Nonreciprocity and Circulation in a Passive Josephson-Junction Ring.

Building large-scale superconducting quantum circuits will require miniaturization and integration of supporting devices including microwave circulators, which are currently bulky, stand-alone components. Here, we report the measurement of microwave scattering from a ring of Josephson junctions, with dc-only control fields. We detect the effect of quasiparticle tunneling, and dynamically classify the system at its operating design point into different quasiparticle sectors. We optimize the device within one of the quasiparticle sectors, where we observe an unambiguous signature of nonreciprocal 3-port scattering within that sector. This enables operation as a circulator, and at the optimal circulation point, we observe on-resonance insertion loss of 2 dB, isolation of 14 dB, power reflectance of -11 dB, and a bandwidth of 200 MHz, averaged over the 3 input ports.

Confirmation of the recognition of Culiseta (Culiseta) indica Edwards, 1920 as a distinct species based on integrated morphological and molecular data.

Theobaldia indica Edwards, 1920, classified as a subspecies of Culiseta (Culiseta) alaskaensis (Ludlow, 1906), was recently restored to its original species status, as Culiseta (Culiseta) indica (Edwards), based on comprehensive assessments of morphological, ecological and distributional data. Predating the recognition of indica as a separate species, we collected specimens of this nominal taxon in the Western Himalayan region of India during 20152017, and used morphological and molecular studies to assess its taxonomic status. Our detailed examination of adult morphology, male genitalia and larval characteristics revealed significant distinctions between putative Cs. alaskaensis alaskaensis and Cs. alaskaensis indica, and sequencing of the barcode region of the mitochondrial COI gene yielded a Kimura 2 parameter genetic distance of 5.9% between them, well above the standard 23% commonly accepted to indicate separate species. These results strongly support the formal recognition of Cs. indica as a separate species. Furthermore, the geographical distribution of Cs. indica provides additional evidence in support of its species status.

Interactions between Leishmania parasite and sandfly: a review.

Leishmaniasis transmission cycles are maintained and sustained in nature by the complex crosstalk of the Leishmania parasite, sandfly vector, and the mammalian hosts (human, as well as zoonotic reservoirs). Regardless of the vast research on human host-parasite interaction, there persists a substantial knowledge gap on the parasite's development and modulation in the vector component. This review focuses on some of the intriguing aspects of the Leishmania-sandfly interface, beginning with the uptake of the intracellular amastigotes from an infected host to the development of the parasite within the sandfly's alimentary canal, followed by the transmission of infective metacyclic stages to another potential host. Upon ingestion of the parasite, the sandfly hosts an intricate repertoire of immune barriers, either to evade the parasite or to ensure its homeostatic coexistence with the vector gut microbiome. Sandfly salivary polypeptides and Leishmania exosomes are co-egested with the parasite inoculum during the infected vector bite. This has been attributed to the modulation of the parasite infection and subsequent clinical manifestation in the host. While human host-based studies strive to develop effective therapeutics, a greater understanding of the vector-parasite-microbiome and human host interactions could help us to identify the targets and to develop strategies for effectively preventing the transmission of leishmaniasis.

Identification and molecular characterization of Culex flavivirus in Culex quinquefasciatus (Diptera: Culicidae): first report from India.

BACKGROUND: Culex quinquefasciatus is a notorious vector known to transmit pathogens such as Wuchereria bancrofti (causing Lymphatic filariasis) and flaviviruses such as West Nile virus in India and St. Louis Encephalitis virus in the USA. It is the vector of the Rift Valley Fever virus, also on the African continent. Mosquitoes also harbor other non-pathogenic insect-specific flaviviruses (ISFs), such as Culex flavivirus (CxFV) and Aedes flavivirus. Recent studies have implicated ISFs interfering with the vectorial efficiency of the pathogenic arbo-viruses. METHODS: One hundred specimens of the Cx. quinquefasciatus population in two urban areas in Kerala State, India, were screened to have an understanding of the prevalence of these flaviviruses in this vector species. Viral RNA was extracted from individual specimens and was subjected to RT-PCR towards amplification of the CxFV non-structural protein 5 (NS5) gene. RESULTS: Among the 100 specimens, 7.0% were found to be harboring CxFV infection. The phylogenetic analysis of the gene sequences showed that the virus isolates were genetically related to Kenya, with 98-99% sequence similarities. CONCLUSION: This is the first report on the occurrence of CxFV from Cx. quinquefasciatus from India. The occurrence of these viruses in mosquitoes could play a critical role in disease vector management.

Region-specific improvisation on WHO case definition and environmental risk factors associated with dengue: a case-control analysis from Kerala, India.

