bluuebunny/crossref_metadata_2025 huggingface dataset:
Remarkable optical limiting and stabilization effects of a malononitrile derivative on 1064 nm pulsed laser
Authors: Wang Liuheng , Zhao Yuxia , Guan Jinxin , Wu Feipeng
Published: June 2013

A malononitrile derivative, 2-[2,5-bis-(4-diethylamino-benzylidene)-cyclopentylidene]-malononitrile (S2), is reported to exhibit a much more remarkable optical limiting and stabilization behaviors on 1064 nm pulsed laser compared with a typical stilbazolium dye, 4-[2-(4-diethylamino-phenyl)-vinyl]-1-ethyl-pyridinium (R1). The optical limiting mechamisms of S2 and R1 under ns pulsed laser are both due to a two-photon absorption induced excited state absorption process. A superior large excited state absorption cross section of 2.6 × 10−15 cm2 at 1064 nm is found as the main reason to the remarkable optical limiting effect of S2. Meanwhile, S2 presents higher thermal stability and equivalent photochemical stability compared with R1.
Direct mapping of surface plasmon dispersion using imaging scatterometry
Authors: Constant Thomas J. , Hibbins Alastair P. , Lethbridge Alfred J. , Roy Sambles J. , Stone Edmund K. , Vukusic Pete
Published: June 2013

The iso-frequency contours of diffracted surface plasmons on metallic bigratings have been directly recorded using imaging scatterometry. Metallic rectangular bigratings, formed of two “crossed” surface relief gratings, are used to demonstrate this measurement technique. By deepening one of the constituent gratings, control of the surface plasmon dispersion anisotropy is shown in the recorded iso-frequency maps. Collating the iso-frequency contours over a range of wavelengths from 500 nm to 700 nm leads to a three-dimensional map of the surface plasmon dispersion.
Superconducting film magnetic flux transformer with micro- and nanosized branches
Authors: Ichkitidze Levan
Published: June 2013

The object of the study is a superconducting film magnetic flux transformer comprising two square shaped loops with the tapering active strips and a magnetosensitive film element between them. It is shown that splitting of the active strips into parallel micro- and nanosized superconducting branches and slits increases the gain factor of the transformer, i. e., the concentration of an external magnetic field on the magnetosensitive element, by a factor of more than four.
Feasibility study of a self-guided cognitive behaviour therapy Internet intervention for cancer carers
Authors: Scott Karen , Beatty Lisa
Published: June 2013

Despite the evidence base for Internet-delivered self-help programmes, their application to cancer carers has not been reported. This feasibility study evaluated a 6-week internet cognitive behaviour therapy (CBT) programme for early stage cancer carers. The study participants comprised 13 carers who were recruited over a 17-month period. Measures included distress, quality of life and programme engagement. Changes over time were measured using effect sizes (Cohen’s d), whereas acceptibility was assessed using qualitative feedback. Low enrolment and high attrition rates resulted in a failure to demonstrate feasibility. Large improvements in negative affect (d = 0.88) and emotional functioning (d = 0.62) were found. For treatment completers, the intervention holds promise in reducing distress. However, in light of the serious challenges with recruitment and retention, further research is needed to resolve participation barriers.
Identifying host species driving transmission of schistosomiasis japonica, a multihost parasite system, in China
Authors: Rudge James W. , Webster Joanne P. , Lu Da-Bing , Wang Tian-Ping , Fang Guo-Ren , Basáñez María-Gloria
Published: June 2013

Understanding disease transmission dynamics in multihost parasite systems is a research priority for control and potential elimination of many infectious diseases. In China, despite decades of multifaceted control efforts against schistosomiasis, the indirectly transmitted helminthSchistosoma japonicumremains endemic, partly because of the presence of zoonotic reservoirs. We used mathematical modeling and conceptual frameworks of multihost transmission ecology to assess the relative importance of various definitive host species forS. japonicumtransmission in contrasting hilly and marshland areas of China. We examine whether directing control interventions against zoonotic reservoirs could further reduce incidence of infection in humans or even eliminate transmission. Results suggest that, under current control programs, infections in humans result from spillover of transmission among zoonotic reservoirs. Estimates of the basic reproduction number within each species suggest that bovines (water buffalo and cattle) maintained transmission in the marshland area and that the recent removal of bovines from this area could achieve local elimination of transmission. However, the sole use of antifecundityS. japonicumvaccines for bovines, at least at current efficacies, may not achieve elimination in areas of comparable endemicity where removal of bovines is not a feasible option. The results also suggest that rodents drive transmission in the hilly area. Therefore, although targeting bovines could further reduce and potentially interrupt transmission in marshland regions of China, elimination ofS. japonicumcould prove more challenging in areas where rodents might maintain transmission. In conclusion, we show how mathematical modeling can give important insights into multihost transmission of indirectly transmitted pathogens.
Intrinsic connectivity networks in healthy subjects explain clinical variability in Alzheimer’s disease
Authors: Lehmann Manja , Madison Cindee M. , Ghosh Pia M. , Seeley William W. , Mormino Elizabeth , Greicius Michael D. , Gorno-Tempini Maria Luisa , Kramer Joel H. , Miller Bruce L. , Jagust William J. , Rabinovici Gil D.
Published: June 2013

