Major Break Research Articles

Parsing variance by marker type: Testing biogeographic hypotheses and differential contribution of historical processes to population structure in a desert lizard.

A fundamental goal of population genetic studies is to identify historical biogeographic patterns and understand the processes that generate them. However, localized demographic events can skew population genetic inference. Assessing populations with multiple types of genetic markers, each with unique mutation rates and responses to changes in population size, can help to identify potentially confounding population-specific demographic processes. Here, we compared population structure and connectivity inferred from microsatellites and restriction site-associated DNA loci among 17 populations of an arid-specialist lizard, the desert night lizard, Xantusia vigilis, in central California to test among historical processes structuring population genetic diversity. We found that both marker types yielded generally concordant insights into population genetic structure including a major phylogenetic break maintained between two populations separated by less than 10 km, suggesting that either marker type could be used to understand generalized demographic patterns across the region for management purposes. However, we also found that the effects of demography on marker discordance could be used to elucidate population histories and distinguish among competing biogeographic hypotheses. Our results suggest that comparisons of within-population diversity across marker types provide powerful opportunities for leveraging marker discordance, particularly for understanding the creation and maintenance of contact zones among clades.

Long distance dispersal and oceanographic fronts shape the connectivity of the keystone sponge Phakellia ventilabrum in the deep northeast Atlantic

Little is known about dispersal in deep-sea ecosystems, especially for sponges, which are abundant ecosystem engineers. Understanding patterns of gene flow in deep-sea sponges is essential, especially in areas where rising pressure from anthropogenic activities makes difficult to combine management and conservation. Here, we combined population genomics and oceanographic modelling to understand how Northeast Atlantic populations (Cantabrian Sea to Norway) of the deep-sea sponge Phakellia ventilabrum are connected. The analysis comprised ddRADseq derived SNP datasets of 166 individuals collected from 57 sampling stations from 17 different areas, including two Marine Protected Areas, one Special Area of Conservation and other areas with different levels of protection. The 4,017 neutral SNPs used indicated high connectivity and panmixis amongst the majority of areas (Ireland to Norway), spanning ca. 2,500-km at depths of 99–900 m. This was likely due to the presence of strong ocean currents allowing long-distance larval transport, as supported by our migration analysis and by 3D particle tracking modelling. On the contrary, the Cantabrian Sea and Roscoff (France) samples, the southernmost areas in our study, appeared disconnected from the remaining areas, probably due to prevailing current circulation patterns and topographic features, which might be acting as barriers for gene flow. Despite this major genetic break, our results suggest that all protected areas studied are well-connected with each other. Interestingly, analysis of SNPs under selection replicated results obtained for neutral SNPs. The relatively low genetic diversity observed along the study area, though, highlights the potential fragility of this species to changing climates, which might compromise resilience to future threats.

Phosphorylation of DNA-PKcs at the S2056 cluster ensures efficient and productive lymphocyte development in XLF-deficient mice

The nonhomologous end-joining (NHEJ) pathway is a major DNA double-strand break repair pathway in mammals and is essential for lymphocyte development. Ku70 and Ku80 heterodimer (KU) initiates NHEJ, thereby recruiting and activating the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs). While DNA-PKcs deletion only moderately impairs end-ligation, the expression of kinase-dead DNA-PKcs completely abrogates NHEJ. Active DNA-PK phosphorylates DNA-PKcs at two clusters-PQR around S2056 (S2053 in mouse) and ABCDE around T2609. Alanine substitution at the S2056 cluster moderately compromises end-ligation on plasmid-based assays. But, mice carrying alanine substitution at all five serine residues within the S2056 cluster (DNA-PKcsPQR/PQR) display no defect in lymphocyte development, leaving the physiological significance of S2056 cluster phosphorylation elusive. Xlf is a nonessential NHEJ factor. Xlf -/- mice have substantial peripheral lymphocytes that are completely abolished by the loss of DNA-PKcs, the related ATM kinases, other chromatin-associated DNA damage response factors (e.g., 53BP1, MDC1, H2AX, and MRI), or RAG2-C-terminal regions, suggesting functional redundancy. While ATM inhibition does not further compromise end-ligation, here we show that in XLF-deficient background, DNA-PKcs S2056 cluster phosphorylation is critical for normal lymphocyte development. Chromosomal V(D)J recombination from DNA-PKcsPQR/PQRXlf -/- B cells is efficient but often has large deletions that jeopardize lymphocyte development. Class-switch recombination junctions from DNA-PKcsPQR/PQRXlf -/- mice are less efficient and the residual junctions display decreased fidelity and increased deletion. These findings establish a role for DNA-PKcs S2056 cluster phosphorylation in physiological chromosomal NHEJ, implying that S2056 cluster phosphorylation contributes to the synergy between XLF and DNA-PKcs in end-ligation.

