bluuebunny/crossref_metadata_2025 huggingface dataset:
Transection of the sciatic nerve and reinnervation in adult rats: muscle and endplate morphology
Authors: IJKEMA‐PAASSEN J. , MEEK M. F. , GRAMSBERGEN A.
Published: June 2010

The functional recovery after peripheral nerve lesions is generally poor. We studied whether changes in muscles after reinnervation might explain such disappointing results. The functional recovery after peripheral nerve lesions is generally poor. Changes in muscle morphology and neuromuscular innervation might partly explain this lack of compensation. In order to test this hypothesis, we studied muscular differentiation in the soleus, gastrocnemius and tibialis anterior muscles at 7, 15 and 21 weeks after a sciatic nerve lesion in adult rats.

In the gastrocnemius and tibialis muscles the percentages of type II muscles fibres were decreased at 7 and 15 weeks but at 21 weeks they again approached normal values. The soleus muscle, however, was permanently decreased in size and this muscle, in contrast to the normal soleus muscle, contained mainly type II fibres. The morphology of the endplates showed distinct stages of degeneration and reinnervation. Two weeks after denervation, in rats in which reinnervation was prevented, all 3 muscles contained considerable numbers of morphologically abnormal endplates and, after 7 weeks, no endplates were detected. During reinnervation, endplates showing signs of acetylcholinesterase activity were observed in all 3 muscles from 7 weeks. At later ages a shift towards morphologically normal endplates occurred, but complete recovery was not observed. Endplates in all 3 muscles were polyneurally innervated at 7 weeks. Although these percentages decreased over age, polyneural innervation was still present at 21 weeks.

We conclude that the changes in the distribution of fibre types, abnormal endplate morphology and polyneural innervation may in part explain the poor functional recovery after peripheral nerve lesions.
In vivo and in vitro heel expansion in relation to shoeing and frog pressure
Authors: ROEPSTORFF L. , JOHNSTON C. , DREVEMO S.
Published: June 2010

The objective of this study was to validate a simple method to measure the mediolateral expansion of the heels and to apply this method in an in vivo experiment. It was also the aim to quantify the mediolateral expansion in different areas of the heel using an in vitro model.

In the in vitro study, 5 right and 5 left distal forelimb specimens from 5 Standardbreds were mounted vertically in a custom‐made compressive test machine. The heel expansion was measured using optical kinematic analysis and a potentiometer system. Specimens were tested unshod, with frog pressure and with the weightbearing rim raised. In the in vivo study, a potentiometer system was fitted to the left forelimb of 5 Standardbred trotters. Measurements were performed with the horses at hand, in walk and in trot. They were tested unshod, shod with a standard 8 mm iron shoe and finally with a shoe combined with an inflatable hoof‐cushion. The results showed a good correlation between the 2 measurement systems (r = 0.98).

This study describes the effect of different frog pressures on heel movement. Increased pressure on the frog and the sole increased heel expansion, but some heel expansion still occurred when the frog and sole were unsupported. The study supports, therefore, both the depression and the pressure theory. The significance of these results is the manipulation of heel movement as affected by farrier techniques and its possible relationship to health of the hoof. Further studies are needed to apply this knowledge correctly to farrier practice.
Effects of heel and toe elevation upon the digital joint angles in the standing horse
Authors: CREVIER‐DENOIX N. , ROOSEN C. , DARDILLAT C. , POURCELOT P. , JERBI H. , SANAA M. , DENOIX J.‐M.
Published: June 2010

Five sound mature horses, age 8‐14 years, with toe angles 45.5‐55.0° were placed on a specially designed platform with only the left forelimb weightbearing, which allowed the successive production of 7 different conditions of foot orientation: neutral position (N), 5, 10, 15° heel (H5, H10, H15) and toe (T5, T10, T15) elevation, performed according to 2 different sequences. For each condition, 2 lateromedial radiographs were taken to evaluate the metacarpophalangeal joint (MPJ) and both interphalangeal joint (PIPJ and DIPJ) angles, respectively. In addition, two‐dimensional (2‐D) kinematic recordings, using reflective skin markers placed laterally on the left forelimb joints, were performed. The value of each joint angle (JA) and its angular variation to N (AV) were considered for statistical analysis.

For all JA and their AV determined radiographically, the condition effect was significant and the sequence did not influence the differences between conditions. The relationships between the JA and the conditions (in the sequence: T15, T10, T5, N, H5, H10, H15) were overall linear for the 3 joints. The maximal range T15‐H15 was ± mean s.d. 6.9 ± 2.0 for MPJ (dorsal angle decrease), 7.3 ± 1.0° and 29.5 ± 1.8 for PIPJ and DIPJ (palmar angle decrease), respectively. Contrary to JA and in spite of large variations in hoof conformation, AV did not show any significant horse effect.

Wide differences were observed between the digital JA measured radiographically and from kinematics, which could be related to cutaneous displacement. Heel elevation induced elbow flexion, whereas a slight extension was observed with toe elevation. These movements, even slight (mean elbow angle amplitude: 3.6 ± 1.3), may have consequences upon flexor tendon tension.
Three‐dimensional kinematics of the proximal interphalangeal joint: effects of raising the heels or the toe
Authors: DEGUEURCE C. , CHATEAU H. , JERBI H. , CREVIER‐DENOIX N. , POURCELOT P. , AUDIGIÉ F. , PASQUI‐BOUTARD V. , GEIGER D. , DENOIX J.‐M.
Published: June 2010

The proximal interphalangeal joint (PIPJ) has always been considered as a low‐motion joint with an almost constant angle during loading of the limb. Until very recently, its motion was not taken into account in kinematic studiesin vivo. Recentin vivo studies yielded surprisingly high rangesof motion in this joint. The aim of this study was to measure, in terms of the 3 possible rotations (flexion/extension, collateromotion and axial rotation), the movements of the PIPJin vitroduring limb loading in a neutral position (500‐6000 N) and after the addition of heel and toe wedges (6° and 12°). The joint coordinate system, as it was recently described for use in the horse, was used to compute the 3 components of rotation.

