Hemoglobin Subunit-Subunit Affinity-Determinant of Hemoglobin Formation

Hemoglobin A₂ is often elevated in β-thalassemia and decreased in α-thalassemia. This might be due to hemoglobin subunit-subunit affinity variation. It has been inferred from the study of abnormal hemoglobins that the a subunits have higher affinity for β subunits than for δ subunits. However, only in one study has the affinity of α, β, and δ subunits for each other been measured. In this work we have attempted to measure the hemoglobin subunit-subunit affinity with somewhat different approach, i.e., hybridization of hemoglobin A and A₂. It is shown that hybridization and recombination of equal amounts of hemoglobins A and A₂ lead always to the formation of more hemoglobin A than A₂. Incubation of pure α, β, and δ subunits forms more hemoglobin A than A₂ as the availability of a subunits declines. It is concluded that hemoglobin a subunits have approximately four-fold higher affinity for β subunits than for the δ subunits under these experimental conditions. This subunit-subunit affinity difference, which has been attributed to the variation in molecular electrostatic charges, explains the variation of hemoglobin A₂ levels in thalassemia syndromes

Minimum Makespan Multi-vehicle Dial-a-Ride

Dial a ride problems consist of a metric space (denoting travel time between vertices) and a set of m objects represented as source-destination pairs, where each object requires to be moved from its source to destination vertex. We consider the multi-vehicle Dial a ride problem, with each vehicle having capacity k and its own depot-vertex, where the objective is to minimize the maximum completion time (makespan) of the vehicles. We study the "preemptive" version of the problem, where an object may be left at intermediate vertices and transported by more than one vehicle, while being moved from source to destination. Our main results are an O(log^3 n)-approximation algorithm for preemptive multi-vehicle Dial a ride, and an improved O(log t)-approximation for its special case when there is no capacity constraint. We also show that the approximation ratios improve by a log-factor when the underlying metric is induced by a fixed-minor-free graph.Comment: 22 pages, 1 figure. Preliminary version appeared in ESA 200

Planetary atlases

Two kinds of planetary map atlases are in production. Atlases of the first kind contain reduced-scale versions of maps in hard-bound books with dimensions of 11 x 14 inches. These new atlases are intended to: (1) provide concise but comprehensive references to the geography of the planets needed by planetary scientists and others; and (2) allow inexpensive access to the planetary map dataset without requiring acquisition and examination of tens or hundreds of full-size map sheets. Two such atlases have been published and a third is in press. Work was begun of an Atlas of the Satellite of the Outer Planets. The second kind of atlas is a popular or semi-technical version designed for commercial publication and distribution. The first edition, The Atlas of the Solar System, is nearly ready for publication. New funding and contracting constraints now make it unlikely that the atlas can be published in the format originally planned. Currently, the possibility of publishing the maps through the U.S. Geological Survey as a series of folios in the I-map series is being explored. The maps are global views of each solid-surface body of the Solar System. Each map shows airbrushed relief, albedo, and, where available, topography. A set of simplified geologic maps is also included. All of the maps are on equal-area projections. Scales are 1:40,000,000 for the Earth and Venus; 1:2,000,000 for the Saturnian satellites Mimas and Enceladus and the Uranian satellite Miranda; 1:100,000 for the Martian satellites, Phobos and Deimos; and 1:10,000,000 for all other bodies

How effective are exercise and physical therapy for chronic low back pain?

Exercise is more effective for chronic low back pain than treatment with medication plus return to usual activity and as effective as conventional physiotherapy. The evidence is less consistent in showing that any particular exercise format provides greater benefit or that exercise provides a long-term increase in function or a decrease in pain or disability. (Grade of recommendation: A, based on systematic reviews of randomized controlled trials [RCTs].

Pacing Strategy, Muscle Fatigue, and Technique in 1500-m Speed-Skating and Cycling Time Trials

