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Poly (ADP-ribose) glycohydrolase (PARG) inhibitors are currently under clinical development for the treatment of DNA repair-deficient cancers; however, their precise mechanism of action is still unclear. Here, we report that PARG inhibition leads to excessive PARylated poly (ADP-ribose) polymerase 1 (PARP1) reducing the ability of PARP1 to properly localize to sites of DNA damage. Strikingly, the mis-localized PARP1 accumulates as aggregates throughout the nucleus. Abrogation of the catalytic activity of PARP1 prevents aggregate formation, indicating that PAR chains play a key role in this process. Finally, we find that PARP1 nuclear aggregates were highly persistent and were associated with cleaved cytoplasmic PARP1, ultimately leading to cell death. Overall, our data uncover an unexpected mechanism of PARG inhibitor cytotoxicity, which will shed light on the use of these drugs as anti-cancer therapeutics. [Display omitted] • PARG inhibition causes nuclear PARP1 aggregation in response to DNA damage • PARP1 aggregates cause the mis-localization of PARP1 away from damage sites • PARP1 aggregates are formed through PAR chains • PARP1 aggregates are associated with cell death Paradkar et al. report that PARG inhibitors induce the formation of nuclear and highly persistent PARP1 aggregates in response to DNA damage. These aggregates require PAR chain synthesis for their formation and cause the mis-localization of PARP1 away from sites of DNA damage, leading to cytotoxicity across cancer cell lines. [ABSTRACT FROM AUTHOR]

Background: Studies on the association between serum vitamin B6 status and colorectal cancer prognosis are limited and have yielded inconsistent results. This study investigated the association of pyridoxal 5′-phosphate (PLP) and pyridoxic acid ratio (PAr) index with colorectal cancer survival. Methods: A total of 1286 colorectal cancer patients diagnosed since 2010 were selected from the Guangdong Colorectal Cancer Cohort study. Serum levels of PLP, pyridoxal, and 4-pyridoxic acid were measured using ultra-high-performance liquid chromatography–tandem mass spectrometry. The study followed overall mortality and colorectal cancer-specific mortality until December 2023. Multivariable Cox proportional hazards regression models were applied to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs). Restricted cubic spline and stratified analysis were performed. Results: During a median follow-up of 77.36 months, 331 deaths were recorded, with 293 specifically attributed to colorectal cancer. Higher PLP levels were associated with a longer overall survival (HRQ4 vs. Q1, 0.63; 95% CI: 0.46, 0.87; p for trend = 0.008) and colorectal cancer-specific survival (HRQ4 vs. Q1, 0.62; 95% CI: 0.44, 0.87; p for trend = 0.006). Non-linear associations were observed between serum PLP and overall and colorectal cancer-specific survival (p for non-linear < 0.05). However, PAr was not significantly associated with either overall survival (HRQ4 vs. Q1, 1.03; 95% CI: 0.75, 1.41) or colorectal cancer-specific survival (HRQ4 vs. Q1, 1.01; 95% CI: 0.72, 1.42). The association between serum PLP and both overall survival and colorectal cancer-specific survival (p for interaction < 0.05) varied by alcohol drinking status. Conclusions: Higher serum PLP levels, but not PAr, may be associated with improved overall and colorectal cancer-specific survival. [ABSTRACT FROM AUTHOR]

Pentatricopeptide repeat (PPR) proteins bind RNA and are present in mitochondria and chloroplasts of Eukaryota. In fungi, they are responsible for controlling mitochondrial genome expression, mainly on the posttranscriptional level. Candida albicans is a human opportunistic pathogen with a facultative anaerobic metabolism which, unlike the model yeast Saccharomyces cerevisiae , possesses mitochondrially encoded respiratory Complex I (CI) subunits and does not tolerate loss of mtDNA. We characterized the function of 4 PPR proteins of C. albicans that lack orthologs in S. cerevisiae and found that they are required for the expression of mitochondrially encoded CI subunits. We demonstrated that these proteins localize to mitochondria and are essential to maintain the respiratory capacity of cells. Deletion of genes encoding these PPR proteins results in changes in steady-state levels of mitochondrial RNAs and proteins. We demonstrated that C. albicans cells lacking CaPpr4, CaPpr11, and CaPpr13 proteins show no CI assembly, whereas the lack of CaPpr7p results in a decreased CI activity. CaPpr13p is required to maintain the bicistronic NAD4L–NAD5 mRNA, whereas the other 3 PPR proteins are likely involved in translation-related assembly of mitochondrially encoded CI subunits. In addition, we show that CaAep3p, which is an ortholog of ScAep3p, performs the evolutionary conserved function of controlling expression of the ATP8–ATP6 mRNA. We also show that C. albicans cells lacking PPR proteins express a higher level of the inducible alternative oxidase (AOX2) which likely rescues respiratory defects and compensates for oxidative stress. [ABSTRACT FROM AUTHOR]

In the citizen science project “Storytelling about caring cultures at the end of life. Students and citizen scientists are doing research in intergenerational and intercultural exchange (SoKuL)”, students (n=6) reported in qualitative interviews and focus groups on their learning experiences in the project.The students were able to gain varied and sustainable experiences. As a result of their participation in the project, they perceived personal development, which they describe as valuable for their internship and their future profession in elderly care. This concerns the development of an attitude that makes it easier to deal with and address the topics of dying, death & mourning and a learning process in conducting dialogues.The in-depth learning experiences of the participating students illustrate the interventional nature of the research project. The participation of citizen scientists as co-researchers not only serves the advancement of knowledge in sciences. Their participation in the project was accompanied by a transformative learning process.

