bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coordination chemistry of Ca sites at the surface of nanosized hydroxyapatite: interaction with H2O and CO
Authors: Bolis Vera , Busco Claudia , Martra Gianmario , Bertinetti Luca , Sakhno Yuriy , Ugliengo Piero , Chiatti Fabio , Corno  Marta , Roveri Norberto 
Published: February 2012

The affinity towards water of a selection of well-defined, nanostructured hydroxyapatite (HA) samples was investigated by H2O vapour adsorption microcalorimetry and infrared (IR) spectroscopy. A large hydrophilicity of all investigated materials was confirmed. The surface features of hydrated HA were investigated on the as-synthesized samples pre-treated in mild conditions atT=303 K, whereas dehydrated HA features were characterized on samples activated atT=573 K. The relatively large hydrophilicity of the hydrated surface (−ΔadsH∼100–50 kJ mol−1) was due to the interaction of water with the highly polarized H2O molecules strongly coordinated to the surface Ca2+cations. At the dehydrated surface, exposing coordinatively unsaturated (cus) Ca2+cations, H2O was still molecularly adsorbed but more strongly (−ΔadsH∼120–90 kJ mol−1). The use of CO adsorption to quantify the Lewis acidic strength of HA surface sites revealed only a moderate strength ofcusCa2+cations, as confirmed by both microcalorimetric and IR spectroscopic measurements andab initiocalculations. This result implies that the large HA/H2O interaction energy is due to the interplay betweencusCa2+sites and nearby hydrophilic PO4groups, not revealed by the CO probe. The lower density ofcusCa2+cations at the 573 K activated HA surface with respect to the pristine one did not affect the whole hydrophilicity of the surface, as the polarizing effect of Ca sites is so strong to extend up to the fourth hydrated layer, as confirmed by both high-coverage microcalorimetric and IR spectroscopic data. No specific effects due to the investigated specimen preparation method and/or different morphology were observed.
The record of Himalayan erosion preserved in the sedimentary rocks of the Hatia Trough of the Bengal Basin and the Chittagong Hill Tracts, Bangladesh
Authors: Najman Y. , Allen R. , Willett E. A. F. , Carter A. , Barfod D. , Garzanti E. , Wijbrans J. , Bickle M. J. , Vezzoli G. , Ando S. , Oliver G. , Uddin M. J. 
Published: February 2012

AbstractThe Cenozoic sedimentary succession of Bangladesh provides an archive of Himalayan erosion. However, its potential as an archive is currently hampered by a poor lithostratigaphic framework with limited age control. We focus on the Hatia Trough of the Bengal Basin and the adjacent fold belt of the Chittagong Hill Tracts which forms the outermost part of the west‐propagating Indo‐Burmese wedge. We present a basin‐wide seismic stratigraphic framework for the Neogene rocks, calibrated by biostratigraphy, which divides the succession into three seismically distinct and regionally correlatable Megasequences (MS). MS1 extends to NN15‐NN16 (ca. 2.5–3.9 Ma), MS2 to NN19‐NN20 (ca. 0.4–1.9 Ma) and MS3 to present day. Our seismic mapping, thermochronological analyses of detrital mineral grains, isotopic analyses of bulk rock, heavy mineral and petrographic data, show that the Neogene rocks of the Hatia Trough and Chittagong Hill Tracts are predominantly Himalayan‐derived, with a subordinate arc‐derived input possibly from the Paleogene IndoBurman Ranges as well as the Trans‐Himalaya. Our seismic data allow us to concur with previous work that suggests folding of the outer part of the west‐propagating wedge only commenced recently, within the last few million years. We suggest that it could have been the westward encroachment and final abutment of the Chittagong Hill Tracts fold belt onto the already‐uplifted Shillong Plateau that caused diversion of the palaeo‐Brahmaputra to the west of the plateau as the north‐east drainage route closed.
Late Cretaceous‐Palaeogene stratigraphic and basin evolution in the Zhepure Mountain of southern Tibet: implications for the timing of India‐Asia initial collision
Authors: Hu Xiumian , Sinclair Hugh D. , Wang Jiangang , Jiang Hehe , Wu Fuyuan 
Published: February 2012

