bluuebunny/crossref_metadata_2025 huggingface dataset:
Single cell analysis applied to antibody fragment production with Bacillus megaterium: development of advanced physiology and bioprocess state estimation tools
Authors: David Florian , Berger Antje , Hänsch Robert , Rohde Manfred , Franco-Lara Ezequiel
Published: April 2011

Background

Single cell analysis for bioprocess monitoring is an important tool to gain deeper insights into particular cell behavior and population dynamics of production processes and can be very useful for discrimination of the real bottleneck between product biosynthesis and secretion, respectively.

Results

Here different dyes for viability estimation considering membrane potential (DiOC2(3), DiBAC4(3), DiOC6(3)) and cell integrity (DiBAC4(3)/PI, Syto9/PI) were successfully evaluated for Bacillus megaterium cell characterization. It was possible to establish an appropriate assay to measure the production intensities of single cells revealing certain product secretion dynamics. Methods were tested regarding their sensitivity by evaluating fluorescence surface density and fluorescent specific concentration in relation to the electronic cell volume. The assays established were applied at different stages of a bioprocess where the antibody fragment D1.3 scFv production and secretion by B. megaterium was studied.

Conclusions

It was possible to distinguish between live, metabolic active, depolarized, dormant, and dead cells and to discriminate between high and low productive cells. The methods were shown to be suitable tools for process monitoring at single cell level allowing a better process understanding, increasing robustness and forming a firm basis for physiology-based analysis and optimization with the general application for bioprocess development.
Advances in modelling of biomimetic fluid flow at different scales
Authors: Saha Sujoy Kumar , Celata Gian Piero
Published: April 2011

The biomimetic flow at different scales has been discussed at length. The need of looking into the biological surfaces and morphologies and both geometrical and physical similarities to imitate the technological products and processes has been emphasized. The complex fluid flow and heat transfer problems, the fluid-interface and the physics involved at multiscale and macro-, meso-, micro- and nano-scales have been discussed. The flow and heat transfer simulation is done by various CFD solvers including Navier-Stokes and energy equations, lattice Boltzmann method and molecular dynamics method. Combined continuum-molecular dynamics method is also reviewed.
Analytical model for the photocurrent-voltage characteristics of bilayer MEH-PPV/TiO2 photovoltaic devices
Authors: Chen Chong , Wu Fan , Geng Hongwei , Shen Wei , Wang Mingtai
Published: April 2011

The photocurrent in bilayer polymer photovoltaic cells is dominated by the exciton dissociation efficiency at donor/acceptor interface. An analytical model is developed for the photocurrent-voltage characteristics of the bilayer polymer/TiO2 photovoltaic cells. The model gives an analytical expression for the exciton dissociation efficiency at the interface, and explains the dependence of the photocurrent of the devices on the internal electric field, the polymer and TiO2 layer thicknesses. Bilayer polymer/TiO2 cells consisting of poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene] (MEH-PPV) and TiO2, with different thicknesses of the polymer and TiO2 films, were prepared for experimental purposes. The experimental results for the prepared bilayer MEH-PPV/TiO2 cells under different conditions are satisfactorily fitted to the model. Results show that increasing TiO2 or the polymer layer in thickness will reduce the exciton dissociation efficiency in the device and further the photocurrent. It is found that the photocurrent is determined by the competition between the exciton dissociation and charge recombination at the donor/acceptor interface, and the increase in photocurrent under a higher incident light intensity is due to the increased exciton density rather than the increase in the exciton dissociation efficiency.
TF-Cluster: A pipeline for identifying functionally coordinated transcription factors via network decomposition of the shared coexpression connectivity matrix (SCCM)
Authors: Nie Jeff , Stewart Ron , Zhang Hang , Thomson James A , Ruan Fang , Cui Xiaoqi , Wei Hairong
Published: April 2011

Background

Identifying the key transcription factors (TFs) controlling a biological process is the first step toward a better understanding of underpinning regulatory mechanisms. However, due to the involvement of a large number of genes and complex interactions in gene regulatory networks, identifying TFs involved in a biological process remains particularly difficult. The challenges include: (1) Most eukaryotic genomes encode thousands of TFs, which are organized in gene families of various sizes and in many cases with poor sequence conservation, making it difficult to recognize TFs for a biological process; (2) Transcription usually involves several hundred genes that generate a combination of intrinsic noise from upstream signaling networks and lead to fluctuations in transcription; (3) A TF can function in different cell types or developmental stages. Currently, the methods available for identifying TFs involved in biological processes are still very scarce, and the development of novel, more powerful methods is desperately needed.

Results

We developed a computational pipeline called TF-Cluster for identifying functionally coordinated TFs in two steps: (1) Construction of a shared coexpression connectivity matrix (SCCM), in which each entry represents the number of shared coexpressed genes between two TFs. This sparse and symmetric matrix embodies a new concept of coexpression networks in which genes are associated in the context of other shared coexpressed genes; (2) Decomposition of the SCCM using a novel heuristic algorithm termed "Triple-Link", which searches the highest connectivity in the SCCM, and then uses two connected TF as a primer for growing a TF cluster with a number of linking criteria. We applied TF-Cluster to microarray data from human stem cells and Arabidopsis roots, and then demonstrated that many of the resulting TF clusters contain functionally coordinated TFs that, based on existing literature, accurately represent a biological process of interest.

