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Highly effective antiretroviral therapy (ART) has transformed human immunodeficiency virus (HIV) care in the past 3 decades. 30 years ago, how many would have imagined that a single-tablet daily ART regimen containing different drug classes could achieve sustained HIV-1 suppression and halt disease progression to acquired immunodeficiency syndrome (AIDS)? Despite this remarkable achievement, challenges in HIV care remain that require further innovation for ART. In this review, we focus on newly approved antiretroviral agents and those undergoing phase 2/3 clinical trials. These new antiretrovirals hold great promise to expand treatment options and fill gaps in HIV care.

An experiment was conducted with three managements varied in tillage, crop establishments, residue, fertilizer, water to evaluate crop behaviour, irrigation water use, crop productivity and profitability of crops in an individual and in system mode. Three management systems were conventional system [TPR (transplanted rice)–CTW (conventional-till wheat)], partial CA [TPR–ZTW (zero–till wheat)] and full CA [ZTDSR (ZT direct seeded rice)–ZTW]. Rice plant growth (shoot and root) behaves similarly in CT and ZT based systems up to 40 days after sowing and after that TPR–ZTW recorded higher growth followed by TPR–CTW and lowest with ZTDSR. However, reverse trend in growth was observed with wheat in order of ZTDSR–ZTW > TPR–ZTW > TPR–CTW. Lower NDVI values were observed with ZTDSR and higher values with TPR throughout the crop season. Full CA based wheat recorded higher NDVI values than other management systems during the crop growth period. Higher wheat yield attributing character was recorded with ZTDSR–ZTW and lowest with farmer’s practices (TPR–CTW). On 2-years mean basis, ZTDSR–ZTW system produced similar crop yields to TPR–ZTW and TPR–CTW with 28% less irrigation water and 29% higher returns compared to TPR–CTW. However, TPR–ZTW improved system productivity and net returns by 8 and 37% respectively, compared to TPR–CTW while saving of 14% irrigation water. ZTDSR recorded a yield loss of 10%; while wheat registered a yield gain of 21% with ZTDSR–ZTW. CA based management practices slowed down the DSR crop growth and yield but increased same for wheat crop which is ultimately helpful in sustaining productivity and profitability of rice–wheat system (RWS) in North West India.

In Indo-Gangetic plains (IGP) of India, natural resources (soil, water, and environment) are degrading under the conventional–till (CT)-based management practices in rice–wheat cropping system. A long-term field experiment was conducted to understand the soil bacterial diversity and abundance under different sets of management scenarios (Sc). The study comprised of four scenarios, namely, -Sc.I CT-based rice–wheat system (farmers’ practice); Sc.II, partial conservation agriculture (CA) based in which rice is under CT—wheat and mungbean under zero-tillage (ZT); Sc.III, full CA-based in which rice–wheat–mungbean are under ZT and Sc.IV, where maize–wheat–mungbean are under ZT. These scenarios varied in cropping system, tillage, and crop residue management practices. Using Illumina MiSeq sequencing technology, the variable regions V3–V4 of 16S rRNA were sequenced and the obtained reads were analyzed to study the diversity patterns in the scenarios. Results showed the presence of 53 bacterial phyla across scenarios. The predominant phyla in all scenarios were Proteobacteria, Acidobacteria, Actinobacteria, and Bacteroideteswhich accounted for more than 70% of the identified phyla. However, the rice-based systems (Sc.I, Sc.II, and Sc.III) were dominated by phylum Proteobacteria;however, maize-based system (Sc.IV) was dominated by Acidobacteria. The class DA052and Acidobacteriiaof Acidobacteriaand Bacteroidetesof Bacteroidiawere exceptionally higher in Sc.IV. Shannon diversity index was 8.8% higher in Sc.I, 7.5% in Sc.II, and 2.7% in Sc.III compared to Sc.IV. The findings revealed that soil bacterial diversity and abundance are influenced by agricultural management practices as bacterial diversity under full CA-based management systems (Sc.III and Sc.IV) was lower when compared to farmer’s practice (Sc.I) and partial CA (Sc.II) scenarios.

