Cities in the Global South face rapid urbanization challenges and often suffer an acute lack of infrastructure and governance capacities. Smart Cities Mission, in India, launched in 2015, aims to offer a novel approach for urban renewal of 100 cities following an area‐based development approach, where the use of ICT and digital technologies is particularly emphasized. This article presents a critical review of the design and implementation framework of this new urban renewal program across selected case‐study cities. The article examines the claims of the so‐called “smart cities” against actual urban transformation on‐ground and evaluates how “inclusive” and “sustainable” these developments are. We quantify the scale and coverage of the smart city urban renewal projects in the cities to highlight who the program includes and excludes. The article also presents a statistical analysis of the sectoral focus and budgetary allocations of the projects under the Smart Cities Mission to find an inherent bias in these smart city initiatives in terms of which types of development they promote and the ones it ignores. The findings indicate that a predominant emphasis on digital urban renewal of selected precincts and enclaves, branded as “smart cities,” leads to deepening social polarization and gentrification. The article offers crucial urban planning lessons for designing ICT‐driven urban renewal projects, while addressing critical questions around inclusion and sustainability in smart city ventures.`

Attitudes and habits are extremely resistant to change, but a disruption of the magnitude of the COVID-19 pandemic has the potential to bring long-term, massive societal changes. During the pandemic, people are being compelled to experience new ways of interacting, working, learning, shopping, traveling, and eating meals. Going forward, a critical question is whether these experiences will result in changed behaviors and preferences in the long term. This paper presents initial findings on the likelihood of long-term changes in telework, daily travel, restaurant patronage, and air travel based on survey data collected from adults in the United States in Spring 2020. These data suggest that a sizable fraction of the increase in telework and decreases in both business air travel and restaurant patronage are likely here to stay. As for daily travel modes, public transit may not fully recover its pre-pandemic ridership levels, but many of our respondents are planning to bike and walk more than they used to. These data reflect the responses of a sample that is higher income and more highly educated than the US population. The response of these particular groups to the COVID-19 pandemic is perhaps especially important to understand, however, because their consumption patterns give them a large influence on many sectors of the economy.

Use of psychostimulants, such as cocaine, is associated with an increased risk of human immunodeficiency virus (HIV) infection. Dopaminergic signaling within the nucleus accumbens (NAc) is critically implicated in both disease states, mediating the addictive and reinforcing effects of cocaine and perpetuating HIV replication throughout the central nervous system (CNS). Cocaine and HIV induce neurobehavioral deficits separately; however, little is known regarding how they interact to dysregulate neuroimmune function or how this impacts relapse vulnerability. We have previously shown that inhibition of dopamine D3 receptor (D3R) signaling using MC-25-41, a novel and highly selective D3R partial agonist, attenuates cocaine-seeking behavior. Here, we sought to characterize changes in neuroimmune function in a rat model of combined HIV and cocaine use disorders across abstinence and examined the therapeutic efficacy of MC-25-41 in the presence of this comorbidity. Male rats were systemically treated with the HIV protein gp120 after establishing a history of cocaine self-administration and then, following 21 days of abstinence, were administered a systemic injection of MC-25-41 (10 mg/kg) prior to cue reactivity testing. Glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (Iba1) immunoreactivity were analyzed after 5 or 21 days of cocaine abstinence as an index of glial cell levels. We demonstrate that inhibition of D3R signaling significantly attenuates cue-induced cocaine seeking among control rats but not gp120-exposed rats. Moreover, we show that NAc core GFAP and Iba1 expression is impaired by 5 days of abstinence, which persists into protracted abstinence and cue reactivity testing. However, we also demonstrate that neither gp120 nor D3R inhibition significantly altered NAc core GFAP or Iba1 expression. Altogether, these results reveal significant changes in glial cell function across cocaine abstinence and unique behavioral interactions with gp120 may inhibit the effectiveness of medication regimens, which highlights the need to consider these comorbidities when treating HIV infection.

Bacterial lipopolysaccharides (LPS) are structural components of the outer membranes of Gram-negative bacteria and also are potent inducers of inflammation in mammals. Higher vertebrates are extremely sensitive to LPS, but lower vertebrates, like fish, are resistant to their systemic toxic effects. However, the effects of LPS on the fish intestinal mucosa remain unknown. Edwardsiella ictaluri is a primitive member of the Enterobacteriaceae family that causes enteric septicemia in channel catfish (Ictalurus punctatus). E. ictaluri infects and colonizes deep lymphoid tissues upon oral or immersion infection. Both gut and olfactory organs are the primary sites of invasion. At the systemic level, E. ictaluri pathogenesis is relatively well characterized, but our knowledge about E. ictaluri intestinal interaction is limited. Recently, we observed that E. ictaluri oligo-polysaccharide (O-PS) LPS mutants have differential effects on the intestinal epithelia of orally inoculated catfish. Here we evaluate the effects of E. ictaluri O-PS LPS mutants by using a novel catfish intestinal loop model and compare it to the rabbit ileal loop model inoculated with Salmonella enterica serovar Typhimurium LPS. We found evident differences in rabbit ileal loop and catfish ileal loop responses to E. ictaluri and S. Typhimurium LPS. We determined that catfish respond to E. ictaluri LPS but not to S. Typhimurium LPS. We also determined that E. ictaluri inhibits cytokine production and induces disruption of the intestinal fish epithelia in an O-PS-dependent fashion. The E. ictaluri wild type and ΔwibT LPS mutant caused intestinal tissue damage and inhibited proinflammatory cytokine synthesis, in contrast to E. ictaluri Δgne and Δugd LPS mutants. We concluded that the E. ictaluri O-PS subunits play a major role during pathogenesis, since they influence the recognition of the LPS by the intestinal mucosal immune system of the catfish. The LPS structure of E. ictaluri mutants is needed to understand the mechanism of interaction.