With the hoof in neutral position, low‐amplitude flexion movements (7.9°) were observed. They were not associated with collateromotion or axial rotation. The flexion of the joint increased exponentially with load suggesting that, during the midstance phase, heavy loads are necessary to evoke substantial flexion. Raising the heels induced an early flexion of the joint with an increase of its total amplitude. Raising the toe produced an extension at 500 N, beyond which the amount of flexion was reduced.

These results show that PIPJ flexion/extension duringin vitroloading remains substantially smaller than suggested byin vivostudies based on skin markers. Raising the toe or heel directly affects the behaviour of this joint, but does not induce motion outside the sagittal plane. Hoof wedges are commonly used in clinical practice for purposes other than affecting PIPJ motion. In these cases, their biomechanical effects on this joint should be taken into account.
Electromyographic and kinematic indicators of fatigue in horses: a pilot study
Authors: COLBORNE G. R. , BIRTLES D. M. , CACCHIONE I. C.
Published: June 2010

Muscle fatigue can be quantified using Fourier analysis of the recorded EMG signal. Median frequency is the frequency at which the Fourier profile is bisected, and this measure typically shifts to smaller values during fatigue. This technique was combined with kinematic analysis to describe the time course of fatigue in horses galloping on an inclined treadmill. It was hypothesised that EMG median frequency would decrease in tandem with changes in kinematic variables through the exercise test. Three fit Thoroughbred horses had retroreflective markers placed on their hooves and withers. Surface electrodes were attached to the skin over the forelimb deltoid muscle. After warm‐up at walk and trot, each horse galloped at 110% VO2max on a treadmill inclined to 7.5% until fatigue onset. Kinematic data were recorded at 200 Hz for 5 s at 30s intervals, and raw EMG data were recorded at 1024 Hz for 3 s at 15 s intervals. Fatigue onset was the point in time when the horse could not keep up with the treadmill speed with minimal encouragement. One horse performed the entire exercise test on the same lead, while the other 2 horses changed leads periodically, interrupting the changes in both the EMG and kinematic measurements. Overall, through the course of the trials, mean stride length increased by 0.34 m and stride duration increased by 0.03 s. Vertical excursion of the trunk marker increased by 0.03 m. For the horse that did not change lead, median frequency of the EMG signal decreased by 36%. In the other 2 horses, lead changes were interspersed between smaller decreases in median frequency, whereupon median frequency recovered to starting levels immediately following a lead change. The median frequency decreased by 12‐20% between lead changes. Kinematic changes are more global indictors of fatigue, while the EMG indicators are dependent upon lead changes.
Locomotion evaluation for racing in Thoroughbreds
Authors: BARREY E. , EVANS S. E. , EVANS D. L. , CURTIS R. A. , QUINTON R. , ROSE R. J.
Published: June 2010

The potential racing and locomotory profile of a Thoroughbred yearling should be taken into account for its training programme and racing career. A gait test has been designed to assist the trainer in this task. The aim of this study was to investigate the temporal and kinetic locomotory variables of Thoroughbreds at the gallop, in relationship to their racing ability. Thirty Thoroughbred horses in race training were tested at maximal speed during a training session. The training exercise consisted of a warming‐up session at trot and canter for 10 min followed by a gallop session at increasing speed on a dirt track 1942 m long. The maximal speed was measured for the last 800 m before the finishing post. An accelerometric device attached to the girth provided quantitative information about the kinetic and temporal variables of the gallop such as: stride length (SL), stride frequency (SF), times elapsed between each hoof midstance phase (HIND, DIAGO, FORE), regularity of the strides (REG), mean vector of propulsion (VPROP), energy of propulsion (EPROP) and energy of loading (ELOAD). The performance records (number of wins, placings and average earning/start [PERF]) were used to analyse the relationship with the gait measurements. The mean maximum speed was 15.26 m/s. Several locomotory variables were significantly (P<0.05) correlated to the gallop speed: SL (0.90), SF (0.75), DIAGO (0.42), REG (‐0.47), VPROP (0.52), ELOAD (0.56) and EPROP (0.65). There were significant correlations between PERF and the following gait variables: REG (0.79), DIAGO (0.43), SF (0.42), SL (‐0.32) and ELOAD (‐0.40). The horses that won short distance races (<1400 m) had a larger relative ground contact duration and higher stride frequency than horses that won in longer distance races. The gait test was easy to perform and provided useful locomotory variables that may be used to evaluate the racing ability of the Thoroughbreds in training.
Changes due to age in the kinematics of trotting Andalusian foals
Authors: CANO M. R. , MIRO F. , MONTERDE J. G. , DIZ A. , MARTIN J. , GALISTEO A. M.
Published: June 2010

