A sea of change has occurred in China since the 1978 economic reforms. Bringing together the work of leading scholars specializing in urban China, this book examines what has happened to the Chinese ...city undergoing multiple transformations during the reform era, with an emphasis on new processes of urban formation and the consequent reconstituted urban spaces. With arguments against the convergence thesis that sees cities everywhere becoming more Western in form and suggestions that the Chinese city is best seen as a multiplex city, Restructuring the Chinese City is an indispensable text for Chinese specialists, urban scholars and advanced students in urban geography, urban planning and China studies.
Summary Background Western Cambodia is the epicentre of Plasmodium falciparum multidrug resistance and is facing high rates of dihydroartemisinin–piperaquine treatment failures. Genetic tools to ...detect the multidrug-resistant parasites are needed. Artemisinin resistance can be tracked using the K13 molecular marker, but no marker exists for piperaquine resistance. We aimed to identify genetic markers of piperaquine resistance and study their association with dihydroartemisinin–piperaquine treatment failures. Methods We obtained blood samples from Cambodian patients infected with P falciparum and treated with dihydroartemisinin–piperaquine. Patients were followed up for 42 days during the years 2009–15. We established in-vitro and ex-vivo susceptibility profiles for a subset using piperaquine survival assays. We determined whole-genome sequences by Illumina paired-reads sequencing, copy number variations by qPCR, RNA concentrations by qRT-PCR, and protein concentrations by immunoblotting. Fisher’s exact and non-parametric Wilcoxon rank-sum tests were used to identify significant differences in single-nucleotide polymorphisms or copy number variants, respectively, for differential distribution between piperaquine-resistant and piperaquine-sensitive parasite lines. Findings Whole-genome exon sequence analysis of 31 culture-adapted parasite lines associated amplification of the plasmepsin 2 –plasmepsin 3 gene cluster with in-vitro piperaquine resistance. Ex-vivo piperaquine survival assay profiles of 134 isolates correlated with plasmepsin 2 gene copy number. In 725 patients treated with dihydroartemisinin–piperaquine, multicopy plasmepsin 2 in the sample collected before treatment was associated with an adjusted hazard ratio (aHR) for treatment failure of 20·4 (95% CI 9·1–45·5, p<0·0001). Multicopy plasmepsin 2 predicted dihydroartemisinin–piperaquine failures with 0·94 (95% CI 0·88–0·98) sensitivity and 0·77 (0·74–0·81) specificity. Analysis of samples collected across the country from 2002 to 2015 showed that the geographical and temporal increase of the proportion of multicopy plasmepsin 2 parasites was highly correlated with increasing dihydroartemisinin–piperaquine treatment failure rates (r=0·89 95% CI 0·77–0·95, p<0·0001, Spearman’s coefficient of rank correlation). Dihydroartemisinin–piperaquine efficacy at day 42 fell below 90% when the proportion of multicopy plasmepsin 2 parasites exceeded 22%. Interpretation Piperaquine resistance in Cambodia is strongly associated with amplification of plasmepsin 2–3 , encoding haemoglobin-digesting proteases, regardless of the location. Multicopy plasmepsin 2 constitutes a surrogate molecular marker to track piperaquine resistance. A molecular toolkit combining plasmepsin 2 with K13 and mdr1 monitoring should provide timely information for antimalarial treatment and containment policies. Funding Institut Pasteur in Cambodia, Institut Pasteur Paris, National Institutes of Health, WHO, Agence Nationale de la Recherche, Investissement d’Avenir programme, Laboratoire d’Excellence Integrative “Biology of Emerging Infectious Diseases”.
Plasmodium falciparum resistance to artemisinin derivatives in southeast Asia threatens malaria control and elimination activities worldwide. To monitor the spread of artemisinin resistance, a ...molecular marker is urgently needed. Here, using whole-genome sequencing of an artemisinin-resistant parasite line from Africa and clinical parasite isolates from Cambodia, we associate mutations in the PF3D7_1343700 kelch propeller domain ('K13-propeller') with artemisinin resistance in vitro and in vivo. Mutant K13-propeller alleles cluster in Cambodian provinces where resistance is prevalent, and the increasing frequency of a dominant mutant K13-propeller allele correlates with the recent spread of resistance in western Cambodia. Strong correlations between the presence of a mutant allele, in vitro parasite survival rates and in vivo parasite clearance rates indicate that K13-propeller mutations are important determinants of artemisinin resistance. K13-propeller polymorphism constitutes a useful molecular marker for large-scale surveillance efforts to contain artemisinin resistance in the Greater Mekong Subregion and prevent its global spread.
