Chlorophyll Fluorescence in Wheat Breeding for Heat and Drought Tolerance.

The constantly growing need to increase the production of agricultural products in changing climatic conditions makes it necessary to accelerate the development of new cultivars that meet the modern demands of agronomists. Currently, the breeding process includes the stages of genotyping and phenotyping to optimize the selection of promising genotypes. One of the most popular phenotypic methods is the pulse-amplitude modulated (PAM) fluorometry, due to its non-invasiveness and high information content. In this review, we focused on the opportunities of using chlorophyll fluorescence (ChlF) parameters recorded using PAM fluorometry to assess the state of plants in drought and heat stress conditions and predict the economically significant traits of wheat, as one of the most important agricultural crops, and also analyzed the relationship between the ChlF parameters and genetic markers.

Toll-Like Receptor 2 Attenuates the Formation and Progression of Angiotensin II-Induced Abdominal Aortic Aneurysm in ApoE-/- Mice.

INTRODUCTION: We demonstrated Toll-like receptor (TLR) 4 in the pathogenesis of angiotensin II (AngII)-mediated abdominal aortic aneurysm (AAA) formation. Here, we study TLR2 in the AAA formation. METHODS: Male ApoE-/- and ApoE-/-TLR2-/- mice were treated with AngII. Mice were injected with the TLR2 agonist Pam3CSK4. The incidence and severity of AAA were determined. MCP-1, MCP-5, RANTES, CXCL10, CCR5, and CXCR3 were analyzed. M1 and M2 macrophages in the aorta were detected by flow cytometry. RESULTS: These studies demonstrated an increase in AAA formation in TLR2-/- mice and a decrease by Pam3CSK4. Pam3CSK4 decreased the ratio of M1/M2 and the levels of RANTES, CXCL10, CCR5, and CXCR3. Furthermore, Pam3CSK4 treatment 1 week following AngII retarded the progression of AAA. CONCLUSION: These data demonstrated a protective effect of TLR2 signaling on AAA in association with a decrease in the ratio of M1 to M2 macrophages and the expression of chemokines and their receptors. Furthermore, the treatment of Pam3CSK4 after AngII demonstrated a marked retardation of lesion progression. Given the fact that most AAA patients are detected late in the disease process, these findings suggest that TLR2 stimulation may play a therapeutic role in retarding disease progression.

Non-Foliar Photosynthesis in Pea (Pisum sativum L.) Plants: Beyond the Leaves to Inside the Seeds.

In addition to leaves, photosynthesis can occur in other green plant organs, including developing seeds of many crops. While the majority of studies examining photosynthesis are concentrated on the leaf level, the role of other green tissues in the production of total photoassimilates has been largely overlooked. The present work studies the photosynthetic behavior of leaves and non-foliar (pericarps, coats, and cotyledons) organs of pea (Pisum sativum L.) plants at the middle stage of seed maturation. The Chl a fluorescence transient was examined based on OJIP kinetics using the FluorPen FP 110. A discrepancy was observed between the performance index (PIABS) for foliar and non-foliar plant tissues, with the highest level noted in the leaves. The number of absorbed photons (ABS) and captured energy flow (TRo) per reaction center (RC) were elevated in the non-foliar tissues, which resulted in a faster reduction in QA. Conversely, the energy dissipation flux per RC (DIo/RC and PHI_Do) indicated an increase in the overall dissipation potential of active reaction centers of photosystem II. This phenomenon was attributed to the presence of a higher number of inactive RCs in tissues that had developed under low light intensity. Furthermore, the expression of genes associated with proteins and enzymes that regulate ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCo) activity was observed, including chaperonins Cpn60α and Cpn60ß, RuBisCO activase, as well as phosphoribulokinase. The expression of these genes was found to differ between foliar and non-foliar tissues, indicating that the activation state of RuBisCO may be modified in response to light intensity. Overall, the present study provides insights into the mechanisms by which non-foliar green tissues of plants adapt to efficient light capture and utilization under low light conditions.

Neoadjuvant sunitinib plus exemestane in post-menopausal women with hormone receptor-positive/HER2-negative early-stage breast cancer (SUT_EXE-08): a phase I/II trial.