Conclusions

TF-Cluster can be used to identify a set of TFs controlling a biological process of interest from gene expression data. Its high accuracy in recognizing true positive TFs involved in a biological process makes it extremely valuable in building core GRNs controlling a biological process. The pipeline implemented in Perl can be installed in various platforms.
Direct ethanol production from cellulosic materials using a diploid strain of Saccharomyces cerevisiaewith optimized cellulase expression
Authors: Yamada Ryosuke , Taniguchi Naho , Tanaka Tsutomu , Ogino Chiaki , Fukuda Hideki , Kondo Akihiko
Published: April 2011

Background

Hydrolysis of cellulose requires the action of the cellulolytic enzymes endoglucanase, cellobiohydrolase and β-glucosidase. The expression ratios and synergetic effects of these enzymes significantly influence the extent and specific rate of cellulose degradation. In this study, using our previously developed method to optimize cellulase-expression levels in yeast, we constructed a diploid Saccharomyces cerevisiae strain optimized for expression of cellulolytic enzymes, and attempted to improve the cellulose-degradation activity and enable direct ethanol production from rice straw, one of the most abundant sources of lignocellulosic biomass.

Results

The engineered diploid strain, which contained multiple copies of three cellulase genes integrated into its genome, was precultured in molasses medium (381.4 mU/g wet cell), and displayed approximately six-fold higher phosphoric acid swollen cellulose (PASC) degradation activity than the parent haploid strain (63.5 mU/g wet cell). When used to ferment PASC, the diploid strain produced 7.6 g/l ethanol in 72 hours, with an ethanol yield that achieved 75% of the theoretical value, and also produced 7.5 g/l ethanol from pretreated rice straw in 72 hours.

Conclusions

We have developed diploid yeast strain optimized for expression of cellulolytic enzymes, which is capable of directly fermenting from cellulosic materials. Although this is a proof-of-concept study, it is to our knowledge, the first report of ethanol production from agricultural waste biomass using cellulolytic enzyme-expressing yeast without the addition of exogenous enzymes. Our results suggest that combining multigene expression optimization and diploidization in yeast is a promising approach for enhancing ethanol production from various types of lignocellulosic biomass.
Soluble triggering receptor on myeloid cells-1 is expressed in the course of non-infectious inflammation after traumatic lung contusion: a prospective cohort study
Authors: Bingold Tobias M , Pullmann Barbara , Sartorius Sven , Geiger Emanuel V , Marzi Ingo , Zacharowski Kai , Wissing Heimo , Scheller Bertram
Published: April 2011

Introduction

The triggering receptor expressed on myeloid cells-1 (TREM-1) is known to be expressed during bacterial infections. We investigated whether TREM-1 is also expressed in non-infectious inflammation following traumatic lung contusion.

Methods

In a study population of 45 adult patients with multiple trauma and lung contusion, we obtained bronchoalveolar lavage (BAL) (blind suctioning of 20 ml NaCl (0.9%) via jet catheter) and collected blood samples at two time points (16 hours and 40 hours) after trauma. Post hoc patients were assigned to one of four groups radiologically classified according to the severity of lung contusion based on the initial chest tomography. Concentration of soluble TREM-1 (sTREM-1) and bacterial growth were determined in the BAL. sTREM-1, IL-6, IL-10, lipopolysaccharide binding protein, procalcitonin, C-reactive protein and leukocyte count were assessed in blood samples. Pulmonary function was evaluated by the paO2/FiO2 ratio.

Results

Three patients were excluded due to positive bacterial growth in the initial BAL. In 42 patients the severity of lung contusion correlated with the levels of sTREM-1 16 hours and 40 hours after trauma. sTREM-1 levels were significantly (P < 0.01) elevated in patients with severe contusion (2,184 pg/ml (620 to 4,000 pg/ml)) in comparison with patients with mild (339 pg/ml (135 to 731 pg/ml)) or no (217 pg/ml (97 to 701 pg/ml)) contusion 40 hours following trauma. At both time points the paO2/FiO2 ratio correlated negatively with sTREM-1 levels (Spearman correlation coefficient = -0.446, P < 0.01).

Conclusions

sTREM-1 levels are elevated in the BAL of patients following pulmonary contusion. Furthermore, the levels of sTREM-1 in the BAL correlate well with both the severity of radiological pulmonary tissue damage and functional impairment of gas exchange (paO2/FiO2 ratio).
The Conundrum of Estrogen Receptor Oscillatory Activity in the Search for an Appropriate Hormone Replacement Therapy
Authors: Della Torre Sara , Biserni Andrea , Rando Gianpaolo , Monteleone Giuseppina , Ciana Paolo , Komm Barry , Maggi Adriana
Published: April 2011

