Multiregional Emergence of Mobile Pastoralism and Nonuniform Institutional Complexity across Eurasia

In this article I present a new archaeological synthesis concerning the earliest formation of mobile pastoralist economies across central Eurasia. I argue that Eurasian steppe pastoralism developed along distinct local trajectories in the western, central, and (south)eastern steppe, sparking the development of regional networks of interaction in the late fourth and third millennia BC. The “Inner Asian Mountain Corridor” exemplifies the relationship between such incipient regional networks and the process of economic change in the eastern steppe territory. The diverse regional innovations, technologies, and ideologies evident across Eurasia in the mid-third millennium BC are cast as the building blocks of a unique political economy shaped by “nonuniform” institutional alignments among steppe populations throughout the second millennium BC. This theoretical model illustrates how regional channels of interaction between distinct societies positioned Eurasian mobile pastoralists as key players in wide-scale institutional developments among traditionally conceived “core” civilizations while also enabling them to remain strategically independent and small-scale in terms of their own sociopolitical organization. The development of nonuniform institutional complexity among Eurasian pastoralists demonstrates a unique political and economic structure applicable to societies whose variable political and territorial scales are inconsistent with commonly understood evolutionary or corporate sociopolitical typologies such as chiefdoms, states, or empires

An Inverse Agonist Ligand of the PTH Receptor Partially Rescues Skeletal Defects in a Mouse Model of Jansen’s Metaphyseal Chondrodysplasia

Jansen’s metaphyseal chondrodysplasia (JMC) is a rare disease of bone and mineral ion physiology that is caused by activating mutations in PTHR1. Ligand‐independent signaling by the mutant receptors in cells of bone and kidney results in abnormal skeletal growth, excessive bone turnover, and chronic hypercalcemia and hyperphosphaturia. Clinical features further include short stature, limb deformities, nephrocalcinosis, and progressive losses in kidney function. There is no effective treatment option available for JMC. In previous cell‐based assays, we found that certain N‐terminally truncated PTH and PTHrP antagonist peptides function as inverse agonists and thus can reduce the high rates of basal cAMP signaling exhibited by the mutant PTHR1s of JMC in vitro. Here we explored whether one such inverse agonist ligand, [Leu11,dTrp12,Trp23,Tyr36]‐PTHrP(7‐36)NH2 (IA), can be effective in vivo and thus ameliorate the skeletal abnormalities that occur in transgenic mice expressing the PTHR1‐H223R allele of JMC in osteoblastic cells via the collagen‐1α1 promoter (C1HR mice). We observed that after 2 weeks of twice‐daily injection and relative to vehicle controls, the IA analog resulted in significant improvements in key skeletal parameters that characterize the C1HR mice, because it reduced the excess trabecular bone mass, bone marrow fibrosis, and levels of bone turnover markers in blood and urine. The overall findings provide proof‐of‐concept support for the notion that inverse agonist ligands targeted to the mutant PTHR1 variants of JMC can have efficacy in vivo. Further studies of such PTHR1 ligand analogs could help open paths toward the first treatment option for this debilitating skeletal disorder. © 2019 American Society for Bone and Mineral Research.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154322/1/jbmr3913-sup-0001-Supinfo.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154322/2/jbmr3913.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154322/3/jbmr3913_am.pd

Condensin I Recruitment to Base Damage-Enriched DNA Lesions Is Modulated by PARP1

Condensin I is important for chromosome organization and segregation in mitosis. We previously showed that condensin I also interacts with PARP1 in response to DNA damage and plays a role in single-strand break repair. However, whether condensin I physically associates with DNA damage sites and how PARP1 may contribute to this process were unclear. We found that condensin I is preferentially recruited to DNA damage sites enriched for base damage. This process is dictated by PARP1 through its interaction with the chromosome-targeting domain of the hCAP-D2 subunit of condensin I

The Hominin Sites and Paleolakes Drilling Project:High-Resolution Paleoclimate Records from the East African Rift System and Their Implications for Understanding the Environmental Context of Hominin Evolution

