Atmospheric CO2 decline and the timing of CAM plant evolution

Background and Aims: CAM photosynthesis is hypothesized to have evolved in atmospheres of low CO2 concentration in recent geological time because of its ability to concentrate CO2 around Rubisco and boost water use efficiency relative to C3 photosynthesis. We assess this hypothesis by compiling estimates of when CAM clades arose using phylogenetic chronograms for 73 CAM clades. We further consider evidence of how atmospheric CO2 affects CAM relative to C3 photosynthesis. Results: Where CAM origins can be inferred, strong CAM is estimated to have appeared in the past 30 million years in 46 of 48 examined clades, after atmospheric CO2 had declined from high (near 800 ppm) to lower (<450 ppm) values. In turn, 21 of 25 clades containing CAM species (but where CAM origins are less certain) also arose in the past 30 million years. In these clades, CAM is probably younger than the clade origin. We found evidence for repeated weak CAM evolution during the higher CO2 conditions before 30 million years ago, and possible strong CAM origins in the Crassulaceae during the Cretaceous period prior to atmospheric CO2 decline. Most CAM-specific clades arose in the past 15 million years, in a similar pattern observed for origins of C4 clades. Conclusions: The evidence indicates strong CAM repeatedly evolved in reduced CO2 conditions of the past 30 million years. Weaker CAM can pre-date low CO2 and, in the Crassulaceae, strong CAM may also have arisen in water-limited microsites under relatively high CO2. Experimental evidence from extant CAM species demonstrates that elevated CO2 reduces the importance of nocturnal CO2 fixation by increasing the contribution of C3 photosynthesis to daily carbon gain. Thus, the advantage of strong CAM would be reduced in high CO2, such that its evolution appears less likely and restricted to more extreme environments than possible in low CO2

The influence of syntactic knowledge on reading comprehension varies as a function of oral vocabulary in Spanish-speaking children

Background: Reading comprehension is a complex process influenced by many factors. However, the abilities that are known to influence reading comprehension may not contribute equally for children with different levels of oral language. Aims: Here we examined the relationship of two factors known to influence reading comprehension (morphology and syntax) in a group of children who varied in their levels of oral vocabulary. Method: Two hundred seventy-three typically developing Spanish-speaking fourth graders were assessed on non-verbal intelligence, word and pseudoword reading, oral vocabulary, morphological awareness and syntax, along with reading comprehension ability. Standardised oral language scores within this group ranged from the first to the 99th percentile. Mediated multiple regression with moderation was used to assess (1) whether the influence of oral vocabulary on reading comprehension was mediated by decoding, morphology or syntax and (2) whether the effects of syntax on reading comprehension varied as a function of oral vocabulary levels. Results: There was a direct positive relationship between vocabulary and reading comprehension, and this was mediated by word reading and syntax, but not by pseudoword reading or morphology. Furthermore, the relation between syntax and reading comprehension was moderated by oral vocabulary such that the strength of this relationship diminished as oral vocabulary levels increased. Conclusions: These findings suggest that longitudinal research is necessary to explore the possibility that a syntax intervention might be beneficial for readers with low oral vocabulary.FEDER 2014-2020Consejería de Economía, Conocimiento, Empresas y Universidad US-126479

The effects of morphological and syntactic knowledge on reading comprehension in Spanish speaking children

Reading comprehension is a complex task requiring many underlying skills. Syntactic awareness and morphological awareness are two such skills that have been shown to be related to reading comprehension. However, the majority of studies have been carried out in English, and very few have explored these skills in monolingual Spanish speaking children. Here we explored to what extent syntactic awareness and morphological awareness contributed to text comprehension in Spanish. 501 typically developing Spanish speaking 4th graders were assessed on non-verbal intelligence, word and nonword reading, oral vocabulary, morphological and syntactic knowledge, along with reading comprehension ability. After excluding children with poor decoding or low non-verbal intelligence, 234 children were retained for analysis. Multiple linear regression modelling was used to assess the unique contribution of each variable to reading comprehension. As per findings reported in English, syntactic knowledge was a significant predictor of comprehension after controlling for age, gender, non-verbal IQ, word reading and oral vocabulary, as well as morphological knowledge. In contrast, and contrary to results normally reported for English speaking children, morphological knowledge did not explain any variance in reading comprehension beyond that explained by the control variables. These results highlight the important contribution of syntactic knowledge to text comprehension in Spanish speaking children, as well as the importance of undertaking research in languages other than English.Ministerio de Economía y Competitividad PSI2015-65656-

