Facilitation of macrofaunal assemblages in marinas by the habitat-forming invader Amathia verticillata (Bryozoa: Gymnolaemata) across a spatiotemporal scale.

Widespread habitat-forming invaders inhabiting marinas, such as the spaghetti bryozoan Amathia verticillata, allow exploring facilitation processes across spatiotemporal contexts. Here we investigate the role of this bryozoan as habitat for native and exotic macrofaunal assemblages across different ecoregions of Western Mediterranean and East Atlantic coasts, and a monthly variation over a year. While only 7 (all peracarid crustaceans) of the 54 associated species were NIS, they dominated macrofaunal assemblages in terms of abundance, raising the potential for invasional meltdown. NIS richness and community structure differed among marinas but not among ecoregions, highlighting the importance of marina singularities in modulating facilitation at spatial scale. Despite facilitation did not depend on bryozoan abundance fluctuations, it was affected by its deciduous pattern, peaking in summer and disappearing in late winter. Monitoring A. verticillata in marinas, especially in summer periods, may improve the detection and management of multiple associated NIS.

The icope Intrinsic Capacity Screening Tool: Measurement Structure and Predictive Validity of Dependence and Hospitalization.

OBJECTIVES: To evaluate the measurement structure of the ICOPE screening tool (IST) of intrinsic capacity and to find out whether the IST as a global measure adds explanatory power over and above its domains in isolation to predict the occurrence of adverse health outcomes such as dependence and hospitalization in community-dwelling older people. DESIGN: Secondary analysis of a cohort study, the Toledo Study of Healthy Ageing. SETTING: Province of Toledo, Spain. PARTICIPANTS: Community-dwelling older people. MEASUREMENTS: Items equal or similar to those of the IST were introduced as a reflective-formative construct in a Structural Equation Model to evaluate its measurement structure and its association with dependence for basic and instrumental activities and hospitalization over a three-year period. RESULTS: A total of 1032 individuals were analyzed. Mean age was 73.5 years (sd 5.4). The least preserved indicators were ability to recall three words (18%) and to perform chair stands (54%). Vision and hearing items did not form a single sensory domain, so six domains were considered. Several cognition items did not show sufficiently strong and univocal associations with the domain. After pruning the ill-behaved items, the measurement model fit was excellent (Satorra-Bentler scaled chi-square: 10.3, degrees of freedom: 11, p=0.501; CFI: 1.000; RMSEA: 0.000, 90% CI: 0.000-0.031, p value RMSEA<=0.05: 1; SRMR: 0.055). In the structural model, the cognition domain items were not associated as expected with age (p values 0.158 and 0.293), education (p values 0.190 and 0.432) and dependence (p values 0.654 and 0.813). The IST included as a composite in a model with the individual domains showed no statistically significant associations with any of the outcomes (dependence for basic activities: 0.162, p=0.167; instrumental: -0.052, p=0.546; hospitalization: 0.145, p=0.167), while only the mobility domain did so for dependence (basic: -0.266, p=0.005; instrumental: -0.138, p=0.019). The model fit of the last version was good (Satorra-Bentler scaled chi-square: 52.1, degrees of freedom: 52, p=0.469; CFI: 1.000; TLI: 1.000; RMSEA: 0.01, 90% CI: 0.000-0.02, p value RMSEA<=0.05: 1; SRMR: 0.071). The IST operationalized as the sum of non-impaired domains was not associated after covariate adjustment (dependence for basic activities: -0.065, p=0.356; instrumental: -0.08, p=0.05; hospitalization: -0.003, p=0.949) either. CONCLUSION: The cognitive domain of the IST, and probably other of its items, may need a reformulation. A global measure of intrinsic capacity such as the IST does not add explanatory power to the individual domains that constitute it. So far, our results confirm the importance of checking the findings of the IST with a second confirmatory step, as described in the WHO's ICOPE strategy.

Impact of outdoor air pollution on severity and mortality in COVID-19 pneumonia.

