Visible-light metallaphotoredox strategies for organic transformations through the cleavage of Csp3-Cl bonds

Recentment, la generació de radicals actius mitjançant metodologies fotocatalítiques amb llum visible ha permès la construcció d’una gran varietat d’enllaços CC. La inèrcia dels cloroalcans ha impedit el seu ús com a socis d'acoblament predominants tant en reaccions d'acoblament creuat convencionals com fotocatalítiques. De fet, s’han desenvolupat escassos exemples que utilitzin clorurs d’alquil inactivats com a fragments de síntesi, els quals presenten limitacions a l’hora d’aplicar-se de manera general. En aquesta direcció, aquesta tesi descriu el desenvolupament d’una nova família de complexos tetradentats de Co i Ni capaços d’activar diferents clorurs d’alquil. La disponibilitat, versatilitat i modelatge d’aquests lligands ens permet la modificació controlada de la primera esfera de coordinació del metall a partir del canvi de les propietats electròniques i estructurals del lligand. La col.lecció de divuit nous complexos de Co i Ni significa un nou escenari per al desenvolupament de metodologies sintètiques.Recientemente, la generación de radicales activos mediante metodologías fotocatalíticas con luz visible ha permitido la construcción de una gran variedad de enlaces CC. La inercia de los cloroalcanos ha impedido su uso como socios de ensamblaje predominantes tanto en reacciones de ensamblaje cruzado convencionales como fotocatalíticas. De hecho, se han desarrollado escasos ejemplos que utilicen cloruros de alquilo inactivados como fragmentos de síntesis, que presentan limitaciones a la hora de aplicarse de forma general. En esta dirección, esta tesis describe el desarrollo de una nueva familia de complejos tetradentados de Co i Ni capaces de activar diferentes cloruros de alquil. La disponibilidad, versatilidad y modelado de estos ligandos permite la modificación controlada de la primera esfera de coordinación del metal a partir del cambio de las propiedades electrónicas y estructurales del ligando. La colección de dieciocho nuevos complejos de Co i Ni significa un nuevo escenario para el desarrollo de metodologías sintéticas.Recent photocatalytic methods based on the visible-light-induced generation of reactive radicals have allowed the construction of a large variety of CC bonds. The inertness of chloroalkanes has precluded them as prevailing coupling partners in both conventional and photocatalytic cross-coupling reactions. In fact, few examples of using unactivated alkyl chlorides as building blocks have been developed, presenting limitations in their applicability for a general methodology. In this line, this thesis describes the development of a new familiy of tetradentate aminopyridine Co and Ni complexes able to activate different chloroalkanes. The ligand availability, modularity and versatility let us the tune the first coordination sphere of the metal by changing the electronic and structural features of the ligand. A collection of eighteen new Co and Ni complexes have been studied presenting a playground for synthetic methodology development

Soil enzymes associated with carbon and nitrogen cycling in invaded and native secondary forests of northwestern Argentina

Background and aims: Alien success has frequently been associated with changes in the concentrations of soil nutrients. We aim to investigate the effects of plant invasion on soil nutrients, potential enzyme activity and litter elemental composition and stoichiometry - Methods: We compared stands of secondary forest invaded by Ligustrum lucidum and those dominated by natives, and performed litter chemical analyses on 3 native and 2 exotic tree species - Results: Soils of invaded sites had 20 and 30 % increase in β-glucosidase and alkaline phosphatase activity, higher Olsen-phosphorus (P) and potassium (K) concentrations and lower nitrogen (N) concentration and N:P, N:K and ammonium:Olsen-P ratios. Invaded and non-invaded sites differed in their overall nutrient composition and enzyme activity. Natives and exotics differed in nine of the 16 litter elemental composition and stoichiometry variables analyzed - Conclusions: The low N:P ratio in litter, the decrease in soil N in invaded stands and the low N concentration of exotics suggest that N is the limiting nutrient and that exotic success is related to higher N uptake and use efficiency. The higher investment in the acquisition of soil resources, higher nutrient uptake and use efficiency of limiting nutrients contribute to the success of exotics in this subtropical forest