The possibility of a causal relationship between Earth history processes and hominin evolution in Africa has been the subject of intensive paleoanthropological research for the last 25 years. One fundamental question is: can any geohistorical processes, in particular, climatic ones, be characterized with sufficient precision to enable temporal correlation with events in hominin evolution and provide support for a possible causal mechanism for evolutionary changes? Previous attempts to link paleoclimate and hominin evolution have centered on evidence from the outcrops where the hominin fossils are found, as understanding whether and how hominin populations responded to habitat change must be examined at the local basinal scale. However, these outcrop records typically provide incomplete, low-resolution climate and environmental histories, and surface weathering often precludes the application of highly sensitive, state-of-the-art paleoenvironmental methods. Continuous and well-preserved deep-sea drill core records have provided an alternative approach to reconstructing the context of hominin evolution, but have been collected at great distances from hominin sites and typically integrate information over vast spatial scales. The goal of the Hominin Sites and Paleolakes Drilling Project (HSPDP) is to analyze climate and other Earth system dynamics using detailed paleoenvironmental data acquired through scientific drilling of lacustrine depocenters at or near six key paleoanthropological sites in Kenya and Ethiopia. This review provides an overview of a unique collaboration of paleoanthropologists and earth scientists who have joined together to explicitly explore key hypotheses linking environmental history and mammalian (including hominin) evolution and potentially develop new testable hypotheses. With a focus on continuous, high-resolution proxies at timescales relevant to both biological and cultural evolution, the HSPDP aims to dramatically expand our understanding of the environmental history of eastern Africa during a significant portion of the Late Neogene and Quaternary, and to generate useful models of long-term environmental dynamics in the regionpublishersversionPeer reviewe

A Surprising Prevention Success: Why Did the HIV Epidemic Decline in Zimbabwe?

Daniel Halperin and colleagues examine reasons for the remarkable decline in HIV in Zimbabwe, in the context of severe social, political, and economic disruption

Affected Experiencers

Numerous languages permit an NP that is not selected by the verb to be added to a clause, with several different possible interpretations. We divide such non-selected arguments into possessor, benefactive, attitude holder, and affected experiencer categories, on the basis of syntactic and semantic differences between them. We propose a formal analysis of the affected experiencer construction. In our account, a syntactic head Aff(ect) introduces the experiencer argument, and adds a conventional implicature to the effect that any event of the type denoted by its syntactic sister is the source of the experiencer’s psychological experience. Hence, our proposal involves two tiers of meaning: the at-issue meaning of the sentence, and some not-at-issue meaning (an implicature). A syntactic head can introduce material on both tiers. Additionally, we allow two parameters of variation: (i) the height of the attachment of Aff, and (ii) how much of the semantics is at-issue and how much is an implicature. We show that these two parameters account for the attested variation across our sample of languages, as well as the significant commonalities among them. Our analysis also accounts for significant differences between affected experiencers and the other types of non-selected arguments, and we also note a generalization to the effect that purely not-at-issue non-selected arguments can only be weak or clitic pronouns

Using ecological and field survey data to establish a national list of the wild bee pollinators of crops