The relationship between exposure to air pollution and the severity of coronavirus disease 2019 (COVID-19) pneumonia and other outcomes is poorly understood. Beyond age and comorbidity, risk factors for adverse outcomes including death have been poorly studied. The main objective of our study was to examine the relationship between exposure to outdoor air pollution and the risk of death in patients with COVID-19 pneumonia using individual-level data. The secondary objective was to investigate the impact of air pollutants on gas exchange and systemic inflammation in this disease. This cohort study included 1548 patients hospitalised for COVID-19 pneumonia between February and May 2020 in one of four hospitals. Local agencies supplied daily data on environmental air pollutants (PM10, PM2.5, O3, NO2, NO and NOX) and meteorological conditions (temperature and humidity) in the year before hospital admission (from January 2019 to December 2019). Daily exposure to pollution and meteorological conditions by individual postcode of residence was estimated using geospatial Bayesian generalised additive models. The influence of air pollution on pneumonia severity was studied using generalised additive models which included: age, sex, Charlson comorbidity index, hospital, average income, air temperature and humidity, and exposure to each pollutant. Additionally, generalised additive models were generated for exploring the effect of air pollution on C-reactive protein (CRP) level and SpO2/FiO2 at admission. According to our results, both risk of COVID-19 death and CRP level increased significantly with median exposure to PM10, NO2, NO and NOX, while higher exposure to NO2, NO and NOX was associated with lower SpO2/FiO2 ratios. In conclusion, after controlling for socioeconomic, demographic and health-related variables, we found evidence of a significant positive relationship between air pollution and mortality in patients hospitalised for COVID-19 pneumonia. Additionally, inflammation (CRP) and gas exchange (SpO2/FiO2) in these patients were significantly related to exposure to air pollution.

Risk of Frailty According to the Values of the Ankle-Brachial Index in the Toledo Study for Healthy Aging.

BACKGROUND: Vascular function (VF) is a general term used to describe the regulation of blood flow, arterial pressure, capillary recruitment, filtration and central venous pressure, it´s well known that age has direct effects on the VF, and this may affect the frailty status. OBJECTIVES: To analyse the association between Frailty Trait Scale 5 (FTS 5) with VF and its changes at values below and above a nadir. DESIGN: Prospective population-based cohort study. SETTING AND PARTICIPANTS: Data from 1.230 patients were taken from the first wave (2006-2009) of the Toledo Study for Healthy Aging. MEASUREMENTS: Frailty was evaluated using FTS 5, which evaluates 5 items: Body mass index, progressive Romberg, physical activity, usual gait speed and hand grip strength. VF was assessed using the ankle-brachial index (ABI) as an indirect measure of VF. Screening for cardiovascular and cerebrovascular disease was also performed by self-reporting and by searching medical records, and was used as exclusion criteria. RESULTS: The optimal ABI cut-off point that maximized the adjusted R2 was 1.071. We observed a statistically significant association for FTS 5 score above and below the ABI cut-off points. For every tenth that the ABI decreased below the cut-off point the patient had an increase in the FTS 5 score of 0.47 points and in every tenth that increased above the cut-off point the increase in the FTS 5 score was 0.41 points. Of all FTS 5 items, the gait speed was the only item that showed a significant association with an ABI changes 0.28 and 0.21 points for every tenth below and above the cut-off point, respectively. CONCLUSIONS: Frailty is highly associated with VF. In addition, FTS 5 and its gait speed criteria are useful to detect VF impairments, via changes in ABI.

Insights into Palladium Deactivation during Advanced Oxidation Processes.

A key step in creating efficient and long-lasting catalysts is understanding their deactivation mechanism(s). On this basis, the behavior of a series of Pd/corundum materials during several hydrogen adsorption/desorption cycles was studied using temperature-programmed desorption coupled with mass spectrometry and aberration-corrected transmission electron microscopy. The materials, prepared by impregnation and by sputtering, presented uniform well-dispersed Pd nanoparticles. In addition, single atoms and small clusters of Pd were only detected in the materials prepared by impregnation. Upon exposure to hydrogen, the Pd nanoparticles smaller than 2 nm and the single atoms did not present any change, while the larger ones presented a core-shell morphology, where the core was Pd and the shell was PdH x . The results suggest that the long-term activity of the materials prepared by impregnation can be attributed solely to the presence of small clusters and single atoms of Pd.

The Medium-Term Changes in Health-Related Behaviours among Spanish Older People Lifestyles during Covid-19 Lockdown.

