Primate retinal cones express phosphorylated tau associated with neuronal degeneration yet survive in old age

Photoreceptor cells have high energy demands and suffer significantly with age. In aged rodents both rods and cones are lost, but in primates there is no evidence for aged cone loss, although their function declines. Here we ask if aged primate cones suffer from reduced function because of declining metabolic ability. Tau is a microtubule associated protein critical for mitochondrial function in neurons. Its phosphorylation is a feature of neuronal degeneration undermining respiration and mitochondrial dynamics. We show that total tau is widely distributed in the primate outer retina with little age-related change, being present in both rods and cones and their processes. However, all cones specifically accumulate phosphorylated tau, which was not seen in rods. The presence of this protein will likely undermine cone cell function. However, tau phosphorylation inhibits apoptosis. These data may explain why aged primate cones have reduced function but appear to be resistant to cell death. Consequently, therapies designed to remove phosphorylated tau may carry the risk of inducing cone photoreceptor cell death and further undermine ageing visual function

Imagining Mexico in 1910: Visions of the Patria in the Centennial Celebration in Mexico City

Mexico’s 1910 Centenario reflected a popular trend in Western Europe and its former colonies to use centenaries of important historical events to promote political programmes and philosophies through the construction of historical memory. Centennial organisers in Mexico linked Miguel Hidalgo y Costilla and Jose´ Maria Morelos to President Porfirio Dı´az in words and symbols, and associated state formation and civic culture with Liberal leaders and policies, such as public education, material progress and secularism. The planners also promoted Morelos as a mestizo icon and symbol for national identity and integration, while they simultaneously celebrated Mexico’s pre-Columbian cultures and criticised contemporary natives as impediments to progress. The Centennial’s audience included hundreds of thousands of Mexicans as well as foreigners from around the globe, who came away with different impressions based on their cultural perspectives, political philosophies and material interests. Following the overthrow of Dı´az in 1911, Mexico’s revolutionary governments continued to use Independence Day celebrations to promote their programmes, including some whose origins lay in the Porfiriato. As we approach the bicentenary of Latin American independence, competing visions of patrias will likely surface and provide insights into the construction of historical memory and contemporary political discourse

Experimental Exposure to Urban and Pink Noise Affects Brain Development and Song Learning in Zebra Finches (Taenopygia guttata)

Recently, numerous studies have observed changes in bird vocalizations—especially song—in urban habitats. These changes are often interpreted as adaptive, since they increase the active space of the signal in its environment. However, the proximate mechanisms driving cross-generational changes in song are still unknown. We performed a captive experiment to identify whether noise experienced during development affects song learning and the development of song-control brain regions. Zebra finches (Taeniopygia guttata) were bred while exposed, or not exposed, to recorded traffic urban noise (Study 1) or pink noise (Study 2). We recorded the songs of male offspring and compared these to fathers’ songs. We also measured baseline corticosterone and measured the size of song-control brain regions when the males reached adulthood (Study 1 only). While male zebra finches tended to copy syllables accurately from tutors regardless of noise environment, syntax (the ordering of syllables within songs) was incorrectly copied affected by juveniles exposed to noise. Noise did not affect baseline corticosterone, but did affect the size of brain regions associated with song learning: these regions were smaller in males that had been had been exposed to recorded traffic urban noise in early development. These findings provide a possible mechanism by which noise affects behaviour, leading to potential population differences between wild animals occupying noisier urban environments compared with those in quieter habitats

Post-Quantum Hash-Based Signatures for Secure Boot

The potential development of large-scale quantum computers is raising concerns among IT and security research professionals due to their ability to solve (elliptic curve) discrete logarithm and integer factorization problems in polynomial time. All currently used, public-key cryptography algorithms would be deemed insecure in a post-quantum setting. In response, the United States National Institute of Standards and Technology has initiated a process to standardize quantum-resistant cryptographic algorithms, focusing primarily on their security guarantees. Additionally, the Internet Engineering Task Force has published two quantum-secure signature schemes and has been looking into adding quantum-resistant algorithms in protocols. In this work, we investigate two post-quantum, hash-based signature schemes published by the Internet Engineering Task Force and submitted to the National Institute of Standards and Technology for use in secure boot. We evaluate various parameter sets for the use-cases in question and we prove that post-quantum signatures would not have material impact on image signing. We also study the hierarchical design of these signatures in different scenarios of hardware secure boot

A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.

This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.3448Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.We thank all participants of all the studies included for enabling this research by their participation in these studies. Computer resources for this project have been provided by the high-performance computing centers of the University of Michigan and the University of Regensburg. Group-specific acknowledgments can be found in the Supplementary Note. The Center for Inherited Diseases Research (CIDR) Program contract number is HHSN268201200008I. This and the main consortium work were predominantly funded by 1X01HG006934-01 to G.R.A. and R01 EY022310 to J.L.H

Curcumin and Graphene Oxide Incorporated into Alginate Hydrogels as Versatile Devices for the Local Treatment of Squamous Cell Carcinoma

With the aim of preparing hybrid hydrogels suitable for use as patches for the local treatment of squamous cell carcinoma (SCC)-affected areas, curcumin (CUR) was loaded onto graphene oxide (GO) nanosheets, which were then blended into an alginate hydrogel that was crosslinked by means of calcium ions. The homogeneous incorporation of GO within the polymer network, which was confirmed through morphological investigations, improved the stability of the hybrid system compared to blank hydrogels. The weight loss in the 100–170 °C temperature range was reduced from 30% to 20%, and the degradation of alginate chains shifted to higher temperatures. Moreover, GO enhanced the stability in water media by counteracting the de-crosslinking process of the polymer network. Cell viability assays showed that the loading of CUR (2.5% and 5% by weight) was able to reduce the intrinsic toxicity of GO towards healthy cells, while higher amounts were ineffective due to the antioxidant/prooxidant paradox. Interestingly, the CUR-loaded systems were found to possess a strong cytotoxic effect in SCC cancer cells, and the sustained CUR release (~50% after 96 h) allowed long-term anticancer efficiency to be hypothesized

Post-Quantum LMS and SPHINCS+ Hash-Based Signatures for UEFI Secure Boot

The potential development of large-scale quantum computers is raising concerns among IT and security research professionals due to their ability to solve (elliptic curve) discrete logarithm and integer factorization problems in polynomial time. This would jeopardize IT security as we know it. In this work, we investigate two quantum-safe, hash-based signature schemes published by the Internet Engineering Task Force and submitted to the National Institute of Standards and Technology for use in secure boot. We evaluate various parameter sets for the use-case in question and we prove that post-quantum signatures with less than one second signing and less than 10ms verification would not have material impact (less than1‰) on secure boot. We evaluate the hierarchical design of these signatures in hardware-based and virtual secure boot. In addition, we develop Hardware Description Language code and show that the code footprint is just a few kilobytes in size which would fit easily in almost all modern FPGAs. We also analyze and evaluate potential challenges for integration in existing technologies and we discuss considerations for vendors embarking on a journey of image signing with hash-based signatures