Photoperiod and larval body size: integrated factors controlling onset of the moulting cycle in Heliconius melpomene (Lepidoptera)

In Heliconius melpomene , ecdysis to each stadium is asynchronous in continuous light, but is synchronized with respect to the time of day in an LD 12:12 photoperiod regime-generally occurring during the early part of the photophase. This is a consequence of synchronism in the time of day of onset of the moulting cycle, which occurs approximately 24 hours before ecdysis. There is variation in the number of days taken to complete an instar, however. Onset of the moulting cycle is gated by photoperiod, and occurs at the first gate following attainment by the larvae of a certain threshold size, indicated by weight. By depriving larvae of food, the time at which threshold size is obtained can be delayed; this results in a delay in the time of onset of the moulting cycle. Possible biological advantages in the wild of the existence of a threshold size for onset of the moulting cycle, and of synchronism in the time of day of ecdysis, have been suggested.     

Apport de la fusion d’images tomoscintigraphiques avec la tomodensitométrie X ou l’imagerie par résonance magnétique en pathologie osseuse : expérience du service de médecine nucléaire de Sfax

The aim of our study was to assess the contribution of image fusion of SPECT combined with computed tomography (SPECT-CT) or magnetic resonance imaging (SPECT-MRI) in our daily practice of bone scintigraphy. Seventeen patients underwent a SPECT image fusion, SPECT-CT or MRI in addition to conventional bone scintigraphy. These acquisitions are made separately with images stored in DICOM format. The fusion was operated after a manual coregistration of the images. Results show that in 35.29% of cases, the image fusion allowed to pinpoint the exact location of increased uptake seen on the whole body scan and/or on static images. In 35.29% of cases, the fusion has confirmed a diagnosis doubtful in planar imaging. In five patients, representing 29.41% of cases, the fusion has corrected a diagnosis. In one patient (5.88% of cases), the fusion has eliminated a false positive related to increased uptake visualized on the whole body scan. In two patients (11.11% of cases), the fusion has eliminated false negative of bone scan in one case and of MRI in the other case. Finally, in nine patients (50% of cases), the fusion has influenced the therapeutic management.     

In vivo respiratory-gated micro-CT imaging in small-animal oncology models

Micro-computed tomography(micro-CT) is becoming an accepted research tool for the noninvasive examination of laboratory animals such as mice and rats, but to date, in vivo scanning has largely been limited to the evaluation of skeletal tissues. We use a commercially available micro-CT device to perform respiratory gated in vivo acquisitions suitable for thoracic imaging. The instrument is described, along with the scan protocol and animal preparation techniques. Preliminary results confirm that lung tumors as small as 1 mm in diameter are visible in vivo with these methods. Radiation dose was evaluated using several approaches, and was found to be approximately 0.15 Gy for this respiratory-gated micro-CT imaging protocol. The combination of high-resolution CT imaging and respiratory-gated acquisitions appears well-suited to serial in vivo scanning.     

The mechanical properties of tail tendon fascicles from lubricin knockout, wild type and heterozygous mice

The purpose of this study was to analyze the effects of lubricin on tendon stiffness and viscoelasticity.A total of 36 mice were tested with 12 mice in each of the following groups: lubricin knock-out (−/−), heterozygous (+/−) and wild-type (+/+). A ramp test was used to determine the elastic modulus by pulling the fascicles to 2.5% strain amplitude at a rate of 0.05 mm/s. Then, followed by a relaxation test that pulled the fascicles to 5% strain amplitude at a rate of 2 mm/s. The fascicles were allowed to relax for 2 min at the maximum strain and a single-cycle relaxation ratio was used to characterize viscoelastic properties.There was no significant difference in the Young’s modulus between the three groups (p > 0.05), but the knockout mice had a significantly (p < 0.05) lower relaxation ratio than the wild type mice.Based on these data, we concluded that lubricin expression has an effect on the viscoelastic properties of tendon fascicles. The clinical significance of this finding, if any, remains to be demonstrated.     

Pituitary Mri Findings in Patients With Pituitary and Ectopic Acth-Dependent Cushing Syndrome: Does A 6-Mm Pituitary Tumor Size Cut-Off Value Exclude Ectopic Acth Syndrome?

