bluuebunny/crossref_metadata_2025 huggingface dataset:
Something old, something new and something very old: drugs for treating type 2 diabetes
Authors: Kaiser D , Oetjen E
Published: February 2014

Diabetes mellitus belongs to the most rapidly increasing diseases worldwide. Approximately 90–95% of these patients suffer from type 2 diabetes mellitus, which is characterized by peripheral insulin resistance and the progressive loss of beta‐cell function and mass. Considering the complications of this chronic disease, a reliable anti‐diabetic treatment is indispensable. An ideal oral anti‐diabetic drug should not only correct glucose homeostasis but also preserve or even augment beta‐cell function and mass, ameliorate the subclinical inflammation present under insulin‐resistant conditions and prevent the macro‐ and microvascular consequences of diabetes in order to reduce the mortality. Despite the many anti‐diabetic drugs already in use, there is an ongoing research for additional drugs, guided by different concepts of the pathogenesis of type 2 diabetes. This review will briefly summarize current oral anti‐diabetic drugs. In addition, emerging strategies for the treatment of diabetes will be described, among them the inhibition of glucagon action and anti‐inflammatory drugs. Their suitability as ‘ideal anti‐diabetic drugs’ will be discussed.
Reproductive delays in mammals: an unexplored avenue for post‐copulatory sexual selection
Authors: Orr Teri J. , Zuk Marlene
Published: February 2014

Numerous mammalian taxa exhibit reproductive delays, pauses in reproduction that occur between mating and fertilization, between fertilization and implantation of the embryo, or after an embryo has implanted. Of the 27 mammalian orders, 9 are known to exhibit reproductive delays, including Diptrotodontia, Dasyuromorphia, Eulipotyphyta, Cingulata, Carnivora, Rodentia, Chiroptera, Lagomorpha and Cetartiodactyla. Most researchers interested in delays have focused on their evolutionary origins. However, the consequences of these delays have not been considered fully. Given the lengthening of the period over which reproduction occurs, it is possible that this unique aspect of reproduction facilitates post‐copulatory sexual selection. When considered in the context of sexual selection, delays may allow sperm competition and female manipulation of fertilization (cryptic female choice) as well as other post‐copulatory processes. We investigate the potential for reproductive delays to facilitate post‐copulatory sexual selection and suggest avenues for research that may further our knowledge of sexual selection. We also provide a general review of reproductive delays in mammals.
Characterization of common marmoset dysgerminoma‐like tumor induced by the lentiviral expression of reprogramming factors
Authors: Yamaguchi Saori , Marumoto Tomotoshi , Nii Takenobu , Kawano Hirotaka , Liao Jiyuan , Nagai Yoko , Okada Michiyo , Takahashi Atsushi , Inoue Hiroyuki , Sasaki Erika , Fujii Hiroshi , Okano Shinji , Ebise Hayao , Sato Tetsuya , Suyama Mikita , Okano Hideyuki , Miura Yoshie , Tani Kenzaburo
Published: February 2014

Recent generation of induced pluripotent stem (iPSCs) has made a significant impact on the field of human regenerative medicine. Prior to the clinical application of iPSCs, testing of their safety and usefulness must be carried out using reliable animal models of various diseases. In order to generate iPSCs from common marmoset (CM; Callithrix jacchus), one of the most useful experimental animals, we have lentivirally transduced reprogramming factors, including POU5F1 (also known as OCT3/4), SOX2, KLF4, and c‐MYC into CM fibroblasts. The cells formed round colonies expressing embryonic stem cell markers, however, they showed an abnormal karyotype denoted as 46, X, del(4q), +mar, and formed human dysgerminoma‐like tumors in SCID mice, indicating that the transduction of reprogramming factors caused unexpected tumorigenesis of CM cells. Moreover, CM dysgerminoma‐like tumors were highly sensitive to DNA‐damaging agents, irradiation, and fibroblast growth factor receptor inhibitor, and their growth was dependent on c‐MYC expression. These results indicate that DNA‐damaging agents, irradiation, fibroblast growth factor receptor inhibitor, and c‐MYC‐targeted therapies might represent effective treatment strategies for unexpected tumors in patients receiving iPSC‐based therapy.
Procedural Modelling of Urban Road Networks
Authors: Beneš Jan , Wilkie Alexander , Křivánek Jaroslav
Published: February 2014

We present a model for growing procedural road networks in and close to cities. The main idea of our paper is that a city cannot be meaningfully simulated without taking its neighbourhood into account. A simple traffic simulation that considers this neighbourhood is then used to grow new major roads and to influence the locations of minor road growth. Waterways are introduced and used to help position the city nuclei on the map. The resulting cities are formed by allowing several smaller settlements to grow together and to form a rich road structure, much like in real world, and require only minimal per‐city input, allowing for batch generation.
Expression of Prox1, D2‐40, and WT1 in spindle cell hemangioma
Authors: Wang Lei , Gao Tianwen , Wang Gang
Published: February 2014

Background

Spindle cell hemangioma is a benign vascular proliferation that usually occurs on acral sites. A recent report showed focal positive staining of Prox1 in spindle cell hemangioma.

Methods

We performed an immunohistochemical study of spindle cell hemangioma with antibodies to CD31, D2‐40, Prox1, smooth muscle actin (SMA) and Wilms tumor‐1 (WT‐1).