The purpose of this study was to evaluate the effect of growth on biokinematic characteristics at the trot in a group of 9 Andalusian foals from age 12 to 36 months in order to identify which stride variables change or remain invariable. Biokinematic analysis was performed by using a computer‐assisted videography system (25 Hz frame rate). An increase in stride length as well as the fore‐ and hindlimb stride duration was found. A tendency to increase flexion of the shoulder, elbow and carpal joints was observed while the forelimb fetlock increased its maximal extension. In the hindlimb, most of the differences were exhibited by the hip and stifle joints, which showed a tendency to a lesser flexion with age. However, at landing the extension was bigger. The hindlimb fetlock extended more in older foals, whereas flexion decreased. Significant differences in the maximal extension and flexion instants in the forelimb joints were not detected (except in the elbow joint). The same was found in the angular range of motion (ARM) of the scapula inclination and the shoulder and forelimb fetlock joints. Differences in retraction‐protraction angles in both the fore‐and hindlimbs were very slight, and ARM values for these parameters were similar in all age groups.
Body centre of mass movement in the lame horse
Authors: BUCHNER H. H. F. , OBERMÜLLER S. , SCHEIDL M.
Published: June 2010

The body centre of mass (BCM) is a key factor in the analysis of equine gait, as its position and movement determines the distribution and magnitude of loads on the limbs. Changes in the BCM movement are proposed to be important factors in the lameness management of horses. In this study, changes in the position and the 3‐dimensional (3‐D) movement of the BCM in horses with induced forelimb lameness were studied using a kinematic, segmental method.

The kinematics of 30 markers representing 20 body segments were recorded in 12 horses while trotting (3.9 m/s) on a treadmill using a high speed video system. A transient lameness model, evoking pressure‐induced pain on the hoof sole, was used to induce 2 degrees of forelimb lameness. Based on segmental inertial data from Buchneret al. (1997) 3‐D segmental centres of mass as well as the BCM were calculated. The changes in BCM movement due to lameness and the influence of selected segments on the total centre of mass were analysed.

During moderate forelimb lameness, vertical displacement of the BCM showed a 34% reduced amplitude during the stance phase of the lame limb and a 9% increased amplitude during the stance phase of the sound forelimb. In the sagittal direction, the BCM during midstance moved 9 mm backwards during the stance phase of the lame forelimb. Transversal movements showed a slight, but significant shift of the BCM to the side of the sound forelimb. Head/neck segment movement changed in a sagittal as well as in a vertical direction, but only a small amount, insufficient for considerable BCM position changes.

The results show a similar pattern of BCM and trunk movement and only small adaptations of BCM position due to lameness. The influence of the sagittal position of the BCM has to be seen as a minor factor in lameness management compared to the dynamic influences of a changed vertical BCM movement and the moment caused by the typical head and neck movement.
Assessment of gait irregularities in the horse: eye vs. gait analysis
Authors: WEISHAUPT M. A. , WIESTNER T. , HOGG H. P. , JORDAN P. , AUER J. A. , BARREY E.
Published: June 2010

The purpose of this study was to verify the sensitivity of 2 gait analysis methods in detecting subtle lameness and to compare the results to the traditional orthopaedic evaluation. Twenty‐two horses were evaluated (1) subjectively by 3 different experienced clinicians and (2) objectively with synchronised ground reaction force and accelerometric gait measurements on a treadmill. The horses were assigned for each of the 3 methods independently to one of 3 groups (GR): sound, lameness front limb, lameness hindlimb. Additionally, for each horse, the affected limb (AL) and degree of lameness (DL) were defined. The accordance between the 3 assessment methods for the categorical variables was tested with a Spearman correlation analysis. The relationship between vertical ground reaction forces and dorsoventral as well as mediolateral accelerations were studied using a Pearson correlation matrix.

Significant correlation was found between the clinical GR and GR based on force (r = 0.51, P<0.05) and acceleration data (r = 0.47, P<0.05), respectively, and between AL based on clinical and ground reaction force (r = 0.65, P<0.05) assessment. No significant correlation was found, neither for GR between the 2 measuring methods, nor for DL between the 3 assessment methods. The Pearson correlation matrix revealed significant correlations between peak vertical forces and dorsoventral acceleration in the hindlimbs. We conclude that the measurement of kinetic parameters represents a helpful complementary tool in the assessment of subtle gait alterations. However, this information needs to be interpreted carefully and always related to the clinical observation.
Three‐dimensional kinematics of the equine spine during canter
Authors: FABER M. , JOHNSTON C. , SCHAMHARDT H. C. , VAN WEEREN P. R. , ROEPSTORFF L. , BARNEVELD A.
Published: June 2010

Most research on equine kinematics has previously been performed in the walking and/or trotting animal. This is also true for the few studies on the kinematics of the equine back. These studies have, for the major part, focused on the flexion‐extension movement in the sagittal plane. However, vertebrae can rotate in 3 dimensions. This study was designed to determine all 3 rotations in various segments of the vertebral column of a cantering horse. Five Dutch Warmblood horses were measured during treadmill canter (7.3 m/s). Steinmann pins were inserted into the dorsal spinous processes of 8 thoracic (T), lumbar (L) and sacral (S) vertebrae and into bothtubera coxae.A set of 4 markers was rigidly attached to each pin. The marker data were used to calculate a rotation matrix that was subsequently decomposed into 3 orthogonal rotations (flexion/extension [FE]; lateral bending [LB] and axial rotation [AR]). For the 3 rotations the variability between the horses was low for FE, slightly larger for AR and largest for LB. The maximal range of motion (mean ± s.d.) for FE, LB and AR was 15.8 ± 1.3°, 5.2 ± 0.7° and 7.8 ± 1.2°, respectively. With respect to relative angles, the largest FE motion was found between L5 and S3 with values for the range of motion up to 8.6°. Simultaneous rotation of successive vertebrae was observed particularly during the single support and suspension phases in the stride cycle, which increases spinal stability. For all rotations, a close correlation was observed between the timing of the vertebral rotations and the pro‐ and retraction of the limbs.
Effects of treadmill speed on the mechanics of the back in the trotting saddlehorse
Authors: ROBERT C. , AUDIGIÉ F. , VALETTE J. P. , POURCELOT P. , DENOIX J.‐M.
Published: June 2010