Although previous studies have emphasized the vulnerability of the default mode network (DMN) in Alzheimer’s disease (AD), little is known about the involvement of other functional networks and their relationship to clinical phenotype. To test whether clinicoanatomic heterogeneity in AD is driven by the involvement of specific networks, network connectivity was assessed in healthy subjects by seeding regions commonly and specifically atrophied in three clinical AD variants: early-onset AD (age at onset, <65 y; memory and executive deficits), logopenic variant primary progressive aphasia (language deficits), and posterior cortical atrophy (visuospatial deficits). Four-millimeter seed regions of interest were used to obtain intrinsic connectivity maps in 131 healthy controls (age, 65.5 ± 3.5 y). Atrophy patterns in independent cohorts of AD variant patients and their correspondence to connectivity networks in controls were also assessed. The connectivity maps of commonly atrophied regions of interest support posterior DMN and precuneus network involvement across AD variants, whereas seeding regions specifically atrophied in each AD variant revealed distinct, syndrome-specific connectivity patterns. Goodness-of-fit analysis of each connectivity map with network templates showed the highest correspondence between the early-onset AD seed connectivity map and anterior salience and right executive-control networks, the logopenic aphasia seed connectivity map and the language network, and the posterior cortical atrophy seed connectivity map and the higher visual network. Connectivity maps derived from controls matched regions commonly and specifically atrophied in the patients. Our findings indicate that the posterior DMN and precuneus network are commonly affected in AD variants, whereas syndrome-specific neurodegenerative patterns are driven by the involvement of specific networks outside the DMN.
Energy-dependent motion of TonB in the Gram-negative bacterial inner membrane
Authors: Jordan Lorne D. , Zhou Yongyao , Smallwood Chuck R. , Lill Yoriko , Ritchie Ken , Yip Wai Tak , Newton Salete M. , Klebba Phillip E.
Published: June 2013

Gram-negative bacteria acquire iron with TonB-dependent uptake systems. The TonB–ExbBD inner membrane complex is hypothesized to transfer energy to outer membrane (OM) iron transporters. Fluorescence microscopic characterization of green fluorescent protein (GFP)-TonB hybrid proteins revealed an unexpected, restricted localization of TonB in the cell envelope. Fluorescence polarization measurements demonstrated motion of TonB in living cells, which likely was rotation. By determining the anisotropy of GFP-TonB in the absence and presence of inhibitors, we saw the dependence of its motion on electrochemical force and on the actions of ExbBD. We observed higher anisotropy for GFP-TonB in energy-depleted cells and lower values in bacteria lacking ExbBD. However, the metabolic inhibitors did not change the anisotropy of GFP-TonB inΔexbBDcells. These findings demonstrate that TonB undergoes energized motion in the bacterial cell envelope and that ExbBD couples this activity to the electrochemical gradient. The results portray TonB as an energized entity in a regular array underlying the OM bilayer, which promotes metal uptake through OM transporters by a rotational mechanism.
Tuning gene expression with synthetic upstream open reading frames
Authors: Ferreira Joshua P. , Overton K. Wesley , Wang Clifford L.
Published: June 2013

We engineered short ORFs and used them to control the expression level of recombinant proteins. These short ORFs, encoding a two-amino acid peptide, were placed upstream of an ORF encoding a protein of interest. Insertion of these upstream ORFs (uORFs) resulted in suppression of protein expression. By varying the base sequence preceding the uORF, we sought to vary the translation initiation rate of the uORF and subsequently control the degree of this suppression. Using this strategy, we generated a library of RNA sequence elements that can specify protein expression over a broad range of levels. By also using multiple uORFs in series and non-AUG start codons, we were able to generate particularly low expression levels, allowing us to achieve expression levels spanning three orders of magnitude. Modeling supported a mechanism where uORFs shunt the flow of ribosomes away from the downstream protein-coding ORF. With a lower translation initiation rate at the uORF, more ribosomes “leak” past the uORF; consequently, more ribosomes are able to reach and translate the downstream ORF. We report expression control by engineering uORFs and translation initiation to be robust, predictable, and reproducible across all cell types tested. We propose control of translation initiation as a primary method of choice for tuning expression in mammalian systems.
Vibrio
effector protein, VopQ, forms a lysosomal gated channel that disrupts host ion homeostasis and autophagic flux
Authors: Sreelatha Anju , Bennett Terry L. , Zheng Hui , Jiang Qiu-Xing , Orth Kim , Starai Vincent J.
Published: June 2013

Defects in normal autophagic pathways are implicated in numerous human diseases—such as neurodegenerative diseases, cancer, and cardiomyopathy—highlighting the importance of autophagy and its proper regulation. Herein we show that
Vibrio parahaemolyticus
uses the type III effector VopQ (Vibrio outer protein Q) to alter autophagic flux by manipulating the partitioning of small molecules and ions in the lysosome. This effector binds to the conserved V
o
domain of the vacuolar-type H
+
-ATPase and causes deacidification of the lysosomes within minutes of entering the host cell. VopQ forms a gated channel ∼18 Å in diameter that facilitates outward flux of ions across lipid bilayers. The electrostatic interactions of this type 3 secretion system effector with target membranes dictate its preference for host vacuolar-type H
+
-ATPase–containing membranes, indicating that its pore-forming activity is specific and not promiscuous. As seen with other effectors, VopQ is exploiting a eukaryotic mechanism, in this case manipulating lysosomal homeostasis and autophagic flux through transmembrane permeation.
Encoded multisite two-photon microscopy
Authors: Ducros Mathieu , Houssen Yannick Goulam , Bradley Jonathan , de Sars Vincent , Charpak Serge
Published: June 2013