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DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
► We examine the city-making of Hebi, a medium-sized Chinese city. ► We conceptualize the process as a so-called ‘administrative urbanization’. ► The role of the local state in the production and ...development of the new urban space is direct and forceful. ► City people are not fully considered, and it is unclear who the major beneficiaries are.
China’s rapid growth over the last three decades has attracted much academic attention. In the post-reform era, economic growth has been paralleled by rapid urbanization. China’s urbanization experience has been shaped heavily by the state through national urban policies as well as through local administrative means. Much has been written about large Chinese cities in the more developed coastal regions, such as Beijing, Shanghai and Guangzhou, but little is known about the process of city-making in medium-sized and small Chinese cities, especially those in the less developed central and western regions of the country. This paper sheds light on the processes of urban transformation in Hebi, a medium-sized inland city in Henan Province, emphasizing the critical role that the local state has played in city-making, the mechanisms and processes of change, and the resultant impacts on the city. As a mining city, Hebi has been threatened by depleting natural resources. To invigorate the city, a new city center has been built to attract new enterprises. Through intensive interviews and fieldwork conducted in 2007 and 2008, we examine what the city government of Hebi has done to turn the newly constructed urban space into a new administrative and economic center of the city. With the establishment of new enterprises, the local economy has been diversified, although coal continues to be a major component of Hebi’s economy. The role of the local state in the production and development of the new urban space is direct and forceful. As local state policies on urban development have been implemented by strong administrative means, we conceptualize the contemporary Chinese model of urbanization as “administrative urbanization”. One problem with this kind of state-dominated urbanization and city-making is that the needs of the people are not fully considered, and it is unclear who the major beneficiaries are. More case studies are needed to determine how economic and political forces are driving China’s land-based urban development, the extent to which local states are understood as entrepreneurial, profit-seeking and pro-growth, the relationship between the local state and other stake-holders in local urban development, and who has benefited from administrative urbanization.
Through a review of the literature, the author identifies the achievements as well as the deficiencies in the study of China's urbanization and urbanism in the second half of the 20th century. A ...number of issues that merit scholarly research are suggested and the need for theorization is emphasized. During the last half century, Chinese cities underwent dramatic transformations as a consequence of two major systemic changes. During the first three decades after the socialist revolution of 1949, sustained low levels of urbanization and a brief episode of antiurbanism accompanied centralized planning and city-based industrialization. Since the economic reforms of 1978 Chinese cities have witnessed major economic and spatial shifts away from the socialist patterns. Among the many facets of urban transformation since 1978 are a more heterogeneous urban population, rural - urban migration, spatial reorganization through urban land-use change, new housing development, globalization, suburbanization, polycentric restructuring of urban form, and changes in the spatial/administrative systems of cities. It is argued that, as the Chinese economy is inherently political, political economy perspectives should be foregrounded to enrich our understanding of the complexity of China's economic and urban transformation. In this regard, the continuously powerful and multiple roles of the Party-state as the ultimate decisionmaker, regulator, and participant in the urban economy should be emphasized, despite globalization and decentralization of administrative and fiscal powers from the central to local levels. The Chinese trajectory of urban development is seen as more different from than similar to the experiences of other economies undergoing structural change away from socialism, and context-based country-specific theorization of urban change is called for. More general theories of urban transformation which are applicable to a number of former socialist nations, and which transcend the idiosyncrasies of individual countries, should be developed where possible. A closer engagement among scholars working on the urban development of China and those working on other former socialist countries is necessary if 'the socialist city' is to become a firm typology of cities.
Elucidating population structure and levels of genetic diversity and recombination is necessary to understand the evolution and adaptation of species. Candida albicans is the second most frequent ...agent of human fungal infections worldwide, causing high-mortality rates. Here we present the genomic sequences of 182 C. albicans isolates collected worldwide, including commensal isolates, as well as ones responsible for superficial and invasive infections, constituting the largest dataset to date for this major fungal pathogen. Although, C. albicans shows a predominantly clonal population structure, we find evidence of gene flow between previously known and newly identified genetic clusters, supporting the occurrence of (para)sexuality in nature. A highly clonal lineage, which experimentally shows reduced fitness, has undergone pseudogenization in genes required for virulence and morphogenesis, which may explain its niche restriction. Candida albicans thus takes advantage of both clonality and gene flow to diversify.
