Search

Diverse modifications of the original morphological features occur throughout the taphonomic history of osteological remains, which may lead in erroneous interpretations about the formation of an accumulation as well as taxonomic misidentifications. Here, we present a neo-taphonomic study in order to analyze and interpret the modifications generated by digestion on osteoderms of the armadillo Dasypus novemcinctus obtained from scats produced by Puma concolor. Results reveal intense breakage and modifications of the articular and broken edges, dorsal surface, bone tissues, and ornamentation pattern of the osteoderms. This work describes for the first time the modifications caused by digestion in armadillo osteoderms, improving the knowledge of preservation of this type of skeletal element and providing a modern analog that can be used to distinguish archeological and paleontological accumulations formed by predators from those generated by other processes. The recognition that digestion modifies the original ornamentation pattern is particularly significant because ornamentation features are used in nearly all taxonomic and phylogenetic studies of fossil cingulates. We use this new information to re-evaluate osteoderms recovered from carnivore coprolites of the classic Middle Miocene La Venta site (Colombia), which formed the basis for recognizing and characterizing the dasypodid species Nanoastegotherium prostatum. We highlight the importance of knowing with certainty the origin and taphonomic history of remains since, in the particular case of cingulates, taxonomic identification also has important biostratigraphic, paleoecological, paleoenvironmental, and paleobiogeographical implications.

Testicular teratomas and teratocarcinomas are the most common testicular germ cell tumors in early childhood and young men, and they are frequently found unilaterally in the left testis. In 129/SvJ mice carrying a heterozygous copy of the potent modifier of tumor incidence Ter, a point mutation in the dead-end homolog one gene (Dnd1Ter/+), ∼70% of the unilateral teratomas arise in the left testis. We previously showed that in mice, left/right differences in vascular architecture are associated with reduced hemoglobin saturation and increased levels of the hypoxia inducible factor-1 alpha (HIF-1α) in the left compared to the right testis. To test the hypothesis that systemic reduction of oxygen availability in Dnd1Ter/+ mice would lead to an increased incidence of bilateral tumors, we placed pregnant females from 129/SvJ Dnd1Ter/+ intercross matings in a hypobaric chamber for 12-h intervals. Our results show that in 129/SvJ Dnd1Ter/+ male gonads, the incidence of bilateral teratoma increased from 3.3% to 64% when fetuses were exposed to acute low oxygen conditions for 12-h between E13.8 and E14.3. The increase in tumor incidence correlated with the maintenance of high expression of pluripotency genes Oct4, Sox2 and Nanog, elevated activity of the Nodal signaling pathway, and suppression of germ cell mitotic arrest. We propose that the combination of heterozygosity for the Ter mutation and hypoxia causes a delay in male germ cell differentiation that promotes teratoma initiation.

The bleak Alburnus alburnus is a medium body-size leuciscid fish that is naturally distributed across central European and western Asian fresh waters. However, during the last two decades A. alburnus has been widely introduced elsewhere in Europe and in northern Africa, mostly as a forage species for game fishes. Given its relatively recent history of invasion in non-native Eurasian waters, where it can become highly abundant, A. alburnus poses a serious risk to native communities where introduced. This study provides a review and meta-analysis of the biological traits of A. alburnus coupled with insights into its invasiveness. In its native range, A. alburnus has a moderate lifespan, inhabiting lakes or still waters in medium-to-large rivers, where it feeds mainly on zooplankton. However, non-native A. alburnus populations display high phenotypic plasticity in their biological attributes. Thus, growth, reproductive and/or dietary traits have adapted to local environmental conditions, with the species also invading lotic (stream) ecosystems. Feeding changes to benthic invertebrates, plant material and detritus when zooplankton is scarce. Such plasticity, including broad physiological tolerance, is likely to facilitate the species' adaptation and invasion of new habitats in the near future.