Speed related changes in trunk mechanics have not yet been investigated, although high‐speed training is currently used in the horse. To evaluate the effects of speed on back kinematics and trunk muscles activity, 4 saddle horses were recorded while trotting on a horizontal treadmill at speeds ranging from 3.5 to 6 m/s. The 3‐dimensional (3‐D) trajectories of skin markers on the left side of the horse and the dorsal midline of the trunk were established. Electrical activity was simultaneously obtained from thelongissimus dorsi(LD) andrectus abdominis(RA) muscles using surface electrodes. Ten consecutive strides were analysed for each horse at each of the 5 velocity steps. Electromyographic and kinematic data were time‐standardised to the duration of the stride cycle and compared using an analysis of variance. The back extended during the first part of each diagonal stance phase when the RA was active and the back flexed during the second part of each diagonal stance phase when the LD was active. The onset and end of muscle activity came earlier in the stride cycle and muscle activity intensity increased when speed increased. The amplitude of vertical movement of the trunk and the maximal angles of flexion decreased with increasing speed, whereas the extension angles remained unchanged. This resulted in a decreased range of back flexion‐extension. This study confirms that the primary role of trunk muscles is to control the stiffness of the back rather than to induce movements. Understanding the effects of speed on the back of healthy horses is a prerequisite for the prevention and treatment of back pathology.
Segmentalin vivovertebral kinematics at the walk, trot and canter: a preliminary study
Authors: HAUSSLER K. K. , BERTRAM J. E. A. , GELLMAN K. , HERMANSON J. W.
Published: June 2010

Understanding the pathophysiology of equine back problems, for clinical evaluation, treatment or injury prevention, requires understanding of the normal 3‐dimensional motion characteristics of the vertebral column. Recent studies have investigated regional vertebral kinematics; however, there are no reported measures of directin vivosegmental vertebral kinematics in exercising horses. Relative movements between 2 adjacent vertebrae were recorded for 3 horses that were clinically sound and did not have a known history of a back problem. A transducer consisting of 2 fixtures and an array of liquid metal strain gauges (LMSGs) was used to measure 3‐dimensional segmental vertebral motion. The transducer was attached directly to Steinmann pins implanted in the dorsal spinous processes of adjacent vertebrae in 3 vertebral regions: thoracic (T14 to T16), lumbar (L1 to L3) and lumbosacral (L6 to S2). Rotational displacements between adjacent vertebrae were calculated from the differential outputs of the LMSG array during walk, trot and canter on a treadmill. Peak magnitudes of dorsoventral flexion, lateral bending and axial rotation were recorded continuously for each stride. The largest motion of the 3 instrumented vertebral segments was at the lumbosacral junction. In general, the greatest magnitude of segmental vertebral motion occurred during the canter and the least during the trot. The dynamic and continuous measure of 3‐dimensionalin vivosegmental vertebral motion provides an important new perspective for evaluating vertebral motion and back problems in horses.
Evaluation of the EMG activity of the long back muscle during induced back movements at stance
Authors: PEHAM C. , FREY A. , LICKA T. , SCHEIDL M.
Published: June 2010

In this study we investigated the activity of the main back muscle (Musculus longissimus) by surface electromyography (EMG) during induced extension and lateral flexion at stance. Measurements were taken of 15 horses (age 5‐20 years, 450‐700 kg bwt) without signs of back pain. Reflecting markers were placed on the head, spinous processes of T5, T12, T16, L3 and on 2 of the sacral bones. The surface EMG electrodes were situated on theMusculus longissimuson both sides of the dorsal spinous processes of T12, T16 and L3.

In all horses and all movements (extension, lateral flexion to the left and right), the EMG on both sides of the dorsal spinous process of T12 had the highest, and the EMG on both sides of the spinous process of L3, the lowest amplitude (30% of T12). At T16 the amplitude of the EMG signal was 60% of that at T12. There was no time shift between the EMG signals at the different locations (T12, T16, L3). There was a very high correlation between motion and amplitude of the EMG signal of extension, with correlation coefficients of 0.78 at L3, 0.80 at T16 and 0.75 at T12. The correlation of the lateral flexion between amplitude of the EMG and motion was lower, with 0.38 at L3, 0.43 at T16 and 0.39 at T12. This investigation showed that the EMG of theMusculus longissimusduring spinal reflexes should be derived on both sides of T12, because this is important for the clinical use of surface EMG.
The Transition Between Real and Complex Superconducting Order Parameter Phases in UPt
3
Authors: Strand J. D. , Bahr D. J. , Van Harlingen D. J. , Davis J. P. , Gannon W. J. , Halperin W. P.
Published: June 2010

Mind the Gap

The symmetry of the pairing gap is one of the most important properties of a superconductor. Whereas conventional superconductors such as lead have a gap that is uniform in momentum space, the enigmatic cuprates have point nodes and a characteristic
d
-wave symmetry. The heavy fermion compound UPt
3
has long been known to exhibit unconventional pairing. Now,

Strand
et al.

(p.
1368
) have measured the momentum space dependence of UPt
3
's superconducting gap as a function of temperature. A real gap with line nodes was observed to develop first; then, at a lower critical temperature, a complex component appeared, with the total gap expected to become fully uniform at absolute zero.
Quaternary Ammonium (Hypo)iodite Catalysis for Enantioselective Oxidative Cycloetherification
Authors: Uyanik Muhammet , Okamoto Hiroaki , Yasui Takeshi , Ishihara Kazuaki
Published: June 2010

Eye for an I

Oxidative catalysis is largely the domain of transition metals, whether iron in an enzyme, or rarer palladium in a synthetic system. These metals can efficiently shuttle between oxidation states, easing the transfer of hydrogen and oxygen atoms between hydrocarbons and oxidants.