The advent of scanning two-photon microscopy (2PM) has created a fertile new avenue for noninvasive investigation of brain activity in depth. One principal weakness of this method, however, lies with the limit of scanning speed, which makes optical interrogation of action potential-like activity in a neuronal network problematic. Encoded multisite two-photon microscopy (eMS2PM), a scanless method that allows simultaneous imaging of multiple targets in depth with high temporal resolution, addresses this drawback. eMS2PM uses a liquid crystal spatial light modulator to split a high-power femto-laser beam into multiple subbeams. To distinguish them, a digital micromirror device encodes each subbeam with a specific binary amplitude modulation sequence. Fluorescence signals from all independently targeted sites are then collected simultaneously onto a single photodetector and site-specifically decoded. We demonstrate that eMS2PM can be used to image spike-like voltage transients in cultured cells and fluorescence transients (calcium signals in neurons and red blood cells in capillaries from the cortex) in depth in vivo. These results establish eMS2PM as a unique method for simultaneous acquisition of neuronal network activity.
Transformation of the neural code for tactile detection from thalamus to cortex
Authors: Vázquez Yuriria , Salinas Emilio , Romo Ranulfo
Published: June 2013

Significance

Place a hand on the hood of a car and ask, is it running or not? Answering this involves the sequential activation of many neurons, from mechanoreceptors under the skin to cortical neurons whose activity is closely related to the evoked internal sensation. We investigate how vibratory stimuli are represented in two steps along this processing chain during a detection task. We find that activity changes from a “literal” code, in which neural responses faithfully track the stimulus, to a more abstract and robust one, from which other neurons can more easily infer whether a stimulus was presented or not.
Modeling the Influence of Parr Predation by Walleyes and Brown Trout on the Long‐Term Population Dynamics of Chinook Salmon in Lake Michigan: A Stage Matrix Approach
Authors: Krueger Damon M. , Rutherford Edward S. , Mason Doran M.
Published: June 2013

Predation events during ontogeny may have long‐term consequences for fish population abundance and variability. We used a stage‐based matrix model to evaluate Walleye Sander vitreus and Brown Trout Salmo trutta predation on Chinook Salmon Oncorhynchus tshawytscha parr of the Muskegon River stock and the relative influence of parr predation on the long‐term population dynamics and recruitment of Chinook Salmon in Lake Michigan. The model predicted the number of Chinook Salmon individuals in each stage (fry, smolts, and lake age 0 [recruits] through lake age 4) and forecasted population trajectories based on demographic data (e.g., survival, growth, and fecundity). The relative influence of parr predation was compared with influences of environmental stochasticity in the egg stage and Alewife Alosa pseudoharengus abundance (prey for lake‐stage salmon) on Chinook Salmon fecundity, recruitment, and population growth. To simulate environmental stochasticity and the influence of Alewife abundance, we varied Chinook Salmon stage‐specific survival rates, growth rates, maturity schedule, and carrying capacity. Relative to a baseline recruitment scenario, removal of stocked Brown Trout resulted in a significant increase in parr survival and long‐term Chinook Salmon abundance. Walleye predation on parr had little apparent influence on Chinook Salmon population dynamics. Predation on parr during out‐migration was positively correlated with variation in Chinook Salmon population stability and was negatively correlated with population growth, suggesting that Brown Trout have a significant negative effect on Chinook Salmon recruitment and long‐term population stability. The negative effects of variation in egg survival rates and Alewife abundance on Chinook Salmon recruitment and population growth rates were similar to the negative effects from parr predation scenarios. Our study suggests that management decisions to promote Great Lakes Chinook Salmon populations may require evaluation of trout stocking practices in nursery habitats.
A weak vector-valued Banach-Stone theorem
Authors: Candido Leandro , Galego Elói
Published: June 2013

For a locally compact Hausdorff space

X
X

and a Banach space

E
E

, we denote by

C
0

(
X
,
E
)

C_0(X, E)

the space of

E
E

-valued continuous functions on

X
X

which vanish at infinity, endowed with the supremum norm. In the spirit of the classical Banach-Stone theorem, we prove that if

C
0

(
X
,
E
)

C_0(X, E)

is isomorphic to

C

0

(
Y
,
E
)

C_{0}(Y, E)

, where

E
E

has non-trivial cotype and such that

E
E

is separable or

E
∗

E^*

has the Radon-Nikodým property, then either

X
X

and

Y
Y

are finite or

X
X

and

Y
Y

have the same cardinality. In other words, we obtain a vector-valued extension of a 1978 B. Cengiz result, the scalar case

E
=

R

E=\mathbb R

or

E
=

C

.

E=\mathbb C.
Mathematical models of immune-induced cancer dormancy and the emergence of immune evasion
Authors: Wilkie Kathleen P. , Hahnfeldt Philip
Published: June 2013