19 Páginas.-- 7 Figuras, ATP-citrate lyase is a central integrator of cellular metabolism in the interface of protein, carbohydrate, and lipid metabolism. The physiological consequences as well as the molecular mechanisms orchestrating the response to long-term pharmacologically induced Acly inhibition are unknown. We report here that the Acly inhibitor SB-204990 improves metabolic health and physical strength in wild-type mice when fed with a high-fat diet, while in mice fed with healthy diet results in metabolic imbalance and moderated insulin resistance. By applying a multiomic approach using untargeted metabolomics, transcriptomics, and proteomics, we determined that, in vivo, SB-204990 plays a role in the regulation of molecular mechanisms associated with aging, such as energy metabolism, mitochondrial function, mTOR signaling, and folate cycle, while global alterations on histone acetylation are absent. Our findings indicate a mechanism for regulating molecular pathways of aging that prevents the development of metabolic abnormalities associated with unhealthy dieting. This strategy might be explored for devising therapeutic approaches to prevent metabolic diseases., This work was funded by grants from the Ministerio de Economía y Competitividad, Instituto de Salud Carlos III, co-funded by Fondos FEDER (PI15/00134, PI18/01590, CPII19/00023 to A.M.M.) and the Ministerio de Ciencia e Innovación (PID2021-123965OB-100 to A.M.M.). A.M.M. is funded by the Junta de Andalucía P20_00480, the Spanish Society of Diabetes, and CSIC 202220I059. M.S.K. is funded by the Nordea Foundation (#02-2017-1749), the Novo Nordisk Foundation (#NNF17OC0027812), the Neye Foundation, the Lundbeck Foundation (#R324-2019-1492), the Ministry of Higher Education and Science of Denmark (#0238-00003B). V.C.G. is funded by the Instituto de Salud Carlos III (CP19/00046), co-funded by FEDER. F.M. is funded by the CIBERDEM of the Instituto de Salud Carlos III. A.M.M. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. We acknowledge the support of the group of basic research on diabetes of the Spanish Society of Diabetes.

A finales de 2021, Grupo Culmárex, inicia su colaboración con el laboratorio experimental LIMIA, instalaciones que el Gobierno Balear tiene en Andraxt, gracias a un acuerdo de colaboración con la Consellería de Agricultura, agua y alimentación. Este programa de colaboración, permitirá avances significativos en la crianza de dorada, lubina y corvina y promoverá la innovación en acuicultura en las Islas Baleares., Trabajos desarrollados en el marco de proyectos nacionales y europeos: CDTI INNOVACIÓN IDI20220242 COFINANCIADO POR FEMP CDTI INVERSIÓN IDI20200554 COFINANCIADO POR FEMP

Sulfate radicals (SO) reactivity against gram-negative (E. coli) and gram-positive (E. faecalis) bacteria and Contaminants of Emerging Concern (CECs) (Diclofenac-DCF, Sulfamethoxazole-SMX and Trimethoprim-TMP) was investigated through laser flash photolysis (LFP) technique. Analysis of the lifetime of SO in presence of cell-wall compounds of bacteria and CECs allowed determining reactivity of SO towards these compounds. Results showed that SO reacts with common cell-wall components through H-abstraction mechanism (k < 10 Ms). By contrast, k > 10 Ms were found using aromatic amino acids (AAA) only present in Porins of the gram-negative outer-membrane. The intermediates detected from the reaction of SO with the AAA confirmed the involvement of electron transfer processes. Moreover, k values determined for DCF, TMP and SMX also agreed with an electron transfer mechanism. Interestingly, bacteria and CECs removal at pilot plant scale by UV-C/SO is in accordance with the k obtained using the LFP: E. coli > E. faecalis and DCF > TMP ≅ SMX., This work is part of a project that has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant Agreement No 765860 (AQUAlity). Authors also acknowledge the Spanish Ministry of Science and Innovation (Projects PID2019–110441RB-C32 and PID2019–110441RB-C33). PhD Scholarship from CONACYT for J. Flores-Garcia (709358) is acknowledged.

Photosensitized thymine<>thymine (Thy<>Thy) formation and repair can be mediated by carbazole (Cbz). The former occurs from the Cbz triplet excited state via energy transfer, while the latter takes place from the singlet excited state via electron transfer. Here, fundamental insight is provided into the role of the topology and excited state multiplicity, as factors governing the balance between both processes. This has been achieved upon designing and synthesizing different isomers of trifunctional systems containing one Cbz and two Thy units covalently linked to the rigid skeleton of the natural deoxycholic acid. The results shown here prove that the Cbz photosensitized dimerization is not counterbalanced by repair when the latter, instead of operating through-space, has to proceed through-bond., Financial support from the Spanish Government (grant SEV-2016-0683), Generalitat Valenciana (PROMETEO/2017/075 and PROMETEO/2021/077), and Technical University of Valencia (Predoctoral FPI fellowship for P.M.) is gratefully acknowledged. G.S. thanks CTI-CSIC for the use of computational facilities.

