Intricacies of aging and Down syndrome.

Down syndrome is the most frequently occurring genetic condition, with a substantial escalation in risk associated with advanced maternal age. The syndrome is characterized by a diverse range of phenotypes, affecting to some extent all levels of organization, and its progeroid nature - early manifestation of aspects of the senile phenotype. Despite extensive investigations, many aspects and mechanisms of the disease remain unexplored.

Candidate molecular targets uncovered in mouse lifespan extension studies.

Introduction: Multiple interventions have demonstrated an increase in mouse lifespan. However, non-standardized controls, sex or strain-specific factors, and insufficient focus on targets, hinder the translation of these findings into clinical applications.

Areas Covered: We examined the effects of genetic and drug-based interventions on mice from databases DrugAge, GenAge, the Mouse Phenome Database, and publications from PubMed that led to a lifespan extension of more than 10%, identifying specific molecular targets that were manipulated to achieve the maximum lifespan in mice.

Structural insights into regulation of CNNM-TRPM7 divalent cation uptake by the small GTPase ARL15.

Cystathionine-β-synthase (CBS)-pair domain divalent metal cation transport mediators (CNNMs) are an evolutionarily conserved family of magnesium transporters. They promote efflux of Mg ions on their own and influx of divalent cations when expressed with the transient receptor potential ion channel subfamily M member 7 (TRPM7). Recently, ADP-ribosylation factor-like GTPase 15 (ARL15) has been identified as CNNM-binding partner and an inhibitor of divalent cation influx by TRPM7.

Optically stimulated electron paramagnetic resonance: Simplicity, versatility, information content.

A simple technique for observing optically stimulated electron paramagnetic resonance (OSEPR) is proposed and investigated. The versatility and information content of the described technique is demonstrated by the example of the OSEPR spectra of systems that are unpopular for this type of spectroscopy: a crystal with rare-earth ions Nd and a doped semiconductor GaAs. In addition, the OSEPR spectrum of atomic cesium is presented, in which an optical nonlinearity is observed that makes it possible to estimate the Rabi frequency for the relevant optical transition.

Burst kinetics and CNNM binding are evolutionarily conserved properties of phosphatases of regenerating liver.

Phosphatases of regenerating liver (PRL or PTP4A) are a family of enigmatic protein phosphatases implicated in cell growth and metabolism. Despite their relevance in metastatic cancer, much remains unknown about the PRL family. They act as pseudophosphatases to regulate the CNNM family of magnesium transporters yet also have enzymatic activity on unknown substrates.

Structural insights into regulation of TRPM7 divalent cation uptake by the small GTPase ARL15.

Cystathionine-β-synthase (CBS)-pair domain divalent metal cation transport mediators (CNNMs) are an evolutionarily conserved family of magnesium transporters. They promote efflux of Mg ions on their own or uptake of divalent cations when coupled to the transient receptor potential ion channel subfamily M member 7 (TRPM7). Recently, ADP-ribosylation factor-like GTPase 15 (ARL15) has been identified as CNNM binding partner and an inhibitor of divalent cation influx by TRPM7.

Spin Noise in Birefringent Media.

It is known that linear birefringence of the medium essentially hinders measuring the Faraday effect. For this reason, optically anisotropic materials have never been considered as objects of the Faraday-rotation-based spin noise spectroscopy. We show, both theoretically and experimentally, that strong optical anisotropy that may badly suppress the regular Faraday rotation of the medium, practically does not affect the measurement of the spatially uncorrelated spin fluctuations.

Structural basis of 3'-end poly(A) RNA recognition by LARP1.

La-related proteins (LARPs) comprise a family of RNA-binding proteins involved in a wide range of posttranscriptional regulatory activities. LARPs share a unique tandem of two RNA-binding domains, La motif (LaM) and RNA recognition motif (RRM), together referred to as a La-module, but vary in member-specific regions. Prior structural studies of La-modules reveal they are pliable platforms for RNA recognition in diverse contexts.

Structural basis for feedforward control in the PINK1/Parkin pathway.

PINK1 and parkin constitute a mitochondrial quality control system mutated in Parkinson's disease. PINK1, a kinase, phosphorylates ubiquitin to recruit parkin, an E3 ubiquitin ligase, to mitochondria. PINK1 controls both parkin localization and activity through phosphorylation of both ubiquitin and the ubiquitin-like (Ubl) domain of parkin.

Role of ubiquitin-protein ligase UBR5 in the disassembly of mitotic checkpoint complexes.

The mitotic (or spindle assembly) checkpoint system ensures accurate chromosome segregation in mitosis by preventing the onset of anaphase until correct bipolar attachment of sister chromosomes to the mitotic spindle is attained. It acts by promoting the assembly of a mitotic checkpoint complex (MCC), composed of mitotic checkpoint proteins BubR1, Bub3, Mad2, and Cdc20. MCC binds to and inhibits the action of ubiquitin ligase APC/C (anaphase-promoting complex/cyclosome), which targets for degradation regulators of anaphase initiation.

The double lives of phosphatases of regenerating liver: A structural view of their catalytic and noncatalytic activities.

Phosphatases of regenerating liver (PRLs) are protein phosphatases involved in the control of cell growth and migration. They are known to promote cancer metastasis but, despite over 20 years of study, there is still no consensus about their mechanism of action. Recent work has revealed that PRLs lead double lives, acting both as catalytically active enzymes and as pseudophosphatases.

Crystal structure of an archaeal CorB magnesium transporter.