Cancer dormancy, a state in which cancer cells persist in a host without significant growth, is a natural forestallment of progression to manifest disease and is thus of great clinical interest. Experimental work in mice suggests that in immune-induced dormancy, the longer a cancer remains dormant in a host, the more resistant the cancer cells become to cytotoxic T-cell-mediated killing. In this work, mathematical models are used to analyse the possible causative mechanisms of cancer escape from immune-induced dormancy. Using a data-driven approach, both decaying efficacy in immune predation and immune recruitment are analysed with results suggesting that decline in recruitment is a stronger determinant of escape than increased resistance to predation. Using a mechanistic approach, the existence of an immune-resistant cancer cell subpopulation is considered, and the effects on cancer dormancy and potential immunoediting mechanisms of cancer escape are analysed and discussed. The immunoediting mechanism assumes that the immune system selectively prunes the cancer of immune-sensitive cells, which is shown to cause an initially heterogeneous population to become a more homogeneous, and more resistant, population. The fact that this selection may result in the appearance of decreasing efficacy in T-cell cytotoxic effect with time in dormancy is also demonstrated. This work suggests that through actions that temporarily delay cancer growth through the targeted removal of immune-sensitive subpopulations, the immune response may actually progress the cancer to a more aggressive state.
Three-dimensional vasculature reconstruction of tumour microenvironment via local clustering and classification
Authors: Zhu Yanqiao , Li Fuhai , Vadakkan Tegy J. , Zhang Mei , Landua John , Wei Wei , Ma Jinwen , Dickinson Mary E. , Rosen Jeffrey M. , Lewis Michael T. , Zhan Ming , Wong Stephen T. C.
Published: June 2013

The vasculature inside breast cancers is one important component of the tumour microenvironment. The investigation of its spatial morphology, distribution and interactions with cancer cells, including cancer stem cells, is essential for elucidating mechanisms of tumour development and treatment response. Using confocal microscopy and fluorescent markers, we have acquired three-dimensional images of vasculature within mammary tumours and normal mammary gland of mouse models. However, it is difficult to segment and reconstruct complex vasculature accurately from the
in vivo
three-dimensional images owing to the existence of uneven intensity and regions with low signal-to-noise ratios (SNR). To overcome these challenges, we have developed a novel three-dimensional vasculature segmentation method based on local clustering and classification. First, images of vasculature are clustered into local regions, whose boundaries well delineate vasculature even in low SNR and uneven intensity regions. Then local regions belonging to vasculature are identified by applying a semi-supervised classification method based on three informative features of the local regions. Comparison of results using simulated and real vasculature images, from mouse mammary tumours and normal mammary gland, shows that the new method outperforms existing methods, and can be used for three-dimensional images with uneven background and low SNR to achieve accurate vasculature reconstruction.
Tumour–stromal interactions generate emergent persistence in collective cancer cell migration
Authors: Chang William K. , Carmona-Fontaine Carlos , Xavier Joao B.
Published: June 2013

Cancer cell collective migration is a complex behaviour leading to the invasion of cancer cells into surrounding tissue, often with the aid of stromal cells in the microenvironment, such as macrophages or fibroblasts. Although tumour–tumour and tumour–stromal intercellular signalling have been shown to contribute to cancer cell migration, we lack a fundamental theoretical understanding of how aggressive invasion emerges from the synergy between these mechanisms. We use a computational self-propelled particle model to simulate intercellular interactions between co-migrating tumour and stromal cells and study the emergence of collective movement. We find that tumour–stromal interaction increases the cohesion and persistence of migrating mixed tumour–stromal cell clusters in a noisy and unbounded environment, leading to increased cell cluster size and distance migrated by cancer cells. Although environmental constraints, such as vasculature or extracellular matrix, influence cancer migration
in vivo
, our model shows that cell–cell interactions are sufficient to generate cohesive and persistent movement. From our results, we conclude that inhibition of tumour–stromal intercellular signalling may present a viable therapeutic target for disrupting collective cancer cell migration.
The impact of protein-conjugate polysaccharide vaccines: an endgame for meningitis?
Authors: Maiden Martin C. J.
Published: June 2013

The development and implementation of conjugate polysaccharide vaccines against invasive bacterial diseases, specifically those caused by the encapsulated bacteria
Neisseria meningitidis
,
Haemophilus influenzae
and
Streptococcus pneumoniae
, has been one of the most effective public health innovations of the last 25 years. These vaccines have resulted in significant reductions in childhood morbidity and mortality worldwide, with their effectiveness due in large part to their ability to induce long-lasting immunity in a range of age groups. At the population level this immunity reduces carriage and interrupts transmission resulting in herd immunity; however, these beneficial effects can be counterbalanced by the selection pressures that immunity against carriage can impose, potentially promoting the emergence and spread of virulent vaccine escape variants. Studies following the implementation of meningococcal serogroup C vaccines improved our understanding of these effects in relation to the biology of accidental pathogens such as the meningococcus. This understanding has enabled the refinement of the implementation of conjugate polysaccharide vaccines against meningitis-associated bacteria, and will be crucial in maintaining and improving vaccine control of these infections. To date there is little evidence for the spread of virulent vaccine escape variants of the meningococcus and
H. influenzae
, although this has been reported in pneumococci.
MicroRNA-138 and SIRT1 form a mutual negative feedback loop to regulate mammalian axon regeneration
Authors: Liu Chang-Mei , Wang Rui-Ying , Saijilafu  , Jiao Zhong-Xian , Zhang Bo-Yin , Zhou Feng-Quan
Published: June 2013

Regulated gene expression determines the intrinsic ability of neurons to extend axons, and loss of such ability is the major reason for the failed axon regeneration in the mature mammalian CNS. MicroRNAs and histone modifications are key epigenetic regulators of gene expression, but their roles in mammalian axon regeneration are not well explored. Here we report microRNA-138 (miR-138) as a novel suppressor of axon regeneration and show that SIRT1, the NAD-dependent histone deacetylase, is the functional target of miR-138. Importantly, we provide the first evidence that miR-138 and SIRT1 regulate mammalian axon regeneration in vivo. Moreover, we found that SIRT1 also acts as a transcriptional repressor to suppress the expression of miR-138 in adult sensory neurons in response to peripheral nerve injury. Therefore, miR-138 and SIRT1 form a mutual negative feedback regulatory loop, which provides a novel mechanism for controlling intrinsic axon regeneration ability.
An IKKα–E2F1–BMI1 cascade activated by infiltrating B cells controls prostate regeneration and tumor recurrence
Authors: Ammirante Massimo , Kuraishy Ali I. , Shalapour Shabnam , Strasner Amy , Ramirez-Sanchez Claudia , Zhang Weizhou , Shabaik Ahmed , Karin Michael
Published: June 2013

