These results suggest that the bone abnormalities present in RTT patients may be at least partially reversible using gene-based therapies that are currently being developed [58] and [59]. However, it is also possible that significant amelioration of bone phenotypes may also be achieved using pharmacological strategies. Of particular importance for this approach is to identify the mechanisms by which MeCP2 deficiency results in altered bone properties. Whilst we show that MeCP2 is expressed in osteocytes, the protein

is widely expressed throughout the body and it is possible that metabolic and endocrine perturbations elsewhere in the body also impact on bone homeostasis. The precise molecular role of MeCP2 in the nucleus remains unclear [4], [6], [60] and [61], but it is generally Galunisertib mouse considered to regulate gene expression. As collagen is the most abundant gene product learn more and structural determinant in bone, we conducted an initial analysis

of collagen content and distribution using sirius red staining. The decreased levels of intense sirius red stain observed in the MeCP2-deficient mice is consistent with reduced collagen [56] and the patches of reduced staining resemble those features characteristic of early osteoporosis [17]. Indeed, the osteopathic features of RTT (minimal bone deformity, low energy bone fractures, and tendency towards spinal curvature) are similar to those reported in collagen type 1 genetic disorder (osteogenesis imperfecta; brittle bone disease) [62] pointing towards the possible

importance of collagen defects in RTT. In addition to structural protein, we also investigated the resorptive properties of the bone in terms of TRAP staining. The lack of any difference in osteoclast number between genotypes is consistent with a previous report [29] and suggests the possible absence of any primary defect in bone remodelling. Similarly, the limited effects seen in SAXS analysis the bone at the nanometre scale indicates minimal change in the mineral phase of bone, but there is an indication that the amount and slightly more macroscale tissue organisation is affected. CYTH4 Despite this finding, qualitative analysis by scanning electron microscopy did reveal altered trabecular architecture (widely spaced and thin trabeculae) in Mecp2stop/y mice, consistent with the overall osteoporotic picture and suggesting clear structural differences between genotypes which would be consistent with reduce bone integrity. The cortical area surrounding the central rod and plate mass showed characteristic pits in Mecp2stop/y which were much less numerous in wild-type controls. These could result from increased nutrient foramina or poorly laden osteoporotic bone due to osteoblast dysfunction. The quantitative μCT findings from only the trabecular portion of L5 vertebrae were carried out and the results are consistent with the SEM findings in that the trabecular thickness was significantly reduced in Mecp2stop/y mice.

Many patients who have contraindications for pegIFN therapy due to comorbidities may be eligible for this pegIFN-free therapy. This study is limited by the small sample size

for each of the 3 genotypes under investigation. The small size limits the ability to determine the impact of baseline http://www.selleckchem.com/products/Staurosporine.html characteristics on response. In addition, patients with cirrhosis, who have lower response rates to pegIFN/RBV therapy, were not included in this study.40 Arms were enrolled sequentially in this small exploratory study. This design may result in some imbalance in baseline and disease characteristics between arms. In summary, this exploratory study characterized the safety and antiviral activity of ombitasvir and ABT-450/r with or without RBV in patients with HCV genotypes 1, 2, or 3 infection. The regimens were generally well-tolerated

and SVR was achieved in most patients with HCV genotype 1 or 2 infection, but low SVR rates were observed in HCV genotype 3-infected patients. While regimens including an additional direct-acting antiviral agent may be needed to maximize SVR rates across patient populations with negative predictors of response, the results of this study support the continued exploration of this 2 direct-acting antiviral regimen. This study was funded by AbbVie Inc. The authors would like to express their gratitude to the study participants and coordinators who made this study possible. The study investigators were Humberto Aguilar, Bruce R. Bacon, Dasatinib mw Michael Bennett, Pedram Enayati, Gregory T.

Everson, Bradley Freilich, Eliot Godofsky, Daniel Jackson, Kris Kowdley, Eric Lawitz, Maribel Rodriguez-Torres, Vinod Rustgi, Aasim Sheikh, Greg Sullivan, and Fredrick Weber. The authors also thank Travis Yanke, Christian Naylor, Protein tyrosine phosphatase Jim Watson, Jan Hairrell, Lois Larsen, Martin King, Lindsey Haas, Christine Collins, Gretja Schnell, Jill Beyer, Tom Reisch, Preethi Krishnan, and Rakesh Tripathi of AbbVie and Michele Heckaman for their contributions. AbbVie sponsored the study, contributed to its design, participated in the collection, analysis, and interpretation of the data, and in the writing, reviewing, and approval of the abstract. Medical writing support was provided by Christine Ratajczak of AbbVie. This manuscript contains information on the investigational products ombitasvir and ABT-450/r and investigational use of ribavirin. “
“Each year, seasonal influenza is responsible for three to five million severe illnesses and 250,000 to 500,000 deaths worldwide. An accurate and complete understanding of the mechanisms of immunity to influenza is critical in order to assess the risk posed by new virus variants and to optimize immunization strategies.