Objective: Expert opinion and a consensus statement on Cushing syndrome (CS) indicate that in a patient with a clinical presentation and biochemical studies consistent with a pituitary etiology, the presence of a pituitary tumor ≥6 mm is highly suggestive of Cushing disease (CD). The purpose of the present study was to determine the optimal pituitary tumor size that can differentiate between patients with CD and ectopic adrenocorticotrophic hormone (ACTH) secretion (EAS) and obviate the need for inferior petrosal sinus sampling (IPSS).Methods: We performed a retrospective study of 130 patients seen between 2000 and 2012 including 104 patients with CD and 26 patients with EAS.Results: A pituitary lesion was reported in 6/26 (23%) patients with EAS and 71/104 (68.3%) patients with CD, with median (range) sizes of 5 mm (3–14) and 8 mm (2–31), respectively. All tumors in the EAS group measured ≤6 mm except for 1 that measured 14 mm. The presence of a pituitary tumor >6 mm in size had 40% sensitivity and 96% specificity for the diagnosis of CD. ACTH levels >209 pg/mL and serum potassium <2.7 mmol/L were found in patients with EAS. All patients with EAS had a 24-hour urine free cortisol (UFC) >3.4 times the upper limit of normal (×ULN)Conclusion: Pituitary incidentalomas as large as 14 mm in size can be seen in patients with EAS. However, the 6-mm tumor size cut-off value provided 96% specificity and may be a reasonable threshold to proceed with surgery without the need for IPSS when the biochemical data support a pituitary etiology.Abbreviations: ACTH = adrenocorticotropic hormone CD = Cushing disease CRH = corticotropin-releasing hormone CS = Cushing syndrome EAS = ectopic ACTH secretion IPSS = inferior petrosal sinus sampling HDDST = high-dose dexamethasone suppression test LDDST = low-dose dexamethasone suppression test MRI = magnetic resonance imaging UFC = urine free cortisol ULN = upper limit of normal     

Geraniol inhibits prostate cancer growth by targeting cell cycle and apoptosis pathways

The progression of prostate cancer is associated with escape from cell cycle arrest and apoptosis under androgen-depleted conditions. Here, we found that geraniol, a naturally occurring monoterpene, induces cell cycle arrest and apoptosis in cultured cells and tumor grafted mice using PC-3 prostate cancer cells. Geraniol modulated the expression of various cell cycle regulators and Bcl-2 family proteins in PC-3 cells in vitro and in vivo. Furthermore, we showed that the combination of sub-optimal doses of geraniol and docetaxel noticeably suppresses prostate cancer growth in cultured cells and tumor xenograft mice. Therefore, our findings provide insight into unraveling the mechanisms underlying escape from cell cycle arrest and apoptosis and developing therapeutic strategies against prostate cancer.     

An Emerging Allee Effect Is Critical for Tumor Initiation and Persistence

Tumor cells develop different strategies to cope with changing microenvironmental conditions. A prominent example is the adaptive phenotypic switching between cell migration and proliferation. While it has been shown that the migration-proliferation plasticity influences tumor spread, it remains unclear how this particular phenotypic plasticity affects overall tumor growth, in particular initiation and persistence. To address this problem, we formulate and study a mathematical model of spatio-temporal tumor dynamics which incorporates the microenvironmental influence through a local cell density dependence. Our analysis reveals that two dynamic regimes can be distinguished. If cell motility is allowed to increase with local cell density, any tumor cell population will persist in time, irrespective of its initial size. On the contrary, if cell motility is assumed to decrease with respect to local cell density, any tumor population below a certain size threshold will eventually extinguish, a fact usually termed as Allee effect in ecology. These results suggest that strategies aimed at modulating migration are worth to be explored as alternatives to those mainly focused at keeping tumor proliferation under control.     

Paclitaxel stimulates chromosomal fusion and instability in cells with dysfunctional telomeres: implication in multinucleation and chemosensitization

The anticancer effect of paclitaxel is attributable principally to irreversible promotion of microtubule stabilization and is hampered upon development of chemoresistance by tumor cells. Telomere shortening, and eventual telomere erosion, evoke chromosomal instability, resulting in particular cellular responses. Using telomerase-deficient cells derived from mTREC−/−p53−/− mice, here we show that, upon telomere erosion, paclitaxel propagates chromosomal instability by stimulating chromosomal end-to-end fusions and delaying the development of multinucleation. The end-to-end fusions involve both the p- and q-arms in cells in which telomeres are dysfunctional. Paclitaxel-induced chromosomal fusions were accompanied by prolonged G2/M cell cycle arrest, delayed multinucleation, and apoptosis. Telomere dysfunctional cells with mutlinucleation eventually underwent apoptosis. Thus, as telomere erosion proceeds, paclitaxel stimulates chromosomal fusion and instability, and both apoptosis and chemosensitization eventually develop.     