Citizen science is increasingly credited for promoting scientific literacy and having the potential to empower and engage local people in conservation. However, rigorous evaluation of citizen science outcomes is limited, particularly those related to social capital and environmental stewardship. Social science can help to address this gap as it can identify barriers that hinder the success of citizen science programs and drivers that promote positive outcomes, such as social norms, community engagement, and effective communication strategies. However, little has been written about how academic partners in social science fields can engage with citizen science practitioners. In this paper we describe seven design components essential to the success of a long-term research collaboration between academic social scientists and staff of Billion Oyster Project (BOP), a nonprofit environmental organization whose mission is to restore oyster reefs to New York Harbor through citizen science, restoration, and public education initiatives. We describe how over an eight-year period, social science methodologies and findings were used to inform BOP’s environmental citizen science and volunteer programing and management. We argue that collaborative research is essential for the advancement of our field, and that action-driven research partnerships should become a key component of effective citizen science programs. [ABSTRACT FROM AUTHOR]

Abstract Background Despite evidence supporting the high correlation of the novel platelet-to-albumin ratio (PAR) with survival in diverse malignancies, its prognostic relevance in nasopharyngeal carcinoma (NPC) remains underexplored. This study aimed to examine the link between PAR and overall survival (OS) in NPC and to establish a predictive model based on this biomarker. Methods We retrospectively assembled a cohort consisting of 858 NPC patients who underwent concurrent chemoradiotherapy (CCRT). Utilizing the maximally selected log-rank method, we ascertained the optimal cut-off point for the PAR. Subsequently, univariate and multivariate Cox proportional hazards models were employed to discern factors significantly associated with OS and to construct a predictive nomogram. Further, we subjected the nomogram’s predictive accuracy to rigorous independent validation. Results The discriminative optimal PAR threshold was determined to be 4.47, effectively stratifying NPC patients into two prognostically distinct subgroups (hazard ratio [HR] = 0.53; 95% confidence interval [CI]: 0.28–0.98, P = 0.042). A predictive nomogram was formulated using the results from multivariate analysis, which revealed age greater than 45 years, T stage, N stage, and PAR score as independent predictors of OS. The nomogram demonstrated a commendable predictive capability for OS, with a C-index of 0.69 (95% CI: 0.64–0.75), surpassing the performance of the conventional staging system, which had a C-index of 0.56 (95% CI: 0.65–0.74). Conclusions In the context of NPC patients undergoing CCRT, the novel nutritional-inflammatory biomarker PAR emerges as a promising, cost-efficient, easily accessible, non-invasive, and potentially valuable predictor of prognosis. The predictive efficacy of the nomogram incorporating the PAR score exceeded that of the conventional staging approach, thereby indicating its potential as an enhanced prognostic tool in this clinical setting.

Black pepper (Piper nigrum L.), is a woody perennial climbing plant belonging to family Piperaceae and the most consumed spice in the world. Although the support tree Gliricidia (Gliricidia sepium) is pruned 3 to 4 times per year, pepper vines are not annually pruned in Sri Lanka. The characteristic cylindrical compact canopy of pepper is inefficient in intercepting solar radiation compared to most other vine crops. Therefore, this study was conducted to investigate the effect of different canopy pruning practices on the Photosynthetically Active Radiation (PAR) interception efficiency of the plant canopy and its effect on the yield. Four treatments on pruning practices were compared to each other. Treatments were, T1 – Control (no pruning); T2 - maintaining cone-shaped canopy by pruning only the plagiotropic branches; T3 - partial pruning of lateral branches of only the upper half (layer 1 and layer 2) of the canopy; and T4 - removal of 25% of lateral branches allowing uniform distribution of sunlight all over the canopy (loose canopy). The results revealed that T2 and T4 pruning methods significantly improved the yield (P<0.05) compared to T1 and T3. Hence, both modifying the cone-shaped canopy and maintaining a loose canopy all over the plant are better pruning practices to maximize yield through efficient PAR absorption. Therefore, adopting either of these pruning methods can be recommended as better practices for farmers to maximize their crop yield. [ABSTRACT FROM AUTHOR]

Background: Despite evidence supporting the high correlation of the novel platelet-to-albumin ratio (PAR) with survival in diverse malignancies, its prognostic relevance in nasopharyngeal carcinoma (NPC) remains underexplored. This study aimed to examine the link between PAR and overall survival (OS) in NPC and to establish a predictive model based on this biomarker. Methods: We retrospectively assembled a cohort consisting of 858 NPC patients who underwent concurrent chemoradiotherapy (CCRT). Utilizing the maximally selected log-rank method, we ascertained the optimal cut-off point for the PAR. Subsequently, univariate and multivariate Cox proportional hazards models were employed to discern factors significantly associated with OS and to construct a predictive nomogram. Further, we subjected the nomogram’s predictive accuracy to rigorous independent validation. Results: The discriminative optimal PAR threshold was determined to be 4.47, effectively stratifying NPC patients into two prognostically distinct subgroups (hazard ratio [HR] = 0.53; 95% confidence interval [CI]: 0.28–0.98, P = 0.042). A predictive nomogram was formulated using the results from multivariate analysis, which revealed age greater than 45 years, T stage, N stage, and PAR score as independent predictors of OS. The nomogram demonstrated a commendable predictive capability for OS, with a C-index of 0.69 (95% CI: 0.64–0.75), surpassing the performance of the conventional staging system, which had a C-index of 0.56 (95% CI: 0.65–0.74). Conclusions: In the context of NPC patients undergoing CCRT, the novel nutritional-inflammatory biomarker PAR emerges as a promising, cost-efficient, easily accessible, non-invasive, and potentially valuable predictor of prognosis. The predictive efficacy of the nomogram incorporating the PAR score exceeded that of the conventional staging approach, thereby indicating its potential as an enhanced prognostic tool in this clinical setting. [ABSTRACT FROM AUTHOR]

ABSTRACTInstantaneous determinations of photosynthetically active radiation (PAR) over the sea from the Ocean and Land Color Instrument (OLCI) on Sentinel-3 are compared with in-situ measurements at the island of Lampedusa in the central Mediterranean Sea. Radiative transfer calculations show that the PAR measured at the island site is representative for open ocean conditions. Satellite data show a good agreement (5.2% positive bias, R2 = 0.97) with in-situ data, in line with similar analyses for other satellite sensors. Larger satellite-in situ differences are found during summer, and the possible role of aerosols in degrading PAR estimate has been investigated by comparing AOD values measured at Lampedusa and derived by OLCI. The relative difference between OLCI and in-situ PAR appears to be negatively correlated with the relative differences between OLCI and in-situ AOD, suggesting that a more accurate determination of AOD, in particular, for cases with AOD > 0.2, mostly related to Saharan dust, may lead to improved satellite PAR estimates.

