An insight into transfer hydrogenation reactions catalysed by iridium(iii) bis-n-heterocyclic carbenes

A variety of [M(L)2(L')2{kC,C'-bis(NHC)}]BF4 complexes (M = Rh or Ir; L = CH3CN or wingtip group; L' = I– or CF3COO–; NHC=N-heterocyclic carbene) have been tested as pre-catalysts for the transfer hydrogenation of ketones and imines. The conversions and TOF's obtained are closely related to the nature of the ligand system and metal centre, more strongly coordinating wingtip groups yielding more active and recyclable catalysts. Theoretical calculations at the DFT level support a classic stepwise metal-hydride pathway against the concerted Meerwein–Ponndorf–Verley (MPV) mechanism. The calculated catalytic cycle involves a series of ligand rearrangements due to the high trans effect of the carbene and hydrido ligands, which are more stable when situated in mutual cis positions. The reaction profiles obtained for the complexes featuring an iodide or a trifluoroacetate in one of the apical positions agree well with the relative activity observed for both catalysts

Early life risk factors and their cumulative effects as predictors of overweight in Spanish children

Objectives: To explore early life risk factors of overweight/obesity at age 6 years and their cumulative effects on overweight/obesity at ages 2, 4 and 6 years. Methods: Altogether 1031 Spanish children were evaluated at birth and during a 6-year follow-up. Early life risk factors included: parental overweight/obesity, parental origin/ethnicity, maternal smoking during pregnancy, gestational weight gain, gestational age, birth weight, caesarean section, breastfeeding practices and rapid infant weight gain collected via hospital records. Cumulative effects were assessed by adding up those early risk factors that significantly increased the risk of overweight/obesity. We conducted binary logistic regression models. Results: Rapid infant weight gain (OR 2.29, 99% CI 1.54–3.42), maternal overweight/obesity (OR 1.93, 99% CI 1.27–2.92), paternal overweight/obesity (OR 2.17, 99% CI 1.44–3.28), Latin American/Roma origin (OR 3.20, 99% CI 1.60–6.39) and smoking during pregnancy (OR 1.61, 99% CI 1.01–2.59) remained significant after adjusting for confounders. A higher number of early life risk factors accumulated was associated with overweight/obesity at age 6 years but not at age 2 and 4 years. Conclusions: Rapid infant weight gain, parental overweight/obesity, maternal smoking and origin/ethnicity predict childhood overweight/obesity and present cumulative effects. Monitoring children with rapid weight gain and supporting a healthy parental weight are important for childhood obesity prevention

ALPK1 missense pathogenic variant in five families leads to ROSAH syndrome, an ocular multisystem autosomal dominant disorder

Purpose: To identify the molecular cause in five unrelated families with a distinct autosomal dominant ocular systemic disorder we called ROSAH syndrome due to clinical features of retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache. Methods: Independent discovery exome and genome sequencing in families 1, 2, and 3, and confirmation in families 4 and 5. Expression of wild-type messenger RNA and protein in human and mouse tissues and cell lines. Ciliary assays in fibroblasts from affected and unaffected family members. Results: We found the heterozygous missense variant in the ɑkinase gene, ALPK1, (c.710C>T, [p.Thr237Met]), segregated with disease in all five families. All patients shared the ROSAH phenotype with additional low-grade ocular inflammation, pancytopenia, recurrent infections, and mild renal impairment in some. ALPK1 was notably expressed in retina, retinal pigment epithelium, and optic nerve, with immunofluorescence indicating localization to the basal body of the connecting cilium of the photoreceptors, and presence in the sweat glands. Immunocytofluorescence revealed expression at the centrioles and spindle poles during metaphase, and at the base of the primary cilium. Affected family member fibroblasts demonstrated defective ciliogenesis. Conclusion: Heterozygosity for ALPK1, p.Thr237Met leads to ROSAH syndrome, an autosomal dominant ocular systemic disorder

El yacimiento arqueológico de La Mosquita (Villalaín, Burgos). Avances en el estudio del hábitat rupestre y los centros de culto en el norte de Burgos