BACKGROUND: Region-specific variations may occur in symptomatic manifestations that need to be addressed by dynamic case definitions. Environmental risk factors for dengue also vary widely across geographic settings. Our aim was to study the test positivity rate of the World Health Organization (WHO) 2009 probable dengue case definition and to suggest region-specific improvisations to it. The study also analyses the sociodemographic and environmental risk factors of dengue fever in South Kerala, India. METHODS: A case-control study was conducted in South Kerala from 2017 to 2019. Dengue reverse transcription polymerase chain reaction (RT-PCR)-positive and RT-PCR-negative 'probable dengue' patients were compared to identify significant symptoms for a modified definition of dengue. A group of afebrile community controls was compared with RT-PCR-positive dengue cases to study the environmental and behavioural risk factors. RESULTS: Arthralgia, palmar erythema and rashes have high discriminatory power (odds ratio [OR] >3) for identifying dengue. Redness of eyes, altered consciousness, abdominal distension and chills were found to moderately discriminate (OR 2-3) dengue. The adjusted analysis showed the presence of mosquito breeding sites (indoor p=0.02, outdoor p=0.03), solid waste dumping (p<0.001) and open water drainage in the compound (p=0.007) as significant predictors. CONCLUSIONS: Regional modifications should be considered when using the WHO definition in endemic settings. Control of mosquito breeding at the household level is the key towards dengue prevention.

Detection of recombinant dengue virus 2 NS1 protein in Aedes aegypti mosquitoes using commercial Dengue NS1 ELISA kit.

Dengue, a vector-borne disease remains as one of the most serious public health problems globally. Incidence of this disease is on an increasing trend and currently over a billion people in tropical and subtropical regions are at risk. In the absence of an operational vaccine, prevention of dengue virus (DENV) is primarily focused upon controlling mosquito vectors. Mosquito vector surveillance programmes require simple and rapid tools to detect mosquitoes infected with DENV. Here, we tested the commercially available DENV Detect™ NS1 ELISA kit (InBios International, Inc.) for detection of recombinant DENV-NS1 protein in Aedes mosquito samples. The kit was evaluated to find out the minimum detection limit of recombinant DENV-2 NS1 protein following the manufacturer's instructions. Initially, the NS1 protein detection threshold of the kit was determined and later the assay was standardized for detection of NS1 protein in Aedes aegypti mosquito pools containing 5, 10 and 25 mosquitoes. The ELISA kit displayed high sensitivity towards detection of recombinant dengue virus-2 NS1 protein in mosquito pools (up to 25 mosquitoes per pool) at 25 pico gram concentration. Since the commercial NS1 ELISA is highly sensitive and follows a very simple procedure, it could be employed for DENV surveillance in Aedes aegypti mosquitoes, after carrying out laboratory and field bioassays with DENV infected specimens.

Epidemiological and clinical characterization of dengue virus serotypes during 2017-2019 in southern Kerala, India.

BACKGROUND: In the context of the largest dengue outbreak in the state of Kerala, India in 2017, along with global evidence of changing epidemiology of dengue virus and its distribution, this study was planned to understand the epidemiological pattern of dengue infection and contemplate the clinical presentations of different serotypes. METHODS: This cross-sectional study was conducted in the Thiruvananthapuram and Kollam districts of Kerala, India, spanning 3 y from 2017 to 2019. We recruited adult patients based on the World Health Organization case definition of probable dengue fever to study their virological, spatial and clinical characteristics. RESULTS: Dengue infection was identified in 113 (33.9%) of the 333 probable dengue patients recruited. Dengue virus 1 (DENV1), along with its combinations (59.09%), was the predominant serotype during 2017, followed by DENV2. There was a marked increase in the proportion of DENV4 cases (34.56%) and concurrent infections (26%) in 2019. DENV3 infections were more likely to present with warning signs (adjusted relative risk 6.14 [95% confidence interval 1.3 to 29.4]) and a significantly lower platelet count (p=0.02). CONCLUSIONS: The results highlight the hyperendemicity of dengue infection in the state and the changing pattern of dengue virus predominance along with redominance. The rise in DENV4 and concurrent infections put forth the possibility of a more severe future outbreak.

Nation-wide vector surveillance on Zika and Dengue did not indicate transmission of the American lineage-pandemic Zika virus in India.