OBJECTIVES: The aim was to evaluate general changes and investigate the association between diet quality, physical activity (PA), and sedentary time (ST) during COVID-19 lockdown and the subsequent 7-month changes in health-related behaviours and lifestyles in older people. PARTICIPANTS: 1092 participants (67-97y) from two Spanish cohorts were included. DESIGN: Telephone-based questionaries were used to evaluate health-related behaviours and lifestyle. Multinomial logistic regression analyses with diet quality, PA, and ST during lockdown as predictors for health-related behaviours changes post-lockdown were applied. RESULTS: Diet quality, PA, and ST significantly improved post-lockdown, while physical component score of the SF-12 worsened. Participants with a low diet quality during lockdown had higher worsening of post-lockdown ST and anxiety; whereas those with high diet quality showed less likelihood of remaining abstainers, worsening weight, and improving PA. Lower ST was associated with a higher likelihood of remaining abstainers, and worsening weight and improving social contact; nevertheless, higher ST was linked to improvement in sleep quality. Lower PA was more likely to decrease alcohol consumption, while higher PA showed the opposite. However, PA was more likely to be associated to remain abstainers. CONCLUSIONS: Despite improvements in lifestyle after lockdown, it had health consequences for older people. Particularly, lower ST during lockdown seemed to provide the most medium-term remarkable lifestyle improvements.

Impact of nutritional status according to GLIM criteria on the risk of incident frailty and mortality in community-dwelling older adults.

BACKGROUND & AIMS: Poor nutritional status leads to multiple adverse outcomes, but few studies have assessed its role as a risk factor for incident frailty and death in community-dwelling older adults. Hence, the aim of this paper is to assess the role of nutritional status using the Global Leadership Initiative on Malnutrition (GLIM) criteria in the risk of frailty and mortality in Spanish community-dwelling older adults. METHODS: We used data from two waves (waves 2 (2011-2013) and 3 (2015-2017)) from the Toledo Study of Healthy Ageing, which is an observational, prospective cohort (average follow-up = 3.18 years) of 1660 older (≥65 years) adults living in the community. Nutritional status categories were defined according to the GLIM criteria, which uses a two-step approach. First, screening for malnutrition risk. Once positive, individuals were classified as malnourished according to some phenotypic (body mass index, grip strength and unintentional weight loss) and etiologic (disease burden/inflammation and reduced food intake or assimilation) criteria. Frailty was assessed using both the Frailty Index (FI) and Frailty Trait Scale (FTS). Mortality data was obtained through the National Death Index. RESULTS: From the 1660 older adults, 248 participants (14.04%) were classified as 'at malnutrition risk' (AMR) and 209 (12.59%) as malnourished (MN). AMR and MN subjects were older and with worse functional status (frailer). Adjusted cross-sectional analysis showed an association between nutritional status and frailty by both FI and FTS. Adjusted longitudinal analyses showed that AMR was associated with higher risk of frailty, using both the FTS (OR: 1.262; 95% CI: 1.078-1.815) and the FI (OR: 1.116; 95% CI: 1.098-1.686), while being malnourished was associated with higher mortality risk (OR: 1.748; 95% CI: 1.073-2.849), but not with incident frailty at follow-up period. CONCLUSIONS: Nutritional status, assessed through GLIM, predicts in a dose-dependent manner the risk of frailty and death. Being at malnutrition risk predicts the risk of becoming frail at follow-up period, whereas being malnourished predicts mortality. These findings highlight the importance of assessing the nutritional status of community-dwelling older adults to identify the ones at risk of developing frailty or death and inform targeted nutrition-focused interventions.

Effects of the age/rage axis in the platelet activation.

Platelet activity is essential in cardiovascular diseases. Therefore our objective was to evaluate the main effects of activating RAGE in platelets which are still unknown. A search for RAGE expression in different databases showed poor or a nonexistent presence in platelets. We confirmed the expression in platelets and secreted variable of RAGE (sRAGE). Platelets from elderly adults expressed in resting showed 3.2 fold more RAGE from young individuals (p < 0.01) and 3.3 fold with TRAP-6 (p < 0.001). These results could indicate that the expression of RAGE is more inducible in older adults. Then we found that activating RAGE with AGE-BSA-derived from methylglyoxal and subthreshold TRAP-6, showed a considerable increase with respect to the control in platelet aggregation and expression of P-selectin (respectively, p < 0.01). This effect was almost completely blocked by using a specific RAGE inhibitor (FSP-ZM1), confirming that RAGE is important for the function and activation platelet. Finally, we predict the region stimulated by AGE-BSA is located in region V of RAGE and 13 amino acids are critical for its binding. In conclusion, the activation of RAGE affects platelet activation and 13 amino acids are critical for its stimulation, this information is crucial for future possible treatments for CVD.

