Human DDX17 Unwinds Rift Valley Fever Virus Non-Coding RNAs

Rift Valley fever virus (RVFV) is a mosquito-transmitted virus from the Bunyaviridae family that causes high rates of mortality and morbidity in humans and ruminant animals. Previous studies indicated that DEAD-box helicase 17 (DDX17) restricts RVFV replication by recognizing two primary non-coding RNAs in the S-segment of the genome: the intergenic region (IGR) and 5′ non-coding region (NCR). However, we lack molecular insights into the direct binding of DDX17 with RVFV non-coding RNAs and information on the unwinding of both non-coding RNAs by DDX17. Therefore, we performed an extensive biophysical analysis of the DDX17 helicase domain (DDX17_135–555) and RVFV non-coding RNAs, IGR and 5’ NCR. The homogeneity studies using analytical ultracentrifugation indicated that DDX17_135–555, IGR, and 5’ NCR are pure. Next, we performed small-angle X-ray scattering (SAXS) experiments, which suggested that DDX17 and both RNAs are homogenous as well. SAXS analysis also demonstrated that DDX17 is globular to an extent, whereas the RNAs adopt an extended conformation in solution. Subsequently, microscale thermophoresis (MST) experiments were performed to investigate the direct binding of DDX17 to the non-coding RNAs. The MST experiments demonstrated that DDX17 binds with the IGR and 5’ NCR with a dissociation constant of 5.77 ± 0.15 µM and 9.85 ± 0.11 µM, respectively. As DDX17_135–555 is an RNA helicase, we next determined if it could unwind IGR and NCR. We developed a helicase assay using MST and fluorescently-labeled oligos, which suggested DDX17_135–555 can unwind both RNAs. Overall, our study provides direct evidence of DDX17_135–555 interacting with and unwinding RVFV non-coding regions.     

Radon and moisture impacts from interventions integrated with housing energy retrofits

Energy retrofits can reduce air exchange, raising the concern of whether indoor radon and moisture levels could increase. This pre/post-intervention study explored whether simple radon interventions implemented in conjunction with energy retrofits can prevent increases in radon and moisture levels. Treatment homes (n = 98) were matched with control (no energy retrofits or radon intervention) homes (n = 12). Control homes were matched by geographic location and foundation type. t-tests were used to determine whether post-energy retrofit radon and moisture level changes in treatment homes significantly differed from those in control homes. The radon interventions succeeded in preventing statistically significant increases in first floor radon using arithmetic (p = 0.749) and geometric means (p = 0.120). In basements, arithmetic (p = 0.060) and geometric (p = 0.092) mean radon levels statistically significantly increased, consistent with previous studies which found that basement radon levels may increase even if first floor levels remain unchanged. Changes in infiltration were related to changes in radon (p = 0.057 in basements; p = 0.066 on first floors). Only 58% of the change in infiltration was due to air sealing, with the rest due to weather changes. There was no statistically significant association between air sealing itself and radon levels on the first floor (p = 0.664). Moisture levels also did not significantly increase.     

Lamin-Related Congenital Muscular Dystrophy Alters Mechanical Signaling and Skeletal Muscle Growth

Laminopathies are a clinically heterogeneous group of disorders caused by mutations in the LMNA gene, which encodes the nuclear envelope proteins lamins A and C. The most frequent diseases associated with LMNA mutations are characterized by skeletal and cardiac involvement, and include autosomal dominant Emery–Dreifuss muscular dystrophy (EDMD), limb-girdle muscular dystrophy type 1B, and LMNA-related congenital muscular dystrophy (LMNA-CMD). Although the exact pathophysiological mechanisms responsible for LMNA-CMD are not yet understood, severe contracture and muscle atrophy suggest that mutations may impair skeletal muscle growth. Using human muscle stem cells (MuSCs) carrying LMNA-CMD mutations, we observe impaired myogenic fusion with disorganized cadherin/β catenin adhesion complexes. We show that skeletal muscle from Lmna-CMD mice is unable to hypertrophy in response to functional overload, due to defective fusion of activated MuSCs, defective protein synthesis and defective remodeling of the neuromuscular junction. Moreover, stretched myotubes and overloaded muscle fibers with LMNA-CMD mutations display aberrant mechanical regulation of the yes-associated protein (YAP). We also observe defects in MuSC activation and YAP signaling in muscle biopsies from LMNA-CMD patients. These phenotypes are not recapitulated in closely related but less severe EDMD models. In conclusion, combining studies in vitro, in vivo, and patient samples, we find that LMNA-CMD mutations interfere with mechanosignaling pathways in skeletal muscle, implicating A-type lamins in the regulation of skeletal muscle growth.     

Building human agency: a timely manifesto

The 2009 Passive and Low Energy Architecture Conference (PLEA), held in Québec City, Canada, was themed ‘Architecture, Energy and the Occupant's Perspective’, with the ambition of positioning building inhabitants as key ‘active’ determinants of energy performance in ‘passive’ design through adaptive opportunities. Conference delegates committed to a Manifesto that embodied both the key longstanding priorities of PLEA and explicitly conveyed the priorities of the conference hosts. The Manifesto is examined in terms of how it captures and represents a shift in thinking that has occurred over the past few years, away from technological and technocratic solutions to comfort provisioning and towards reframing building energy consumption as a social and ethical challenge in which comfort plays a key role.