Influència dels electròlits i el pH en el comportament fàsic de les mescles aquoses de gelatina/maltodextrina, per obtenir emulsions del tipus aigua-en-aigua

Treballs Finals de Grau de Química, Facultat de Química, Universitat de Barcelona, Any: 2016, Tutors: Maria Sarret Pons, Jordi Esquena Moret i Yoran BeldengrünThe main objective of this work is to study the effect of different electrolytes and pH on the spontaneous formation of water-in-water emulsions. Water-in-water (W/W) emulsions are a less known group of emulsions which are based on the immiscibility of two compounds which are soluble in water. Although they are thermodynamically unstable, W/W emulsions could be kept for some time due to its kinetic metastability, without any surfactant. Subsequently, obtaining microgels from these emulsions could offer a new type of encapsulation with delayed release of active ingredients or drugs. In this work, aqueous mixtures of gelatin and maltodextrin have been studied from its phase diagrams. Initially, the study of electrolytes has been made following the Hofmeister series, thereby, according to the capacity of hydration of ions, studying salts with different free energy of hydration (CsNO3 i LiCl). It was expected that salts had opposite effect on the phase separation of the system, but it was observed that the two salts favour the miscibility of polymers and the precipitation of a coacervate. Then, the effect of pH by adding acetic acid has been studied, observing an interesting result: acid medium favours the miscibility between the polymers, without precipitation. This phenomenon opens a new way: the neutralization of acid medium with sodium hydroxide could favour the spontaneous formation of emulsions. It has been verified that the addition of NaOH produces an instantaneous phase separation, however, obtaining emulsions from this phase separation has not been ensured. Due to the high system instability, many experimental factors could affect the formation of these emulsions. Future further work is required with more detailed studie

Can eukaryotic cells monitor the presence of unreplicated DNA?

Completion of DNA replication before mitosis is essential for genome stability and cell viability. Cellular controls called checkpoints act as surveillance mechanisms capable of detecting errors and blocking cell cycle progression to allow time for those errors to be corrected. An important question in the cell cycle field is whether eukaryotic cells possess mechanisms that monitor ongoing DNA replication and make sure that all chromosomes are fully replicated before entering mitosis, that is whether a replication-completion checkpoint exists. From recent studies with smc5–smc6 mutants it appears that yeast cells can enter anaphase without noticing that replication in the ribosomal DNA array was unfinished. smc5–smc6 mutants are proficient in all known cellular checkpoints, namely the S phase checkpoint, DNA-damage checkpoint, and spindle checkpoint, thus suggesting that none of these checkpoints can monitor the presence of unreplicated segments or the unhindered progression of forks in rDNA. Therefore, these results strongly suggest that normal yeast cells do not contain a DNA replication-completion checkpoint

Spindle-independent condensation-mediated segregation of yeast ribosomal DNA in late anaphase

Mitotic cell division involves the equal segregation of all chromosomes during anaphase. The presence of ribosomal DNA (rDNA) repeats on the right arm of chromosome XII makes it the longest in the budding yeast genome. Previously, we identified a stage during yeast anaphase when rDNA is stretched across the mother and daughter cells. Here, we show that resolution of sister rDNAs is achieved by unzipping of the locus from its centromere-proximal to centromere-distal regions. We then demonstrate that during this stretched stage sister rDNA arrays are neither compacted nor segregated despite being largely resolved from each other. Surprisingly, we find that rDNA segregation after this period no longer requires spindles but instead involves Cdc14-dependent rDNA axial compaction. These results demonstrate that chromosome resolution is not simply a consequence of compacting chromosome arms and that overall rDNA compaction is necessary to mediate the segregation of the long arm of chromosome XII