AbstractThis article presents combined stratigraphic, sedimentological, subsidence and provenance data for the Cretaceous–Palaeogene succession from the Zhepure Mountain of southern Tibet. This region records the northernmost sedimentation of the Tethyan passive margin of India, and this time interval represents the transition into continental collision with Asia. The uppermost Cretaceous Zhepure Shanpo and Jidula formations record the transition from pelagic into upper slope to delta‐plain environments. The Palaeocene–lower Eocene Zongpu Formation records a carbonate ramp that is overlain by the deep‐water Enba Formation (lower Eocene). The upper part of the Enba Formation records shallowing into a storm‐influenced, outer shelf environment. Detrital zircon U–Pb and Hf isotopic data indicate that the terrigenous strata of the Enba Formation were sourced from the Lhasa terrane. Unconformably overlying the Enba Formation is the Zhaguo Formation comprising fluvial deposits with evidence of recycling from the underlying successions. Backstripped subsidence analysis indicates shallowing during latest Cretaceous‐earliest Palaeocene time (Zhepure Shanpo and Jidula formations) driven by basement uplift, followed by stability (Zongpu Formation) until early Eocene time (Enba Formation) when accelerated subsidence occurred. The provenance, subsidence and stratigraphy suggest that the Enba and Zhaguo formations record foredeep and wedge‐top sedimentation respectively within the early Himalayan foreland basin. The underlying Zongpu Formation is interpreted to record the accumulation of a carbonate ramp at the margin of a submarine forebulge. The precursor tectonic uplift during latest Cretaceous time could either record surface uplift over a mantle plume related to the Réunion hotspot, or an early signal of lithospheric flexure related to oceanic subduction, continental collision or ophiolite obduction. The results indicate that the collision of India with Asia occurred before late Danian (ca. 62 Ma) time.
Incidence, risk factors and outcome of histological transformation in follicular lymphoma
Authors: Conconi Annarita , Ponzio Carlotta , Lobetti‐Bodoni Chiara , Motta Maddalena , Rancoita Paola M.V. , Stathis Anastasios , Moccia Alden A. , Mazzucchelli Luca , Bertoni Francesco , Ghielmini Michele , Cavalli Franco , Zucca Emanuele 
Published: February 2012

SummaryHistological transformation (HT) into diffuse large B‐cell lymphoma (DLBCL) was documented in 37 of the 281 (13%; 95% CI, 9–18) follicular lymphoma (FL) patients treated at our institute from 1979 to 2007. HT occurred at a median of 2·75 years from initial FL diagnosis and HT rate was 15% at 10 years and 26% at 14 years, with a plateau from that point onward. Patients with bulky or extranodal disease, or those diagnosed before 1990 had a significantly higher risk of HT. When initial treatment strategies were taken into account, a reduced HT risk was seen in the patients initially managed with a ‘watch and wait’ policy, while the risk appeared significantly increased in the small subset of 18 patients initially managed with rituximab plus chemotherapy (P = 0·0005). HT was associated with a significantly shorter cause‐specific survival (P = 0·0002). Predictors of survival after HT were the Follicular Lymphoma International Prognostic Index at diagnosis, as well as age and performance status at the time of HT. Our data confirm the adverse clinical outcome of FL after HT. In keeping with previous isolated reports, our findings suggest that there is a subgroup of patients in whom HT may not occur.
ACTN4 gene amplification and actinin‐4 protein overexpression drive tumour development and histological progression in a high‐grade subset of ovarian clear‐cell adenocarcinomas
Authors: Yamamoto Sohei , Tsuda Hitoshi , Honda Kazufumi , Takano Masashi , Tamai Seiichi , Imoto Issei , Inazawa Johji , Yamada Tesshi , Matsubara Osamu 
Published: February 2012

