Flexible Working and Couples' Coordination of Time Schedules

Using previously unexploited data on time scheduling in the employment and household contexts, we investigate the effect of flexible working on couples' coordination of their daily work time schedules in the UK. We consider three distinct dimensions of flexible working: flexibility of daily start and finish times (flexitime), flexibility of work times over the year (annualised hours), and generalised control of working hours. We find that in couples with flexitime there is greater spouse synchronization in daily working times by nearly one hour. The effect is driven by couples with dependent children. However, we find the effect in couples with children of any age (under 16), suggesting it does not stem from the childcare requirements of young children. Robustness checks indicate that flexitime is not endogenous, suggesting that an expansion of flexitime would increase couples' work time coordination. There is less evidence that broader control over working hours increases daily synchronous working time and no evidence that annualised hours increase synchronous time on a daily basis. The weaker relationships with daily synchronous time for these two flexibility measures are consistent with their broader scope (control over amount of hours as well as timing) and longer time span

The Impact of Eliminating a Child Benefit on Birth Timing and Infant Health

We study the effects of the cancellation of a sizeable child benefit in Spain on birth timing and neonatal health. In May 2010, the government announced that a 2,500-euro universal "baby bonus" would stop being paid to babies born on or after January 1st, 2011. We use detailed micro data from birth certificates from 2000 to 2011, and find that more than 2,000 families were able to anticipate the date of birth of their babies from (early) January 2011 to (late) December 2010 (for a total of about 9,000 births a week nationally). This shifting of deliveries led to a significant increase in the number of low birth weight babies, as well as a peak in neonatal mortality. These results suggest that announcement effects are important in shaping economic decisions and outcomes. They also provide new, credible evidence highlighting the negative health consequences of scheduling births for non-medical reasons

Social norms, partnerships and children

This paper presents a social norms interpretation to explain cross-country differences in partnership formation rates. Social norms are modeled as a constraint on the allocation of household labor that diminishes the gains of entering a partnership, especially for highly educated women with a higher opportunity cost of time. Results using individual level data from 7 waves of the European Community Household Panel (1995–2001) confirm the predictions from the theory. These results are robust to controlling for country varying factors such as childcare policies and divorce rates, and are mostly driven by marriage (as opposed to cohabitation) decisions. Given that household formation is a necessary prerequisite to having children, our results potentially shed light onto the process of below replacement fertility and the economic challenges associated with it

Vaccinia-related kinase 1 (VRK1) is an upstream nucleosomal kinase required for the assembly of 53BP1 foci in response to ionizing radiation-induced DNA damage

Cellular responses to DNA damage require the formation of protein complexes in a highly organized fashion. The complete molecular components that participate in the sequential signaling response to DNA damage remain unknown. Here we demonstrate that vaccinia-related kinase 1 (VRK1) in resting cells plays an important role in the formation of ionizing radiationinduced foci that assemble on the 53BP1 scaffold protein during the DNA damage response. The kinase VRK1 is activated by DNA double strand breaks induced by ionizing radiation (IR) and specifically phosphorylates 53BP1 in serum-starved cells. VRK1 knockdown resulted in the defective formation of 53BP1 foci in response to IR both in number and size. This observed effect on 53BP1 foci is p53- and ataxia-telangiectasia mutated (ATM)-independent and can be rescued with VRK1 mutants resistant to siRNA. VRK1 knockdown also prevented the activating phosphorylation of ATM, CHK2, and DNA-dependent protein kinase in response to IR. VRK1 activation in response to DNA damage is a novel and early step in the signaling of mammalian DNA damage responses.This work was supported in part by Ministerio de Ciencia e Innovación Grants SAF2010-14935 and CSD2007-0017, Junta de Castilla y León Grants CSI006A11-2 and GR-15, and the Kutxa-Fundación Inbiomed. Supported by Junta para la Ampliación de Estudios-CSIC-Fondo Social Europeo fellowships.Peer Reviewe

Global methylome scores correlate with histological subtypes of colorectal carcinoma and show different associations with common clinical and molecular features

