IP6K3 and IPMK variations in LOAD and longevity: evidence for a multifaceted signaling network at the crossroad between neurodegeneration and survival

Several studies reported that genetic variants predisposing to neurodegeneration were at higher frequencies in centenarians than in younger controls, suggesting they might favor also longevity. IP6K3 and IPMK regulate many crucial biological functions by mediating synthesis of inositol poly- and pyrophosphates and by acting non-enzymatically via protein–protein interactions. Our previous studies suggested they affect Late Onset Alzheimer Disease (LOAD) and longevity, respectively. Here, in the same sample groups, we investigated whether variants of IP6K3 also affect longevity, and variants of IPMK also influence LOAD susceptibility. We found that: i) a SNP of IP6K3 previously associated with increased risk of LOAD increased the chance to become long-lived, ii) SNPs of IPMK, previously associated with decreased longevity, were protective factors for LOAD, as previously observed for UCP4. SNP-SNP interaction analysis, including our previous data, highlighted phenotype-specific interactions between sets of alleles. Moreover, linkage disequilibrium and eQTL data associated to analyzed variants suggested mitochondria as crossroad of interconnected pathways crucial for susceptibility to neurodegeneration and/or longevity. Overall, data support the view that in these traits interactions may be more important than single polymorphisms. This phenomenon may contribute to the non-additive heritability of neurodegeneration and longevity and be part of the missing heritability of these traits

Utjecaj induciranog tranzijentnog toka na transport u prirodnim vodonosnicima

In situ remediation is an effective technique to reduce risk caused by contaminated aquifers. However, low groundwater-flow velocity – typical in natural aquifers – hinders dilution, thereby reducing remediation efficiency. A possible strategy to overcome this problem consists of forcing the flow field by means of a geo-engineered system of alternate pumping. This work is aimed at investigating the coupled effect of geo-engineered unsteady flow and natural aquifer heterogeneity on remediation. Here we introduce an innovative analytical formulation to quantify dilution in 3D heterogeneous porous media under the effect of alternate pumping. Our solution relies on a simplified first-order framework, which limits the solution to point-like sources, weakly heterogeneous media, and slowly oscillating transient flows. Our results indicate that the efficiency of the unsteady flow field is mostly ruled by local-scale dispersion. Furthermore, we analyze several schemes of alternate pumping, thereby showing that inducing a forced rotation in the mean trajectory enhances remediation efficiency.Sanacija podzemnih voda je uspješna metoda smanjivanja rizika uzrokovanog zagađenim vodonosnicima. Prirodni vodonosnici su obilježeni malim brzinama podzemne vode što otežava razrjeđivanje, a time i efikasnost procesa sanacije. Navedeni problem se potencijalno može riješiti prisilnim protjecanjem ako se uvede sustav izmjeničnog utiskivanja. U ovom radu će se istražiti povezani utjecaj takvog projektiranog nestacionarnog tečenja i prirodne heterogenosti vodonosnika na proces sanacije. Uveden je inovativni analitički pristup za procjenu razrjeđenja u 3D heterogenom poroznom mediju pod utjecajem izmjeničnog utiskavanja. Predloženo rješenje spada u klasu prvog reda, što ga ograničava na točkaste izvore, blago heterogeni medij i tranzijentne tokove sa sporim promjenama. Ostvareni rezultati su ukazali da je efikasnost polja nestacionarnog tečenja dominatno pod utjecaj disperzije na lokalnoj skali. Nadalje, analizirano je nekoliko različitih shema izmjeničnog utiskivanja, što je ukazalo da induciranje prisilne rotacije u srednjoj trajektoriji toka povećava efikasnost procesa sanacije

Tongtong Practices of Bakun Benguet: Its Historical and Political Relevance

Tongtong is a justice system that evolves from the customs and traditions. It is a traditional way of conflict resolution in Benguet wherein a council of elders will mediate and help settle the disputes in the community. This study explored the Tongtong practice of Sinacbat, Bakun, Benguet as an alternative dispute resolution that reflects the barangays’ way of dealing with disputes within the community. Through the use of key informant interviews and focus group discussions, the researchers unveiled how the Tongtong system is being culturally practiced in barangay Sinacbat. The researchers concluded that the situations where Tongtong is being practiced in the community are on Land Disputes, Marital Problems, Family Problems, Community Disputes and Violations of the Cultural norms. The process of Tongtong usually starts when the concerned parties subject themselves to the cultural practice. It will be followed by finding out the root cause of the dispute, and then negotiation on the settlement will transpire followed by the elders giving their advice. This practice is significant to the community because it serves as a reminder to the community from their forefathers to not be misguided and commit wrongdoings. And due to its efficiency and effectiveness it is credited