Contaminants of emerging concern (CECs) constitute a wide class of organic molecules, which are found dissolved in wastewaters. Chemical properties of CECs are as wide as their chemical structures; nevertheless, most of the CECs can be removed from wastewaters using Advanced Oxidation Processes (AOPs). However, there are examples of CECs that have proven recalcitrant to AOPs. In such cases, Advanced Reduction Processes (ARPs) include those techniques able to achieve degradation of contaminants by producing highly reactive reducing radicals. Organic photocatalysts have demonstrated to be an efficient alternative to other types of photocatalysts in AOPs. Moreover, several organic photocatalysts, according to their redox properties, could also act as reductants under appropriate scenarios, a process that has been much less explored than oxidation. As an example, Riboflavin (RF) is a natural water-soluble molecule, well-known as vitamin B2. The photophysical and redox properties of RF have been extensively applied for the oxidative photodegradation of contaminants in water. More recently, the potential of RF has been expanded to the photoreduction of more recalcitrant pollutants. For instance, benzotriazoles UV-stabilizers (BUVSs) constitute a vast family of recalcitrant contaminants, which have been successfully degraded in the presence of a commercially available derivative of RF (2′,3′,4′,5′-tetraacetylated riboflavin, RFTA) and visible light, assisted by an amine, which acts as electron donor to the excited states of RFTA, generating the RFTA.. This species ultimately produces the reduction of the selected BUVSs. Photophysical experiments demonstrated the key role of the radical anion RFTA., and allowed determining the rate constants that were correlated to the observed photodegradations., The authors would like to acknowledge H2020/Marie Skłodowska-Curie Actions under the AQUAlity project (Reference: 765860), Consellería d'Educació, Investigació, Cultura i Esport (PROMETEO/2017/075) and the Spanish Ministry of Science, Innovation and Universities (PID2019–110441RB-C33 financed by MCIN/AEI/10.13039/501100011033) are gratefully acknowledged.

Impaired mucociliary clearance (MCC) is a key feature of many airway diseases, including asthma, bronchiectasis, chronic obstructive pulmonary disease, cystic fibrosis, and primary ciliary dyskinesia. To improve MCC and develop new treatments for these diseases requires a thorough understanding of how mucus concentration, mucus composition, and ciliary activity affect MCC, and how different therapeutics impact this process. Although differentiated cultures of human airway epithelial cells are useful for investigations of MCC, the extent of ciliary coordination in these cultures varies, and the mechanisms controlling ciliary orientation are not completely understood. By introducing a pattern of ridges and grooves into the underlying collagen substrate, we demonstrate for the first time, to our knowledge, that changes in the extracellular matrix can induce ciliary alignment. Remarkably, 90% of human airway epithelial cultures achieved continuous directional mucociliary transport (MCT) when grown on the patterned substrate. These cultures maintain transport for months, allowing carefully controlled investigations of MCC over a wide range of normal and pathological conditions. To characterize the system, we measured the transport of bovine submaxillary gland mucin (BSM) under several conditions. Transport of 5% BSM was significantly reduced compared with that of 2% BSM, and treatment of 5% BSM with the reducing agent tris(2-carboxyethyl)phosphine (TCEP) reduced viscosity and increased the rate of MCT by approximately twofold. Addition of a small amount of high-molecular-weight DNA increased mucus viscosity and reduced MCT by ∼75%, demonstrating that the composition of mucus, as well as the concentration, can have significant effects on MCT. Our results demonstrate that a simple patterning of the collagen substrate results in highly coordinated ciliated cultures that develop directional MCT, and can be used to investigate the mechanisms controlling the regulation of ciliary orientation. Furthermore, the results demonstrate that this method provides an improved system for studying the effects of mucus composition and therapeutic agents on MCC.