Androgen-deprived prostate cancer (PCa) is infiltrated by B lymphocytes that produce cytokines that activate IκB kinase α (IKKα) to accelerate the emergence of castration-resistant tumors. We now demonstrate that infiltrating B lymphocytes and IKKα are also required for androgen-dependent expansion of epithelial progenitors responsible for prostate regeneration. In these cells and in PCa cells, IKKα phosphorylates transcription factor E2F1 on a site that promotes its nuclear translocation, association with the coactivator CBP, and recruitment to critical genomic targets that include Bmi1, a key regulator of normal and cancerous prostate stem cell renewal. The IKKα–BMI1 pathway is also activated in human PCa.
Insights into population ecology from long‐term studies of red grouseLagopus lagopus scoticus
Authors: Martínez‐Padilla Jesus , Redpath Steve M. , Zeineddine Mohammed , Mougeot François
Published: June 2013

Long‐term studies have been the backbone of population ecology. The red grouseLagopus lagopus scoticusis one species that has contributed widely to this field since the 1950s. This paper reviews the trajectory and profound impact that these studies have had.

Red grouse research has combined long‐term studies of marked individuals with demographic studies over wide geographical areas and replicated individual‐ and population‐level manipulations.

A main focus has been on understanding the causes of population cycles in red grouse, and in particular the relative importance of intrinsic (behaviour) and extrinsic (climate, food limitation and parasite) mechanisms.

Separate studies conducted in different regions initially proposed either the nematode parasiteTrichostrongylus tenuisor changes in male aggressiveness in autumn as drivers of population cycles.

More recent experiments suggest that parasites are not a necessary cause for cycles and have highlighted that behavioural and parasite‐mediated mechanisms are interrelated. Long‐term experiments show that parasites and aggressiveness interact.

Two outstanding questions remain to be tested experimentally. First, what intrinsic mechanism causes temporal variation in patterns of male aggressiveness? The current favoured mechanism is related to patterns of kin structuring although there are alternative hypotheses. Second, how do the dual, interacting mechanisms, affect population dynamics?

Red grouse studies have had an important impact on the field of population ecology, in particular through highlighting: (1) the impact of parasites on populations; (2) the role of intrinsic mechanisms in cyclic dynamics and (3) the need to consider multiple, interacting mechanisms.
Chronic Alcohol Consumption Increases the Expression of Uncoupling Protein‐2 and ‐4 in the Brain
Authors: Graw Jan A. , von Haefen Clarissa , Poyraz Deniz , Möbius Nadine , Sifringer Marco , Spies Claudia D.
Published: June 2013

Background

Chronic alcohol consumption leads to oxidative stress in a variety of cells, especially in brain cells because they have a reduced oxidative metabolism of alcohol. Uncoupling proteins (UCPs) are anion channels of the inner mitochondrial membrane, which can decouple internal respiration. “Mild uncoupling” of the mitochondrial respiratory chain leads to a reduced production of free radicals (reactive oxygen species) and a reduction in oxidative cell stress. The extent to which chronic alcohol consumption regulates UCP‐2 and ‐4 in the brain is still unknown.

Methods

We examined the effects of a 12‐week 5% alcohol diet in the brain of male Wistar rats (n = 34). Cerebral gene and protein expression of UCP‐2, ‐4, as well as Bcl‐2, and the release of cytochrome c out of the mitochondria were detected by real‐time polymerase chain reaction and Western blot analysis. The percentage of degenerated cells was determined by Fluoro–Jade B staining of brain slices.

Results

Brains of rats with a chronic alcohol diet showed an increased gene and protein expression of UCP‐2 and ‐4. The expression of the antiapoptotic protein Bcl‐2 in the brain of the alcohol‐treated animals was decreased significantly, whereas cytochrome c release from mitochondria was increased. In addition increased neurodegeneration could be demonstrated in the alcohol‐treated animals.

Conclusions

Chronic alcohol consumption leads to a cerebral induction of UCP‐2 and ‐4 with a simultaneous decrease in the antiapoptotic protein Bcl‐2, cytochrome c release from mitochondria and increased neurodegeneration. This study reveals a compensatory effect of UCP‐2 and ‐4 in the brain during chronic alcohol consumption.
Loss of Control of Alcohol Use and Severity of Alcohol Dependence in Non‐Treatment‐Seeking Heavy Drinkers Are Related to Lower Glutamate in Frontal White Matter
Authors: Ende Gabriele , Hermann Derik , Demirakca Traute , Hoerst Mareen , Tunc‐Skarka Nuran , Weber‐Fahr Wolfgang , Wichert Svenja , Rabinstein Juri , Frischknecht Ulrich , Mann Karl , Vollstädt‐Klein Sabine
Published: June 2013

Background

The development and maintenance of alcohol use disorders (AUD) have been hypothesized to be associated with an imbalance of glutamate (GLU) homeostasis. White matter (WM) loss, especially in anterior brain regions, has been reported in alcohol dependence, which may involve disturbances in both myelin and axonal integrity. Frontal lobe dysfunction plays an important role in addiction, because it is suggested to be associated with the loss of control over substance use. This study investigated magnetic resonance spectroscopy (MRS)‐detectable Glu levels in frontal WM of non‐treatment‐seeking heavy drinkers and its associations with AUD symptoms.