Results

The endothelial cells in spindle cell hemangioma were positive for CD31 and Prox1, focally positive for D2‐40 and negative for WT‐1, whereas the myoid spindle cells around the endothelial cells were weakly positive for WT‐1.

Conclusion

Our results suggest that spindle cell hemangioma is a lymphatic malformation.
Nevus anelasticus: how should such lesions be classified?
Authors: Wang Annie R. , Kent Kathryn , Jagdeo Jared , Robinson‐Bostom Leslie , Bercovitch Lionel
Published: February 2014

Nevus anelasticus represents a rare entity that is most commonly classified as a connective tissue nevus. It typically presents before 20 years of age with asymmetrically distributed white‐to‐skin‐toned or pink‐to‐red papules or plaques on the trunk and upper extremities. The lesion is defined histopathologically by the absence or degeneration of elastic fibers in the dermis. We report the case of a healthy 17‐year‐old female who presented with an asymptomatic slowly progressive plaque on the right inferior areola. Histopathologic examination showed the absence of elastic fibers in the papillary and upper reticular dermis and fragmented elastic tissue fibers in the deep reticular dermis. Although there is ongoing controversy regarding the nosology of this uncommon disorder, we propose that it is a distinct entity based on its histopathologic and clinical features.
Endocrine mucin‐producing sweat gland carcinoma occurring on extra‐facial site: a case report
Authors: Tsai Jia‐Huei , Hsiao Tzu‐Lin , Chen Yi‐Ying , Hsiao Cheng‐Hsiang , Liau Jau‐Yu
Published: February 2014

Cutaneous endocrine mucin‐producing sweat gland carcinoma (EMPSGC) is a very rare low‐grade malignant neoplasm analogous to the mammary solid‐papillary carcinoma. It frequently expresses neuroendocrine markers and may show mucinous differentiation. Although the nodules are circumscribed, myoepithelial cells cannot be showed in most cases and about half of the cases are associated with invasive mucinous carcinoma. Hence, it has been suggested to be invasive and the precursor lesion of some primary cutaneous mucinous carcinomas. After being recognized as a distinct entity, all cases reported to date occurred either in the periocular region or on the cheek. Two thirds of the patients were female. Herein we present an unusual case of in situ EMPSGC on the chest wall skin of a middle‐aged man.
Steatocystoma multiplex associated with bilateral preauricular sinuses
Authors: Fernandez‐Flores Angel , Cuesta César Cosme Álvarez , García Carlos Suárez , del Río José Sánchez
Published: February 2014

Steatocystoma multiplex is characterized by the development of numerous steatocystomas. The condition has occasionally been related to congenital bilateral preauricular sinuses. Herein, we present the third case of such an association, a 34‐year‐old male who was born with bilateral preauricular sinuses that were surgically repaired. When he was 14 years old, he presented with multiple steatocystomas on his forehead and temples, one of which was biopsied. There was no family history of the condition.
The routine use of iron stain for biopsies of dermatoses of the legs
Authors: Northcutt Alan D. , Tschen Jaime A.
Published: February 2014

Background

Our goal was to study the utility of the routine use of the Gomori iron stain in the evaluation of leg biopsies of inflammatory lesions.

Methods

One hundred consecutive skin biopsies from the legs were evaluated with hematoxylin and eosin and Gomori iron stains. Iron positivity was semi‐quantitatively graded from trace to 4+.

Results

Forty‐two (42) cases were positive with the Gomori iron stain as follows: stasis dermatitis (14), Schamberg's disease (7), folliculitis (2), psoriasis (2), trauma (2), arthropod bite (2), allergic contact dermatitis (2), lichen simplex chronicus (1), senile purpura (1), vascular ectasia (1), lobular capillary hemangioma (1), scar (1), pretibial pigmented patches (1), tinea (1), lentigo maligna (1), traumatic fat necrosis (1), lichen planus (1) and fixed drug eruption (1). Twelve of 14 cases of stasis dermatitis had 2+ or greater iron staining; 8 cases were 3+ or 4+. All other diagnoses had trace or 1+ staining for iron except for one scar (2+). One of 19 samples (5.3%) of ‘normal’ leg skin controls showed iron stain positivity, and was graded as trace.

Conclusions

After correcting for iron staining in 5.3% of normal leg skin controls, we observed Gomori iron positivity in 36.7% of 100 consecutive leg biopsies. We suggest that routine application of an iron stain on biopsies of dermatoses from the legs is useful. Stasis dermatitis and Schamberg's disease are the most frequent iron positive diagnoses, and the diagnosis is aided by the pattern of hemosiderin deposition. Negative iron stain is also useful in suggesting the presence of melanin pigment in macrophages in lichenoid and other dermatoses. To confirm a truly negative iron stain, study of the section at ×400 rather than ×100 is recommended.
Prognostic impact of fat tissue loss and cachexia assessed by computed tomography scan in elderly patients with diffuse large B‐cell lymphoma treated with immunochemotherapy
Authors: Camus Vincent , Lanic Helene , Kraut Jerôme , Modzelewski Romain , Clatot Florian , Picquenot Jean M. , Contentin Nathalie , Lenain Pascal , Groza Luminata , Lemasle Emilie , Fronville Carole , Cardinael Nathalie , Fontoura Marie‐Laure , Chamseddine Ali , Brehar Oana , Stamatoullas Aspasia , Leprêtre Stéphane , Tilly Hervé , Jardin Fabrice
Published: February 2014

Objectives

Approximately 30% of DLBCL patients are older than 70 yr. This study evaluated the prognostic impact of a cachexia score (CS) including fat tissue loss (adipopenia) and sarcopenia as assessed by computed tomography (CT scan) in elderly DLBCL patients treated with chemotherapy and rituximab (R).

