Adaptation of the yeast gene knockout collection is near-perfectly predicted by fitness and diminishing return epistasis

Adaptive evolution of clonally dividing cells and microbes is the ultimate cause of cancer and infectious diseases. The possibility of constraining the adaptation of cell populations, by inhibiting proteins enhancing the evolvability, has therefore attracted interest. However, our current understanding of how genes influence adaptation kinetics is limited, partly because accurately measuring adaptation for many cell populations is challenging. We used a high-throughput adaptive laboratory evolution platform to track the adaptation of >18,000 cell populations corresponding to single-gene deletion strains in the haploid yeast deletion collection. We report that the preadaptation fitness of gene knockouts near-perfectly (R-2= 0.91) predicts their adaptation to arsenic, leaving at the most a marginal role for dedicated evolvability gene functions. We tracked the adaptation of another >23,000 gene knockout populations to a diverse range of selection pressures and generalized the almost perfect (R-2=0.72-0.98) capacity of preadaptation fitness to predict adaptation. We also reconstructed mutations in FPS1, ASK10, and ARR3, which together account for almost all arsenic adaptation in wild-type cells, in gene deletions covering a broad fitness range and show that the predictability of arsenic adaptation can be understood as a by global epistasis, where excluding arsenic is more beneficial to arsenic unfit cells. The paucity of genes with a meaningful evolvability effect on adaptation diminishes the prospects of developing adjuvant drugs aiming to slow antimicrobial and chemotherapy resistance

Analys av en statlig utredning – en diskursanalys om hur missbruk, beroende, tvång och individ beskrivs i missbruksutredningen (SOU 2011:35)

The purpose of this study was to analyze from a discourse analytic perspective how The Substance Abuse commissions final report, Improved interventions for substance abuse and dependence - the individual, knowledge and responsibility (SOU 2011:35) (Bättre insatser vid missbruk och beroende – individen, kunskapen och ansvaret), chapter 7, constructs discourses in relation to concepts such as substance abuse, substance addiction and the individual in relation to coercion. The starting point of the study was that through a qualitative approach in the form of critical discourse analysis and discourse theory analyze different concepts. We found three different discourses in the context of SOU 2011:35, chapter 7. The analysis found that a medical discourse has come the farthest in a striving for hegemony in the construct of substance abuse and substance dependence, as well as the individual came to appear as distinct depending on the perception of substance abuse and substance addiction, as well as the measures advocated. A social discourse and penal discourse is less perceptible in SOU 2011:35. This also has implications for what SOU 2011:35 proposes a change to legislation

Nulägesanalys trädgård

Rapporten Nulägesanalys - trädgård har genomförts inom ramen för projektgruppen Insatsstyrka trädgård. Syftet med inventeringen har varit att ge svar på vem som jobbar med trädgårdsvetenskap, vilka forskargrupper och med vilka forskningsämnen, samt identifiera framtida arbetsfält inom ämnet trädgårdsvetenskap och därmed ge uppslag för framtida utveckling av forskningsfält, utbildning och samverkan. I detta ingår att kartlägga trädgårdsvetenskaplig forskning, utbildning och samverkan vid SLU. Nulägesanalysen förväntas därmed ge en grund för fortsatt strategiskt arbete med att utveckla ämnet trädgårdsvetenskap (Horticultural Science) utifrån inventerade resurser och förutsättningar

Genetically controlled mtDNA deletions prevent ROS damage by arresting oxidative phosphorylation

Deletion of mitochondrial DNA in eukaryotes is currently attributed to rare accidental events associated with mitochondrial replication or repair of double-strand breaks. We report the discovery that yeast cells arrest harmful intramitochondrial superoxide production by shutting down respiration through genetically controlled deletion of mitochondrial oxidative phosphorylation genes. We show that this process critically involves the antioxidant enzyme superoxide dismutase 2 and two-way mitochondrial-nuclear communication through Rtg2 and Rtg3. While mitochondrial DNA homeostasis is rapidly restored after cessation of a short-term superoxide stress, long-term stress causes maladaptive persistence of the deletion process, leading to complete annihilation of the cellular pool of intact mitochondrial genomes and irrevocable loss of respiratory ability. This shows that oxidative stress-induced mitochondrial impairment may be under strict regulatory control. If the results extend to human cells, the results may prove to be of etiological as well as therapeutic importance with regard to age-related mitochondrial impairment and disease

