bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanisms and clinical applications of chromosomal instability in lymphoid malignancy
Authors: Krem Maxwell M. , Press Oliver W. , Horwitz Marshall S. , Tidwell Timothy 
Published: May 2015

SummaryLymphocytes are unique among cells in that they undergo programmed DNA breaks and translocations, but that special property predisposes them to chromosomal instability (CIN), a cardinal feature of neoplastic lymphoid cells that manifests as whole chromosome‐ or translocation‐based aneuploidy. In several lymphoid malignancies translocations may be the defining or diagnostic markers of the diseases. CIN is a cornerstone of the mutational architecture supporting lymphoid neoplasia, though it is perhaps one of the least understood components of malignant transformation in terms of its molecular mechanisms. CIN is associated with prognosis and response to treatment, making it a key area for impacting treatment outcomes and predicting prognoses. Here we will review the types and mechanisms of CIN found in Hodgkin lymphoma, non‐Hodgkin lymphoma, multiple myeloma and the lymphoid leukaemias, with emphasis placed on pathogenic mutations affecting DNA recombination, replication and repair; telomere function; and mitotic regulation of spindle attachment, centrosome function, and chromosomal segregation. We will discuss the means by which chromosome‐level genetic aberrations may give rise to multiple pathogenic mutations required for carcinogenesis and conclude with a discussion of the clinical applications of CIN and aneuploidy to diagnosis, prognosis and therapy.
Abnormal corticosteroid signalling in airway smooth muscle: mechanisms and perspectives for the treatment of severe asthma
Authors: Chachi L. , Gavrila A. , Tliba O. , Amrani Y. 
Published: May 2015

SummaryGrowing in vivo evidence supports the concept that airway smooth muscle produces various immunomodulatory factors that could contribute to asthma pathogenesis via the regulation of airway inflammation, airway narrowing and remodelling. Targeting ASM using bronchial thermoplasty has provided undeniable clinical benefits for patients with uncontrolled severe asthma who are refractory to glucocorticoid therapy. The present review will explain why the failure of glucocorticoids to adequately manage patients with severe asthma could derive from their inability to affect the immunomodulatory potential of ASM. We will support the view that ASM sensitivity to glucocorticoid therapy can be blunted in severe asthma and will describe some of the factors and mechanisms that could be responsible for glucocorticoid insensitivity.
Landscape‐scale modelling of erosion processes and soil carbon dynamics under land‐use and climate change in agroecosystems
Authors: Lacoste M. , Viaud V. , Michot D. , Walter C. 
Published: May 2015

SummarySoil organic carbon (SOC) sequestration and soil redistribution are linked to soil properties, land use, farming system and climate. In a global‐change context, landscape and climate changes are expected and will most probably have impacts on changes in the soil. Soil change was simulated from 2010 to 2100 in an 86‐ha hedgerow landscape under different scenarios of landscape and climate changes. These scenarios combined contrasting land uses, hedgerow networks and climates. Two models were combined to evaluate the impact of these scenarios on soils: LandSoil, a soil redistribution model, and a SOC model based on RothC‐26.3. A soil thickness of 105 cm was considered. The results indicate that the main factor influencing soil degradation was land‐use change: when compared with the baseline business‐as‐usual landscape, the landscape with the most intensive agricultural systems had the greatest soil erosion (+0.26 t ha−1 year−1) and reduced mean SOC stocks (−17 t ha−1 after 90 years). The second significant factor was climate change, followed by hedgerow network density. Sensitivity to climate change differed between landscapes, and the most sensitive were those with continuous winter wheat. The results indicate that a hedgerow landscape is well adapted to protect soil (regarding carbon storage and soil erosion) in a context of climate change. However, this type of landscape is highly sensitive to cropping intensification and should be protected.
Improved estimates of organic carbon using proximally sensed vis–NIR spectra corrected by piecewise direct standardization
Authors: Ji W. , Viscarra Rossel R. A. , Shi Z. 
Published: May 2015