Yamamoto S, Tsuda H, Honda K, Takano M, Tamai S, Imoto I, Inazawa J, Yamada T & Matsubara O  (2012) Histopathology 60,1073–1083
ACTN4 gene amplification and actinin‐4 protein overexpression drive tumour development and histological progression in a high‐grade subset of ovarian clear‐cell adenocarcinomasAims:  Actinin‐4, encoded by the ACTN4 gene located on chromosome 19q13.2, enhances cell motility by bundling the actin cytoskeleton. We assessed how ACTN4/actinin‐4 alterations contribute to the tumorigenesis of ovarian clear‐cell adenocarcinomas (CCAs).Methods and results:  Fluorescence in‐situ hybridization analysis demonstrated that ACTN4 amplification (≥4 ACTN4 copies in ≥40% of cells) occurred in 27 (33%) of 81 CCAs and genomic gains of ACTN4 were associated strongly with immunohistochemical actinin‐4 overexpression, poorly differentiated tumour histology and shorter patient survival (all P < 0.05). From the 27 ACTN4‐amplified CCAs, 23 tumours with adjacent putative precursor lesions were selected and examined for ACTN4/actinin‐4 alterations with respect to their intratumoral heterogeneity. In this selected cohort, none of the precursors lacking cytological atypia exhibited gains of ACTN4 or actinin‐4 overexpression; 50% of the atypical endometrioses and 75% of the borderline CCAFs showed low‐level gains of ACTN4 and actinin‐4 overexpression, respectively. In 12 of 23 ACTN4‐amplified CCAs, intratumoral heterogeneity for ACTN4 alterations was documented in carcinomatous components; the better differentiated carcinoma components exhibited fewer alterations than those with poorly differentiated histology.Conclusion:  Accumulative genomic gains of ACTN4, causing actinin‐4 protein overexpression, drive the development and progression of ovarian CCAs with high‐grade histology.
MUC5AC, cytokeratin 20 and HER2 expression and K‐RAS mutations within mucinogenic growth in congenital pulmonary airway malformations
Authors: Rossi Giulio , Gasser Bernard , Sartori Giuliana , Migaldi Mario , Costantini Matteo , Mengoli Maria Cecilia , Piccioli Silvia , Cavazza Alberto , Rivasi Francesco 
Published: February 2012

Rossi G, Gasser B, Sartori G, Migaldi M, Costantini M, Mengoli M C, Piccioli S, Cavazza A & Rivasi F  (2012) Histopathology 60, 1133–1143MUC5AC, cytokeratin 20 and HER2 expression and K‐RAS mutations within mucinogenic growth in congenital pulmonary airway malformationsAims:  To analyse the expression of several mucins (MUC1, MUC2, MUC3, MUC5AC and MUC6), epidermal growth factor receptor (EGFR), v‐erb‐b2 erythroblastic leukaemia viral oncogene homologue 2 (HER2), thyroid transcription factor‐1 (TTF‐1), caudal type homeobox 2 (CDX2) and cytokeratin 20 (CK20), and the presence of mutations of EGFR, KRAS and HER2 in congenital pulmonary airway malformations (CPAM).Methods and results:  Forty‐one cases of CPAM and six pulmonary sequestrations were included. TTF‐1 expression was observed in all cases but was not seen in mucinogenic growths in CPAM. CDX2 expression was completely negative. MUC1 expression was noted in 12 (29%) CPAM and in 33% sequestrations. MUC5AC was noted in only five cases (26%) by immunohistochemistry and was found in the mucinogenic proliferations of type 1 CPAM. No immunolabelling was noted for the other mucins. EGFR was expressed variably in almost all cases, while HER2 and CK20 was seen exclusively in the mucinogenic proliferations. All mucinous growths were characterized by KRAS mutations. No EGFR and HER2 gene alterations were identified.Conclusions:  KRAS mutations and MUC5AC, CK20 and HER2 expression was seen in all mucinogenic proliferations, supporting the neoplastic nature of these cytologically bland growths. These findings emphasize the importance of complete surgical resection of such lesions.
Somatic mutations of the KEAP1 gene in common solid cancers
Authors: Yoo Nam Jin , Kim Hyung Ran , Kim Yoo Ri , An Chang Hyeok , Lee Sug Hyung 
Published: February 2012

Yoo N J, Kim H R, Kim Y R, An C H & Lee S H  (2012) Histopathology 60, 943–952Somatic mutations of the KEAP1 gene in common solid cancersAims:  KEAP1 inhibits nuclear factor erythroid 2‐related factor 2 (NRF2)‐induced cytoprotection, and is considered to be a candidate tumour suppressor. Somatic mutation of NRF2 has been analysed in a wide variety of human cancers, whereas somatic mutation of KEAP1 has been reported only in lung and gall bladder cancers. The aim of our study was to investigate whether KEAP1 mutations are widespread in human cancers.Methods and results:  We analysed 499 cancer tissues from lung, breast, colon, stomach, liver, larynx and prostate, and leukaemias, by single‐strand conformation polymorphism analysis. We detected somatic mutations of KEAP1 in gastric (11.1%), hepatocellular (8.9%), colorectal (7.8%), lung (4.6%), breast (2.0%) and prostate (1.3%) carcinomas. Allelic losses of the KEAP1 locus were identified in 42.9% of cancers with KEAP1 mutations, but no NRF2 mutations were detected in these cancers. The NRF2‐activated cytoprotective proteins (NAD(P)H dehydrogenase quinone 1 and glutamine‐cysteine ligase catalytic subunit) were expressed in all of the cancers with KEAP1 mutations.Conclusions:  Our data show that KEAP1 mutations occur widely in solid cancers, irrespective of histological type. Biallelic inactivation of KEAP1 and increased levels of cytoprotective proteins in the cancers suggest that KEAP1 mutations might protect cancer cells from oxidative insults and play a role in the development of solid cancers.
Immune cell activation by trophoblast‐derived microvesicles is mediated by syncytin 1
Authors: Holder Beth S. , Tower Clare L. , Forbes Karen , Mulla Melissa J. , Aplin John D. , Abrahams Vikki M. 
Published: February 2012

