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Adaptive challenges that humans faced as they expanded across the globe left specific molecular footprints that can be decoded in our today's genomes. Different sets of metrics are used to identify genomic regions that have undergone selection. However, there are fewer methods capable of pinpointing the allele ultimately responsible for this selection. Here, we present PopHumanVar, an interactive online application that is designed to facilitate the exploration and thorough analysis of candidate genomic regions by integrating both functional and population genomics data currently available. PopHumanVar generates useful summary reports of prioritized variants that are putatively causal of recent selective sweeps. It compiles data and graphically represents different layers of information, including natural selection statistics, as well as functional annotations and genealogical estimations of variant age, for biallelic single nucleotide variants (SNVs) of the 1000 Genomes Project phase 3. Specifically, PopHumanVar amasses SNV-based information from GEVA, SnpEFF, GWAS Catalog, ClinVar, RegulomeDB and DisGeNET databases, as well as accurate estimations of iHS, nSL and iSAFE statistics. Notably, PopHumanVar can successfully identify known causal variants of frequently reported candidate selection regions, including EDAR in East-Asians, ACKR1 (DARC) in Africans and LCT/MCM6 in Europeans. PopHumanVar is open and freely available at https://pophumanvar.uab.cat., Graphical Abstract Graphical AbstractPopHumanVar is an interactive online application that is designed to facilitate the exploration and thorough analysis of candidate genomic regions by integrating both functional and population genomics data currently available. PopHumanVar generates useful summary reports of prioritized variants that are putatively causal of recent selective sweeps.

Diet selection and performance of Criollo Chaqueno and Brahman × Criollo Chaqueno were studied in three seasons in the dry forests of the Bolivian Chaco using direct observations. During the dry season (DS) and the rainy season (RS), the Criollo cattle diet consisted of a higher proportion (P 0.05) for the crossbreds. Other than for the Criollos, the body weight of the crossbreds decreased (P < 0.05) from the DS to the transition period. Especially during the DS, Criollos made more use of forage resources from shrubs and trees and thus, seem to be better adapted to year-round forest grazing compared with the crossbreds.

Despite good responses to first-line treatment with platinum-based combination chemotherapy, most ovarian cancer patients will relapse and eventually develop platinum-resistant disease with poor prognosis. Although reports suggest that integrin-linked kinase (ILK) is a potential target for ovarian cancer treatment, identification of ILK downstream effectors has not been fully explored. The purpose of this study was to investigate the molecular and biological effects of targeting ILK in cisplatin-resistant ovarian cancer. Western blot analysis showed that phosphorylation levels of ILK were higher in cisplatin-resistant compared with cisplatin-sensitive ovarian cancer cells. Further immunohistochemical analysis of ovarian cancer patient samples showed a significant increase in phosphorylated ILK levels in the tumor tissue when compared to normal ovarian epithelium. Targeting ILK by small-interfering RNA (siRNA) treatment reduced cisplatin-resistant cell growth and invasion ability, and increased apoptosis. Differential gene expression analysis by RNA sequencing (RNA-Seq) upon ILK-siRNA transfection followed by Ingenuity Pathway Analysis (IPA) and survival analysis using the Kaplan&ndash, Meier plotter database identified multiple target genes involved in cell growth, apoptosis, invasion, and metastasis, including several non-coding RNAs. Taken together, results from this study support ILK as an attractive target for ovarian cancer and provide potential ILK downstream effectors with prognostic and therapeutic value.

Genomic analysis of the kelp fly Fucellia costalis (Family Anthomyiidae) from Asilomar beach, Pacific Grove, California, resulted in the assembly of its complete mitogenome. The mitogenome is 16,17...