Objective: Each year, around one million people die by suicide. Despite its recognition as a public health concern, large-scale research on causal determinants of suicide attempt risk is scarce. Here, we leverage results from a recent genome-wide association study (GWAS) of suicide attempt to perform a data-driven screening of traits causally associated with suicide attempt. Methods: We performed a hypothesis-generating phenome-wide screening of causal relationships between suicide attempt risk and 1520 traits, which have been systematically aggregated on the Complex-Traits Genomics Virtual Lab platform. We employed the latent causal variable (LCV) method, which uses results from GWAS to assess whether a causal relationship can explain a genetic correlation between two traits. If a trait causally influences another one, the genetic variants that increase risk for the causal trait will also increase the risk for the outcome inducing a genetic correlation. Nonetheless, a genetic correlation can also be observed when traits share common pathways. The LCV method can assess whether the pattern of genetic effects for two genetically correlated traits support a causal association rather than a shared aetiology. Results: Our approach identified 62 traits that increased risk for suicide attempt. Risk factors identified can be broadly classified into (1) physical health disorders, including oesophagitis, fibromyalgia, hernia and cancer; (2) mental health-related traits, such as depression, substance use disorders and anxiety; and (3) lifestyle traits including being involved in combat or exposure to a war zone, and specific job categories such as being a truck driver or machine operator. Conclusions: Suicide attempt risk is likely explained by a combination of behavioural phenotypes and risk for both physical and psychiatric disorders. Our results also suggest that substance use behaviours and pain-related conditions are associated with an increased suicide attempt risk, elucidating important causal mechanisms that underpin this significant public health problem.

Mutations in SPAG1, a dynein axonemal assembly factor (DNAAF) that facilitates the assembly of dynein arms in the cytoplasm before their transport into the cilium, result in primary ciliary dyskinesia (PCD), a genetically heterogenous disorder characterized by chronic oto-sino-pulmonary disease, infertility and laterality defects. To further elucidate the role of SPAG1 in dynein assembly, we examined its expression, interactions and ciliary defects in control and PCD human airway epithelia. Immunoprecipitations showed that SPAG1 interacts with multiple DNAAFs, dynein chains and canonical components of the R2TP complex. Protein levels of dynein heavy chains (DHCs) and interactions between DHCs and dynein intermediate chains (DICs) were reduced in SPAG1 mutants. We also identified a previously uncharacterized 60 kDa SPAG1 isoform, through examination of PCD subjects with an atypical ultrastructural defect for SPAG1 variants, that can partially compensate for the absence of full-length SPAG1 to assemble a reduced number of outer dynein arms. In summary, our data show that SPAG1 is necessary for axonemal dynein arm assembly by scaffolding R2TP-like complexes composed of several DNAAFs that facilitate the folding and/or binding of the DHCs to the DIC complex.

SUMMARYThere is currently no established intervention for Cockayne syndrome, a disease characterized by progressive early onset neurodegeneration with features of premature aging. Here, we tested if acetyl-CoA precursors, citrate and beta-hydroxybutyrate, could reduce features of Cockayne syndrome in three model systems. We identified the gene Helicase 89B as a homologue of CSB in drosophila and found that the ketone beta-hydroxybutyrate rescued features of premature aging in Hel89B deficient flies. In mammals, loss of the citrate carrier Indy exacerbated the phenotype of Csbm/m mice which was rescued by a ketogenic diet. The rescue effect appeared to be mediated through ketone stimulated histone acetylation and facilitation of transcriptional readthrough of secondary DNA structures. These findings link a ketogenic diet with transcriptional resolution of secondary structures and DNA repair.

Mounting evidence suggests that DNA damage plays a central role in aging. Multiple tiers of defense have evolved to reduce the accumulation of DNA damage, including reducing damaging molecules, repairing DNA damage, and inducing senescence or apoptosis in response to persistent DNA damage. Mutations in or failure of these pathways can lead to accelerated or premature aging and age-related decline in vital organs, supporting the hypothesis that maintaining a pristine genome is paramount for human health. Understanding how we cope with DNA damage could inform on the aging process and further on how deficient DNA maintenance manifests in age-related phenotypes. This knowledge may lead to the development of novel interventions promoting healthspan.