Investors’ reactions on the publication of integrated reports. Evidence from European stock markets

The last decades brought to stock market investors’ attention several key issues regarding companies’ activity, besides the financial statements. These issues, such as environmental, social, or corporate governance policies are nowadays included in integrated reports issued by many listed companies worldwide. Although these topics seem to currently attract a high interest in the media, our study’s aim is to determine whether the listed firms’ release of Integrated Reports has any bearing on the issuers’ performance on the capital market as assessed by market value, return, and risk. In this respect, we analysed three different stock market time series’ reactions – daily close prices, daily logarithmic returns, and risk measured by the Expected Shortfall – to the publication of integrated reports, for a sample of 48 companies, listed on various European stock markets. In order to identify any sudden changes in the analysed time series behaviour, immediately after the publication date, we used the Bai-Perron multiple structural breaks test. Our results show that no consistent, significant reactions occur within the analysed time series immediately after the publication of integrated reports, but only isolated, circumstantial reactions seem to appear. Moreover, it seems that the markets show common significant reactions to certain events, marked by major structural breaks, but none of these events could be related to the publication of integrated reports. Within this context, our paper manages to prove that although it currently constitutes a hot topic worldwide, integrated reporting is not a key feature in the investors’ short-term decisionmaking process.

Power Generation by Shock Absorber

Abstract: In a country like India, two-wheeler vehicles are predominant over four wheelers. According to data taken from internet, around 20 million two wheelers were sold in 2017/18, as compared to 4 million four wheelers. And this demand keeps on increasing in India. Keeping this mind, a huge potential of energy is being wasted every day. This project is one of the methods to harvest those wasted energy. That’s why this project is under energy recovery. All the major advancements and break through has been done mostly on four wheelers. To name some energy recovery mechanisms, regenerative brakes, regenerative shocks, MGU-H, MGU-K. Even the companies like AUDI and BMW have started launching commercial vehicles which come with energy recovery systems. The main purpose of the dampers is to keep the tires in contact with the ground all the time. Other functions include to absorb the vibrations produced due to irregularities of the surface. This prototype aims to convert these vibrational energies into electricity which otherwise would have been wasted. In a way it can be called Regenerative dampers, which is completely mechanical in nature. This prototype uses a rack and pinion arrangement to convert the reciprocating motion of the bike front fork into a linear motion. The motor is coupled to a DC generator which produces electricity. Our main focus is on two wheelers so, the energy stored can be used to increase the engine efficiency as extra load on alternator is reduced. The aim for this prototype is to produce a current of 0.3A and 12 V (DC), which would be sufficient to charge the batteries and run other auxiliary system of a motorcycle.