The importance of wild bees for crop pollination is well established, but less is known about which species contribute to service delivery to inform agricultural management, monitoring and conservation. Using sites in Great Britain as a case study, we use a novel qualitative approach combining ecological information and field survey data to establish a national list of crop pollinating bees for four economically important crops (apple, field bean, oilseed rape and strawberry). A traits data base was used to establish potential pollinators, and combined with field data to identify both dominant crop flower visiting bee species and other species that could be important crop pollinators, but which are not presently sampled in large numbers on crops flowers. Whilst we found evidence that a small number of common, generalist species make a disproportionate contribution to flower visits, many more species were identified as potential pollinators, including rare and specialist species. Furthermore, we found evidence of substantial variation in the bee communities of different crops. Establishing a national list of crop pollinators is important for practitioners and policy makers, allowing targeted management approaches for improved ecosystem services, conservation and species monitoring. Data can be used to make recommendations about how pollinator diversity could be promoted in agricultural landscapes. Our results suggest agri-environment schemes need to support a higher diversity of species than at present, notably of solitary bees. Management would also benefit from targeting specific species to enhance crop pollination services to particular crops. Whilst our study is focused upon Great Britain, our methodology can easily be applied to other countries, crops and groups of pollinating insects.LH was funded by NERC QMEE CDT. EJB was funded by a BBSRC Ph.D. studentship under grant BB/F016581/1. LB was was supported by the Scholarship Program of the German Federal Environmental Foundation (Deutsche Bundesstiftung Umwelt, DBU, AZ 20014/302). AJC was funded by the BBSRC and Syngenta UK as part of a case award Ph.D. (grant no. 1518739). AE was funded by the Swiss National Science Foundation (grant number 405940-115642). DG and A-MK were funded by grant PCIN2014-145-C02-02 (MinECo; EcoFruit project BiodivERsA-FACCE2014-74). MG was supported by Establishing a UK Pollinator Monitoring and Research Partnership (PMRP) a collaborative project funded by Defra, the Welsh and Scottish Governments, JNCC and project partners’. GAdG was funded via research projects BO-11-011.01-051 and BO-43-011.06-007, commissioned by the Dutch Ministry of Agriculture, Nature and Food Quality. DK was funded by the Dutch Ministry of Economic Affairs (BO-11-011.01-011). AK-H was funded by the NKFIH project (FK123813), the Bolyai János Fellowship of the MTA, the ÚNKP-19-4-SZIE-3 New National Excellence Program of the Ministry for Innovation and Technology, and together with RF by the Hungarian Scientific Research Fund OTKA 101940. MM was funded by Waitrose & Partners, Fruition PO, and the University of Worcester. MM was funded by grant INIA-RTA2013-00139-C03-01 (MinECo and FEDER). BBP and RFS were funded by the UK Natural Environment Research Council as part of Wessex BESS (ref. NE/J014680/1). NJV was funded by the Walloon Region (Belgium) Direction générale opérationnelle de l’Agriculture, des Ressources naturelles et de l’Environnement (DGO3) for the "Modèle permaculturel" project on biodiversity in micro-farms, FNRS/FWO joint programme EOS — Excellence Of Science CliPS: Climate change and its impact on Pollination Services (project 30947854)". CW was funded by the Deutsche Forschungsgemeinschaft (DFG) (Project number 405945293). BW was funded by the Natural Environment Research Council (NERC) under research programme NE/N018125/1 ASSIST – Achieving Sustainable Agricultural Systems www.assist.ceh.ac.uk. TB and TO are supported by BBSRC, NERC, ESRC and the Scottish Government under the Global Food Security Programme (Grant BB/R00580X/1)

Allosteric Regulation of Fibronectin/α5β1 Interaction by Fibronectin-Binding MSCRAMMs

Citation: Liang, X. W., Garcia, B. L., Visai, L., Prabhakaran, S., Meenan, N. A. G., Potts, J. R., . . . Hook, M. (2016). Allosteric Regulation of Fibronectin/alpha(5)beta(1) Interaction by Fibronectin-Binding MSCRAMMs. Plos One, 11(7), 17. doi:10.1371/journal.pone.0159118Adherence ofmicrobes to host tissues is a hallmark of infectious disease and is often mediated by a class of adhesins termed MSCRAMMs (Microbial Surface Components Recognizing Adhesive Matrix Molecules). Numerous pathogens express MSCRAMMs that specifically bind the heterodimeric human glycoprotein fibronectin (Fn). In addition to roles in adhesion, Fn-binding MSCRAMMs exploit physiological Fn functions. For example, several pathogens can invade host cells by a mechanism whereby MSCRAMM-bound Fn bridges interaction with alpha(5)beta(1) integrin. Here, we investigate two Fn-binding MSCRAMMs, FnBPA (Staphylococcus aureus) and BBK32 (Borrelia burgdorferi) to probe structure-activity relationships of MSCRAMM-induced Fn/alpha(5)beta(1) integrin activation. Circular dichroism, fluorescence resonance energy transfer, and dynamic light scattering techniques uncover a conformational rearrangement of Fn involving domains distant from the MSCRAMM binding site. Surface plasmon resonance experiments demonstrate a significant enhancement of Fn/alpha(5)beta(1) integrin affinity in the presence of FnBPA or BBK32. Detailed kinetic analysis of these interactions reveal that this change in affinity can be attributed solely to an increase in the initial Fn/alpha(5)beta(1) on-rate and that this rate-enhancement is dependent on high-affinity Fn-binding by MSCRAMMs. These data implicate MSCRAMM-induced perturbation of specific intramolecular contacts within the Fn heterodimer resulting in activation by exposing previously cryptic alpha(5)beta(1) interaction motifs. By correlating structural changes in Fn to a direct measurement of increased Fn/alpha(5)beta(1) affinity, this work significantly advances our understanding of the structural basis for the modulation of integrin function by Fn-binding MSCRAMMs