Mass-loading, pile-up, and mirror-mode waves at comet 67P/Churyumov-Gerasimenko

International audienceThe data from all Rosetta plasma consortium instruments and from the ROSINA COPS instrument are used to study the interaction of the solar wind with the outgassing cometary nucleus of 67P/Churyumov-Gerasimenko. During 6 and 7 June 2015, the interaction was first dominated by an increase in the solar wind dynamic pressure, caused by a higher solar wind ion density. This pressure compressed the draped magnetic field around the comet, and the increase in solar wind electrons enhanced the ionization of the outflow gas through collisional ionization. The new ions are picked up by the solar wind magnetic field, and create a ring/ring-beam distribution, which, in a high-β plasma, is unstable for mirror mode wave generation. Two different kinds of mirror modes are observed: one of small size generated by locally ionized water and one of large size generated by ionization and pickup farther away from the comet

T Follicular Helper Cell-Dependent Clearance of a Persistent Virus Infection Requires T Cell Expression of the Histone Demethylase UTX

Epigenetic changes, including histone methylation, control T cell differentiation and memory formation, though the enzymes that mediate these processes are not clear. We show that UTX, a histone H3 lysine 27 (H3K27) demethylase, supports T follicular helper (Tfh) cell responses that are essential for B cell antibody generation and the resolution of chronic viral infections. Mice with a T cell-specific UTX deletion had fewer Tfh cells, reduced germinal center responses, lacked virus-specific immunoglobulin G (IgG), and were unable to resolve chronic lymphocytic choriomeningitis virus infections. UTX-deficient T cells showed decreased expression of interleukin-6 receptor-α and other Tfh cell-related genes that were associated with increased H3K27 methylation. Additionally, Turner Syndrome subjects, who are predisposed to chronic ear infections, had reduced UTX expression in immune cells and decreased circulating CD4(+) CXCR5(+) T cell frequency. Thus, we identify a critical link between UTX in T cells and immunity to infection

Homicide committed under a strong influence of psychical agitation

Darba izpētes temats ir KL 120.pants - slepkavība, kas izdarīta stipra psihiska uzbudinājuma stāvoklī. Bakalaura darba mēŗkis ir sniegt plašu interpretāciju un ieskatu par KL 120.pantu un tam piemērojamām sankcijām, un spēt nošķirt no citiem līdzīgiem sastāviem. Darbs sastāv no 4 nodaļām. Tā autore 1.nodaļā pēta slepkavības vēsturisko attīstību, sākot no 1885.gada Sodu likuma līdz pat 2005.gadā pieņemtajam jaunajam Latvijas Kimināllikumam. 2.nodaļā autore veic šī noziedzīgā nodarījuma juridisko analīzi, interpretējot tā sastāvu un pamatojot to ar Latvijas tiesu instanču nolēmumiem. 3.nodaļā autore pievērš uzmanību KL 120.panta līdzīgiem sastāviem - 117.panta 4.daļai un 118.panta 3.daļai un mēģina tos uskatāmi norobežot no slepkavības, kas izdarīta stipra psihiska uzbudinājuma stāvoklī. Lai pilnvērtīgāk izprastu un izskaidrotu 120.pantā kvalificētās slepkavības sastāvu, autore salīdzina vairākus ārvalstu normatīvos aktus, kuros sniegts atšķirīgs tiesiskais regulējums mūsu KL 120.panta izpratnēThe theme of the bachelor’s research is Section 120 of the Criminal Law, which is „Murder Commited in a State of Extreme Mental Agitation.” The aim of the bachelor’s paper is to provide wide interpretation and insigth into Section 120 of the Criminal Law and sanctions adjustable to it, as well as the capability to distinguish it from other similar corpus delicti. The paper consists of four parts. In the first part the author investigates historical development of murder, from the Punishment Law of year 1885 till new the Criminal Law of Latvia, adopted in 2005. In the second part the author provides legal analysis of this criminal offence, interprets its corpus delicti and substantiates it with judgements of Latvia’s courts. In the third part the author describes similar corpus delicti of Section 120 of the Criminal Law – paragraph 4 of Section 117 and paragraph 3 of Section 118, and tries to explicitly distinguish them from a murder commited in a state of extreme mental agitation. In order to valuably comprehend and explain corpus delicti of murder qualified in Section 120, the author compares several foreign normative acts, in which is provided different judicial regulation for the purpose of Section 120 of the Criminal Law

Upplýsingaskipti milli samrunaaðila : lögmæti upplýsingaskipta samrunaaðila í óvissu lagaumhverfi