Contemporary vaccine development relies less on empirical methods of vaccine construction, and now employs a powerful array of precise engineering strategies to construct immunogenic live vaccines. In this review, we will survey various engineering techniques used to create attenuated vaccines, with an emphasis on recent advances and insights. We will further explore the adaptation of attenuated strains to create multivalent vaccine platforms for immunization against multiple unrelated pathogens. These carrier vaccines are engineered to deliver sufficient levels of protective antigens to appropriate lymphoid inductive sites to elicit both carrier-specific and foreign antigen-specific immunity. Although many of these technologies were originally developed for use in Salmonella vaccines, application of the essential logic of these approaches will be extended to development of other enteric vaccines where possible. A central theme driving our discussion will stress that the ultimate success of an engineered vaccine rests on achieving the proper balance between attenuation and immunogenicity. Achieving this balance will avoid over-activation of inflammatory responses, which results in unacceptable reactogenicity, but will retain sufficient metabolic fitness to enable the live vaccine to reach deep tissue inductive sites and trigger protective immunity. The breadth of examples presented herein will clearly demonstrate that genetic engineering offers the potential for rapidly propelling vaccine development forward into novel applications and therapies which will significantly expand the role of vaccines in public health.

Osteosarcoma is the most common bone cancer in children and adolescents. Although 70% of patients with localized disease are cured with chemotherapy and surgical resection, patients with metastatic osteosarcoma are typically refractory to treatment. Numerous lines of evidence suggest that cytotoxic T lymphocytes (CTLs) limit the development of metastatic osteosarcoma. We have investigated the role of PD-1, an inhibitory TNFR family protein expressed on CTLs, in limiting the efficacy of immune-mediated control of metastatic osteosarcoma. We show that human metastatic, but not primary, osteosarcoma tumors express a ligand for PD-1 (PD-L1) and that tumor-infiltrating CTLs express PD-1, suggesting this pathway may limit CTLs control of metastatic osteosarcoma in patients. PD-L1 is also expressed on the K7M2 osteosarcoma tumor cell line that establishes metastases in mice, and PD-1 is expressed on tumor-infiltrating CTLs during disease progression. Blockade of PD-1/PD-L1 interactions dramatically improves the function of osteosarcoma-reactive CTLs in vitro and in vivo, and results in decreased tumor burden and increased survival in the K7M2 mouse model of metastatic osteosarcoma. Our results suggest that blockade of PD-1/PD-L1 interactions in patients with metastatic osteosarcoma should be pursued as a therapeutic strategy.

Background: The current influenza vaccines are effective against seasonal influenza, but cannot be manufactured in a timely manner for a sudden pandemic or to be cost-effective to immunize huge flocks of birds. We propose a novel influenza vaccine composing a bacterial carrier and a plasmid cargo. In the immunized subjects, the bacterial carrier invades and releases its cargo into host cells where the plasmid expresses viral RNAs and proteins for reconstitution of attenuated influenza virus. Here we aimed to construct a mouse Poll-driven plasmid for efficient production of influenza virus. Results: A plasmid was constructed to express all influenza viral RNAs and proteins. This all-in-one plasmid resulted in 10(5)-10(6) 50 % tissue culture infective dose (TCID50)/mL of influenza A virus in baby hamster kidney (BHK-21) cells on the third day post-transfection, and also reconstituted influenza virus in Madin-Darby canine kidney (MDCK) and Chinese hamster ovary (CHO) cells. A 6-unit plasmid was constructed by deleting the HA and NA cassettes from the all-in-one plasmid. Cotransfection of BHK-21 cells with the 6-unit plasmid and the two other plasmids encoding the HA or NA genes resulted in influenza virus titers similar to those produced by the 1-plasmid method. Conclusions: An all-in-one plasmid and a 3-plasmid murine Poll-driven reverse genetics systems were developed, and efficiently reconstituted influenza virus in BHK-21 cells. The all-in-one plasmid may serve as a tool to determine the factors inhibiting virus generation from a large size plasmid. In addition, we recommend a simple and robust "1 + 2" approach to generate influenza vaccine seed virus.