SummaryWe investigated the use of piecewise direct standardization (PDS) to remove the effects of water and other environmental factors from proximally sensed (field) visible–near infrared (vis–NIR) spectra. Our hypothesis was that the PDS‐standardized field spectra can be used to predict soil carbon effectively with calibrations derived from existing spectroscopic databases of spectra recorded in the laboratory on dried, ground and sieved samples. In our experiments we used field spectra recorded in situ with a portable spectrometer at 124 sites in 11 paddy fields in Zhejiang Province, China. We sampled the soil at these same sites, recorded their spectra in the laboratory and measured their soil organic carbon (SOC) contents with a conventional laboratory technique. Two‐thirds of the samples were used to relate the laboratory spectra to SOC by partial least squares regression (PLSR), and the remaining one‐third was used as an independent validation dataset. We selected a representative set of samples from corresponding field and laboratory spectra that we could use as the PDS transfer set. Piecewise direct standardization was used to relate each wavelength in the laboratory spectra to the corresponding wavelength and its neighbours in the field spectra. The field spectra of the validation samples were then corrected with PDS so that they acquired the characteristics of the spectra measured under laboratory conditions. The approach was evaluated by (i) quantifying the similarity between the PDS‐standardized spectra and their corresponding laboratory spectra, (ii) measuring the accuracy of their SOC predictions on the independent validation dataset and (iii) comparing these results with those of direct standardization (DS). Both PDS and DS led to considerable improvements in the predictions of SOC (R2 = 0.71, R2 = 0.60, respectively), compared with those with original field spectra (R2 = 0.03). However, fewer transfer samples were needed with PDS to obtain similar results.
Sebum, inflammasomes and the skin: current concepts and future perspective
Authors: Oyewole Anne O. , Birch‐Machin Mark A. 
Published: May 2015

AbstractIncreasing evidence has identified ultraviolet radiation (UVR) as the skins most potent mutagen as over exposure results in sunburn, inflammation and DNA damage, thus contributing to a photo‐ageing phenotype and possibly skin carcinogenesis. The lipid‐rich sebum secreted onto the surface of the skin plays an important physiological role in protecting the skin against external challenges. When skin is photosensitised by UVR, the lipid constituents of sebum are easily oxidised, generating several lipid photo‐oxidative products (e.g. squalene peroxides). These photo‐oxidative products have been shown to exert diverse toxicological, biological and immunological effects in the skin and have therefore been implicated in several detrimental skin alterations including premature skin ageing. The involvement of lipid peroxidation products in UVR‐induced inflammatory responses has been inadequately studied and highly controversial. Furthermore, it is unclear to what extent these oxidative products contribute to the underlying mechanisms of skin photo‐ageing. Therefore, this viewpoint essay will discuss the current knowledge on the effect of UVR exposure on skin surface lipids and how these may mediate UVR‐induced inflammatory responses which may be key contributors to photo‐damage in skin. This essay will also examine the potential role of inflammasomes (innate immune complexes) in the inflammatory response associated with UVR‐induced lipid peroxidation. Limited evidence is available on the interactions between sebaceous lipids, downstream mediators and concomitant immune response in sun‐exposed skin and clearer elucidation may lead to novel biomarkers of photo‐ageing and the incorporation of new molecules into current skin therapies which better target oxidised lipids and or downstream mediators/pathways.
Discordant human epidermal growth factor receptor 2 overexpression in primary and metastatic upper gastrointestinal adenocarcinoma signifies poor prognosis
Authors: Hedner Charlotta , Tran Lena , Borg David , Nodin Björn , Jirström Karin , Eberhard Jakob 
Published: May 2015

AimsTargeted therapy with trastuzumab has proved to be effective for patients with gastric cancer overexpressing the human epidermal growth factor receptor 2 (HER2). Further studies are needed to determine the best method for assessment of HER2 overexpression. Moreover, the prognostic value of HER2 overexpression, including the significance of tumour heterogeneity, remains unclear.Methods and resultsHER2 overexpression and gene copy alterations were assessed by immunohistochemistry and silver in‐situ hybridization, respectively, on tissue microarrays with primary tumours and a subset of paired lymph node metastases from 174 patients with oesophageal or gastric adenocarcinoma. Cox proportional hazards modelling was applied to assess the prognostic impact of HER2 overexpression, intratumoural heterogeneity and conversion from primary tumour to metastasis. The correlation between protein expression and gene amplification was in line with previous studies. Primary–metastatic conversion was observed in 12.9% of the cases. HER2 overexpression or intratumoural heterogeneity was not prognostic, but primary–metastatic conversion was an independent predictor of a shorter overall survival (hazard ratio = 4.93).ConclusionsAs trastuzumab is emerging as an important targeted therapy for patients with upper gastointestinal cancer, these results underline the importance of further studies addressing the occurrence and clinical significance of discrepant HER2 expression in primary tumours and metastases.
The effect of subduction on the sulphur, carbon and redox budget of lithospheric mantle
Authors: Evans K.A. , Powell R. 
Published: May 2015