Uyanik
et al.

(p.
1376
; see the Perspective by
French
) now show that iodine can take the place of the metal to catalytically activate peroxide during the formation of benzofuran derivatives. Pairing iodide anions with chiral ammonium cations allowed the generation of stereoselectivity at levels similar to those seen with metal complexes bearing chiral ligands.
Biodiversity Conservation Research, Training, and Policy in São Paulo
Authors: Joly Carlos A. , Rodrigues Ricardo R. , Metzger Jean Paul , Haddad Célio F. B. , Verdade Luciano M. , Oliveira Mariana C. , Bolzani Vanderlan S.
Published: June 2010

The BIOTA-FAPESP program is linking a decade of research on biodiversity into public policy in the state of São Paulo.
The Neuropeptide Oxytocin Regulates Parochial Altruism in Intergroup Conflict Among Humans
Authors: De Dreu Carsten K. W. , Greer Lindred L. , Handgraaf Michel J. J. , Shalvi Shaul , Van Kleef Gerben A. , Baas Matthijs , Ten Velden Femke S. , Van Dijk Eric , Feith Sander W. W.
Published: June 2010

Oxytocin and Intergroup Conflict

Human society is organized into groups, such as those based on nationality or religion, which can lead to intergroup conflicts, with sometimes devastating consequences. Intergroup conflict engages a human behavior termed parochial altruism: For example, a soldier who fights against the enemy at risk to themselves to protect their country is a parochial altruist.

De Dreu
et al.

(p.
1408
; see the cover; see the News story by

Miller

) have discovered a role for oxytocin, a neuropeptide produced in the hypothalamus, in regulating parochial altruism during human intergroup competition and conflict. Oxytocin is already known to play a role in trusting behavior, and naturally occurring genetic variants of the oxytocin receptor exist within the human population. Administration of oxytocin modulated defense-related aggression toward competing groups, but did not affect unprovoked, hateful behavior. Thus, there may be a neurobiological basis for intergroup conflict in humans.
Getting to the Critical Nucleus of Aerosol Formation
Authors: Zhang Renyi
Published: June 2010

A better understanding of how aerosols form in the atmosphere could greatly improve climate models.
Clean, Green Chiral Reactions—Just Add a Salt
Authors: French Andrew N.
Published: June 2010

An ammonium iodide salt can perform selective organic oxidation reactions and replace more toxic metal catalysts.
Warm-Blooded “Sea Dragons”?
Authors: Motani Ryosuke
Published: June 2010

Marine reptiles from the Age of Dinosaurs could maintain a constant body temperature.
Pulling Apart Molecular Magnetism
Authors: Jarillo-Herrero Pablo
Published: June 2010

Mechanical control can be used to probe and tune the magnetic properties of single molecules.
Beyond
Kon-Tiki
: Did Polynesians Sail to South America?
Authors: Lawler Andrew
Published: June 2010

After decades of taboo and controversy, Pacific Rim archaeologists are finding new evidence that Polynesians reached South America before Europeans did, voyaging across the world's largest ocean around 1200 C.E.
Changing Time in the South Pacific
Authors: Lawler Andrew
Published: June 2010

Archaeologists are deeply at odds over when Polynesians fanned out across the vast northern, central, and eastern Pacific Ocean. For the moment, those who argue for a swift and late settlement seem to have the upper hand.
Northern Exposure in Doubt
Authors: Lawler Andrew
Published: June 2010

While researchers are making strides in demonstrating a connection between South America and Polynesia, the idea that California Indians learned from Hawaiians faces an uphill struggle. Questions about timing make many archaeologists skeptical.
Gatekeeper Mutations Mediate Resistance to BRAF-Targeted Therapies
Authors: Whittaker Steven , Kirk Ruth , Hayward Robert , Zambon Alfonso , Viros Amaya , Cantarino Neus , Affolter Annette , Nourry Arnaud , Niculescu-Duvaz Dan , Springer Caroline , Marais Richard
Published: June 2010

Gatekeeper mutations in BRAF confer drug resistance.
Systemic Delivery of scAAV9 Expressing SMN Prolongs Survival in a Model of Spinal Muscular Atrophy
Authors: Valori Chiara F. , Ning Ke , Wyles Matthew , Mead Richard J. , Grierson Andrew J. , Shaw Pamela J. , Azzouz Mimoun
Published: June 2010

An adeno-associated virus vector expressing the survival motor neuron protein rescues mice with spinal muscular atrophy.
Micrometastases + Math = Model of Breast Cancer Dormancy
Authors: Hansel Donna E.
Published: June 2010

Mathematical modeling helps predict the extent of dormant breast cancer micrometastases.
Stretching for Good Blood Vessels
Authors: Ng Kenneth W.
Published: June 2010

Dynamic stretching improves the mechanical strength of foreign body vascular grafts for potential use in vascular bypass surgery.
Characterization of Immune Responses to Capsid Protein p24 of Human Immunodeficiency Virus Type 1 and Implications for Detection
Authors: Tang Shixing , Zhao Jiangqin , Wang Aifeng , Viswanath Ragupathy , Harma Harri , Little Richard F. , Yarchoan Robert , Stramer Susan L. , Nyambi Phillipe N. , Lee Sherwin , Wood Owen , Wong Eric Y. , Wang Xue , Hewlett Indira K.
Published: June 2010

