Mutation pattern of paired immunoglobulin heavy and light variable domains in chronic lymphocytic leukemia B cells

B-cell chronic lymphocytic leukemia (CLL) patients display leukemic clones bearing either germline or somatically mutated immunoglobulin heavy variable (IGHV ) genes. Most information on CLL immunoglobulins (Igs), such as the definition of stereotyped B-cell receptors (BCRs), was derived from germline unmutated Igs. In particular, detailed studies on the distribution and nature of mutations in paired heavy- and light-chain domains of CLL clones bearing mutated Igs are lacking. To address the somatic hyper-mutation dynamics of CLL Igs, we analyzed the mutation pattern of paired IGHV-diversity-joining (IGHV-D-J ) and immunoglobulin kappa/lambda variable-joining (IGK/LV-J ) rearrangements of 193 leukemic clones that displayed ≥ 2% mutations in at least one of the two immunoglobulin variable (IGV ) genes (IGHV and/or IGK/LV ). The relationship between the mutation frequency in IGHV and IGK/LV complementarity determining regions (CDRs) and framework regions (FRs) was evaluated by correlation analysis. Replacement (R) mutation frequency within IGK/LV chain CDRs correlated significantly with mutation frequency of paired IGHV CDRs in λ but not κ isotype CLL clones. CDRs of IGKV-J rearrangements displayed a lower percentage of R mutations than IGHVs. The frequency/pattern of mutations in kappa CLL Igs differed also from that in κ-expressing normal B cells described in the literature. Instead, the mutation frequency within the FRs of IGHV and either IGKV or IGLV was correlated. Notably, the amount of diversity introduced by replaced amino acids was comparable between IGHVs and IGKVs. The data indicate a different mutation pattern between κ and λ isotype CLL clones and suggest an antigenic selection that, in κ samples, operates against CDR variation.     

Botanical information in the Italian Biodiversity Network: One year of data aggregation and future perspectives

Since its formal institution in May 2012, the Italian Biodiversity Network is aggregating data from several research centres, for a total of ca. 1.5 million records. Botanical data made ca. 50% of the total, and range from primary biodiversity data to ecological, morpho-anatomical and taxonomical information. However, this is only a small portion of the total amount of botanical data which could be aggregated and exposed to the scientific community, professionals and citizens. In this paper we present the current status of data aggregation of the Network and its impact on digitalisation of biodiversity data, research, conservation and environmental management and education in Italy.     

Methylation loss at H19 imprinted gene correlates withmethylenetetrahydrofolate reductase gene promoter hypermethylation in semen samples from infertile males

Aberrant methylation at the H19 paternal imprinted gene has been identified in different cohorts of infertile males. The causes of H19 methylation errors are poorly understood. In this study, we investigated the methylation status of the H19 gene in semen DNA samples from infertile males affected by MTHFR gene promoter hypermethylation. DNA from normal and abnormal semen samples harbouring MTHFR gene promoter hypermethylated, hmMTHFR-nor and hmMTHFR-abn, and without MTHFR methylation, MTHFR-nor and MTHFR-abn, were investigated for methylation status in the H19 locus using bisulfite-treated DNA PCR, followed by cloning and sequencing. The prevalence of H19 hypomethylated clones was 20% in hmMTHFR-nor and 0% in MTHFR-nor semen samples (p < 0.05), and 28% in hmMTHFR-abn compared with 16% in MTHFR-abn semen samples (p > 0.05). These results underscore the association between H19 methylation defects and hypermethylation of the MTHFR gene promoter in normal semen samples and suggest that aberrant methylation at H19 may occur in the normal sperm of infertile males affected by MTHFR gene dysfunction. These findings provide new insights into the mechanisms causing abnormal methylation in imprinted genes and, in turn, male infertility.     

EGFR-targeted therapy

Anti-Epidermal Growth Factor Receptor (EGFR) therapies have been recently developed for the treatment of multiple cancer types. At the time when they were introduced in clinical practice, there was little knowledge of the molecular bases of tumor sensitivity and resistance to these novel targeted compounds. By using the framework of anti-EGFR inhibitors as treatment for colorectal cancer patients, we will review the knowledge we have reached until now in improving the development of a personalized cancer therapy and we will try to indicate the future challenges this field will face in the future.     