Methods

This retrospective analysis included 80 DLBCL patients older than 70 yr treated with R‐CHOP or R‐miniCHOP. Skeletal muscle (SM) and visceral (V) and subcutaneous (S) adipose (A) tissues were measured by analysing CT images at the third lumbar (L3) level.

Results

The median age of the patients was 78 yr. Forty‐four and 46 patients were considered sarcopenic and adipopenic, respectively. The median progression‐free survival (PFS) was 13.6 months in the adipopenic group and 49.4 months in the non‐adipopenic group [hazard ratio (HR) = 2.27; 95% confidence interval (CI): 1.3–4; P = 0.0042]. The median overall survival (OS) was 25.7 months in the adipopenic group and 57.1 months in the non‐adipopenic group (HR = 1.93; 95% CI: 1.05–3.55; P = 0.0342). A two‐point CS including adipopenia and sarcopenia was created and defined two distinct risk groups with differences in outcomes that were highly significant. The CS was predictive of the prognosis in a multivariate analysis including body mass index (BMI) (< or ≥25 kg/m2), age (< or ≥80 yr), international prognostic index (IPI) and albuminaemia (HR = 3.67; 95% CI = 1.93–6.97; P < 0.0001).

Conclusion

A CS including sarcopenia and adipopenia, assessed by a single CT scan slice, predicts outcome independent of BMI and the IPI.
Early botulinum toxin treatment for spastic pes equinovarus – a randomized double‐blind placebo‐controlled study
Authors: Fietzek U. M. , Kossmehl P. , Schelosky L. , Ebersbach G. , Wissel J.
Published: February 2014

Background and purpose

Spastic pes equinovarus is a frequent pathological posture of the lower extremity. Botulinum toxin (BoNT/A) has been successfully applied to treat lower limb spasticity. However, the best time to initiate treatment remains unclear. A beneficial effect of an early treatment has been suggested in previous studies.

Methods

A single‐centre double‐blind randomized placebo‐controlled trial was performed to investigate the efficacy of BoNT/A to reduce muscle hypertonicity at the ankle. Fifty‐two patients with unilateral or bilateral spastic pes equinovarus with a modified Ashworth score (mAS) of at least 1+ after stroke, traumatic brain injury or hypoxic encephalopathy were allocated to receive either BoNT/A or placebo treatment. A second, open injection was optional at week 12. Patients received unilateral or bilateral injections with 230 or 460 U onabotulinumtoxinA, respectively. The course of the mAS was explored during the open study phase.

Results

Patients who had received BoNT/A treatment had lower mAS compared with placebo at week 12 (P < 0.01). During the open label phase, patients from the placebo group showed further deterioration of muscle tone despite starting from a similar baseline and receiving BoNT treatment. Spastic feet that had received BoNT/A in the first cycle had comparatively lower mAS scores over all follow‐up data and at week 24 (P < 0.01).

Conclusions

The study demonstrates a reduction of muscular hypertonicity in spastic pes equines with BoNT/A treatment given during the first 3 months after the lesion. Exploratory analyses of the course of muscular hypertonicity during the open phase favour earlier to later treatment.
Silkworm strains that can be clearly destined towards either embryonic diapause or direct development by adjusting a single ambient parameter during the preceding generation
Authors: Egi Yuichi , Akitomo Shion , Fujii Tsuguru , Banno Yutaka , Sakamoto Katsuhiko
Published: February 2014

In the silkworm, Bombyx mori (Lepidoptera: Bombycidae), embryonic diapause is under maternal control and the decision between diapause and direct development in bivoltine strains depends on environmental factors such as temperature and photoperiod experienced by the preceding generation. We reared ten bivoltine silkworm strains (c10, g32, k06, n25, p21, p22, p24, p44, p50 and p63) under various thermal and light conditions and examined the incidence of embryonic diapause in the next generation to identify strains in which the incidence of diapause can be controlled within the range of 0 to 100% by adjusting a single ambient parameter. Some strains were clearly destined towards either diapause or direct development. The diapause incidence in the c10, p22 and p50 strains was controlled by temperature during the egg stage (0% at 18°C and 100% at 25°C), that in the p50 strain was also determined to be dependent on illumination during the egg stage (0% under continuous darkness and 100% under continuous illumination), and photoperiod during the larval stage regulated diapause in p44 and p50 (0% and 100% under long‐day and short‐day photoperiod, respectively), when all other external parameters remained constant under each experimental condition. These diapause‐controllable silkworm strains might serve as model systems for studies of insect diapause, especially for the differential screening of related factors.
Mutations to a glycine loop in the catalytic site of human Lon changes its protease, peptidase and ATPase activities
Authors: Ambro Ľuboš , Pevala Vladimír , Ondrovičová Gabriela , Bellová Jana , Kunová Nina , Kutejová Eva , Bauer Jacob
Published: February 2014