To further refine our current nanoparticle-based HIV-1 p24 antigen assay, we investigated immune responses to p24 to identify diagnostically significant immune dominant epitopes (IDEs) in HIV-infected human sera, to address cross-reactivity of anti-p24 antibodies to different subtypes, and to identify new biomarkers that distinguish acute from chronic HIV infection for more accurate incidence estimation. We identified two major linear epitope regions, located in the CypA binding loop and adjacent helices and at the end of the C-terminal domain. Most sera (86%) from acutely HIV-1-infected individuals reacted with multiple peptides, while 60% and 30% of AIDS patient samples reacted with multiple and single peptides, respectively. In contrast, 46% and 43% of chronically HIV-1-infected individuals reacted with one and none of the peptides, respectively, and only 11% reacted with multiple p24 peptides, indicating a progression of immune responses from polyclone-like during acute infection to monoclone-like or a nonresponse to linear epitopes during chronic infection. Anti-p24 antibodies (subtype B) show broad cross-reactivity to different HIV-1 subtypes, and the synergistic action of different combinations of anti-HIV antibodies improves capture and detection of divergent HIV-1 subtypes. Our results indicate that the modified peptide immunoassay is sensitive and specific for the rapid identification of HIV-1 p24 IDEs and for investigation of immune responses to p24 during natural HIV-1 infection. The data provide the foundation for development and refinement of new assays for improved p24 antigen testing as future tools for rapid and accurate diagnosis as part of early intervention strategies and estimations of incidence.
Establishment of an Aerosol Challenge Model of Tuberculosis in Rhesus Macaques and an Evaluation of Endpoints for Vaccine Testing
Authors: Sharpe S. A. , McShane H. , Dennis M. J. , Basaraba R. J. , Gleeson F. , Hall G. , McIntyre A. , Gooch K. , Clark S. , Beveridge N. E. R. , Nuth E. , White A. , Marriott A. , Dowall S. , Hill A. V. S. , Williams A. , Marsh P. D.
Published: June 2010

The establishment of an aerosol challenge model in nonhuman primates (NHPs) for the testing of vaccines against
Mycobacterium tuberculosis
would assist the global effort to optimize novel vaccination strategies. The endpoints used in preclinical challenge studies to identify measures of disease burden need to be accurate and sensitive enough to distinguish subtle differences and benefits afforded by different tuberculosis (TB) vaccine regimens when group sizes are inevitably small. This study sought to assess clinical and nonclinical endpoints as potentially sensitive measures of disease burden in a challenge study with rhesus macaques by using a new protocol of aerosol administration of
M. tuberculosis
. Immunological and clinical readouts were assessed for utility in vaccine evaluation studies. This is the first example of TB vaccine evaluation with rhesus macaques where long-term survival was one of the primary endpoints. However, we found that in NHP vaccine efficacy studies with maximum group sizes of six animals, survival did not provide a valuable endpoint. Two approaches used in human clinical trials for the evaluation of the gamma interferon (IFN-γ) response to vaccination (enzyme-linked immunospot [ELISpot] assay and enzyme-linked immunosorbent assay [ELISA]) were included in this study. The IFN-γ profiles induced following vaccination were found not to correlate with protection, nor did the level of purified protein derivative (PPD)-specific proliferation. The only readout to reliably distinguish vaccinated and unvaccinated NHPs was the determination of lung lesion burden using magnetic resonance (MR) imaging combined with stereology at the end of the study. Therefore, the currently proposed key markers were not shown to correlate with protection, and only imaging offered a potentially reliable correlate.
Identification of
Mycoplasma mycoides
subsp.
mycoides
Small Colony Genes Coding for T-Cell Antigens
Authors: Totté Philippe , Mather Arshad , Reslan Lina , Boublik Yvan , Niang Mamadou , Du Plessis Dion , Dedieu Laurence
Published: June 2010

Genes of the
Mycoplasma mycoides
subsp
. mycoides
small colony biotype (
Mmm
SC) coding for proteins capable of eliciting protective T-cell memory responses have potential for incorporation into a recombinant subunit vaccine against contagious bovine pleuropneumonia (CBPP). Here we used lymphocytes from cattle that had completely recovered from infection to screen products of
Mmm
SC genes for recognition by CD4
+
effector memory (Tem) and central memory (Tcm) T lymphocytes. Six
Mmm
SC genes (
abc
,
gapN
,
glpO
,
lppA
,
lppB
, and
ptsG
) were expressed as histidine-tagged recombinant polypeptides, or synthetic overlapping peptides, before inclusion in proliferation and gamma interferon (IFN-γ) assays. Only two
Mmm
SC antigens, LppA and PtsG, consistently induced recall proliferation from immune CD4
+
T cells and IFN-γ production in all animals tested. Moreover, LppA and PtsG were shown to possess epitopes recognized by both short-lived CD4
+
Tem and long-lived CD4
+
Tcm cells.
Diagnosis of Amebic Liver Abscess and Amebic Colitis by Detection of
Entamoeba histolytica
DNA in Blood, Urine, and Saliva by a Real-Time PCR Assay
Authors: Haque Rashidul , Kabir Mamun , Noor Zannatun , Rahman S. M. Mazidur , Mondal Dinesh , Alam Faisal , Rahman Intekhab , Al Mahmood Abdullh , Ahmed Nooruddin , Petri William A.
Published: June 2010