Association of a single nucleotide polymorphism in the ubxn6 gene with long-term non-progression phenotype in HIV-positive individuals.

OBJECTIVES: The long-term non-progressors (LTNPs) are a heterogeneous group of HIV-positive individuals characterized by their ability to maintain high CD4+ T-cell counts and partially control viral replication for years in the absence of antiretroviral therapy. The present study aims to identify host single nucleotide polymorphisms (SNPs) associated with non-progression in a cohort of 352 individuals. METHODS: DNA microarrays and exome sequencing were used for genotyping about 240 000 functional polymorphisms throughout more than 20 000 human genes. The allele frequencies of 85 LTNPs were compared with a control population. SNPs associated with LTNPs were confirmed in a population of typical progressors. Functional analyses in the affected gene were carried out through knockdown experiments in HeLa-P4, macrophages and dendritic cells. RESULTS: Several SNPs located within the major histocompatibility complex region previously related to LTNPs were confirmed in this new cohort. The SNP rs1127888 (UBXN6) surpassed the statistical significance of these markers after Bonferroni correction (q = 2.11 × 10-6). An uncommon allelic frequency of rs1127888 among LTNPs was confirmed by comparison with typical progressors and other publicly available populations. UBXN6 knockdown experiments caused an increase in CAV1 expression and its accumulation in the plasma membrane. In vitro infection of different cell types with HIV-1 replication-competent recombinant viruses caused a reduction of the viral replication capacity compared with their corresponding wild-type cells expressing UBXN6. CONCLUSIONS: A higher prevalence of Ala31Thr in UBXN6 was found among LTNPs within its N-terminal region, which is crucial for UBXN6/VCP protein complex formation. UBXN6 knockdown affected CAV1 turnover and HIV-1 replication capacity.

Intragastric pH effect of 20mg of levo-pantoprazole versus 40mg of racemic pantoprazole the first seven days of treatment in patients with gastroesophageal reflux disease. / Efecto sobre el pH intragástrico de 20mg de levopantoprazol versus 40mg de pantoprazol racémico durante los primeros 7 días de tratamiento en pacientes con enfermedad por reflujo gastroesofágico.

INTRODUCTION/AIM: Levo-pantoprazole, the S-enantiomer of pantoprazole, is a proton pump inhibitor that has been shown in animal studies to be faster and stronger than its racemic formulation. There are no studies on humans and therefore our aim was to evaluate the effects of levo-pantoprazole versus racemic pantoprazole on intragastric pH. MATERIALS AND METHODS: A randomized controlled study was conducted on patients with erosive gastroesophageal reflux disease that were given 20mg of levo-pantoprazole (n = 15) versus 40mg of racemic pantoprazole (n = 15) for 7 days. Baseline and end-of-treatment symptom evaluation and intragastric pH measurement were carried out. RESULTS: There were no differences between the groups in the baseline evaluations. From 40 to 115min after the first dose of levo-pantoprazole, the mean intragastric pH was higher, compared with that of racemic pantoprazole (p < 0.05). After one week, levo-pantoprazole and racemic pantoprazole significantly reduced intragastric acid production and its esophageal exposure (p < 0.05). Even though there was no statistically significant difference, a larger number of patients that received levo-pantoprazole stated that their heartburn improved within the first 3 days. CONCLUSIONS: The S-enantiomer of pantoprazole (levo-pantoprazole) had a faster and stronger effect with respect to acid suppression, compared with its racemic formulation. Although the effect on symptoms was faster with levo-pantoprazole, occurring within the first days of treatment, it was equivalent to that of the racemate at one week of treatment.

Fibroblast activation and abnormal extracellular matrix remodelling as common hallmarks in three cancer-prone genodermatoses.