Backgrounds: Platelet‐to‐albumin ratio (PAR) is a new systemic inflammatory prognostic indicator associated with many inflammatory diseases. However, its role in radiation cystitis (RC) is obscure. This study aimed to explore whether PAR could be used as an effective parameter for predicting the RC risk in local advanced cervical cancer (CC) treated with radiotherapy. Methods: A total of 319 local advanced CC patients who received radical radiotherapy at Fujian Cancer Hospital were enrolled between December 2018 and January 2021. Demographics and clinical parameters were retrospectively analyzed. Univariate and multivariate analyses were used to identify the risk factors for RC. Backward and stepwise regression was applied to construct two monograms‐one with primary significant factors and the other with extra inflammatory biomarkers. A DeLong test was applied to compare the prediction abilities of two nomograms. Calibration curves and decision curve analysis (DCA) evaluated its prediction consistency, discrimination ability, and clinical net benefit. Results: Univariate analysis showed that age, tumor size, stage, total radiation dose, pelvic radiation dose, Systemic Immune‐Inflammation Index (SII), platelet‐to‐lymphocyte ratio (PLR), and PAR were significantly associated with RC occurrence (all p < 0.05). Multivariate analyses indicated that age, tumor size, stage, total radiation dose, and PAR were independent factors (all p < 0.05). Then, the area under curve (AUC) value of the nomogramSII+PAR was higher (AUC = 0.774) compared to that of the baseline nomogram (AUC = 0.726) (pDelong = 0.02). Also, the five‐cross validation confirmed the stability of the nomogramSII+PAR. Moreover, the calibration curve and DCA exhibited the nomograms' good prediction consistency and clinical practicability. Conclusions: PAR and SII could be valued for CC patients who are treated with radiation therapy. The nomogram based on PAR and SII could stratify patients who need extra intervention and nursing care to prevent bladder radiation damage and improve patients' quality of life. [ABSTRACT FROM AUTHOR]

Fetal sex affects fetal and maternal health outcomes in pregnancy, but this connection remains poorly understood. As the placenta is the route of fetomaternal communication and derives from the fetal genome, placental gene expression sex differences may explain these outcomes. We utilized next generation sequencing to study the normal human placenta in both sexes in first and third trimester to generate a normative transcriptome based on sex and gestation. We analyzed 124 first trimester (T1, 59 female and 65 male) and 43 third trimester (T3, 18 female and 25 male) samples for sex differences within each trimester and sex-specific gestational differences. Placenta shows more significant sexual dimorphism in T1, with 94 T1 and 26 T3 differentially expressed genes (DEGs). The sex chromosomes contributed 60.6% of DEGs in T1 and 80.8% of DEGs in T3, excluding X/Y pseudoautosomal regions. There were 6 DEGs from the pseudoautosomal regions, only significant in T1 and all upregulated in males. The distribution of DEGs on the X chromosome suggests genes on Xp (the short arm) may be particularly important in placental sex differences. Dosage compensation analysis of X/Y homolog genes shows expression is primarily contributed by the X chromosome. In sex-specific analyses of first versus third trimester, there were 2815 DEGs common to both sexes upregulated in T1, and 3263 common DEGs upregulated in T3. There were 7 female-exclusive DEGs upregulated in T1, 15 female-exclusive DEGs upregulated in T3, 10 male-exclusive DEGs upregulated in T1, and 20 male-exclusive DEGs upregulated in T3. This is the largest cohort of placentas across gestation from healthy pregnancies defining the normative sex dimorphic gene expression and sex common, sex specific and sex exclusive gene expression across gestation. The first trimester has the most sexually dimorphic transcripts, and the majority were upregulated in females compared to males in both trimesters. The short arm of the X chromosome and the pseudoautosomal region is particularly critical in defining sex differences in the first trimester placenta. As pregnancy is a dynamic state, sex specific DEGs across gestation may contribute to sex dimorphic changes in overall outcomes. • Fetal and maternal health outcomes due to the placenta are sexually dimorphic, therefore sequencing was performed. • Sex differences were more prevalent in first trimester, and derived mostly from sex chromosomes. • Genes common to both sexes were identified, as well as genes exclusive to each sex. • This is the largest normative placenta transcriptome atlas stratified by sex across gestation. • Genes identified may account for changes during placentation or overall outcomes based on sex. [ABSTRACT FROM AUTHOR]

Participatory Action Research (PAR) brings unique ethical challenges. Scholars have developed seven ethical principles to address these challenges. So far, little has been published on how these ethical principles (are put to) work in different fields. We used the principles to evaluate our collaboration with co-researchers with developmental language disorder (DLD). This article aims to explore how the principles helped to reflect on the ongoing research practice. First, we needed to simplify the language of the principles so that the co-researchers could understand how they relate to concrete practices. Second, the co-researchers needed to be reminded of specific events before they could relate the principles to their own experiences. Lastly, for an evaluation of (co-) researchers dealing with multiple roles, from friend to colleague and client, this theme has been specifically included to the principle of personal integrity, so that it cannot be overlooked. Looking through a care ethical lens, we suggest speaking of practical insights rather than (ethical) principles, as it more clearly communicates that these insights are based on learning by doing and are not fixed, but build on (good) practices, whilst still allowing enough room for adjustments to the particularities inherent to each research process. [ABSTRACT FROM AUTHOR]

In the Initial Orbit Determination (IOD) context, Admissible Regions are subsets of parameter space of orbital elements that are reckoned as functions of the tracking measurement variables. Physically acceptable orbits, e.g., orbits with negative energies, constitute an Admissible Region. This paper defines sets of orbits that satisfy constraints imposed by the measurement variables. Using a probabilistic representation of constraints on some of the orbital parameters the Admissible Region can be further constrained to give a Probabilistic Admissible Region (PAR). PAR gives a particle cloud representation of the initial probability density function (pdf) of the state of a Resident Space Object (RSO). This paper presents a geometric solution to the Probabilistic Admissible Region (G-PAR). G-PAR is a set of algorithms sharing the same underlying template that geometrically maps postulated statistics on some orbital elements and statistics of the measurement process to the uncertainty in the states. The proposed scheme gives a simple closed-form solution for mapping particles to get the PAR pdf for the first time. This speeds up the PAR initial orbit determination with a single partial state measurement. The effectiveness of the proposed G-PAR is shown on diverse combinations of sensors and prior knowledge. [ABSTRACT FROM AUTHOR]