These alterations directly increased the rate of biliary sterol excretion and increased

uptake of LDL cholesterol by the liver via the up-regulation of LDL-R. This study was supported by the National Council of Scientific and Technological Development (CNPq, Brazil; CNPq No. 480068/2009-7). We thank Maria Terezinha Bahia (Chagas’ Disease Laboratory, Federal University of Ouro Preto) for the use of the real-time PCR ABI 7300 equipment (Applied Biosystems). M.O.S and M.L.P were sponsored by a fellowship from CAPES and CNPq, respectively. We are also grateful to Rinaldo Cardoso dos Santos for his suggestions and careful review of the manuscript. “
“There has been an error with regard to Fig. 1. The orientation selleck products of ICP gene cassette is given from EcoRI to HindIII where it should be from HindIII to EcoRI. This error is deeply regretted. The correct map of T-DNA is given below. “
“Acerola (Malpighia emarginata D.C.), also known as Barbados Cherry, is a tropical

fruit of great economic and nutritional value because of its high content of vitamin C, which is associated with the presence of carotenoids, anthocyanins, iron and calcium. Acerola’s consumption in natura is limited because it is a small fruit with relatively large seeds and is very perishable. The fruit, however, has a good pulp yield, facilitating the development of several see more industrial products. Acerola has been processed in the form of juices, jams, ice creams, syrups, liqueurs and fruit syrups, among other products ( Soares Filho & Oliveira, 2003). In this context, processed products, such as frozen pulp and concentrated pulp, have economic importance; pulp production is a profitable activity that allows the freshly harvested perishable fruit to be stored and reprocessed off-season. The preservation of nutritional constituents during processing represents a major challenge for the traditional

techniques of pulp production. Processing generally involves heat treatment that can reduce the nutritional and organoleptic quality of the product. Over the years, new processing technologies have emerged to reduce or to eliminate the exposure Gemcitabine molecular weight of the fruit to heat. Ohmic heating is one alternative pulp pasteurization process. This technology can provide rapid and uniform heating, resulting in less thermal damage to labile substances such as vitamins and pigments (Castro et al., 2004 and Sarang et al., 2008). Ohmic heating is defined as a process where electric currents pass through foods to heat them by internally generated energy, without involving any heating medium or heat transfer surface (Castro, Teixeira, Salengke, Sastry, & Vicente, 2003). This heating technology is particularly interesting for viscous products and foods containing particulates because it simultaneously generates heat in both phases and does not need to transfer heat either through a solid–liquid interface or within a solid (de Alwis and Fryer, 1990, Imai et al.

This script evaluates the Wigner matrix rotations and the commutator-relations involved and is available directly from the authors upon request. this website The NMR sample of the ATP binding domain of DnaK from Thermus thermophilus was prepared as explained previously [16]. The protein concentration was ∼50 μM in 100% H2O containing 150 mM 15NH4Cl, 0.5 mM ADP, 50 mM (NH4)H2PO4, 5 mM MgCl2, 1 mM DTT, 1 mM NaN3 and 75 mM Tris pH 7.5. The NMR experiment shown in Fig. 4 is

a 1H-coupled 15N–1H HSQC, obtained from a standard 15H–1H HSQC by removing the 180° proton decoupling pulse during the indirect nitrogen evolution. The experiment was performed on a Bruker Avance III 500 MHz (11.7 T) spectrometer using an HCN inverse RT probe. The spectrum was recorded with 48 complex points in the indirect dimension, a sweep-width of 1000 Hz, and was processed using nmrPipe [42]. Dr. John Kirkpatrick is acknowledged for helpful discussions and for help with recording NMR spectra, Dr. Jochen Reinstein (MPI Heidelberg), Dr. Ralf Seidel and Petra Herde (MPI Dortmund) are acknowledged for providing purified