SummaryEnvelope glycoproteins of human endogenous retrovirus (HERV), such as syncytin 1 (HERV‐W), are highly expressed in the placenta and some family members have immunomodulatory properties. Placental microvesicles (MV), which are shed into the maternal circulation during pregnancy, have been demonstrated to induce immune cell activation. Therefore, the aim of this study was to investigate the immunological properties of the highly expressed placental HERV‐W protein, syncytin 1, and its potential involvement in placental MV modulation of immune cell activity. The MV shed from first trimester, normal term and pre‐eclamptic term placentas, and from the BeWo trophoblast cell line, all contain syncytin 1. Recombinant syncytin 1 and syncytin 1‐positive BeWo trophoblast MV both induced peripheral blood mononuclear cell (PBMC) activation, indicated through production of cytokines and chemokines. Reducing syncytin 1 content in BeWo MV inhibited PBMC activation. Recombinant syncytin 1 and syncytin‐1‐positive BeWo MV dampened PBMC responses to lipopolysaccharide challenge. Our findings suggest that syncytin 1 is shed from the placenta into the maternal circulation in association with MV, and modulates immune cell activation and the responses of immune cells to subsequent lipopolysaccharide stimulation. These studies implicate placental MV‐associated HERV in fetal regulation of the maternal immune system.
Regulatory T‐cell therapy for inflammatory bowel disease: more questions than answers
Authors: Himmel Megan E. , Yao Yu , Orban Paul C. , Steiner Theodore S. , Levings Megan K. 
Published: February 2012

SummaryT regulatory (Treg) cells are critical for maintaining immune homeostasis and establishing tolerance to foreign, non‐pathogenic antigens including those found in commensal bacteria and food. Because of their multiple suppressive mechanisms, Tregs represent a promising strategy for engineering tolerance to self and non‐self antigens in chronic inflammatory diseases. Already in clinical trials in the transplantation setting, the question remains whether this therapy would be effective for the treatment of mucosal inflammatory diseases that do not pose an immediate threat to life. In this review we will discuss evidence from both animal models and patients suggesting that Treg therapy would be beneficial in the context of inflammatory bowel disease (IBD). We will examine the role of T‐cell versus Treg dysfunction in IBD and discuss the putative antigens that could be potential targets of antigen‐directed Treg therapy. Finally, the challenges of using Treg therapy in IBD will be discussed, with a specific emphasis on the role that the microbiota may play in the outcome of this treatment. As Treg therapy becomes a bedside reality in the field of transplantation, there is great hope that it will soon also be deployed in the setting of IBD and ultimately prove more effective than the current non‐specific immunosuppressive therapies.
Comparative study of regulatory T cells expanded ex vivo from cord blood and adult peripheral blood
Authors: Fan Huahua , Yang Jie , Hao Jun , Ren Yana , Chen Liang , Li Guiping , Xie Rufeng , Yang Yiming , Gao Feng , Liu Mingyao 
Published: February 2012