Hydrogen generated in severe accidental conditions poses a threat to nuclear containment once it exceeds the flammability limit in the air. A passive Autocatalytic Recombiner (PAR) device is one of the best options to tackle this scenario. In view of this, we have developed a novel breed of bimetallic Pt–Pd nano-catalysts supported over cordierite by a chemical reduction route. Pt–Pd particles with dimensions ∼4.5–11.5 nm were found to be in a metallic state and amorphous in nature. They were assessed for H 2 and O 2 recombination reactions and found to be catalytically active for the same. Their activity was also established in the presence of various probable contaminants viz. CO, CO 2 , CH 4 , relative humidity, and catalyst wetness. • Pt + Pd bimetallic catalyst was developed for hydrogen mitigation under severe accident conditions. • Ceramic support was used for enhanced properties of the catalyst. • Catalyst exhibits unaltered catalytic activity in presence of various poisons. • Catalyst retains its activity in presence of CO for wider range of concentrations. • Activation energy calculated and compared to earlier reported catalyst. [ABSTRACT FROM AUTHOR]

The evolution of the smart grid has enabled residential users to manage the ever-growing energy demand in an efficient manner. The smart grid plays an important role in managing this huge energy demand of residential households. A home energy management system enhances the efficiency of the energy infrastructure of smart homes and provides an opportunity for residential users to optimize their energy consumption. Smart homes contribute significantly to reducing electricity consumption costs by scheduling domestic appliances effectively. This residential appliance scheduling problem is the motivation to find an optimal appliance schedule for users that could balance the load profile of the home and helps in minimizing electricity cost (EC) and peak-to-average ratio (PAR). In this paper, we have focused on appliance scheduling on the consumer side. Two novel home energy management models are proposed using multiple scheduling options. The residential appliance scheduling problem is formulated using the multiple knapsack technique. Serial and parallel scheduling algorithms of home appliances namely MKSI (Multiple knapsacks with serial implementation) and MKPI (Multiple knapsacks with parallel implementation) are proposed to reduce electricity cost and PAR. Price-based demand response techniques are incorporated to shift appliances from peak hours to off-peak hours to optimize energy consumption. The proposed algorithms are tested on real-time datasets and evaluated based on time of use pricing tariff and critical peak pricing. The performance of both the algorithms is compared with the unscheduled scenario and existing algorithm. Simulations show that both proposed algorithms are efficient methods for home energy management to minimize PAR and electricity bills of consumers. The proposed MKSI algorithm achieves cost reduction of 20.26% and 42.53% for TOU and CPP, respectively as compared to the unscheduled scenario while PAR is reduced by 45.07% and 39.51% for TOU and CPP, respectively. The proposed MKPI algorithm achieves 22.33% and 46.36% cost reduction compared to the unscheduled case for TOU and CPP while the PAR ratio is reduced by 46.47% and 41.16% for TOU and CPP respectively. [ABSTRACT FROM AUTHOR]

Adprhl2 (OMIM: 610624) mutation associated stress-induced childhood-onset neurodegeneration with variable ataxia and seizures (CONDSIAS, OMIM: 618170) is a sporadic neurodegenerative disease with poor prognosis. ADPRHL2 encodes ADP-ribosylhydrolase 3 (ARH3), which participates in ADP-ribosylation to remove poly-ADP ribose (PAR). We found a new compound heterozygous mutation in the ADPRHL2 gene c.580C > T (p.Gln194Ter) and c.803-1G > A in a 30-month-old boy, who showed gait instability, abnormal EEG, and developmental delay after respiratory infection. He died of convulsions 4 months after onset. By constructing a mutant plasmid and using Western blot to detect the expression of ARH3 and PAR, it was demonstrated that the ADPRHL2 gene c.580C > T (p.Gln194Ter) and c.803-1G > A is pathogenic according to ACMG guidelines.

Abstract Inherited retinal degenerations (IRDs) are a group of untreatable and commonly blinding diseases characterized by progressive photoreceptor loss. IRD pathology has been linked to an excessive activation of cyclic nucleotide-gated channels (CNGC) leading to Na+- and Ca2+-influx, subsequent activation of voltage-gated Ca2+-channels (VGCC), and further Ca2+ influx. However, a connection between excessive Ca2+ influx and photoreceptor loss has yet to be proven. Here, we used whole-retina and single-cell RNA-sequencing to compare gene expression between the rd1 mouse model for IRD and wild-type (wt) mice. Differentially expressed genes indicated links to several Ca2+-signalling related pathways. To explore these, rd1 and wt organotypic retinal explant cultures were treated with the intracellular Ca2+-chelator BAPTA-AM or inhibitors of different Ca2+-permeable channels, including CNGC, L-type VGCC, T-type VGCC, Ca2+-release-activated channel (CRAC), and Na+/Ca2+ exchanger (NCX). Moreover, we employed the novel compound NA-184 to selectively inhibit the Ca2+-dependent protease calpain-2. Effects on the retinal activity of poly(ADP-ribose) polymerase (PARP), sirtuin-type histone-deacetylase, calpains, as well as on activation of calpain-1, and − 2 were monitored, cell death was assessed via the TUNEL assay. While rd1 photoreceptor cell death was reduced by BAPTA-AM, Ca2+-channel blockers had divergent effects: While inhibition of T-type VGCC and NCX promoted survival, blocking CNGCs and CRACs did not. The treatment-related activity patterns of calpains and PARPs corresponded to the extent of cell death. Remarkably, sirtuin activity and calpain-1 activation were linked to photoreceptor protection, while calpain-2 activity was related to degeneration. In support of this finding, the calpain-2 inhibitor NA-184 protected rd1 photoreceptors. These results suggest that Ca2+ overload in rd1 photoreceptors may be triggered by T-type VGCCs and NCX. High Ca2+-levels likely suppress protective activity of calpain-1 and promote retinal degeneration via activation of calpain-2. Overall, our study details the complexity of Ca2+-signalling in photoreceptors and emphasizes the importance of targeting degenerative processes specifically to achieve a therapeutic benefit for IRDs. Video Abstract