By the use of in vivo imaging, we investigated the dynamics of estrogen receptor (ER) activity in intact, ovariectomized, and hormone-replaced estrogen response element-luciferase reporter mice. The study revealed the existence of a long-paced, noncircadian oscillation of ER transcriptional activity. Among the ER-expressing organs, this oscillation was asynchronous and its amplitude and period were tissue dependent. Ovariectomy affected the amplitude but did not suppress ER oscillations, suggesting the presence of tissue endogenous oscillators. Long-term administration of raloxifene, bazedoxifene, combined estrogens alone or with basedoxifene to ovariectomized estrogen response element-luciferase mice showed that each treatment induced a distinct spatiotemporal profile of ER activity, demonstrating that the phasing of ER activity among tissues may be regulated by the chemical nature and the concentration of circulating estrogen. This points to the possibility of a hierarchical organization of the tissue-specific pacemakers. Conceivably, the rhythm of ER transcriptional activity translates locally into the activation of specific gene networks enabling ER to significantly change its physiological activity according to circulating estrogens. In reproductive and nonreproductive organs this hierarchical regulation may provide ER with the signaling plasticity necessary to drive the complex metabolic changes occurring at each female reproductive status. We propose that the tissue-specific oscillatory activity here described is an important component of ER signaling necessary for the full hormone action including the beneficial effects reported for nonreproductive organs. Thus, this mechanism needs to be taken in due consideration to develop novel, more efficacious, and safer hormone replacement therapies.
Gonadal Pathology and Tumor Risk in Relation to Clinical Characteristics in Patients with 45,X/46,XY Mosaicism
Authors: Cools M. , Pleskacova J. , Stoop H. , Hoebeke P. , Van Laecke E. , Drop S. L. S. , Lebl J. , Oosterhuis J. W. , Looijenga L. H. J. , Wolffenbuttel K. P. ,   on behalf of the Mosaicism Collaborative Group
Published: April 2011

Context:

Gonadectomy is avoided whenever possible in boys with 45,X/46,XY. However, no clinical markers are currently available to guide clinicians in predicting gonadal tumor risk or hormone production.

Objective:

The objective of the study was to test the hypothesis that gonadal histology and risk for development of a malignant germ cell tumor are reflected by the clinical presentation of a 45,X/46,XY individual.

Design:

The design of the study was the correlation of clinical data [external masculinization score (EMS), pubertal outcome] with pathology data (gonadal phenotype, tumor risk).

Setting:

This was a multicenter study involving two multidisciplinary disorder of sex development teams.

Patients:

Patients included genetically proven 45,X/46,XY (and variants) cases, of whom at least one gonadal biopsy or gonadectomy specimen was available, together with clinical details.

Interventions:

Patients (n = 48) were divided into three groups, based on the EMS. Gonadal histology and tumor risk were assessed on paraffin-embedded samples (n = 87) by morphology and immunohistochemistry on the basis of established criteria.

Main Outcome Measures:

Gonadal differentiation and tumor risk in the three clinical groups were measured. Clinical outcome in patients with at least one preserved gonad was also measured.

Results:

Tumor risk in the three groups was significantly related to the gonadal differentiation pattern (P < 0.001). In boys, hormone production was sufficient and was not predicted by the EMS.

Conclusions:

The EMS reflects gonadal differentiation and tumor risk in patients with 45,X/46,XY. In boys, testosterone production is often sufficient, but strict follow-up is warranted because of malignancy risk, which appears inversely related to EMS. In girls, tumor risk is limited but gonads are not functional, making gonadectomy the most reasonable option.
Acute Cervical Myelopathy from Hereditary Multiple Exostoses: Case Report
Authors: Wen Dennis Y. , Bergman Thomas A. , Haines Stephen J.
Published: April 2011

A case of hereditary multiple exostoses with acute cervical myelopathy, tetraplegia, and apnea is reported. Neurological complications as a result of osteochondromas in hereditary multiple exostoses are rare. The majority of osteochondromas in the cervical spine arise from the neural arch. Magnetic resonance imaging and computed tomography are invaluable in localizing the origin of the lesion and its relationship to the spinal cord. Decompressive laminectomy usually results in excellent functional recovery. Where significant dorsal spinal cord compression exists without neurological deficit, prophylactic decompression can be recommended.
Cystic Optic Glioma
Authors: Gower David J. , Pollay Michael , Shuman Robert M. , Brumback Roger A.
Published: April 2011

A pilocytic astrocytoma of the optic nerve, chiasm, hypothalamus, or third ventricle is a relatively common tumor of childhood. This case report illustrates such a tumor, originating from this location, which is unusual because of the association with two very large cystic extensions into the middle cranial fossa and into the third ventricle. The massive size and extent of this tumor and cysts was demonstrated on a magnetic resonance imaging (MRI) scan, with gadolinium enhancement. This case illustrates a novel macroscopic appearance for a pilocytic glioma of the anterior third ventricle. The purpose of this report is to alert clinicians to the varied morphology this tumor may present as we apply increasingly our improved radiological, operative, and histopathological techniques. (Neurosurgery 26:133-137, 1990)
Utilization of Unilateral and Bilateral Stereotactically Placed Adrenomedullary-Striatal Autografts in Parkinsonian Humans: Rationale, Techniques, and Observations
Authors: Apuzzo Michael L. J. , Neal John H. , Waters Cheryl H. , Appley Alan J. , Boyd Stuart D. , Couldwell William T. , Wheelock Vickie H. , Weiner Leslie P.
Published: April 2011

