The impact of the American Civil War on city growth

This paper analyzes the persistence of the shock caused by the American Civil War on the relative city size distribution of the United States. Our fi�ndings suggest that the effects of this shock were permanent, which sharply contrasts with previous results regarding World War II for Japanese and German cities. It should be taken into account that the conflict considered in this paper took place at an earlier stage of the industrialization and urbanization processes. Moreover, our results are determined by the fact that the battles were fought in the open �field, not in urban areas. Some related evidence regarding the presence of a safe harbour effect is reported.

Training in personal defense techniques and its influence on the stress threshold of students

Training in self-defense techniques is carried out regularly in both civil and military contexts. Self-defense techniques are put into practice in dangerous situations such us a threat or a physical attack, which can generate great stress on the individual. When carrying out this study, we wanted to analyze the influence that training in self-defense techniques has on the stress experienced by students in a dangerous situation or while being attacked. For this reason, I have compared the measure of stress experienced by 14 students during their performance, facing situations of physical threat that they perform in simulated self-defense practices, which are carried out in this training. The student’s stress was measured with the Determination Test (DT) of the Vienna Test System. These defense practices against simulated attack situations take place at two different moments within the training course, one at the beginning and another once the training course has finished; therefore, the students have completely learned the defense techniques. I carried out the first measure of stress in situations of physical threat, in the simulation at the beginning of the training course, when the students had not yet learned any self-defense techniques. The second measurement was performed 21 days later, when the students had received self-defense training. This came during the simulation of situations of physical threat that is developed once the teaching of these techniques has finished and occurs at the end of the training course. The results show that the stress tolerance threshold increases with training. The results obtained in the variables measured pre and post show a decrease in the "median reaction time to the stimuli" and an increase in the variables "number of stimuli answered" and "correct reactions". This demonstrates that these subjects achieved a stress tolerance threshold in stressful situations with the highest physical threat, which was at the end of this formation. Therefore, there is an important degree of difference in the stress resistance of the subjects before the simulation of the first day of training, and that of the last day once they had already learned the self-defense techniques.   These findings could contribute to highlighting the usefulness of this type of training both in military units and in civilian entities, not only to improve technical knowledge of self-defense but also to promote a more adaptive stress response in this type of situation

Dental Epithelial Stem Cells Express the Developmental Regulator Meis1

MEIS1 is a key developmental regulator of several organs and participates in stem cell maintenance in different niches. However, despite the murine continuously growing incisor being a well described model for the study of adult stem cells, Meis1 has not been investigated in a dental context. Here, we uncover that Meis1 expression in the tooth is confined to the epithelial compartment. Its expression arises during morphogenesis and becomes restricted to the mouse incisor epithelial stem cell niche, the labial cervical loop. Meis1 is specifically expressed by Sox2(+) stem cells, which give rise to all dental epithelial cell lineages. Also, we have found that Meis1 in the incisor is coexpressed with potential binding partner Pbx1 during both embryonic and adult stages. Interestingly, Meis2 is present in different areas of the forming tooth and it is not expressed by dental epithelial stem cells, suggesting different roles for these two largely homologous genes. Additionally, we have established the expression patterns of Meis1 and Meis2 during tongue, hair, salivary gland and palate formation. Finally, analysis of Meis1-null allele mice indicated that, similarly, to SOX2, MEIS1 is not essential for tooth initiation, but might have a role during adult incisor renewal.Peer reviewe

The habits of physical activity of the older women in Spain

Dada la inexistencia de estudios precedentes de hábitos de actividad física en el conjunto de mujeres mayores de 65 años en España, la investigación persigue comprobar las posibles desigualdades y diferencias en la práctica de actividad física semanal de las mujeres mayores con respecto a los hombres. La metodología cuantitativa empleada ha consistido en la aplicación de un cuestionario estructurado a una muestra aleatoria de las mujeres y varones mayores de 65 años en España. Las conclusiones obtenidas revelan que en este grupo socio demográfico de las personas mayores de 65 años, y a diferencia de los otros grupos con menor edad, un mayor porcentaje de mujeres que de varones realiza actividad física semanal (sin incluir el pasear). Esta desigualdad viene acompañada y quizás explicada por una serie de diferencias en la relación con la práctica de actividad física por parte de las mujeres mayores en comparación a gran parte de los hombres mayores, y que quizás configuren lo que podría denominarse como una cultura deportiva femenina de las mujeres mayores: tanto en las actividades practicadas, como en el espacio utilizado, el modo de organización de la actividad, y en el modo de acudir a la actividad

