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Urban ponds in India have for a long time been used for multiple purposes and have been accessible to a wide range of social groups; they thus often represent an urban commons. However, recent transformations of urban ponds into infrastructure that serves more limited uses have been accompanied by enclosure and social exclusion. Using an urban political ecology approach that is enriched with the concepts of environmental imaginaries and (un)commoning, this paper examines the ideational foundations and societal mechanisms underpinning the transformation of the pondscape of Navsari, a small city in the state of Gujarat. Based on interviews and field observations, the study found that the small-town elite’s imaginary of the 'modern city' underpinned the shift to the ponds becoming part of Navsari’s drinking water infrastructure; this led to the enclosure of the ponds and thus the ideational and physical separation of residents from these waterbodies and the exclusion of traditional user groups. This socio-ecological transformation of the pondscape, however, was not characterised by simple, linear processes of uncommoning driven by local elites: the dismantling of the urban commons (in the form of waste dumping by multiple actors) largely preceded the creation of infrastructure; enclosures and exclusions remained imperfect and spatially variable; and in some places informal resource-use rules continued or were recreated by local communities. This research points to how important it is for urban political ecology to consider the imaginaries and practices of multiple actors – including those beyond the metropolitan areas – in the construction of a nuanced narrative of dispossession in the neoliberal city.

This special issue of SAMAJ, composed of six empirical papers and this introduction seeks to throw light on environmental politics in contemporary urban India. Adopting a deliberately broad understanding of the environment, to include environmental amenities, urban natural resources and the built environment, the diverse case studies within this issue contribute to an interlinked set of discussions on the politicization of India’s urban environment. In doing so they engage with the ways that the environment is entwined with questions of urban citizenship; the role environmental knowledge(s) play(s) in urban environmental politics; and the situated character of urban political ecologies. While these papers employ diverse entry points into the environmental politics of Leh, Puri, Chennai, Bangalore and Delhi they all pay close attention to everyday practices and situated dynamics. As this perspective is applied across various city sizes the results demonstrate on the one hand the heterogeneity of India’s urban environments and on the other the pervasiveness of similar environmental politics across diverse sites. The insights from these papers aptly highlight the analytical challenge of considering issues of temporality and intersectionality whilst also recognizing the multi-scalar political-economic and social factors that shape contemporary urban power dynamics and the reproduction of particular urban environments.

Early treatment with rt-PA is critical for favorable outcome of acute stroke. However, only a very small proportion of stroke patients receive this treatment, as most arrive at hospital too late to be eligible for rt-PA therapy.We developed a "Mobile Stroke Unit", consisting of an ambulance equipped with computed tomography, a point-of-care laboratory system for complete stroke laboratory work-up, and telemedicine capabilities for contact with hospital experts, to achieve delivery of etiology-specific and guideline-adherent stroke treatment at the site of the emergency, well before arrival at the hospital. In a departure from current practice, stroke patients could be differentially treated according to their ischemic or hemorrhagic etiology even in the prehospital phase of stroke management. Immediate diagnosis of cerebral ischemia and exclusion of thrombolysis contraindications enabled us to perform prehospital rt-PA thrombolysis as bridging to later intra-arterial recanalization in one patient. In a complementary patient with cerebral hemorrhage, prehospital diagnosis allowed immediate initiation of hemorrhage-specific blood pressure management and telemedicine consultation regarding surgery. Call-to-therapy-decision times were 35 minutes.This preliminary study proves the feasibility of guideline-adherent, etiology-specific and causal treatment of acute stroke directly at the emergency site.

