Urchin grazing of kelp gametophytes in warming oceans.

Sea urchins can cause extensive damage to kelp forests, and their overgrazing can create extensive barren areas, leading to a loss of biodiversity. Barrens may persist when the recruitment of kelp, which occurs through the microscopic haploid gametophyte stage, is suppressed. However, the ecology of kelp gametophytes is poorly understood, and here we investigate if grazing by juvenile urchins on kelp gametophytes can suppress kelp recruitment and if this is exacerbated by climate change. We compared grazing of Ecklonia radiata gametophytes by two species of juvenile urchins, the tropical Tripneustes gratilla and the temperate Centrostephanus rodgersii, at winter (19°C), summer (23°C), and ocean warming (26°C) temperatures for the low-latitude range edge of E. radiata, which is vulnerable to ocean warming. We examined the rate of recovery of gametophytes following grazing and determined whether they survived and formed sporophytes after ingestion by sea urchins. Both T. gratilla and C. rodgersii grazed E. radiata gametophytes, reducing their abundance compared to no grazing controls. Surprisingly, temperature did not influence grazing rates, but gametophytes did not recover from grazing in the ocean warming (26°C) treatment. Gametophytes survived ingestion by both species of sea urchin and formed sporophytes after ingestion by T. gratilla, but not C. rodgersii. These results suggest complex grazer-gametophyte interactions, in which both negative (reduced abundance and poor recovery with warming) and positive (facilitated recruitment) effects are possible. Small grazers may play a more important role in kelp ecosystem function than previously thought and should be considered in our understanding of alternate stable states.

Association of Circulating Tumor Cells and Tumor Molecular Profile With Clinical Outcomes in Patients With Previously Untreated Metastatic Colorectal Cancer: A Pooled Analysis of the Phase III VISNÚ-1 and Phase II VISNÚ-2 Randomized Trials.

BACKGROUND: The bCTC count is a well-established prognostic biomarker in mCRC, as well as in other tumor types. The aim of this analysis was to evaluate the prognostic/predictive role of the bCTC count (≥3 vs. <3) in previously untreated mCRC. PATIENTS AND METHODS: The study involved 589 untreated mCRC patients included in the intention-to-treat population of 2 randomized clinical trials (phase III VISNU-1 [NCT01640405] and phase II VISNU-2 [NCT01640444] studies). RESULTS: Of the 589 patients, 349 (59.2%) had bCTC≥3 and 240 (40.7%) had bCTC<3. Multivariate analysis showed that the bCTC count is an independent prognostic factor for overall survival (OS) (HR 0.59, 95% CI 0.48-0.72; P = 0.000) and potential for progression-free survival (PFS) (P = 0.0549). Median OS was 32.9 and 19.5 months in patients with bCTC<3 and bCTC≥3 (P <0.001), respectively. This effect was also observed comparing OS in RASwt patients from both studies. Other prognostic factors were: ECOG-PS, primary tumor site, number of metastatic sites and surgery of the primary tumor. Median OS was lower for patients treated with anti-VEGF versus anti-EGFR (22.3 vs. 33.3 months, P <0.0001) while there were no significant differences in PFS according to the targeted treatment received. CONCLUSION: This post-hoc analysis of 2 randomized studies confirms the poor prognosis of patients with bCTC≥3 but this is not associated with other adverse independent prognostic factors such as RAS/BRAF mutations.

[EDP-938, a new antiviral with inhibitory activity against the nucleoprotein of the respiratory syncytial virus]. / EDP-938, un nuevo antiviral con actividad inhibidora frente a la nucleoproteína del virus respiratorio sincitial.

The absence of an effective vaccine against respiratory syncytial virus (RSV) has led to the development of various drugs with the ability to inhibit or block its replicative activity. The first generation, called fusion inhibitors, bind to the protein on the viral surface and prevent the virus from binding and entering the cell. However, its low efficacy has determined the start of studies with second-generation compounds capable of binding or blocking the nucleoprotein (N); most of these compounds are analogs of 1,4-benzodiazepines. EDP-938 has shown high efficacy against RSV. The first trials in humans have shown that this antiviral is rapidly absorbed after oral administration and has a half-life of between 11-18 hours Administration for seven days of multiple oral doses of up to 600 mg/day or 300 mg/day/twice a day, there were hardly any significant adverse effects and the viral load in the lower respiratory tract decreased significantly.