Lon, also called protease La, is an ATP‐dependent protease present in all kingdoms of life. It is involved in protein quality control and several regulatory processes. Eukaryotic Lon possesses three domains, an N‐terminal domain, an ATPase domain and a proteolytic domain. It requires ATP hydrolysis to digest larger, intact proteins, but can cleave small, fluorogenic peptides such as Glu‐Ala‐Ala‐Phe‐MNA by only binding, but not hydrolyzing, ATP. Both ATPase and peptidase activities can be stimulated by the binding of a larger protein substrate, such as β‐casein. To better understand its mechanism of action, we have prepared several point mutants of four conserved residues of human Lon (G893A, G893P, G894A, G894P, G894S, G893A‐G894A, G893P‐G894A, G893A‐G894P, T880V, W770A, W770P) and studied their ATPase, protease and peptidase activities. Our results show that mutations to Gly894 enhance its basal ATPase activity but do not change its β‐casein‐stimulated activity. The loop containing Gly893 and Gly894, which flanks Lon's proteolytic active site, therefore appears to be involved in the conformational change that occurs upon substrate binding. Furthermore, mutations to Trp770 have the same general effects on the ATPase activity as mutations to Gly893, indicating that Trp770 is involved in ATPase stimulation. We have also established that this loop does not need to move in order to cleave small, fluorogenic peptides, but does move during the digestion of β‐casein. Finally, we also noted that Lon's ability to digest small peptides can be inhibited by moderate ATP concentrations.

Database

Lon (Endopeptidase La), EC 4.4.21.53

Structured digital abstract

• hLonP cleaves beta casein by protease assay (1, 2, 3, 4, 5, 6)

• hLon and hLon bind by cross-linking study (View interaction)
New unloading compliance correlation for throughwall circumferentially cracked pipe to measure crack growth during fracture tests
Authors: Chattopadhyay J. , Venkatramana W. , Dutta B. K.
Published: February 2014

Crack growth is generally measured during fracture experiment of specimen or component. The unloading compliance technique is commonly used for this purpose because of its simplicity. It infers the crack length from unloading compliance of cracked component. The pre‐requisite of this technique is the availability of an equation that correlates crack length with unloading compliance. While such correlations are available for compact tension and three‐point bend specimens, it is not available for big components such as pipe or pipe bend. Development of such a correlation for throughwall circumferentially cracked (TCC) straight pipe under bending, therefore, forms the objective of the present study. However, the challenge to develop such correlation for TCC pipe is that the equation should contain not only crack length as a function but also the current deformation or load level as a parameter. This is attributed to the fact that the circular cross section of the pipe ovalizes during deformation leading to change of bending stiffness of the cracked body. New compliance correlations have been proposed for TCC pipe under bending load considering these complexities. Elastic‐perfectly plastic material behaviour has been assumed to characterize the material stress–strain response. However, it has been shown that error due to this approximation with respect to the actual stress–strain behaviour is negligible if one chooses flow stress equal to average of yield and ultimate strength. The proposed correlations are expressed in terms of normalized parameters to make them independent of specific values of geometric dimensions such as radius, thickness and span length of four‐point bending loading system. Effectiveness of this normalization has also been verified by carrying out a sensitivity study.
Firm‐Level Competition and Exchange Rate Exposure: Evidence from a Global Survey of Firms
Authors: Bergbrant Mikael C. , Campbell Kaysia , Hunter Delroy M.
Published: February 2014

We examine the effect of competition on exchange rate exposure using survey data from 55 countries. We find that exposure increases with the intensity of competition. Exposure is higher when firms face price competition in international and domestic product markets and when rivals compete using an unfair financial advantage. Furthermore, competition is a leading determinant of exposure, dominating the usual determinants. Exposure also increases with several determinants not previously empirically examined, such as firm‐level financial constraints. These results hold for small, large, foreign‐involved, and purely domestic firms. Finally, import‐only firms have higher exposure than export‐only firms. Our survey results are likely to capture exposure before firms’ hedging actions.
In situ light and phosphorus manipulations reveal potential role of biofilm algae in enhancing enzyme‐mediated decomposition of organic matter in streams
Authors: Rier Steven T. , Shirvinski Jonathan M. , Kinek Keith C.
Published: February 2014

Biofilms play crucial roles in the carbon and nutrient dynamics of stream ecosystems. Measuring extracellular enzyme activities can reveal universal patterns in C, N and P dynamics at the microbial level and enhance our understanding of how microorganisms influence ecosystem‐level processes.

Because algae may potentially enhance the activities of enzymes produced by heterotrophic microorganisms for degrading allochthonous organic matter, more work is needed to understand how factors that influence biofilm algae could in turn alter activities of these enzymes and how these influences alter the demand for inorganic nutrients.

The purpose of this study was to use extracellular enzymes (alkaline or acid phosphatase, β‐glucosidase, β‐xylosidase, leucine aminopeptidase and phenol oxidase) to examine the response of biofilms to in situ shade and phosphorus manipulations in two streams with contrasting DOC quantity and quality.

Despite the water column nutrient ratios indicating P limitation in both streams, shade had the biggest effect on algal and bacterial biomass.

Enzyme results clearly demonstrated the positive effects of algae on the activities of both hydrolytic and oxidative enzymes in stream biofilms. In most cases, we observed at least a doubling in activities between the shaded and ambient treatments, with P additions indicating enhanced P demand under ambient light. Furthermore, similar phenol oxidase activities between the two streams suggests pH or enzyme inhibitors might have played a role or that a proportion of the measured enzyme activities was directed at the degradation of fine particulate organic matter embedded in the biofilm matrix in addition to water column DOC.