Neoadjuvant endocrine therapy (NET) for hormone receptor-positive (HR+) breast cancer might be as effective as chemotherapy, with a better toxicity profile. Blocking a crucial process such as angiogenesis with sunitinib may have a synergistic effect with NET. We aimed to assess the efficacy and safety of neoadjuvant sunitinib plus exemestane in early-stage HR+/HER2-negative breast cancer. In this phase I/II study, postmenopausal women with HR+/HER2- stage II-III breast cancer received neoadjuvant exemestane at conventional dose of 25mg plus sunitinib in a 3 + 3 design at 25mg (3/1weeks scheme) or 37.5mg continuous dose, for 6 months. Coprimary endpoints were the recommended dose of sunitinib combined with exemestane and objective response. Secondary endpoints included safety and biomarkers of early response. For 15 months, 18 patients were enrolled, 15 at sunitinib 25mg and 3 at 37.5mg. Median age was 73, 77% of patients had T2 tumors and 67% node-positive disease. The most common grade 2 toxicity was asthenia (44%), as was hypertension (22%) for grade 3. No grade 4-5 were reported. Twelve patients (66%) achieved an objective response. VEGFR-2 levels significantly decreased after one month of treatment. Differential gene expression analysis showed downregulation of ESR1, PGR and NAT1 in post-treatment samples and upregulation of EGFR, MYC, SFRP1, and FOXC1. PAM50 analysis on 83% of patients showed a prevalence of luminal A subtype, both in pre-treatment (63.6%) and post-treatment tumors (54.5%). Sunitinib plus exemestane was associated with substantial yet reversible toxicities, providing safety, efficacy and biological impact insights of combining an antiangiogenic drug with hormone therapy in early-stage breast cancer.Trial registration: Registered with ClinicalTrials.gov, NCT00931450. 02/07/2009.

Characterizing the underwater soundscape at the site of a proposed port in northeast Iceland.

Finnafjörður is a small fjord in northeast Iceland, where the planned construction of a large port has the potential to meaningfully change the marine soundscape and ecosystem. In this study, we used one year (2021/22) of passive acoustic recordings to characterize the pre-construction soundscape, including broadband and decidecade sound pressure levels (SPL), frequency-weighted sound exposure levels, seasonal and diel variability and identified regular types of sound. Finnafjörður is relatively quiet with median decidecade levels centered between 25 Hz and 50 kHz of 74.5 to 86.3 dB re 1 µPa. Wind and rain dominate ambient SPL, while anthropogenic sources only occasionally contributed to the soundscape. Regular biological sound sources include humpback whales, toothed whales, and fish. This baseline soundscape description can be used for noise management during port construction, to monitor future changes in the region, and to act as a framework for comprehensive impact assessments as ports are developed globally.

Prosigna Assay for Treatment Decisions in Early Breast Cancer: A Decision Impact Study.

Introduction: Therapeutic decisions in early breast cancer are based on clinico-pathological features which are subject to intra- and inter-observer variability. This single-center decision impact study aimed to evaluate the effects of the Prosigna assay on physicians' adjuvant treatment choices. Methods: Between 09/2017 and 02/2018, formalin-fixed tumor samples from 52 newly diagnosed, postmenopausal, hormone receptor-positive, HER2-negative breast cancer (T1-T2; pN0-N1a) patients were analyzed. Pre-test clinical judgements and Prosigna test results were compared. Results: The mean age was 59 (42-77). Invasive ductal carcinoma (79.2%), grade 2 (52.8%) and T1c-N0 tumors (43.4%) were represented. There was 40.4% discordance between the pre- and post-test risk of recurrences. No significant change was observed in the clinical intermediate risk category, while there was a net reclassification of low-risk patients into a high Prosigna recurrence risk group. In addition, clinically determined intrinsic subtypes were 34.6% discordant with the Prosigna results, which is largely driven by the reclassification of the luminal A tumors into the Prosigna-assessed luminal B group. Before the Prosigna test, endocrine treatment was the primary choice in 20 patients (39.2%), and chemotherapy was recommended to 31 patients (60.8%). Overall, the Prosigna assay led to a change in treatment choice for one patient. Conclusions: Although conventional risk assessment methods are relatively inexpensive with shorter turnaround times, their accuracy and value for risk reduction are suboptimal. According to our results, the Prosigna assay was found to be a relevant tool for the clinical decision making process. Long-term follow-up of these patients will elucidate the potential benefits of using multigene molecular tests as biomarkers for treatment.

Ecotoxicological effects of suspended sediments on marine microalgae using flow cytometry and pulse-amplitude modulation (PAM) fluorometry.