Changes in Food Security Status During Undergraduate Enrollment.

OBJECTIVE: To explore changes in student food security status (FSS) during college enrollment and correlates of those changes. DESIGN: Two cross-sectional surveys (2016 and 2019). PARTICIPANTS: Undergraduates (n = 338) at a public university who completed both surveys. VARIABLES MEASURED: Food security status (US Department of Agriculture 10- and 18-item measures), demographics, and grade point average (GPA). ANALYSIS: Chi-square tests of goodness of fit for representativeness, McNemar-Bowker and paired samples Wilcoxon signed rank test for within-student FSS differences over time, logistic regression for the relationship between demographics and FSS over time, and ANCOVA for the relationship between FSS and GPA. Critical P ≤ 0.05 unless otherwise noted. RESULTS: The prevalence of food insecurity was 22.4% in 2016 and 41.0% in 2019, and the McNemar-Bowker test indicated a significant asymmetrical relationship in FSS over time (P < 0.001). Almost half of the respondents (47.0%) reported experiencing food insecurity at least once. In multivariate analyses controlling for other demographic variables, first-generation students had the most consistent risk of food insecurity with lower FSS in 2016 (P < 0.001) and 2019 (P < 0.001), and they were more likely to have worsened FSS over time (P = 0.05). Food insecurity at either time was related to a lower 2019 GPA (P < 0.001). CONCLUSIONS AND IMPLICATIONS: Food security status measured cross-sectionally cannot capture changes in student FSS, which many students may experience. Longitudinal research is needed to better understand the role of demographic and student factors in FSS changes over time. Food resources should be offered to all students, as many will need them at some point.

Experience and Utility of the Protocol Kidney Biopsy in the First Year of Kidney Transplantation.

BACKGROUND: Protocol kidney biopsy (PKB) in kidney transplant is a useful tool for graft monitoring because the subclinical detection of histologic lesions helps to modulate immunosuppression. We analyze our experience. METHODS: We performed a descriptive study that analyzed the PKB results at the fourth to sixth month and the first year post transplant of patients with kidney transplant followed in our hospital between January 2015 and June 2021. RESULTS: A total of 100 patients and 134 biopsy results were included, of which 71 were obtained between the fourth and sixth month and 63 at the first year. The mean age was 57.8 years, and 66% were men. Unknown etiology was the most common underlying kidney disease (31%), followed by diabetes mellitus (15%) and polycystic kidney disease (14%). A total of 80% had panel-reactive antibody < 50%. Induction therapy consisted of thymoglobulin (51%) and basiliximab (49%), and maintenance therapy consisted of corticosteroids and tacrolimus (100%), mycophenolate mofetil (82%), and mammalian target of rapamycin inhibitor (18%). Of the total of the PKB results (n = 134), 19 episodes of subclinical rejection (14%) and 10 with borderline changes (7.4%) were observed. Regarding other findings, there were cases of nephrocalcinosis (4.4%), immunoglobulin A nephropathy (2.2%), and BK nephropathy (1.5%). The PKB brought about a change in the therapeutic attitude in 45 cases (33%) of the total number of biopsies, the most frequent change being the administration of boluses of methylprednisolone (12.6%) and the change to mammalian target of rapamycin inhibitor (8.9%). CONCLUSIONS: In our experience, PKB is a useful tool for monitoring and evaluating histologic changes without clinical expression in the kidney graft, allowing us to adapt the treatment during the first year of kidney transplant.

[The Victoria and Yamagata Lineages of Influenza B Viruses, unknown and undervalued]. / Los linajes Victoria y Yamagata de los virus gripales B, desconocidos y poco valorados.