This study provides further evidence that algae might contribute to the degradation of terrestrial organic matter through indirect influences on extracellular enzyme activities and possibly priming.
Rainfall and temperatures changes have confounding impacts on Phytophthora cinnamomi occurrence risk in the southwestern USA under climate change scenarios
Authors: Thompson Sally E. , Levin Simon , Rodriguez‐Iturbe Ignacio
Published: February 2014

Global change will simultaneously impact many aspects of climate, with the potential to exacerbate the risks posed by plant pathogens to agriculture and the natural environment; yet, most studies that explore climate impacts on plant pathogen ranges consider individual climatic factors separately. In this study, we adopt a stochastic modeling approach to address multiple pathways by which climate can constrain the range of the generalist plant pathogen Phytophthora cinnamomi (Pc): through changing winter soil temperatures affecting pathogen survival; spring soil temperatures and thus pathogen metabolic rates; and changing spring soil moisture conditions and thus pathogen growth rates through host root systems. We apply this model to the southwestern USA for contemporary and plausible future climate scenarios and evaluate the changes in the potential range of Pc. The results indicate that the plausible range of this pathogen in the southwestern USA extends over approximately 200 000 km2 under contemporary conditions. While warming temperatures as projected by the IPCC A2 and B1 emissions scenarios greatly expand the range over which the pathogen can survive winter, projected reductions in spring rainfall reduce its feasible habitat, leading to spatially complex patterns of changing risk. The study demonstrates that temperature and rainfall changes associated with possible climate futures in the southwestern USA have confounding impacts on the range of Pc, suggesting that projections of future pathogen dynamics and ranges should account for multiple pathways of climate–pathogen interaction.
No general soil carbon sequestration under Central European short rotation coppices
Authors: Walter Katja , Don Axel , Flessa Heinz
Published: February 2014

Wood from short rotation coppices (SRCs) is discussed as bioenergy feedstock with good climate mitigation potential inter alia because soil organic carbon (SOC) might be sequestered by a land‐use change (LUC) from cropland to SRC. To test if SOC is generally enhanced by SRC over the long term, we selected the oldest Central European SRC plantations for this study. Following the paired plot approach soils of the 21 SRCs were sampled to 80 cm depth and SOC stocks, C/N ratios, pH and bulk densities were compared to those of adjacent croplands or grasslands. There was no general trend to SOC stock change by SRC establishment on cropland or grassland, but differences were very site specific. The depth distribution of SOC did change. Compared to cropland soils, the SOC density in 0–10 cm was significantly higher under SRC (17 ± 2 in cropland and 21 ± 2 kg C m−3 in SRC). Under SRC established on grassland SOC density in 0–10 cm was significantly lower than under grassland. The change rates of total SOC stocks by LUC from cropland to SRC ranged from −1.3 to 1.4 Mg C ha−1 yr−1 and −0.6 Mg C ha−1 yr−1 to +0.1 Mg C ha−1 yr−1 for LUC from grassland to SRC, respectively. The accumulation of organic carbon in the litter layer was low (0.14 ± 0.08 Mg C ha−1 yr−1). SOC stocks of both cropland and SRC soils were correlated with the clay content. No correlation could be detected between SOC stock change and soil texture or other abiotic factors. In summary, we found no evidence of any general SOC stock change when cropland is converted to SRC and the identification of the factors determining whether carbon may be sequestered under SRC remains a major challenge.
Extinctions and the loss of ecological function in island bird communities
Authors: Boyer Alison G. , Jetz Walter
Published: February 2014

Aim

Because of the negative impact that ongoing biodiversity loss may have on ecosystem properties that are critical for humans, understanding the relationship between extinction and functional diversity over time is of critical importance for conservation. However, empirical evidence concerning the sensitivity of vertebrate community function to species loss is very limited. Here we assess documented prehistoric and historic extinctions of birds on Pacific islands in an effort to quantify the consequences of extinctions for functional structure and diversity in natural communities over broad spatial scales.

Location

Forty‐four islands from across the Pacific.

Methods

We estimated functional aspects of island bird communities before and after Holocene extinctions based on body size, foraging niche, diet and activity period. We used four separate metrics to measure ecological function: functional diversity (FD), functional richness (FRic), functional evenness and functional divergence. We employed null models to separate the effects of observed extinctions from changes expected due to declining species richness.

Results

We find that Holocene bird extinctions led to substantial changes in community‐level functional diversity. Observed declines in FD and FRic were predictable from the pre‐extinction composition of communities, and did not differ from null model expectations. Across all islands, we observed non‐random changes in functional trait composition, with shifts away from ground‐level foraging, granivory and herbivory after extinctions. Extinctions have resulted in the loss of up to 80% of original functional diversity on some islands and caused a sharp decrease in the variety of ecological functions provided by birds.