BackgroundAt the start of the coronavirus disease 2019 (COVID-19) pandemic, widespread blood shortages were anticipated. We sought to determine how hospital blood supply and blood utilization were affected by the first wave of COVID-19.Study design and methodsWeekly red blood cell (RBC) and platelet (PLT) inventory, transfusion, and outdate data were collected from 13 institutions in the United States, Brazil, Canada, and Denmark from March 1st to December 31st of 2020 and 2019. Data from the sites were aligned based on each site's local first peak of COVID-19 cases, and data from 2020 (pandemic year) were compared with data from the corresponding period in 2019 (pre-pandemic baseline).ResultsRBC inventories were 3% lower in 2020 than in 2019 (680 vs. 704, p

The high ecological and economic value of seagrass has been long recognized, with these foundational habitats providing myriad ecosystem services. Yet through cumulative anthropogenic impacts, seagrasses are exhibiting extensive declines globally. A litany of studies and active restoration trials have demonstrated practicalmethodologies to restore seagrass habitats and effectively return critical habitat functions to degraded coastal zone systems worldwide. Seagrass loss along the U.S. West Coast has precipitated decades of seagrass protection, conservation, and restoration efforts. Yet, mitigation transplanting efforts have prioritized Zostera marina (narrow-leaved eelgrass) in shallow, protected environments, while a dearth of information is available on species inhabiting offshore islands and exposed mainland coasts. In this study, we conducted a novel transplant of Zostera pacifica, a wide-leaved species found in depths of 7 - 20 m along the offshore islands and mainland coast of California. Transplants were conducted at three geographically distinct sites in Santa Monica Bay, coupled with continuous monitoring of biophysical parameters providing insight into physical drivers at transplant and donor sites. Utilizing in situ data, and environmental thresholds adapted from the literature for Z. marina, we performed exposure analyses to evaluate factors influencing Z. pacifica transplant performance. Exceedances of threshold values for environmental parameters, specifically, wave exposure and near-bed flow speeds (Hrms > 0.59mand Urms > 0.1ms-1), photosynthetically active radiation (< 3 and > 5 mol m-2 day-1) and dissolved oxygen (< 3mgO2 L-1) exposure impacted transplant survivorship. These results suggest Z. pacifica persist in biophysically dynamic conditions and are sensitive to exceedances of thresholds, underlining the importance of pre-transplant site-selection processes to this species. These data represent the first holistic study of Z. pacifica transplanting on an exposed mainland coast, which provides a view into the baseline environmental envelopes within existing Z. pacifica habitat, and further, may serve as a model for investigating scalable open coast seagrass restoration for temperate regions. [ABSTRACT FROM AUTHOR]

Inherited retinal degenerations (IRDs) are a group of untreatable and commonly blinding diseases characterized by progressive photoreceptor loss. IRD pathology has been linked to an excessive activation of cyclic nucleotide-gated channels (CNGC) leading to Na+- and Ca2+-influx, subsequent activation of voltage-gated Ca2+-channels (VGCC), and further Ca2+ influx. However, a connection between excessive Ca2+ influx and photoreceptor loss has yet to be proven. Here, we used whole-retina and single-cell RNA-sequencing to compare gene expression between the rd1 mouse model for IRD and wild-type (wt) mice. Differentially expressed genes indicated links to several Ca2+-signalling related pathways. To explore these, rd1 and wt organotypic retinal explant cultures were treated with the intracellular Ca2+-chelator BAPTA-AM or inhibitors of different Ca2+-permeable channels, including CNGC, L-type VGCC, T-type VGCC, Ca2+-release-activated channel (CRAC), and Na+/Ca2+ exchanger (NCX). Moreover, we employed the novel compound NA-184 to selectively inhibit the Ca2+-dependent protease calpain-2. Effects on the retinal activity of poly(ADP-ribose) polymerase (PARP), sirtuin-type histone-deacetylase, calpains, as well as on activation of calpain-1, and − 2 were monitored, cell death was assessed via the TUNEL assay. While rd1 photoreceptor cell death was reduced by BAPTA-AM, Ca2+-channel blockers had divergent effects: While inhibition of T-type VGCC and NCX promoted survival, blocking CNGCs and CRACs did not. The treatment-related activity patterns of calpains and PARPs corresponded to the extent of cell death. Remarkably, sirtuin activity and calpain-1 activation were linked to photoreceptor protection, while calpain-2 activity was related to degeneration. In support of this finding, the calpain-2 inhibitor NA-184 protected rd1 photoreceptors. These results suggest that Ca2+ overload in rd1 photoreceptors may be triggered by T-type VGCCs and NCX. High Ca2+-levels likely suppress protective activity of calpain-1 and promote retinal degeneration via activation of calpain-2. Overall, our study details the complexity of Ca2+-signalling in photoreceptors and emphasizes the importance of targeting degenerative processes specifically to achieve a therapeutic benefit for IRDs. 9rDzNFNpqNfiW7CgYpAk_t Video Abstract [ABSTRACT FROM AUTHOR]