PurposeParkinson’s disease (PD) is a neurodegenerative disorder associated with progressive disability. While the precise aetiology is unknown, there is evidence of significant genetic and environmental influences on individual risk. The Australian Parkinson’s Genetics Study seeks to study genetic and patient-reported data from a large cohort of individuals with PD in Australia to understand the sociodemographic, genetic and environmental basis of PD susceptibility, symptoms and progression.ParticipantsIn the pilot phase reported here, 1819 participants were recruited through assisted mailouts facilitated by Services Australia based on having three or more prescriptions for anti-PD medications in their Pharmaceutical Benefits Scheme records. The average age at the time of the questionnaire was 64±6 years. We collected patient-reported information and sociodemographic variables via an online (93% of the cohort) or paper-based (7%) questionnaire. One thousand five hundred and thirty-two participants (84.2%) met all inclusion criteria, and 1499 provided a DNA sample via traditional post.Findings to date65% of participants were men, and 92% identified as being of European descent. A previous traumatic brain injury was reported by 16% of participants and was correlated with a younger age of symptom onset. At the time of the questionnaire, constipation (36% of participants), depression (34%), anxiety (17%), melanoma (16%) and diabetes (10%) were the most reported comorbid conditions.Future plansWe plan to recruit sex-matched and age-matched unaffected controls, genotype all participants and collect non-motor symptoms and cognitive function data. Future work will explore the role of genetic and environmental factors in the aetiology of PD susceptibility, onset, symptoms, and progression, including as part of international PD research consortia.

Benzotriazole UV-stabilizers (BUVSs) are commonly used in industry as solar filters, due to their strong UV light absorption. Because of their extended usage, environmental contamination of waters due to BUVSs constitutes a growing concern. Direct photodegradation of BUVSs is not efficient due to their intrinsic thermal pathways to release the absorbed light. Nevertheless, their abatement in natural environments could be assisted by chromophoric dissolved organic matter. Among the BUVSs, three representative candidates were selected, UV-326, UV-327 and UV-328, to demonstrate the potential of Riboflavin (RF) as a natural visible-light absorbing photocatalyst for the abatement of these recalcitrant pollutants under reductive conditions. The use of visible light and DABCO, as a model sacrificial electron donor, generates the radical anion RFTA. This key species reacts with the solar filters, achieving their reductive abatement from the medium. Moreover, the participation of every potential reactive species has been investigated by photophysical techniques, together with determination of the quenching rate constant for every reaction pathway. Consequently, evidence supported the main role of the reductive photodegradation pathway, being RFTA the key species in the abatement of BUVSs., This research was funded by H2020/Marie Skłodowska-Curie Actions under the AQUAlity project (Reference: 765860) and European Union's Horizon 2020 Research and Innovation Program under European Research Council (ERC) through the HyMAP project (grant agreement No. 648319). Project PID2019-110441RB-C33 financed by MCIN/AEI/10.13039/501100011033 and AEI-MICINN/FEDER, UE through the Nympha Project (PID2019-106315RB-I00), the regional government of “Comunidad de Madrid” and the European Structural Funds through their financial support to FotoArt-CM project (S2018/NMT-4367) are also acknowledged.

Background Gatipotuzumab is a humanized monoclonal antibody recognizing the carbohydrate-induced epitope of the tumor-associated mucin-1 (TA-MUC1). This study aimed to evaluate the efficacy and safety of switch maintenance therapy with gatipotuzumab in patients with TA-MUC1-positive recurrent ovarian, fallopian tube, or primary high-grade serous peritoneal cancer. Patients and methods In this double-blind, randomized, placebo-controlled, phase II trial, patients with at least stable disease (SD) following chemotherapy were randomized 2:1 to receive intravenous gatipotuzumab (500 mg followed by 1700 mg 1 week later) or placebo every 3 weeks until tumor progression or unacceptable toxicity occurred. Stratification factors were the number of prior chemotherapy lines (2 versus 3-5), response versus SD after the most recent chemotherapy, and progression-free survival (PFS), Highlights • Evaluation of the efficacy and safety of a switch maintenance therapy with gatipotuzumab. • Patients with TA-MUC1-positive recurrent ovarian, fallopian tube, or primary high-grade serous peritoneal cancer evaluated. • Gatipotuzumab is a humanized monoclonal antibody recognizing the carbohydrate-induced tumor-associated epitope mucin-1. • Gatipotuzumab was well tolerated, with mild to moderate infusion-related reactions. • Gatipotuzumab switch maintenance therapy does not improve outcome in TA-MUC1-positive ovarian cancer patients.