OBJECTIVES: Following the Public Health Emergency of International Concern declared on Zika by the World Health Organization during 2016, the Indian Council of Medical Research carried out nationwide vector surveillance for Zika and Dengue viruses (ZIKV and DENV) in India as a preparedness measure in 2016-19. METHODS: High-risk zones distributed to 49 Districts in 14 states/union territories were included in the study. Seven ICMR institutions participated, following a standard operating protocol. Aedes specimens sampled weekly were processed by multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) for ZIKV/DENV and random samples crosschecked with real-time RT-PCR for ZIKV. RESULTS: Altogether, 79 492 Aedes specimens in 6492 pools were processed; 3 (0.05%) and 63 (0.97%) pools, respectively, were found positive for ZIKV and DENV. ZIKV infections were recorded in Aedes aegypti sampled during the 2018 sporadic Zika outbreak in Jaipur, Rajasthan. However, these belonged to the Asian lineage of the virus, already circulating in the country. Both Ae. aegypti and Aedes albopictus distributed to 8 states/union territories were found to be infected with DENV. Both sexes of Ae. albopictus were infected, indicating transovarial transmission. CONCLUSION: This investigation evinced no active transmission of the American lineage-pandemic Zika virus in India during the pandemic period.

Incrimination of Aedes aegypti and Aedes albopictus as vectors of dengue virus serotypes 1, 2 and 3 from four states of Northeast India.

Dengue is an important vector borne disease with a great public health concern worldwide. Northeast India has experienced dengue almost every year for a decade. As studies on dengue vectors from this region are limited, we undertook an investigation to detect natural infection of the dengue virus (DENV) in potential dengue vectors of this region. Adult Aedes mosquitoes which were collected were subjected to RT-PCR for detection of infecting dengue serotype. Minimum infection rate was also determined for each positive pool. Out of the total 6229 adult Aedes mosquitoes collected, Aedes aegypti (63.3 %) was abundant in comparison to Aedes albopictus (36.7 %). These specimens (515 mosquito pools) were subjected to RT-PCR for detection of DENV-1, 2, 3 and 4. RT-PCR revealed the existence of DENV in both male as well as female mosquito pools suggesting natural transovarial transmission of DENV in this region. A total of 54 pools tested were positive for DENV-1, 2, 3 serotypes. This study revealed the occurence of DENV in both the potential dengue vectors from this region along with evidence of transovarial transmission which helps in persistence of the virus in nature.

Molecular modelling analysis of T219A mutant envelope protein revealed novel virulence enhancing factors in Dengue virus isolated from Kerala state, India.

Dengue virus (DENV) is an emerging health threat and its envelope glycoprotein E, is involved in the anchoring and fusion mechanisms. Anchoring followed by conformational changes of E-protein are responsible for the fusion and entry of DENV into host. The variation in the conformation of the E-protein due to mutations, results in its altered binding with antibodies (Abs) and also its receptors. This leads to failure of neutralization of DENV and enhance the infection. In our earlier studies we have identified T219A mutation in the E-protein of DENV and the present study is focused on the impact of this mutation on the conformation of E-protein and also its binding variation with Abs and Fc-γ receptor. A comparative molecular modelling studies of wild type and T219A mutant E-proteins revealed that, the mutation induced several conformational variations in the E-protein and resulted in the variable binding orientation with altered affinities. Further, the mutation was also observed to enhance the fusion mechanism by Fc-γ receptors that mediate the efficient entry of DENV into host cell through altered membrane fusion mechanism. Such conformational variations of E-protein could be the responsible factors for enhanced virulence of DENV infections.

Enhanced non-Markovian behavior in quantum walks with Markovian disorder.

Non-Markovian quantum effects are typically observed in systems interacting with structured reservoirs. Discrete-time quantum walks are prime example of such systems in which, quantum memory arises due to the controlled interaction between the coin and position degrees of freedom. Here we show that the information backflow that quantifies memory effects can be enhanced when the particle is subjected to uncorrelated static or dynamic disorder. The presence of disorder in the system leads to localization effects in 1-dimensional quantum walks. We shown that it is possible to infer about the nature of localization in position space by monitoring the information backflow in the reduced system. Further, we study other useful properties of quantum walk such as entanglement, interference and its connection to quantum non-Markovianity.

Detection of natural infection of Leishmania donovani (Kinetoplastida: Trypanosomatidae) in Phlebotomus argentipes (Diptera: Psychodidae) from a forest ecosystem in the Western Ghats, India, endemic for cutaneous leishmaniasis.

