Structural and biochemical characterization of a new type of lectin isolated from carp eggs.

A previously unidentified glycoprotein present in the eggs of the carp (Cyprinus carpio) was isolated and structurally characterized. The protein binds to a Sepharose 4B matrix and can be eluted with 0.4 M N-acetylglucosamine. The protein has an apparent molecular mass of 26686.3 Da. On the basis of gel-filtration chromatography, the protein appears to be present in solution as a monomer. The sequence of its 238 amino acids, the position of its four disulphide bridges and the composition of its single N-linked carbohydrate chain were determined. The lectin shows a very low agglutinating activity for human A-type erythrocytes and interacts with both Gram-positive and -negative bacteria. These latter interactions are inhibited by N-acetylglucosamine. A database search shows that its amino acid sequence is similar to that of the members of an invertebrate lectin family that includes tachylectin-1. Tachylectin-1 is present in the amoebocytes of the horseshoe crab, Tachypleus tridentatus, and plays a role in the innate defence system of this species. Homologous genes are also present in other fish, having 85% identity with a gene expressed in the oocytes of the crucian carp (Carassius auratus gibelio) and 78% identity with a gene in the cDNA library of the zebrafish (Danio rerio)

Magnetic fabric of Pleistocene continental clays from the hanging-wall of an active low-angle normal fault (Altotiberina Fault, Italy)

Anisotropy of magnetic susceptibility (AMS) represents a valuable proxy able to detect subtle strain effects in very weakly deformed sediments. During the last decades a large number of AMS studies have documented that in compressive tectonic settings the maximum susceptibility axes (i.e. the magnetic lineations) are parallel to fold axes (and thrust faults) and local bedding strikes, while in extensional regimes they are perpendicular to the normal faults and, thus, parallel to the strata dip directions. One of the most striking active tectonic structures of the northern Apennines is represented by the Altotiberina Fault (ATF), a NE-dipping low-angle normal fault bounding the High Tiber Valley. The ATF represents a primary detachment of the Plio-Quaternary extensional tectonics affecting the Apennine belt. The long-lasting activity of the ATF produced 5 km of total displacement and up to 1200-m-thick basin infill of syn-tectonic, sandy-clayey continental succession. Thus, the AMS analysis of the sediments lying above the ATF represents a unique opportunity to document the strain field affecting the hanging-wall of low-angle normal faults. We collected 129 oriented cores at 12 different localities within the High Tiber Valley, and measured the AMS with a spinner Multi-Function Kappabridge. Most of the sites show a magnetic fabric typical of sediments at the earliest stages of deformation, characterized by oblate AMS ellipsoids and a well defined magnetic lineation, while prolate AMS ellipsoids at two sites are suggestive of pervasive tectonic effects. The magnetic lineation is well-developed at all sites and 20 has a prevailing N-S direction. At five sites the bedding is tilted and the magnetic lineation is subparallel to local bed-strikes, implying that these sites underwent a maximum horizontal shortening along an E-W direction. At two sites the magnetic lineation is sub-perpendicular to the trend of the ATF, and may be related to extensional strain. Our results reveal the existence of both compressional and extensional structures at the hangingwall of the ATF, and suggest that the early Pleistocene sequence of the High Tiber Valley is arranged in gently, local folds (hardly visible in the field) ~N-S trending. We interpret these compressivestructures as the result of local superficial stress induced by irregularities of the fault plane at depth. Accordingly, the strain field we documented from the High Tiber Valley can not be used to infer the regional tectonic regime acting during the ATF activity. We conclude that the long-lasting debate on the extensional vs. compressional Plio-Quaternary tectonics of the Apennines orogenic belt should be revised evaluating the importance of compressional structures resulting by local effects

Magnetic fabric of Pleistocene continental clays from the hanging-wall of an active low-angle normal fault (Altotiberina Fault, Italy)

Anisotropy of magnetic susceptibility (AMS) represents a valuable proxy able to detect subtle strain effects in very weakly deformed sediments. In compressive tectonic settings, the magnetic lineation is commonly parallel to fold axes, thrust faults, and local bedding strike, while in extensional regimes, it is perpendicular to normal faults and parallel to bedding dip directions. The Altotiberina Fault (ATF) in the northern Apennines (Italy) is a Plio-Quaternary NNW–SSE low-angle normal fault; the sedimentary basin (Tiber basin) at its hanging-wall is infilled with a syn-tectonic, sandy-clayey continental succession. We measured the AMS of apparently undeformed sandy clays sampled at 12 sites within the Tiber basin. The anisotropy parameters suggest that a primary sedimentary fabric has been overprinted by an incipient tectonic fabric. The magnetic lineation is well developed at all sites, and at the sites from the western sector of the basin it is oriented sub-perpendicular to the trend of the ATF, suggesting that it may be related to extensional strain. Conversely, the magnetic lineation of the sites from the eastern sector has a prevailing N–S direction. The occurrence of triaxial to prolate AMS ellipsoids and sub-horizontal magnetic lineations suggests that a maximum horizontal shortening along an E–W direction occurred at these sites. The presence of compressive AMS features at the hanging-wall of the ATF can be explained by the presence of gently N–Strending local folds (hardly visible in the field) formed by either passive accommodation above an undulated fault plane, or rollover mechanism along antithetic faults. The long-lasting debate on the extensional versus compressive Plio-Quaternary tectonics of the Apennines orogenic belt should now be revised taking into account the importance of compressive structures related to local effects

A standardized comparison of peri-operative complications after minimally invasive esophagectomy: Ivor Lewis versus McKeown.

