DNA methylation is widespread across social Hymenoptera

SummaryGenomic imprinting is an epigenetic phenomenon by which the expression of a gene is influenced by the parent from which it is inherited. The evolutionary causes of imprinting are mysterious but it is likely to represent a form of within-genome conflict [1]. For instance, alleles inherited from the father and the mother will be in conflict over treatment of relatives to which they are differently related. In this context, natural selection may favor alleles with effects that differ depending on the allele's parental origin [1,2]. This ‘kinship theory of imprinting’ has been developed and tested largely in the context of parental provisioning of offspring [1,2]. Given their haplodiploid genetic system and interspecific variation in social traits, the Hymenoptera (ants, bees, and wasps) provide a large variety of novel contexts in which to examine this theory [2]. However, aside from evidence that imprinting determines sex in the parasitic wasp Nasonia vitripennis [3], and a QTL that appears to be paternally inherited in the honeybee [4], nothing is known about imprinting in this group of animals. Here we provide evidence that CpG methylation, a hallmark of imprinting, is ubiquitously present in social insects but the proportion of methylated sites varies substantially among species and developmental stages

Legitimacy in conflict: concepts, practices, challenges

The study of legitimacy in situations of conflict and peacebuilding has increased in recent years. However, current work on the topic adopts many assumptions, definitions, and understandings from classical legitimacy theory, which centers on the relationship between the nation-state and its citizens. In this introduction, we provide a detailed critical overview of current theories of legitimacy and legitimation and demonstrate why they have only limited applicability in conflict and post-conflict contexts, focusing on the three main areas that the articles included in this special issue examine: audiences for legitimacy, sources of legitimacy, and legitimation. In particular, we show how conflict and post-conflict contexts are marked by the fragmentation and personalization of power; the proliferation and fragmentation of legitimacy audiences; and ambiguity surrounding legitimation strategies

The Luminal Progenitor Compartment of the Normal Human Mammary Gland Constitutes a Unique Site of Telomere Dysfunction

Telomeres are essential for genomic integrity, but little is known about their regulation in the normal human mammary gland. We now demonstrate that a phenotypically defined cell population enriched in luminal progenitors (LPs) is characterized by unusually short telomeres independently of donor age. Furthermore, we find that multiple DNA damage response proteins colocalize with telomeres in >95% of LPs but in <5% of basal cells. Paradoxically, 25% of LPs are still capable of exhibiting robust clonogenic activity in vitro. This may be partially explained by the elevated telomerase activity that was also seen only in LPs. Interestingly, this potential telomere salvage mechanism declines with age. Our findings thus reveal marked differences in the telomere biology of different subsets of primitive normal human mammary cells. The chronically dysfunctional telomeres unique to LPs have potentially important implications for normal mammary tissue homeostasis as well as the development of certain breast cancers

Modify the redefined: strategic human resource development maturity at a crossroads

This integrative literature review reports on strategic human resource development (SHRD) models that examine the strategic embeddedness of HRD (SHRD maturity) in organizations. A review and critique of all existing SHRD models is provided, exemplifying their limitations and building upon their strengths to inform a modified SHRD framework. The latter suggests an enhanced set of strategic components to assess SHRD maturity. This paper further outlines how SHRD aspirations can be practiced within complex, dynamic, and continually changing business and economic environments. The SHRD literature is advanced by new insights on how HRD scholars and practitioners could assess and enhance the maturity of their HRD interventions in the context of constantly changing (dynamic) environments. The modified SHRD framework further contributes to the academic literature with its enhanced set of strategic characteristics, as well as with its SHRD pointers, all of which can offer a better evaluation of SHRD maturity during periods of business and economic complexity and uncertainty

Activity-dependent degeneration of axotomized neuromuscular synapses in Wld(S) mice

AbstractActivity and disuse of synapses are thought to influence progression of several neurodegenerative diseases in which synaptic degeneration is an early sign. Here we tested whether stimulation or disuse renders neuromuscular synapses more or less vulnerable to degeneration, using axotomy as a robust trigger. We took advantage of the slow synaptic degeneration phenotype of axotomized neuromuscular junctions in flexor digitorum brevis (FDB) and deep lumbrical (DL) muscles of Wallerian degeneration-Slow (WldS) mutant mice. First, we maintained ex vivo FDB and DL nerve-muscle explants at 32°C for up to 48h. About 90% of fibers from WldS mice remained innervated, compared with about 36% in wild-type muscles at the 24-h checkpoint. Periodic high-frequency nerve stimulation (100Hz: 1s/100s) reduced synaptic protection in WldS preparations by about 50%. This effect was abolished in reduced Ca2+ solutions. Next, we assayed FDB and DL innervation after 7days of complete tetrodotoxin (TTX)-block of sciatic nerve conduction in vivo, followed by tibial nerve axotomy. Five days later, only about 9% of motor endplates remained innervated in the paralyzed muscles, compared with about 50% in 5day-axotomized muscles from saline-control-treated WldS mice with no conditioning nerve block. Finally, we gave mice access to running wheels for up to 4weeks prior to axotomy. Surprisingly, exercising WldS mice ad libitum for 4weeks increased about twofold the amount of subsequent axotomy-induced synaptic degeneration. Together, the data suggest that vulnerability of mature neuromuscular synapses to axotomy, a potent neurodegenerative trigger, may be enhanced bimodally, either by disuse or by hyperactivity

Legitimacy and the cost of government

While previous research documents a negative relationship between government size and economic growth, suggesting an economic cost of big government, a given government size generally affects growth differently in different countries. As a possible explanation of this differential effect, we explore whether perceived government legitimacy (measured by satisfaction with the way democracy works) influences how a certain government size affects growth. On the positive side, a legitimate government may get away with being big since legitimacy can affect people's behavioral response to, and therefore the economic growth cost of, taxation and government expenditures. On the negative side, legitimacy may make voters less prone to acquire information, which in turn facilitates interest-group oriented or populist policies that harm growth. A panel-data analysis of up to 30 developed countries, in which two different measures of the size of government are interacted with government legitimacy, reveals that legitimacy exacerbates a negative growth effect of government size in the long run. This could be interpreted as governments taking advantage of legitimacy in order to secure short-term support at a long-term cost to the economy

Synaptic NMDA receptor activity boosts intrinsic antioxidant defenses

Intrinsic antioxidant defenses are important for neuronal longevity. We found that in rat neurons, synaptic activity, acting via NMDA receptor (NMDAR) signaling, boosted antioxidant defenses by making changes to the thioredoxin-peroxiredoxin (Prx) system. Synaptic activity enhanced thioredoxin activity, facilitated the reduction of overoxidized Prxs and promoted resistance to oxidative stress. Resistance was mediated by coordinated transcriptional changes; synaptic NMDAR activity inactivated a previously unknown Forkhead box O target gene, the thioredoxin inhibitor Txnip. Conversely, NMDAR blockade upregulated Txnip in vivo and in vitro, where it bound thioredoxin and promoted vulnerability to oxidative damage. Synaptic activity also upregulated the Prx reactivating genes Sesn2 (sestrin 2) and Srxn1 (sulfiredoxin), via C/EBPβ and AP-1, respectively. Mimicking these expression changes was sufficient to strengthen antioxidant defenses. Trans-synaptic stimulation of synaptic NMDARs was crucial for boosting antioxidant defenses; chronic bath activation of all (synaptic and extrasynaptic) NMDARs induced no antioxidative effects. Thus, synaptic NMDAR activity may influence the progression of pathological processes associated with oxidative damage