Weak-anchoring effects in a thin pinned ridge of nematic liquid crystal

A theoretical investigation of weak-anchoring effects in a thin two-dimensional pinned static ridge of nematic liquid crystal resting on a flat solid substrate in an atmosphere of passive gas is performed. Specifically, we solve a reduced version of the general system of governing equations recently derived by Cousins et al. [Proc. Roy. Soc. A}, 478(2259):20210849, 2022] valid for a symmetric thin ridge under the one-constant approximation of the Frank--Oseen bulk elastic energy with pinned contact lines to determine the shape of the ridge and the behaviour of the director within it. Numerical investigations covering a wide range of parameter values indicate that the energetically-preferred solutions can be classified in terms of the Jenkins--Barratt--Barbero--Barberi critical thickness into five qualitatively different types of solution. In particular, the theoretical results suggest that anchoring breaking occurs close to the contact lines. The theoretical predictions are supported by the results of physical experiments for a ridge of the nematic 4'-pentyl-4-biphenylcarbonitrile (5CB). In particular, these experiments show that the homeotropic anchoring at the gas--nematic interface is broken close to the contact lines by the stronger rubbed planar anchoring at the nematic--substrate interface. A comparison between the experimental values of and the theoretical predictions for the effective refractive index of the ridge gives a first estimate of the anchoring strength of an interface between air and 5CB to be $(9.80\pm1.12)\times10^{-6}\,{\rm N m}^{-1}$ at a temperature of $(22\pm1.5)^\circ$C

Weak-anchoring effects in a thin pinned ridge of nematic liquid crystal

A theoretical investigation of weak-anchoring effects in a thin two-dimensional pinned static ridge of nematic liquid crystal resting on a flat solid substrate in an atmosphere of passive gas is performed. Specifically, we solve a reduced version of the general system of governing equations recently derived by Cousins et al. [Proc. R. Soc. A 478, 20210849 (2022)] valid for a symmetric thin ridge under the one-constant approximation of the Frank-Oseen bulk elastic energy with pinned contact lines to determine the shape of the ridge and the behavior of the director within it. Numerical investigations covering a wide range of parameter values indicate that the energetically preferred solutions can be classified in terms of the Jenkins-Barratt-Barbero-Barberi critical thickness into five qualitatively different types of solution. In particular, the theoretical results suggest that anchoring breaking occurs close to the contact lines. The theoretical predictions are supported by the results of physical experiments for a ridge of the nematic 4 ′ -pentyl-4-biphenylcarbonitrile (5CB). In particular, these experiments show that the homeotropic anchoring at the gas-nematic interface is broken close to the contact lines by the stronger rubbed planar anchoring at the nematic-substrate interface. A comparison between the experimental values of and the theoretical predictions for the effective refractive index of the ridge gives a first estimate of the anchoring strength of an interface between air and 5CB to be (9.80 ± 1.12) × 10^(− 6) Nm^(−1) at a temperature of (22 ± 1.5)∘C

SPARC, FOXP3, CD8 and CD45 Correlation with Disease Recurrence and Long-Term Disease-Free Survival in Colorectal Cancer

BACKGROUND: SPARC is a matricellular protein involved in tissue remodelling, cell migration and angiogenesis, while forkhead box P3 (FOXP3) protein functions as a transcription factor involved in immune cell regulation. Both SPARC and FOXP3 can play an anti-tumorigenic role in cancer progression. The aim was to determine if SPARC, FOXP3, CD8 and CD45RO expression levels are associated with colorectal cancer (CRC) stage, disease outcome and long-term cancer-specific survival (CSS) in stage II and III CRC. METHODS AND FINDINGS: SPARC expression was initially assessed in 120 paired normal and stage I-IV CRCs. Subsequently, approximately 1000 paired patient samples of stage II or III CRCs in tissue microarrays were stained for SPARC, FOXP3, CD8 or CD45RO. Proportional hazards modelling assessed correlations between these markers and clinicopathological data, including disease outcome and cancer specific survival (CSS). Both SPARC and FOXP3 expression were significantly greater in CRC than normal colon (p<0.0001). High SPARC expression correlated with good disease outcome (≥60 mths without disease recurrence, p = 0.0039) and better long-term CSS in stage II CRC (<0.0001). In stage III CRC, high SPARC expression correlated with better long-term CSS (p<0.0001) and less adjuvant chemotherapy use (p = 0.01). High FOXP3 correlated with a good disease outcome, better long-term CSS and less adjuvant chemotherapy use in stage II (p<0.0037, <0.0001 and p = 0.04 respectively), but not in stage III CRC. High CD8 and CD45RO expression correlated with better disease outcome in stage II CRC, and better CSS, but the differences were not as marked as for SPARC and FOXP3. CONCLUSIONS: These data suggest that high SPARC and FOXP3 are associated with better disease outcome in stage II CRC and may be prognostic indicators of CSS. Further assessment of whether these markers predict patients at high risk of recurrence with stage II CRC and functional studies of these effects are underway

Regulation of type 1 diabetes development and B-cell activation in nonobese diabetic mice by early life exposure to a diabetogenic environment