Abstract Microbes are increasingly employed as cell factories to produce biomolecules. This often involves the expression of complex heterologous biosynthesis pathways in host strains. Achieving maximal product yields and avoiding build-up of (toxic) intermediates requires balanced expression of every pathway gene. However, despite progress in metabolic modeling, the optimization of gene expression still heavily relies on trial-and-error. Here, we report an approach for in vivo, multiplexed Gene Expression Modification by LoxPsym-Cre Recombination (GEMbLeR). GEMbLeR exploits orthogonal LoxPsym sites to independently shuffle promoter and terminator modules at distinct genomic loci. This approach facilitates creation of large strain libraries, in which expression of every pathway gene ranges over 120-fold and each strain harbors a unique expression profile. When applied to the biosynthetic pathway of astaxanthin, an industrially relevant antioxidant, a single round of GEMbLeR improved pathway flux and doubled production titers. Together, this shows that GEMbLeR allows rapid and efficient gene expression optimization in heterologous biosynthetic pathways, offering possibilities for enhancing the performance of microbial cell factories.

Abstract Site-specific recombinases such as the Cre-LoxP system are routinely used for genome engineering in both prokaryotes and eukaryotes. Importantly, recombinases complement the CRISPR-Cas toolbox and provide the additional benefit of high-efficiency DNA editing without generating toxic DNA double-strand breaks, allowing multiple recombination events at the same time. However, only a handful of independent, orthogonal recombination systems are available, limiting their use in more complex applications that require multiple specific recombination events, such as metabolic engineering and genetic circuits. To address this shortcoming, we develop 63 symmetrical LoxP variants and test 1192 pairwise combinations to determine their cross-reactivity and specificity upon Cre activation. Ultimately, we establish a set of 16 orthogonal LoxPsym variants and demonstrate their use for multiplexed genome engineering in both prokaryotes (E. coli) and eukaryotes (S. cerevisiae and Z. mays). Together, this work yields a significant expansion of the Cre-LoxP toolbox for genome editing, metabolic engineering and other controlled recombination events, and provides insights into the Cre-LoxP recombination process.

Purpose: Fusarium keratitis is a severe infection of the anterior eye, frequently leading to keratoplasty or surgical removal of the affected eye. A major risk factor for infection is the use of contact lenses. Inadequate hygiene precautions and mold-growth permissive storage fluids are important risk factors for fungal keratitis. The aim of this study was to comparatively analyze contact lens storage fluids disinfection efficacy against Fusarium species. Methods: Eleven commercially available storage fluids were tested. The storage fluids were classified according to their active ingredients myristamidopropyldimethylamine (Aldox), polyhexanide and hydrogen peroxide. Efficacy was tested against isolates belonging to the Fusarium solani and Fusarium oxysporum species complexes as the most common agents of mould keratitis. Tests were carried out based on DIN EN ISO 14729. Results: All Aldox and hydrogen peroxide (H2O2) based fluids were effective against Fusarium spp., while the majority of polyhexanide based storage fluids showed only limited or no antifungal effects. Efficacy of polyhexanide could be restored by the addition of the pH-regulating agent tromethamine - an additive component in one commercially available product. Conclusions: In summary, the use of Aldox- or hydrogen peroxide-based storage fluids may reduce the risk of Fusarium keratitis, while polyhexanide-based agents largely lack efficacy against Fusarium.

Abstract The generation of genetic diversity via mutagenesis is routinely used for protein engineering and pathway optimization. Current technologies for random mutagenesis often target either the whole genome or relatively narrow windows. To bridge this gap, we developed CoMuTER (Confined Mutagenesis using a Type I-E CRISPR-Cas system), a tool that allows inducible and targetable, in vivo mutagenesis of genomic loci of up to 55 kilobases. CoMuTER employs the targetable helicase Cas3, signature enzyme of the class 1 type I-E CRISPR-Cas system, fused to a cytidine deaminase to unwind and mutate large stretches of DNA at once, including complete metabolic pathways. The tool increases the number of mutations in the target region 350-fold compared to the rest of the genome, with an average of 0.3 mutations per kilobase. We demonstrate the suitability of CoMuTER for pathway optimization by doubling the production of lycopene in Saccharomyces cerevisiae after a single round of mutagenesis.