Microalgal bioassays were conducted to evaluate the ecotoxicological effects of suspended sediments (SS) collected from coastal environments. Growth inhibition was assessed for six microalgal species, and multiple endpoints were measured using flow cytometry (FCM) and pulse-amplitude modulation (PAM) fluorometry for three species (Dunaliella tertiolecta, Isochrysis galbana, and Phaeodactylum tricornutum). Among these, the EC50 for growth inhibition of D. tertiolecta (6700 mg L-1) was notably lower compared to the other species, and among several endpoints, esterase activity was the most inhibited. Species-specific responses to SS exposure were identified, with D. tertiolecta exhibiting greater susceptibility across most endpoints. Meanwhile, measurements of Fo', Fm', and Y(NPQ) in P. tricornutum using PAM fluorometry revealed greater sensitivity. Based on the results of this study and review, the tentative predicted no-effect concentration was calculated as 12.1 mg L-1. Overall, this study provides novel insights into SS ecotoxicity, establishing a crucial baseline for future investigations.

Discovery of VU6016235: A Highly Selective, Orally Bioavailable, and Structurally Distinct Tricyclic M4 Muscarinic Acetylcholine Receptor Positive Allosteric Modulator (PAM).

Herein, we report structure-activity relationship (SAR) studies to develop novel tricyclic M4 PAM scaffolds with improved pharmacological properties. This endeavor involved a "tie-back" strategy to replace a 5-amino-2,4-dimethylthieno[2,3-d]pyrimidine-6-carboxamide core, which led to the discovery of two novel tricyclic cores. While both tricyclic cores displayed low nanomolar potency against both human and rat M4 and were highly brain-penetrant, the 2,4-dimethylpyrido[4',3':4,5]thieno[2,3-d]pyrimidine tricycle core provided lead compound, VU6016235, with an overall superior pharmacological and drug metabolism and pharmacokinetics (DMPK) profile, as well as efficacy in a preclinical antipsychotic animal model.

Improved diagnostic efficiency of CRC subgroups revealed using machine learning based on intestinal microbes.

BACKGROUND: Colorectal cancer (CRC) is a common cancer that causes millions of deaths worldwide each year. At present, numerous studies have confirmed that intestinal microbes play a crucial role in the process of CRC. Additionally, studies have shown that CRC can be divided into several consensus molecular subtypes (CMS) based on tumor gene expression, and CRC microbiomes have been reported related to CMS. However, most previous studies on intestinal microbiome of CRC have only compared patients with healthy controls, without classifying of CRC patients based on intestinal microbial composition. RESULTS: In this study, a CRC cohort including 339 CRC samples and 333 healthy controls was selected as the discovery set, and the CRC samples were divided into two subgroups (234 Subgroup1 and 105 Subgroup2) using PAM clustering algorithm based on the intestinal microbial composition. We found that not only the microbial diversity was significantly different (Shannon index, p-value < 0.05), but also 129 shared genera altered (p-value < 0.05) between the two CRC subgroups, including several marker genera in CRC, such as Fusobacterium and Bacteroides. A random forest algorithm was used to construct diagnostic models, which showed significantly higher efficiency when the CRC samples were divided into subgroups. Then an independent cohort including 187 CRC samples (divided into 153 Subgroup1 and 34 Subgroup2) and 123 healthy controls was chosen to validate the models, and confirmed the results. CONCLUSIONS: These results indicate that the divided CRC subgroups can improve the efficiency of disease diagnosis, with various microbial composition in the subgroups.

Toughness and Thermoresponsive Hydrogel for Sandwich Smart Window with Adaptive Solar Modulation and Energy Saving.