Microbes, including viruses, influence type 1 diabetes (T1D) development, but many such influences remain undefined. Previous work on underlying immune mechanisms has focussed on cytokines and T cells. Here, we compared two nonobese diabetic (NOD) mouse colonies, NODlow and NODhigh, differing markedly in their cumulative T1D incidence (22% vs. 90% by 30 weeks in females). NODhigh mice harbored more complex intestinal microbiota, including several pathobionts; both colonies harbored segmented filamentous bacteria (SFB), thought to suppress T1D. Young NODhigh females had increased B-cell activation in their mesenteric lymph nodes. These phenotypes were transmissible. Co-housing of NODlow with NODhigh mice after weaning did not change T1D development, but T1D incidence was increased in female offspring of co-housed NODlow mice, which were exposed to the NODhigh environment both before and after weaning. These offspring also acquired microbiota and B-cell activation approaching those of NODhigh mice. In NODlow females, the low rate of T1D was unaffected by cyclophosphamide but increased by PD-L1 blockade. Thus, environmental exposures that are innocuous later in life may promote T1D progression if acquired early during immune development, possibly by altering B-cell activation and/or PD-L1 function. Moreover, T1D suppression in NOD mice by SFB may depend on the presence of other microbial influences. The complexity of microbial immune regulation revealed in this murine model may also be relevant to the environmental regulation of human T1D

Dipeptidyl peptidase-1 inhibition in patients hospitalised with COVID-19: a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial

Background Neutrophil serine proteases are involved in the pathogenesis of COVID-19 and increased serine protease activity has been reported in severe and fatal infection. We investigated whether brensocatib, an inhibitor of dipeptidyl peptidase-1 (DPP-1; an enzyme responsible for the activation of neutrophil serine proteases), would improve outcomes in patients hospitalised with COVID-19. Methods In a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial, across 14 hospitals in the UK, patients aged 16 years and older who were hospitalised with COVID-19 and had at least one risk factor for severe disease were randomly assigned 1:1, within 96 h of hospital admission, to once-daily brensocatib 25 mg or placebo orally for 28 days. Patients were randomly assigned via a central web-based randomisation system (TruST). Randomisation was stratified by site and age (65 years or ≥65 years), and within each stratum, blocks were of random sizes of two, four, or six patients. Participants in both groups continued to receive other therapies required to manage their condition. Participants, study staff, and investigators were masked to the study assignment. The primary outcome was the 7-point WHO ordinal scale for clinical status at day 29 after random assignment. The intention-to-treat population included all patients who were randomly assigned and met the enrolment criteria. The safety population included all participants who received at least one dose of study medication. This study was registered with the ISRCTN registry, ISRCTN30564012. Findings Between June 5, 2020, and Jan 25, 2021, 406 patients were randomly assigned to brensocatib or placebo; 192 (47·3%) to the brensocatib group and 214 (52·7%) to the placebo group. Two participants were excluded after being randomly assigned in the brensocatib group (214 patients included in the placebo group and 190 included in the brensocatib group in the intention-to-treat population). Primary outcome data was unavailable for six patients (three in the brensocatib group and three in the placebo group). Patients in the brensocatib group had worse clinical status at day 29 after being randomly assigned than those in the placebo group (adjusted odds ratio 0·72 [95% CI 0·57–0·92]). Prespecified subgroup analyses of the primary outcome supported the primary results. 185 participants reported at least one adverse event; 99 (46%) in the placebo group and 86 (45%) in the brensocatib group. The most common adverse events were gastrointestinal disorders and infections. One death in the placebo group was judged as possibly related to study drug. Interpretation Brensocatib treatment did not improve clinical status at day 29 in patients hospitalised with COVID-19

Atmospheric CO2 decline and the timing of CAM plant evolution

Background and aimsCAM photosynthesis is hypothesized to have evolved in atmospheres of low CO2 concentration in recent geological time because of its ability to concentrate CO2 around Rubisco and boost water use efficiency relative to C3 photosynthesis. We assess this hypothesis by compiling estimates of when CAM clades arose using phylogenetic chronograms for 73 CAM clades. We further consider evidence of how atmospheric CO2 affects CAM relative to C3 photosynthesis.ResultsWhere CAM origins can be inferred, strong CAM is estimated to have appeared in the past 30 million years in 46 of 48 examined clades, after atmospheric CO2 had declined from high (near 800 ppm) to lower (&lt;450 ppm) values. In turn, 21 of 25 clades containing CAM species (but where CAM origins are less certain) also arose in the past 30 million years. In these clades, CAM is probably younger than the clade origin. We found evidence for repeated weak CAM evolution during the higher CO2 conditions before 30 million years ago, and possible strong CAM origins in the Crassulaceae during the Cretaceous period prior to atmospheric CO2 decline. Most CAM-specific clades arose in the past 15 million years, in a similar pattern observed for origins of C4 clades.ConclusionsThe evidence indicates strong CAM repeatedly evolved in reduced CO2 conditions of the past 30 million years. Weaker CAM can pre-date low CO2 and, in the Crassulaceae, strong CAM may also have arisen in water-limited microsites under relatively high CO2. Experimental evidence from extant CAM species demonstrates that elevated CO2 reduces the importance of nocturnal CO2 fixation by increasing the contribution of C3 photosynthesis to daily carbon gain. Thus, the advantage of strong CAM would be reduced in high CO2, such that its evolution appears less likely and restricted to more extreme environments than possible in low CO2