Increasing phylogenetic stochasticity at high elevations on summits across a remote North American wilderness

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150529/1/ajb21328-sup-0002-AppendixS2.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150529/2/ajb21328-sup-0003-AppendixS3.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150529/3/ajb21328-sup-0004-AppendixS4.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150529/4/ajb21328.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150529/5/ajb21328-sup-0009-AppendixS9.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150529/6/ajb21328-sup-0005-AppendixS5.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150529/7/ajb21328-sup-0007-AppendixS7.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150529/8/ajb21328-sup-0006-AppendixS6.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150529/9/ajb21328-sup-0008-AppendixS8.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150529/10/ajb21328_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150529/11/ajb21328-sup-0001-AppendixS1.pd

Dynamic Energy Landscapes of Riboswitches Help Interpret Conformational Rearrangements and Function

Riboswitches are RNAs that modulate gene expression by ligand-induced conformational changes. However, the way in which sequence dictates alternative folding pathways of gene regulation remains unclear. In this study, we compute energy landscapes, which describe the accessible secondary structures for a range of sequence lengths, to analyze the transcriptional process as a given sequence elongates to full length. In line with experimental evidence, we find that most riboswitch landscapes can be characterized by three broad classes as a function of sequence length in terms of the distribution and barrier type of the conformational clusters: low-barrier landscape with an ensemble of different conformations in equilibrium before encountering a substrate; barrier-free landscape in which a direct, dominant “downhill” pathway to the minimum free energy structure is apparent; and a barrier-dominated landscape with two isolated conformational states, each associated with a different biological function. Sharing concepts with the “new view” of protein folding energy landscapes, we term the three sequence ranges above as the sensing, downhill folding, and functional windows, respectively. We find that these energy landscape patterns are conserved in various riboswitch classes, though the order of the windows may vary. In fact, the order of the three windows suggests either kinetic or thermodynamic control of ligand binding. These findings help understand riboswitch structure/function relationships and open new avenues to riboswitch design

Effects of polychlorinated dibenzo-p-dioxins in epidermal metabolism

The study described here was performed to investigate effects of TCDD on epidermal metabolism in TCDD sensitive C57BL/6J- and less sensitive DBA/2J-mice in vivo. TCDD and the PCDD mixtures were applied orally and topicall

EOS ® orthopaedic imaging system to study patellofemoral kinematics : Assessment of uncertainty

The author extends his thanks to Dr. A. Asselineau, Pr David Mitton, Mr. Sébastien Laporte and Mr. Benjamin Aubert for their assistance.Background:Accurate knowledge of knee joint kinematics, especially patellofemoral joint kinematics, is essential for prosthetic evaluation so as to further improve total knee arthroplasty performances. Improving the evaluation of the functioning of the extensor apparatus appears, in this respect, particularly important in this optimization effort. Objectives:The aim of this study was to propose a new experimental setup for the analysis of knee joint kinematics and to validate its relevance in terms of accuracy and uncertainty. The technique developed herein combines 3D reconstruction imaging with the use of a motion capture system. Material and methods: Eight pairs of fresh-frozen cadaver specimens with no evidence of previous knee surgery were studied using a new test rig where the femur remains fixed and the tibia is free to rotate. The flexion—extension cycles were executed using computer-controlled traction of the quadriceps tendon combined with an antagonist force applied to the distal part of the tibia. Knee joint kinematics were tracked using an optoelectronic motion capture system after a preliminary stage of data acquisition of bone geometry and markers position. This stage was carried out using a new digital stereophotogrammetric system, EOS® , combined with specific 3D reconstruction software that also determined the coordinate system used in the kinematic analysis. The resulting uncertainty was assessed as was its impact on the estimated kinematics. Results:Test results on eight knees validated the setup designed for the analysis of knee joint kinematics during the flexion—extension cycle. More specifically, the statistical results show that measurement uncertainty for rotations and translations remains below 0.4 and 1.8 mm, respectively, for the tibia and 0.4 and 1.2 mm for the patella (±2 S.D. for all four measurements)

Di(2-ethylhexyl)phthalate alters carbohydrate enzyme activities and foci incidence in rat liver.

The effect of di(2-ethylhexyl)phthalate (DEHP) on diethylnitrosamine (DEN)-initiated preneoplastic liver lesions with expression of gamma-glutamyltranspeptidase (GGTase) and loss of adenosine triphosphatase (ATPase) as well as alterations of hepatic carbohydrate metabolism in male and female Sprague-Dawley rats have been investigated. Two treatment schedules have been compared with respect to their sensitivity by the histochemical demonstration of preneoplastic islands and by the biochemical determination of alterations in enzyme activities of liver homogenates and of serum, the last indicating hepatotoxicity. For initiation, a single dose of DEN was given, followed by treatment with various doses of DEHP given three times weekly by gavage for 7 or 11 consecutive weeks. As histochemical enzyme markers, the expression of positive GGTase as well as the deficiency in ATPase were used for identification of liver foci. The weanling female rats (protocol A) were found to be more sensitive to the carcinogenic effect of DEN in view of foci incidence than the mature male rats which underwent partial hepatectomy prior to DEN application. The administration of 200 mg DEHP/kg body wt increased the incidence of ATPase-deficient foci in both male and female rats; however, concentrations of 1000 and 2000 mg DEHP/kg decreased the incidence of liver foci. The number of foci with expression of GGTase was only slightly increased in female rats following a DEHP concentration of 50 mg/kg, and 200 mg/kg body wt. DEHP alone did not induce preneoplastic lesions that could be identified by these two markers. Biochemical investigations indicate that DEHP alters the metabolic pattern in liver. An increase of the NADP-linked enzymes glucose-6-phosphate dehydrogenase (G6PDH), malic enzyme, extra-mitochondrial ICDH as well as an enhancement of NAD-dependent α-G3PDH and lactate dehydrogenase were found following DEHP administration. On the other hand the glycolytic enzymes pyruvate kinase (PK) and enolase as well as the gluconeogenetic enzyme fructose-1,6-bisphosphatase (FBPase) were significantly reduced. In protocol B (male rats) the reactions of PK, FBPase and malic enzyme were more altered after DEHP exposure than in protocol A, while the activity of G6PDH was more increased in protocol A. Most enzymes being involved in the carbohydrate metabolism are influenced by DEHP in a dose-dependent manner. There was no increase in serum FBPase activity in both male and female rats after DEHP treatment but a reduction of glutamate-oxalate-transaminase and glutamate-pyruvate-transaminase activities was observed. This and the fact that the control and DEHP-treated animals had similar weight gains indicate that DEHP does not exert a significant hepatotoxicity effect