La Conférence 2009 sur l'Architecture Passive et Basse Energie (PLEA), qui s'est tenue à Québec, au Canada, avait pour thème « Architecture, Energie et la Perspective de l'Occupant », avec pour ambition de positionner les habitants d'immeubles comme principaux déterminants « actifs » de la performance énergétique dans un design « passif » par des opportunités d'adaptation. Les délégués de la conférence se sont engagés en faveur d'un Manifeste qui, tout à la fois, incarne les principales priorités qui sont depuis longtemps celles des Conférences PLEA et traduit explicitement les priorités des hôtes de la conférence. Cet article examine le Manifeste quant à la manière dont il appréhende et reflète le changement intervenu au cours de ces dernières années dans la manière de voir les choses, consistant à se détourner d'un confort fourni par des solutions technologiques et technocratiques et à aller dans le sens d'un recadrage de la consommation énergétique des immeubles considérée comme un défi social et éthique dans lequel le confort joue un rôle clé.

Mots clés: comportement adaptatif, agence, confort, fourniture du confort, qualité environnementale intérieure, habitants, manifeste, Conférence sur l'Architecture Passive et Basse Energie (PLEA)     

Reconceptualizing Architectural Education for a More Diverse Future: Perceptions and Visions of Architectural Students

This article argues that the field of architecture must engage diversity in two senses of the word simultaneously: both in terms of its demographic composition and in terms of the substantive domain of architecture. Increasing the participation of women and minorities in the field should also mean increasing the substantive domain of the profession, and vice versa. We substantiate this argument within the realm of architectural education through a research study involving nearly 650 students at six different architecture schools. The purpose of the study was to investigate the ways in which both the content and the form of architectural education might impede or support the progress of women and minority students. In particular, we focus on three aspects of the “hidden curriculum”: studio pedagogy; social dynamics; and ideals and expectations. We find that women and members of some ethnic groups (particularly African-Americans and Latinos) do tend to experience the social dynamics and pedagogical practices of their educational milieu differently, often more negatively, than their male or majority counterparts. Our findings also reveal that many women and minorities feel that their career goals may be mismatched with the profession as it is currently defined. To the extent that our school programs ignore the dynamics of the hidden curriculum, not only might we be turning away potentially talented students, but we might be crippling a profession that must operate in a rapidly changing cultural and economic context. In that regard, we believe that all students will benefit from a collective reassessment of architecture's pedagogical conventions and of the definitional scope of the field.     

On the Anatomy of Human Hacking

ABSTRACT

Human hacking is a nontechnical kind of intrusion that relies heavily on human manipulation. Its impact is continuously giving serious concern in the Information technology arena which has often been undermined due to the ease with which this technique is widely used to infiltrate networks through unsuspecting individuals that are undeniably considered the “weakest link” in the security circle. Security awareness that brings about behavioral change, reduces employees' vulnerability, and protects against threats exploiting employees' vulnerability having a positive impact overall on risks related to information assets. Strategies for developing and implementing a successful information security awareness program are presented in this article, which also provides an introduction to the subject of human hacking while discussing the various counter-measures available to minimize the likelihood of such occurrences and their financial, reputation, psychological, and legal ramifications.     

Less cyber,more café: Enhancing existing small businesses across the digital divide with ICTs

About 10% of the world has access to information and communication technologies (ICTs). Telecenters and cyber cafés are one prevalent way to increase access. This paper suggests increasing access through currently existing, local businesses where people already gather and where proprietors already posses existing business relationships with suppliers and customers. This paper questions the prevailing emphasis on the “cyber'' characteristics of access, e.g., computing and internet access as is currently known, and attempts to refocus the conversation by considering computing and access in the context of the “café,” e.g., as public life in the sense of Habermas, which permits an in situ evolution of relevant access. This analysis is based on extant literature and direct ethnographic research in several public places in six countries. We offer example design perspectives based on a reflection of “third places” as inspiration for appropriate innovation in the provision of computing and communications. © 2005 Wiley Periodicals, Inc.     

Global Concerns with B Vitamin Statuses: Biofortification,Fortification, Hidden Hunger,Interactions, and Toxicity

The prevalence of undernutrition due to insufficient energy intake has been reduced by nearly 50% since 1990. This reduction is largely attributed to improved yields of staple crops, such as wheat, rice, and maize; however, these improvements did little for micronutrient deficiencies that affect an estimated two billion people worldwide. Starchy staple crops are energy dense but are often lacking in one or more B vitamins, making resource‐constrained people who consume monotonous diets comprised predominantly of these staples at risk for developing deficiency. B vitamin deficiencies occur due to a poor overall nondiversified diet and rarely occur alone. Many B vitamins are essential cofactors involved in the metabolism of other nutrients, including other B vitamins, whereby the deficiency of one B vitamin affects the metabolism and status measurements of another. Food fortification efforts have nearly eradicated diseases of extreme B vitamin deficiency, such as beriberi from thiamin deficiency and pellagra from niacin deficiency. However, subclinical deficiency, sometimes referred to as hidden hunger, is still common especially in low‐income countries. Most dietary B vitamins, due to their water‐soluble nature, are not a concern for excessive intakes, but synthetic forms used for fortification and supplements sometimes can have adverse effects when consumed in high amounts. Biofortified crops offer a long‐term sustainable method to increase the amount of dietary B vitamins for people who rely on staple crops for most of their caloric intake. Efforts have been made to improve B vitamin content of crops, especially for thiamin, vitamin B₆, and folate, but none have undergone human feeding trials; therefore, more research is needed to provide sustainable and scalable solutions in many parts of the world.