Fucus spiralis L. is a broadly distributed monoecious intertidal seaweed. The specific status of F. spiralis however is debatable. Here, we contribute to the bioinformatics and systematics of F. spiralis by analysing the complete mitochondrial and plastid genomes of a specimen from California, U.S.A. The F. spiralis mitogenome is 36,396 base pairs (bp) in length and contains 67 genes, and the plastid genome is 125,066 bp in length and contains 171 genes. The F. spiralis genomes are 99.7% and 99.8% similar in nucleotide sequence to F. vesiculosus, and support the revised classification of F. spiralis to Fucus vesiculosus var. spiralis.

Lepanthes variabilis, a new species from Costa Rica, is described and illustrated. It is endemic to the northern part of the Talamanca mountain range, from 2750–2850 m. It is compared to the similar L. minutilabia, which also occurs in Costa Rica.

Geckos owe their remarkable stickiness to millions of dry, hard setae on their toes. In this study, we discovered that gecko setae stick more strongly the faster they slide, and do not wear out after 30 000 cycles. This is surprising because friction between dry, hard, macroscopic materials typically decreases at the onset of sliding, and as velocity increases, friction continues to decrease because of a reduction in the number of interfacial contacts, due in part to wear. Gecko setae did not exhibit the decrease in adhesion or friction characteristic of a transition from static to kinetic contact mechanics. Instead, friction and adhesion forces increased at the onset of sliding and continued to increase with shear speed from 500 nm s −1 to 158 mm s −1 . To explain how apparently fluid-like, wear-free dynamic friction and adhesion occur macroscopically in a dry, hard solid, we proposed a model based on a population of nanoscopic stick–slip events. In the model, contact elements are either in static contact or in the process of slipping to a new static contact. If stick–slip events are uncorrelated, the model further predicted that contact forces should increase to a critical velocity ( V *) and then decrease at velocities greater than V *. We hypothesized that, like natural gecko setae, but unlike any conventional adhesive, gecko-like synthetic adhesives (GSAs) could adhere while sliding. To test the generality of our results and the validity of our model, we fabricated a GSA using a hard silicone polymer. While sliding, the GSA exhibited steady-state adhesion and velocity dependence similar to that of gecko setae. Observations at the interface indicated that macroscopically smooth sliding of the GSA emerged from randomly occurring stick–slip events in the population of flexible fibrils, confirming our model predictions.

Dos especies nuevas de Borreria son descritas: la primera, Borreria johnwoodii del cerrado del Parque Nacional Noel Kempff Mercado; la segunda, Borreria siberiana del Bosque Nublado Yungueño entre 2600 y 3100 m sobre el nivel del mar. Declieuxia cordigera es registrado por primera vez para Bolivia. Borreria nectarifera es tratado como sinónimo de B. eryngioides var. affinis. Two new species of Borreria are described: the first, Borreria johnwoodii from the Campo Cerrado area of the Noel Kempff Mercado National Park; the second, Borreria siberiana from the cloud forest of the Yungas, between 2600 and 3100 m above sea level. Declieuxia cordigera is recorded for the first time from Bolivia. Borreria nectarifera is shown to be synonymous with B. eryngioides var. affinis. Fil: Salas, Roberto Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Nordeste. Instituto de Botánica del Nordeste (i); Argentina Fil: Soto, Daniel. Universidad Autónoma Gabriel René Moreno; Bolivia Fil: Cabral, Elsa Leonor. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Nordeste. Instituto de Botánica del Nordeste (i); Argentina

We investigated the effects of orientation angle on the adhesion of single gecko setae using dual-axis microelectromechanical systems force sensors to simultaneously detect normal and shear force components. Adhesion was highly sensitive to the pitch angle between the substrate and the seta's stalk. Maximum lateral adhesive force was observed with the stalk parallel to the substrate, and adhesion decreased smoothly with increasing pitch. The roll orientation angle only needed to be roughly correct with the spatular tuft of the seta oriented grossly towards the substrate for high adhesion. Also, detailed measurements were made to control for the effect of normal preload forces. Higher normal preload forces caused modest enhancement of the observed lateral adhesive force, provided that adequate contact was made between the seta and the substrate. These results should be useful in the design and manufacture of gecko-inspired synthetic adhesives with anisotropic properties, an area of substantial recent research efforts.