On how Cattle Egret (Bubulcus ibis) spread to the Americas: meteorological tools to assess probable colonization trajectories

The Cattle Egret (Bubulcus ibis) is native to the old world. Before 1877 no Cattle Egrets had been sighted in the Americas. There are no written records of this species being transported to or escaping from captivity in South America and there is enough evidence to suggest that individuals are capable of making the crossing from Africa to the Americas unaided. Since long-distance movements of species are partly dependent on meteorological events we analyze the possibility of B. ibis crossing the Atlantic Ocean aided only by wind conditions evaluating existing theories and shedding light on their feasibility through the analysis of weather patterns and atmospheric circulation. Zonal and meridional wind components taken from the Twentieth Century Reanalysis Project were used to calculate trajectories between different points along the West African coast and South America between 1871 and 1920 in two seasons (March–April and September–October). From a total of 192,864 trajectories analyzed, 1,695 with origin in the west coast of Africa reached the NE coast of South America or the Caribbean islands in less than a week (successful trajectories). The probability of these successful trajectories originating in Central Africa was above 0.65 for the majority of the destinations analyzed. Particularly, in Guyana and Suriname where B. ibis was first sighted, the probability of the origin being Central Africa was 0.84, most of them occurring during March. Several weather events favored not only the colonization of the Cattle Egret but also its establishment and spread all throughout the Americas.     

In vitro Anti-Tumor Effects of Statins on Head and Neck Squamous Cell Carcinoma: A Systematic Review

Background

Statins are commonly used against arteriosclerotic disease, but recent retrospective analyses have suggested that statins also prevent cancer. The aim of this systematic review is to verify the vitro anti-tumor effects of statins on head and neck squamous cell carcinoma.

Methods

Studies were gathered by searching Cochrane, MEDLINE, EMBASE, LILACS, and PubMed, up until May 9, 2015, with no time or language restrictions. Only in vitro studies that discuss the effect of statins on head and neck carcinoma were selected.

Results

Of 153 identified papers, 14 studies met the inclusion criteria. These studies demonstrated that statins had a significant effect on head and neck squamous cell carcinoma cell lines and influenced cell viability, cell cycle, cell death, and protein expression levels involved in pathways of carcinogenesis, which corroborates with the potential in vitro anti-tumor effects. It provides highlights about the biological mechanisms of statins used alone or associated with traditional therapy for cancer.

Conclusions

Though there are few studies on the topic, currently available evidence suggests that statins shows that preclinical experiments supports the potentiality of statin as an adjuvant agent in chemotherapy and/or radiotherapy approaches routinely used in the management of HNSCC and should undergo further clinical assessment.     

Genetic studies of various Prosopis species (Leguminosae,Section Algarobia) co‐occurring in oases of the Atacama Desert (northern Chile)

In the Atacama Desert from northern Chile (19–24°S), Prosopis (Leguminosae) individuals are restricted to oases that are unevenly distributed and isolated from each other by large stretches of barren landscape constituting an interesting study model as the degree of connectivity between natural populations depends on their dispersal capacity and the barriers imposed by the landscape. Our goal was to assess the genetic diversity and the degree of differentiation among groups of Prosopis individuals of different species from Section Algarobia and putative hybrids (hereafter populations) co‐occurring in these isolated oases from the Atacama Desert and determine whether genetic patterns are associated with dispersal barriers. Thirteen populations were sampled from oases located on three hydrographic basins (Pampa del Tamarugal, Rio Loa, and Salar de Atacama; northern, central, and southern basins, respectively). Individuals genotyped by eight SSRs show high levels of genetic diversity (H _O = 0.61, A _r = 3.5) and low but significant genetic differentiation among populations (F _ST = 0.128, F _ST‐ENA = 0.129, D _JOST = 0.238). The AMOVA indicates that most of the variation occurs within individuals (79%) and from the variance among individuals (21%); almost, the same variation can be found between basins and between populations within basins. Differentiation and structure results were not associated with the basins, retrieving up to four genetic clusters and certain admixture in the central populations. Pairwise differentiation comparisons among populations showed inconsistencies considering their distribution throughout the basins. Genetic and geographic distances were significantly correlated at global and within the basins considered (p < .02), but low correlation indices were obtained (r < .37). These results are discussed in relation to the fragmented landscape, considering both natural and non‐natural (humans) dispersal agents that may be moving Prosopis in the Atacama Desert.