DnaK-ABD. We thank Dr. Christopher Waudby for critical reading of the manuscript. NDW acknowledges the Federation of European Biochemical Societies (FEBS) for a long-term postdoctoral fellowship. This research is supported by the Biotechnology and Biological Sciences Research Council (BBSRC). DFH is a BBSRC David Phillips Fellow. “
“Accurate

temperature control during NMR experiments is AZD2014 supplier a prerequisite for dynamic and structural investigations [1], [2] and [3]. This requirement is particularly challenging however in high-resolution solid-state spectroscopy with magic angle spinning (MAS) when employing high gas flow rates for driving and bearing, with a separate flow to control of the temperature. High-power radio-frequency (rf) irradiation and friction can lead to significant heating of the sample that cannot be monitored accurately by variable-temperature control units. Several approaches for determining the sample temperatures in solid-state NMR experiments have been reported. NMR thermometers can exploit the temperature dependence of the isotropic chemical shifts of specific compounds containing 13C [1], [2] and [3], 15N [4], 31P [5] and [6], 119Sn [7], [8] and [9], 207Pb [10], [11] and [12] and 1H [13] and [14]. Very recently, spin–lattice relaxation rates of 79Br in KBr powder have been exploited, in addition to chemical shifts, for the determination of the sample temperature under magic-angle spinning conditions over a wide temperature range from 20 to 320 K [15]. Monitoring isotropic chemical shifts to calibrate the sample temperature presupposes a perfect stability of the static magnetic field. It can be difficult to satisfy this requirement in solid-state NMR measurements. Solid-state NMR probes typically do not incorporate any field-frequency lock.

Moreover, the adjoining area is affected by the flows and sediment transported through the strait from the Vistula Lagoon (Chechko 2007). The decreasing trends of the mean (MG) and sorting (σG) values from Yantarny to the south-west confirms the predominant direction of sediment transport along the Sambian coast ( Figure 6). The short transport and quick deposition

is registered by rapid changes in the indices ( Figure 6). A similar effect is recorded by the significant changeability of the mean (MG) and sorting (σG) on the 5 km long stretch located near the Vistula mouth, with an accumulative rate of about 4–6 m year−1 ( Zawadzka-Kahlau 1999) ( Figure 6). Owing to the concave deformation of the coastline, longshore sediment transport is directed from the north-east and the south-west, and the convergence zone migrates significant distances

under http://www.selleckchem.com/products/MDV3100.html the influence of relatively small changes in the direction of wind-generated waves (Kobelyanskaya & Leont’yev 2011). In accordance with the wind direction during the research in July–September 2008 (SW-WN, 72.9%), the convergence zone was migrating along the central and north-eastern part of the spit. The character of the 11 km long stretch located on profiles 16p–4mv, and also that of the 4.5 km long stretch located between profiles 9a and 10a, is balanced and accumulative. To the east of profile 9a (profiles 8a–5a) the coastal zone area is balanced http://www.selleckchem.com/products/Vincristine-Sulfate.html and erosive, with a bed load deficit (Figure 7). The predominant north-easterly direction of the local longshore currents is shown mostly by the variability in the sorting (σG) ( Figure 6). In the central part of the Vistula Spit (profiles 3mv–4a), the sediment dynamics is highly variable, with a high probability of significant influences of the across-shore movement of the bed material. 1. The coastal zone along the Vistula Spit comprises one or two foredunes 1–14 m high, a beach 10–45 m wide, 0–2 nearshore bars 0.3–1.9 m in height, and a flattish slope, inclined 0.1–0.60. “
“Several of the 2010 ACRM-ASNR Joint Educational

Conference abstracts were inadvertently omitted from the online publication of these abstracts in October. These abstracts are available in a Correction 3-mercaptopyruvate sulfurtransferase published on the Archives website. We apologize for the oversight. “
“The Mediterranean Sea comprises a series of connected sub-basins with connections to the Atlantic Ocean and Black Sea (Shaltout and Omstedt, 2014). Many oceanographers use the box model concept to describe the oceanic characteristics of the Mediterranean Sea. Tziperman and Speer (1994), for example, used a three-box model to study the thermohaline seasonal cycle of the Mediterranean Sea. The three boxes in this model are arranged and connected vertically as surface, middle, and deep boxes.