The paper, by three geographers, including a noted U.S.-based senior specialist on China's urban and human realm, presents the first known academic study of the country's African migrants. The ...authors examine the emergence of a new African community (primarily traders from West Africa) in the Xiaobei urban district of Guangzhou City, arguing that Xiaobei is not only a space for transacting transnational business but also a place of sojourn where African migrants struggle to make a living without local integration or assimilation. As a "non-state" gateway for burgeoning economic linkages between China and Africa, Xiaobei's spontaneous place-making is strengthened by the aspiring efforts of local entrepreneurs, at the same time that this new transnational space is challenged by an invisible wall between Africans and local residents due to cultural and social differences. The paper notes the impacts of globalization, which appears to be adding a new dimension (ethnicity) to the pattern of residential segregation of Chinese cities. Empirical evidence is provided by a series of surveys conducted by the authors since 2006 and particularly three in 2008. Journal of Economic Literature, Classification Numbers: F220, F230, J150, J610, O180. 5 figures, 2 tables, 81 references.
Horizontal gene transfer (HGT) is a major driving force of bacterial diversification and evolution. For tuberculosis-causing mycobacteria, the impact of HGT in the emergence and distribution of ...dominant lineages remains a matter of debate. Here, by using fluorescence-assisted mating assays and whole genome sequencing, we present unique experimental evidence of chromosomal DNA transfer between tubercle bacilli of the early-branching Mycobacterium canettii clade. We found that the obtained recombinants had received multiple donor-derived DNA fragments in the size range of 100 bp to 118 kbp, fragments large enough to contain whole operons. Although the transfer frequency between M. canettii strains was low and no transfer could be observed among classical Mycobacterium tuberculosis complex (MTBC) strains, our study provides the proof of concept for genetic exchange in tubercle bacilli. This outstanding, now experimentally validated phenomenon presumably played a key role in the early evolution of the MTBC toward pathogenicity. Moreover, our findings also provide important information for the risk evaluation of potential transfer of drug resistance and fitness mutations among clinically relevant mycobacterial strains.
Nonsense-mediated mRNA decay (NMD) is a translation-dependent RNA quality-control pathway targeting transcripts such as messenger RNAs harboring premature stop-codons or short upstream open reading ...frame (uORFs). Our transcription start sites (TSSs) analysis of Saccharomyces cerevisiae cells deficient for RNA degradation pathways revealed that about half of the pervasive transcripts are degraded by NMD, which provides a fail-safe mechanism to remove spurious transcripts that escaped degradation in the nucleus. Moreover, we found that the low specificity of RNA polymerase II TSSs selection generates, for 47% of the expressed genes, NMD-sensitive transcript isoforms carrying uORFs or starting downstream of the ATG START codon. Despite the low abundance of this last category of isoforms, their presence seems to constrain genomic sequences, as suggested by the significant bias against in-frame ATGs specifically found at the beginning of the corresponding genes and reflected by a depletion of methionines in the N-terminus of the encoded proteins.
Mycobacterium tuberculosis (Mtb) strains are classified into different phylogenetic lineages (L), three of which (L2/L3/L4) emerged from a common progenitor after the loss of the MmpS6/MmpL6-encoding ...Mtb-specific deletion 1 region (TbD1). These TbD1-deleted "modern" lineages are responsible for globally-spread tuberculosis epidemics, whereas TbD1-intact "ancestral" lineages tend to be restricted to specific geographical areas, such as South India and South East Asia (L1) or East Africa (L7). By constructing and characterizing a panel of recombinant TbD1-knock-in and knock-out strains and comparison with clinical isolates, here we show that deletion of TbD1 confers to Mtb a significant increase in resistance to oxidative stress and hypoxia, which correlates with enhanced virulence in selected cellular, guinea pig and C3HeB/FeJ mouse infection models, the latter two mirroring in part the development of hypoxic granulomas in human disease progression. Our results suggest that loss of TbD1 at the origin of the L2/L3/L4 Mtb lineages was a key driver for their global epidemic spread and outstanding evolutionary success.
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