The archaeological site of La Mosquita or Paraje de San Miguel is located in a secondary valley on the left bank of the Ebro river, in the municipality of Villalaín (Burgos). The archaeological ensemble is articulated around the La Mosquita cave, a clearly anthropized space over time through the placement of up to 9 cists excavated in the geological site and the detailing of a head and altar, causing a change in orientation. In addition to these elements, clearly pre–Christian elements such as cave paintings have been studied, where an anthropomorph with a horned headdress stands out. Along with these elements, other tombs excavated in the walls of the rocky cliff where the entire complex is located have been located outside the cave. From the study of the same, it has been possible to grant an absolute chronology to the whole, which allows us to delve into the hermit occupation in the Ebro valley.El yacimiento arqueológico de La Mosquita o Paraje de San Miguel se ubica en un valle secundario sobre la margen izquierda del río Ebro, en el término municipal de Villalaín (Burgos). El conjunto arqueológico está articulado en torno a la cueva de La Mosquita, espacio claramente antropizado a lo largo del tiempo mediante la colocación de hasta 9 cistas excavadas en el geológico y el retallado de una cabecera y altar, que provocan un cambio de orientación. Asimismo, se han estudiado elementos claramente precristianos como pinturas rupestres, donde destaca un antropomorfo con un tocado de cuernos. Junto a estos elementos, en el exterior de la cueva se han localizado otras tumbas excavadas en las paredes del farallón rocoso donde se ubica todo el conjunto. A partir del estudio de las mismas se ha podido otorgar una cronología absoluta al conjunto, que permite ahondar en la ocupación eremítica en el valle del Ebro

El yacimiento arqueológico de La Mosquita (Villalaín, Burgos). Avances en el estudio del hábitat rupestre y los centros de culto en el norte de Burgos

The archaeological site of La Mosquita or Paraje de San Miguel is located in a secondary valley on the left bank of the Ebro river, in the municipality of Villalaín (Burgos). The archaeological ensemble is articulated around the La Mosquita cave, a clearly anthropized space over time through the placement of up to 9 cists excavated in the geological site and the detailing of a head and altar, causing a change in orientation. In addition to these elements, clearly pre–Christian elements such as cave paintings have been studied, where an anthropomorph with a horned headdress stands out. Along with these elements, other tombs excavated in the walls of the rocky cliff where the entire complex is located have been located outside the cave. From the study of the same, it has been possible to grant an absolute chronology to the whole, which allows us to delve into the hermit occupation in the Ebro valley.El yacimiento arqueológico de La Mosquita o Paraje de San Miguel se ubica en un valle secundario sobre la margen izquierda del río Ebro, en el término municipal de Villalaín (Burgos). El conjunto arqueológico está articulado en torno a la cueva de La Mosquita, espacio claramente antropizado a lo largo del tiempo mediante la colocación de hasta 9 cistas excavadas en el geológico y el retallado de una cabecera y altar, que provocan un cambio de orientación. Asimismo, se han estudiado elementos claramente precristianos como pinturas rupestres, donde destaca un antropomorfo con un tocado de cuernos. Junto a estos elementos, en el exterior de la cueva se han localizado otras tumbas excavadas en las paredes del farallón rocoso donde se ubica todo el conjunto. A partir del estudio de las mismas se ha podido otorgar una cronología absoluta al conjunto, que permite ahondar en la ocupación eremítica en el valle del Ebro

A well-defined NHC-Ir(III) catalyst for the silylation of aromatic C-H bonds: Substrate survey and mechanistic insights

A well-defined NHC-Ir(iii) catalyst, [Ir(H)2(IPr)(py)3][BF4] (IPr = 1, 3-bis-(2, 6-diisopropylphenyl)imidazol-2-ylidene), that provides access to a wide range of aryl- and heteroaryl-silanes by intermolecular dehydrogenative C-H bond silylation has been prepared and fully characterized. The directed and non-directed functionalisation of C-H bonds has been accomplished successfully using an arene as the limiting reagent and a variety of hydrosilanes in excess, including Et3SiH, Ph2MeSiH, PhMe2SiH, Ph3SiH and (EtO)3SiH. Examples that show unexpected selectivity patterns that stem from the presence of aromatic substituents in hydrosilanes are also presented. The selective bisarylation of bis(hydrosilane)s by directed or non-directed silylation of C-H bonds is also reported herein. Theoretical calculations at the DFT level shed light on the intermediate species in the catalytic cycle and the role played by the ligand system on the Ir(iii)/Ir(i) mechanism