PARP inhibitors protect against sex- and AAG-dependent alkylation-induced neural degeneration

Alkylating agents are commonly used to treat cancer. Although base excision repair (BER) is a major pathway for repairing DNA alkylation damage, under certain conditions, the initiation of BER produces toxic repair intermediates that damage healthy tissues. The initiation of BER by the alkyladenine DNA glycosylase (AAG, a.k.a. MPG) can mediate alkylation-induced cytotoxicity in specific cells in the retina and cerebellum of male mice. Cytotoxicity in both wild-type andAag-transgenic (AagTg) mice is abrogated in the absence of Poly(ADP-ribose) polymerase-1 (PARP1). Here, we tested whether PARP inhibitors can also prevent alkylation-induced retinal and cerebellar degeneration in male and female WT andAagTgmice. Importantly, we found that WT mice display sex-dependent alkylation-induced retinal damage (but not cerebellar damage), with WT males being more sensitive than females. Accordingly, estradiol treatment protects males against alkylation-induced retinal degeneration. InAagTgmale and female mice, the alkylation-induced tissue damage in both the retina and cerebellum is exacerbated and the sex difference in the retina is abolished. PARP inhibitors, much likeParp1gene deletion, protect against alkylation-induced AAG-dependent neuronal degeneration in WT andAagTgmice, regardless of the gender, but their efficacy in preventing alkylation-induced neuronal degeneration depends on PARP inhibitor characteristics and doses. The recent surge in the use of PARP inhibitors in combination with cancer chemotherapeutic alkylating agents might represent a powerful tool for obtaining increased therapeutic efficacy while avoiding the collateral effects of alkylating agents in healthy tissues.National Institutes of Health (U.S.) (Award R01- CA075576)National Institutes of Health (U.S.) (Award R01-CA055042)National Institutes of Health (U.S.) (Award P30-ES02109)National Institutes of Health (U.S.) (Award P30- CA014051

Multicolor stimulated Raman scattering microscopy

Stimulated Raman scattering (SRS) microscopy has opened up a wide range of biochemical imaging applications by probing a particular Raman-active molecule vibrational mode in the specimen. However, the original implementation with picosecond pulse excitation can only realize rapid chemical mapping with a single Raman band. Here we present a novel SRS microscopic technique using a grating-based pulse shaper for excitation and a grating-based spectrograph for detection to achieve simultaneous multicolor SRS imaging with high sensitivity and high acquisition speeds. In particular, we use a linear combination of the measured $CH_2$ and $CH_3$ stretching signals to map the distributions of protein and lipid contents simultaneously.Chemistry and Chemical Biolog

Quantitative Chemical Imaging with Multiplex Stimulated Raman Scattering Microscopy

Stimulated Raman scattering (SRS) microscopy is a newly developed label-free chemical imaging technique that overcomes the speed limitation of confocal Raman microscopy while avoiding the nonresonant background problem of coherent anti-Stokes Raman scattering (CARS) microscopy. Previous demonstrations have been limited to single Raman band measurements. We present a novel modulation multiplexing approach that allows real-time detection of multiple species using the fast Fourier transform. We demonstrate the quantitative determination of chemical concentrations in a ternary mixture. Furthermore, two imaging applications are pursued: (1) quantitative determination of oil content as well as pigment and protein concentration in microalgae cultures; and (2) 3D high-resolution imaging of blood, lipids, and protein distribution in ex vivo mouse skin tissue. We believe that quantitative multiplex SRS uniquely combines the advantage of fast label-free imaging with the fingerprinting capability of Raman spectroscopy and enables numerous applications in lipid biology as well as biomedical imaging.Chemistry and Chemical BiologyEngineering and Applied Science

Perspectivas de los estudiantes sobre el uso de la tecnología para el aprendizaje en la educación superior