THE CIRCADIAN CLOCK GENE PER1 SUPPRESSES CANCER CELL PROLIFERATION AND TUMOR GROWTH AT SPECIFIC TIMES OF DAY

Cell cycle progression is tightly regulated. The expressions of cell cycle regulators, the products of which either promote or inhibit cell proliferation, oscillate during each cell cycle. Cellular proliferation and the expression of cell cycle regulators are also controlled by the circadian clock. Disruption of the circadian clock may thereby lead to deregulated cell proliferation. Mammalian Per2 is a core clock gene, the product of which suppresses cancer cell proliferation and tumor growth in vivo and in vitro. Because Per1, another key clock gene, is mutated in human breast cancers, and because its clock functions are similar and complementary to those of Per2, we have studied its role in modulating breast cancer cell proliferation and tumor growth. We find that breast cancer growth rate is gated by the circadian clock with two daily peaks and troughs, and that they are coupled to the daily expression patterns of clock-controlled genes that regulate cell proliferation. Down-regulation of the expression of tumor Per1 increases cancer cell growth in vitro and tumor growth in vivo by enhancing the circadian amplitude of the two daily tumor growth peaks. The data of the study suggest Per1 has tumor-suppressor function that diminishes cancer proliferation and tumor growth, but only at specific times of day. (Author correspondence: williamhrushesky@gmail.com).     

Recovery cycle of neurons in the inferior colliculus of the FM bat determined with varied pulse-echo duration and amplitude

The recovery cycle of auditory neurons is an important neuronal property which underlies a bat's ability in analyzing returning echoes and to determine target distance (i.e., echo ranging). In the same token, duration selectivity of auditory neurons plays an important role in pulse recognition in bat echolocation. Because insectivorous bats progressively vary the pulse parameters (repetition rate, duration, and amplitude) during hunting, the recovery cycle of auditory neurons is inevitably affected by their selectivity to other co-varying echo parameters. This study examines the effect of pulse duration and amplitude on recovery cycle of neurons in the central nucleus of the inferior colliculus (IC) of the FM bat, Pipistrellus abramus, using biologically relevant pulse-echo (P-E) pairs with varied duration and amplitude difference. We specifically examine how duration selectivity may affect a neuron's recovery cycle. IC neurons have wide range of recovery cycle and best duration (BD) covering P-E intervals and duration occurring different phases of hunting. The recovery cycle of most IC neurons increases with P-E duration and amplitude difference. Most duration-selective IC neurons recover rapidly when stimulated with biologically relevant P-E pairs. As such, neurons with short BD recover rapidly when stimulated with P-E pairs of short duration and small P-E amplitude difference. Conversely, neurons with long BD recover rapidly when stimulated with P-E pairs of long duration and large P-E amplitude difference. These data suggest that bats may potentially utilize the response of IC neurons with different BD and recovery cycle to effectively perform echo detection, recognition of echo duration and echo ranging throughout a target approaching sequence.     

Correction de mouvement respiratoire en TEP/TDM

Respiratory motion reduces overall qualitative and quantitative accuracy in emission tomography imaging. The impact of respiratory motion has been further highlighted in the use of multi-modality imaging devices, where differences in respiratory conditions between the acquisition of anatomical and functional datasets can lead to significant artefacts. Current state of the art in accounting for such effects is the use of respiratory-gated acquisitions. Although such acquisitions may lead to a certain reduction in respiratory motion effects, the improvement is reduced as a result of using only part of the available data to reconstruct the individual gated frames. Approaches to correct the differences in the respiratory motion between the individual gated frames, in order to allow their combination, can be divided in two categories, namely, image or raw data based. The image-based approaches make use of registration algorithms to realign the gated images and, subsequently, sum them together; while the raw data approaches, based on the incorporation of transformations, account for differences in the respiratory motion between individual frames, either prior or during the reconstruction of all of the acquired data. Previous research in this field has demonstrated that a non-rigid local-based model leads to better results compared with an affine model in accounting for respiratory motion between gated frames. In addition, a superior image contrast can be obtained by incorporating the necessary transformation in the reconstruction process in comparison to an image-based approach.     