SummaryIn this study, we expanded regulatory T cells (Tregs) ex vivo from CD4+ CD25+ T cells from cord blood (CB) and CD4+ CD25+ CD127− T cells from adult peripheral blood (APB) and compared the suppressive functions of the newly generated Tregs. The Tregs from CB and APB were expanded either in two cycles with a polyclonal stimulus or in two cycles with an alloantigen stimulus in the first cycle and a polyclonal stimulus in the second cycle. Cell yield after Treg expansion with polyclonal stimulation was greater than that of Tregs expanded with combined alloantigen and polyclonal stimulation. The expanded Tregs expressed high levels of Foxp3, CD39 and cytotoxic T‐lymphocyte antigen‐4 and low levels of CD127, interleukin‐2 and interferon‐γ. After two cycles of expansion, the CB Tregs maintained expression of the GARP gene and showed greater suppressive function than APB Tregs. The CB Tregs that were expanded with two cycles of polyclonal stimulation suppressed not only the polyclonal antigen‐driven responder T (Tresp) cell proliferation but also the HLA mismatched dendritic cell‐driven Tresp cell proliferation. When CB and APB Tregs were expanded with a primary alloantigen stimulus followed by a secondary polyclonal stimulus, the Tregs showed a potent, antigen‐specific suppressive capacity. The Tregs expanded with two cycles of polyclonal stimulation from both CB and APB alleviated acute graft‐versus‐host disease symptoms and prolonged survival in a murine model of graft‐versus‐host disease. In conclusion, CB Tregs expanded with two cycles of polyclonal stimulation had a stronger immunosuppressive function than APB Tregs. It is feasible to obtain human functional alloantigen‐specific Tregs expanded ex vivo from CB and APB in large numbers.
Disruption of the ESX‐5 system of Mycobacterium tuberculosis causes loss of PPE protein secretion, reduction of cell wall integrity and strong attenuation
Authors: Bottai Daria , Di Luca Mariagrazia , Majlessi Laleh , Frigui Wafa , Simeone Roxane , Sayes Fadel , Bitter Wilbert , Brennan Michael J. , Leclerc Claude , Batoni Giovanna , Campa Mario , Brosch Roland , Esin Semih 
Published: February 2012

SummaryThe chromosome of Mycobacterium tuberculosis encodes five type VII secretion systems (ESX‐1–ESX‐5). While the role of the ESX‐1 and ESX‐3 systems in M. tuberculosis has been elucidated, predictions for the function of the ESX‐5 system came from data obtained in Mycobacterium marinum, where it transports PPE and PE_PGRS proteins and modulates innate immune responses. To define the role of the ESX‐5 system in M. tuberculosis, in this study, we have constructed five M. tuberculosis H37Rv ESX‐5 knockout/deletion mutants, inactivating eccA5, eccD5, rv1794 and esxM genes or the ppe25‐pe19 region. Whereas the Mtbrv1794ko displayed no obvious phenotype, the other four mutants showed defects in secretion of the ESX‐5‐encoded EsxN and PPE41, a representative member of the large PPE protein family. Strikingly, the MtbeccD5ko mutant also showed enhanced sensitivity to detergents and hydrophilic antibiotics. When the virulence of the five mutants was evaluated, the MtbeccD5ko and MtbΔppe25‐pe19 mutants were found attenuated both in macrophages and in the severe combined immune‐deficient mouse infection model. Altogether these findings indicate an essential role of ESX‐5 for transport of PPE proteins, cell wall integrity and full virulence of M. tuberculosis, thereby opening interesting new perspectives for the study of this human pathogen.
Formation mechanism of the internal structure of type I protein bodies in rice endosperm: relationship between the localization of prolamin species and the expression of individual genes
Authors: Saito Yuhi , Shigemitsu Takanari , Yamasaki Ryuichi , Sasou Ai , Goto Futami , Kishida Koichi , Kuroda Masaharu , Tanaka Kunisuke , Morita Shigeto , Satoh Shigeru , Masumura Takehiro 
Published: February 2012

SummaryRice prolamins, a group of seed storage proteins, are synthesized on the rough endoplasmic reticulum (ER) and form type I protein bodies (PB‐Is) in endosperm cells. Rice prolamins are encoded by a multigene family. In this study, the spatial accumulation patterns of various prolamin species in rice endosperm cells were investigated to determine the mechanism of formation of the internal structure of PB‐Is. Immunofluorescence microscopic analysis of mature endosperm cells showed that the 10 kDa prolamin is mainly localized in the core of the PB‐Is, the 13b prolamin is localized in the inner layer surrounding the core and the outermost layer, and the 13a and 16 kDa prolamins are localized in the middle layer. Real‐time RT‐PCR analysis showed that expression of the mRNA for 10 kDa prolamin precedes expression of 13a, 13b‐1 and 16 kDa prolamin in the developing stages. mRNA expression for 13b‐2 prolamin occurred after that of the other prolamin species. Immunoelectron microscopy of developing seeds showed that the 10 kDa prolamin polypeptide initially accumulates in the ER, and then 13b, 13a, 16 kDa and 13b prolamins are stacked in layers within the ER. Studies with transgenic rice seeds expressing prolamin–GFP fusion proteins under the control of native and constitutive promoters indicated that the temporal expression pattern of prolamin genes influenced the localization of prolamin proteins within the PB‐Is. These findings indicate that the control of gene expression of prolamin species contributes to the internal structure of PB‐Is.