Abstract This article examines the spatially varying effect of age on single-family house (SFH) prices. Age has been shown to be a key driver for house depreciation and is usually associated with a negative price effect. In practice, however, there exist deviations from this behavior which are referred to as vintage effects. We estimate a spatially varying coefficients (SVC) model to investigate the spatial structures of vintage effects on SFH pricing. For SFHs in the Canton of Zurich, Switzerland, we find substantial spatial variation in the age effect. In particular, we find a local, strong vintage effect primarily in urban areas compared to pure depreciative age effects in rural locations. Using cross validation, we assess the potential improvement in predictive performance by incorporating spatially varying vintage effects in hedonic models. We find a substantial improvement in out-of-sample predictive performance of SVC models over classical spatial hedonic models.

Background Previous studies identified factors influencing regulatory approval to introduction timelines for individual vaccines. However, introduction and uptake timelines have not been comprehensively assessed across the portfolio of Gavi-supported vaccines.Methods We analysed median times between introduction milestones from vaccine licensure to country introduction and uptake across six vaccine-preventable diseases (VPDs), three delivery platforms and 69 Gavi-supported countries. Data were gathered from public, partner and manufacturer records. VPDs and prequalified vaccines analysed included Haemophilus influenzae type b (DTwP-HepB-Hib, pentavalent), pneumococcal disease (pneumococcal conjugate vaccine, PCV), rotavirus diarrhoea (rotavirus vaccine, RVV), cervical cancer (human papillomavirus vaccine, HPV), polio (inactivated polio vaccine, IPV) and meningococcal meningitis (meningococcal group A conjugate vaccine, MenA).Results Median time from first vaccine licensure to first Gavi-supported country introduction across VPDs at a ‘global level’ (Gavi-supported countries) was 5.4 years. Once licensed, MenA vaccines reached first introduction fastest (campaign=0.6 years; routine immunisation (RI)=1.7 years). Most introductions were delayed. Country uptake following first introduction was accelerated for more recently Gavi-supported RI vaccines compared with older ones.Conclusion Factors accelerating timelines across delivery platforms included rapid product prequalifications by WHO, strong initial recommendations by the WHO Strategic Advisory Group of Experts (SAGE) on Immunization, achieving target product profiles on first vaccine licensure within a VPD and completing several VPD milestones at a global level prior to licensure. Milestones required for introduction in Gavi-supported countries should start prior or in parallel to licensure to accelerate uptake of vaccines delivered through diverse delivery platforms.

Spatial separation of the photosynthetic reactions is a key feature of C4 metabolism. In most C4 plants, this separation requires compartmentation of photosynthetic enzymes between mesophyll (M) and bundle sheath (BS) cells. The upstream region of the gene encoding the maize PHOSPHOENOLPYRUVATE CARBOXYLASE 1 (ZmPEPC1) has been shown sufficient to drive M-specific ZmPEPC1 gene expression. Although this region has been well characterized, to date, only few trans-factors involved in the ZmPEPC1 gene regulation were identified. Here, using a yeast one-hybrid approach, we have identified three novel maize transcription factors ZmHB87, ZmCPP8, and ZmOrphan94 as binding to the ZmPEPC1 upstream region. Bimolecular fluorescence complementation assays in maize M protoplasts unveiled that ZmOrphan94 forms homodimers and interacts with ZmCPP8 and with two other ZmPEPC1 regulators previously reported, ZmbHLH80 and ZmbHLH90. Trans-activation assays in maize M protoplasts unveiled that ZmHB87 does not have a clear transcriptional activity, whereas ZmCPP8 and ZmOrphan94 act as activator and repressor, respectively. Moreover, we observed that ZmOrphan94 reduces the trans-activation activity of both activators ZmCPP8 and ZmbHLH90. Using the electromobility shift assay, we showed that ZmOrphan94 binds to several cis-elements present in the ZmPEPC1 upstream region and one of these cis-elements overlaps with the ZmbHLH90 binding site. Gene expression analysis revealed that ZmOrphan94 is preferentially expressed in the BS cells, suggesting that ZmOrphan94 is part of a transcriptional regulatory network downregulating ZmPEPC1 transcript level in the BS cells. Based on both this and our previous work, we propose a model underpinning the importance of a regulatory mechanism within BS cells that contributes to the M-specific ZmPEPC1 gene expression.