The influenza virus B belongs to the family Orthomyxoviriridae and to the genus Influenzavirus B. It has a negative RNA-type genome made up of about 14,648 nucleotides divided into eight different segments that encode about 11 proteins. Before 1980 all influenza B viruses belonged to a single genetic lineage; but in this year two antigenically and genetically distinct lineages emerged which were named B/Victoria/2/1987 and B/Yamagata/16/1988. Intralineage and interlineage genetic exchange processes have been demonstrated; The most frequent of them are those in which the Victoria lineage acquires genes from the Yamagata lineage. It has been proposed that the differences in the evolutionary dynamics of the two lineages are due to the different binding preferences of influenza hemagglutinin to the cellular receptor. The Victoria lineage has shown the ability to bind to cell receptors with sialic acid residues at the α-2,3 and α-2,6 positions; whereas the Yamagata lineage does so exclusively in the human α-2,6 positions of the respiratory tract. Low circulation in recent months may have contributed to the temporary elimination ("extinction") of the Yamagata lineage. Since 2017, almost all of the strains of this lineage belong to clade 3A, when previously multiple circulating clades were detected. Although this clade 3A is diverse at the genetic level and has acquired surrogate mutations in the hemagglutinin gene, these have not determined significant antigenic changes that have made it necessary to replace its antigenic component (B/Pukhet/3073/2013) in the influenza vaccine since 2015.

[Nirmatrelvir plus ritonavir (Paxlovid) a potent SARS-CoV-2 3CLpro protease inhibitor combination]. / Nirmatrelvir más ritonavir (Paxlovid) una potente combinación inhibidora de la proteasa 3CLpro del SARS-CoV-2.

All coronavirus, including SARS-CoV-2, encode two proteases needed for the processing of PP1A and PP1AB polyproteins. The main protease 3CL (chemotripsine-like) gives rise to the formation of NSP11/16 proteins. The 3CL protease has been constituted as one of the possible therapeutic targets for the development of antiviral drugs against SARS-COV-2 due to its highly conserved sequence and structure among all coronaviruses. During the SARS-COV-1 pandemic, a hydroxymethyl ketone derivative (PF-00835231) was identified with an intense inhibitory activity against the 3CL protease. Subsequent chemical modifications gave rise to derivative PF-07321332 (nirmatrelvir) which has shown a high antiviral efficacy against SARS-COV-2. The company's data indicate that it is capable of reducing 89% the risk of hospitalization and death of patients infected with hardly adverse effects. Its effectiveness improves if it is administered orally in the first 24-48 hours and the duration of treatment has been established between 3-5 days. The commercial form has been associated with the antiviral ritonavir that has shown the metabolism of nirmatrelvir, lengthening its average life. This antiviral would be effective against current and future viral variants, since 3CL is not modified in them. The FDA approved this antiviral in November 2021 and EMA is in the final evaluation phase.

Challenging social media threats using collective well-being-aware recommendation algorithms and an educational virtual companion.

Social media have become an integral part of our lives, expanding our interlinking capabilities to new levels. There is plenty to be said about their positive effects. On the other hand, however, some serious negative implications of social media have been repeatedly highlighted in recent years, pointing at various threats to society and its more vulnerable members, such as teenagers, in particular, ranging from much-discussed problems such as digital addiction and polarization to manipulative influences of algorithms and further to more teenager-specific issues (e.g., body stereotyping). The impact of social media-both at an individual and societal level-is characterized by the complex interplay between the users' interactions and the intelligent components of the platform. Thus, users' understanding of social media mechanisms plays a determinant role. We thus propose a theoretical framework based on an adaptive "Social Media Virtual Companion" for educating and supporting an entire community, teenage students, to interact in social media environments in order to achieve desirable conditions, defined in terms of a community-specific and participatory designed measure of Collective Well-Being (CWB). This Companion combines automatic processing with expert intervention and guidance. The virtual Companion will be powered by a Recommender System (CWB-RS) that will optimize a CWB metric instead of engagement or platform profit, which currently largely drives recommender systems thereby disregarding any societal collateral effect. CWB-RS will optimize CWB both in the short term by balancing the level of social media threats the users are exposed to, and in the long term by adopting an Intelligent Tutor System role and enabling adaptive and personalized sequencing of playful learning activities. We put an emphasis on experts and educators in the educationally managed social media community of the Companion. They play five key roles: (a) use the Companion in classroom-based educational activities; (b) guide the definition of the CWB; (c) provide a hierarchical structure of learning strategies, objectives and activities that will support and contain the adaptive sequencing algorithms of the CWB-RS based on hierarchical reinforcement learning; (d) act as moderators of direct conflicts between the members of the community; and, finally, (e) monitor and address ethical and educational issues that are beyond the intelligent agent's competence and control. This framework offers a possible approach to understanding how to design social media systems and embedded educational interventions that favor a more healthy and positive society. Preliminary results on the performance of the Companion's components and studies of the educational and psychological underlying principles are presented.