Methods

Single‐voxel MR spectra optimized for Glu assessment (TE 80 ms) were acquired at 3T from a frontal WM voxel in a group of heavy drinking, non‐treatment‐seeking subjects in comparison with a group of subjects with only light alcohol consumption.

Results

The results corroborate previous findings of increased total choline in heavy drinking subjects. A negative association of Glu levels with severity of alcohol dependence and especially loss of control over time and amount of alcohol intake was observed.

Conclusions

In contrast to the rather unspecific rise in choline‐containing compounds, low Glu in frontal WM may be specific for the shift from nondependent heavy drinking to dependence and does not reflect a simple effect of the amount of alcohol consumption alone.
Measuring psychotic depression
Authors: Østergaard S. D. , Meyers B. S. , Flint A. J. , Mulsant B. H. , Whyte E. M. , Ulbricht C. M. , Bech P. , Rothschild A. J. ,   on behalf of the STOP‐PD Study Group
Published: June 2013

Objective

Psychotic depression (PD) is a highly debilitating condition, which needs intensive monitoring. However, there is no established rating scale for evaluating the severity of PD. The aim of this analysis was to assess the psychometric properties of established depression rating scales and a number of new composite rating scales, covering both depressive and psychotic symptoms, in relation to PD.

Method

The psychometric properties of the rating scales were evaluated based on data from the Study of Pharmacotherapy of Psychotic Depression.

Results

A rating scale consisting of the 6‐item Hamilton melancholia subscale (HAM‐D6) plus five items from the Brief Psychiatric Rating Scale (BPRS), named the HAMD‐BPRS11, displayed clinical validity (Spearman's correlation coefficient between HAMD‐BPRS11 and Clinical Global Impression – Severity (CGI‐S) scores = 0.79–0.84), responsiveness (Spearman's correlation coefficient between change in HAMD‐BPRS11 and Clinical Global Impression – Improvement (CGI‐I) scores = −0.74–−0.78) and unidimensionality (Loevinger's coefficient of homogeneity = 0.41) in the evaluation of PD. The HAM‐D6 fulfilled the same criteria, whereas the full 17‐item Hamilton Depression Scale failed to meet criteria for unidimensionality.

Conclusion

Our results suggest that the HAMD‐BPRS11 is a more valid measure than pure depression scales for evaluating the severity of PD.
Burning season effects on the short‐term post‐fire vegetation dynamics of a Mediterranean heathland
Authors: Céspedes Blanca , Luna Belén , Pérez Beatriz , Urbieta Itziar R. , Moreno José M.
Published: June 2013

Question

What are the short‐term (first 4 yrs) dynamics of a Mediterranean heathland following burning during the early‐ vs the late‐fire season?

Location

Serra da Lousã, Central Portugal.

Methods

The vegetation studied was a 16‐year old heathland with Erica australis (resprouter), Pterospartum tridentatum (resprouter/seeder) and Erica umbellata (seeder) among the dominant species. Four blocks, each with three 50 m × 40 m plots, were established. One plot per block was burned during the early season (ES) and one during the late season (LS), and the third remained unburned. Prior to, and during the first 4 yrs after burning, each burned plot was sampled for species abundance, vigour and richness. The effects of fire through time were tested using random blocks repeated measures ANOVA. Recruitment was modelled as a function of percentage of post‐fire soil covered by litter (%). MANOVA was used to test changes in the relative dominance of the woody species due to fire. Community dynamics were assessed by NMDS ordination analysis.

Results

Fire severity was higher and the percentage of post‐fire soil covered by litter lower in ES than LS burns. The post‐fire plant dynamics were dominated by the resprouting response. Resprouting was not affected by burning season, but ES fires resulted in higher seedling recruitment than LS fires, particularly in the dominant seeder E. umbellata. Seedling recruitment was negatively related to post‐fire soil covered by litter. Additionally, seedling emergence was delayed by nearly 1 yr in LS fires with respect to ES fires. Species richness was higher in ES than LS fires. Fire did not globally affect the relative abundance of the dominant species, although the seeder E. umbellata decreased its relative cover with respect to the other dominant species. Ordination analysis showed that the post‐fire dynamics of the vegetation were on a track of convergence with the community existing before fire.

Conclusion

Burning season differentially affected regeneration, mainly by its effect on seeding, with little effect on resprouting. Burning season and associated changes in fire severity and soil covered by litter could alter the short‐term regeneration dynamics, which can have important implications for managing this highly flammable vegetation.
Culture, Perception, and Artistic Visualization: A Comparative Study of Children's Drawings in Three Siberian Cultural Groups
Authors: Istomin Kirill V. , Panáková Jaroslava , Heady Patrick
Published: June 2013

In a study of three indigenous and non‐indigenous cultural groups in northwestern and northeastern Siberia, framed line tests and a landscape drawing task were used to examine the hypotheses that test‐based assessments of context sensitivity and independence are correlated with the amount of contextual information contained in drawings, and with the order in which the focal and background objects are drawn. The results supported these hypotheses, and inspection of the regression relationships suggested that the intergroup variations in test performance were likely to result from differences in the attention accorded to contextual information, as revealed by the drawings. Social and environmental explanations for the group differences in context sensitivity are also discussed. The conclusions support the argument that cultural differences in artistic styles and perceptual tests reflect the same underlying perceptual tendencies, and they are consistent with the argument that these tendencies reflect corresponding differences in patterns of social and environmental interaction.
GLA mutation as a risk factor for later life small vessel ischaemic disease
Authors: Meschia J. F.
Published: June 2013

