuated pathological damage following LPS/D-GalN injection. Similar levels of protection were seen in mice treated with C3aR antagonist,C5aRmAb or CR2-fH. These data indicate an important role for the C3a and C5a generated by the alternative pathway in LPS/D-GalN-induced FHF. The data further suggest that complement inhibition may be an effective strategy for the adjunctive treatment of fulminant hepatic failure