O envolvimento do tubo digestivo ocorre em cerca de 5% dos casos. Destes, 1/3 localizam-se no esófago e podem ser múltiplos2. Na sua génese têm sido implicadas várias células, incluindo mioblastos, fibroblastos e histiócitos. A maioria dos investigadores sustenta, porém, uma etiologia neural, fundamentada na presença de mielina e na positividade para a proteína S-1003, sendo que a sua designação deriva da acumulação de lisossomas secundários no citoplasma. Os tumores com localização esofágica afetam predominantemente doentes do sexo masculino, com um pico de incidência entre a 4.a e a 6.a décadas de vida. Na sua maioria, são

achados endoscópicos. Quando sintomáticos, a disfagia, a regurgitação e a dor retroesternal são as queixas mais comuns. O aspeto endoscópico habitual é o de um pólipo séssil, com dimensão inferior a 2 cm, de consistência dura e coloração amarelada, recoberto por mucosa normal www.selleckchem.com/products/BIBW2992.html Navitoclax order e situado no 1/3 distal do esófago. A ecoendoscopia digestiva, na qual se observam lesões hipoecoicas ou isoecoicas, homogéneas, com bordos regulares, por vezes com um halo periférico, na dependência da mucosa profunda/submucosa (2.a e

3.a camadas), poderá ter utilidade na realização de biopsia e na avaliação da viabilidade da ressecção4. Histologicamente, são formados por grupos de células ovoides ou poligonais, com citoplasma eosinofílico, delimitados por septos de tecido conjuntivo, localizados na camada mucosa e submucosa. Por vezes, o epitélio a recobrir a lesão apresenta hiperproliferação, associada ou não a alterações pseudoepiteliomatosas, que podem levar a um diagnóstico

erróneo de carcinoma epidermoide quando as biopsias são superficiais. No estudo imuno-histoquímico, a proteína S-100 é o marcador mais característico, Meloxicam embora não específico. Outros marcadores, como o CD57, a enolase neuronal específica, a vimentina e a nestina, podem também estar presentes. A maioria destes tumores é benigna, verificando-se um comportamento maligno em apenas 1-3% dos doentes. A recorrência local, o tamanho superior a 4 cm, o crescimento infiltrativo, o aumento das dimensões da lesão em relação ao tamanho inicial ou a invasão linfática devem aumentar a suspeita de malignidade, que se associa a um risco de mortalidade de 40%5. Não existem consensos relativamente ao tratamento. A excisão, endoscópica ou cirúrgica, é considerada a terapêutica de primeira linha. A opção pelo tratamento endoscópico deverá ser reservada para tumores com <20 mm e ausência de invasão da muscularis própria, associando-se, contudo, a um risco de recorrência de 5-10%. Alguns autores sugerem que lesões de menores dimensões e assintomáticas podem ser vigiadas por ecoendoscopia, com base em relatos de seguimento superior a 10 anos sem evidência de evolução da doença. Face à sua raridade, não está estabelecida a periodicidade de vigilância após a ressecção destes tumores4. Os autores declaram não haver conflito de intereses.

The estimated direct and indirect costs related to the illness ranks high among brain disorders, amounting up to mTOR inhibitor 13.9 billion euros in Europe for the year 2010 alone [4]. The number of PD cases, which currently approximates

1.2 million in Europe (0.3% of the general population) and 1 million in the USA, is expected to double by year 2030 along with the increase of life expectancy in the Western populations [4], [5] and [6]. In the absence of any disease-modifying therapy yet, the socioeconomic and financial burdens incurred by PD will continue to grow and defy our healthcare system over the coming decades. Before any preventive or curative intervention could be designed, a clear and detailed understanding of the molecular mechanisms underlying neurodegeneration in sporadic PD is required. However, despite

decades of research, this is definitely not APO866 the case yet. Many mechanisms have been shown to sensitize neurons to death, including impairment of protein degradation systems, mitochondrial dysfunction and oxidative stress, inflammation, excitotoxicity or enhanced apoptosis. In all likelihood, more than one of these, and possible many others, might be at work in PD but the precise combination and temporal succession of the molecular events leading to cell death remain to be disentangled. Thus far, research into PD pathogenesis has heavily relied upon toxic and transgenic animal models, the engineering of which has derived from rare neurotoxin-induced and monogenic forms of parkinsonism in humans. However, these hypothesis-driven approaches have demonstrated major limitations, Sodium butyrate casting serious doubts about the validity of such models to address the complexity of PD pathogenesis. The recent emergence of more global, unbiased and hypothesis-free disciplines such as GWAS and “omics” may provide new research paradigms