Coding of sinusoidally amplitude modulated acoustic stimuli in the inferior colliculus of the rufous horseshoe bat,Rhinolophus rouxi

Summary Single neuron responses to sinusoidally amplitude modulated (SAM) signals were studied in the inferior colliculus of the horseshoe bat,Rhinolophus rouxi.57% of the neurons responded to SAM stimuli with periodical discharges synchronized to the modulation cycle. The proportion of cells driven by amplitude modulated signals was independent of the best frequency of the neurons. Best modulation frequencies were at or below 100 Hz in about 70% of the neurons. Synchronized activity could be elicited by modulation frequencies up to 400 Hz.Best SAM responses were observed at stimulus intensities 10 dB above threshold. Generally the BMF of a neuron did not change with intensity. The BMF decreased with decreasing modulation depth of the amplitude modulation.A trend for a topographical organization of neurons according to best modulation frequencies was detected. The results did not reveal any significant specialization of the bat's auditory system for coding of amplitude modulations as compared to other mammals.Abbreviations BF best frequency - BMF best modulation frequency - CF constant frequency - FM frequency modulation - IC inferior colliculus - SAM sinusoidal amplitude modulation - SFM sinusoidal frequency modulation     

Population Biology and Breeding Period of the Sand-Bubbler Crab <Emphasis Type="Italic">Dotilla Fenestrata</Emphasis> (Brachyura: Ocypodidae) from Southern Mozambique

The sand-bubbler crab Dotilla fenestrata (Hilgendorf, 1869) is the most common and abundant brachyuran in the intertidal area of many East African sandy shores. Monthly sampling surveys were performed from March 2001 to February 2002 at Praia do Triunfo, Southern Mozambique. At each sampling survey, 15 stations (0.25 m²) were sampled to a depth sediment of 30 cm. Crabs were identified, sexed, and measured for carapace width (mm). A total of 2456 crabs were collected of which 1247 were males (mean ± sd: 5.36 ± 0.04 mm), 938 non-ovigerous females (5.03 ± 0.03 mm) and 271 ovigerous females (5.15 ± 0.06 mm). The overall size frequency distribution showed a unimodal pattern suggesting a stable population with continuous recruitment. A clear sexual dimorphism was observed, with males being larger than ovigerous females, which in turn, were larger than non-ovigerous females. The overall sex ratio did not differ from 1:1. The annual reproductive cycle of Dotilla fenestrata was continuous and ovigerous females were recorded throughout the year, with peaks of occurrence during the warmer months (February–August). Despite of this continuous cycle, few juveniles were observed during the study period. These observations and the maximum size attained by adults supports the hypothesis that for this burrowing crab, recruitment may occur in different habitat than that occupied by adults. However, the studied area is favourable for growth, since the analysed population attains sexual maturity in smaller sizes than that from close areas.     

Cholesterol depletion-induced inhibition of stretch-activated channels is mediated via actin rearrangement

Cholesterol is a critical regulator of lipid bilayer dynamics and plasma membrane organization in eukaryotes. A variety of ion channels have been shown to be modulated by cellular cholesterol and partition into cholesterol-enriched membrane rafts. However, very little is known about functional role of membrane cholesterol in regulation of mechanically gated channels that are ubiquitously present in living cells. In our previous study, the effect of methyl-beta-cyclodextrin (MbCD), cholesterol-sequestering agent, on Ca²⁺-permeable stretch-activated cation channels (SACs) has been described. Here, cell-attached patch-clamp method was employed to search for the mechanisms of cholesterol-dependent regulation of SACs and to clarify functional contribution of lipid bilayer and submembranous cytoskeleton to channel gating. Cholesterol-depleting treatment with MbCD significantly decreased open probability of SACs whereas alpha-cyclodextrin had no effect. F-actin disassembly fully restored high level of SAC activity in cholesterol-depleted cells. Particularly, treatment with cytochalasin D or latrunculin B abrogated inhibitory effect of MbCD on stretch-activated currents. Single channel analysis and fluorescent imaging methods indicate that inhibition of SACs after cholesterol depletion is mediated via actin remodeling initiated by disruption of lipid rafts. Our data reveal a novel mechanism of channel regulation by membrane cholesterol and lipid rafts.     