Thermochromic hydrogels with self-regulating solar transmittance are gaining increasing attention due to their significant potential in the fields of smart windows and energy conservation. Smart windows incorporating viscosity-tough hydrogels as an interlayer exhibit enhanced advantages in resisting external forces. In this study, a tough and thermoresponsive composite hydrogel was developed by incorporating poly(N-isopropylacrylamide) nanoparticles (PNIPAM NPs) and W-doped VO2 into a polyacrylamide-agar (PAM-Agar) double network hydrogel. Upon solar irradiation, thermochromism of PNIPAM NPs could regulate the visible light transmittance of the composite hydrogel and the photothermal effect of W-VO2 contributes to the optical regulation and NIR shielding. The smart window, with the composite hydrogel as an interlayer, demonstrates excellent optical modulation capabilities, with a luminous transmittance (Tum(20 °C)) of 86.81%, high light modulation (ΔTum = 78.89%), a high solar modulation (Tsol) of 83.59%, and a lower critical solution temperature (LCST) of 32.6 °C. The composite hydrogel's superior toughness (0.215 MJ/m3) also enhances the impact resistance of the smart window glass. Additionally, the adhesion between the hydrogel and the glass, with a maximum peeling force of up to 151 N/m (attributed to interactions between the amide groups and the silicon hydroxyl groups), was confirmed through a falling ball experiment. Moreover, the hydrogel exhibits a certain degree of thermal insulation, further promoting its utility in energy-saving applications. In conclusion, this study highlights the significant potential of such composite hydrogels in the development of smart windows for energy-efficient buildings.

PAM50 breast cancer subtypes and survival of patients in rural Ethiopia without adjuvant treatment: a prospective observational study.

PURPOSE: Survival rates of breast cancer (BC) patients are particularly low in rural regions in sub-Saharan Africa (SSA) which is due to limited access to therapy. In recent years, gene expression profiling (GEP) of BC showed a strong prognostic value in patients with local tumour surgery and (neo)adjuvant treatment. The aim of this study was to evaluate the impact of intrinsic subtypes on survival of patients in rural Ethiopia without any (neo)adjuvant therapy. METHODS: In total, 113 female patients from Aira Hospital with histologically proven BC and treated only with surgery were included in this study. All samples were analysed by immunohistochemistry (IHC) for estrogen receptor, progesterone receptor, HER2 and Ki67, as well as RNA-expression analysis for PAM50 subtyping. RESULTS: A positive hormone receptor status was found in 69.0% of the tumours and intrinsic subtyping demonstrated Luminal B to be the most common subtype (34.5%). Follow-up data was available for 79 of 113 patients. Two-year overall survival (OS) was 57.3% and a considerably worse OS was observed in patients with Basal-like BC compared to Luminal A BC. Moreover, advanced tumours showed an increased risk of mortality. CONCLUSION: The OS was very low in the patient cohort that received no (neo)adjuvant treatment. Immunohistochemistry and GEP confirmed endocrine-sensitive tumours in more than half of the patients, with a large proportion of Luminal B, HER2-enriched and Basal-like tumours so that adjuvant chemotherapy should be recommended.

Simplified scalable synthesis of a water-soluble toll-like receptor 2 agonistic lipopeptide adjuvant for use with protein-based viral vaccines.

Toll-like receptors (TLRs) form a key bridge between the innate and adaptive immune systems. The lipopeptide based TLR2 agonists such as Pam2CSK4 are promising vaccine adjuvants but drawbacks include its surfactant like nature and cumbersome synthesis. Although the TLR2 activity of Pam2CS-OMe is commensurate with Pam2CSK4, its water solubility is much less, rendering it ineffective for clinical use. In the present investigation, we designed a synthesis pathway for a novel water-soluble TLR2-active analogue, Pam2CS-DMAPA (13), which enhanced the immunogenicity of recombinant SARS-CoV2 and hepatitis B antigens in mice. Co-formulation of compound 13 with 2 % aluminium hydroxide gel led to a further significant improvement in vaccine immunogenicity. This synthetically simpler compound 13 was water soluble and equally potent to Pam2CSK4 adjuvant, but was superior in terms of manufacturing simplicity and scalability. This makes compound 13 a promising TLR2 targeted adjuvant for further development.

Inetetamab combined with sirolimus and chemotherapy for the treatment of HER2-positive metastatic breast cancer patients with abnormal activation of the PI3K/Akt/mTOR pathway after trastuzumab treatment.