Main conclusions

Our findings illustrate the significant losses of functional diversity that are already taking place on many islands and demonstrate its close connection with the loss of species. Accounting for the functional roles of species allows a more integrative understanding of ecological function and helps to bridge species and ecosystem perspectives in conservation science.
Bootstrap Calibration and Uncertainty Estimation of Downhole NMR Hydraulic Conductivity Estimates in an Unconsolidated Aquifer
Authors: Parsekian A.D. , Dlubac K. , Grunewald E. , Butler J.J. , Knight R. , Walsh D.O.
Published: February 2014

Characterization of hydraulic conductivity (K) in aquifers is critical for evaluation, management, and remediation of groundwater resources. While estimates of K have been traditionally obtained using hydraulic tests over discrete intervals in wells, geophysical measurements are emerging as an alternative way to estimate this parameter. Nuclear magnetic resonance (NMR) logging, a technology once largely applied to characterization of deep consolidated rock petroleum reservoirs, is beginning to see use in near‐surface unconsolidated aquifers. Using a well‐known rock physics relationship—the Schlumberger Doll Research (SDR) equation—K and porosity can be estimated from NMR water content and relaxation time. Calibration of SDR parameters is necessary for this transformation because NMR relaxation properties are, in part, a function of magnetic mineralization and pore space geometry, which are locally variable quantities. Here, we present a statistically based method for calibrating SDR parameters that establishes a range for the estimated parameters and simultaneously estimates the uncertainty of the resulting K values. We used co‐located logging NMR and direct K measurements in an unconsolidated fluvial aquifer in Lawrence, Kansas, USA to demonstrate that K can be estimated using logging NMR to a similar level of uncertainty as with traditional direct hydraulic measurements in unconsolidated sediments under field conditions. Results of this study provide a benchmark for future calibrations of NMR to obtain K in unconsolidated sediments and suggest a method for evaluating uncertainty in both K and SDR parameter values.
Reactive Oxygen Species Induce Procalcitonin Expression in Trigeminal Ganglia Glia
Authors: Raddant Ann C. , Russo Andrew F.
Published: February 2014

Objective

To examine calcitonin gene‐related peptide (CGRP) gene expression under inflammatory conditions using trigeminal ganglia organ cultures as an experimental system. These cultures have increased proinflammatory signaling that may mimic neurogenic inflammation in the migraine state.

Background

The trigeminal nerve sends peripheral pain signals to the central nervous system during migraine. Understanding the dynamic processes that occur within the trigeminal nerve and ganglion may provide insights into events that contribute to migraine pain. A neuropeptide of particular interest is CGRP, which can be elevated and play a causal role in migraine. However, most studies have overlooked a second splice product of the Calca gene that encodes calcitonin (CT), a peptide hormone involved in calcium homeostasis. Importantly, a precursor form of CT called procalcitonin (proCT) can act as a partial agonist at the CGRP receptor and elevated proCT has recently been reported during migraine.

Methods

We used a trigeminal ganglion whole organ explant model, which has previously been demonstrated to induce pro‐inflammatory agents in vitro. Quantitative polymerase chain reaction and immunohistochemistry were used to evaluate changes in messenger ribonucleic acid (mRNA) and protein levels of CGRP and proCT.

Results

Whole mouse trigeminal ganglia cultured for 24 hours showed a 10‐fold increase in CT mRNA, with no change in CGRP mRNA. A similar effect was observed in ganglia from adult rats. ProCT immunoreactivity was localized in glial cells. Cutting the tissue blunted the increase in CT, suggesting that induction required the close environment of the intact ganglia. Consistent with this prediction, there were increased reactive oxygen species in the ganglia, and the elevated CT mRNA was reduced by antioxidant treatment. Surprisingly, reactive oxygen species were increased in neurons, not glia.

Conclusions

These results demonstrate that reactive oxygen species can activate proCT expression from the CGRP gene in trigeminal glia by a paracrine regulatory mechanism. We propose that this glial recruitment pathway may occur following cortical spreading depression and neurogenic inflammation to increase CGRP nociceptive actions in migraine.
Characteristic differences in barrier and hygroscopic properties between normal and cosmetic dry skin. II. Depth profile of natural moisturizing factor and cohesivity
Authors: Feng L. , Chandar P. , Lu N. , Vincent C. , Bajor J. , McGuiness H.
Published: February 2014

Synopsis

Objective

In a previous paper (Lu et al., International Journal of Cosmetic Science, in press), we reported that in comparison with normal skin, cosmetic dry skin characteristically has a thicker stratum corneum (SC) with weaker barrier quality. Our goal here was to obtain a more complete picture of the difference between normal and cosmetic dry skin, by further analysing the data collected from the same clinical study to address two additional aspects of skin: the amount and depth profile of natural moisturizing factor (NMF) and the cohesivity of the SC.

Method

The SC samples were collected by sequential tape stripping in a clinical study consisting of 64 healthy Caucasian female subjects with either normal or cosmetic dry skin. Protein and free amino acids (FAA) on tape strips were extracted and analysed using high‐throughput methods. The level of pyrrolidone carboxylic acid (PCA), the prominent component of NMF, was detected using HPLC analysis.

Results

It was found that dry skin had significantly lower ratios of FAA/protein and PCA/protein across the stripped SC depth, corresponding to a lower hydration level compared with the normal skin. Our results indicated that filaggrin to FAA hydrolysis occurred deeper in dry skin and at a lower level compared with normal skin. In addition, the mass of proteins stripped from dry skin subjects was significantly higher than that from the normal skin counterpart, especially for the first 10–12 tape strips.

