Analysis and test of the central-blue-spot infall hallmark

The infall of material onto a protostar, in the case of optically thick line emission, produces an asymmetry in the blue- and red-wing line emission. For an angularly resolved emission, this translates in a blue central spot in the first-order moment (intensity weighted velocity) map. An analytical expression for the first-order moment intensity as a function of the projected distance was derived, for the cases of infinite and finite infall radius. The effect of a finite angular resolution, which requires the numerical convolution with the beam, was also studied. This method was applied to existing data of several star-forming regions, namely G31.41+0.31 HMC, B335, and LDN 1287, obtaining good fits to the first-order moment intensity maps, and deriving values of the central masses onto which the infall is taking place (G31.41+0.31 HMC: 70-120 $M_\odot$; B335: 0.1 $M_\odot$; Guitar Core of LDN 1287: 4.8 $M_\odot$). The central-blue-spot infall hallmark appears to be a robust and reliable indicator of infall.Comment: Accepted for publication in A&

Scaling Relations and Exponents in the Growth of Rough Interfaces Through Random Media

The growth of a rough interface through a random media is modelled by a continuous stochastic equation with a quenched noise. By use of the Novikov theorem we can transform the dependence of the noise on the interface height into an effective temporal correlation for different regimes of the evolution of the interface. The exponents characterizing the roughness of the interface can thus be computed by simple scaling arguments showing a good agreement with recent experiments and numerical simulations.Comment: 4 pages, RevTex, twocolumns, two figures (upon request). To appear in Europhysics Letter

Histone chaperone activity of Arabidopsis thaliana NRP1 is blocked by cytochrome c

Higher-order plants and mammals use similar mechanisms to repair and tolerate oxidative DNA damage. Most studies on the DNA repair process have focused on yeast and mammals, in which histone chaperone-mediated nucleosome disassembly/reassembly is essential for DNA to be accessible to repair machinery. However, little is known about the specific role and modulation of histone chaperones in the context of DNA damage in plants. Here, the histone chaperone NRP1, which is closely related to human SET/TAF-I, was found to exhibit nucleosome assembly activity in vitro and to accumulate in the chromatin of Arabidopsis thaliana after DNA breaks. In addition, this work establishes that NRP1 binds to cytochrome c, thereby preventing the former from binding to histones. Since NRP1 interacts with cytochrome c at its earmuff domain, that is, its histone-binding domain, cytochrome c thus competes with core histones and hampers the activity of NRP1 as a histone chaperone. Altogether, the results obtained indicate that the underlying molecular mechanisms in nucleosome disassembly/reassembly are highly conserved throughout evolution, as inferred from the similar inhibition of plant NRP1 and human SET/TAF-I by cytochrome c during DNA damage response

Inhibition of the PP2A activity by the histone chaperone ANP32B is long-range allosterically regulated by respiratory cytochrome c

Repair of injured DNA relies on nucleosome dismantling by histone chaperones and de-phosphorylation events carried out by Protein Phosphatase 2A (PP2A). Typical histone chaperones are the Acidic leucine-rich Nuclear Phosphoprotein 32 family (ANP32) members, e.g. ANP32A, which is also a well-known PP2A inhibitor (a.k.a. I1PP2A). Here we report the novel interaction between the endogenous family member B—so-called ANP32B—and endogenous cytochrome c in cells undergoing camptothecin-induced DNA damage. Soon after DNA lesions but prior to caspase cascade activation, the hemeprotein translocates to the nucleus to target the Low Complexity Acidic Region (LCAR) of ANP32B; in a similar way, our group recently reported that the hemeprotein targets the acidic domain of SET/Template Activating Factor-Iß (SET/TAF-Iß), which is another histone chaperone and PP2A inhibitor (a.k.a. I2PP2A). The nucleosome assembly activity of ANP32B is indeed unaffected by cytochrome c binding. Like ANP32A, ANP32B inhibits PP2A activity and is thus herein referred to as I3PP2A. Our data demonstrates that ANP32B-dependent inhibition of PP2A is regulated by respiratory cytochrome c, which induces long-distance allosteric changes in the structured N-terminal domain of ANP32B upon binding to the C-terminal LCAR. In agreement with the reported role of PP2A in the DNA damage response, we propose a model wherein cytochrome c is translocated from the mitochondria into the nucleus upon DNA damage to modulate PP2A activity via its interaction with ANP32B. © 2021 The Author(s

Depression symptoms and mortality in elderly peruvian navy veterans: a retrospective cohort study