Background: We explored the efficacy and safety of inetetamab combined with sirolimus and chemotherapy for the treatment of human epidermal factor receptor 2 (HER2)-positive metastatic breast cancer patients with abnormal activation of the PI3K/Akt/mTOR (PAM) pathway after trastuzumab treatment. Methods: For this prospective multicenter clinical study, HER2-positive metastatic breast cancer patients with PAM pathway mutations confirmed by histology or peripheral blood genetic testing were enrolled from July 2021 to September 2022. Patients were randomly assigned to a trial or control group. The patients in the trial group received inetetamab combined with sirolimus and chemotherapy, while the control group patients received pyrotinib and chemotherapy. The RECIST v1.1 standard was used to evaluate efficacy. Descriptive statistics were used to summarize the clinicopathological features, and the Kaplan-Meier method was used to generate survival curves. The log-rank test was used to compare progression-free survival (PFS) between the two groups. Results: A total of 59 HER2-positive metastatic breast cancer patients with abnormal activation of the PAM pathway were included, of which 37 received inetetamab combined with sirolimus and chemotherapy treatment and 22 received pyrotinib and chemotherapy treatment. The median PFS was 4.64 months in the inetetamab group and 5.69 months in the pyrotinib group, with no statistically significant difference (p = 0.507). The objective response rates were 27.3% for the inetetamab group and 29.4% for the pyrotinib group. The safety assessment indicated that the adverse event (AE) incidences were 86.1% (31/36) in the inetetamab group and 78.9 (15/19) in the pyrotinib group, with 9 (25%) and four (21.1%) Grade 3/4 AEs in the inetetamab and pyrotinib groups, respectively. Conclusions: For metastatic HER2-positive breast cancer patients with abnormal PAM pathway activation and previous trastuzumab treatment, the combination of inetetamab with sirolimus and chemotherapy is equivalent to the combination of pyrotinib and chemotherapy. Therefore, this regimen could be a treatment option for PAM pathway-activated metastatic HER2-positive breast cancer patients.

Endometabolic profiling of pigmented glacier ice algae: the impact of sample processing.

INTRODUCTION: Glacier ice algae, mainly Ancylonema alaskanum and Ancylonema nordenskiöldi, bloom on Greenland Ice Sheet bare ice surfaces. They significantly decrease surface albedo due to their purple-brown pigmentation, thus increasing melt. Little is known about their metabolic adaptation and factors controlling algal growth dynamics and pigment formation. A challenge in obtaining such data is the necessity of melting samples, which delays preservation and introduces bias to metabolomic analysis. There is a need to evaluate the physiological response of algae to melting and establish consistent sample processing strategies for metabolomics of ice microbial communities. OBJECTIVES: To address the impact of sample melting procedure on metabolic characterization and establish a processing and analytical workflow for endometabolic profiling of glacier ice algae. METHODS: We employed untargeted, high-resolution mass spectrometry and tested the effect of sample melt temperature (10, 15, 20 °C) and processing delay (up to 49 h) on the metabolome and lipidome, and complemented this approach with cell counts (FlowCam), photophysiological analysis (PAM) and diversity characterization. RESULTS AND CONCLUSION: We putatively identified 804 metabolites, with glycerolipids, glycerophospholipids and fatty acyls being the most prominent superclasses (> 50% of identified metabolites). Among the polar metabolome, carbohydrates and amino acid-derivatives were the most abundant. We show that 8% of the metabolome is affected by melt duration, with a pronounced decrease in betaine membrane lipids and pigment precursors, and an increase in phospholipids. Controlled fast melting at 10 °C resulted in the highest consistency, and is our recommendation for future supraglacial metabolomics studies.

Predicting invasive disease-free survival in ER-positive, HER2-negative early breast cancer using the PAM50 risk-of-recurrence score: a retrospective analysis using single-center long-term follow-up data of postmenopausal Japanese patients.

BACKGROUND: The prognostic value of the risk-of-recurrence (ROR) score calculated using PAM50 has been validated using clinical trials and patient cohorts. This study aimed to investigate the prognostic value of the PAM50 ROR score in Japanese patients with early breast cancer using long-term follow-up data. METHODS: We enrolled postmenopausal patients with ER-positive, HER2-negative, stage I-II breast cancer who had undergone surgery at the Kyoto University Hospital between 2008 and 2014. The intrinsic subtype and ROR score were calculated using PAM50. The primary endpoint was invasive disease-free survival (IDFS). RESULTS: We enrolled 146 patients, of whom 47 (32%) patients had node-positive disease, and 36 (25%) had received neoadjuvant or adjuvant chemotherapy. The proportions of intrinsic subtypes for luminal A, luminal B, HER2-enriched, and basal-like subtypes were 67%, 27%, 3%, and 2%, respectively. The median follow-up duration was 8.4 (range 6.3-10.0) years, and 21 IDFS events were observed. Based on the ROR score, 37%, 33%, and 30% of the patients were classified as low, intermediate, and high risks, respectively. Patients in the high-risk group had a significantly worse 8-year IDFS rate than those in the low-to-intermediate-risk groups (75.1% vs. 91.6%, p = 0.04). The same trend was observed in patients with and without neoadjuvant or adjuvant chemotherapy. CONCLUSIONS: Using long-term follow-up data, this study showed that the ROR score can predict the prognosis of ER-positive, HER2-negative early breast cancer in Japanese postmenopausal patients. Further investigations are required to confirm the prognostic value of the ROR score in Asian populations.