Sea ice algae play an important role in the Arctic Ocean ecosystem, driving primary production in the spring and sequestering carbon to the deep ocean. Up to 45% of Arctic Ocean primary production occurs in ice‐covered areas; photosynthetically active radiation (PAR) is fundamental to driving this production. Sea ice, and particularly snow, strongly scatter and reflect light, reducing the amount of PAR transmitted to the ice‐ocean interface. The effect that varying thicknesses of sea ice (0.2–3.5 m) and snow (0.01–1 m) have on the value of PAR transmittance at the ice‐ocean interface are considered for a Winter, Spring, and Summer scenario. When characteristic Arctic Ocean conditions (2 m sea ice and ∼0.2 m snowpack) are modeled, there is roughly a two‐fold difference in PAR transmittance at the ice‐ocean interface between the Winter (0.003) and Spring (0.007) scenarios and an order of magnitude difference with the Summer scenario (0.04). The modeled values correlate within one standard deviation of measured values and show good agreement with extended pan‐Arctic Ocean field campaign measurements. The results also indicate that simple exponential decay methods may lead to inaccurate results, and radiative‐transfer modeling is required to accurately predict PAR transmittance at the ice‐ocean interface. Therefore, this study offers a novel mathematical technique to predict the value of PAR transmittance at the ice‐ocean interface. Coupled with year‐round near‐real‐time sea ice and snow thickness remote sensing data, this technique may improve understanding of primary production and carbon budgets in the changing Arctic Ocean. Key Points: An algorithmic procedure to calculate photosynthetically active radiation (PAR) transmittance at the ice‐ocean interface for different types and thicknesses of sea ice and snowPAR transmittance under the ice requires careful radiative‐transfer modeling; simple light attenuation models give poor resultsApparent two‐fold difference in PAR values between Winter and Spring scenarios, and order of magnitude difference with the Summer scenario [ABSTRACT FROM AUTHOR]

Sex chromosome aneuploidies are among the most common variations in human whole chromosome copy numbers, with an estimated prevalence in the general population of 1:400 to 1:1400 live births. Unlike whole-chromosome aneuploidies of autosomes, those of sex chromosomes, such as the 47, XXY aneuploidy that causes Klinefelter Syndrome (KS), often originate from the paternal side, caused by a lack of crossover (CO) formation between the X and Y chromosomes. COs must form between all chromosome pairs to pass meiotic checkpoints and are the product of meiotic recombination that occurs between homologous sequences of parental chromosomes. Recombination between male sex chromosomes is more challenging compared to both autosomes and sex chromosomes in females, as it is restricted within a short region of homology between X and Y, called the pseudo-autosomal region (PAR). However, in normal individuals, CO formation occurs in PAR with a higher frequency than in any other region, indicating the presence of mechanisms that promote the initiation and processing of recombination in each meiotic division. In recent years, research has made great strides in identifying genes and mechanisms that facilitate CO formation in the PAR. Here, we outline the most recent and relevant findings in this field. XY chromosome aneuploidy in humans has broad-reaching effects, contributing significantly also to Turner syndrome, spontaneous abortions, oligospermia, and even infertility. Thus, in the years to come, the identification of genes and mechanisms beyond XY aneuploidy is expected to have an impact on the genetic counseling of a wide number of families and adults affected by these disorders. [ABSTRACT FROM AUTHOR]

A new orthodontic index was proposed by the College of Diplomates to assess the degree of difficulty of cases submitted for the IBO Phase III clinical examinations. This article is the continuation of Parts I and II of the article, which gave a brief insight into the need and the methodology undertaken to formulate this index. A weightage score grading the degree of difficulty was formulated based on the Dental, Cephalometric, and Miscellaneous components. An Aesthetic component was also developed. Further statistical evaluation was done to formulate a cut-off score required for cases submitted for the Phase III examination. This index would help to categorize the malocclusion in a structured manner. [ABSTRACT FROM AUTHOR]

The vertical distribution of light and its spectral composition are critical factors influencing numerous physical, chemical, and biological processes within the oceanic water column. In this study, we present vertically resolved models of downwelling irradiance (ED) at three different wavelengths and photosynthetically available radiation (PAR) on a global scale. These models rely on the SOCA (Satellite Ocean Color merged with Argo data to infer bio-optical properties to depth) methodology, which is based on an artificial neural network (ANN). The new light models are trained with light profiles (ED/PAR) acquired from BioGeoChemical-Argo (BGC-Argo) floats. The model inputs consist of surface ocean color radiometry data (i.e., R r s , PAR, and k d (490) ) derived by satellite and extracted from the GlobColour database, temperature and salinity profiles originating from BGC-Argo, as well as temporal components (day of the year and local time in cyclic transformation). The model outputs correspond to ED profiles at the three wavelengths of the BGC-Argo measurements (i.e., 380, 412, and 490 nm) and PAR profiles. We assessed the retrieval of light profiles by these light models using three different datasets: BGC-Argo profiles that were not used for the training (i.e., 20% of the initial database); data from four independent BGC-Argo floats that were used neither for the training nor for the 20% validation dataset; and the SeaBASS database (in situ data collected from various oceanic cruises). The light models show satisfactory predictions when thus compared with real measurements. From the 20% validation database, the light models retrieve light variables with high accuracies (root mean squared error (RMSE)) of 76.42 μmol quanta m−2 s−1 for PAR and 0.04, 0.08, and 0.09 W m−2 nm−1 for ED380, ED412, and ED490, respectively. This corresponds to a median absolute percent error (MAPE) that ranges from 37% for ED490 and PAR to 39% for ED380 and ED412. The estimated accuracy metrics across these three validation datasets are consistent and demonstrate the robustness and suitability of these light models for diverse global ocean applications. [ABSTRACT FROM AUTHOR]

This paper illustrates the work of creating, infrastructuring, and organising a food-sharing community from the ground up. Drawing on Participatory Action Research (PAR) and a three-year engagement with FoodSharing Stockholm, the paper shows how the processes of starting up a grassroots initiative are shaped by participants' direct experience and knowledge of similar initiatives. The analysis draws attention to: (1) how central activities such as recruiting volunteers, choosing digital tools, and establishing partnerships with food donors are conceived and organised, (2) the concrete challenges of sharing surplus food, such as adopting a distribution model, and negotiating fairness, and (3) how governance and decision-making models are adopted and (re)negotiated over time. The paper introduces the term Collective histories of organising to capture the impact that learning from previous experiences can have on communities' efforts to set up and run; and re-orient design visions towards the consideration and adoption of existing sociotechnical practices, rather than always aiming at novel digital explorations. We outline three emerging dimensions that can characterise "Collective histories of organising" as a concept, (1) configuring capacities, (2) configuring sociotechnical practices, and (3) configuring participation. The paper contributes practical sensitivities to build, sustain, and infrastructure surplus food-sharing initiatives, where these three dimensions are discussed as central concerns designers and other food-sharing communities could learn from. [ABSTRACT FROM AUTHOR]