A limited clinical pilot study involving an amalgam of specialized disciplines including neurology, neuropharmacology, neuropsychology, neurosurgery, neuroanesthesia, neuroradiology, surgical pathology, neuropathology, and urological surgery was organized to clarify issues related to patient selection, optimization of grafting materials, design of a safe, effective, standardized, and reproducible surgical technique, and possible modification of clinical patterns. After initial assessment of 82 Parkinsonian patients for periods of 6 to 20 months, 10 (age, 39-68 years) were selected for unilateral or bilateral adrenomedullary autografts to the caudate nucleus with ependymal and cerebrospinal fluid contact, employing image-directed stereotactic methods. Selection was made only after clear definition of clinical pattern and optimization of medication responses. Adrenal glands were harvested by a retroperitoneal approach (mean estimated blood loss < 75 ml). Care was taken to maximize the graft content of medullary tissue. Stereotactic methods afforded standardized, reproducible, precise targeting and transit trajectory with unilateral or bilateral placement of materials within the striatum (tissue volume, 80 mm3) with access to the ventricular fluid of the frontal horn. Considerable variability in satisfactory donor medullary tissue was encountered. One patient did not undergo grafting because of unsatisfactory medullary tissue. No significant surgical complications were noted and all patients were ready for discharge 7 days after surgery. One patient who manifested no apparent clinical change died 6 weeks after bilateral grafting of unrelated causes during a lithotripsy procedure. Postmortem examination disclosed precise graft placement with a paucity of structurally preserved medullary cells. Postoperative observations, including parameters of clinical observation, medication schedules and records, patient and family commentaries, and imaging studies (computed tomograms and single photon emission computed tomograms), have been made for periods from 16 to 20 months. Sustained improvement in preexisting clinical patterns and reduction in drug requirements were observed in 4 of 8 patients. No increased benefit could be ascribed to bilateral graft placement. These observations would indicate a primary role for stereotactic methodology for cerebral graft placement, as it affords a minimally invasive but precise, safe, and reproducible surgical method. In addition, the clinical observations indicate favorable alterations in the established pattern of the disorder, which would justify further cautious exploration of alternate donor sources or refinements of biological graft site manipulations.
Intracranial and Orbital Metastasis of Hepatocellular Carcinoma: Report of Two Cases
Authors: Wakisaka Shinichiro , Tashiro Manabu , Nakano Shinichi , Kita Toshihiro , Kisanuki Hiroto , Kinoshita Kazuo
Published: April 2011

Two cases of rare intracranial and orbital metastasis of hepatocellular carcinoma are presented. A 61-year-old woman was found to have a metastatic tumor in the right temporo-occipital lobe 1 year after undergoing treatment for a primary hepatoma. An osteolytic tumor was removed from the left orbit of a 58-year-old man and the primary tumor, a hepatoma, was discovered postoperatively. The intracranial and orbital tumors were verified to be hepatocellular carcinoma. Both patients died within 1 year of surgery. The relevant literature is briefly reviewed.
Pheochromocytoma Presenting as a Skull Metastasis with Massive Extracranial and Intracranial Extension
Authors: Grabel Jordan C. , Gottesman Robin I. , Moore Frank , Averbuch Steven , Zappulla Rosario
Published: April 2011

A case of metastatic pheochromocytoma is reported in which the diagnosis was determined on the basis of a painless scalp mass. Subsequent to biopsy and histological diagnosis, further investigations revealed a large skull lesion with intracranial extension, an adrenal mass, and various catechnolamine abnormalities. The radiological characteristics and operative findings of this case are described, and the literature regarding pheochromocytoma with intracranial metastatic extension is reviewed.
Effects of Repeated Temporary Clipping of the Middle Cerebral Artery on Pial Arterial Diameter, Regional Cerebral Blood Flow, and Brain Structure in Cats
Authors: Sakaki Toshisuke , Tsunoda Shigeru , Morimoto Tetsuya , Ishida Taiji , Sasaoka Yasunori
Published: April 2011

Temporary clipping of the major arterial trunk is an important maneuver to control excessive unexpected bleeding in neurosurgical operations; however, repeated temporary clipping can give rise to severe neurological deficits after surgery. The present study was performed to confirm and explain these clinical findings. Initially, a single 20-minute or 1-hour occlusion of the middle cerebral artery was performed in each of 5 cats. Pial arterial diameter was determined by video imaging, regional cerebral blood flow was measured by autoradiography, and cerebral edema and infarction were observed. In the 20-minute occlusion group, no abnormal changes were found 5 hours after recirculation. In the 1-hour occlusion group, pial arteries were dilated by 45%, and regional cerebral blood flow increased to more than twice the resting cortical values. The extent of cerebral edema was 41.2 ± 7.5% (SE) and infarction was 34.5 ± 9.5% (SE) of the hemisphere. In the second experiment, three 20-minute occlusions of the middle cerebral artery in a 1-hour interval were performed in 20 cats. In 10 of them, thiopental (40 mg/kg) was used to protect the brain. In the group without barbiturate treatment, pial arteries were dilated by 40% at the end of experiment, regional cerebral blood flow decreased to about 70% compared with single 20-minute occlusion, cerebral edema was 19.5 ± 8.1% (SE), and infarction was 8.1 ± 3.7% (SE) of the hemisphere. In the treated group, these were only trivial changes. The effect of repeated clipping may cumulatively cause brain damage, and barbiturates should be used whenever repeated clipping is necessary.
Accelerated Non-Muscle Contraction after Subarachnoid Hemorrhage: Cerebrospinal Fluid Testing in a Culture Model
Authors: Yamamoto Yoshihiro , Bernanke David H. , Smith Robert R.
Published: April 2011