Optimization of CRISPR/Cas12a detection assay and its application in the detection of Echinococcus granulosus.

Cystic echinococcosis, resulting from infection with Echinococcus granulosus, poses a significant challenge as a neglected tropical disease owing to the lack of any known effective treatment. Primarily affecting under-resourced, remote, and conflict-ridden regions, the disease is compounded by the limitations of current detection techniques, such as microscopy, physical imaging, ELISA, and qPCR, which are unsuitable for application in these areas. The emergence of CRISPR/Cas12a as a promising tool for nucleic acid detection, characterized by its unparalleled specificity, heightened sensitivity, and rapid detection time, offers a potential solution. In this study, we present a one-pot CRISPR/Cas12a detection method for E. granulosus (genotype G1, sheep strain) integrating recombinase polymerase amplification (RPA) with suboptimal protospacer adjacent motif (PAM) and structured CRISPR RNA (crRNA) to enhance reaction efficiency. The evaluation of the assay's performance using hydatid cyst spiked dog feces and the examination of 62 dog fecal samples collected from various regions of Western China demonstrate its efficacy. The assay permits visual observation of test results about 15 minutes under blue light and displays superior portability and reaction speed relative to qPCR, achieving a sensitivity level of 10 copies of standard plasmids of the target gene. Analytic specificity was verified against four tapeworm species (E. multilocularis, H. taeniaeformis, M. benedeni, and D. caninum) and two other helminths (T. canis and F. hepatica), with negative results also noted for Mesocestoides sp. This study presents a rapid, sensitive, and time-efficient DNA detection method for E. granulosus of hydatid cyst spiked and clinical dog feces, potential serving as an alternative tool for field detection. This novel assay is primarily used to diagnose the definitive host of E. granulosus. Further validation using a larger set of clinical fecal samples is warranted, along with additional exploration of more effective approaches for nucleic acid release.

Seasonal timing of fluorescence and photosynthetic yields at needle and canopy scales in evergreen needleleaf forests.

The seasonal timing and magnitude of photosynthesis in evergreen needleleaf forests (ENFs) has major implications for the carbon cycle and is increasingly sensitive to changing climate. Earlier spring photosynthesis can increase carbon uptake over the growing season or cause early water reserve depletion that leads to premature cessation and increased carbon loss. Determining the start and the end of the growing season in ENFs is challenging due to a lack of field measurements and difficulty in interpreting satellite data, which are impacted by snow and cloud cover, and the pervasive "greenness" of these systems. We combine continuous needle-scale chlorophyll fluorescence measurements with tower-based remote sensing and gross primary productivity (GPP) estimates at three ENF sites across a latitudinal gradient (Colorado, Saskatchewan, Alaska) to link physiological changes with remote sensing signals during transition seasons. We derive a theoretical framework for observations of solar-induced chlorophyll fluorescence (SIF) and solar intensity-normalized SIF (SIFrelative) under snow-covered conditions, and show decreased sensitivity compared with reflectance data (~20% reduction in measured SIF vs. ~60% reduction in near-infrared vegetation index [NIRv] under 50% snow cover). Needle-scale fluorescence and photochemistry strongly correlated (r2 = 0.74 in Colorado, 0.70 in Alaska) and showed good agreement on the timing and magnitude of seasonal transitions. We demonstrate that this can be scaled to the site level with tower-based estimates of LUEP and SIFrelative which were well correlated across all sites (r2 = 0.70 in Colorado, 0.53 in Saskatchewan, 0.49 in Alaska). These independent, temporally continuous datasets confirm an increase in physiological activity prior to snowmelt across all three evergreen forests. This suggests that data-driven and process-based carbon cycle models which assume negligible physiological activity prior to snowmelt are inherently flawed, and underscores the utility of SIF data for tracking phenological events. Our research probes the spectral biology of evergreen forests and highlights spectral methods that can be applied in other ecosystems.