Abstract: Our study was design to determine the association between depressive symptoms and mortality in adults over 60 years old Navy Peruvian Veterans. We performed a retrospective cohort study based on a previous cohort study. A total of 1681 patients over 60 years old were included between 2010–2015. Demographic information, self-reported information about falls, physical frailty assessment, tobacco consumption, hypertension, Type 2 Diabetes Mellitus, Chronic Obstructive Pulmonary Disease and was collected. Depression was assessed by the short form of the Geriatric Depression Scale. We found that depressive symptoms were present in 24.9% of the participants and 40.5% of them died. Mortality risk in patients with depressive symptoms, physical frailty, and male sex was: RR of 23.1 (95% CI: 11.7–45.7), 3.84 (95% CI: 2.16–6.82), and 1.37 (95% CI: 1.07–1.75) respectively. We concluded that depressive symptoms in Peruvian retired military personnel and their immediate relatives are high and are significatively associated with mortality. Also, being male and frail was associated with an increased risk of death. This reinforces that early detection and assessment of depressive symptoms could be an opportunity to improve the health status of older adults

Bounds on the anomalous HZγHZ\gamma vertex arising from the process e+e−→τ+τ−γe^+e^-\to \tau^+ \tau^- \gamma

We obtain limits on the anomalous coupling $HZ\gamma$ through data published by the L3 Collaboration on the process $e^+e^-\to \tau^+\tau^- \gamma$. Our analysis leads to bounds on this coupling of order $10^{-2}$, for an intermediate mass Higgs boson $115 < M_H < 145$ $GeV$, two orders of magnitude above the Standard Model prediction.Comment: 10 pages, 3 figure

Experimental and numerical analyses of ballistic resistance evaluation of combat helmet using Hybrid III headform

Combat helmets are the primary system for protecting the head against ballistic impacts. Generally, combat helmets have been evaluated using a ballistic plasticine head surrogate based on international standards. More realistic human head models have recently been introduced to assess combat helmet performance considering biomechanical requirements. In this work, the Hybrid III dummy head and neck has been introduced to evaluate the performance of the combat helmet against the ballistic impact of live ammunition at different impact locations, considering two different thicknesses of the padding system. A numerical model including a helmet and a Hybrid III head and neck, is developed and validated with our experimental data. The results reveal the influence of the location, where the rear impact leads to the highest risk of brain damage. The effect of pad thickness is closely related to the energy absorbed by the helmet, the backface deformation (BFD), the contact force and the acceleration measured on the head.The authors acknowledge the Ministry of Economy and Competitiveness of Spain and FEDER program under Project RTC-2015-3887-8 and Project DPI2017-88166-R for the financial support of the work. M Rodriguez-Millan acknowledges the Spanish Ministry of Universities, National Program for the Promotion of Talent and its Employability in R&D&I, National Mobility Subprogram of the National Plan for Scientific and Technical Research and Innovation 2021-2023, for the professor's mobility program (PRX21/00329)

PP2A is activated by cytochrome c upon formation of a diffuse encounter complex with SET/TAF-Iß

Intrinsic protein flexibility is of overwhelming relevance for intermolecular recognition and adaptability of highly dynamic ensemble of complexes, and the phenomenon is essential for the understanding of numerous biological processes. These conformational ensembles—encounter complexes—lack a unique organization, which prevents the determination of well-defined high resolution structures. This is the case for complexes involving the oncoprotein SET/template-activating factor-Iß (SET/TAF-Iß), a histone chaperone whose functions and interactions are significantly affected by its intrinsic structural plasticity. Besides its role in chromatin remodeling, SET/TAF-Iß is an inhibitor of protein phosphatase 2A (PP2A), which is a key phosphatase counteracting transcription and signaling events controlling the activity of DNA damage response (DDR) mediators. During DDR, SET/TAF-Iß is sequestered by cytochrome c (Cc) upon migration of the hemeprotein from mitochondria to the cell nucleus. Here, we report that the nuclear SET/TAF-Iß:Cc polyconformational ensemble is able to activate PP2A. In particular, the N-end folded, globular region of SET/TAF-Iß (a.k.a. SET/TAF-Iß ¿C)—which exhibits an unexpected, intrinsically highly dynamic behavior—is sufficient to be recognized by Cc in a diffuse encounter manner. Cc-mediated blocking of PP2A inhibition is deciphered using an integrated structural and computational approach, combining small-angle X-ray scattering, electron paramagnetic resonance, nuclear magnetic resonance, calorimetry and molecular dynamics simulations

Taxanes convert regions of perturbed microtubule growth into rescue sites

Microtubules are polymers of tubulin dimers, and conformational transitions in the microtubule lattice drive microtubule dynamic instability and affect various aspects of microtubule function. The exact nature of these transitions and their modulation by anti -cancer drugs such as Taxol and epothilone, which can stabilize microtubules but also perturb their growth, are poorly understood. Here, we directly visualize the action of fluorescent Taxol and epothilone derivatives and show that microtubules can transition to a state that triggers cooperative drug binding to form regions with altered lattice conformation. Such regions emerge at growing microtubule ends that are in a pre-catastrophe state and inhibit microtubule growth and shortening. Electron microscopy and in vitro dynamics data indicate that taxane accumulation zones represent incomplete tubes that can persist, incorporate tubulin dimers and repeatedly induce microtubule rescues. Thus, taxanes modulate the material properties of microtubules by converting destabilized growing microtubule ends into regions resistant to depolymerization