Conclusion

Our results showed that, compared with normal skin, cosmetic dry skin had a lower NMF level across the SC depth and a lower cohesivity. Such results suggested that NMF levels are critical for cosmetic skin conditions, and lower NMF production may be associated with dry skin. In addition, the NMF level and its depth profile and the SC cohesivity are useful clinical end points for assessing the efficacy of dry skin treatments such as skin moisturizers.
Surgical Treatment of 4 Horses for Cryptorchidism Caused by Failure of Regression of the Cranial Suspensory Ligament of the Testis
Authors: Ortved Kyla F. , Stewart Allison Worster , Fubini Susan L. , Hackett Richard P.
Published: February 2014

Objective

To report surgical management of 4 horses with cryptorchidism caused by failure of regression of the cranial suspensory ligament (CSL).

Study Design

Retrospective case series.

Animals

Cryptorchid horses (n = 4).

Methods

Horses with unilateral or bilateral cryptorchidism caused by failure of regression of the CSL were treated by removing the retained testes through a standing laparoscopic approach (2), flank laparotomy (1), or paramedian celiotomy (1). After identification of the retained testis attached to the caudal pole of the kidney by the CSL, the vascular pedicle and ductus deferens were ligated and removed.

Results

Two horses had bilateral cryptorchidism and 2 horses had unilateral cryptorchidism. Standing laparoscopic cryptorchidectomy was performed successfully in 2 horses and in 2, the retained testes were removed using a flank or paramedian celiotomy. All testes were located in the dorsal aspect of the abdomen just caudal to the kidney and had a well‐developed CSL. All horses recovered successfully from surgery.

Conclusions

Failure of regression of the CSL is an uncommon cause of cryptorchidism in horses; however, affected horses can be treated using surgical approaches that facilitate exploration of the dorsocaudal aspect of the abdomen.
Relationship Between Mechanical Thresholds and Limb Use in Dogs With Coxofemoral Joint OA‐Associated Pain and the Modulating Effects of Pain Alleviation From Total Hip Replacement on Mechanical Thresholds
Authors: Tomas Andrea , Marcellin‐Little Denis J. , Roe Simon C. , Motsinger‐Reif Alison , Lascelles B. Duncan X.
Published: February 2014

Objectives

To compare von Frey mechanical quantitative sensory thresholds (mQSTvF) between pelvic limbs in dogs before unilateral total hip replacement (THR) surgery; to correlate ground reaction forces (GRF) with mQSTvF; to assess changes in mQSTvF after THR surgery.

Study Design

Prospective clinical study.

Animals

Dogs (n = 44).

Methods

mQSTvF and GRF measured using a pressure sensitive walkway were evaluated before, and 3, 6, and 12 months after, unilateral THR. Measurements were recorded from the affected (operated) pelvic limb (APL) and the non‐operated pelvic limb (NPL). Random effects analysis and forwards stepwise linear regression models were used to evaluate the influence of time since surgery and patient factors on mQSTvF thresholds.

Results

There were no significant correlations between mQSTvF data and age, bodyweight or the GRF variables. Preoperative mQSTvF measured at the APL and NPL did not differ (P = .909). mQSTvF thresholds increased significantly after 12 months in NPL (P = .047) and APL (P = .001). In addition to time, APL mQSTvF values were significantly affected by sex (higher in males, P = .010) and body condition score (higher in leaner dogs, P = .035) and NPL mQSTvF values by sex (P = .038).

Conclusion

Successful unilateral THR results in decreased central sensitization after 12 months.
Internal Fixation of Severe Maxillofacial Fractures in Dogs
Authors: Arzi Boaz , Verstraete Frank J.M.
Published: February 2014

Objective

To describe internal fixation for maxillofacial fractures using titanium miniplates and report outcome in 7 dogs.

Study design

Prospective case series.

Animals

Skeletally mature dogs (n = 7) with maxillofacial fractures.

Methods

After CT evaluation of fracture configuration, using a combination of extraoral and intraoral approaches as needed, non‐locking titanium miniplates were contoured to match the normal anatomy of the fractured bones. Plates were secured using non‐locking titanium screws and then covered with a soft‐tissue envelope followed by routine intraoral and extraoral closure.

Results

Fractures healed rapidly after reconstruction with immediate return to normal function and occlusion. Follow‐up time of up to 94 months indicated excellent long‐term function and general lack of complications. One dog developed nasal aspergillosis 1.5 years after surgery and the miniplates were removed without adverse consequences.

Conclusion

Internal fixation for maxillofacial reconstruction using titanium miniplates is an excellent solution for the treatment of comminuted and displaced maxillofacial fractures in dogs.
Regulatory non‐coding transcripts in spermatogenesis: shedding light on ‘dark matter’
Authors: Mukherjee A. , Koli S. , Reddy K. V. R.
Published: February 2014

Global rise in male infertility over the past decades as a result of falling sperm count and quality has been pointed out by different investigations. Therefore, it is important to understand the molecular mechanism of spermatogenesis and its regulation. Mammalian spermatogenesis, a streamlined process through which male germline cells divide and differentiate into mature spermatozoa, is strictly regulated by phase‐specific gene expression which, in turn, is controlled by myriads of regulatory non‐coding RNAs (ncRNAs). Rapid advancement in genome mining technologies has identified role of ncRNAs including microRNAs, PIWI‐interacting RNAs, endogenous small‐interfering RNAs and long non‐coding RNAs as controller of gene expression at transcriptional as well as post‐transcriptional level in different biological context and disease processes. Here, we discuss the recent progress in our understanding about the involvement of these molecules in spermatogenesis. In addition, we describe here the possible roles of long non‐coding RNAs in controlling this process which is not delved so far.
Intentionality, anger, coping, and ego defensiveness in reactive aggressive driving
Authors: Vallières Evelyne F. , Vallerand Robert J. , Bergeron Jacques , McDuff Pierre
Published: February 2014

