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Mitochondrial diseases linked to mutations in mitochondrial (mt) tRNA sequences are common. However, the contributions of these tRNA mutations to the development of diseases is mostly unknown. Mutations may affect interactions with (mt)tRNA maturation enzymes or protein synthesis machinery leading to mitochondrial dysfunction. In human mitochondria, in most cases the first step of tRNA processing is the removal of the 5′ leader of precursor tRNAs (pre-tRNA) catalyzed by the three-component enzyme, mtRNase P. Additionally, one component of mtRNase P, mitochondrial RNase P protein 1 (MRPP1), catalyzes methylation of the R9 base in pre-tRNAs. Tideglusib Despite the central role of 5′ end processing in mitochondrial tRNA maturation, the link between mtRNase P and diseases is mostly unexplored. Here, we investigate how 11 different human disease-linked mutations in (mt)pre-tRNAIle, (mt)pre-tRNALeu(UUR), and (mt)pre-tRNAMet affect the activities of mtRNase P. We find that several mutations weaken the pre-tRNA binding affinity (K D s are approximately two- to sixfold higher than that of wild-type), while the majority of mutations decrease 5′ end processing and methylation activity catalyzed by mtRNase P (up to ∼55% and 90% reduction, respectively). Furthermore, all of the investigated mutations in (mt)pre-tRNALeu(UUR) alter the tRNA fold which contributes to the partial loss of function of mtRNase P. Overall, these results reveal an etiological link between early steps of (mt)tRNA-substrate processing and mitochondrial disease.Adenosquamous proliferation (ASP), characterised by ductal structures with a dual glandular and squamous phenotype within desmoplastic stroma, is essentially a hallmark of various sclerosing lesions of the breast (SL) and breast lesions with sclerosis (BLWS), not including sclerosing adenosis. In radial scar/complex sclerosing lesion (RS/CSL), clonality has been previously demonstrated in microdissected ASP. SL/BLWS encompass a diverse range of pathological entities that historically have an equally diverse list of names, often for histologically alike or identical lesions at different anatomical locations. In common they are comprised of one or more components of fibrocystic or proliferative breast disease and papillomata, which become distorted and even obliterated by a sclerosing process that appears to be associated with and/or secondary to ASP, which in an individual lesion may be inconspicuous at the time of biopsy. The histological overlap of various SL/BLWS with RS/CSL, in which a nidus containing ASP is pathognomonic of early lesions, also supports a common element of ASP across various SL/BLWS. SL/BLWS show an interesting association with low-grade metaplastic carcinoma, particularly low-grade adenosquamous carcinoma (LGASC) with which, they appear to form a histological and possible biological spectrum because ASP and LGASC share similar histological and immunophenotypical characteristics. The presentation of ASP in various SL/BLWS will be discussed.The magnetic-field-tuned superconductor-to-insulator transition was studied in a hybrid system of superconducting indium islands, deposited on an indium oxide (InOx) thin film, which exhibits global superconductivity at low magnetic fields. Vacuum annealing was used to tune the conductivity of the InOx film, thereby tuning the inergrain coupling and the nature of the transition. The hybrid system exhibits a “giant” magnetoresistance above the magnetic-field-tuned superconductor-to-insulator transition (H-SIT), with critical behavior similar to that of uniform InOx films but at much lower magnetic fields, that manifests the duality between Cooper pairs and vortices. A key feature of this hybrid system is the separation between the quantum criticality and the onset of nonequilibrium behavior.Marine primary productivity (PP) is the driving factor in the global marine carbon cycle. Its reconstruction in past climates relies on biogeochemical proxies that are not considered to provide an unequivocal signal. These are often based on the water column flux of biogenic components to sediments (organic carbon, biogenic opal, biomarkers), although other factors than productivity are posited to control the sedimentary contents of the components, and their flux is related to the fraction of export production buried in sediments. Moreover, most flux proxies have not been globally appraised. Here, we assess a proxy to quantify past phytoplankton biomass by correlating the concentration of C37 alkenones in a global suite of core-top sediments with sea surface chlorophyll-a (SSchla) estimates over the last 20 y. SSchla is the central metric to calculate phytoplankton biomass and is directly related to PP. We show that the global spatial distribution of sedimentary alkenones is primarily correlated to SSchla rather than diagenetic factors such as the oxygen concentration in bottom waters, which challenges previous assumptions on the role of preservation on driving concentrations of sedimentary organic compounds. Moreover, our results suggest that the rate of global carbon export to sediments is not regionally constrained, and that alkenones producers play a dominant role in the global export of carbon buried in the seafloor. This study shows the potential of using sedimentary alkenones to estimate past phytoplankton biomass, which in turn can be used to infer past PP in the global ocean.We analyze about 200 naturally occurring networks with distinct dynamical origins to formally test whether the commonly assumed hypothesis of an underlying scale-free structure is generally viable. This has recently been questioned on the basis of statistical testing of the validity of power law distributions of network degrees. Specifically, we analyze by finite size scaling analysis the datasets of real networks to check whether the purported departures from power law behavior are due to the finiteness of sample size. We find that a large number of the networks follows a finite size scaling hypothesis without any self-tuning. This is the case of biological protein interaction networks, technological computer and hyperlink networks, and informational networks in general. Marked deviations appear in other cases, especially involving infrastructure and transportation but also in social networks. We conclude that underlying scale invariance properties of many naturally occurring networks are extant features often clouded by finite size effects due to the nature of the sample data.