The dynamic nature of student discipline and discipline disparities

Researchers have long used end-of-year discipline rates to identify punitive schools, explore sources of inequitable treatment, and evaluate interventions designed to stem both discipline and racial disparities in discipline. Yet, this approach leaves us with a "static view"-with no sense of how disciplinary responses fluctuate throughout the year. What if daily discipline rates, and daily discipline disparities, shift over the school year in ways that could inform when and where to intervene? This research takes a "dynamic view" of discipline. It leverages 4 years of atypically detailed data regarding the daily disciplinary experiences of 46,964 students from 61 middle schools in one of the nation's largest school districts. Reviewing these data, we find that discipline rates are indeed dynamic. For all student groups, the daily discipline rate grows from the beginning of the school year to the weeks leading up to the Thanksgiving break, falls before major breaks, and grows following major breaks. During periods of escalation, the daily discipline rate for Black students grows significantly faster than the rate for White students-widening racial disparities. Given this, districts hoping to stem discipline and disparities may benefit from timing interventions to precede these disciplinary spikes. In addition, early-year Black-White disparities can be used to identify the schools in which Black-White disparities are most likely to emerge by the end of the school year. Thus, the results reported here provide insights regarding not only when to intervene, but where to intervene to reduce discipline rates and disparities.

XLF/Cernunnos loss impairs mouse brain development by altering symmetric proliferative divisions of neural progenitors

XLF/Cernunnos is a component of the ligation complex used in classical non-homologous end-joining (cNHEJ), a major DNA double-strand break (DSB) repair pathway. We report neurodevelopmental delays and significant behavioral alterations associated with microcephaly in Xlf-/- mice. This phenotype, reminiscent of clinical and neuropathologic features in humans deficient in cNHEJ, is associated with a low level of apoptosis of neural cells and premature neurogenesis, which consists of an early shift of neural progenitors from proliferative to neurogenic divisions during brain development. We show that premature neurogenesis is related to an increase in chromatid breaks affecting mitotic spindle orientation, highlighting a direct link between asymmetric chromosome segregation and asymmetric neurogenic divisions. This study reveals thus that XLF is required for maintaining symmetric proliferative divisions of neural progenitors during brain development and shows that premature neurogenesis may play a major role in neurodevelopmental pathologies caused by NHEJ deficiency and/or genotoxic stress.

Trade matters except to war neighbors: The international stock market reaction to 2022 Russia’s invasion of Ukraine

We investigate the role of international trade and proximity to war in international stock markets during the invasion of Ukraine by employing DiD designs and panel data comprising 70 stock markets. We find that differences in trade exposure to warring countries (trade effect) have a substantial and negative impact on non-European equity markets but are irrelevant for European markets. In contrast, differences in the distance to warring countries (proximity effect) have a significant and negative impact on European markets but have no bearing on non-European markets. We find that the relevance of rent from mineral, natural gas, and oil resources and the relevance of metals, ores, and fuels in exports operate as mitigators of the trade effect. Our paper provides valuable empirical evidence regarding the importance of mitigating the vulnerability of financial markets to international trade when a major war breaks out.

The Stock Market Volatility Research between China and ASEAN based on Complex Networks

By constructing the volatility network of stock market indexes in China and ASEAN, the mechanism of transnational market risk transmission and the characteristics of key nodes are analysed. Finding the volatility network is a good description of the linkage and tightness of the various share index volatility. The COVID-19 led to a significant increase in convergence of behaviour patterns of major country share indexes, and significant differences in node changes and topological features of the volatility network. Dynamic analysis shows that the evolution of share index volatility network reflects that the overall risk of volatility network changes with time, the information link structure of the market changes with time, and major emergencies break the original structure and trigger the information connection in the market. The findings of this paper have important implications for understanding the characteristics of transnational risk transmission between the stock markets of China and ASEAN.

Formation of a fringe: A look inside baleen morphology using a multimodal visual approach.

Filter-feeding has been present for hundreds of millions of years, independently evolving in aquatic vertebrates' numerous times. Mysticete whales are a group of gigantic, marine filter-feeders that are defined by their fringed baleen and are divided into two groups: balaenids and rorquals. Recent studies have shown that balaenids likely feed using a self-cleaning, cross-flow filtration mechanism where food particles are collected and then swept to the esophagus for swallowing. However, it is unclear how filtering is achieved in the rorquals (Balaenopteridae). Lunging rorqual whales engulf enormous masses of both prey and water; the prey is then separated from the water through baleen plates lining the length of their upper jaw and positioned perpendicular to flow. Rorqual baleen is composed of both major (larger) and minor (smaller) keratin plates containing embedded fringe that extends into the whale's mouth, forming a filtering fringe. We used a multimodal approach, including microcomputed tomography (µCT) and scanning electron microscopy (SEM), to visualize and describe the variability in baleen anatomy across five species of rorqual whales, spanning two orders of magnitude in body length. For most morphological measurements, larger whales exhibited hypoallometry relative to body length. µCT and SEM revealed that the major and minor plates break away from the mineralized fringes at variable distances from the gums. We proposed a model for estimating the effective pore size to determine whether flow scales with body length or prey size across species. We found that pore size is likely not a proxy for prey size but instead, may reflect changes in resistance through the filter that affect fluid flow.