BACKGROUND: While our institutional approach to esophageal resection for cancer has traditionally favored a minimally invasive (MI) 3-hole, McKeown esophagectomy (MIE 3-hole) during the last five years several factors has determined a shift in our practice with an increasing number of minimally invasive Ivor Lewis (MIE IL) resections being performed. We compared peri-operative outcomes of the two procedures, hypothesizing that MIE IL would be less morbid in the peri-operative setting compared to MIE 3-hole. METHODS: Our institution\u27s IRB-approved esophageal database was queried to identify all patients who underwent totally MI esophagectomy (MIE IL vs. MIE 3-hole) from June 2011 to May 2016. Patient demographics, preoperative and peri-operative data, as well as post-operative complications were compared between the two groups. Post-operative complications were analyzed using the Clavien-Dindo classification system. RESULTS: There were 110 patients who underwent totally MI esophagectomy (MIE IL n = 49 [45%], MIE 3-hole n = 61 [55%]). The majority of patients were men (n = 91, 83%) with a median age of 62.5 (range 31-83). Preoperative risk stratifiers such as ECOG score, ASA, and Charlson Comorbidity Index were not significantly different between groups. Anastomotic leak rate was 2.0% in the MIE IL group compared to 6.6% in the MIE 3-hole group (p = 0.379). The rate of serious (Clavien-Dindo 3, 4, or 5) post-operative complications was significantly less in the MIE IL group (34.7 vs. 59.0%, p = 0.013). Serious pulmonary complications were not significantly different (16.3 vs. 26.2%, p = 0.251) between the two groups. CONCLUSIONS: In this cohort, totally MIE IL showed significantly less severe peri-operative morbidity than MIE 3-hole, but similar rates of serious pulmonary complications and anastomotic leaks. These findings confirm the safety of minimally invasive Ivor Lewis esophagectomies for esophageal cancer when oncologically and clinically appropriate. Minimally invasive McKeown esophagectomy remains a satisfactory and appropriate option when clinically indicated

Asciminib mitigates DNA damage stress signaling induced by cyclophosphamide in the ovary

Cancer treatments often have adverse effects on the quality of life for young women. One of the most relevant negative impacts is the loss of fertility. Cyclophosphamide is one of the most detrimental chemotherapeutic drugs for the ovary. Cyclophosphamide may induce the destruction of dormant follicles while promoting follicle activation and growth. Herein, we demonstrate the in vivo protective effect of the allosteric Bcr-Abl tyrosine kinase inhibitor Asciminib on signalling pathways activated by cyclophosphamide in mouse ovaries. Besides, we provide evidence that Asciminib did not interfere with the cytotoxic effect of cyclophosphamide in MCF7 breast cancer cells. Our data indicate that concomitant administration of Asciminib mitigates the cyclophosphamide-induced ovarian reserve loss without preventing the anticancer potential of cyclophosphamide. Altogether these observations are relevant for the development of effective ferto-protective adjuvants to preserve the ovarian reserve from the damaging effect of cancer therapies

Carnitine palmitoyltransferase I in human carcinomas: a novel role in histone deacetylation?

Carnitine palmitoyl transferase I (CPT1) catalyzes the transport of long-chain fatty acids into mitochondria for beta-oxidation. A link between CPT1 and apoptosis has been suggested on the basis of several experimental data. Nevertheless, results are contradictory about the effective role of CPT1 in cell survival control and cancer development. Conversely, Fatty acid synthase (FAS) enzyme, required for the synthesis of fatty acids, is found over-expressed in tumors and inhibition of FAS triggers apoptosis in human cancer cells. We have studied the tumor-specific modulation of CPT1 and FAS in human colorectal cancer (n = 11) and breast carcinomas (n = 24). CPT1 was significantly decreased in the cytoplasm of tumoral samples (p < or = 0.04), whereas FAS was increased (p < or = 0.04). A striking CPT1 nuclear localization was evident in the tumors (p < or = 0.04). In the nuclear environment the protein would modulate the levels of acetyl/acyl-CoA implicated in the regulation of gene transcription. At this purpose, we performed in vitro experiments using epithelial neoplastic (MCF-7, Caco-2, HepG2 cells) and non neoplastic cell lines (MCF-12F) confirming a nuclear localization of CPT1 protein exclusively in neoplastic cells. Moreover histone deacetylase (HDAC) activity showed significantly higher levels in nuclear extracts from neoplastic than from control cells. HDAC1 and CPT1 proteins coimmunoprecipitated in nuclear extracts from MCF-7 cells. The treatment with HDAC inhibitors such as trichostatin A and butyrate significantly decreased nuclear expression of CPT1 and its bond to HDAC1. We also identified the existence of CPT1A mRNA transcript variant 2 in MCF-7, beside to the classic isoform 1. The peculiar localization of CPT1 in the nuclei of human carcinomas and the disclosed functional link between nuclear CPT1 and HDAC1 propose a new role of CPT1 in the histonic acetylation level of tumors