Stable Artesunate Resistance in A Humanized Mouse Model of <em>Plasmodium falciparum</em>

Plasmodium falciparum, the most devastating human malaria parasite, confers higher morbidity and mortality. Although efforts have been made to develop an effective malaria vaccine, stage- and species-specific short-lived immunity crippled these efforts. Hence, antimalarial drug treatment becomes a mainstay for the treatment of malaria infection in the wake of the unavailability of an effective vaccine. Further, there has been a wide array of antimalarial drugs effective against various developmental stages of P. falciparum due to their different structures, modes of action, and pharmacodynamics as well as pharmacokinetics. The development of resistance against almost all frontline drugs by P. falciparum indicates the need for combination therapy (artemisinin-based combination therapy; ACT) to treat patients with P. falciparum. A higher pool of parasitemia under discontinuous in vivo artemisinin drug pressure in a developed humanized mouse allows the selection of artesunate resistant (ART-R) P. falciparum. Intravenously administered artesunate, using either single flash doses or a 2-day regimen, to the P. falciparum-infected human blood chimeric NOD/SCID.IL-2Rγ−/− immunocompromised (NSG) mice, with progressive dose increments upon parasite recovery, was the strategy deployed to select resistant parasites. Parasite susceptibility to artemisinins and other antimalarial compounds was characterized in vitro and in vivo. P. falciparum has shown to evolve extreme artemisinin resistance as well as co-resistance to antimalarial drugs. Overall, the present information shall be very useful in devising newer therapeutic strategies to treat human malaria infection

The Juvenile Hormone Analogue W-328 Affects Adult Development and Emergence in the Tsetse Fly, Glossina fuscipes fuscipes (Diptera: Glossinidae)

The tsetse fly Glossina fuscipes fuscipes Newstead (Diptera: Glossinidae) transmits protozoan parasites of the genus Trypanosoma, which cause human trypanosomosis

<span style="font-size:10.0pt;font-family: "Times New Roman","serif";mso-fareast-font-family:"Times New Roman";mso-bidi-font-family: Mangal;mso-ansi-language:EN-US;mso-fareast-language:EN-US;mso-bidi-language: HI" lang="EN-US">Physico-chemical properties of binary mixtures of tert-butanol with (nitro-, chloro- and bromo-) benzene at 303.15 K and 308.15 K</span>