In North West-Indo Gangetic Plains (NW-IGP) of India in situ burning of crop residues is practiced by majority of farmers’ which deteriorates soil and environmental quality. Fungi have the potential for lignocellulose degradation and can be used for the in situ decomposition of crop residues. Lignocellulose degrading fungal spp. were isolated and evaluated for the activity of lignocellulolytic enzymes. The lignocellulose degrading fungi were isolated by appearance of zone on carboxy methyl cellulose (CMC) agar media and tannic acid (TA) media. Carboxy methyl cellulase, filter paperase, cellobiase, xylanase and laccase activity were estimated in submerged, as well as solid state fermentation using a mixture of rice and wheat straw in the ratio of 4:1. rice–wheat straw as substrate. The residue left after solid state fermentation was evaluated for carbon/nitrogen ratio, dry mass loss, and loss of cellulose, hemicellulose and lignin. Selected potential isolates were further tested in pot experiment for their effect on wheat plants. The interaction among isolates was also studied. After primary screening, 19 out of a total of 72 fungal isolates were selected based on their enzymatic activity profile and potential to degrade lignocellulosic residues in submerged fermentation. Out of these 19 isolates, 11 were further selected based on their enzymatic secretions in solid state fermentation. All the 11 strains were identified morphologically. Four fungal isolates (RPW 1/3, RPW 1/6, RPWM 2/2 and RZWM 3/2) showed higher enzymatic activities and more loss of dry mass and cell wall constituents over the other isolates. These isolates were identified by ITS region sequencing as Aspergillus flavus, Aspergillus terreus, Penicillium pinophilumand Alternaria alternata. This study revealed that fungal isolates may be used for managing crop residues in conservation agriculture based rice–wheat system of NW-IGP to eliminate ill effects of residue burning.

Antiretroviral therapy (ART) for HIV-1 has dramatically improved outcomes for people living with HIV-1 but requires life-long adherence and can be associated with short and long-term toxicity. Numerous pre-clinical and clinical investigations are underway to develop therapies for immune control of HIV-1 in the absence of ART. The success of chimeric antigen receptor (CAR) cell therapy for hematological malignancy has renewed efforts to develop and investigate CAR cells as strategies to enhance HIV-1 immunity, enable virus control or elimination, and allow ART-free HIV-1 remission. Here, we review the improvements in anti-HIV-1 CAR cell therapy in the two decades since their initial clinical trials were conducted, describe the additional engineering required to protect CAR cells from HIV-1 infection, and preview the current landscape of CAR cell therapies advancing to HIV-1 clinical trials.

A co-formulated, one pill once a day antiretroviral regimen (single-tablet regimen), containing efavirenz, emtricitabine, and tenofovir disoproxyl fumarate (Atripla), revolutionized the antiretroviral therapy landscape. Single-tablet regimens provide not only dosing convenience but help optimize adherence and persistence with antiretroviral therapy to achieve durably suppressed viremia with both individual and societal benefits. Given the many excellent options available now, single-tablet regimens are the preferred choice for initiating antiretroviral therapy in almost all patients with rare exceptions for drug interactions and pregnancy, and for simplification of more complex antiretroviral therapy to a single-tablet regimen. In this special commemorative article, we celebrate this astounding advancement in antiretroviral therapy, championed by John C. Martin while CEO of Gilead Sciences, and its transformative impact on HIV care nationally and globally.