Gildandi lagareglur um samráð keppinauta, þ.e. 10. gr. samkeppnislaga nr. 44/2005 og 101. gr. TFEU, hafa að geyma matskennt orðalag og þykja þær óljósar hvað varðar samstillandi háttsemi samrunaaðila. Ljóst er að samrunaaðilar skiptast með einhverjum hætti á viðskiptalega viðkvæmum upplýsingum í aðdraganda samruna. Samrunaaðilum er þó skylt að verja samkeppni eftir samrunatilkynningu og fram að samþykki yfirvalda. Texti viðeigandi lagareglna hjálpar lítið upp á skýringar hvað varðar lögmæti upplýsingaskipta samrunaaðila og réttarframkvæmd er fátækleg. Markmið ritgerðarinnar er að varpa ljósi á reglur sem gilda um upplýsingaskipti samrunaaðila og bera kennsl á lögmæti slíks samráðs. Við könnun á umræddu efni var dómur Evrópudómstólsins í Altice gegn framkvæmdastjórninni áberandi. Þar staðfesti dómstóllinn ákvörðun framkvæmdastjórnar Evrópusambandsins vegna brots gegn 1. mgr. 4. gr. og 1. mgr. 7. gr samrunareglugerðarinnar, sbr. 17. gr. a. samkeppnislaga. Meðal röksemda framkvæmdastjórnarinnar voru umfangsmikil og ítarleg upplýsingaskipti. Málið gefur til kynna að upplýsingaskipti samrunaaðila geti átt hlut í óheimilli framkvæmd á samruna séu þær umfram það sem nauðsynlegt er til varðveitingar á virði fyrirtækis. Þó má álykta að þetta eigi eingöngu við þegar upplýsingaskipti eru metin samhliða öðrum aðgerðum samrunaaðila sem benda til framkvæmdar á samruna. Álit Evrópudómstólsins í Ernst & Young gegn Konkurrencerådet er til frekari skýringar á gildissviði 1. mgr. 7. gr. samrunareglugerðarinnar. Af því máli er ljóst að samráðsreglur halda gildi sínu hvað varðar háttsemi samrunaaðila þegar aðgerðir þeirra leiða ekki af sér breytingu á yfirráðum til frambúðar. Mat á lögmæti upplýsingaskipta samrunaaðila byggist því alla jafna á 1. mgr. 101. gr. TFEU, sbr. 10. gr. samkeppnislaga, og þeim lagalegu sjónarmiðum sem því tengjast. Þar með skal leggja áherslu á þörf samrunaaðila til að ná því heildarmarkmiði að koma samruna til framkvæmda, að því leyti sem upplýsingaskipti þeirra teljast nauðsynleg viðbót við samruna. Að öðru leyti þykir ljóst að þörf sé á bættri lagaumgjörð til skýringar á réttarstöðu samrunaaðila.Icelandic and EU legislation regarding coordination between competitors, i.e. Articles 10 of the Icelandic competition law no. 44/2005 and 101(1) TFEU, contain subjective language which appear vague with regards to pre-merger coordination. While the exchange of commercially sensitive information between merging parties is to be expected, merging parties are required to maintain competition following notification and until receiving clearance. Current legislation does little in identifying permissible pre-merger information exchange and legal precedent is scarce. This thesis aims to clarify the rules applicable to pre-merger information exchange as well as identify the legality of such coordination. Upon resarch, the judgment of the General Court of the European Union in Altice v. Commission was especially relevant. The court confirmed the Commission’s decision fining merging parties for violating Articles 4(1) and 7(1) EUMR, mirrored by Article 17a of the Icelandic competition law. The Commission observed extensive and detailed information exchange. The judgment implies that information exchange can play a role in prematurely implementing a merger if coordination exceeds that which is necessary to preserve the value of an undertaking. However, it may be determined that this only applies when assessing information exchange in conjunction with actions taken by merging parties that may themselves lead to an implementation of a merger. The European Court of Justice in Ernst & Young v. Konkurrencerådet sheds further light on the scope of Article 7(1) EUMR. The Court found that Article 101(1) TFEU continues to apply to actions taken by merging parties that do not bring about a lasting change of control. Thus, the legality of pre-merger information exchanged must be assessed under Article 101(1) and all supplemental legal doctrines, emphasizing the merging parties particular need to integrate, to the extent that information is ancillary to the merger. Nevertheless, it is clear that an improved legal framework is required to clarify permissible pre-merger activity