CNNM/CorB proteins are a broadly conserved family of integral membrane proteins with close to 90,000 protein sequences known. They are associated with Mg transport but it is not known if they mediate transport themselves or regulate other transporters. Here, we determine the crystal structure of an archaeal CorB protein in two conformations (apo and Mg-ATP bound).

Raman scattering model of the spin noise.

The mechanism of formation of the polarimetric signal observed in the spin noise spectroscopy (SNS) is analyzed from the viewpoint of the light scattering theory. A rigorous calculation of the polarimetric signal (Faraday rotation or ellipticity) recorded in the SNS is presented in the approximation of single scattering. We show that it is most correctly to consider this noise as a result of scattering of the probe light beam by fluctuating susceptibility of the medium.

LARP1 and LARP4: up close with PABP for mRNA 3' poly(A) protection and stabilization.

La-related proteins (LARPs) share a La motif (LaM) followed by an RNA recognition motif (RRM). Together these are termed the La-module that, in the prototypical nuclear La protein and LARP7, mediates binding to the UUU-3'OH termination motif of nascent RNA polymerase III transcripts. We briefly review La and LARP7 activities for RNA 3' end binding and protection from exonucleases before moving to the more recently uncovered poly(A)-related activities of LARP1 and LARP4.

The isolated La-module of LARP1 mediates 3' poly(A) protection and mRNA stabilization, dependent on its intrinsic PAM2 binding to PABPC1.

The protein domain arrangement known as the La-module, comprised of a La motif (LaM) followed by a linker and RNA recognition motif (RRM), is found in seven La-related proteins: LARP1, LARP1B, LARP3 (La protein), LARP4, LARP4B, LARP6, and LARP7 in humans. Several LARPs have been characterized for their distinct activity in a specific aspect of RNA metabolism. The La-modules vary among the LARPs in linker length and RRM subtype.

Studies of Charm Quark Diffusion inside Jets Using Pb-Pb and pp Collisions at sqrt[s_{NN}]=5.02 TeV.

The first study of charm quark diffusion with respect to the jet axis in heavy ion collisions is presented. The measurement is performed using jets with p_{T}^{jet}>60  GeV/c and D^{0} mesons with p_{T}^{D}>4  GeV/c in lead-lead (Pb-Pb) and proton-proton (pp) collisions at a nucleon-nucleon center-of-mass energy of sqrt[s_{NN}]=5.02  TeV, recorded by the CMS detector at the LHC.

PRL3 pseudophosphatase activity is necessary and sufficient to promote metastatic growth.

Phosphatases of regenerating liver (PRLs) are markers of cancer and promote tumor growth. They have been implicated in a variety of biochemical pathways but the physiologically relevant target of phosphatase activity has eluded 20 years of investigation. Here, we show that PRL3 catalytic activity is not required in a mouse model of metastasis.

Calnexin cycle - structural features of the ER chaperone system.

The endoplasmic reticulum (ER) is the major folding compartment for secreted and membrane proteins and is the site of a specific chaperone system, the calnexin cycle, for folding N-glycosylated proteins. Recent structures of components of the calnexin cycle have deepened our understanding of quality control mechanisms and protein folding pathways in the ER. In the calnexin cycle, proteins carrying monoglucosylated glycans bind to the lectin chaperones calnexin and calreticulin, which recruit a variety of function-specific chaperones to mediate protein disulfide formation, proline isomerization, and general protein folding.

Measurement of the average very forward energy as a function of the track multiplicity at central pseudorapidities in proton-proton collisions at .

The average total energy as well as its hadronic and electromagnetic components are measured with the CMS detector at pseudorapidities in proton-proton collisions at a centre-of-mass energy . The results are presented as a function of the charged particle multiplicity in the region . This measurement is sensitive to correlations induced by the underlying event structure over a very wide pseudorapidity region.

Mg-ATP Sensing in CNNM, a Putative Magnesium Transporter.

The family of cystathionine-β-synthase (CBS)-pair domain divalent metal cation transport mediators (CNNMs) is composed of four integral membrane proteins associated with Mg transport. Structurally, CNNMs contain large cytosolic regions composed of a CBS-pair and a cyclic nucleotide-binding homology (CNBH) domain. How these regulate Mg transport activity is unknown.

Azimuthal separation in nearly back-to-back jet topologies in inclusive 2- and 3-jet events in collisions at .

A measurement for inclusive 2- and 3-jet events of the azimuthal correlation between the two jets with the largest transverse momenta, , is presented. The measurement considers events where the two leading jets are nearly collinear ("back-to-back") in the transverse plane and is performed for several ranges of the leading jet transverse momentum. Proton-proton collision data collected with the CMS experiment at a center-of-mass energy of and corresponding to an integrated luminosity of are used.

Measurement of exclusive photoproduction in ultraperipheral pPb collisions at .

Exclusive photoproduction is measured for the first time in ultraperipheral pPb collisions at with the CMS detector. The cross section is b at for photon-proton centre-of-mass energies between 29 and . The differential cross section is measured in the interval as a function of , where is the squared four-momentum transfer at the proton vertex.

Mechanism of thienopyridone and iminothienopyridinedione inhibition of protein phosphatases.

Thienopyridone (TP) has been proposed as a selective inhibitor of phosphatases of regenerating liver (PRL or PTP4A). PRLs are dual specificity phosphatases that promote cancer progression and are attractive anticancer targets. TP and iminothienopyridinedione (ITP), a more potent derivative, were shown to be effective inhibitors but the mechanism of inhibition was not established.