Two distinct long-range synaptic complexes promote different aspects of end processing prior to repair of DNA breaks by non-homologous end joining

Non-homologous end joining is the major double-strand break repair (DSBR) pathway in mammals. DNA-PK is the hub and organizer of multiple steps in non-homologous end joining (NHEJ). Recent high-resolution structures show how two distinct NHEJ complexes "synapse" two DNA ends. One complex includes a DNA-PK dimer mediated by XLF, whereas a distinct DNA-PK dimer forms via a domain-swap mechanism where the C terminus of Ku80 from one DNA-PK protomer interacts with another DNA-PK protomer in trans. Remarkably, the distance between the two synapsed DNA ends in both dimers is the same (∼115Å), which matches the distance observed in the initial description of an NHEJ long-range synaptic complex. Here, a mutational strategy is used to demonstrate distinct cellular function(s) of the two dimers: one promoting fill-in end processing, while the other promotes DNA end resection. Thus, the specific DNA-PK dimer formed (which may be impacted by DNA end structure) dictates the mechanism by which ends will be made ligatable.

NtcA, LexA and heptamer repeats involved in the multifaceted regulation of DNA repair genes recF, recO and recR in the cyanobacterium Nostoc PCC7120

Regulation of DNA repair genes in cyanobacteria is an unexplored field despite some of them exhibiting high radio-resistance. With RecF pathway speculated to be the major double strand break repair pathway in Nostoc sp. strain PCC7120, regulation of recF, recO and recR genes was investigated. Bioinformatic approach-based identification of promoter and regulatory elements was validated using qRT-PCR analysis, reporter gene and DNA binding assays. Different deletion constructs of the upstream regulatory regions of these genes were analysed in host Nostoc as well as heterologous system Escherichia coli. Studies revealed: (1) Positive regulation of all three genes by NtcA, (2) Negative regulation by LexA, (3) Involvement of contiguous heptamer repeats with/without its yet to be identified interacting partner in regulating (i) binding of NtcA and LexA to recO promoter and its translation, (ii) transcription or translation of recF, (4) Translational regulation of recF and recO through non-canonical and distant S.D. sequence and of recR through a rare initiation codon. Presence of NtcA either precludes binding of LexA to AnLexA-Box or negates its repressive action resulting in higher expression of these genes under nitrogen-fixing conditions in Nostoc. Thus, in Nostoc, expression of recF, recO and recR genes is intricately regulated through multiple regulatory elements/proteins. Contiguous heptamer repeats present across the Nostoc genome in the vicinity of start codon or promoter is likely to have a global regulatory role. This is the first report detailing regulation of DSB repair genes in any algae.

Postglacial species arrival and diversity buildup of northern ecosystems took millennia.

What drives ecosystem buildup, diversity, and stability? We assess species arrival and ecosystem changes across 16 millennia by combining regional-scale plant sedimentary ancient DNA from Fennoscandia with near-complete DNA and trait databases. We show that postglacial arrival time varies within and between plant growth forms. Further, arrival times were mainly predicted by adaptation to temperature, disturbance, and light. Major break points in ecological trait diversity were seen between 13.9 and 10.8 calibrated thousand years before the present (cal ka BP), as well as break point in functional diversity at 12.0 cal ka BP, shifting from a state of ecosystem buildup to a state where most habitat types and biotic ecosystem components were in place. Trait and functional diversity stabilized around 8 cal ka BP, after which both remained stable, although changes in climate took place and species inflow continued. Our ecosystem reconstruction indicates a millennial-scale time phase of formation to reach stable and resilient levels of diversity and functioning.