Aim: Research on mesophotic coral ecosystems (MCEs) has increased exponentially in recent decades, and the significance of this ecosystem has been recognised both in terms of biodiversity and distribution. However, this research has mostly focussed on corals and is globally sporadic, with the Indian Ocean remaining largely unexplored and overall MCEs under protected. Hence, baseline data on MCE benthic communities is lacking, but nonetheless essential for developing adequate management strategies. Here, we assess the variation in diversity and community structure of MCEs along the depth gradient and among sites in the Indian Ocean and the environmental parameters that are potentially driving these differences. Location: Egmont Atoll, Chagos Archipelago, central Indian Ocean. Time Period: Present. Major Taxa Studied: Marine benthic invertebrates, plants. Methods: Using a remotely operated vehicle, we collected video transects between 15 and 160 m. We analysed the diversity and composition of benthic communities and used DistLM analysis to determine the environmental drivers of the community structure over the depth gradient and between sites. Results: We observed distinct benthic communities along the depth gradient, with a strong community break observed at ~60 m. We also identified a clear zonation of the benthic taxa with depth. This zonation was primarily driven by downward irradiance and temperature, with additional environmental processes playing a minor role in structuring the benthic communities. Main Conclusions: We show that MCEs in the Chagos Archipelago are distinct communities, and their distribution is driven primarily by irradiance and temperature. Our results highlight the variability in benthic community structure of MCEs, both along the depth gradient and at local geographical scales for the study region. This study showcases the uniqueness of MCEs and will aid in predicting their distribution, potential refugia for shallow reefs, and in developing evidence‐based protection for MCEs, to maintain overall marine biodiversity. [ABSTRACT FROM AUTHOR]

Abstract Backgrounds Platelet‐to‐albumin ratio (PAR) is a new systemic inflammatory prognostic indicator associated with many inflammatory diseases. However, its role in radiation cystitis (RC) is obscure. This study aimed to explore whether PAR could be used as an effective parameter for predicting the RC risk in local advanced cervical cancer (CC) treated with radiotherapy. Methods A total of 319 local advanced CC patients who received radical radiotherapy at Fujian Cancer Hospital were enrolled between December 2018 and January 2021. Demographics and clinical parameters were retrospectively analyzed. Univariate and multivariate analyses were used to identify the risk factors for RC. Backward and stepwise regression was applied to construct two monograms‐one with primary significant factors and the other with extra inflammatory biomarkers. A DeLong test was applied to compare the prediction abilities of two nomograms. Calibration curves and decision curve analysis (DCA) evaluated its prediction consistency, discrimination ability, and clinical net benefit. Results Univariate analysis showed that age, tumor size, stage, total radiation dose, pelvic radiation dose, Systemic Immune‐Inflammation Index (SII), platelet‐to‐lymphocyte ratio (PLR), and PAR were significantly associated with RC occurrence (all p

During the Fukushima Daiichi nuclear accident in 2011, hydrogen explosions occurred in all units from Unit 1 to Unit 3. Consequently, one of the lessons learned from the Fukushima Daiichi accident is the necessity of implementing hydrogen control and mitigation strategies for most Nuclear Power Plants (NPPs). This paper focuses on the incorporation of Passive Autocatalytic Recombiners (PARs) during the design phase of a small modular Pressurized Water Reactor (SMR-PWR) project. The numerical analyses are conducted using the MELCOR v. 2.2 code. Two scenarios are compared: the Total Loss of Feed Water (TLOFW) severe accident with and without PARs. Saphiro’s diagram is utilized to investigate whether the mixture's composition (hydrogen, air, steam) is flammable for both scenarios. It has been observed that the inclusion of PARs leads to a reduction in hydrogen risk (detonative or deflagrative) as the final hydrogen concentration values fall below the flammability limit. This study is preliminary, and further research is required.

Introduction Agriculture plays an essential role in providing food, and in order to achieve sustainability in the agricultural sector, resources must be used in the best possible way. In order to achieve the maximum possible yield, it is necessary for the crop plant to use the environmental factors, water, nutrients, light, and carbon dioxide, with the maximum possible efficiency. The maximum use of the required factors for growth is achieved only when the plant community exerts maximum pressure on these factors. In general, intercropping is one of the ways to achieve sustainable agriculture, with higher yields without increasing agricultural inputs, absorption, and environmental factors productivity. Researchers for the intercropping of corn and mung bean have reported that the mixed cultivation systems used environmental resources more effectively compared to the sole cropping of corn and mung bean. For this reason, nowadays, many plants, especially legumes, are cultivated in an intercropping form due to their ability to fix nitrogen. Due to the lack of resources regarding the effect of planting direction on plant yield, this study was conducted in order to evaluate resources and soil nutrients by changing the planting direction and replacing the intercropping system of the sunflower with cowpea. Materials and Methods This research was conducted in the field of the Agricultural Research Station of Zabol University during 2015-2016. The experiment was performed as a split-plot based on a randomized complete block design with three replications at the Research Farm of the Agricultural Research Institute of Zabol University. The main factor was two levels of planting direction (North-South and East-West), and the secondary factor was intercropping system in five levels, including (100% pure sunflower), (100% pure cowpea ), (50% sunflower + 50% cowpea ) (25% cowpea + 75% sunflower) and (75 % cowpea + 25%sunflower) were considered. Data for studied traits were measured as follows: radiation, temperature, volumetric humidity, calcium, phosphorus, magnesium, potassium, and the land equality ratio. Statistical analysis including, analysis of variance and mean comparisons (least significant difference (LSD) test at the 5% level), were applied to evaluated traits. Results and Discussion The maximum absorption of photosynthetically active radiation (PAR) was in the east-west cultivation direction (77.90%) compared to the north-south treatment, which was 24.6% more than the north-south direction. The analysis of variance indicated that the cultivation direction and intercropping systems on the amount of phosphorus in the soil after harvest were significant at 1% probability level. The comparison of means treatments showed that the amount of phosphorus in the soil in the direction of east-west cultivation was 15% higher compared to the direction of north-south cultivation. The highest amount of soil potassium was obtained in the east-west treatment and the intercropping system of 50% sunflower plus 50% cowpea (24.7 ppm). The lowest amount of soil potassium (16.15 ppm) was obtained in the treatment of east-west cultivation and the intercropping system of 75% sunflower plus 25% cowpea. The relative advantage of intercropping is expressed by the land equivalent ratio. The increase in the ratio of equal land per unit shows the relative usefulness of intercropping compared to sole cropping of each of the mixed components. The comparison of means of the intercropping system showed that among the treatments, the mixture of 75% sunflower plus 25% cowpea had the highest land equivalent ratio (2.54). Conclusion It seems that in order to maintain humidity make maximum use of limited water resources, and obtain high yield, the intercropping system of 75% sunflower plus 25% cowpea and planting direction the prevailing wind of the region (east-west) should be suitable for this region and regions with similar climate and windy conditions. Acknowledgments We would like to thank the chairman and the respected staff of the Agricultural Research Institute of Zabul University, who sincerely accompanied us in the implementation of this thesis.