to explore PD pathogenesis and PD biomarkers, which may respectively pave the way for original neuroprotective or neuroregenerative therapeutic targets and offer early and accurate diagnostic tools. After reappraising some key aspects of PD neuropathology and etiopathogenesis, this review aims to summarize the ultimate advances in PD research in the context of proteomics. We will glance over proteomics techniques from sample preparation to mass spectrometry (MS) analysis before examining the most recent PD-related findings, limitations and future directions. Most available evidence suggests that the lesional core of PD pathology is the damage of dopaminergic cells in the SN pars compacta [7], which results in dopamine (DA) depletion in the striatum and destabilization of the basal ganglia (BG) motor control loops [8]. Nigral neurodegeneration is thus unambiguously linked to motor symptoms, which first become apparent when about 80% of striatal dopaminergic terminals and 50–60% of nigral dopaminergic cell bodies are already lost [9] and [10].

The plastic debris gets encrusted with foulants, increasing in density as fouling progresses. Once the density exceeds that of sea water it can sink well

below the water surface (Costerton and Cheng, 1987, Andrady and Song, 1991 and Railkin, 2003). Subsequent de-fouling in the water column due to foraging of foulants by other organisms or other mechanisms, can decrease its density causing CP-868596 chemical structure the debris to return back to the surface. A slow cyclic ‘bobbing’ motion of floating plastic debris attributed to this cyclic change in density on submersion below a certain depth of water, was proposed by Andrady and Song (1991) and later confirmed (Stevens and Gregory, 1996 and Stevens, 1992). Fouled debris may increase in density enough to ultimately reach benthic regions; plastics do occur commonly in the benthos (Stefatos and Charalampakis, IDH signaling pathway 1999, Katsanevakis et al., 2007 and Backhurst and Cole, 2000). Even an extensively weathered, embrittled plastic material (that falls apart on handling) still has an average molecular weight in the tens of thousands g/mol. The logarithmic plot of the tensile extensibility (%) versus the number-average molecular weight for LDPE that had undergone weathering shown in Fig. 3 illustrates this. Even for the data points at the very left of the plot (corresponding to extensively

degraded or embrittled plastic) the values of Mn ∼ 103–104 g/mol. Even at these lower molecular weights plastics do not undergo ready biodegradation. Ready microbial biodegradability has been observed in oligomers of about Mn ∼ 500 g/mol polyethylenes. Reduction in particle size by light-induced oxidation does is Thymidylate synthase no guarantee of subsequent biodegradability of the meso- or microplastic fragments. High molecular weight plastics used in common applications do not biodegrade at an appreciable rate as microbial species that can metabololize polymers are rare in nature. This

is particularly true of the marine environment, with the exception of biopolymers such as cellulose and chitin. Recent work, however, has identified several strains of microbes capable of biodegrading polyethylene (Sivan, 2011) and PVC (Shah et al., 2008). In concentrated liquid culture in the laboratory, Actinomycetes Rhodococcus ruber (strain C208) resulted in a reduction of ca. 8% in the dry weight of the polyolefin within 30 days of incubation ( Gilan et al., 2004). Laccases secreted by the species reduced the average molecular weight of polymer as demonstrated by GPC indicating degradation via scission of main chains. However, this process does not occur in soil or marine environments as the candidate microbes are not available in high enough native concentration and competing easily-assimilable nutrient sources are always present. There is virtually no data on kinetics of mineralisation of plastics in the marine environment. However, biopolymers such as chitins (Poulicek and Jeuniaux, 1991 and Seki and Taga, 1963), chitosan (Andrady et al.

The cross-sectional area is enlarged but the fascicular structure of the nerve is preserved. In patients with traumatic nerve lesions, adding ultrasonography to electrodiagnosis may provide a lot of important complementary information about the localization and the cause of impaired nerve function, both being essential for deciding upon surgical treatment. Ultrasonography not only allows one to precisely localize the site of nerve injury, it also indicates whether a nerve is completely transected or partially dissected or whether the nerve is displaced or even encased by surrounding scar formation or by a fibrous or bony callus after bone fracture [29], [30],