Discovery of VU6007496: Challenges in the Development of an M1 Positive Allosteric Modulator Backup Candidate.

Herein we report progress toward a backup clinical candidate to the M1 positive allosteric modulator (PAM) VU319/ACP-319. Scaffold-hopping from the pyrrolo[2,3-b]pyridine-based M1 PAM VU6007477 to isomeric pyrrolo[3,2-b]pyridine and thieno[3,2-b]pyridine congeners identified several backup contenders. Ultimately, VU6007496, a pyrrolo[3,2-b]pyridine, advanced into late stage profiling, only to be plagued with unanticipated, species-specific metabolism and active/toxic metabolites which were identified in our phenotypic seizure liability in vivo screen, preventing further development. However, VU6007496 proved to be a highly selective and CNS penetrant M1 PAM, with minimal agonism, that displayed excellent multispecies IV/PO pharmacokinetics (PK), CNS penetration, no induction of long-term depression (or cholinergic toxicity) and robust efficacy in novel object recognition (minimum effective dose = 3 mg/kg p.o.). Thus, VU6007496 can serve as another valuable in vivo tool compound in rats and nonhuman primates, but not mouse, to study selective M1 activation.

Fluorescence and electron transfer of Limnospira indica functionalized biophotoelectrodes.

Cyanobacteria play a crucial role in global carbon and nitrogen cycles through photosynthesis, making them valuable subjects for understanding the factors influencing their light utilization efficiency. Photosynthetic microorganisms offer a promising avenue for sustainable energy conversion in the field of photovoltaics. It was demonstrated before that application of an external electric field to the microbial biofilm or cell improves electron transfer kinetics and, consequently, efficiency of power generation. We have integrated live cyanobacterial cultures into photovoltaic devices by embedding Limnospira indica PCC 8005 cyanobacteria in agar and PEDOT:PSS matrices on the surface of boron-doped diamond electrodes. We have subjected them to varying external polarizations while simultaneously measuring current response and photosynthetic performance. For the latter, we employed Pulse-Amplitude-Modulation (PAM) fluorometry as a non-invasive and real-time monitoring tool. Our study demonstrates an improved light utilization efficiency for L. indica PCC 8005 when immobilized in a conductive matrix, particularly so for low-intensity light. Simultaneously, the impact of electrical polarization as an environmental factor influencing the photosynthetic apparatus diminishes as matrix conductivity increases. This results in only a slight decrease in light utilization efficiency for the illuminated sample compared to the dark-adapted state.

Enhancing microplastic removal from natural water using coagulant aids.

Microplastic (MP) pollution poses a significant environmental challenge, underscoring the need for improved water treatment methods. This study investigates the effectiveness of coagulation, flocculation, and sedimentation processes for removing microbeads, focusing on key factors that influence removal efficiency. Among the coagulants tested, polyaluminium chloride (PAC) demonstrated superior performance by enhancing the aggregation of microplastics with flocs. Optimal treatment conditions were determined to be 0.4 mmol/L PAC and 3 mg/L polyacrylamide (PAM) at pH 8 (before adding PAC), with rapid stirring at 240 rpm for 1 min, followed by slow stirring at 35 rpm for 13 min, and a sedimentation period of 25 min. Under these conditions, removal efficiencies exceeded 95 % for a range of microbeads (10-1000 µm: Polystyrene (PS), Polypropylene (PP), Polyvinyl chloride (PVC), Polyamide (PA), Polyethylene (PE), and Polyurethane (PU)) from natural water samples. Without PAM, PAC alone achieved a 97 % removal rate for PS microbeads. The addition of PAM maintained high removal efficiency, while aluminium sulphate and ferric chloride were less effective, with removal rates of 67 % and 48 % for PS microbeads, respectively. PAM enhanced MP removal across various coagulants and microbead types, with maximum efficiency observed at PAM concentrations of ≥3 mg/L. The treatment also demonstrated that organic matter in Regent's Park pond water could further improve MP removal. Size significantly impacts removal efficiency: larger microbeads (1 mm to >250 µm) were removed more effectively (95 %) compared to smaller ones (10 to <250 µm), which had a lower removal rate of 49 %. Denser microbeads like PVC (density 1.38 g/cm³) settled more efficiently than lighter microbeads such as PE (density 0.97 g/cm³). These findings suggest a need for advanced technologies to better remove lighter, smaller MPs from water.