Purpose: To evaluate pacing behavior and peripheral and central contributions to muscle fatigue in 1500-m speed-skating and cycling time trials when a faster or slower start is instructed. Methods: Nine speed skaters and 9 cyclists, all competing at regional or national level, performed two 1500-m time trials in their sport. Athletes were instructed to start faster than usual in 1 trial and slower in the other. Mean velocity was measured per 100 m. Blood lactate concentrations were measured. Maximal voluntary contraction (MVC), voluntary activation (VA), and potentiated twitch (PT) of the quadriceps muscles were measured to estimate central and peripheral contributions to muscle fatigue. In speed skating, knee, hip, and trunk angles were measured to evaluate technique. Results: Cyclists showed a more explosive start than speed skaters in the fast-start time trial (cyclists performed first 300 m in 24.70 ± 1.73 s, speed skaters in 26.18 ± 0.79 s). Both trials resulted in reduced MVC (12.0% ± 14.5%), VA (2.4% ± 5.0%), and PT (25.4% ± 15.2%). Blood lactate concentrations after the time trial and the decrease in PT were greater in the fast-start than in the slow-start trial. Speed skaters showed higher trunk angles in the fast-start than in the slow-start trial, while knee angles remained similar. Conclusions: Despite similar instructions, behavioral adaptations in pacing differed between the 2 sports, resulting in equal central and peripheral contributions to muscle fatigue in both sports. This provides evidence for the importance of neurophysiological aspects in the regulation of pacing. It also stresses the notion that optimal pacing needs to be studied sport specifically, and coaches should be aware of this

Mitochondrial and chloroplast stress responses are modulated in distinct touch and chemical inhibition phases

Previous studies have identified a range of transcription factors that modulate retrograde regulation of mitochondrial and chloroplast functions in Arabidopsis (Arabidopsis thaliana). However, the relative importance of these regulators and whether they act downstream of separate or overlapping signaling cascades is still unclear. Here, we demonstrate that multiple stress-related signaling pathways, with distinct kinetic signatures, converge on overlapping gene sets involved in energy organelle function. The transcription factor ANAC017 is almost solely responsible for transcript induction of marker genes around 3 to 6 h after chemical inhibition of organelle function and is a key regulator of mitochondrial and specific types of chloroplast retrograde signaling. However, an independent and highly transient gene expression phase, initiated within 10 to 30 min after treatment, also targets energy organelle functions, and is related to touch and wounding responses. Metabolite analysis demonstrates that this early response is concurrent with rapid changes in tricarboxylic acid cycle intermediates and large changes in transcript abundance of genes encoding mitochondrial dicarboxylate carrier proteins. It was further demonstrated that transcription factors AtWRKY15 and AtWRKY40 have repressive regulatory roles in this touch-responsive gene expression. Together, our results show that several regulatory systems can independently affect energy organelle function in response to stress, providing different means to exert operational control

Metabonomics adds a new dimension to fragile X syndrome

Fragile X syndrome is the most common cause of inherited intellectual disability, but the underlying pathophysiology is complex and effective treatments are lacking. In a recent study of fragile X mental retardation 1 (Fmr1) knockout mice, the metabolic profile of the fragile X brain was determined using proton high-resolution magic angle spinning nuclear magnetic resonance spectroscopy. This analysis revealed deficiencies in four metabolic categories: neurotransmission, osmoregulation, energy metabolism and oxidative stress response. Abnormalities in the metabolic phenotype were linked to the fragile X mental retardation protein using an integrated metabolome and interactome mapping approach, allowing a global picture of the disorder to emerge

An intact signal peptide on dengue virus E protein enhances immunogenicity for CD8+ T cells and antibody when expressed from modified vaccinia Ankara

Dengue is a global public health concern and this is aggravated by a lack of vaccines or antiviral therapies. Despite the well-known role of CD8(+) T cells in the immunopathogenesis of Dengue virus (DENV), only recent studies have highlighted the importance of this arm of the immune response in protection against the disease. Thus, the majority of DENV vaccine candidates are designed to achieve protective titers of neutralizing antibodies, with less regard for cellular responses. Here, we used a mouse model to investigate CD8(+) T cell and humoral responses to a set of potential DENV vaccines based on recombinant modified vaccinia virus Ankara (rMVA). To enable this study, we identified two CD8(+) T cell epitopes in the DENV-3 E protein in C57BL/6 mice. Using these we found that all the rMVA vaccines elicited DENV-specific CD8(+) T cells that were cytotoxic in vivo and polyfunctional in vitro. Moreover, vaccines expressing the E protein with an intact signal peptide sequence elicited more DENV-specific CD8(+) T cells than those expressing E proteins in the cytoplasm. Significantly, it was these same ER-targeted E protein vaccines that elicited antibody responses. Our results support the further development of rMVA vaccines expressing DENV E proteins and add to the tools available for dengue vaccine development.Parts of this work were supported by the InstitutoNacional de Ciência e Tecnologia de Vacinas–INCTV (National Insti-tute of Science and Technology of Vaccines) and by a FAPEMIGPPM grant (CBB, PPM-00461-11). BRQ was a CAPES/PDSE fellow-ship recipient (8815-11-9). FGF is a CNPq fellowship recipient. DCTis an ARC Future Fellow (FT110100310)