A new focus of transmission of Leishmania donovani causing cutaneous manifestations (CL) was reported by us earlier, in the Western Ghats region of Thiruvananthapuram district, Kerala, India. 12,253 sand fly specimens, comprising of three species belonging to the genus Phlebotomus (24.7%) and 16 species belonging to the genus Sergentomyia (57.3%) were collected from the region during 2012-2014. Among Phlebotomus species, Phlebotomus argentipes was found predominant (77.3%), followed by Phlebotomus colabaensis (21.7%) and Phlebotomus stantoni (1.6%). From these collections, 793 P. argentipes (88 pools), 123 P. colabaensis (31 pools) and three P. stantoni (three pools) female specimens were processed for detection of natural infection with L. donovani parasites using a multiple genetic marker (kinetoplast DNA; 3'UTR of HSP70 gene & HSP70 gene) approach. Five pools of P. argentipes specimens (Unfed (one), Fulfed (one) and Gravid (two)) among these, were found positive for L. donovani infection. HSP70 gene sequences of the parasites in the vector species was found genetically identical with the human isolates reported earlier, evincing the role of P. argentipes in the transmission of CL in this region. This is the first finding of natural infection of P. argentipes with L. donovani (causing CL) from India.

Microevolutionary trends of dengue virus-3 in Kerala, India.

Envelope gene is of great evolutionary significance and had been targeted as the vaccine candidate for dengue virus. We analyzed partial sequences of this gene to understand its genetic variability among viral isolates from Kerala state, India, if any. The current study focused on the evolutionary trends of this phylogenetically important gene among DENV-3 isolates through 2008 to 2010 outbreaks. The results gave an insight into the microevolutionary trends of the dengue viral genome. A unique mutation was recorded in the Domain II of the Envelope gene (EDII) of the viral genome at the amino acid position 219 (A219T). The evolutionary implication of this non-synonymous mutation near the EDI/EDII hinge remains to be explored. The study also provided knowledge on the genetic ancestral history of the viral isolates. Two variants of different phylogenetic origin were recorded in Kerala State. The findings in the study have significant implications on the development of dengue vaccines based on the Envelope gene of the virus.

Temporal distribution and behaviour of sand flies (Diptera: Psychodidae) in a cutaneous leishmaniasis focus of the Kani Tribe settlements in the Western Ghats, India.

The temporal distribution of sand flies in relation to environmental factors was studied in the Kani tribe settlements located on the southernmost part of the Western Ghats, Kerala, India, between June 2012 and May 2013. This area is known for occurrence of cutaneous leishmaniasis (CL) cases. Employing hand-held aspirator, light trap and sticky-trap collection methods, a total of 7874 sand fly specimens, comprising 19 species was collected. Sergentomyia baghdadis was predominant species, followed by Phlebotomus argentipes. Sand fly abundance was significantly higher indoors (χ(2)=9241.8; p=0.0001) than outdoors. Mean density of P. argentipes in human dwellings, cattle sheds and outdoors was 7.2±2.9, 27.33±21.1 and 0.64±0.2 females/per man-hour (MHR), respectively. No sand fly species other than P. argentipes was obtained from cattle sheds. Although, sand fly populations were prevalent throughout the year, their abundance fluctuated with seasonal changes. Multiple regression analysis with backward elimination indicated that the increase in precipitation and relative humidity contributed to a significant positive association with the increase in sand fly abundance, while the increase in temperature showed no association. Fully engorged female sand flies tested for blood meal source showed multiple host-blood feeding. Analysis of resting populations of sand flies collected from human shelters indicated that the populations were found maximum on interior walls at 6-8 and >8 ft height, including ceiling during summer (F=83.7, df=6, p=0.001) and at the lower half of the wall at 0 and 0-2 ft height, during monsoon season (F=41.4, df=6, p=0.001). In cooler months, no preference to any height level (F=1.67, df=6, p=0.2) was observed. Proportion of females sand flies with Sella's classification of abdominal stages, namely full-fed, half-gravid and gravid females did not vary significantly (t=1.98, p=0.13827) indoors, confirming their endophilic behaviour. Risk of CL transmission in these tribal settlements is discussed.

Morphological and molecular characterization of the ecological, biological and behavioural variants of the JE vector Culex tritaeniorhynchus: an assessment of its taxonomic status.