The cause of chronic cerebral vasospasm after subarachnoid hemorrhage has been studied intensively, but it is still controversial whether the observable luminal narrowing should be attributed to the contraction of vascular smooth muscle cells or whether it results from some organic change in the wall. A proliferation of myointimal cells, accompanied by increased deposition of collagen, as well as myonecrosis, have been frequently observed several days after aneurysm rupture. Studies from our laboratory showed that these myointimal cells had characteristics identical to myofibroblasts. In this study, we quantitatively and morphologically examined the effect of cerebrospinal fluid on the ability of myofibroblasts to alter collagen matrices using an in vitro model. Myofibroblasts contract the collagen matrix by rearranging or compacting the framework of collagen fibers. Cerebrospinal fluid obtained from patients with recently ruptured aneurysms significantly accelerated lattice contraction, especially when the patient developed symptomatic vasospasm. This study suggests that myofibroblasts in the spastic artery can produce a contractile force that contributes to chronic vasospasm, tightening the proliferated collagen. Some unknown agent present in bloody cerebrospinal fluid accelerates the rearrangement of the collagen lattice by myofibroblasts, both of which have, until now, been considered non-contractile components.
Acoustic Schwannoma and Epidermoid Cyst Occurring as a Single Cerebellopontine Angle Mass
Authors: Goodman Robert R. , Torres Roland A. A. , McMurtry James G.
Published: April 2011

The case of a 66-year-old man with a 3-year progressive hearing loss and a homogeneous left cerebellopontine angle mass on magnetic resonance imaging scan is described. At surgery, the major portion of the mass was a typical encapsulated, solid, acoustic schwannoma, but the most rostral portion was a distinct, flaky, cystic mass without a welldefined capsule, typical of an epidermoid cyst. The radiographic and operative findings of this unique coexistence of two different benign cerebellopontine angle masses are presented.
Venous Thromboembolism after Brain Tumor Surgery: A Retrospective Review
Authors: Levi Allan D. O. , Wallace Christopher M. , Bernstein Mark , Walters Beverly C.
Published: April 2011

We retrospectively reviewed the incidence rate of clinical postoperative deep vein thrombosis and/or pulmonary embolism in 1703 patients undergoing initial craniotomy for meningioma, glioma, or cerebral metastasis. The incidence rate of clinical thromboembolic complications was 1.59% for all tumor groups within the first 4 weeks of surgery. Patients undergoing surgery for meningiomas had a statistically significant increased risk of thromboembolism despite fewer overall perioperative risk factors, when compared with the other tumor groups. The tumor-specific incidence rates of deep vein thrombosis and/or pulmonary embolism for meningioma, glioma, and metastasis were 3.09%, 0.97%, and 1.03%, respectively. Whether this difference was a result of increased surgical time or an inherent property of meningiomas could not be ascertained.
Acute Aggravation of Subdural Effusion Associated with Pachymeningitis Carcinomatosa: Case Report
Authors: Kamada Kyousuke , Isu Toyohiko , Houkin Kiyohiro , Ohsato Takao , Katoh Masahito , Kojima Hideaki
Published: April 2011

The authors present a case of acute aggravation of subdural effusion associated with pachymeningitis carcinomatosa. Microscopic examination of a surgical specimen revealed diffuse involvement of the dura mater by a metastatic adenocarcinoma in which the tumor cells invaded venules located in the areolar layer in particular. The rapid increase in capillarv transmural pressure resulted in extravasation of plasma components, causing an increase in subdural effusion.
The tumor suppressor geneTrp53protects the mouse lens against posterior subcapsular cataracts and the BMP receptor Acvr1 acts as a tumor suppressor in the lens
Authors: Wiley Luke A. , Rajagopal Ramya , Dattilo Lisa K. , Beebe David C.
Published: April 2011

We previously found that lenses lacking the Acvr1 gene, which encodes a bone morphogenetic protein (BMP) receptor, had abnormal proliferation and cell death in epithelial and cortical fiber cells. We tested whether the tumor suppressor protein p53 (encoded by Trp53) affected this phenotype. Acvr1 conditional knockout (Acvr1CKO) mouse fiber cells had increased numbers of nuclei that stained for p53 phosphorylated on serine 15, an indicator of p53 stabilization and activation. Deletion of Trp53 rescued the Acvr1CKO cell death phenotype in embryos and reduced Acvr1-dependent apoptosis in postnatal lenses. However, deletion of Trp53 alone increased the number of fiber cells that failed to withdraw from the cell cycle. Trp53CKO and Acvr1;Trp53DCKO (double conditional knockout), but not Acvr1CKO, lenses developed abnormal collections of cells at the posterior of the lens that resembled posterior subcapsular cataracts. Cells from human posterior subcapsular cataracts had morphological and molecular characteristics similar to the cells at the posterior of mouse lenses lacking Trp53. In Trp53CKO lenses, cells in the posterior plaques did not proliferate but, in Acvr1;Trp53DCKO lenses, many cells in the posterior plaques continued to proliferate, eventually forming vascularized tumor-like masses at the posterior of the lens. We conclude that p53 protects the lens against posterior subcapsular cataract formation by suppressing the proliferation of fiber cells and promoting the death of any fiber cells that enter the cell cycle. Acvr1 acts as a tumor suppressor in the lens. Enhancing p53 function in the lens could contribute to the prevention of steroid- and radiation-induced posterior subcapsular cataracts.
C. elegans: model host and tool for antimicrobial drug discovery
Authors: Ewbank Jonathan J. , Zugasti Olivier
Published: April 2011