In this study, college students in a large public university in the U.S. were surveyed regarding what technologies they use most frequently for learning, what technologies they value for learning, and how they perceive technology effectiveness to support their learning. The results revealed that technology use and value were closely aligned with laptops and these were detailed as the most used and valued for learning, which underscores the importance of mobile and portable devices in supporting anytime anywhere learning. In terms of using software for learning, search engines, file-sharing tools, digital libraries, videos, and wikis obtained the best results, suggesting that students are adopting self-directed, approaches to their learning. Additionally, collaboration tools were perceived as the most important for learning which highlights the need to design better teaching strategies and learning interactions to support collaborative practices that use technology. Overall, the majority of participants perceived that technology was effective in fostering discussion, collaboration, and interaction. This enable experiential learning, supporting organization, planning, and resource management, and facilitating a personalized learning experience. The results also revealed statistically significant differences between the experiences of undergraduate and graduate students about the effectiveness of technology. Implications for integrating Web 2.0 technologies into teaching and learning practices are discussed.     En este estudio, los estudiantes universitarios en una gran universidad pública en los EE. UU. fueron encuestados con respecto a qué tecnologías utilizan con más frecuencia para aprender, qué tecnologías valoran para el aprendizaje y cómo perciben efectividad de la tecnología para respaldar su aprendizaje. Los resultados revelaron que el uso y el valor de la tecnología estaban estrechamente alineados con ordenadores portátiles y teléfonos inteligentes, éstos fueron detallados como los más utilizados y valorados para el aprendizaje, lo que subraya la importancia de los dispositivos móviles y portátiles para respaldar el aprendizaje en cualquier momento y lugar. En términos de uso de software para el aprendizaje, los motores de búsqueda, las herramientas para compartir archivos, las bibliotecas digitales, los videos y los wikis obtuvieron los mejores resultados, lo que sugiere que los estudiantes están adoptando enfoques autodirigidos para su aprendizaje. Además, las herramientas de colaboración fueron percibidas como las más importantes para el aprendizaje, lo que destaca la necesidad de diseñar mejores estrategias de enseñanza e interacciones de aprendizaje para respaldar las prácticas de colaboración que utilizan la tecnología. En general, la mayoría de los participantes percibió que la tecnología era eficaz para fomentar el debate, la colaboración y la interacción. Esto permite el aprendizaje experiencial, apoya la organización, la planificación, la gestión de recursosy facilitar una experiencia de aprendizaje personalizada. Los resultados también revelaron diferencias estadísticamente significativas entre las experiencias de los estudiantes de pregrado y posgrado acerca de la efectividad de la tecnología. Se discuten las implicaciones para integrar las tecnologías Web 2.0 en las prácticas de enseñanza y aprendizaj

Remediating small-scale migratory fish barriers with floating fish ramps

Instream barriers are a well-documented stressor for diadromous fish species, and can be numerous and costly to remediate. In New Zealand, previous experiments have investigated the swimming ability of indigenous migratory fish over small ramps, but this work has not led to the development of cost-effective ramps that can be deployed by river managers. This study built on previous research and investigated the effect of ramp surface type on the swimming ability of two species of diadromous fish; inanga (Galaxias maculatus) a weak swimmer, and redfin bully (Gobiomorphus huttoni) a moderate climber, in an effort to inform the design of a floating plastic ramp that could be installed at low head instream barriers. Three phases of tank trials in the Hawke’s Bay tested different ramp substrates, including rock climbing holds, and small and large raised Miradrain® cusps. The results indicated that a linear arrangement of small cusps provided an optimal surface for swimming species such as inanga while redfin bully passage rates did not differ between the surfaces tested. The addition of spat rope reduced velocities and increased depth on all surfaces, and increased passage rates for inanga on ramps with large cusps, and redfin bullies on both cusp sizes. Fish surveys were conducted at 4 lowland streams in Hawke’s Bay in order to characterise fish communities, investigate the impact of barriers on their distribution, and evaluate the success of ramp installations in facilitating passage. Fish communities were impacted by barriers to varying degrees depending on the climbing ability of different species present. Inanga and redfin bully abundances were lower above the barriers, whereas eel abundances were similar between upstream and downstream reaches. Rotomoulded plastic floating ramps lined with small cusps were installed at barriers on 2 streams, the Awanui and the Irongate. Inanga were found above the barrier in the Awanui Stream 12 months after a ramp was installed, but fish did not pass over the wooden weir on the Irongate Stream. Buoyancy issues with the Irongate ramp are thought to have reduced its utility and potentially hindered fish passage. The buoyancy issues have since been overcome, and further monitoring is required to assess whether fish passage is consequently improved. These results show that floating rotomoulded ramps can be an effective and cost-effective tool for remediating small scale instream barriers to migratory fish.

Three is not a crowd: working collaboratively across institutions: the White Rose Libraries partnership at the universities of Leeds, Sheffield and York

The White Rose Libraries, consisting of the libraries of the universities of Leeds, Sheffield and York, have worked together since 2004 on a number of collaborative projects. In 2015 new permanent staff and a new service model meant that we have stepped up our commitment to collaboration. This article outlines how the partnership now operates and what it has been able to achieve. It considers both the challenges that such collaborations face, and the reasons for the White Rose Libraries’ ongoing success