Noscapine (NSC) is a benzyl-isoquinoline alkaloid discovered in 1930 as an antitussive agent. Recently, NSC has also been reported to exhibit antitumor activity and, according to computational studies, it is able to attack the protease enzyme of Coronavirus (COVID-19) and thus could be used as antiviral for COVID-19 pandemic. Therefore, an increasing use of this drug could be envisaged in the coming years. NSC is readily metabolized with a half-life of 4.5 h giving rise to cotarnine, hydrocotarnine, and meconine, arising from the oxidative breaking of the Csingle bondC bond between isoquinoline and phthalide moieties. Because of its potentially increasing use, high concentrations of NSC but also its metabolites will be delivered in the environment and potentially affect natural ecosystems. Thus, the aim of this work is to investigate the degradation of NSC in the presence of naturally occurring photocatalysts. As a matter of fact, the present contribution has demonstrated that NSC can be efficiently degraded in the presence of a derivative of the natural organic dye Riboflavin (RFTA) upon exposure to visible light. Indeed, a detailed study of the mechanism involved in the photodegradation revealed the similarities between the biomimetic and the photocatalyzed processes. In fact, the main photoproducts of NSC were identified as cotarnine and opianic acid based on a careful UPLC-MS2 analysis compared to the independently synthesized standards. The former is coincident with one of the main metabolites obtained in humans, whereas the latter is related to meconine, a second major metabolite of NSC. Photophysical experiments demonstrated that the observed oxidative cleavage is mediated mainly by singlet oxygen in a medium in which the lifetime of 1O2 is long enough, or by electron transfer to the triplet excited state of RFTA if the photodegradation occurs in aqueous media, where the 1O2 lifetime is very short., This work has been partially funded by the European Union, under the Marie Skłodowska-Curie scheme (Grant No 765860, AQUAlity). The Generalitat Valenciana (PROMETEO/2017/075) and the Spanish Government (Grant PID2019-110441RB-C33 financed by MCIN/AEI/10.13039/501100011033) are also gratefully acknowledged.

An in vivo experiment was conducted at the College of Agriculture, CMU, Musuan, Bukidnon, Philippines on corn and peanut seeds in order to assess the antifungal effects of the different concentrations of powdered Bidens pilosa leaves against postharvest pathogens. B. pilosa powder was thoroughly mixed at varying amounts as treatments to corn and peanut seeds and observed for the presence of fungal growths during the observation period of up to 35 days. Data gathering revealed the occurrence of 5 fungal species namely Aspergillus flavus, A. niger, Fusarium sp., Rhizopus sp., and M. phaseolina. The best antifungal treatment is the chemical fungicide Captan, however, T5 (30 g of B. pilosa/kilo of seeds) shows the potential to inhibit the growth of A. flavus, Rhizopus sp., and A. niger in corn while T4 (20 g of B. pilosa/kilo of seeds) had the potential to inhibit or prevent the growth of the two Aspergillus spp. in peanut. It was also noted that for corn, the least fungal count with a value of 1.00 was noted in T5 (30 g of B. pilosa/kilo of seeds) while for peanut, T4 (20 g of B. pilosa/kilo of seeds) had the potential to limit the growth of pathogenic fungi with a fungal count value of 1.33. The application of B. pilosa did not affect significantly the percentage germination of corn but with peanut, T5 (30 g of B. pilosa/kilo of seeds) shows a promising performance. On Seedling Vigor Index (SVI), the application of B. pilosa did not significantly influence the SVI of corn but for peanut, T5 (30 g of B. pilosa/kilo of seeds) has shown potential as it shows a better performance as compared with the other treatments. In this research, B. pilosa exhibited its potential as a biofungicide.