A dual-axis piezoresistive MEMS force sensor was used to investigate the role of orientation angle on the adhesion of gecko hairs, called setae. Previous work showed that the lateral adhesion force of a single seta pulled parallel to a surface is highly dependant upon the "pitch" angle between the seta's stalk and the substrate (K. Autumn et al., 2000). This work is the first to examine the effect of the "roll" orientation angle of the stalk under similar lateral pulls along a substrate. We find that the adhesion is near the maximum value for a wide roll angle range from -43deg to +43deg, and smoothly drops off to the frictional force at plusmn 85 M These angles relate physically to the orientation and spread of a splayed tuft of spatula-shaped terminations at the end of each seta. These spatulae make intimate contact with the substrate and enhance adhesion above traditional friction forces.

The Myc proto-oncogene is known to regulate p53-dependent apoptosis through the Myc -> ARF -| MDM2 -| p53 pathway. We had previously shown that this pathway could be exploited to increase sensitivity to anti-cancer drugs. Specifically, small increases in Myc levels obtained by inhibiting the Myc-targeting microRNA-34a resulted in enhanced apoptotic response of B-cells to bortezomib (Sotillo et al, Oncogene 2010). However, many Myc-driven tumors are deficient in p53 activity. Thus, we sought to determine whether transient up-regulation of Myc also increases cell death in response to chemotherapeutic drugs in p53-deficient backgrounds. We chose to study this in human Burkitt's lymphoma cell lines and murine B-lymphoid cells isolated from bone marrows of p53ER™ knock-in mice and subsequently transduced with a Myc-expressing retrovirus (Amaravadi et al, J Clin Inv 2007, Yu et al, Blood 2007). This latter system allowed us to distinguish between p53-dependent (cells treated with tamoxifen) and independent (no tamoxifen added) cell death. We also considered that Myc expression is regulated not only transcriptionally, most notably by the bromodomain containing protein 4 (BRD4), but also post-transcriptionally by the glycogen synthase kinase 3β (GSK3-β). GSK3-β phosphorylates Myc on its Thr58 residue, targeting it for proteasomal degradation, and inhibition of GSK3-β activity results in stabilization of Myc protein (Chung et al, J Clin Inv 2012). Using the GSK3-β inhibitor CHIR 99021, we transiently increased Myc protein levels prior to treating B-lymphoma cells with chemotherapeutic drugs. Remarkably, pharmacological stabilization of Myc strongly enhanced p53-independent doxorubicin-induced apoptosis in the p53ER™/Myc system as well as in Burkitt's lymphoma cell lines with inactive p53. This enhancement was accompanied by cleavage of caspase 8 with concomitant de-regulation of the death receptor pathway genes, indicating engagement of the extrinsic apoptotic pathway. In contrast, we did not observe any significant differences in the intrinsic pro-apoptotic genes (BAX, BAK, BIM). To determine whether chemosensitization was mediated by Myc or other GSK3-β targets, we used a BRD4 inhibitor (iBET-151) at concentrations that were sufficient to prevent the CHIR 99021-mediated increase in Myc levels but didn't grossly affect cell viability. Inhibition of Myc with iBET-151 abrogated the increase in apoptosis brought about by CHIR 99021 and doxorubicin, suggesting that Myc is key to chemosensitization by CHIR 99021. Our results suggest that Myc stabilization could be a viable adjuvant therapy, even for tumors with p53 loss or MDM2 amplification. Citation Format: Elena Sotillo-Piñeiro, Colleen T. Harrington, Daniel Soto De Jesus, Andrei Thomas-Tikhonenko. Transient upregulation of Myc with GSK3-β inhibitors in B-cell lymphomas enhances p53-independent apoptotic responses to chemotherapy. [abstract]. In: Proceedings of the AACR Special Conference on Myc: From Biology to Therapy; Jan 7-10, 2015; La Jolla, CA. Philadelphia (PA): AACR; Mol Cancer Res 2015;13(10 Suppl):Abstract nr B33.