PI3K-AKT, JAK2-STAT3 pathways and cell-cell contact regulate maspin subcellular localization.

BACKGROUND: Maspin (SERPINB5) is a potential tumor suppressor gene with pleiotropic biological activities, including regulation of cell proliferation, death, adhesion, migration and gene expression. Several studies indicate that nuclear localization is essential for maspin tumor suppression activity. We have previously shown that the EGFR activation leads to maspin nuclear localization in MCF-10A cells. The present study investigated which EGFR downstream signaling molecules are involved in maspin nuclear localization and explored a possible role of cell-cell contact in this process. METHODS: MCF-10A cells were treated with pharmacological inhibitors against EGFR downstream pathways followed by EGF treatment. Maspin subcellular localization was determined by immunofluorescence. Proteomic and interactome analyses were conducted to identify maspin-binding proteins in EGF-treated cells only. To investigate the role of cell-cell contact these cells were either treated with chelating agents or plated on different cell densities. Maspin and E-cadherin subcellular localization was determined by immunofluorescence. RESULTS: We found that PI3K-Akt and JAK2-STAT3, but not MAP kinase pathway, regulate EGF-induced maspin nuclear accumulation in MCF-10A cells. We observed that maspin is predominantly nuclear in sparse cell culture, but it is redistributed to the cytoplasm in confluent cells even in the presence of EGF. Proteomic and interactome results suggest a role of maspin on post-transcriptional and translation regulation, protein folding and cell-cell adhesion. CONCLUSIONS: Maspin nuclear accumulation is determined by an interplay between EGFR (via PI3K-Akt and JAK2-STAT3 pathways) and cell-cell contact. Video Abstract.

Effect of Dendritic Side Groups on the Mobility of Modified Poly(epichlorohydrin) Copolymers.

The macromolecular dynamics of dendronized copolymer membranes (PECHs), obtained by chemical modification of poly(epichlorohydrin) with the dendron 3,4,5-tris[4-(n-dodecan-1-yloxy)benzyloxy] benzoate, was investigated. In response to a thermal treatment during membrane preparation, these copolymers show an ability to change their shape, achieve orientation, and slightly crystallize, which was also observed by CP-MAS NMR, XRD, and DSC. The phenomenon was deeply analyzed by dielectric thermal analysis. The dielectric spectra show the influence of several factors such as the number of dendritic side groups, the orientation, their self-assembling dendrons, and the molecular mobility. The dielectric spectra present a sub-Tg dielectric relaxation, labelled as γ, associated with the mobility of the benzyloxy substituent of the dendritic group. This mobility is not related to the percentage of these lateral chains but is somewhat hindered by the orientation of the dendritic groups. Unlike other less complex polymers, the crystallization was dismantled before the appearance of the glass transition (αTg). Only after that, clearing transition (αClear) can be observed. The PECHs were flexible and offered a high free volume, despite presenting a high degree of modifications. However, the molecular mobility is not independent in each phase and the self-assembling dendrons can be eventually fine-tuned according to the percentage of grafted groups.