Mental impact of Covid-19 among Spanish healthcare workers: a large longitudinal survey

Depression; Epidemiology; Mental healthDepressió; Epidemiologia; Salut mentalDepresión; Epidemiología; Salud mentalAims Longitudinal data on the mental health impact of the coronavirus disease 2019 (Covid-19) pandemic in healthcare workers is limited. We estimated prevalence, incidence and persistence of probable mental disorders in a cohort of Spanish healthcare workers (Covid-19 waves 1 and 2) -and identified associated risk factors. Methods 8996 healthcare workers evaluated on 5 May–7 September 2020 (baseline) were invited to a second web-based survey (October–December 2020). Major depressive disorder (PHQ-8 ≥ 10), generalised anxiety disorder (GAD-7 ≥ 10), panic attacks, post-traumatic stress disorder (PCL-5 ≥ 7), and alcohol use disorder (CAGE-AID ≥ 2) were assessed. Distal (pre-pandemic) and proximal (pandemic) risk factors were included. We estimated the incidence of probable mental disorders (among those without disorders at baseline) and persistence (among those with disorders at baseline). Logistic regression of individual-level [odds ratios (OR)] and population-level (population attributable risk proportions) associations were estimated, adjusting by all distal risk factors, health care centre and time of baseline interview. Results 4809 healthcare workers participated at four months follow-up (cooperation rate = 65.7%; mean = 120 days S.D. = 22 days from baseline assessment). Follow-up prevalence of any disorder was 41.5%, (v. 45.4% at baseline, p < 0.001); incidence, 19.7% (S.E. = 1.6) and persistence, 67.7% (S.E. = 2.3). Proximal factors showing significant bivariate-adjusted associations with incidence included: work-related factors [prioritising Covid-19 patients (OR = 1.62)], stress factors [personal health-related stress (OR = 1.61)], interpersonal stress (OR = 1.53) and financial factors [significant income loss (OR = 1.37)]. Risk factors associated with persistence were largely similar. Conclusions Our study indicates that the prevalence of probable mental disorders among Spanish healthcare workers during the second wave of the Covid-19 pandemic was similarly high to that after the first wave. This was in good part due to the persistence of mental disorders detected at the baseline, but with a relevant incidence of about 1 in 5 of HCWs without mental disorders during the first wave of the Covid-19 pandemic. Health-related factors, work-related factors and interpersonal stress are important risks of persistence of mental disorders and of incidence of mental disorders. Adequately addressing these factors might have prevented a considerable amount of mental health impact of the pandemic among this vulnerable population. Addressing health-related stress, work-related factors and interpersonal stress might reduce the prevalence of these disorders substantially. Study registration number: NCT0455656

Transcription of ribosomal genes can cause nondisjunction

Mitotic disjunction of the repetitive ribosomal DNA (rDNA) involves specialized segregation mechanisms dependent on the conserved phosphatase Cdc14. The reason behind this requirement is unknown. We show that rDNA segregation requires Cdc14 partly because of its physical length but most importantly because a fraction of ribosomal RNA (rRNA) genes are transcribed at very high rates. We show that cells cannot segregate rDNA without Cdc14 unless they undergo genetic rearrangements that reduce rDNA copy number. We then demonstrate that cells with normal length rDNA arrays can segregate rDNA in the absence of Cdc14 as long as rRNA genes are not transcribed. In addition, our study uncovers an unexpected role for the replication barrier protein Fob1 in rDNA segregation that is independent of Cdc14. These findings demonstrate that highly transcribed loci can cause chromosome nondisjunction

Sgs1’s roles in DNA end resection, HJ dissolution, and crossover suppression require a two-step SUMO regulation dependent on Smc5/6