790-795<span style="font-size:10.0pt;font-family: " times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";mso-bidi-font-family:="" mangal;mso-ansi-language:en-us;mso-fareast-language:en-us;mso-bidi-language:="" hi"="" lang="EN-US">The density (<span style="font-size:10.0pt;font-family: Symbol;mso-ascii-font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" mso-hansi-font-family:"times="" roman";mso-bidi-font-family:mangal;mso-ansi-language:="" en-us;mso-fareast-language:en-us;mso-bidi-language:hi;mso-char-type:symbol;="" mso-symbol-font-family:symbol"="" lang="EN-US"><span style="font-size:10.0pt;font-family: " times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";mso-bidi-font-family:="" mangal;mso-ansi-language:en-us;mso-fareast-language:en-us;mso-bidi-language:="" hi"="" lang="EN-US">), viscosity (<span style="font-size:10.0pt;font-family: Symbol;mso-ascii-font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" mso-hansi-font-family:"times="" roman";mso-bidi-font-family:mangal;mso-ansi-language:="" en-us;mso-fareast-language:en-us;mso-bidi-language:hi;mso-char-type:symbol;="" mso-symbol-font-family:symbol"="" lang="EN-US"><span style="font-size:10.0pt;font-family: " times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";mso-bidi-font-family:="" mangal;mso-ansi-language:en-us;mso-fareast-language:en-us;mso-bidi-language:="" hi"="" lang="EN-US">) and speed of sound (u) of three binary liquid mixtures of tert-butanol with (nitro-, chloro- and bromo-) benzene have been measured over the entire composition range at 303.15 K, 308.15 K and atmospheric pressure. From the experimental data, excess molar volume (VE), isentropic compressibility (κs), excess Gibbs free energy of activation (<span style="font-size:10.0pt;font-family:Symbol; mso-ascii-font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" mso-hansi-font-family:"times="" roman";mso-bidi-font-family:mangal;mso-ansi-language:="" en-us;mso-fareast-language:en-us;mso-bidi-language:hi;mso-char-type:symbol;="" mso-symbol-font-family:symbol"="" lang="EN-US"><span style="font-size:10.0pt;font-family: " times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";mso-bidi-font-family:="" mangal;mso-ansi-language:en-us;mso-fareast-language:en-us;mso-bidi-language:="" hi"="" lang="EN-US">G*E), deviation parameters like viscosity (<span style="font-size: 10.0pt;font-family:Symbol;mso-ascii-font-family:" times="" new="" roman";mso-fareast-font-family:="" "times="" roman";mso-hansi-font-family:"times="" roman";mso-bidi-font-family:="" mangal;mso-ansi-language:en-us;mso-fareast-language:en-us;mso-bidi-language:="" hi;mso-char-type:symbol;mso-symbol-font-family:symbol"="" lang="EN-US">), speed of sound (<span style="font-size:10.0pt;font-family: Symbol;mso-ascii-font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" mso-hansi-font-family:"times="" roman";mso-bidi-font-family:mangal;mso-ansi-language:="" en-us;mso-fareast-language:en-us;mso-bidi-language:hi;mso-char-type:symbol;="" mso-symbol-font-family:symbol"="" lang="EN-US"><span style="font-size:10.0pt;font-family: " times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";mso-bidi-font-family:="" mangal;mso-ansi-language:en-us;mso-fareast-language:en-us;mso-bidi-language:="" hi"="" lang="EN-US">u) and isentropic compressibility (<span style="font-size:10.0pt; font-family:Symbol;mso-ascii-font-family:" times="" new="" roman";mso-fareast-font-family:="" "times="" roman";mso-hansi-font-family:"times="" roman";mso-bidi-font-family:="" mangal;mso-ansi-language:en-us;mso-fareast-language:en-us;mso-bidi-language:="" hi;mso-char-type:symbol;mso-symbol-font-family:symbol"="" lang="EN-US">κs) are obtained. These functions have been fitted to Redlich-Kister polynomial equation to derive the coefficients and standard deviations.</span

Identification of microsatellite markers for differentiating some Basmati and non-Basmati rice varieties

519-526Microsatellite marker (SSR) analysis was used to differentiate premium traditional Basmati rice varieties from other cheaper cross-bred Basmati/long-grain rice varieties and monitor the cases of adulteration in milled rice samples. Thirteen rice cultivars (4 commercial traditional Basmati, 6 cross-bred Basmati and 3 non-Basmati varieties) were evaluated for allelic diversity using 35 SSR markers. A total of 123 alleles (79-345 bp) were detected; 25 of these were present in Basmati rice varieties only. Polymorphism information content (PIC) value, which is indicative of level of polymorphism, varied from 0.0 (RM167) to 0.858 (RM252), with an average value of 0.447. SSR analysis generated polymorphism sufficient to differentiate all the 13 rice genotypes. Of the 35 markers, 16 showed amplification of a different allele in one or more of the traditional/cross-bred Basmati rice varieties than in IR36 (indica) and Azucena (japonica). Some SSRs (RM60, RM84, RM252, RM171, and RM257) were found unique among the closely related traditional Basmati rice varieties. Traditional Basmati rice varieties could be differentiated from one or more of the cross-bred Basmati rice varieties by allelic polymorphism at 27 of the 35 SSR loci; the most useful markers being RM171, RM1, RM44, RM110, RM229, RM234, RM242, and RM255. Rice varieties were clustered in three groups (indica, japonica, Basmati groups), which correspond well to their known pedigree data. This paper provides effective means to the Basmati traders for varietal differentiation and monitoring adulteration cases using milled rice samples

Zinc Phthalocyanine Nanowires based Flexible Sensor For Room Temperature Cl-2 Detection

We have fabricated highly sensitive and Cl-2 selective flexible sensor by depositing solution processed zinc phthalocyanine nanowires onto the flexible PET substrate and studied its Cl-2 sensing characteristics in Cl-2 concentration range 5-1500 ppb. The flexible sensor has a minimum detection limit as low as 5 ppb of Cl, and response as high as 550% within 10 seconds. Interestingly, the sensor exhibited enhanced and faster response kinetics under bending conditions. The gas sensing mechanism of sensor has been discussed on the basis of XPS and Raman spectroscopic studies which revealed that zinc ions were the preferred sites for Cl-2 interactions