Impact of motion induced artifacts on automatic registration of lung tumors in Tomotherapy

PurposeTomotherapy MV-CT acquisitions of lung tumors lead to artifacts due to breathing-related motion. This could preclude the reliability of tumor based positioning. We investigate the effect of these artifacts on automatic registration and determine conditions under which correct positioning can be achieved.Materials and methodsMV-CT and 4D-CT scans of a dynamic thorax phantom were acquired with various motion amplitudes, directions, and periods. For each acquisition, the average kV-CT image was reconstructed from the 4D-CT data and rigidly registered with the corresponding MV-CT scan in a region of interest. Different kV–MV registration strategies have been assessed.ResultsAll tested registration methods led to acceptable registration errors (within 1.3 ± 1.2 mm) for motion periods of 3 and 6 s, regardless of the motion amplitude, direction, and phase difference. However, a motion period of 5 s, equal to half the Tomotherapy gantry period, induced asymmetric artifacts within MV-CT and significantly degraded the registration accuracy.ConclusionsAs long as the breathing period differs from 5 s, positioning based on averaged images of the tumor provides information about its daily baseline shift, and might therefore contribute to reducing margins, regardless of the registration method.     

Haptic discrimination of size and texture in squirrel monkeys ( Saimiri sciureus )

The present study analyzed haptic abilities of four squirrel monkeys. Using a two-alternative forced-choice procedure, stimuli were presented in a visually opaque box, allowing unrestrained test subjects to grab through a small opening and touch the discriminanda. Difference thresholds were determined by a modified method of limits. In the first experiment we determined size difference thresholds for the discrimination of circular cylinders using standard stimuli differing in diameter from 10 mm to 35 mm. In the second experiment a texture difference threshold was obtained for the discrimination of grooved surfaces (groove width 2-7 mm).The squirrel monkeys achieved a mean size difference threshold of 8% stimulus difference. The linear increase of absolute thresholds as a function of the starting stimulus size showed that haptic size discriminations in squirrel monkeys correspond to Weber's law. Three of the animals achieved a texture difference of 10% stimulus difference, while one monkey showed a distinctively lower haptic acuity. An analysis of the exploratory behavior points to a subject-related difference in the significance of cutaneous and kinesthetic information during size discriminations. Whereas differences in the animals' exploratory behavior did not correlate with the size difference threshold a subject achieved, different thresholds for texture discrimination can be explained by the different exploratory procedures the monkeys used to touch grooved surfaces. The low difference thresholds determined for the squirrel monkeys in the present study point to the significance of unrestrained test conditions for the assessment of the haptic capacity of a species.     

Haptic discrimination of size and texture in squirrel monkeys (Saimiri sciureus)

The present study analyzed haptic abilities of four squirrel monkeys. Using a two-alternative forced-choice procedure, stimuli were presented in a visually opaque box, allowing unrestrained test subjects to grab through a small opening and touch the discriminanda. Difference thresholds were determined by a modified method of limits. In the first experiment we determined size difference thresholds for the discrimination of circular cylinders using standard stimuli differing in diameter from 10 mm to 35 mm. In the second experiment a texture difference threshold was obtained for the discrimination of grooved surfaces (groove width 2-7 mm). The squirrel monkeys achieved a mean size difference threshold of 8% stimulus difference. The linear increase of absolute thresholds as a function of the starting stimulus size showed that haptic size discriminations in squirrel monkeys correspond to Weber's law. Three of the animals achieved a texture difference of 10% stimulus difference, while one monkey showed a distinctively lower haptic acuity. An analysis of the exploratory behavior points to a subject-related difference in the significance of cutaneous and kinesthetic information during size discriminations. Whereas differences in the animals' exploratory behavior did not correlate with the size difference threshold a subject achieved, different thresholds for texture discrimination can be explained by the different exploratory procedures the monkeys used to touch grooved surfaces. The low difference thresholds determined for the squirrel monkeys in the present study point to the significance of unrestrained test conditions for the assessment of the haptic capacity of a species.