The RecQ helicase Sgs1 plays critical roles during DNA repair by homologous recombination, fromend resection to Holliday junction (HJ) dissolution. Sgs1 has both pro- and anti-recombinogenic roles, and therefore its activity must be tightly regulated. However, the controls involved in recruitment and activation of Sgs1 at damaged sites are unknown. Here we show a two-step role for Smc5/6 in recruiting and activating Sgs1 through SUMOylation. First, auto-SUMOylation of Smc5/6 subunits leads to recruitment of Sgs1 as part of the STR (Sgs1–Top3–Rmi1) complex, mediated by two SUMO-interacting motifs (SIMs) on Sgs1 that specifically recognize SUMOylated Smc5/6. Second, Smc5/6-dependent SUMOylation of Sgs1 and Top3 is required for the efficient function of STR. Sgs1 mutants impaired in recognition of SUMOylated Smc5/6 (sgs1-SIMΔ) or SUMO-dead alleles (sgs1-KR) exhibit unprocessed HJs at damaged replication forks, increased crossover frequencies during double-strand break repair, and severe impairment in DNA end resection. Smc5/6 is a key regulator of Sgs1’s recombination functions.We thank the Aragon laboratory for discussions and critical reading of the manuscript.We thank the Clinical Sciences Centre Proteomics Facility (P. Cutillas and P. Faull) for help and advice on our proteomic analysis. Work in J.T.-R.’s laboratory is supported by grants BFU2015-71308-P and BFU2013-50245-EXP from the Spanish Ministry of Economy and Competitivity.Work in the Aragon laboratory was supported by the intramural programme of the Medical Research Council UK and the Wellcome Trust (100955)

Structure of the N-terminal domain of the protein Expansion: an 'Expansion' to the Smad MH2 fold

Gene-expression changes observed in Drosophila embryos after inducing the transcription factor Tramtrack led to the identification of the protein Expansion. Expansion contains an N-terminal domain similar in sequence to the MH2 domain characteristic of Smad proteins, which are the central mediators of the effects of the TGF- signalling pathway. Apart from Smads and Expansion, no other type of protein belonging to the known kingdoms of life contains MH2 domains. To compare the Expansion and Smad MH2 domains, the crystal structure of the Expansion domain was determined at 1.6 A˚ resolution, the first structure of a non-Smad MH2 domain to be characterized to date. The structure displays the main features of the canonical MH2 fold with two main differences: the addition of an -helical region and the remodelling of a protein-interaction site that is conserved in the MH2 domain of Smads. Owing to these differences, to the new domain was referred to as N-MH2. Despite the presence of the N-MH2 domain, Expansion does not participate in TGF- signalling; instead, it is required for other activities specific to the protostome phyla. Based on the structural similarities to the MH2 fold, it is proposed that the N-MH2 domain should be classified as a new member of the Smad/FHA superfamily. 1

Patrones musculares en el canto. Un estudio piloto.

En estudios electromiográficos realizados previamente en diferentes cantantes, observamos cómo durante la emisión de la voz se producía la activación de los músculos espiradores y en paralelo se producía la contracción de los músculos intercostales externos, potentes inspiradores. Dadas estas observaciones, hemos realizado un estudio piloto con una cantante analizando el comportamiento conjunto de los músculos antes mencionados y del diafragma. Durante dife - rentes vocalizaciones hemos medido paralelamente la actividad muscular con electromiografía (EMG) y hemos observado el retorno diafragmático mediante ecografía. Los resultados apuntan a que el ascenso del diafragma está directamente relacionado con la nota emitida. Así, en el caso de una nota grave, el diafragma retorna lentamente acompañando el sonido. En el caso de las notas agudas, el diafragma se mantiene casi inmóvil durante la mayor parte de la emisión sonora y sólo al final de la vocalización se produce su ascenso de manera lenta. Se observa que durante la espiración en el canto, los músculos intercostales ex - ternos actúan elevando y fijando las costillas lo que impide el ascenso libre del diafragma, que se mantiene en tensión y se eleva de manera lenta y controlada gracias a la presión ejercida por los músculos del abdome