Inositol Polyphosphate Multikinase (IPMK), a Gene Coding for a Potential Moonlighting Protein, Contributes to Human Female Longevity

Biogerontological research highlighted a complex and dynamic connection between aging, health and longevity, partially determined by genetic factors. Multifunctional proteins with moonlighting features, by integrating different cellular activities in the space and time, may explain part of this complexity. Inositol Polyphosphate Multikinase (IPMK) is a potential moonlighting protein performing multiple unrelated functions. Initially identified as a key enzyme for inositol phosphates synthesis, small messengers regulating many aspects of cell physiology, IPMK is now implicated in a number of metabolic pathways affecting the aging process. IPMK regulates basic transcription, telomere homeostasis, nutrient-sensing, metabolism and oxidative stress. Here, we tested the hypothesis that the genetic variability of IPMK may affect human longevity. Single-SNP (single nuclear polymorphism), haplotype-based association tests as well as survival analysis pointed to the relevance of six out of fourteen genotyped SNPs for female longevity. In particular, haplotype analysis refined the association highlighting two SNPs, rs2790234 and rs6481383, as major contributing variants for longevity in women. Our work, the first to investigate the association between variants of IPMK and longevity, supports IPMK as a novel gender-specific genetic determinant of human longevity, playing a role in the complex network of genetic factors involved in human survival

The genome sequence of the highly acetic acid-tolerant zygosaccharomyces bailii-derived interspecies hybrid strain ISA1307, isolated from a sparkling wine plant

In this work, it is described the sequencing and annotation of the genome of the yeast strain ISA1307, isolated from a sparkling wine continuous production plant. This strain, formerly considered of the Zygosaccharomyces bailii species, has been used to study Z. bailii physiology, in particular, its extreme tolerance to acetic acid stress at low pH. The analysis of the genome sequence described in this work indicates that strain ISA1307 is an interspecies hybrid between Z. bailii and a closely related species. The genome sequence of ISA1307 is distributed through 154 scaffolds and has a size of around 21.2 Mb, corresponding to 96% of the genome size estimated by flow cytometry. Annotation of ISA1307 genome includes 4385 duplicated genes (~90% of the total number of predicted genes) and 1155 predicted single-copy genes. The functional categories including a higher number of genes are 'Metabolism and generation of energy', 'Protein folding, modification and targeting' and 'Biogenesis of cellular components'. The knowledge of the genome sequence of the ISA1307 strain is expected to contribute to accelerate systems-level understanding of stress resistance mechanisms in Z. bailii and to inspire and guide novel biotechnological applications of this yeast species/strain in fermentation processes, given its high resilience to acidic stress. The availability of the ISA1307 genome sequence also paves the way to a better understanding of the genetic mechanisms underlying the generation and selection of more robust hybrid yeast strains in the stressful environment of wine fermentations.This research was supported by FCT and FEDER through POFC-COMPETE [contracts PEst-OE/EQB/ LA0023/2011_ research line: Systems and Synthetic Biology PTDC/AGR-ALI/102608/2008, PEst-C/BIA/ UI4050/2011, and post-doctoral grant to M.P. (SFRH/BPD/73306/2010) and PhD grants to J.F.G. (SFRH/ BD/80065/2011) and F.C.R. (SFRH/BD/82226/2011)]. U.G. acknowledges the Austrian Science Fund (FWF, special research project F3705)

Sabotage in Contests: A Survey

A contest is a situation in which individuals expend irretrievable resources to win valuable prize(s). ‘Sabotage’ is a deliberate and costly act of damaging a rival’s' likelihood of winning the contest. Sabotage can be observed in, e.g., sports, war, promotion tournaments, political or marketing campaigns. In this article, we provide a model and various perspectives on such sabotage activities and review the economics literature analyzing the act of sabotage in contests. We discuss the theories and evidence highlighting the means of sabotage, why sabotage occurs, and the effects of sabotage on individual players and on overall welfare, along with possible mechanisms to reduce sabotage. We note that most sabotage activities are aimed at the ablest player, the possibility of sabotage reduces productive effort exerted by the players, and sabotage may lessen the effectiveness of public policies, such as affirmative action, or information revelation in contests. We discuss various policies that a designer may employ to counteract sabotage activities. We conclude by pointing out some areas of future research

Towards Graphene Nanoribbon-based Electronics

The successful fabrication of single layer graphene has greatly stimulated the progress of the research on graphene. In this article, focusing on the basic electronic and transport properties of graphene nanoribbons (GNRs), we review the recent progress of experimental fabrication of GNRs, and the theoretical and experimental investigations of physical properties and device applications of GNRs. We also briefly discuss the research efforts on the spin polarization of GNRs in relation to the edge states.Comment: 9pages,10figure