Identification and characterization of mercaptopyrimidine-based small molecules as inhibitors of nonhomologous DNA end joining.

Mercaptopyrimidine derivatives are heterocyclic compounds with potent biological activities including antiproliferative, antibacterial, and anti-inflammatory properties. The present study describes the synthesis and characterization of several mercaptopyrimidine derivatives through condensation of 5,6-diamino-2-mercaptopyrimidin-4-ol with various heterocyclic and aromatic aldehydes. Previous studies have shown that SCR7, synthesized from 5,6-diamino-2-mercaptopyrimidin-4-ol, induced cytotoxicity by targeting cancer cells by primarily inhibiting DNA Ligase IV involved in nonhomologous end joining, one of the major DNA double-strand break repair pathways. Inhibition of DNA repair pathways is considered as an important strategy for cancer therapy. Due to limitations of SCR7 in terms of IC50 in cancer cells, here we have designed, synthesized, and characterized potent derivatives of SCR7 using 5,6-diamino-2-mercaptopyrimidin-4-ol as the starting material. Several synthesized imine compounds exhibited significant improvement in inhibition of end joining and cytotoxicity up to 27-fold lower concentrations than SCR7. Among these, two compounds, SCR116 and SCR132, showed increased cancer cell death in a Ligase IV-dependent manner. Treatment with the compounds also led to reduction in V(D)J recombination efficiency, cell cycle arrest at G2/M phase, accumulation of double-strand breaks inside cells, and improved anti-cancer potential when combined with γ-radiation and radiomimetic drugs. Thus, we describe novel inhibitors of NHEJ with higher efficacy and potential, which can be developed as cancer therapeutics.

Norwegian Development Aid: A Paradigm Shift in the Making?

Norway has remained committed to allocating one percent of its Gross National Income in developing aid. Poverty reduction has also stayed as an overarching objective for the aid budget. The commitment to these traditional pillars in Norwegian aid is also accompanied by major changes: reduced focus on partner countries and bilateral aid and an expanding emphasis on supporting global action, the rise of a flourishing number of new thematic priorities and delivery through multilateral channels. This article maps the evolving continuities and changes in Norwegian development aid since the early 1990s. It relies on an analytical framework based on Peter Halls work on paradigm shifts and his distinction between first, second and third order changes. The explanation for the evolving profile of Norwegian aid is found in a combination of domestic driving forces. Based on Matthew Wood’s concepts of puzzling and powering dynamics behind paradigm shifts the article identifies the forces behind evolving aid policies. One is depolitisation behind Norwegian aid – a broad political and popular support and consensus but limited debate leaving much space for foreign policy and self-interest to shape implementation and selection of instruments. A second is linked to a change in the policy arena and the growing dominance of the Ministry of Foreign Affairs. This has led to a multifaceted and fragmented aid profile allowing various dimensions of development aid policies to be shaped by different interests and priorities. It has not yet reached a stage where we can identify a major break with the past and a radical policy transformation. The new focus on climate issues and migration may have the potential to change that and give self-interests a stronger influence over long-term development aid and its objectives. Changes in coalition politics may have the potential to change the majority behind the one percent target and the commitment to poverty reduction.

Using advanced metering infrastructure data to evaluate consumer compliance with water advisories during a water service interruption

Water main breaks disrupt services provided by utilities and result in Water Service Interruptions (WSIs). Water utilities can manage WSIs through water advisories, which request that consumers limit their water use. The performance of water advisories depends on consumer compliance and decisions to conserve water. This research explores customer compliance with water advisories using water consumption data collected through Advanced Metering Infrastructure (AMI). AMI provides high temporal and spatial resolution of water consumption data, which is analyzed to identify changes in water use behaviors. This research explores water use changes during a major water main break in Orange County, North Carolina, that caused a significant WSI, limiting water supply for more than 80,000 people. Customers were asked to reduce water use to essential purposes only and to boil water over the course of two days in November 2018. This research analyzes hourly consumption data to evaluate water consumption trends during the WSI and in response to water advisories. Statistical analysis is used to estimate the number of consumers who complied with utility notifications and to evaluate the volume of water saved. Regression analysis is applied to explore compliance across different user segments. Results provide insight about the level and variation of water conservation that can be expected during a WSI.