Primary ciliary dyskinesia (PCD) is a rare lung disease caused by mutations that impair the function of motile cilia, resulting in chronic upper and lower respiratory disease, reduced fertility, and a high prevalence of situs abnormalities. The disease is genetically and phenotypically heterogeneous, with causative mutations in50 genes identified, and clinical phenotypes ranging from mild to severe. Absence of

[EN] Organic photocatalysts could employ visible light to produce photodegradation of pollutants; however, their low photostability prevents their reuse even when they are supported on solid materials. Herein, to obtain a Riboflavin (RF)-based photocatalyst robust and recyclable, RF has been covalently anchored to silica particles, converting the known homogeneous photocatalyst into a new heterogeneous one (SiO2-RF). To enhance the photostability of SiO2-RF, generation of the RF triplet excited state and subsequent singlet oxygen were prevented by ensuring a complete shell of RF moieties on the silica spheres. Moreover, adsorption of organic pollutants such as phenol, ortho-phenylphenol, 2,4,6-trichlomphenol and pentachlorophenol on the surface of SiO2-RF is favored in aqueous media, facilitating electron transfer from the pollutants to the short-lived first singlet excited state of RF. Photophysical measurements provided evidence on the photocatalytic mechanism for SiO2-RF., YY The authors would like to acknowledge H2020/Marie Skodowska-Curie Actions under the AQUAlity project (Reference: 765860) , Con-selleria d'Educacio, Investigacio, Cultura i Esport (PROMETEO/2017/075) , the Spanish Ministry of Science, Innovation and Universities (PID2019-110441RB-C33 and SEV-2016-0683) . O. Cabezuelo is indebted to the Universitat Polite cnica de Valencia for the Predoctoral FPI fellowship (FPI-UPV/Subprograma 1) . R. M.-H. acknowledges Fondo Social Europeo (FSE) 2014-2020 Generalitat Valenciana (APOSTD-2019/124) .

Introduction/Background* Clinical trials consistently demonstrate the detrimental impact of progressive disease (PD) on patients’ health-related quality of life (HRQoL). Progression-free survival (PFS) is an established regulatory endpoint. However, PFS is often excluded as an efficacy endpoint on the basis that — PFS is not patient relevant — in early benefit assessment by select EU health technology agencies. The PRIMA/ENGOT-OV26/GOG-3012 (NCT02655016) Phase 3 trial showed niraparib significantly prolongs median PFS vs placebo in patients with AOC responsive to 1L platinum (Pt)-based chemotherapy, (CT), regardless of biomarker status. This post-hoc analysis of PRIMA is the first study to examine the relationship between HRQoL and PD in a broad frontline AOC maintenance treatment setting. Methodology In PRIMA, patients with AOC responsive to 1L Pt CT were randomised 2:1 to once-daily, maintenance niraparib or placebo. Impact of PD on patient HRQoL, irrespective of treatment, was evaluated within the pooled ITT population by comparing HRQoL at the last on-treatment (pre-progression) visit with HRQoL at end of treatment (EOT), +4 weeks, +8w, +12w, and +24w. Assessments included FOSI, EORTC QLQ-C30, EQ-5D-VAS, and EORTC QLQ-OV28 abdominal/GI symptom scale. ANCOVA was applied with treatment as a fixed effect and HRQoL at last on-treatment visit as a continuous covariate. Mixed models for repeated measurements (MMRM) evaluated cumulative HRQoL changes. Result(s)* Significant reductions in HRQoL from pre- to post-progression were observed across all measures. Compared with pre-progression, FOSI scores (Least-squares mean [95% CI]) were lower at EOT+4w (-2.2 [-2.8, -1.6]) and EOT+24w (-1.7 [-2.3, -1.1]); each p Conclusion* These findings demonstrate HRQoL is negatively impacted by PD in AOC. Preservation of HRQoL, an important therapy goal in the maintenance setting particularly for asymptomatic patients, can be achieved with PFS prolongation. PFS is of significant relevance and clinically important for AOC patients.

T-cell activation and cellular expansion by common gamma chain cytokines such as Interleukin-2 is necessary for adaptive immunity. However, when unregulated these same pathways promote pathologies ranging from autoimmune disorders to cancer. While the functional role of Interleukin-2 and downstream effector molecules is relatively clear, the repertoire of phosphoregulatory proteins downstream of this pathway is incomplete. To identify phosphoproteins downstream of common gamma chain receptor, YT cells were radiolabeled with [32P]-orthophosphate and stimulated with Interleukin-2. Subsequently, tyrosine phosphorylated proteins were immunopurified and subjected to tandem mass spectrometry—leading to the identification of CrkL. Phosphoamino acid analysis revealed concurrent serine phosphorylation of CrkL and was later identified as S114 by mass spectrometry analysis. S114 was inducible through stimulation with Interleukin-2 or T-cell receptor stimulation. Polyclonal antibodies were generated against CrkL phospho-S114, and used to show its inducibility by multiple stimuli. These findings confirm CrkL as an Interleukin-2 responsive protein that becomes phosphorylated at S114 by a kinase/s downstream of PI3K and MEK/ERK signaling.