BACKGROUND & OBJECTIVES: Culex tritaeniorhynchus (Diptera: Culicidae), an important vector of Japanese encephalitis belongs to the Culex vishnui subgroup which includes two other vector species namely, Cx. Vishnui and Cx. pseudovishnui. Many varieties and types of Cx. tritaeniorhynchus have been reported, besides populations that exhibit behavioural and biological differences. This study was undertaken to find out whether Cx. tritaeniorhynchus populations exhibiting behavioural and biological variations, and those from different geographical areas, are comprised of more than one taxon or belong to a single taxon. METHODS: Morphological characterization was done by examining 153 morphological and morphometric characters in the larval (75), pupal (60) and adult stages (18) of five geographical populations of Cx. tritaeniorhynchus. Molecular characterization was done by PCR amplification of mitochondrial cytochrome c oxidase (COI) gene sequences (DNA barcodes) and another hypervariable genetic marker, the ribosomal DNA (16S). One-way ANOVA, principal component analysis (PCA) and discriminant factor analysis (DFA) were done for statistical analyses using the statistical package SPSS IBM version 19.0. RESULTS: Morphological characterization showed that no intraspecific differentiation can be made among the five geographical populations of Cx. tritaeniorhynchus. Molecular characterization done by DNA barcoding also showed that the COI sequences of all the five populations of Cx. tritaeniorhynchus grouped into a single taxonomic clade plus the genetic differentiation among these was non-significant and the overall gene flow among the populations was very high. Analysis of the ribosomal DNA also confirmed that the Cx. tritaeniorhynchus populations belonged to a single taxon. INTERPRETATION & CONCLUSION: Culex tritaeniorhynchus is a taxon that does not involve cryptic species.

Cutaneous leishmaniasis caused by Leishmania donovani in the tribal population of the Agasthyamala Biosphere Reserve forest, Western Ghats, Kerala, India.

Cutaneous leishmaniasis (CL), a neglected tropical disease, is reported to be prevalent in tribal villages located in the Agasthyamala Biosphere Reserve forests of Western Ghats, Kerala state, India. We carried out an investigation to characterize the species of Leishmania parasites involved in these infections prevalent among one of the oldest human tribal populations in India. Skin aspirates collected from 13 clinically diagnosed cases were subjected to histopathological investigations, serological rapid tests using 'rk39' and molecular diagnostics. Clinical manifestations recorded among the patients were hypo-pigmented erythematous nodules/papules on limbs and other parts of the body. Histopathological investigations of these skin lesions among patients showed Leishman-Donovan bodies in macrophages. None of the patients were found to be positive for rk39 tests, which detect active visceral leishmaniasis. Using three different genetic markers [kinetoplast minicircle DNA, 3' UTR region of heat-shock protein 70 (Hsp70) and Hsp70 gene] we identified the parasite species involved in these infections to be Leishmania donovani. The 6-phosphogluconate (6-PGDH) gene sequences of the parasite isolates from Western Ghats indicated close genetic relatedness to L. donovani isolates reported from Sri Lanka, also causing CL. This could be cited as another instance of 'local endemism' of organisms in this single 'bio-geographic unit'.

Sergentomyia (Neophlebotomus) monticola, a new species of sand fly (Diptera: Psychodidae) from the Western Ghats, Thiruvananthapuram District, Kerala, India.

Sergentomyia (Neophlebotomus) monticola, a new species of sand fly (Diptera: Psychodidae), from the Kani tribal settlements, Thiruvananthapuram District, Kerala, southern India was described. These settlements were located in the Western Ghats, which is one of the 25 biodiversity hotspots in the world. Morphological characters of male and female specimens of Sergentomyia (Neophlebotomus) monticola were described with illustrations and its taxonomic position is defined within the genus. The DNA barcode analysis showed that both male and female specimens of the species were belonging to a single taxonomic category. The genetic distance with the most similar taxonomic neighbour was 14.61%, which confirms its distinctness from its congeners. Voucher specimens of the new species were deposited at the museum, Vector Control Research Centre (Indian Council of Medical Research), Puducherry, India, Zoological Survey of India, India and Smithsonian National Museum of Natural History (NMNH), Washington, D.C., USA.

Genetic characterization of dengue viruses prevalent in Kerala State, India.

Dengue fever is re-emerging as a major scourge in south-east Asian countries, affecting about 50-100 million people and causing about 25,000 deaths annually. The Indian population as a whole is at risk of succumbing to this disease. This study genetically characterized viruses causing dengue infection in Kerala, one of the worst affected states of the country, during the disease outbreaks in 2008-2010. All four serotypes of dengue virus (DENV), DENV-1, DENV-2, DENV-3 and DENV-4, were found to be prevalent in the state. The genotypes recognized for these were III, IV, III and I, respectively. Phylogenetic analysis showed that the re-emergence of serotype DENV-4 reported in Maharashtra and Andhra Pradesh recently is spreading to different regions of the country. The circulation of all four DENV serotypes in Kerala may lead to an increase in the prevalence of more severe complications of this emerging disease, such as dengue haemorrhagic fever and dengue shock syndrome.