Fungal eye infections can lead to loss of vision and blindness. The disease is most prevalent in the tropics, although case numbers in moderate climates are increasing as well. This study aimed to determine the dominating filamentous fungi causing eye infections in Germany and their antifungal susceptibility profiles in order to improve treatment, including cases with unidentified pathogenic fungi. As such, we studied all filamentous fungi isolated from the eye or associated materials that were sent to the NRZMyk between 2014 and 2020. All strains were molecularly identified and antifungal susceptibility testing according to the EUCAST protocol was performed for common species. In total, 242 strains of 66 species were received. Fusarium was the dominating genus, followed by Aspergillus, Purpureocillium, Alternaria, and Scedosporium. The most prevalent species in eye samples were Fusarium petroliphilum, F. keratoplasticum, and F. solani of the Fusarium solani species complex. The spectrum of species comprises less susceptible taxa for amphotericin B, natamycin, and azoles, including voriconazole. Natamycin is effective for most species but not for Aspergillus flavus or Purpureocillium spp. Some strains of F. solani show MICs higher than 16 mg/L. Our data underline the importance of species identification for correct treatment.

Background: In view of a shortage of health care costs, monetary aspects of psychotherapy become increasingly relevant. The present study examined the pre-post reduction of impairment and direct health care costs depending on therapy termination (regularly terminated, dropout with an unproblematic reason, and dropout with a quality-relevant reason) and the association of symptom and cost reduction.Methods: In a naturalistic longitudinal study, we examined a disorder heterogeneous sample of N = 584 outpatients who were either treated with cognitive-behavioral, psychodynamic, or psychoanalytic therapy. Depression, anxiety, stress, and somatization were assessed with the Patient Health Questionnaire (PHQ). Annual amounts of inpatient costs, outpatient costs, medication costs, days of hospitalization, work disability days, utilization of psychotherapy, and utilization of pharmacotherapy 1 year before therapy and 1 year after therapy were provided by health care insurances. Symptom and cost reduction were analyzed using t-tests. Associations between symptom and cost reduction were examined using partial correlations and hierarchical linear models.Results: Patients who terminated therapy regularly showed the largest symptom reduction (d = 0.981–1.22). Patients who dropped out due to an unproblematic reason and patients who terminated early due to a quality-relevant reason showed significant but small effects of symptom reductions (e.g., depression: d = 0.429 vs. d = 0.366). For patients with a regular end and those dropping out due to a quality-relevant reason, we observed a significant reduction of work disability (diff in % of pre-test value = 56.3 vs. 42.9%) and hospitalization days (52.8 vs. 35.0%). Annual inpatient costs decreased in the group with a regular therapy end (31.5%). Furthermore, reduction of symptoms on the one side and reduction of work disability days and psychotherapy utilization on the other side were significant correlated (r = 0.091–0.135).Conclusion: Health care costs and symptoms were reduced in each of the three groups. The average symptom and cost reduction of patients with a quality-relevant dropout suggested that not each dropout might be seen as therapy failure.

Objectives: Though sulfur dioxide (SO2) is used widely at workplaces, itseffects on humans are not known. Thresholds are report-edwithout reference to gender or age and occupational exposure limits are basedon effects on lung functioning,although localized effects in the upper airways can be expected.This study’s aim is to determine thresholds with respect to age and gender and suggests a new approach to risk assessment using breathing reflexes presumably triggered by trigeminal receptors in the upper airways. Methods: Odor thresholds were determined by the ascending method of limits in groups stratified by age and gender.Subjects rated intensities of different olfactory and trigeminal perceptions at different concentrations of SO2. During the presentation of the concentrations, breathing movements were measured by respiratory inductive plethysmography. Results: Neither age nor gender effects were observed for odor threshold. Only ratings of nasal irritation were influenced bygender. A benchmark dose analysis on relative respiratory depth revealed a 10%-deviation from baseline at about 25.27 mg/m3. Conclusion: The proposed new approach to risk assessment appearsto be sustainable. We discuss whether a 10%-deviation of breathingdepth is relevant.