The milliped family Tingupidae (Chordeumatida) on Kodiak Island, Alaska, USA, a geographically remote record of indigenous Diplopoda

With documentation of an unidentifiable adult female and juvenile Tingupidae (Chordeumatida), Kodiak Island, Alaska, becomes the westernmost indigenous diplopod locality in North America including continental islands. The northernmost and most proximate locality, Yakutat, lies ca. 935 mi (1,496 km) to the eastnortheast, while Haines, the type locality of Tingupa tlingitorum Shear and Shelley, some 1,196 mi (1,914 km) in this direction, is the most proximate familial site. Kodiak is also one of the most remote indigenous milliped localities in the Pacific, the most proximate ones to the west and south, Kamchatka, Russia, and the Hawaiian Islands, United States, being over 3,300 mi (5, 280 km) distant. Tingupidae is recorded for the first time from Canada excluding the Queen Charlotte Islands, and geographically remote, ostensibly indigenous records from the North Pacific Ocean and environs are tabulated

The Role of Transporters in Future Chemotherapy

The expression of membrane transporter is often altered in cancer cells compared to their corresponding healthy cells. Since these proteins, classified into solute carriers (SLCs) and ATP-binding cassettes (ABCs), can carry not only endogenous compounds, nutrients, and metabolites, but also drugs across the cell membranes, they have a crucial role in drug exposure and clinical outcomes of chemotherapeutics. Curiously, up-regulation of SLCs can be exploited to deliver chemotherapeutics, their prodrugs, and diagnostic radio-tracers to gain cancer cell-selective targeting, as exemplified with L-type amino acid transporter 1 (LAT1). SLCs can also be inhibited to limit the nutrient uptake of cancer cells and thus, cell growth and proliferation. Furthermore, LAT1 can be utilized to deliver ABC-inhibitors selectively into the cancer cells to block the efflux of other chemotherapeutics suffering from acquired or intrinsic efflux transport-related multidrug resistance (MDR). Taking into account the current literature, compounds that can affect transporter up- or down-regulation of transporters in a cancer cell-selective manner could be a valuable tool and promising chemotherapy form in the future

Ovarian and Breast Cancer Risks Associated With Pathogenic Variants in RAD51C and RAD51D

Background: The purpose of this study was to estimate precise age-specific tubo-ovarian carcinoma (TOC) and breast cancer (BC) risks for carriers of pathogenic variants in RAD51C and RAD51D. Methods: We analyzed data from 6178 families, 125 with pathogenic variants in RAD51C, and 6690 families, 60 with pathogenic variants in RAD51D. TOC and BC relative and cumulative risks were estimated using complex segregation analysis to model the cancer inheritance patterns in families while adjusting for the mode of ascertainment of each family. All statistical tests were two-sided. Results: Pathogenic variants in both RAD51C and RAD51D were associated with TOC (RAD51C: relative risk [RR] = 7.55, 95% confidence interval [CI] = 5.60 to 10.19; P = 5 x 10(-40); RAD51D: RR = 7.60, 95% CI = 5.61 to 10.30; P = 5 x 10(-39)) and BC (RAD51C: RR =1.99, 95% CI = 1.39 to 2.85; P = 1.55 x 10(-4); RAD51D: RR = 1.83, 95% CI = 1.24 to 2.72; P = .002). For both RAD51C and RAD51D, there was a suggestion that the TOC relative risks increased with age until around age 60 years and decreased thereafter. The estimated cumulative risks of developing TOC to age 80 years were 11% (95% CI = 6% to 21%) for RAD51C and 13% (95% CI = 7% to 23%) for RAD51D pathogenic variant carriers. The estimated cumulative risks of developing BC to 80 years were 21% (95% CI = 15% to 29%) for RAD51C and 20% (95% CI = 14% to 28%) for RAD51D pathogenic variant carriers. Both TOC and BC risks for RAD51C and RAD51D pathogenic variant carriers varied by cancer family history and could be as high as 32-36% for TOC, for carriers with two first-degree relatives diagnosed with TOC, or 44-46% for BC, for carriers with two first-degree relatives diagnosed with BC. Conclusions: These estimates will facilitate the genetic counseling of RAD51C and RAD51D pathogenic variant carriers and justify the incorporation of RAD51C and RAD51D into cancer risk prediction models.Peer reviewe

Kharlovka 1-6 on the Kola Peninsula: One of the Oldest Gressbakken House Sites in Northern Fennoscandia

The remains of a semi-subterranean house were discovered at the Kharlovka 1-6 site on the Barents Sea coast of the Kola Peninsula, Russia. Despite suffering from erosion, features such as a double stone-boarded hearth and chimney pipe together with diagnostic finds allow us to attribute the house to the so-called Gressbakken type. The artefact assemblage includes stone tools, bone and antler tools and adornments, asbestos-tempered pottery, an amber pendant and a copper tubular bead. Numerous faunal remains are primarily represented by marine species of mammals and birds. Radiocarbon dates on charcoal point to the period 2600–2300 calBC, which is also supported by the artefact types, elevation of the cultural layer and construction type of the house. When accounting for the early dates of Kharlovka 1-6 and several other dwellings, it can be assumed that the Gressbakken house tradition emerged around 2600–2300 calBC. This date is somewhat earlier than previously thought