Click here to view the accompanying paper in this issue.
A novel SACS mutation results in non‐ataxic spastic paraplegia and peripheral neuropathy
Authors: Gregianin E. , Vazza G. , Scaramel E. , Boaretto F. , Vettori A. , Leonardi E. , Tosatto S. C. E. , Manara R. , Pegoraro E. , Mostacciuolo M. L.
Published: June 2013

Background and purpose

Mutations in the SACS gene are commonly associated with autosomal recessive spastic ataxia of Charlevoix‐Saguenay (ARSACS), a complex neurodegenerative disorder characterized by progressive degeneration of the cerebellum and spinal cord tracts. The aim of this study was to identify the genetic cause of the disease in an Italian family with spastic paraplegia and peripheral neuropathy.

Methods

Affected subjects were subjected to a comprehensive neurological examination including electromyography and brain magnetic resonance imaging. Genetic studies included exclusion of known disease genes, genome‐wide linkage analysis using high density single nucleotide polymorphism genotyping and candidate gene sequencing.

Results

Molecular analyses revealed a novel missense mutation in the SACS gene (c.11,104A>G) occurring in a homozygous state in patients and absent in 700 Italian control chromosomes. The mutation led to the amino acid substitution p.Thr3702Ala in the sacsin protein, in a possible protein−protein interaction site of UBE3A binding domain.

Conclusion

This study broadens the genetic spectrum of SACS mutations and expands the clinical ARSACS phenotype suggesting that the SACS gene can be considered in patients with non‐canonical ARSACS clinical presentations.
The Confusions and Exuberances of Biopolitics
Authors: Rutherford Paul , Rutherford Stephanie
Published: June 2013

This paper is the first of a two‐part exploration of the significance of biopolitics to the study of geography. Our first paper surveys the emergent field of biopolitics by looking at the philosophical underpinnings of the concept and some of the ways in which scholars, including geographers, have utilized the concept as an analytical tool. Throughout the papers, we make the argument for a greater degree of empirical rigor and conceptual clarity in the way the term biopolitics is deployed and operationalized.
Concerted interaction between origin recognition complex (ORC), nucleosomes and replication originDNAensures stableORC–origin binding
Authors: Hizume Kohji , Yagura Masaru , Araki Hiroyuki
Published: June 2013

Chromosomal replication origins, whereDNAreplication is initiated, are determined in eukaryotic cells by specific binding of a six‐subunit origin recognition complex (ORC). Many biochemical analyses have showed the detailed properties of theORC–DNAinteraction. However, because of the lack ofin vitroanalysis, the molecular architecture of theORC–chromatin interaction is unclear. Recently, mainly fromin vivoanalyses, a role of chromatin in theORC–origin interaction has been reported, including the existence of a specific pattern of nucleosome positioning around origins and of a specific interaction between chromatin—or core histones—and Orc1, a subunit ofORC. Therefore, to understand howORCestablishes its interaction with originin vivo, it is essential to know the molecular mechanisms of theORC–chromatin interaction. Here, we show thatORCpurified from yeast binds more stably to origin‐containing reconstituted chromatin than to nakedDNAand forms a nucleosome‐free region at origins. Molecular imaging using atomic force microscopy (AFM) shows thatORCassociates with the adjacent nucleosomes and forms a larger complex. Moreover, stable binding ofORCto chromatin requires linkerDNA. Thus,ORCestablishes its interaction with origin by binding to both nucleosome‐free originDNAand neighboring nucleosomes.
Molecular cloning, sequencing and structural studies of granulocyte–macrophage colony‐stimulating factor (GM‐CSF) from Indian water buffalo (Bubalus bubalis)
Authors: Sugumar Thennarasu , Pugalenthi Ganesan , Harishankar Murugesan , Dhinakar Raj G
Published: June 2013

Granulocyte–macrophage colony‐stimulating factor (GM‐CSF) is a cytokine that is essential for growth and development of progenitors of granulocytes and monocytes/macrophages. In this study, we report molecular cloning, sequencing and characterization of GM‐CSF from Indian water buffalo, Bubalus bubalis. In addition, we performed sequence and structural analysis for buffalo GM‐CSF. Buffalo GM‐CSF has been compared with 17 mammalian GM‐CSFs using multiple sequence alignment and phylogenetic tree. Three‐dimensional model for buffalo GM‐CSF and human receptor complex was built using homology modelling to study cross‐reactivity between two species. Detailed analysis was performed to study GM‐CSF interface and various interactions at the interface.
Has Europe Been Catching Up? An Industry Level Analysis of Venture Capital Success over 1985–2009
Authors: Kräussl Roman , Krause Stefan
Published: June 2013

After nearly two decades of US leadership during the 1980s and 1990s, are Europe's venture capital (VC) markets in the 2000s finally catching up regarding the provision of financing and successful exits, or is the performance gap as wide as ever? Are we amid an overall VC performance slump with no encouraging news? We attempt to answer these questions by tracking over 40,000 VC‐backed firms stemming from six industries in 13 European countries and the USA between 1985 and 2009; determining the type of exit – if any – each particular firm's investors choose for the venture.
Radiotherapy in the Management of Far‐Advanced Cutaneous Malignancies
Authors: COOPER JAY S.
Published: June 2013