BACKGROUND: Recessive dystrophic epidermolysis bullosa (RDEB), Kindler syndrome (KS) and xeroderma pigmentosum complementation group C (XPC) are three cancer-prone genodermatoses whose causal genetic mutations cannot fully explain, on their own, the array of associated phenotypic manifestations. Recent evidence highlights the role of the stromal microenvironment in the pathology of these disorders. OBJECTIVES: To investigate, by means of comparative gene expression analysis, the role played by dermal fibroblasts in the pathogenesis of RDEB, KS and XPC. METHODS: We conducted RNA-Seq analysis, which included a thorough examination of the differentially expressed genes, a functional enrichment analysis and a description of affected signalling circuits. Transcriptomic data were validated at the protein level in cell cultures, serum samples and skin biopsies. RESULTS: Interdisease comparisons against control fibroblasts revealed a unifying signature of 186 differentially expressed genes and four signalling pathways in the three genodermatoses. Remarkably, some of the uncovered expression changes suggest a synthetic fibroblast phenotype characterized by the aberrant expression of extracellular matrix (ECM) proteins. Western blot and immunofluorescence in situ analyses validated the RNA-Seq data. In addition, enzyme-linked immunosorbent assay revealed increased circulating levels of periostin in patients with RDEB. CONCLUSIONS: Our results suggest that the different causal genetic defects converge into common changes in gene expression, possibly due to injury-sensitive events. These, in turn, trigger a cascade of reactions involving abnormal ECM deposition and underexpression of antioxidant enzymes. The elucidated expression signature provides new potential biomarkers and common therapeutic targets in RDEB, XPC and KS. What's already known about this topic? Recessive dystrophic epidermolysis bullosa (RDEB), Kindler syndrome (KS) and xeroderma pigmentosum complementation group C (XPC) are three genodermatoses with high predisposition to cancer development. Although their causal genetic mutations mainly affect epithelia, the dermal microenvironment likely contributes to the physiopathology of these disorders. What does this study add? We disclose a large overlapping transcription profile between XPC, KS and RDEB fibroblasts that points towards an activated phenotype with high matrix-synthetic capacity. This common signature seems to be independent of the primary causal deficiency, but reflects an underlying derangement of the extracellular matrix via transforming growth factor-ß signalling activation and oxidative state imbalance. What is the translational message? This study broadens the current knowledge about the pathology of these diseases and highlights new targets and biomarkers for effective therapeutic intervention. It is suggested that high levels of circulating periostin could represent a potential biomarker in RDEB.

Deep sequencing and miRNA profiles in alcohol-induced neuroinflammation and the TLR4 response in mice cerebral cortex.

Alcohol abuse can induce brain injury and neurodegeneration, and recent evidence shows the participation of immune receptors toll-like in the neuroinflammation and brain damage. We evaluated the role of miRNAs as potential modulators of the neuroinflammation associated with alcohol abuse and the influence of the TLR4 response. Using mice cerebral cortex and next-generation sequencing (NGS), we identified miRNAs that were differentially expressed in the chronic alcohol-treated versus untreated WT or TLR4-KO mice. We observed a differentially expression of miR-183 Cluster (C) (miR-96/-182/-183), miR-200a and miR-200b, which were down-regulated, while mirR-125b was up-regulated in alcohol-treated WT versus (vs.) untreated mice. These miRNAs modulate targets genes related to the voltage-gated sodium channel, neuron hyperexcitability (Nav1.3, Trpv1, Smad3 and PP1-γ), as well as genes associated with innate immune TLR4 signaling response (Il1r1, Mapk14, Sirt1, Lrp6 and Bdnf). Functional enrichment of the miR-183C and miR-200a/b family target genes, revealed neuroinflammatory pathways networks involved in TLR4 signaling and alcohol abuse. The changes in the neuroinflammatory targets genes associated with alcohol abuse were mostly abolished in the TLR4-KO mice. Our results show the relationship between alcohol intake and miRNAs expression and open up new therapeutically targets to prevent deleterious effects of alcohol on the brain.

Chemical vapor deposition growth of boron-carbon-nitrogen layers from methylamine borane thermolysis products.

This work investigates the growth of B-C-N layers by chemical vapor deposition using methylamine borane (MeAB) as the single-source precursor. MeAB has been synthesized and characterized, paying particular attention to the analysis of its thermolysis products, which are the gaseous precursors for B-C-N growth. Samples have been grown on Cu foils and transferred onto different substrates for their morphological, structural, chemical, electronic and optical characterizations. The results of these characterizations indicate a segregation of h-BN and graphene-like (Gr) domains. However, there is an important presence of B and N interactions with C at the Gr borders, and of C interacting at the h-BN-edges, respectively, in the obtained nano-layers. In particular, there is a significant presence of C-N bonds, at Gr/h-BN borders and in the form of N doping of Gr domains. The overall B:C:N contents in the layers is close to 1:3:1.5. A careful analysis of the optical bandgap determination of the obtained B-C-N layers is presented, discussed and compared with previous seminal works with samples of similar composition.