A motivational sequence was used as a theoretical framework for studying reactive aggressive driving. Study 1 tested the validity of the sequence “perceived intentionality‐anger‐reactive aggressive driving” and assessed the impact of coping on anger and reactive aggressive driving. The ecological validity of the same sequence was verified in Study 2 with a large sample of adult drivers, while examining the role of ego defensiveness as a determinant of anger and aggressive driving. Study 1 showed the proposed sequence was supported and that coping strategies intervened at both anger and reaction levels, depending if the situation was perceived as intentional or not. Study 2 showed that anger mediated the impact of coping and ego defensiveness on driving aggression. Sobel tests confirmed the anger mediation effect in both studies.
The contributions of interpersonal attachment and friendship group identification to depressive symptoms in a nonclinical sample
Authors: Rosenthal Harriet E. S. , Somers Nadia , Fleming Piers , Walsh Judi
Published: February 2014

Drawing on previous literature from the separate areas of adult attachment and group processes, we explored attachment and group identification as predictors for depressive symptoms in a nonclinical sample. We found that attachment anxiety and friendship group identification predicted scores on the Beck Depression Inventory, such that higher attachment anxiety resulted in higher depressive symptoms, and greater friendship group identification resulted in lower depressive symptoms. Mediational analysis suggested that group identification partially mediated the effect of attachment avoidance on depressive symptoms, but did not mediate the effect of attachment anxiety on depressive symptoms.
Postprandial C‐peptide to glucose ratio as a predictor of β‐cell function and its usefulness for staged management of type 2 diabetes
Authors: Lee Eun Young , Hwang Sena , Lee Seo Hee , Lee Yong‐ho , Choi A Ra , Lee Youngki , Lee Byung‐Wan , Kang Eun Seok , Ahn Chul Woo , Cha Bong Soo , Lee Hyun Chul
Published: February 2014

Aims/Introduction

Type 2 diabetes is characterized by progressive deterioration of β‐cell function. Recently, it was suggested that the C‐peptide‐to‐glucose ratio after oral glucose ingestion is a better predictor of β‐cell mass than that during fasting. We investigated whether postprandial C‐peptide‐to‐glucose ratio (PCGR) reflects β‐cell function, and its clinical application for management of type 2 diabetes.

Materials and Methods

We carried out a two‐step retrospective study of 919 Korean participants with type 2 diabetes. In the first step, we evaluated the correlation of PCGR level with various markers for β‐cell function in newly diagnosed and drug‐naïve patients after a mixed meal test. In the second step, participants with well‐controlled diabetes (glycated hemoglobin <7%) were divided into four groups according to treatment modality (group I: insulin, group II: sulfonylurea and/or dipeptityl peptidase IV inhibitor, group III: metformin and/or thiazolidinedione and group IV: diet and exercise group).

Results

In the first step, PCGR was significantly correlated with various insulin secretory indices. Furthermore, PCGR showed better correlation with glycemic indices than homeostatic model assessment of β‐cell function (HOMA‐β). In the second step, the PCGR value significantly increased according to the following order: group I, II, III, and IV after adjusting for age, sex, body mass index and duration of diabetes. The cut‐off values of PCGR for separating each group were 1.457, 2.870 and 3.790, respectively (P < 0.001).

Conclusions

We suggest that PCGR might be a useful marker for β‐cell function and an ancillary parameter in the choice of antidiabetic medication in type 2 diabetes.
Comparison of four cardiovascular risk prediction functions among Chinese patients with diabetes mellitus in the primary care setting
Authors: Jiao Fang Fang , Lam Cindy Lo Kuen , Fung Colman , McGhee Sarah Morag
Published: February 2014

Aims/Introduction

To assess the feasibility, convergent validity and sensitivity of four cardiovascular risk prediction functions in Chinese diabetic patients in the primary care setting.

Materials and Methods

A cross‐sectional study of 1,140 diabetic patients was carried out to compare four cardiovascular risk functions, which were respectively developed from the Framingham heart study, the USA–People's Republic of China Collaborative Study of Cardiovascular and Cardiopulmonary Epidemiology cohort (PRC), the United Kingdom Prospective Diabetes Study (UKPDS) and the Joint Asia Diabetes Evaluation program (JADE). Feasibility was assessed by the percentage of patients with complete data for risk prediction. Convergent validity was measured by Spearman's rank correlation, paired Wilcoxon signed‐rank sum test and Bland–Altman plots. Effect size differences between clinical risk groups were used to assess the sensitivity.

Results

Risk prediction was feasible by the Framingham, UKPDS and PRC risk functions in more than 98% patients, whereas just 74% of patients had complete data for the JADE function. The annual total coronary heart disease (CHD) risk predicted by the JADE and the UKPDS functions showed excellent agreement with no significant difference, and a correlation of 0.8048. The Framingham and the PRC functions predicted significantly lower CHD risk than those by the UKPDS and the JADE functions. The UKPDS and the Framingham functions were more sensitive in differentiating clinical risk groups.

Conclusions

The UKPDS risk engine showed good feasibility, convergent validity and sensitivity in predicting CHD risk in Chinese diabetic patients. The JADE function showed excellent agreement with the UKPDS risk engine, but it was less feasible in the primary care setting.