Combined sub-optimal doses of Rosuvastatin and Bexarotene impairs angiotensin II-induced arterial mononuclear cell adhesion through inhibition of Nox5 signaling pathways and increased RXR/PPARα and RXR/PPARγ interactions

Aim: Mononuclear cell (MC) infiltration into the arterial subendothelium is a key event in atherogenesis. Rosuvastatin (Rosu) and bexarotene (Bex) exert anti-inflammatory activity, but serious dose-related adverse effects have emerged. The need for safer and effective strategies to prevent and treat atherosclerosis led us to test the effect of combined use of both drugs on angiotensin II (Ang-II)-induced arterial MC recruitment. Results: Vehicle, Rosu (10-30 nM), Bex (0.3-1 μM), or a combination of both were administered to human umbilical arterial endothelial cells (HUAECs) 20 h before stimulation with 1 μM Ang-II (4 h). Surprisingly, a combination of Rosu (10 nM)+Bex (0.3 μM), which did not influence Ang-II-induced MC recruitment when either stimulus was studied alone, significantly reduced this response. This effect was accompanied by diminished Ang-II-induced ICAM-1, VCAM-1, and CX3CL1 endothelial expression and CXCL1, CXCL8, CCL2, and CCL5 production. Preincubation of HUAECs with Rosu+Bex inhibited Nox5 expression and Nox5-induced RhoA activation stimulated by Ang-II through increased RXRα, PPARα, and PPARγ expression in addition to RXRα/PPARα and RXRα/PPARγ interactions. In vivo, combined but not single administration of Rosu (1.25 mg/kg/day) and Bex (10 mg/kg/day) significantly diminished Ang-II-induced arteriolar leukocyte adhesion in the cremasteric microcirculation of C57BL/6 mice and atherosclerotic lesion formation in apoE(-/-) mice subjected to an atherogenic diet. Innovation and conclusion: Combined administration of Bex+Rosu at suboptimal doses may constitute a new alternative and effective therapy in the control of the vascular inflammation associated to cardiometabolic disorders, since they synergize in their anti-inflammatory actions and may counteract their associated adverse effects

Unidad Técnica de Biblioteca y Documentación de la Estación Experimental de Aula Dei (CSIC) (Z-EEAD)

2 Pag. A-3, 1 Fot., 1 Map.Información actualizada de la Unidad Técnica de Biblioteca y Documentación (UTBD) de la Estación Experimental de Aula Dei (EEAD-CSIC), una de las 78 Bibliotecas que conforman la Red de Bibliotecas CSIC, en consonancia con la proporcionada en reciente Plan Estratégico CSIC 2010-2013. Incluye relación de Prestaciones de servicio ofrecidas para el período 2010-2013.Peer reviewe

Implications of the use of organic fertilizers for antibiotic resistance gene distribution in agricultural soils and fresh food products. A plot-scale study

The spread of antibiotic resistance genes (ARG) into agricultural soils, products, and foods severely limits the use of organic fertilizers in agriculture. In order to help designing agricultural practices that minimize the spread of ARG, we fertilized, sown, and harvested lettuces and radish plants in experimental land plots for two consecutive agricultural cycles using four types of fertilizers: mineral fertilization, sewage sludge, pig slurry, or composted organic fraction of municipal solid waste. The analysis of the relative abundances of more than 200,000 ASV (Amplicon Sequence Variants) identified a small, but significant overlap (<10%) between soil's and fertilizer microbiomes. Clinically relevant ARG were found in higher loads (up to 100 fold) in fertilized soils than in the initial soil, particularly in those treated with organic fertilizers, and their loads grossly correlated to the amount of antibiotic residues found in the corresponding fertilizer. Similarly, low, but measurable ARG loads were found in lettuce (tetM, sul1) and radish (sul1), corresponding the lowest values to samples collected from minerally fertilized fields. Comparison of soil samples collected along the total period of the experiment indicated a relatively year-round stability of soil microbiomes in amended soils, whereas ARG loads appeared as unstable and transient. The results indicate that ARG loads in soils and foodstuffs were likely linked to the contribution of bacteria from organic fertilizer to the soil microbiomes, suggesting that an adequate waste management and good pharmacological and veterinarian practicesmay significantly reduce the presence of these ARGs in agricultural soils and plant products.Postprint (published version

Degradation of Penicillinic Antibiotics and β-Lactamase Enzymatic Catalysis in a Biomimetic Zn-Based Metal–Organic Framework