Global Performance of Executive Function Is Predictor of Risk of Frailty and Disability in Older Adults.

INTRODUCTION: The executive function is a complex set of skills affected during the aging process and translate into subclinical cerebrovascular disease. Postural instability or motor slowness are some clinical manifestations, being consubstantial with the frailty phenotype, genuine expression of aging. Executive dysfunction is also considered a predictor of adverse health events in the elderly. AIM: To study whether the executive dysfunction can be used as an early marker for frailty and the viability of use as a predictor of mortality, hospitalization and/or disability in a Mediterranean population. DESIGN: A population-based cohort study using data from the Toledo Study for Healthy Aging (TSHA). METHODS: 1690 Spanish elders aged ≥65 years underwent a neuropsychological evaluation in order to measure executive function. To assess whether the accumulation of dysfunctions (in severity and amplitude) could increase the predictive value of adverse health events in relation to each dimension separately an executive dysfunction cumulative index was constructed. Cox proportional hazards model was used to examine mortality and hospitalization over 5.02 and 3.1 years of follow-up, respectively. RESULTS: Executive dysfunction is a powerful predictor of mortality, frailty and disability. Cumulative differences in executive function are associated with high risk of frailty and disability, thus, for each one point increment in the executive function index, the risk of death increased by 7 %, frailty by 13% and disability by 11% (P<0.05). Moreover, the executive impairment exhibits a strong positive tendency with age, comorbidity and mortality. CONCLUSIONS: Cumulative differences in four executive dimensions widely used in clinical practice improves the ability to predict frailty and disability compared to each dimension separately.

Gait Velocity and Chair Sit-Stand-Sit Performance Improves Current Frailty-Status Identification.

Frailty is characterized by a loss of functionality and is expected to affect 9.9% of people aged 65 and over. Here, current frailty classification is compared with a collection of selected kinematic parameters. A total of 718 elderly subjects (319 males and 399 females; age: 75.4 ± 6.1 years), volunteered to participate in this study and were classified according to Fried's criteria. Both the 30-s chair stand test (CST) and the 3-m walking test were performed and a set of kinematic parameters were obtained from a single inertial unit. A decision tree analysis was used to: 1) identify the most relevant frailty-related parameters and 2) compare validity of this classification. We found that a selected set of parameters from the 30-s CST (i.e., range of movement, acceleration, and power) were better at identifying frailty status than both the actual outcome of the test (i.e., cycles' number) and the normally used criteria (i.e., gait speed). For the pre-frail status, AUC improves from 0.531 using the actual test outcome and 0.516 with gait speed to 0.938 with the kinematic parameters criteria. In practice, this could improve the presyndrome identification and perform the appropriate actions to postpone the progression into the frail status.

Identification of the Photoreceptor Transcriptional Co-Repressor SAMD11 as Novel Cause of Autosomal Recessive Retinitis Pigmentosa.

Retinitis pigmentosa (RP), the most frequent form of inherited retinal dystrophy is characterized by progressive photoreceptor degeneration. Many genes have been implicated in RP development, but several others remain to be identified. Using a combination of homozygosity mapping, whole-exome and targeted next-generation sequencing, we found a novel homozygous nonsense mutation in SAMD11 in five individuals diagnosed with adult-onset RP from two unrelated consanguineous Spanish families. SAMD11 is ortholog to the mouse major retinal SAM domain (mr-s) protein that is implicated in CRX-mediated transcriptional regulation in the retina. Accordingly, protein-protein network analysis revealed a significant interaction of SAMD11 with CRX. Immunoblotting analysis confirmed strong expression of SAMD11 in human retina. Immunolocalization studies revealed SAMD11 was detected in the three nuclear layers of the human retina and interestingly differential expression between cone and rod photoreceptors was observed. Our study strongly implicates SAMD11 as novel cause of RP playing an important role in the pathogenesis of human degeneration of photoreceptors.