Volumetric and compressibility studies for (L-arginine + D-maltose monohydrate + water) system in the temperature range of (298.15 to 308.15) K

<p>The density and speed of sound of L-arginine (0.025–0.2 mol kg⁻¹) in aqueous + D-maltose (0–6 mass% of maltose in water) were obtained at temperatures of (298.15, 303.15 and 308.15) K. The apparent molar volume, limiting apparent molar volume, transfer volume, as well as apparent molar compressibility, limiting apparent molar compressibility, transfer compressibility, pair and triple interaction coefficients, partial molar expansibilities, coefficient of thermal expansion and also the hydration number, were calculated using the experimental density and speed of sound values. The results have been discussed in terms of solute–solute and solute–solvent interactions in these systems. Solute–solvent (hydrophilic–ionic group and hydrophilic–hydrophilic group) interactions were found to be dominating over solute–solute (hydrophobic–hydrophilic group) interactions in the solution, which increases with increase in maltose concentration.</p

Responses of Glossina fuscipes fuscipes to visually attractive stationary devices baited with 4-methylguaiacol and certain repellent compounds in waterbuck odour

BACKGROUND : A blend of compounds (pentanoic acid, guaiacol, δ-octalactone and geranylacetone) identified in waterbuck (Kobus defassa) body odour referred to as waterbuck repellent compounds (WRC) and a synthetic repellent 4-methylguaiacol have previously been shown to repel tsetse flies from the morsitans group. However, these repellents have not been evaluated on palpalis group tsetse flies. In this study, we evaluated the effect of these repellents on catches of Glossina fuscipes fuscipes (major vector of human sleeping sickness) in biconical traps and on sticky small targets which are visually attractive to palpalis group flies. The attractive devices were baited with different doses and blends of the repellent compounds. We also assessed the effect of removal of individual constituents in the synthetic blend of WRC on catches of G. f. fuscipes. METHODOLOGY/PRINCIPAL FINDINGS: The study was conducted in western Kenya on four islands of Lake Victoria namely Big Chamaunga, Small Chamaunga, Manga and Rusinga. The tsetse fly catches from the treatments were modeled using a negative binomial regression to determine their effect on catches. In the presence of WRC and 4-methylguaiacol (released at ≈2 mg/h and ≈1.4 mg/h respectively), catches of G. f. fuscipes were significantly reduced by 33% (P<0.001) and 22% (P<0.001) respectively in biconical traps relative to control. On sticky small targets the reduction in fly catches were approximately 30% (P<0.001) for both 4-methylguiacol and WRC. In subtractive assays, only removal of geranylacetone from WRC significantly increased catches (by 1.8 times; P <0.001) compared to the complete blend of WRC. CONCLUSIONS/SIGNIFICANCE : We conclude that WRC and 4-methylguaiacol reduce catches of G. f. fuscipes at stationary visually attractive traps and suggest that they may serve as broad spectrum repellents for Glossina species. We recommend further studies to investigate the effects of these compounds on reduction of G. f. fuscipes attracted to human hosts as this may lead to development of new strategies of reducing the prevalence and incidence of sleeping sickness.S1 Table. Fly catches for each experiment.S2 Table. Collected data that was analysed.European Union’s integrated Biological Control Applied Research Programme; UK Department for International Development; Swedish International Development Cooperation Agency; Swedish Agency for Development and Cooperation; University of Pretoria; South African National Research Foundation’s IFRR; Kenyan Governmenthttp://journals.plos.org/plosntdshj2020Zoology and Entomolog

Responses of Glossina fuscipes fuscipes to visually attractive stationary devices baited with 4-methylguaiacol and certain repellent compounds in waterbuck odour.