Far‐advanced cutaneous malignancies for which no other treatment is feasible may be benefitted by radiotherapy. The treatments of two such cases by techniques of modern radiotherapy are described and illustrated.
Scalp Reduction for Correction of Cutis Aplasia Congenita
Authors: McCRAY MICHAEL K. , ROENIGK HENRY H.
Published: June 2013

A case of cutis aplasia congenita is presented that was managed successfully by the technique of scalp reduction. A review of this congenital anomaly and its modes of surgical treatment are given. Scalp reduction is an excellent way of correcting both cicatricial and non‐cicatricial alopecias.
Surgical Treatment of Carcinoma of the Lip
Authors: TRIAS A. ANDRES , FRESNEDA A. CAMPS , SEMERARO C.
Published: June 2013

The authors' experience in treating carcinomas of the lips by surgery with occasional adjunctive radiotherapy is reported. Types of surgical techniques for various levels of tumors, cure rates, and cosmetic results are described and illustrated.
Wound Healing: A Review. IV. Systemic Medications Affecting Wound Healing
Authors: POLLACK SHELDON V.
Published: June 2013

Physicians performing dermatologic surgery should include a thorough drug history in their preoperative assessments of patients. Such information may allow for the discontinuation, if desired, of drugs that negatively influence the wound‐healing process. In some instances, the surgeon may find it useful, during the perioperative period, to substitute a drug known to impede wound healing with another possessing no untoward effects. In other situations, as in the treatment of keloids, physicians may wish to introduce drugs known to reduce scar formation into the biologic environment in which wound healing ensues.
Subdermal Basal‐Cell Carcinoma
Authors: GRANDE DONALD J. , WHITAKER DUANE C. , KORANDA FRANK C.
Published: June 2013

A case of recurrent basal‐cell carcinoma at the mandibular ramus presented clinically with a subdermal nodule. The patient had previously been treated with aggressive curettage and electrodesiccation which had penetrated through the dermis. The authors postulate that either incomplete extirpation of the neoplasm with the curet or iatrogenic deep implantation of the tumor during the procedure may have led to the presentation of the recurrence as a subdermal nodule.
Epidermal Cell Outgrowth from CO2 Laser‐ and Scalpel‐Cut Explants: Implications for Wound Healing
Authors: MORENO RUBEN A. , HEBDA PATRICIA A. , ZITELLI JOHN A. , ABELL EDWARD
Published: June 2013

Abstract
We set out to determine if the slow healing of CO2 laser‐incised skin wounds compared with that of scalpel‐incised wounds is the result of an inhibitory effect of the CO2 laser energy on the rate of epithelialization. We compared the rate of epidermal outgrowth from laser‐and scalpel‐cut explants in vitro. The onset of epidermal cell outgrowth (epiboly) from CO2 laser‐incised skin was delayed, but there was no difference in the rate of epidermal cell outgrowth. These studies suggest that a delay in onset of epidermal migration, not a decreased rate of epidermal migration, contributes to the slower epithelialization of CO2 laser‐incised skin wounds.
Cutaneous Meningioma
Authors: SERWATKA LINDA M. , MELLETTE J. RAMSEY
Published: June 2013

Abstract
A case of a subcutaneous meningioma is presented. It is uncommonly encountered but, because of its superficial location, is apt to present to a dermatologist. Meningioma should be included in the differential diagnosis of lesions of the scalp, especially the midline, face, and paraspinal areas. Biopsy, especially of type III, can be potentially complicated by infection or leakage of cerebrospinal fluid. Suspicion of the nature of the lesion and appropriate additional studies may avoid these complications.
CO2 Laser Treatment of Trichoepithelioma with Focused and Defocused Beam
Authors: SAWCHUK WILLIAM S. , HEALD PETER W.
Published: June 2013

Abstract
A patient with multiple trichoepithelioma was treated with the carbon dioxide (CO2) laser. The beam was utilized in a defocused mode for debulking and exposing the tumors. The focused mode was used for destruction of the dermal remnants of the tumors and in the sculpting of lesions to match the contour of the external ear. Examination of lesional tissue for the presence of estrogen or progesterone receptors revealed the absence of these receptors.
Laser Vermilion Ablation for Actinic Cheilitis
Authors: DAVID LAURENCE M.
Published: June 2013

A new surgical procedure employing a carbon dioxide laser for treating actinic cheilitis is described. Eight patients having biopsy‐proven actinic cheilitis and one patient having clinically evident actinic cheilitis but biopsy‐proven superficial basal cell carcinoma were treated by vermilion ablation using the carbon dioxide laser.

After an average follow‐up period of 34 months (27 to 38 months), no patient has had a recurrence of cheilitis. Normal contour of the treated lip has been preserved in all patients, while none has had significant post‐treatment scarring.
Surgical Repair of Atresia of Nasal Passages
Authors: HARAHAP MARWALI
Published: June 2013

Surgical correction of nasal atresia following healing of smallpox lesions in a 15‐year‐old girl is presented. The surgical technique used was complete excision of the scars and resurfacing of the resulting wound with grafts of full‐thickness retroauricular skin. Particular attention was paid to prevention of postoperative contracture.
Dermabrasion for the Treatment of a Giant Seborrheic Keratosis
Authors: PEPPER ELLENDEE
Published: June 2013

A man presented for removal of a giant seborrheic keratosis. Dermabrasion removal of this lesion provided technical ease with good cosmetic results.