AbstractSubduction of hydrated lithospheric mantle introduces HO, ferric iron, oxidized carbon and sulphur to the subduction zone system. The fate of these components is poorly known, but is intimately linked to the global geochemical cycles of iron, carbon and sulphur, the genesis of arc‐related ore deposits, the temporal evolution of mantle redox state and subduction‐related earthquakes and magmatism. thermocalc is used to provide first‐order constraints on the effect of subduction zone metamorphism on metamorphic redistribution of iron, carbon, sulphur and water in ultramafic rocks via construction of P−T and T‐X(O) pseudosections with open system calculation of the effect of fluid loss. The calculations replicate observed mineral assemblages in high‐P to low‐T ultramafic rocks at P−T conditions consistent with those suggested by other workers. The results are consistent with open system fluid loss without significant fluid infiltration. Water loss is complete by 850 C, the corresponding depth of fluid loss being consistent with that inferred for earthquakes in subducting slabs. Losses of carbon and sulphur are relatively minor, at around <5% and <1%, respectively, so it is envisaged that most carbon and sulphur subducted in ultramafic lithologies is transported to >5 GPa, below the depths of the source zone for arc volcanoes. Oxygen activity for rocks in closed systems that evolve with a fixed redox budget is calculated to change from ΔFMQ −1 at 350 C to over ΔFMQ +3 at 850 C. This result emphasizes the need to consider redox budget as well as oxygen activity when the results of experiments performed at fixed oxygen activity relative to some buffer are interpreted in the context of natural systems. In open systems, devolatilization is calculated to increase the redox budget and oxygen activity of the residue via loss of methane and HS at the brucite‐out and serpentine‐out reactions respectively. No fluid‐induced mechanism for oxidation of sub‐arc mantle by transfer of redox budget from hydrated ultramafic lithologies to the overlying sub‐arc mantle was identified, although further thermodynamic data on fluid species such as S are required to confirm this.
Assembly, trafficking and function of α1β2γ2 GABAA receptors are regulated by N‐terminal regions, in a subunit‐specific manner
Authors: Wong Lik‐Wei , Tae Han‐Shen , Cromer Brett A. 
Published: May 2015

AbstractGABAA receptors are pentameric ligand‐gated ion channels that mediate inhibitory fast synaptic transmission in the central nervous system. Consistent with recent pentameric ligand‐gated ion channels structures, sequence analysis predicts an α‐helix near the N‐terminus of each GABAA receptor subunit. Preceding each α‐helix are 8–36 additional residues, which we term the N‐terminal extension. In homomeric GABAC receptors and nicotinic acetylcholine receptors, the N‐terminal α‐helix is functionally essential. Here, we determined the role of the N‐terminal extension and putative α‐helix in heteromeric α1β2γ2 GABAA receptors. This role was most prominent in the α1 subunit, with deletion of the N‐terminal extension or further deletion of the putative α‐helix both dramatically reduced the number of functional receptors at the cell surface. Conversely, deletion of the β2 or γ2 N‐terminal extension had little effect on the number of functional cell surface receptors. Additional deletion of the putative α‐helix in the β2 or γ2 subunits did, however, decrease both functional cell surface receptors and incorporation of the γ2 subunit into mature receptors. In the β2 subunit only, α‐helix deletions affected GABA sensitivity and desensitization. Our findings demonstrate that N‐terminal extensions and α‐helices make key subunit‐specific contributions to assembly, consistent with both regions being involved in inter‐subunit interactions.image
N‐terminal α‐helices and preceding sequences of eukaryotic pentameric ligand‐gated ion channels are absent in prokaryotic homologues, suggesting they may not be functionally essential. Here, we show that in heteropentameric α1β2γ2 GABAA receptors, the role of these segments is highly subunit dependent. The extension preceding the α‐helix in the α subunit is crucial for assembly and trafficking, but is of little importance in β and γ subunits. Indeed, robust receptor levels remain when the extension and α‐helix are removed in β or γ subunits.
Phenolic compounds prevent the oligomerization of α‐synuclein and reduce synaptic toxicity
Authors: Takahashi Ryoichi , Ono Kenjiro , Takamura Yusaku , Mizuguchi Mineyuki , Ikeda Tokuhei , Nishijo Hisao , Yamada Masahito 
Published: May 2015