For almost four decades, the nematode Caenorhabditis elegans has been of great value in many fields of biological research. It is now used extensively in studies of microbial pathogenesis and innate immunity. The worm lacks an adaptive immune system and relies solely on its innate immune defences to cope with pathogen attack. Infectious microbes, many of which are of clinical interest, trigger specific mechanisms of innate immunity, and provoke the expression of antifungal or antibacterial polypeptides. In this review, we highlight some of these families of antimicrobial peptides (AMPs) and proteins that are candidates for the development of novel antibiotics. In addition, we describe how systems of C. elegans infection provide an increasing number of possibilities for large-scale in vivo screens for the discovery of new antimicrobial drugs. These systems open promising perspectives for innovative human therapies.
A clinical and experimental overview of sirenomelia: insight into the mechanisms of congenital limb malformations
Authors: Garrido-Allepuz Carlos , Haro Endika , González-Lamuño Domingo , Martínez-Frías María Luisa , Bertocchini Federica , Ros Maria A.
Published: April 2011

Sirenomelia, also known as sirenomelia sequence, is a severe malformation of the lower body characterized by fusion of the legs and a variable combination of visceral abnormalities. The causes of this malformation remain unknown, although the discovery that it can have a genetic basis in mice represents an important step towards the understanding of its pathogenesis. Sirenomelia occurs in mice lacking Cyp26a1, an enzyme that degrades retinoic acid (RA), and in mice that develop with reduced bone morphogenetic protein (Bmp) signaling in the caudal embryonic region. The phenotypes of these mutant mice suggest that sirenomelia in humans is associated with an excess of RA signaling and a deficit in Bmp signaling in the caudal body. Clinical studies of sirenomelia have given rise to two main pathogenic hypotheses. The first hypothesis, based on the aberrant abdominal and umbilical vascular pattern of affected individuals, postulates a primary vascular defect that leaves the caudal part of the embryo hypoperfused. The second hypothesis, based on the overall malformation of the caudal body, postulates a primary defect in the generation of the mesoderm. This review gathers experimental and clinical information on sirenomelia together with the necessary background to understand how deviations from normal development of the caudal part of the embryo might lead to this multisystemic malformation.
Implementing a Statutory Minimum Wage in Hong Kong: Appreciating International Experiences but Recognizing Local Conditions
Authors: Price Rohan , Ho John Kong Shan
Published: April 2011

The much debated Minimum Wage Ordinance eventually secured passage in the Hong Kong Legislative Council on 17 July 2010 and is to take effect on 1 May 2011. A Minimum Wage Council established under the Ordinance has made recommendations to the Chief Executive on the initial minimum wage level. This paper compares the minimum wage legislation in Hong Kong with that of other Western jurisdictions and seeks to identify what the former can learn from these international experiences in setting a statutory minimum wage. In the final analysis, it is argued that these experiences provide a good platform for implementing a broadly similar regime in the Special Administrative Region, albeit one with ‘Hong Kong characteristics’.
Wildlife Reforms in Scotland
Authors: Reid Colin T.
Published: April 2011

The Wildlife and Natural Environment (Scotland) Bill was introduced to the Scottish Parliament in 2010. The Bill proposes a number of significant changes to the law in Scotland, replacing most of the existing law on game and poaching and introducing new controls on the use of snares. Further provisions will ban the release of non-native species and introduce new control measures for those that are in the wild. Other measures adjust the law on deer, Sites of Special Scientific Interest, wildlife licensing and muirburn. Although making many welcome changes, the Bill is a miscellany of assorted reforms rather than the expression of a single vision for the future of wildlife law, aspects of which will remain in a fragmented state.
Mental Gymnastics and Intellectual Acrobatics: The Meanings of Statutory and Common Law ‘Bad Character’
Authors: Huxley Phil
Published: April 2011

Historically the common law allowed the prosecution to prove the defendant's guilt by adducing not only factual evidence, but also evidence of his bad character. The latter could take the form of evidence that the defendant had done the same thing on previous occasions as he was charged with today. This was known as similar fact evidence (SFE). Under the Criminal Justice Act 2003 the common law rules as to the admissibility of evidence of bad character were abolished and replaced with a statutory scheme which is capable of being used to admit some, but by no means all, of what was SFE at common law. This article considers alternative meanings of the two-word phrase ‘bad character’; whether SFE which is not admissible under the Act is nevertheless admissible at common law; the relationship between the statutory scheme and the common law; and crucially, the jury direction at common law.
Undesirable Posters and Dubious Symbols: Anglo-German Legal Solutions to the Display of Right-Wing Symbolism and Propaganda
Authors: Newman Christopher J. , Rackow Peter
Published: April 2011

