Cu(I) Controls Conformational States in Human Atox1 Metallochaperone: An EPR and Multiscale Simulation Study

Atox1 is a human copper metallochaperone that is responsible for transferring copper ions from the main human copper transporter, hCtr1, to ATP7A/B in the Golgi apparatus. Atox1 interacts with the Ctr1 C-terminal domain as a dimer, although it transfers the copper ions to ATP7A/B in a monomeric form. The copper binding site in the Atox1 dimer involves Cys12 and Cys15, while Lys60 was also suggested to play a role in the copper binding. We recently showed that Atox1 can adopt various conformational states, depending on the interacting protein. In the current study, we apply EPR experiments together with hybrid quantum mechanics-molecular mechanics molecular dynamics simulations using a recently developed semiempirical density functional theory approach, to better understand the effect of Atox1's conformational states on copper coordination. We propose that the flexibility of Atox1 occurs owing to protonation of one or more of the cysteine residues, and that Cys15 is an important residue for Atox1 dimerization, while Cys12 is a critical residue for Cu(I) binding. We also show that Lys60 electrostatically stabilizes the Cu(I)-Atox1 dimer

Natural disturbance impacts on trade-offs and co-benefits of forest biodiversity and carbon

With accelerating environmental change, understanding forest disturbance impacts on trade-offs between biodiversity and carbon dynamics is of high socio-economic importance. Most studies, however, have assessed immediate or short-term effects of disturbance, while long-term impacts remain poorly understood. Using a tree-ring-based approach, we analysed the effect of 250 years of disturbances on present-day biodiversity indicators and carbon dynamics in primary forests. Disturbance legacies spanning centuries shaped contemporary forest co-benefits and trade-offs, with contrasting, local-scale effects. Disturbances enhanced carbon sequestration, reaching maximum rates within a comparatively narrow post-disturbance window (up to 50 years). Concurrently, disturbance diminished aboveground carbon storage, which gradually returned to peak levels over centuries. Temporal patterns in biodiversity potential were bimodal; the first maximum coincided with the short-term post-disturbance carbon sequestration peak, and the second occurred during periods of maximum carbon storage in complex old-growth forest. Despite fluctuating local-scale trade-offs, forest biodiversity and carbon storage remained stable across the broader study region, and our data support a positive relationship between carbon stocks and biodiversity potential. These findings underscore the interdependencies of forest processes, and highlight the necessity of large-scale conservation programmes to effectively promote both biodiversity and long-term carbon storage, particularly given the accelerating global biodiversity and climate crises

Measurement of the Generalized Forward Spin Polarizabilities of the Neutron

The generalized forward spin polarizabilities $\gamma_0$ and $\delta_{LT}$ of the neutron have been extracted for the first time in a $Q^2$ range from 0.1 to 0.9 GeV$^2$. Since $\gamma_0$ is sensitive to nucleon resonances and $\delta_{LT}$ is insensitive to the $\Delta$ resonance, it is expected that the pair of forward spin polarizabilities should provide benchmark tests of the current understanding of the chiral dynamics of QCD. The new results on $\delta_{LT}$ show significant disagreement with Chiral Perturbation Theory calculations, while the data for $\gamma_0$ at low $Q^2$ are in good agreement with a next-to-lead order Relativistic Baryon Chiral Perturbation theory calculation. The data show good agreement with the phenomenological MAID model.Comment: 5 pages, 2 figures, corrected typo in author name, published in PR

Triggers of self-conscious emotions in the sexually transmitted infection testing process

<p>Abstract</p> <p>Background</p> <p>Self-conscious emotions (shame, guilt and embarrassment) are part of many individuals' experiences of seeking STI testing. These emotions can have negative impacts on individuals' interpretations of the STI testing process, their willingness to seek treatment and their willingness to inform sexual partners in light of positive STI diagnoses. Because of these impacts, researchers have called for more work to be completed on the connections between shame, guilt, embarrassment and STI testing. We examine the specific events in the STI testing process that trigger self-conscious emotions in young adults who seek STI testing; and to understand what it is about these events that triggers these emotions.</p> <p>Semi-structured interviews with 30 adults (21 women, 9 men) in the Republic of Ireland.</p> <p>Findings</p> <p>Seven specific triggers of self-conscious emotions were identified. These were: having unprotected sex, associated with the initial reason for seeking STI testing; talking to partners and peers about the intention to seek STI testing; the experience of accessing STI testing facilities and sitting in clinic waiting rooms; negative interactions with healthcare professionals; receiving a positive diagnosis of an STI; having to notify sexual partners in light of a positive STI diagnosis; and accessing healthcare settings for treatment for an STI. Self-conscious emotions were triggered in each case by a perceived threat to respondents' social identities.</p> <p>Conclusion</p> <p>There are multiple triggers of self-conscious emotions in the STI testing process, ranging from the initial decision to seek testing, right through to the experience of accessing treatment. The role of self-conscious emotions needs to be considered in each component of service design from health promotion approaches, through facility layout to the training of all professionals involved in the STI testing process.</p

The Q^2 evolution of the generalized Gerasimov-Drell-Hearn integral for the neutron using a He-3 target