Langkanya pupuk subsidi dari pemerintah menjadi permasalahan utama bagi petani bawang merah di Desa Puhkerep, Rejoso, Nganjuk. Kondisi ini memaksa para petani untuk membeli pupuk impor di desa lain yang harganya melebihi harga wajar hingga mencapai dua kali lipat. Maka dari itu, peneliti berinisiatif melakukan pemberdayaan pada warga dengan membuat Pupuk Organik Cair (POC) Jakaba Super sebagai alternatif pupuk bagi petani. Tujuan pemberdayaan ini adalah untuk memberikan keterampilan pembuatan POC Jakaba Super guna menekan biaya pengeluaran modal petani sebagai solusi alternatif. Metode yang digunakan adalah metode PAR (Participatory Action Research) untuk menemukan suatu hal serta mengkorelasikan jalannya penelitian terhadap proses perubahan sosial. Pengambilan data menggunakan observasi dengan menggunakan beberapa teknik PAR, yaitu Kalender Musim, Daily Routine, Diagram Venn, Trend and Change, serta Transect, Pohon Masalah dan Pohon Harapan. Sasaran kegiatan ini adalah perwakilan kelompok tani di Dusun Tinampuh, Puhkerep, dan Kentingan. Pemberdayaan berbasis penelitian ini dilakukan dalam beberapa tahapan yaitu wawancara semi-terstruktur, observasi dan teknik PAR, perencanaan pemberdayaan, implementasi pemberdayaan, monitoring, dan evaluasi. Hasil dari kegiatan ini yaitu terdapat kemajuan pemahaman warga tentang POC Jakaba Super dan antusiasme warga untuk membuat POC tersebut untuk ke depannya.

This paper describes how a collective of Latine youth and adult allies used art-based approaches in a participatory action research project to better understand the ways in which young U.S. Latines make meaning of wellbeing. In this study, we interviewed 19 individuals who identified as Latino/a/e, ages 19–24, from Colorado, Washington state and New Jersey. Our team intentionally chose art-based approaches, including music and painting, as analytical tools and healing methods to synthesize the responses of the Latine youth we interviewed. We found that Latine youth and young adults initially struggle with defining wellbeing, considering it to be an overly abstract concept or something only achievable through expensive, Western-based medical practices. We also found that many Latine youth often link the root cause of a majority of their mental health issues to numerous systemic terrors such as racism, capitalism and sexism that directly harm their most intimate and supportive relationships: their immediate or extended family and friendships. Young Latine adults have identified these components as pillars of their wellbeing, along with the need for intergenerational conversations, a sense of convivencia, rootedness with freedom of movement and our right to healing and joy.

In water-cooled power reactor, hydrogen is generated in case of steam zirconium reaction during severe accident condition and later on in addition to hydrogen; CO is also generated during molten corium concrete interaction after reactor pressure vessel failure. Passive Autocatalytic Recombiners (PARs) are provided in the containment for hydrogen management. The performance of the PARs in presence of hydrogen and carbon monoxide along with air has been evaluated. Depending on the conditions, CO may either react with oxygen to form carbon dioxide (CO2) or act as catalyst poison, reducing the catalyst activity and hence the hydrogen conversion efficiency. CFD analysis has been carried out to determine the effect of CO on catalyst plate temperature for 2 & 4% v/v H2 and 1–4% v/v CO with air at the recombiner inlet for a reported experiment. The results of CFD simulations have been compared with the reported experimental data for the model validation. The reaction at the recombiner plate is modelled based on diffusion theory. The developed CFD model has been used to predict the maximum catalyst temperature and outlet species concentration for different inlet velocity and temperatures of the mixture gas. The obtained results were used to fit a correlation for obtaining removal rate of carbon monoxide inside PAR as a function of inlet velocity and concentrations.

Abstract It is estimated that up to half of global methane (CH4) emissions are derived from microbial processes in aquatic ecosystems. However, it is not fully understood which factors explain the spatial and temporal variability of these emissions. For example, light has previously been shown to both inhibit and stimulate aerobic methane‐oxidizing bacteria (i.e., methanotrophs) in the water column. These contrasting results indicate that the mechanisms that light has on CH4 oxidation are not yet clearly known, even less so for benthic aerobic methanotrophs. Here, we tested whether light reaching the seafloor can inhibit methanotrophic activity on the sediment surface. We sampled and distributed over 40 intact sediment cores from two coastal sites (illuminated 10 m, and a dark site at 33 m water depth) into 0, 50, and 100 PAR light treatments. After 10 days, we found no difference between treatments for each site in pore‐water CH4 concentrations, relative abundance of aerobic methanotrophs, or the number of RNA transcripts related to methane oxidation. Our results suggest that light attenuation in coastal waters does not significantly affect aerobic methanotrophs in coastal sediments.