Isoflavonoids and lignans in legumes : Nutritional and health aspects in humans

Peer reviewe

Metformin and Its Sulfenamide Prodrugs Inhibit Human Cholinesterase Activity

The results of epidemiological and pathophysiological studies suggest that type 2 diabetes mellitus (T2DM) may predispose to Alzheimer’s disease (AD). The two conditions present similar glucose levels, insulin resistance, and biochemical etiologies such as inflammation and oxidative stress. The diabetic state also contributes to increased acetylcholinesterase (AChE) activity, which is one of the factors leading to neurodegeneration in AD. The aim of this study was to assess in vitro the effects of metformin, phenformin, and metformin sulfenamide prodrugs on the activity of human AChE and butyrylcholinesterase (BuChE) and establish the type of inhibition. Metformin inhibited 50% of the AChE activity at micromolar concentrations (2.35 μmol/mL, mixed type of inhibition) and seemed to be selective towards AChE since it presented low anti-BuChE activity. The tested metformin prodrugs inhibited cholinesterases (ChE) at nanomolar range and thus were more active than metformin or phenformin. The cyclohexyl sulfenamide prodrug demonstrated the highest activity towards both AChE (IC50 = 890 nmol/mL, noncompetitive inhibition) and BuChE (IC50 = 28 nmol/mL, mixed type inhibition), while the octyl sulfenamide prodrug did not present anti-AChE activity, but exhibited mixed inhibition towards BuChE (IC50 = 184 nmol/mL). Therefore, these two bulkier prodrugs were concluded to be the most selective compounds for BuChE over AChE. In conclusion, it was demonstrated that biguanides present a novel class of inhibitors for AChE and BuChE and encourages further studies of these compounds for developing both selective and nonselective inhibitors of ChEs in the future

The specialized tomograph rotary table design in the T-Flex CAD system

Статья "Проектирование поворотного стола специализированного томографа в T-Fleх CAD" посвящена актуальной проблеме обеспечения правильного расположения объектов контроля в томографических комплексах. Представлен вариант конструкции поворотного стола, спроектированный в среде T-Fleх CAD.The article "Designing of the Rotary Table of the Specialized Tomograph in the T-Flex CAD system" is devoted to the urgent problem of the object correct arrangement control in a tomographic complex. The rotary table embodiment is designed with the T-Flex CAD system

Capturing Emerging Realities in Citizen Engagement in Science in Social Media : A Social Media Analytics Protocol for the Allinteract Study

In the digital era, social media has become a space for the socialization and interaction of citizens, who are using social networks to express themselves and to discuss scientific advances with citizens from all over the world. Researchers are aware of this reality and are increasingly using social media as a source of data to explore citizens' voices. In this context, the methods followed by researchers are mainly based on the content analysis using manual, automated or combined tools. The aim of this article is to share a protocol for Social Media Analytics that includes a Communicative Content Analysis (CCA). This protocol has been designed for the Horizon 2020 project Allinteract, and it includes the social impact in social media methodology. The novel contribution of this protocol is the detailed elaboration of methods and procedures to capture emerging realities in citizen engagement in science in social media using a Communicative Content Analysis (CCA) based on the contributions of Communicative Methodology (CM).Peer reviewe

Screening of HELQ in breast and ovarian cancer families

Several high and moderate risk alleles have been identified for breast and ovarian cancer predisposition and most of them encode proteins that function in DNA repair. A prospective candidate for breast and ovarian cancer susceptibility is the HELQ helicase that has a role in the resolution of DNA interstrand cross-links. HELQ interacts with the RAD51 paralog complex BCDX2. Two components of the complex, RAD51C and RAD51D, increase the risk of ovarian cancer especially, and the other two, RAD51B and XRCC2 have been associated with breast cancer risk. To investigate the role of HELQ in cancer predisposition, we screened the gene for germline variation in 185 Finnish breast or ovarian cancer families and performed haplotype analyses for 1517 breast cancer cases, 308 ovarian cancer cases, and 1234 population controls using five common polymorphisms at the HELQ gene locus. No truncating mutations were identified among the families. One putatively pathogenic missense mutation c.1309A > G was identified but no additional carriers were observed in the subsequent genotyping of 332 familial breast or ovarian cancer patients. Furthermore, the haplotype distribution did not differ between breast or ovarian cancer cases and population controls. Our results indicate that HELQ is not a major breast and ovarian cancer susceptibility gene in the Finnish population. However, we cannot rule out rare risk-variants in the Finnish or other populations and larger datasets are needed to further assess the role of HELQ especially in ovarian cancer predisposition.Peer reviewe