We present data on the inclusive scattering of polarized electrons from a polarized He-3 target at energies from 0.862 to 5.06 GeV, obtained at a scattering angle of 15.5 degrees. Our data include measurements from the quasielastic peak, through the resonance region, to the beginning of the deep inelastic regime, and were used to determine the spin difference in the virtual photoabsorption cross section. We extract the extended Gerasimov-Drell-Hearn integral for the neutron in the range of 4-momentum transfer squared Q^2 of 0.1-0.9 GeV.Comment: 14 pages of text when TeXed in preprint format with figures embedded. RevTeX format. Three eps figure

Q^2 Evolution of the Neutron Spin Structure Moments using a He-3 Target

We have measured the spin structure functions $g_1$ and $g_2$ of $^3$He in a double-spin experiment by inclusively scattering polarized electrons at energies ranging from 0.862 to 5.07 GeV off a polarized $^3$He target at a 15.5$^{\circ}$ scattering angle. Excitation energies covered the resonance and the onset of the deep inelastic regions. We have determined for the first time the $Q^2$ evolution of $\Gamma_1(Q^2)=\int_0^{1} g_1(x,Q^2) dx$, $\Gamma_2(Q^2)=\int_0^1 g_2(x,Q^2) dx$ and $d_2 (Q^2) = \int_0^1 x^2[ 2g_1(x,Q^2) + 3g_2(x,Q^2)] dx$ for the neutron in the range 0.1 GeV$^2$ $\leq Q^2 \leq$ 0.9 GeV$^2$ with good precision. $\Gamma_1(Q^2)$ displays a smooth variation from high to low $Q^2$. The Burkhardt-Cottingham sum rule holds within uncertainties and $d_2$ is non-zero over the measured range.Comment: 5 pages, 2 figures, submitted to Phys. Rev. Lett.. Updated Hermes data in Fig. 2 (top panel) and their corresponding reference. Updated the low x extrapolation error Fig. 2 (middle panel). Corrected references to ChiPT calculation

Malaria and other vector-borne infection surveillance in the U.S. Department of Defense Armed Forces Health Surveillance Center-Global Emerging Infections Surveillance program: review of 2009 accomplishments

Vector-borne infections (VBI) are defined as infectious diseases transmitted by the bite or mechanical transfer of arthropod vectors. They constitute a significant proportion of the global infectious disease burden. United States (U.S.) Department of Defense (DoD) personnel are especially vulnerable to VBIs due to occupational contact with arthropod vectors, immunological naiveté to previously unencountered pathogens, and limited diagnostic and treatment options available in the austere and unstable environments sometimes associated with military operations. In addition to the risk uniquely encountered by military populations, other factors have driven the worldwide emergence of VBIs. Unprecedented levels of global travel, tourism and trade, and blurred lines of demarcation between zoonotic VBI reservoirs and human populations increase vector exposure. Urban growth in previously undeveloped regions and perturbations in global weather patterns also contribute to the rise of VBIs. The Armed Forces Health Surveillance Center-Global Emerging Infections Surveillance and Response System (AFHSC-GEIS) and its partners at DoD overseas laboratories form a network to better characterize the nature, emergence and growth of VBIs globally. In 2009 the network tested 19,730 specimens from 25 sites for Plasmodium species and malaria drug resistance phenotypes and nearly another 10,000 samples to determine the etiologies of non-Plasmodium species VBIs from regions spanning from Oceania to Africa, South America, and northeast, south and Southeast Asia. This review describes recent VBI-related epidemiological studies conducted by AFHSC-GEIS partner laboratories within the OCONUS DoD laboratory network emphasizing their impact on human populations

Electrotransfer of Single-Stranded or Double-Stranded DNA Induces Complete Regression of Palpable B16.F10 Mouse Melanomas

Enhanced tumor delivery of plasmid DNA with electric pulses in vivo has been confirmed in many preclinical models. Intratumor electrotransfer of plasmids encoding therapeutic molecules has reached Phase II clinical trials. In multiple preclinical studies, a reduction in tumor growth, increased survival or complete tumor regression have been observed in control groups in which vector or backbone plasmid DNA electrotransfer was performed. This study explores factors that could produce this antitumor effect. The specific electrotransfer pulse protocol employed significantly potentiated the regression. Tumor regression was observed after delivery of single-stranded or double-stranded DNA with or without CpG motifs in both immunocompetent and immunodeficient mice, indicating the involvement of the innate immune system in response to DNA. In conclusion, this study demonstrated that the observed antitumor effects are not due to a single factor, but to a combination of factors

Proceedings of the Sixth International Workshop on Web Caching and Content Distribution

OVERVIEW The International Web Content Caching and Distribution Workshop (WCW) is a premiere technical meeting for researchers and practitioners interested in all aspects of content caching, distribution and delivery on the Internet. The 2001 WCW meeting was held on the Boston University Campus. Building on the successes of the five previous WCW meetings, WCW01 featured a strong technical program and record participation from leading researchers and practitioners in the field. This report includes all the technical papers presented at WCW'01. Note: Proceedings of WCW'01 are published by Elsevier. Hardcopies of these proceedings can be purchased through the workshop organizers. As a service to the community, electronic copies of all WCW'01 papers are accessible through Technical Report BUCS‐TR‐2001‐017, available from the Boston University Computer Science Technical Report Archives at http://www.cs.bu.edu/techreps. [Ed.note: URL outdated. Use http://www.bu.edu/cs/research/technical-reports/ or http://hdl.handle.net/2144/1455 in this repository to access the reports.]Cisco Systems; InfoLibria; Measurement Factory Inc; Voler