[Plitidepsin, an inhibitor of the cell elongation factor eEF1a, and molnupiravir an analogue of the ribonucleoside cytidine, two new chemical compounds with intense activity against SARS-CoV-2]. / Plitidepsina, un inhibidor del factor de elongación celular eEF1a y molnupiravir un análogo del ribonucleósido citidina, dos nuevos compuestos químicos con intensa actividad frente al SARS-CoV-2.

The knowledge of the replicative cycle of SARS-CoV-2 and its interactions with cellular proteins has opened a new therapeutic possibility based on blocking those essential for the virus. The cellular protein elongation factor eEF1A could be a good target. Among its natural inhibitors are didemnins and their related chemical compounds such as plitidepsin. In human cell culture, this compound is capable of inhibiting the virus with a potency 27,5 times that of remdesivir. It must be administered intravenously. Of the ribonucleoside analogues, molnupiravir (MK-4483/EIDD-2801) (hydroxy-cytidine) determines a lethal mutagenesis on SARS-CoV-2. In animals, after oral administration, the pulmonary viral load decreases 25,000 times and when administered as prophylaxis, approximately 100,000 times. It prevents the transmission of the virus and eliminates its presence in the oropharynx. Both chemicals have started Phase I / II human clinical trials.

[Impact of hygienic and social distancing measures against SARS-CoV-2 on respiratory infections caused by other viruses]. / Impacto de las medidas higiénicas y de distanciamiento social frente al SARS-CoV-2 sobre las infecciones respiratorias causadas por otros virus.

OBJECTIVE: To control the pandemic caused by SARS-CoV-2, the implementation of social and hygienic confinement measures was determined in all countries. These measures reduce the circulation of most respiratory viruses that are transmitted preferentially by air and contact. METHODS: The impact of these measures on non-Covid respiratory viruses during the period August-December 2020 and 2019 has been comparatively analyzed. To all nasopharyngeal aspirates that were negative against SARS-CoV-2 by RT-PCR and the suspicion of acute respiratory infection persisted, were subjected to a new RT-PCR that simultaneously and differentially amplifies 21 different respiratory viruses. RESULTS: In the year of the pandemic, a 36.6% decrease was detected in the number of respiratory samples studied and 66% in their positivity in relation to 2019. All viruses showed reduction percentages of between 40-100%. The only viruses that circulated during and after national lockdown were rhinovirus (74.1%), adenovirus (10.1%), and enterovirus (9.6%). CONCLUSIONS: The measures used to control the SARS-CoV-2 infection have also affected the community circulation of most respiratory viruses including influenza and respiratory syncytial virus.

PI3K-AKT, JAK2-STAT3 pathways and cell–cell contact regulate maspin subcellular localization

Background Maspin (SERPINB5) is a potential tumor suppressor gene with pleiotropic biological activities, including regulation of cell proliferation, death, adhesion, migration and gene expression. Several studies indicate that nuclear localization is essential for maspin tumor suppression activity. We have previously shown that the EGFR activation leads to maspin nuclear localization in MCF-10A cells. The present study investigated which EGFR downstream signaling molecules are involved in maspin nuclear localization and explored a possible role of cell–cell contact in this process. Methods MCF-10A cells were treated with pharmacological inhibitors against EGFR downstream pathways followed by EGF treatment. Maspin subcellular localization was determined by immunofluorescence. Proteomic and interactome analyses were conducted to identify maspin-binding proteins in EGF-treated cells only. To investigate the role of cell–cell contact these cells were either treated with chelating agents or plated on different cell densities. Maspin and E-cadherin subcellular localization was determined by immunofluorescence. Results We found that PI3K-Akt and JAK2-STAT3, but not MAP kinase pathway, regulate EGF-induced maspin nuclear accumulation in MCF-10A cells. We observed that maspin is predominantly nuclear in sparse cell culture, but it is redistributed to the cytoplasm in confluent cells even in the presence of EGF. Proteomic and interactome results suggest a role of maspin on post-transcriptional and translation regulation, protein folding and cell–cell adhesion. Conclusions Maspin nuclear accumulation is determined by an interplay between EGFR (via PI3K-Akt and JAK2-STAT3 pathways) and cell–cell contact.