AbstractLewy bodies, mainly composed of α‐synuclein (αS), are pathological hallmarks of Parkinson's disease and dementia with Lewy bodies. Epidemiological studies showed that green tea consumption or habitual intake of phenolic compounds reduced Parkinson's disease risk. We previously reported that phenolic compounds inhibited αS fibrillation and destabilized preformed αS fibrils. Cumulative evidence suggests that low‐order αS oligomers are neurotoxic and critical species in the pathogenesis of α‐synucleinopathies. To develop disease modifying therapies for α‐synucleinopathies, we examined effects of phenolic compounds (myricetin (Myr), curcumin, rosmarinic acid (RA), nordihydroguaiaretic acid, and ferulic acid) on αS oligomerization. Using methods such as photo‐induced cross‐linking of unmodified proteins, circular dichroism spectroscopy, the electron microscope, and the atomic force microscope, we showed that Myr and RA inhibited αS oligomerization and secondary structure conversion. The nuclear magnetic resonance analysis revealed that Myr directly bound to the N‐terminal region of αS, whereas direct binding of RA to monomeric αS was not detected. Electrophysiological assays for long‐term potentiation in mouse hippocampal slices revealed that Myr and RA ameliorated αS synaptic toxicity by inhibition of αS oligomerization. These results suggest that Myr and RA prevent the αS aggregation process, reducing the neurotoxicity of αS oligomers.
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To develop disease modifying therapies for α‐synucleinopathies, we examined effects of phenolic compounds on α‐synuclein (αS) oligomerization. Phenolic compounds, especially Myricetin (Myr) and Rosmarinic acid (RA), inhibited αS oligomerization and secondary structure conversion. Myr and RA ameliorated αS synaptic toxicity on the experiment of long‐term potentiation. Our results suggest that Myr and RA prevent αS aggregation process and reduce the neurotoxicity of αS oligomers. Phenolic compounds are good candidates of disease modifying drugs for α‐synucleinopathies.
‘Language of the past’ – Exploring past tense disruption during autobiographical narration in neurodegenerative disorders
Authors: Irish Muireann , Kamminga Jody , Addis Donna Rose , Crain Stephen , Thornton Rosalind , Hodges John R. , Piguet Olivier 
Published: May 2015

Compromised retrieval of autobiographical memory (ABM) is well established in neurodegenerative disorders. The recounting of autobiographical events is inextricably linked to linguistic knowledge, yet no study to date has investigated whether tense use during autobiographical narration is disrupted in dementia syndromes. This study investigated the incidence of correct past tense use during ABM narration in patients with Alzheimer's disease (AD, n = 10) and semantic dementia (SD, n = 10) in comparison with healthy older Controls (n = 10). Autobiographical narratives were analysed for episodic content (internal/external) and classified according to tense use (past/present). Across both patient groups, use of the past tense was significantly compromised relative to Controls, with increased levels of off‐target present tense verbs observed. Voxel‐based morphometry analyses based on structural MRI revealed differential associations between past tense use and regions of grey matter intensity in the brain. Bilateral temporal cortices were implicated in the SD group, whereas frontal, lateral, and medial temporal regions including the right hippocampus emerged in AD. This preliminary study provides the first demonstration of the disruption of specific linguistic constructs during autobiographical narration in AD and SD. Future studies are warranted to clarify at what point in the disease trajectory such deficits in tense use emerge, and whether these deficits are a product or contributing factor in memory disruption in these syndromes.
Genetic rescue: a safe or risky bet?
Authors: Waller Donald M. 
Published: May 2015

