ATM is involved in cell‐cycle control through the regulation of retinoblastoma protein phosphorylation

Ataxia telangiectasia mutated protein (ATM) is a member of the phosphatidylinositol‐3 kinase (PI3K) family, which has a role in the cellular response to DNA double‐strand breaks (DSBs). In the present study, we evaluated the role of ATM in cell‐cycle control in dopaminergic rat neuroblastoma B65 cells. For this purpose, ATM activity was either inhibited pharmacologically with the specific inhibitor KU‐55933, or the ATM gene was partially silenced by transfection with small interfering RNA (siRNA). Our data indicate that although ATM inhibition did not affect the cell cycle, both treatments specifically decreased the levels of cyclin A and retinoblastoma protein (pRb), phosphorylated at Ser780. Furthermore, ATM inhibition decreased the active form of p53, which is phosphorylated at Ser15, and also decreased Bax and p21 expression. Using H₂O₂ as a positive control of DSBs, caused a rapid pRb phosphorylation, this was prevented by KU‐55933 and siRNA treatment. Collectively, our data demonstrate how a new molecular network on ATM regulates the cell cycle through the control of pRb phosphorylation. These findings support a new target of ATM. J. Cell. Biochem. 110: 210–218, 2010. © 2010 Wiley‐Liss, Inc.     

A clinical and molecular portrait of non-metastatic anal squamous cell carcinoma

Anal squamous cell carcinoma (ASCC) is a rare gastrointestinal malignancy associated with high-risk Human papillomavirus (HPV) infection. Despite improved outcomes in non-metastatic ASCC, definitive chemoradiotherapy constitutes the standard treatment for localized disease. Evidences for predictive and prognostic biomarkers are limited. Here, we performed a viral, immune, and mutational characterization of 79 non-metastatic ASCC patients with complete definitive chemoradiotherapy. HPV-16 was detected in 91% of positive cases in single infections (78%) or in coinfections with multiple genotypes (22%). Fifty-four percent of non-metastatic ASCC cases displayed mutations affecting cancer driver genes such as PIK3CA (21% of cases), TP53 (15%), FBXW7 (9%), and APC (6%). PD-L1 expression was detected in 57% of non-metastatic ASCC. Increased PD-L1 positive cases (67%) were detected in patients with complete response compared with non-complete response to treatment (37%) (p = 0.021). Furthermore, patients with PD-L1 positive tumors were significantly associated with better disease-free survival (DFS) and overall survival (OS) compared with patients with PD-L1 negative tumors (p = 0.006 and p = 0.002, respectively). PD-L1 expression strongly impacts CR rate and survival of non-metastatic ASCC patients after standard definitive chemoradiotherapy. PD-L1 expression could be used to stratify good versus poor responders avoiding the associated morbidity with abdominal perineal resection.     

The situation of penduline tit (Remiz pendulins) in southern Europe: A new stage of its expansion

Summary The present status ofRemiz pendulinus in the Iberian Peninsula is updated after a new expansive stage, so that we can distinguish four expansive waves. The recent spreading resulted in an extension by ca. 200 km of the breeding area following the river Tajo and by ca. 300 km following the Guadiana. Likewise,Remiz pendulinus has colonized the only remaining great river in the Iberian Peninsula, the Guadalquivir, at least along 170 km. This range extention is considerable and compares with a similar development in Central Europe. A factor possibly supporting the expansion may have been the artificial creation of wetlands (reservoirs), improving existing and creating new habitats suitable for the species. At present,Remiz pendulinus breeds discontinuously from the southern coast of Finland to the southern coast of Spain.

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Zusammenfassung Die heutige Verbreitung der Beutelmeise (Remiz pendulinus) auf der Iberischen Halbinsel wird nach einer neuerlichen Ausbreitungsphase in 4 Karten für die Zeiträume 1960–1970, 1971 und 1972, 1973–1978 und 1979–1989 dargestellt. Die jüngste Ausbreitungswelle führte zu einer Erweiterung des Brutgebietes um ca. 200 km entlang des Tajo und um ca. 300 km entlang des Guadiana. Außerdem besiedelt die Beutelmeise jetzt auch den letzten übriggebliebenen Fluß der Iberischen Halbinsel, den Guadalquivir, auf einer Länge von mindestens 170 km. Diese Ausbreitung ist von ihrer Ausdehnung her noch weitreichender als die in jüngster Zeit in Mitteleuropa festgestellte. Möglicherweise wird diese letzte Ausbreitungswelle durch den künstlichen Bau von neuen Feuchtgebieten (Stauseen) begünstigt, die für die Art neue Lebensräume darstellen. Die Beutelmeise ist heute von der Südküste Finnlands bis zum südlichen Spanien als Brutvogel verbreitet.

     

The new tools revolutionizing Vibrio science

As microbiologists we live in exciting times. A variety of technical and conceptual developments, particularly in the last decade have revolutionized the field of microbiology, redrawing the landscape, and entirely redefining what is possible. Perhaps this paradigm shift is no more apparent than in the study of vibrios. The family Vibrionaceae are almost unique as a group of bacteria to study in microbiology: they are genomically, phylogenetically and functionally diverse yet a distinct group of environmental bacteria encompassing important human and animal pathogens as well as non-pathogenic species such as ecologically critical symbionts. Sensitive to physiochemical stimuli, they are among the fasting replicating bacteria studied, capable of responding almost immediately to favourable environmental conditions such as those afforded by climate warming. Characterized by an unusual double chromosome and frequently carrying numerous cryptic plasmids – their genomes are often pockmarked with insertion elements, transposons, prophages and integrases – paying testament to past genomic promiscuity. With a strong affinity for environmental niches in freshwater and marine systems, they are among the most numerous bacteria present in our oceans, coasts and freshwater environments. As such they offer something for almost anyone interested in microbiology and represent an excellent example of field of microbiology that has benefitted hugely by advances across a gamut of disciplines – not just microbiological – but encompassing genomics, genetics, oceanography, ecological, earth observations sciences and data visualization, among others. We will briefly outline some of the most exciting, innovative and translational scientific advances that are currently being applied to these ecologically, environmentally and clinically important bacteria.