The Rise of Native Lordships at Pashash, a.d. 200–600, North Highlands of Ancash, Peru

ABSTRACT This article examines the rise of native, segmentary lordships in the highlands of north-central Peru. It reports on new excavations and mapping at the seat of a prehispanic polity, Pashash (Recuay culture), a large hilltop center that developed after the collapse of Chavín civilization. Fieldwork revealed monumental constructions and two special activity contexts radiocarbon-dated to ca. a.d. 200–400: an offering area in a large palatial compound and a room-complex with chambers closed off and sealed with feasting refuse. Multiple lines of evidence help reconstruct a regional picture for the establishment of wealthy local elites. Cultural innovations explicitly link new leaders to roles in defense and warfare, economic production, and early burial cult within a high-status compound. The current data underscore a major break from earlier systems of authority and elite material culture, comprising an organizational pattern that was a precursor to the ethnic polities that predominated in later Andean prehistory.

Beta HPV Deregulates Double-Strand Break Repair.

Beta human papillomavirus (beta HPV) infections are common in adults. Certain types of beta HPVs are associated with nonmelanoma skin cancer (NMSC) in immunocompromised individuals. However, whether beta HPV infections promote NMSC in the immunocompetent population is unclear. They have been hypothesized to increase genomic instability stemming from ultraviolet light exposure by disrupting DNA damage responses. Implicit in this hypothesis is that the virus encodes one or more proteins that impair DNA repair signaling. Fluorescence-based reporters, next-generation sequencing, and animal models have been used to test this primarily in cells expressing beta HPV E6/E7. Of the two, beta HPV E6 appears to have the greatest ability to increase UV mutagenesis, by attenuating two major double-strand break (DSB) repair pathways, homologous recombination, and non-homologous end-joining. Here, we review this dysregulation of DSB repair and emerging approaches that can be used to further these efforts.

An Uncertain Future for EU-Level Collective Bargaining: The New Rules of the Game After EPSU

Abstract The General Court of the European Union (GCEU) in EPSU and Goudriaan vs. Commission and the Court of Justice of the European Union (CJEU) in the subsequent appeal judgment reached an identical conclusion on a key aspect of the system of EU level collective bargaining. The Courts held that Article 155(2) of the Treaty on the Functioning of the European Union (TFEU) does not impose any obligation on the European Commission to send a social partner agreement to the Council. This is in line with the Commission’s recent interpretation of Article 155(2) TFEU that subordinates the implementation of the European agreements to a positive assessment of their appropriateness. This article critically assesses the GCEU and CJEU rulings in EPSU and argues that they confirm a major break with the praxis of European collective bargaining that will have negative consequences for the social partners’ autonomy and role in the EU. In order to better understand this break, the article examines how and when the Commission changed its approach to European social dialogue, resulting in the new interpretation of Article 155(2) TFEU, and proposes a hypothesis to understand why. The article concludes by describing the consequences of the new reading of Article 155(2) TFEU for the idea of collective autonomy in EU law as well as for the practice of EU level social dialogue and collective bargaining.

An unproblematized truth: Foucault, biopolitics, and the making of a sociological canon

Foucault’s argument that a major break occurred in the nature of power in the European Eighteenth century—an unprecedented socialization of medicine and concern for the health of bodies and populations, the birth of biopolitics—has become since the 1990s a dominant narrative among sociologists but is rarely if ever scrutinized in its premises. This article problematizes Foucault’s periodization about the politics of health and the way its story has been solidified into an uncritical account. Building on novel historiographic work, it challenges the modernist bias of histories of biopolitics and public health and considers an earlier and more plural history of collective practices of health of which the story told by Foucault is just one important episode. Finally, it discusses the implications of this revised model for wider sociological debates on the link between modernity, health and the body.