This article seeks to examine the approach of the judiciary in both England and Germany in respect of certain manifestations of extreme right-wing images. The article will start by looking at the legislative framework governing the display of such images within the two jurisdictions. Following on from this, there will be an examination of the doctrinal and rights-based arguments that arise when such offences are dealt with by criminal prosecution. The article will then draw together different decisions of appeal courts in the two jurisdictions and conclude the discussion by noting both the similarities and divergent practices within the respective legal systems.
Ecological Influences on State Police District Activity
Authors: Johnson Richard R. , Billings Ashley N.
Published: April 2011

Ecological explanations for differences in aggregate-level officer activity across districts within a police agency have been tested within the context of municipal police agencies, but have yet to be tested at the state police level. Using data publicly available from the Indiana State Police Department and the US Census Bureau, district ecological factors such as crime rate, social disorganisation level, calls for service, supervisor span of control, perceived danger, and proportion of probationary officers were investigated for their relationship to several district-level outputs. Unlike similar studies involving municipal law enforcement agencies, the factors with the highest predictive value of district outputs were the level of calls for service, crime rate, and supervisor span of control. The potential research differences between municipal and state police agencies are also discussed.
Good performance of an immunoassay based method for nevirapine measurements in human breast milk
Authors: Salado-Rasmussen Kirsten , Theilgaard Zahra Persson , Chiduo Mercy , Pedersen Court , Gerstoft Jan , Katzenstein Terese Lea
Published: April 2011

Background: Understanding the distribution of antiretro-virals in breastfeeding HIV-positive mothers is essential, both for prevention of mother-to-child HIV transmission and for research on the development of drug resistance. The ARK nevirapine (NVP)-test is an immunoassay method for nevirapine measurements, developed and validated for plasma use. In this study, the ARK NVP-test was evaluated for measurement of nevirapine concentrations in breast milk. High performance liquid chromatography (HPLC) is the method currently used to determine nevirapine in breast milk. This method, however, requires complicated extraction techniques. The ARK method employs an immunoassay technology and requires a small sample volume (40 μL) and no pre-treatment of the samples.

Methods: Commercial enzyme and antibody were used and calibration standards and quality controls were prepared from pooled breast milk from HIV-uninfected women. Clinical samples from HIV-infected women receiving a single-dose of nevirapine were analyzed.

Results: Precision and accuracy were evaluated with two concentrations of quality control materials analyzed in three replicates on four different days and was <4%, and between 96.5% and 104.6%, respectively. Clinical samples were analyzed and CVs ranged from 0.0% to 11.1%. The median nevirapine concentration in breast milk 1 week post-partum was 0.29 μg/mL (range 0.11–0.90 μg/mL) in women treated with a single-dose of nevirapine.

Conclusions: The ease of use and small sample volume makes the ARK assay an attractive alternative to HPLC analyses for determinations of nevirapine concentrations in breast milk.
Organo acidurien/Organic Acidurias
Authors: Sass Jörn Oliver
Published: April 2011

Bei der Bestimmung der organischen Säuren im Urin handelt es sich um eine bewährte Untersuchung im Rahmen des selektiven Screenings auf angeborene Stoffwechselstörungen. Unter Anwendung von Gaschromatographie und Massenspektrometrie kann auf diesem Weg zur Diagnose zahlreicher Krankheiten beigetragen werden. Für eine wegweisende Auswertung der Analysendaten ist es essentiell, dass der Anforderer der Untersuchung dem Labor klinische Basisinformationen zur Verfügung stellt. Verbreitung des Wissens über Organoazidopathien und ihre Einbeziehung in die Differentialdiagnostik, insbesondere (pädiatrisch-)neurologischer Krankheitsbilder, ist angesichts der in vielen Fällen vorhandenen Behandlungsmöglichkeiten von besonderer Bedeutung.
Update: Thrombozytopathie/Thrombocytopathy: an update
Authors: Drogies Tim , Braunert Leanthe , Thiery Joachim , Brügel Mathias
Published: April 2011

Der Begriff Thrombozytopathie bezeichnet angeborene oder erworbene funktionelle Störungen der Thrombozytenfunktion. Aufgrund der Vielzahl von möglichen pathophysiologischen Ursachen, basierend auf der Komplexität thrombozytärer Funktionsabläufe und Stoffwechselprozesse, zeigen Thrombozytopathien eine außerordentlich hohe klinische Variabilität. Eine Abbildung der Pathophysiologie ist mit den verfügbaren labordiagnostischen Verfahren nur sehr eingeschränkt möglich, da sich für verschiedene Thrombozytopathien sehr variable Sensitivitäten und Spezifitäten ergeben. Nicht zuletzt wird die Interpretation durch die hohe intraund interindividuelle Variabilität der Thrombozytenfunktion erschwert. In der Routine-Abklärung von Thrombozytopathien stehen eine detaillierte Anamnese und klinische Untersuchung in Kombination mit aggregometrischen Basisverfahren weiterhin im Vordergrund.
Embodied semantic processing: The body-object interaction effect in a non-manual task
Authors: Wellsby Michele , Siakaluk Paul D. , Owen William J. , Pexman Penny M.
Published: April 2011