The noninvasive diagnosis of amebic liver abscess is challenging, as most patients at the time of diagnosis do not have a concurrent intestinal infection with
Entamoeba histolytica
. Fecal testing for
E. histolytica
parasite antigen or DNA is negative in most patients. A real-time PCR assay was evaluated for detection of
E. histolytica
DNA in blood, urine, and saliva samples from amebic liver abscess as well as amebic colitis patients in Bangladesh. A total of 98 amebic liver abscess and 28 amebic colitis patients and 43 control subjects were examined. The real-time PCR assay detected
E. histolytica
DNA in 49%, 77%, and 69% of blood, urine, and saliva specimens from the amebic liver abscess patients. For amebic colitis the sensitivity of the real-time PCR assay for detection of
E. histolytica
DNA in blood, urine, and saliva was 36%, 61%, and 64%, respectively. All blood, urine, and saliva samples from control subjects were negative by the real-time PCR assay for
E. histolytica
DNA. When the real-time PCR assay results of the urine and saliva specimens were taken together (positive either in urine or saliva), the real-time PCR assay was 97% and 89% sensitive for detection of
E. histolytica
DNA in liver abscess and intestinal infection, respectively. We conclude that the detection of
E. histolytica
DNA in saliva and urine could be used as a diagnostic tool for amebic liver abscess.
Potency of Anidulafungin Compared to Nine Other Antifungal Agents Tested against
Candida
spp.,
Cryptococcus
spp., and
Aspergillus
spp.: Results from the Global SENTRY Antimicrobial Surveillance Program (2008)
Authors: Messer Shawn A. , Jones Ronald N. , Moet Gary J. , Kirby Jeffrey T. , Castanheira Mariana
Published: June 2010

The SENTRY Antimicrobial Surveillance Program regularly monitors global susceptibility rates for a spectrum of both novel and established antifungal agents. Anidulafungin and the other echinocandins displayed sustained, excellent activity against
Candida
spp. and
Aspergillus fumigatus
, with ≥98% of MIC results at ≤2 μg/ml. Six yeast isolates (all
Candida glabrata
) showing caspofungin MIC values of ≥0.5 μg/ml were further analyzed for potential
fks
hot spot (HS) mutations; three isolates had confirmed mutations in the
fks1
HS1 region (S645P), and three exhibited mutations in the
fks2
HS1 region (S645F and S645P).
Quantitative Analysis of a Urine-Based Assay for Detection of Lipoarabinomannan in Patients with Tuberculosis
Authors: Shah Maunank , Martinson Neil A. , Chaisson Richard E. , Martin Desmond J. , Variava Ebrahim , Dorman Susan E.
Published: June 2010

Urinary lipoarabinomannan (LAM) detection is a promising approach for rapid diagnosis of active tuberculosis (TB). In microbiologically confirmed TB patients, quantitative LAM detection results increased progressively with bacillary burden and immunosuppression. Patients with disseminated TB and/or advanced HIV are target populations for whom urine LAM detection may be particularly useful.
Helcococcus kunzii
Isolated from a Sow with Purulent Urocystitis
Authors: Grattarola Carla , Bellino Claudio , Tursi Massimiliano , Maggi Elisa , D'Angelo Antonio , Gianella Paola , Dondo Alessandro , Cagnasso Aurelio
Published: June 2010

Helcococcus kunzii
has never been reported in veterinary medicine. The isolation of
H. kunzii
from a sow with purulent urocystitis is described, suggesting this organism's potential pathogenic role in swine.
Development and Evaluation of a Novel Single-Nucleotide-Polymorphism Real-Time PCR Assay for Rapid Detection of Fluoroquinolone-Resistant
Mycoplasma bovis
Authors: Ben Shabat M. , Mikula I. , Gerchman I. , Lysnyansky I.
Published: June 2010

Monitoring of the susceptibility of
Mycoplasma bovis
field isolates to antibiotics is important for the appropriate choice of treatment. However,
in vitro
susceptibility testing of mycoplasmas is technically demanding and time-consuming, especially for clinical isolates, and is rarely performed in mycoplasma diagnostic laboratories. Thus, the development of methods allowing rapid real-time detection of resistant strains of
M. bovis
in clinical samples is a high priority for successful treatment. In this study, a novel TaqMan single-nucleotide-polymorphism (SNP) real-time PCR assay, which enables the rapid identification of
M. bovis
strains with different susceptibilities to fluoroquinolones, was developed and evaluated. The TaqMan SNP real-time PCR assay is based on the amplification of a 97-bp fragment of the
parC
quinolone resistance-determining region (QRDR) and allows the specific detection of four possible genotypes: GAC or GAT (susceptible to fluoroquinolones) and AAC or AAT (resistant to fluoroquinolones). Four TaqMan minor groove binder (MGB) probes identifying 1-base mismatches were designed and applied in a dual-probe assay with two reaction tubes. The TaqMan SNP real-time PCRs developed are highly specific for
M. bovis
, with a detection limit of 5 fg/μl (about 5
M. bovis
genomes). In addition, all four SNP real-time PCR tests have almost the same efficiency (97.7% [GAC], 94% [AAC], 99.99% [GAT], and 98% [AAT]). Taken together, the data suggest that this SNP real-time PCR assay has potential as a routine diagnostic test for the detection of decreased susceptibility of
M. bovis
to fluoroquinolones.
Ancestral Lineages of Human Enterotoxigenic
Escherichia coli
Authors: Steinsland Hans , Lacher David W. , Sommerfelt Halvor , Whittam Thomas S.
Published: June 2010

