The NAD+-Dependent Histone Deacetylase Sirtuin-2 is Upregulated during Myogenesis and Promotes the Differentiation of C2C12 Myoblasts

The postnatal growth and regenerative capacity of skeletal muscle rely on the successful activation and differentiation of muscle stem cells known as satellite cells. Although the NAD+-dependent protein deacetylase sirtuin-2 (Sirt2) has been suggested to have a role as a redox sensor during myogenesis, and in the regulation of metabolism, microtubule dynamics, and exit from the cell cycle exit, it is not known if Sirt2 has a regulatory role in muscle stem cell differentiation. This study aimed to elucidate the regulation of Sirt2 during the myogenic program of muscle satellite cells. The C2C12 mouse myoblast cell line was used to examine the regulatory mechanisms of Sirt2 during the differentiation process. Several cell lines were used during experimentation including wild type (-) cells, cells supplemented with the Sirt2 inhibitor BML-266, and cells which were transfected with CRISPR/Cas9 plasmids to generate both Sirt2 knockdown (SKO) and control plasmid (CC) lines. Assays were conducted at time points from 0h-96h following the induction of differentiation to assess Sirt2 regulation and downstream interactions. Sirt2 mRNA and protein expression were elevated during the early stages of differentiation at the 12h time point in the (-) cells. A significant decrease in the myotube fusion index of both BML-266 and SKO cell lines was observed, indicating Sirt2 deacetylase activity is important in regulating the normal formation of myotubes. Immunoprecipitation experimentation was performed to evaluate Sirt2 protein interactions and possible downstream signaling targets. Sirt2 was observed to interact with the cell cycle inhibitor retinoblastoma (pRB), as well as p21 and E2F1 a regulator of cellular proliferation. The acetylation status of E2F1 was significantly decreased at the 12h time point coinciding with the increased Sirt2 protein expression observed at the same point. These results indicate that Sirt2 mediates its control of myogenesis through interaction and complex formation with proteins associated with the cell cycle, and that this interaction mediates exit from the cell cycle and the induction of terminal differentiation leading to the formation of myofibers. Elucidation of Sirt2 as a regulator of differentiation during myogenesis thus presents a possible therapeutic target in conditions such as aging, as expression of the sirtuins and their cofactor NAD+ both decrease in aged phenotypes

Design for Sustainable Behaviour: investigating design methods for influencing user behaviour

This research aims to develop a design tool for product and service innovation which influences users towards more sustainable behaviour, reducing resource use and leading to a lower carbon footprint for everyday activities. The paper briefly explains the reasoning behind the tool and its structure, and presents an example application to water conservation with concept ideas generated by design students

Good theories in need of better data:Combining clinical and social psychological approaches to study the mechanisms linking relationships and health

The study of intimate relationships and health is a fast-growing discipline with numerous well-developed theories, many of which outline specific interpersonal behaviors and psychological pathways that may give rise to good or poor health. In this article, we argue that the study of relationships and health can move toward interrogating these mechanisms with greater precision and detail, but doing so will require a shift in the nature of commonly used research methods in this area. Accordingly, we draw heavily on the science of behavior change and discuss six key methodologies that may galvanize the mechanistic study of relationships and health: dismantling studies, factorial studies, experimental therapeutics, experimental mediation research, multiple assessments, and recursive modeling. We provide empirical examples for each strategy and outline new ways in which a given approach may be used to study the mechanisms linking intimate relationships and health. We conclude by discussing the key challenges and limitations for using these research strategies as well as novel ideas about how to integrate this work into existing paradigms within the field.Immediate accessThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Colonization of the Scottish islands via long-distance Neolithic transport of red deer (Cervus elaphus)

Red deer (Cervus elaphus) have played a key role in human societies throughout history, with important cultural significance and as a source of food and materials. This relationship can be traced back to the earliest human cultures and continues to the present day. Humans are thought to be responsible for the movement of a considerable number of deer throughout history, although the majority of these movements are poorly described or understood. Studying such translocations allows us to better understand ancient human–wildlife interactions, and in the case of island colonizations, informs us about ancient human maritime practices. This study uses DNA sequences to characterise red deer genetic diversity across the Scottish islands (Inner and Outer Hebrides and Orkney) and mainland using ancient deer samples, and attempts to infer historical colonization events. We show that deer from the Outer Hebrides and Orkney are unlikely to have originated from mainland Scotland, implying that humans introduced red deer from a greater distance. Our results are also inconsistent with an origin from Ireland or Norway, suggesting long-distance maritime travel by Neolithic people to the outer Scottish Isles from an unknown source. Common haplotypes and low genetic differentiation between the Outer Hebrides and Orkney imply common ancestry and/or gene flow across these islands. Close genetic proximity between the Inner Hebrides and Ireland, however, corroborates previous studies identifying mainland Britain as a source for red deer introductions into Ireland. This study provides important information on the processes that led to the current distribution of the largest surviving indigenous land mammal in the British Isles