Background. The typical methylation patterns associated with cancer are hypermethylation at gene promoters and global genome hypomethylation. Aberrant CpG island hypermethylation at promoter regions and global genome hypomethylation have not been associated with histological colorectal carcinomas (CRC) subsets. Using Illumina’s 450 k Infinium Human Methylation beadchip, the methylome of 82 CRCs were analyzed, comprising different histological subtypes: 40 serrated adenocarcinomas (SAC), 32 conventional carcinomas (CC) and 10 CRCs showing histological and molecular features of microsatellite instability (hmMSI‐H), and, additionally, 35 normal adjacent mucosae. Scores reflecting the overall methylation at 250 bp, 1 kb and 2 kb from the transcription starting site (TSS) were studied. Results. SAC has an intermediate methylation pattern between CC and hmMSI‐H for the three genome locations. In addition, the shift from promoter hypermethylation to genomic hypomethylation occurs at a small sequence between 250 bp and 1 Kb from the gene TSS, and an asymmetric distribution of methylation was observed between both sides of the CpG islands (N vs. S shores). Conclusion. These findings show that different histological subtypes of CRC have a particular global methylation pattern depending on sequence distance to TSS and highlight the so far underestimated importance of CpGs aberrantly hypomethylated in the clinical phenotype of CRCs.This work was supported by two grants from Instituto de Salud Carlos III, Ministerio de Sanidad, Spain and FEDER funds (refs: PI12-1232, PI18-0144) and another from the European Union’s Horizon 2020 research and innovation program (ref. 848098

The physics of spreading processes in multilayer networks

The study of networks plays a crucial role in investigating the structure, dynamics, and function of a wide variety of complex systems in myriad disciplines. Despite the success of traditional network analysis, standard networks provide a limited representation of complex systems, which often include different types of relationships (i.e., "multiplexity") among their constituent components and/or multiple interacting subsystems. Such structural complexity has a significant effect on both dynamics and function. Throwing away or aggregating available structural information can generate misleading results and be a major obstacle towards attempts to understand complex systems. The recent "multilayer" approach for modeling networked systems explicitly allows the incorporation of multiplexity and other features of realistic systems. On one hand, it allows one to couple different structural relationships by encoding them in a convenient mathematical object. On the other hand, it also allows one to couple different dynamical processes on top of such interconnected structures. The resulting framework plays a crucial role in helping achieve a thorough, accurate understanding of complex systems. The study of multilayer networks has also revealed new physical phenomena that remain hidden when using ordinary graphs, the traditional network representation. Here we survey progress towards attaining a deeper understanding of spreading processes on multilayer networks, and we highlight some of the physical phenomena related to spreading processes that emerge from multilayer structure.Comment: 25 pages, 4 figure

Differential Inhibitor Sensitivity between Human Kinases VRK1 and VRK2

Human vaccinia-related kinases (VRK1 and VRK2) are atypical active Ser-Thr kinases implicated in control of cell cycle entry, apoptosis and autophagy, and affect signalling by mitogen activated protein kinases (MAPK). The specific structural differences in VRK catalytic sites make them suitable candidates for development of specific inhibitors. In this work we have determined the sensitivity of VRK1 and VRK2 to kinase inhibitors, currently used in biological assays or in preclinical studies, in order to discriminate between the two proteins as well as with respect to the vaccinia virus B1R kinase. Both VRK proteins and vaccinia B1R are poorly inhibited by inhibitors of different types targeting Src, MEK1, B-Raf, JNK, p38, CK1, ATM, CHK1/2 and DNA-PK, and most of them have no effect even at 100 µM. Despite their low sensitivity, some of these inhibitors in the low micromolar range are able to discriminate between VRK1, VRK2 and B1R. VRK1 is more sensitive to staurosporine, RO-31-8220 and TDZD8. VRK2 is more sensitive to roscovitine, RO 31–8220, Cdk1 inhibitor, AZD7762, and IC261. Vaccinia virus B1R is more sensitive to staurosporine, KU55933, and RO 31–8220, but not to IC261. Thus, the three kinases present a different pattern of sensitivity to kinase inhibitors. This differential response to known inhibitors can provide a structural framework for VRK1 or VRK2 specific inhibitors with low or no cross-inhibition. The development of highly specific VRK1 inhibitors might be of potential clinical use in those cancers where these kinases identify a clinical subtype with a poorer prognosis, as is the case of VRK1 in breast cancer