Body-object interaction (BOI) measures people's perceptions of the ease with which a human body can physically interact with a word's referent. Facilitatory BOI effects, involving faster responses for high BOI words, have been reported in a number of visual word recognition tasks using button press responses. Since BOI effects have only been observed in button-press tasks, it is possible that the effects may be due to priming by high BOI words of the motor system, rather than activation of stored motor information in the lexical semantic system. If this hypothesis is correct, BOI effects should not be observed in tasks using verbal responses. We tested this hypothesis in three versions of a go/no-go semantic categorization task: one version required button press responses, whereas the other two versions required verbal responses. Contrary to the motor priming hypothesis, we observed facilitatory BOI effects in all three versions of the semantic categorization task. These results support the inference that stored motor information is indeed an important component of the lexical semantic system.
Low carbon diet: Reducing the complexities of climate change to human scale
Authors: Nerlich Brigitte , Evans Vyvyan , Koteyko Nelya
Published: April 2011

For many years, cognitive linguists, such as Gilles Fauconnier and Mark Turner, have studied meaning construction through language based on intricate mental mapping operations. Their research suggests that conceptual metaphor and conceptual blending permit human beings to reduce very complex issues to human scale. Climate change is such a complex issue. We ask: How is it linguistically reduced to human scale and, in the process, made amenable to thinking and acting? To address these questions, we have analysed the emergence of lexical compounds around a recent key word in debates about climate change in the English speaking world, namely ‘carbon’. One such compound and metaphor/blend is ‘low carbon diet’. In this article we study how the use of the compound ‘low carbon diet’ in an advertising campaign, a book, and by a catering company in the United States permitted US newspapers to reduce climate change to human scale. We have combined and compared metaphor and blending analysis with media and discourse analysis to shed light on the linguistic framing of a real-world problem, that is, we engaged in applied blending analysis.
Property generation reflects word association and situated simulation
Authors: Santos Ava , Chaigneau Sergio E. , Simmons W. Kyle , Barsalou Lawrence W.
Published: April 2011

The property generation task (i.e. “feature listing”) is often assumed to measure concepts. Typically, researchers assume implicitly that the underlying representation of a concept consists of amodal propositions, and that verbal responses during property generation reveal their conceptual content. The experiments reported here suggest instead that verbal responses during property generation reflect two alternative sources of information: the linguistic form system and the situated simulation system. In two experiments, properties bearing a linguistic relation to the word for a concept were produced earlier than properties not bearing a linguistic relation, suggesting the early properties tend to originate in a word association process. Conversely, properties produced later tended to describe objects and situations, suggesting that late properties tend to originate from describing situated simulations. A companion neuroimaging experiment reported elsewhere confirms that early properties originate in language areas, whereas later properties originate in situated simulation areas. Together, these results, along with other results in the literature, indicate that property generation is a relatively complex process, drawing on at least two systems somewhat asynchronously.
Model for the hydrodynamic dispersion of agglomerates incorporating thermoresponsive additives
Authors: Bava Luciana , Feke Donald L. , Manas-Zloczower Ica , Rowan Stuart J.
Published: April 2011

A phenomenological model for the hydrodynamic dispersion of silica agglomerates modified with a thermoresponsive hydrogel (poly-N-isopropylacrylamide, PNIPAM) is presented. The model well describes experimental observations of the dependence of the dispersion behavior on the presence of additives (water and PNIPAM hydrogels) and applied hydrodynamic stress. Most importantly, the thermosensitivity of the dispersion process is captured by characterizing the agglomerate structure and cohesive force at two different temperatures (above and below the hydrogel transition temperature). The transition in dispersion mechanism between rupture-like and erosion-like regimes with system temperature can also be accommodated within the model.
CC Chemokine Receptor 2 Deficiency Aggravates Cognitive Impairments and Amyloid Pathology in a Transgenic Mouse Model of Alzheimer's Disease
Authors: Naert Gaëlle , Rivest Serge
Published: April 2011

Circulating monocytoid cells have the ability to infiltrate nervous tissue, differentiate into microglia, and clear amyloid-β (Aβ) from the brain of mouse models of Alzheimer's disease. Interaction between the chemokine CCL2 and its CC chemokine receptor 2 (CCR2) plays a critical role in the recruitment of inflammatory monocytes into the injured/diseased brain. Here, we show that CCR2 deficiency aggravates mnesic deficits and amyloid pathology in transgenic mice expressing the chimeric mouse/human β-amyloid precursor protein and presenilin 1 (APPSwe/PS1). Indeed, memory impairment was accelerated and enhanced in APPSwe/PS1/CCR2−/−mice. Apparition of cognitive decline occurred earlier (i.e., at 3 months of age before plaque formation) and correlated with intracellular accumulation of soluble oligomeric forms of Aβ. Memory deficits worsened with age and were aggravated in APPSwe/PS1/CCR2−/−mice compared with their respective control groups. Soluble Aβ assemblies increased significantly in APPSwe/PS1 mice in a context of CCR2 deficiency, whereas the plaque load remained relatively similar in the brain of aging APPSwe/PS1 and APPSwe/PS1/CCR2−/−mice. However, CCR2 deficiency stimulated the expression of TGF-β1, TGF-β receptors, and CX3CR1 transcripts in plaque-associated microglia, a pattern that is characteristic of an antiinflammatory subset of myeloid cells. A decreased expression of CCR2 could play a potential role in the etiology of Alzheimer's disease, a neurodegenerative pathology that could be treated by a genetic upregulation of the transgene in monocytoid cells.