Projected effects of tobacco smoking on worldwide tuberculosis control: mathematical modelling analysis

Objectives Almost 20% of people smoke tobacco worldwide—a percentage projected to rise in many poor countries. Smoking has been linked to increased individual risk of tuberculosis infection and mortality, but it remains unclear how these risks affect population-wide tuberculosis rates

The Composition of Human Milk and Infant Faecal Microbiota Over the First Three Months of Life: A Pilot Study

peer-reviewedHuman milk contains a diverse array of bioactives and is also a source of bacteria for the developing infant gut. The aim of this study was to characterize the bacterial communities in human milk and infant faeces over the first 3 months of life, in 10 mother-infant pairs. The presence of viable Bifidobacterium and Lactobacillus in human milk was also evaluated. MiSeq sequencing revealed a large diversity of the human milk microbiota, identifying over 207 bacterial genera in milk samples. The phyla Proteobacteria and Firmicutes and the genera Pseudomonas, Staphylococcus and Streptococcus were the predominant bacterial groups. A core of 12 genera represented 81% of the microbiota relative abundance in milk samples at week 1, 3 and 6, decreasing to 73% at week 12. Genera shared between infant faeces and human milk samples accounted for 70–88% of the total relative abundance in infant faecal samples, supporting the hypothesis of vertical transfer of bacteria from milk to the infant gut. In addition, identical strains of Bifidobacterium breve and Lactobacillus plantarum were isolated from the milk and faeces of one mother-infant pair. Vertical transfer of bacteria via breastfeeding may contribute to the initial establishment of the microbiota in the developing infant intestine

The design with intent method: A design tool for influencing user behaviour

The official published version can be found at the link below.Using product and system design to influence user behaviour offers potential for improving performance and reducing user error, yet little guidance is available at the concept generation stage for design teams briefed with influencing user behaviour. This article presents the Design with Intent Method, an innovation tool for designers working in this area, illustrated via application to an everyday human–technology interaction problem: reducing the likelihood of a customer leaving his or her card in an automatic teller machine. The example application results in a range of feasible design concepts which are comparable to existing developments in ATM design, demonstrating that the method has potential for development and application as part of a user-centred design process

A New Approach toward Transition State Spectroscopy

Chirped-Pulse millimetre-Wave (CPmmW) rotational spectroscopy provides a new class of information about photolysis transition state(s). Measured intensities in rotational spectra determine species-isomer-vibrational populations, provided that rotational populations can be thermalized. The formation and detection of S0 vinylidene is discussed in the limits of low and high initial rotational excitation. CPmmW spectra of 193 nm photolysis of Vinyl Cyanide (Acrylonitrile) contain J=0-1 transitions in more than 20 vibrational levels of HCN, HNC, but no transitions in vinylidene or highly excited local-bender vibrational levels of acetylene. Reasons for the non-observation of the vinylidene co-product of HCN are discussed.Comment: Accepted by Faraday Discussion

Extensive Pneumatization of the Temporal Bone and Articular Eminence: An Incidental Finding in a Patient With Facial Pain. Case Report and Review of Literature

A 53-year-old Caucasian female presented to the Oral Medicine Department at the hospital of the University of Pennsylvania for consultation regarding facial pain. A panoramic radiograph revealed multilocular radiolucencies in the right articular eminence. A CT scan was then performed, and the radiolucencies were determined to be pneumatization of the articular eminence

Before Kukulkán

This volume illuminates human lifeways in the northern Maya lowlands prior to the rise of Chichén Itzá. This period and area have been poorly understood on their own terms, obscured by scholarly focus on the central lowland Maya kingdoms. "Before Kukulkán" is anchored in three decades of interdisciplinary research at the Classic Maya capital of Yaxuná, located at a contentious crossroads of the northern Maya lowlands. Using bioarchaeology, mortuary archaeology, and culturally sensitive mainstream archaeology, the authors create an in-depth regional understanding while also laying out broader ways of learning about the Maya past. Part 1 examines ancient lifeways among the Maya at Yaxuná, while part 2 explores different meanings of dying and cycling at the settlement and beyond: ancestral practices, royal entombment and desecration, and human sacrifice. The authors close with a discussion of the last years of occupation at Yaxuná and the role of Chichén Itzá in the abandonment of this urban center. "Before Kukulkán" provides a cohesive synthesis of the evolving roles and collective identities of locals and foreigners at the settlement and their involvement in the region’s trajectory. Theoretically informed and contextualized discussions offer unique glimpses of everyday life and death in the socially fluid Maya city. These findings, in conjunction with other documented series of skeletal remains from this region, provide a nuanced picture of the social and biocultural dynamics that operated successfully for centuries before the arrival of the Itzá