Enterotoxigenic
Escherichia coli
(ETEC) is a common cause of diarrhea among children living in and among travelers visiting developing countries. Human ETEC strains represent an epidemiologically and phenotypically diverse group of pathogens, and there is a need to identify natural groupings of these organisms that may help to explain this diversity. Here, we sought to identify most of the important human ETEC lineages that exist in the
E. coli
population, because strains that originate from the same lineage may also have inherited many of the same epidemiological and phenotypic traits. We performed multilocus sequence typing (MLST) on 1,019 ETEC isolates obtained from humans in different countries and analyzed the data against a backdrop of MLST data from 1,250 non-ETEC
E. coli
and eight ETEC isolates from pigs. A total of 42 different lineages were identified, 15 of which, representing 792 (78%) of the strains, were estimated to have emerged >900 years ago. Twenty of the lineages were represented in more than one country. There was evidence of extensive exchange of enterotoxin and colonization factor genes between different lineages. Human and porcine ETEC have probably emerged from the same ancestral ETEC lineage on at least three occasions. Our findings suggest that most ETEC strains circulating in the human population today originate from well-established, globally widespread ETEC lineages. Some of the more important lineages identified here may represent a smaller and more manageable target for the ongoing efforts to develop effective ETEC vaccines.
The Lytic Transcriptome of Kaposi's Sarcoma-Associated Herpesvirus Reveals Extensive Transcription of Noncoding Regions, Including Regions Antisense to Important Genes
Authors: Chandriani Sanjay , Xu Yiyang , Ganem Don
Published: June 2010

Genomewide analyses of the mammalian transcriptome have revealed that large tracts of sequence previously annotated as noncoding are frequently transcribed and give rise to stable RNA. Although the transcription of individual genes of the Kaposi's sarcoma-associated herpesvirus (KSHV) has been well studied, little is known of the architecture of the viral transcriptome on a genomewide scale. Here we have employed a genomewide tiling array to examine the lytic transcriptome of the Kaposi's sarcoma-associated herpesvirus, KSHV. Our results reveal that during lytic growth (but not during latency), there is extensive transcription from noncoding regions, including both intergenic regions and, especially, noncoding regions antisense to known open reading frames (ORFs). Several of these transcripts have been characterized in more detail, including (i) a 10-kb RNA antisense to the major latency locus, including many of its microRNAs as well as its ORFs; (ii) a 17-kb RNA antisense to numerous ORFs at the left-hand end of the genome; and (iii) a 0.7-kb RNA antisense to the viral homolog of interleukin-6 (vIL-6). These studies indicate that the lytic herpesviral transcriptome resembles a microcosm of the host transcriptome and provides a useful system for the study of noncoding RNAs.
Selective Induction of Host Genes by MVA-B, a Candidate Vaccine against HIV/AIDS
Authors: Guerra Susana , González José Manuel , Climent Núria , Reyburn Hugh , López-Fernández Luis A. , Nájera José L. , Gómez Carmen E. , García Felipe , Gatell José M. , Gallart Teresa , Esteban Mariano
Published: June 2010

The aim of this study was to define the effects on antigen-presenting cells of the expression of HIV antigens from an attenuated poxvirus vector. We have analyzed the transcriptional changes in gene expression following infection of human immature monocyte-derived dendritic cells (DC) with recombinant modified vaccinia virus Ankara (MVA) expressing the genes encoding the gp120 and Gag-Pol-Nef antigens of HIV type 1 clade B (referred to as MVA-B) versus parental MVA infection. Using microarray technology and real-time reverse transcription-PCR, we demonstrated that the HIV proteins induced the expression of cytokines, cytokine receptors, chemokines, chemokine receptors, and molecules involved in antigen uptake and processing, including major histocompatibility complex (MHC) genes. Levels of mRNAs for interleukin-1, beta interferon, CCR8, and SCYA20 were higher after HIV antigen production. MVA-B infection also modulated the expression of antigen processing and presentation genes: the gene for MICA was upregulated, whereas those for HLA-DRA and HSPA5 were downregulated. Indeed, the increased expression of the gene for MICA, a glycoprotein related to major histocompatibility complex class I molecules, was shown to enhance the interaction between MVA-B-infected target cells and cytotoxic lymphocytes. The expression profiles of the genes for protein kinases such as JAK1 and IRAK2 were activated after HIV antigen expression. Several genes included in the JAK-STAT and mitogen-activated protein kinase signaling pathways were regulated after HIV antigen expression. Our findings provide the first gene signatures in DC of a candidate MVA-B vaccine expressing four HIV antigens and identified the biological roles of some of the regulatory genes, like that for MICA, which will help in the design of more effective MVA-derived vaccines.
Role of the Kaposi's Sarcoma-Associated Herpesvirus K15 SH3 Binding Site in Inflammatory Signaling and B-Cell Activation
Authors: Pietrek Marcel , Brinkmann Melanie M. , Glowacka Ilona , Enlund Anette , Hävemeier Anika , Dittrich-Breiholz Oliver , Kracht Michael , Lewitzky Marc , Saksela Kalle , Feller Stephan M. , Schulz Thomas F.
Published: June 2010

The Kaposi's sarcoma-associated herpesvirus (KSHV) contains several open reading frames (ORFs) that encode proteins capable of initiating and modulating cellular signaling pathways. Among them is ORF K15, encoding a 12-transmembrane-spanning protein with a cytoplasmic C-terminal domain. Through conserved binding motifs, such as Src homology 2 (SH2) and SH3 binding sites, K15 interacts with cellular proteins, activates the NF-κB, MEK/Erk, and Jun N-terminal protein kinase (JNK) pathways, and induces the expression of several inflammatory and angiogenic genes. In this study, we investigated the role of an SH3 domain binding site centered on a PPLP motif in K15. We screened libraries of cellular SH3 domains to identify signaling molecules interacting with the KSHV PPLP motif. We found its affinities for two Src kinase family members, Lyn and Hck, to exceed those of other viral proteins. While the SH2 binding motif YEEV is essential for the inflammatory response induced by KSHV K15, recruitment of Lyn and Hck to the K15 PPLP motif seems to be dispensable for this inflammatory response. However, the PPLP motif is essential for the decrease in B-cell receptor-mediated signaling induced by K15, as measured by calcium mobilization assays.