β-Lactam antibiotics are one of the most commonly prescribed drugs to treat bacterial infections. However, their use has been somehow limited given the emergence of bacteria with resistance mechanisms, such as β-lactamases, which inactivate them by degrading their four-membered β-lactam rings. So, a total knowledge of the mechanisms governing the catalytic activity of β-lactamases is required. Here, we report a novel Zn-based metal–organic framework (MOF, 1), possessing functional channels capable to accommodate and interact with antibiotics, which catalyze the selective hydrolysis of the penicillinic antibiotics amoxicillin and ceftriaxone. In particular, MOF 1 degrades, very efficiently, the four-membered β-lactam ring of amoxicillin, acting as a β-lactamase mimic, and expands the very limited number of MOFs capable to mimic catalytic enzymatic processes. Combined single-crystal X-ray diffraction (SCXRD) studies and density functional (DFT) calculations offer unique snapshots on the host-guest interactions established between amoxicillin and the functional channels of 1. This allows to propose a degradation mechanism based on the activation of a water molecule, promoted by a Zn-bridging hydroxyl group, concertedly to the nucleophilic attack to the carbonyl moiety and the cleaving of C−N bond of the lactam ring.This work was supported by the MICINN (Spain) (Projects PID2019-104778GB-I00, PID2020-115100GB-I00, and Excellence Units “Severo Ochoa” CEX2021-001230-S and “Maria de Maeztu” CEX2019-000919-M) and the Ministero dell'Istruzione, dell'Università e della Ricerca (Italy). The work has also been funded by Generalitat Valenciana, Prometeo Grupos de Investigación de Excelencia (PROMETEU/2021/054). D.A. also acknowledges the financial support of the European Union - NextGenerationEU under the National Recovery and Resilience Plan (NRRP) of Ministero dell'Università e della Ricerca (MUR) (Project code PE0000021, “Network 4 Energy Sustainable Transition - NEST). Thanks are also extended to the 2019 Post-doctoral Junior Leader-Retaining Fellowship, la Caixa Foundation (ID100010434 and fellowship code LCF/BQ/PR19/11700011), the “Generalitat Valenciana” (SEJI/2020/034) and the “Ramón y Cajal” program (J.F.-S.). E.P. acknowledges the financial support of the European Research Council under the European Union's Horizon 2020 research and innovation programme / ERC Grant Agreement No 814804, MOF-reactors. S.S.-N. thanks a fellowship from MINECO (project number CTQ 2017–86735-P). This study forms part of the Advanced Materials programme (MFA/2022/048) and was supported by MCIN with funding from European Union NextGenerationEU (PRTR-C17.I1) and by Generalitat Valenciana. Financial support from Dipartimento di Chimica e Tecnologie Chimiche (CTC), Università della Calabria, is also gratefully acknowledged for computational investigation

Impaired antigen-specific B-cell responses after Influenza vaccination in kidney transplant recipients receiving co-stimulation blockade with Belatacept

Emerging data suggest that costimulation blockade with belatacept effectively controls humoral alloimmune responses. However, whether this effect may be deleterious for protective anti-infectious immunity remains poorly understood. We performed a mechanistic exploratory study in 23 kidney transplant recipients receiving either the calcineurin-inhibitor tacrolimus (Tac, n=14) or belatacept (n=9) evaluating different cellular immune responses after influenza vaccination such as activated T follicular Helper (Tfh), plasmablasts and H1N1 hemagglutinin (HA)-specific memory B cells (HA(+)mBC) by flow-cytometry, and anti-influenza antibodies by hemagglutination inhibition test (HI), at baseline and days 10, 30 and 90 post-vaccination. The proportion of CD4+CD54RA-CXCR5+ Tfh was lower in belatacept than Tac patients at baseline (1.86%[1.25-3.03] vs 4.88%[2.40-8.27], p=0.01) and remained stable post-vaccination. At M3, HA(+)mBc were significantly higher in Tac-treated patients (0.56%[0.32-1.49] vs 0.27%[0.13-0.44], p=0.04) and correlated with activated Tfh numbers. When stratifying patients according to baseline HA(+)mBc frequencies, belatacept patients with low HA(+)mBC displayed significantly lower HA(+)mBc increases after vaccination than Tac patients (1.28[0.94-2.4] vs 2.54[1.73-5.70], p=0.04). Also, belatacept patients displayed significantly lower seroprotection rates against H1N1 at baseline than Tac-treated patients (44.4% vs 84.6%) as well as lower seroconversion rates at days 10, 30 and 90 after vaccination (50% vs 0%, 63.6% vs 0%, and 63.6% vs 0%, respectively). We show the efficacy of belatacept inhibiting T-dependent antigen-specific humoral immune responses, active immunization should be highly encouraged before starting belatacept therapy