[31] and [32]. http://www.selleckchem.com/products/epz-5676.html Furthermore, ultrasonography may identify fracture fragments compressing nerves in close vicinity to bone fractures or may quantify the amount of nerve retraction after complete nerve transection (Fig. 5). Traumatic neuroma can occur at the site of either partial or complete dissection of the nerve. Neuroma appears as a bulbous concentric enlargement at the terminal end of a transected nerve with homogeneous

texture and hypoechoic echogenicity. In case of only partial dissection, the continuity of the nerve is preserved and neuroma appears as nodular shaped broadening of the nerve contour (Supplementary Fig. 3; to view the figure, please visit the online supplementary file in ScienceDirect). Intraoperative ultrasonography is a promising new field enabling morphological examination of nerve lesions in continuity in order to assess the extent find more of nerve fibrosis and to discriminate between intraneural or perineural fibrosis. [33]. Both information are valuable to estimate the regenerative potential of a nerve lesion. Supplementary Fig. 3.  Longitudinal view of the median nerve

(arrows) at the Ribonucleotide reductase wrist. The median nerve is partially dissected with scar formation within the continuity of the nerve and nodular thickening of the nerve contour. Schwannomas (neurilemmomas) and solitary neurofibromas are the most common benign nerve sheath tumors. Sonographically, they appear as well-defined hypoechoic masses with a fusiform shape and a normal-appearing nerve that enters and exits the tumor (Supplementary Fig. 4; to view the figure, please visit the online supplementary file in ScienceDirect) [34] and [35]. Because of their capsule, schwannoma are located more excentric, while not encapsuled neurofibroma are located more centrally compared to the course of the nerve. Since many nerve fascicles remain intact, benign nerve sheath tumors may be missed with electrodiagnostic studies alone. In contrast to benign tumors, malignant nerve sheath tumors are characterized by rapid growth and progressive neurological symptoms. Their shape is ill-defined and their echotexture is more heterogeneous [35]. Supplementary Fig. 4.

Under an Ohio State University IACUC-approved protocol, sixty-four female (47 day old) rats of equivalent weights were divided into four groups (16 per group): 2 control and 2 treatment groups.

Controls were fed a semi-synthetic diet containing 0.6% calcium and 0.6% phosphorus as published elsewhere [24] for 2 or 4 weeks and β-APN treated animals were fed a diet inclusive of β-aminopropionitrile (0.1% dry weight) for 2 or 4 weeks . The 2 and 4 week-time points were used to allow formation of new bone with varying degrees of cross-linking in limited anatomical areas, without affecting the whole bone. Rats were sacrificed at the assigned time points and intact spines were harvested, dissected free from soft tissue

and stored in 70% ethanol. L3 vertebra from each animal were GSK3235025 equilibrated selleck screening library with phosphate buffered saline, pH 7.8, pulverized and reduced with KBH4 for 1 h. After this time, the pH was adjusted to 4 with acetic acid to destroy excess reagent, the tissue washed extensively with water and freeze dried. The reduced bone was hydrolyzed in 6 M HCl at 107 °C for 22 h and the acid was removed by evaporation. Following preliminary fractionation of cross-linked amino acids by partition chromatography, the intermediate compounds (DHLNL and HLNL) were assayed by ion-exchange chromatography with post-column derivatization and the mature bonds (PYD and DPD) were quantified using RP-HPLC using

their natural fluorescence, as described previously [25]. Cross-link concentrations were expressed relative to collagen content determined by colorimetric measurement of hydroxyproline in the original hydrolysate. It should be noted here that both cortical and trabecular bone were included in the analysis. The endplates of each L2 vertebra were carefully removed with a low speed diamond-coated saw (Isomet, Buehler, Germany) to provide samples with a height of approximately 3 mm. The vertebral Cyclin-dependent kinase 3 body was then isolated from the posterior elements and one of the plane surfaces was glued on a carbon rod with a thin layer of cyanoacrylate glue. The other surface was polished to achieve parallel faces. The average final height was 2.5 mm. The vertebral body was scanned in 70% ethanol by μCT with a 12 μm voxel size (μCT40, Scanco, Switzerland). The reconstructions were segmented with an optimal threshold, separated into trabecular and cortical compartments and standard histomorphometric parameters were computed with the manufacturer’s software (IPL, Scanco, Switzerland). Vertebrae (L5) were fixed in 70% ethanol, dehydrated through a graded series of ethanol and embedded undecalcified in polymethylmethacrylate (PMMA). About 5 millimeter thick blocks containing a sagittal vertebral bone section were cut using a low speed diamond saw (Buehler Isomed, Lake Pluff, USA).