BackgroundA blend of compounds (pentanoic acid, guaiacol, δ-octalactone and geranylacetone) identified in waterbuck (Kobus defassa) body odour referred to as waterbuck repellent compounds (WRC) and a synthetic repellent 4-methylguaiacol have previously been shown to repel tsetse flies from the morsitans group. However, these repellents have not been evaluated on palpalis group tsetse flies. In this study, we evaluated the effect of these repellents on catches of Glossina fuscipes fuscipes (major vector of human sleeping sickness) in biconical traps and on sticky small targets which are visually attractive to palpalis group flies. The attractive devices were baited with different doses and blends of the repellent compounds. We also assessed the effect of removal of individual constituents in the synthetic blend of WRC on catches of G. f. fuscipes.Methodology/principal findingsThe study was conducted in western Kenya on four islands of Lake Victoria namely Big Chamaunga, Small Chamaunga, Manga and Rusinga. The tsetse fly catches from the treatments were modeled using a negative binomial regression to determine their effect on catches. In the presence of WRC and 4-methylguaiacol (released at ≈2 mg/h and ≈1.4 mg/h respectively), catches of G. f. fuscipes were significantly reduced by 33% (PConclusions/significanceWe conclude that WRC and 4-methylguaiacol reduce catches of G. f. fuscipes at stationary visually attractive traps and suggest that they may serve as broad spectrum repellents for Glossina species. We recommend further studies to investigate the effects of these compounds on reduction of G. f. fuscipes attracted to human hosts as this may lead to development of new strategies of reducing the prevalence and incidence of sleeping sickness

Sticky small target: an effective sampling tool for tsetse fly Glossina fuscipes fuscipes Newstead, 1910

Abstract Background Small targets comprising panels of blue and insecticide-treated black netting material each 0.25 × 0.25 m have been shown to attract and kill Glossina fuscipes fuscipes Newstead, 1910 (Diptera: Glossinidae) thereby reducing its population density by over 90% in field trials. However, their attractive ability has not been fully exploited for sampling purposes. Therefore, in this study we assessed the effectiveness of using sticky small targets as sampling tools for G. f. fuscipes in western Kenya. We also determined the influence of colour on the landing response of female and male flies on sticky small targets. Methods Using a series of randomised block experiments, the numbers of tsetse flies caught with sticky small targets were compared with those caught with biconical traps. A negative binomial regression was used to model fly catches. Odds ratios as measures of association between the landing response on the blue or black panel of the sticky small target and the sex of flies were obtained from a multiple logistic regression. Results The results showed that sticky small targets caught 13.5 and 3.6 times more female and male tsetse flies than biconical traps (Z = 9.551, P < 0.0001 and Z = 5.978, P < 0.0001, respectively). Females had a 1.7 times likelihood of landing on the black panel than males (Z = 2.25, P = 0.025). Conclusion This study suggests that sticky small targets are an effective sampling tool for G. f. fuscipes. Therefore, we recommend the use of sticky small targets as an alternative to biconical traps for observational and experimental investigations of G. f. fuscipes

Effects of vector control on the population structure of tsetse (Glossina fuscipes fuscipes) in western Kenya

Displacement rates of tsetse affect performance of targets during vector control. Fly size, one of the indicators of population structure usually obtained from wing measurement, is among the determinants of displacement rates. Although recovery of tsetse in previous intervention areas has been widely reported, the population structure of tsetse that recover is rarely evaluated despite being associated with displacements rates. Previously, intervention trials had reduced tsetse densities by over 90% from >3 flies/trap/day to 9 flies/trap/day. Irrespective of sex, wing shape did not isolate tsetse based on their islands of origin. The fly size from Big and Small Chamaunga did not differ significantly before intervention trials (P = 0.728). However, three years after the intervention flies from Big Chamaunga were significantly smaller than those from Small Chamaunga (P < 0.003). Further, there was an increase in the divergence of wing morphology between flies collected from Big Chamaunga and those from Small Chamaunga after tsetse control. In conclusion, even though populations are not isolated, vector control could influence the population structure of tsetse by exerting size and wing morphology differential selection pressures. Therefore, we recommend further studies to understand the mechanism behind this as it may guide future vector control strategies.The European Union's integrated Biological Control Applied Research Programme (IBCARP) tsetse repellent component grant number IBCARP DCI-FOOD/2014/346-739; UK's Department for International Development (DFID); Swedish International Development Cooperation Agency (Sida); the Swedish Agency for Development and Cooperation (SDC); and the Kenyan Government.http://www.elsevier.com/locate/actatropica2019-03-01hj2018Zoology and Entomolog