Background: CEA is widely used in the follow up of patients with colorectal carcinoma. Aim: To study the value of preoperative CEA as an independent prognostic factor in colorectal carcinoma. Patients and methods: Analysis of 373 operated patients (204 females, age range 21-92 years) with colorectal carcinoma and a mean follow up of 53 months. The cutoff value for CEA was 5 ng/ml. Ninety four percent of patients had an excisable tumor, 79% had involvement of perirectal/pericolonic adipose tissue and 46% had lymph node involvement. Staging was done using Dukes-Turnbull and TNM classifications. Results: CEA was normal in 61% of cases, over 5 ng/ml in 39% and over 15 ng/ml in 22%. There was a strong correlation between mean preoperative CEA and tumor stage, depth and lymph node involvement. During the follow up, 140 patients died, 57 with normal and 83 with elevated CEA. Cancer mortality in patients subjected to a curative excision of the tumor (Dukes A-C2/TNM IIII) was 9% for colonic tumors and 36% for rectal tumors (p

Platinum-based chemotherapy has been used for more than four decades for ovarian cancer patients. Although initially most ovarian tumors respond well to cisplatin treatment, many of the tumors become resistant to chemotherapy. Several drug resistant-associated genes have been identified by gene expression arrays in drug sensitive and drug resistant cells. Recent evidence indicates that posttranscriptional and posttranslational regulation of gene expression governs the function of several proteins associated with cancer initiation, progression and drug resistance. To reveal additional proteins associated with cisplatin resistance, we performed a proteomic analysis in cisplatin sensitive (A2780) and cisplatin resistant (A2780CP20) ovarian cancer cells. Forty-seven, out of 148 identified proteins, were differentially abundant in A2780CP20 compared with A2780 cancer cells. Western blot analysis was used to confirm the proteomic results. Particularly, the Integrin-Linked Kinase-Associated Serine/Threonine Phosphatase 2C (ILKAP) was decreased in A2780CP20 compared with A2780 cells. The phosphorylation levels of the Integrated-Linked Kinase ILK (the major ILKAP effector), protein kinase B (AKT), and glycogen synthase kinase 3β (GSK3β) (two ILK downstream effectors) were higher in A2780CP20 compared with A2780 cells. Small-interference RNA (siRNA)-targeted ILK, reduced the phosphorylation levels of AKT and GSK3β; and reduced cell proliferation and invasion of the A2780CP20 cells. Most important, combination of inactive ILK-targeted siRNA doses plus inactive cisplatin doses reduced cell growth in a synergistic-like way. These results indicate that protein phosphorylation of the ILK/AKT/GSK3β cascade play a vital role in cisplatin resistance, and propose ILK as a therapeutic target for advanced and drug resistant ovarian cancer. Citation Format: Daniel Soto, Fatima Valiyeva, Ileabett Echevarria, Jeyshka Reyes, Pablo E. Vivas-Mejia. Integrin-linked kinase and proximal signaling contributes to the cisplatin resistance of ovarian cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3454. doi:10.1158/1538-7445.AM2014-3454

Research into the gecko’s adhesive system revealed a unique architecture for adhesives using tiny hairs. By using a stiff material (β-keratin) to create a highly structured adhesive, the gecko’s system demonstrates properties not seen in traditional pressure-sensitive adhesives which use a soft, unstructured planar layer. In contrast to pressure sensitive adhesives, the gecko adhesive displays frictional adhesion, in which increased shear force allows it to withstand higher normal loads. Synthetic fibrillar adhesives have been fabricated but not all demonstrate this frictional adhesion property. Here we report the dual-axis force testing of single silicone rubber pillars from synthetic adhesive arrays. We find that the shape of the adhesive pillar dictates whether frictional adhesion or pressure-sensitive behavior is observed. This work suggests that both types of behavior can be achieved with structures much larger than gecko terminal structures. It also indicates that subtle differences in the shape of ...