Small and isolated populations face threats from genetic drift and inbreeding. To rescue populations from these threats, conservation biologists can augment gene flow into small populations to increase variation and reduce inbreeding depression. Spectacular success stories include greater prairie chickens in Illinois (Westermeier et al. ), adders in Sweden (Madsen et al. ) and panthers in Florida (Johnson et al. ). However, we also know that performing such crosses risks introducing genes that may be poorly adapted to local conditions or genetic backgrounds. A classic example of such ‘outbreeding depression’ occurred when different subspecies of ibex from Turkey and the Sinai were introduced to assist recovery of an ibex population in Czechoslovakia (Templeton ). Despite being fertile, the hybrids birthed calves too early, causing the whole population to disappear. In the face of uncertainty, conservation biologists have tended to respect genetic identity, shying away from routinely crossing populations. In this issue of Molecular Ecology, Frankham () compiles empirical data from experimental studies to assess the costs and benefits of between‐population crosses (Fig. ). Crosses screened to exclude those involving highly divergent populations or distinct habitats show large heterosis with few apparent risks of outbreeding depression. This leads Frankham to advocate for using assisted gene flow more widely. But do the studies analysed in this meta‐analysis adequately test for latent outcrossing depression?
Limiting climatic factors and habitats of Erica tetralix at the eastern edge of its distribution range
Authors: Auniņa Liene , Auniņš Ainārs 
Published: May 2015

We determined the limiting climatic factors, as well as the preferred habitats, of Erica tetralix L. at the eastern limit of its distribution range in the eastern Baltic region. It was found that E. tetralix in this region is a typical bog woodland plant preferring the wettest Sphagnum‐rich sites. Northern Atlantic wet heath fragments, base‐rich fens and species‐rich Nardus grasslands were other habitats for the species. The species composition in E. tetralix habitats resembled that found in appropriate habitats within its main distribution range, although the habitats in the eastern Baltic region lack many Atlantic floristic elements characteristic of wet heath.A generalised linear model describing the climatic niche of E. tetralix in Latvia suggests that mild winters, which exhibit a combination of a shallow maximum depth of soil freezing and a large number of days when the air temperature exceeds 0°C, as well as abundant annual and winter precipitation, are the main factors allowing the presence of E. tetralix in Latvia. The climate parameters at the eastern limit of the species’ distribution range are consistent with those recorded as being suitable for E. tetralix elsewhere.Our results reveal a strong relationship between oceanity and the distribution of E. tetralix. The climatic niche model suggests more climatically suitable areas in the Coastal Lowland geobotanical region where the species could potentially be found, most likely in bog woodlands. The future prospects to restore open areas of northern Atlantic wet heath with E. tetralix in Latvia are poor due to the decline in traditional land‐use; these areas have turned into bog woodlands or been converted into agricultural land.
Ultrasonography Leads to Accurate Diagnosis and Management of Painful Acromioclavicular Joint Cyst
Authors: Chang Chien George C. , Best Craig S. , Clay Brian S. , Candido Kenneth D. 
Published: May 2015

AbstractBackgroundAcromioclavicular joint (ACJ) cysts are uncommon causes of shoulder pain. Type 1 ACJ cysts are limited to the ACJ and form in the presence of intact rotator cuff musculature, while type 2 cysts form secondary to biomechanical instability following rotator cuff tear or rupture.Case PresentationA 36‐year‐old overweight male with history of chronic left grade 2 (Rockwood classification) ACJ separation presented with intermittent pain at the distal superoanterior left clavicle. Physical examination revealed small step off at the ACJ and multiple subcutaneous cysts surrounding the ACJ. Ultrasound examination revealed a mild separation of the left ACJ, mild distension of the joint capsule, and a small, well‐circumscribed, compressible hypo‐echoic cyst overlying the clavicle. Palpation of the cyst against the clavicle reproduced the patient's symptoms of intermittent pain. He opted for ultrasound‐guided aspiration and subsequently had full resolution of his symptoms.DiscussionMusculoskeletal ultrasound is useful for diagnosis and management of refractory musculoskeletal conditions that are commonly misdiagnosed on physical examination and translucent to radiographic imaging. Musculoskeletal ultrasound allowed us to exclude rotator cuff pathology, identify ACJ cyst as the pain generator, classify it as a type 1 ACJ cyst, and aid in needle guidance for successful aspiration leading to full resolution of our patient's pain.