The positive-sense single stranded RNA virus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), resulted in a global pandemic with horrendous health and economic consequences not seen in a century. At a finer scale, immunologically, many of these devastating effects by SARS-CoV-2 can be traced to a “cytokine storm” resulting in the simultaneous activation of Janus Kinases (JAKs) and Signal Transducers and Activators of Transcription (STAT) proteins downstream of the many cytokine receptor families triggered by elevated cytokines found in Coronavirus Disease 2019 (COVID-19). In this report, cytokines found in the storm are discussed in relation to the JAK-STAT pathway in response to SARS-CoV-2 and the lessons learned from RNA viruses and previous Coronaviruses (CoVs). Therapeutic strategies to counteract the SARS-CoV-2 mediated storm are discussed with an emphasis on cell signaling and JAK inhibition.

Primary ciliary dyskinesia (PCD) is a rare disorder that affects the biogenesis or function of motile cilia resulting in chronic airway disease. PCD is genetically and phenotypically heterogeneous, with causative mutations identified in over 40 genes; however, the genetic basis of many cases is unknown. Using whole-exome sequencing, we identified three affected siblings with clinical symptoms of PCD but normal ciliary structure, carrying compound heterozygous loss-of-function variants in CFAP221. Computational analysis suggests that these variants are the most damaging alleles shared by all three siblings. Nasal epithelial cells from one of the subjects demonstrated slightly reduced beat frequency (16.5 Hz vs 17.7 Hz, p = 0.16); however, waveform analysis revealed that the CFAP221 defective cilia beat in an aberrant circular pattern. These results show that genetic variants in CFAP221 cause PCD and that CFAP221 should be considered a candidate gene in cases where PCD is suspected but cilia structure and beat frequency appear normal.

El Salt is emerging as a reference site for the study of the extinction of Neanderthal populations in the Eastern Iberian Peninsula during MIS 3. The small vertebrate assemblage analysed in this work is framed within this general objective and comes from Stratigraphic Unit V, the most recent unit with human presence. Nearly 1300 small mammal remains have been studied in order to reconstruct the palaeoecological conditions of this debated period. A total of seven rodents (Microtus arvalis, Microtus duodecimcostatus, Microtus cabrerae, Sciurus vulgaris, Arvicola sapidus, Eliomys quercinus and Apodemus sylvaticus), three insectivores (Talpa occidentalis, Crocidura sp., Sorex sp.) and one lagomorph (Oryctolagus cf. cuniculus) were identified. Palaeocological analyse points to drier conditions in the upper part (Unit V) of the stratigraphic sequence, supporting the hypothesis that an aridification scenario may have played a role in the disappearance of the Neanderthal groups inhabiting this region of the Iberian Peninsula.

It was developed a fed-batch bioprocess to produce a recombinant vaccine against Entamoeba histolytica under operational conditions attainable to large scale bioprocesses. We have produced this recombinant protein in shake flask and stirred tank bioreactor. Initial results in shake flask cultures under different methanol concentration of 0.5, 1.5 and 3% (v/v) produced extracellular protein at quantities of 10, 22 and 33 μg/mL, respectively. Then a scale-up process was performed from shake flask to fermenter by keeping similar volumetric power supply (P/V). The operational conditions were set up in fermenter as those used at commercial scale and supply of pure oxygen was avoided to keep the scalability of the bioprocess. After the scale-up process, the production of the recombinant protein reached 0.43 mg/mL, an improvement in production of 12 times, although the methanol and oxygen limited conditions observed. Maximum volumetric productivity of 3.75 mg/L h was achieved in fermenter cultures against 263.75 µg/L h reached in shake flask. Besides the limited conditions in methanol and oxygen, the yields obtained from the bioprocess were comparable to those observed in Mut+ strains previously reported, then saturated methanol conditions are not necessary to compensate limited oxygen conditions.