Comparison of synonymous and nonsynonymous variation/substitution within and between species at individual genes has become a widely used general approach to detect the effect of selection versus drift. The sibling species group comprised of two cosmopolitan (Drosophila melanogasterand Drosophila simulans) and two island (Drosophila mauritianaand Drosophila sechellia) species has become a model system for such studies. In the present study we reanalyzed the pattern of protein variation in these species, and the results were compared against the patterns of nucleotide variation obtained from the literature, mostly available for melanogasterand simulans. We have mainly focused on the contrasting patterns of variation between the cosmopolitan pair. The results can be summarized as follows: (1) As expected the island species D. mauritianaand D. sechelliashowed much less variation than the cosmopolitan species D. melanogasterand D. simulans. (2) The chromosome 2 showed significantly less variation than chromosome 3 and X in all four species which may indicate effects of past selective sweeps. (3) In contrast to its overall low variation, D. mauritianashowed highest variation for X-linked loci which may indicate introgression from its sibling, D. simulans.(4) An average population of D. simulanswas as heterozygous as that of D. melanogaster(14.4% v.s. 13.9%) but the difference was large and significant when considering only polymorphic loci (37.2% v.s. 26.1%). (5) The species-wise pooled populations of these two species showed similar results (all loci = 18.3% v.s. 20.0%, polymorphic loci = 47.2% v.s. 37.6%). (6) An average population of D. simulanshad more low-frequency alleles than D. melanogaster, and the D. simulansalleles were found widely distributed in all populations whereas the D. melanogasteralleles were limited to local populations. As a results of this, pooled populations of D. melanogastershowed more polymorphic loci than those of D. simulans(48.0% v.s. 32.0%) but the difference was reduced when the comparison was made on the basis of an average population (29.1% v.s. 21.4%). (7) While the allele frequency distributions within populations were nonsignificant in both D. melanogasterand D. simulans, melanogasterhad fewer than simulans, but more than expected from the neutral theory, low frequency alleles. (8) Diallelic loci with the second allele with a frequency less than 20% had similar frequencies in all four species but those with the second allele with a frequency higher than 20% were limited to only melanogaster: the latter group of loci have clinal (latitudinal) patterns of variation indicative of balancing selection. (9) The comparison of D. simulans/D. melanogasterprotein variation gave a ratio of 1.04 for all loci and 1.42 for polymorphic loci, against a ratio of approximately 2-fold difference for silent nucleotide sites. This suggests that the species ratios of protein and silent nucleotide polymorphism are too close to call for selective difference between silent and allozyme variation in D. simulans. In conclusion, the contrasting levels of allozyme polymorphism, distribution of rare alleles, number of diallelic loci and the patterns of geographic differentiation between the two species suggest the role of natural selection in D. melanogaster, and of possibly ancient population structure and recent worldwide migration in D. simulans. Population size differences alone are insufficient as an explanation for the patterns of variation between these two species.

Rhodobacter sphaeroides2.4.1Trespires aerobically via a branched respiratory chain consisting of both cytochrome coxidases and quinol oxidases. Here, genes from chromosome II encoding two distinct quinol oxidases have been characterized. The qoxBAgenes encode a putative heme‐copper quinol oxidase, whereas the qxtABgenes encode a quinol oxidase homologous to the cyanide‐insensitive oxidase of Pseudomonas aeruginosa. No phenotype was observed for mutations in either oxidase in the wild‐type background. A strain containing a qxtAmutation in a cytochrome bc1complex mutant background was unable to grow aerobically. No role was found for the Qox oxidase, nor was a qoxB::lacZtranscriptional fusion expressed under a variety of conditions. These are the first molecular studies to characterize the quinol oxidases of R. sphaeroides2.4.1T.

Rhodobacter sphaeroides 2.4.1T respires aerobically via a branched respiratory chain consisting of both cytochrome c oxidases and quinol oxidases. Here, genes from chromosome II encoding two distinct quinol oxidases have been characterized. The qoxBA genes encode a putative heme-copper quinol oxidase, whereas the qxtAB genes encode a quinol oxidase homologous to the cyanide-insensitive oxidase of Pseudomonas aeruginosa. No phenotype was observed for mutations in either oxidase in the wild-type background. A strain containing a qxtA mutation in a cytochrome bc1 complex mutant background was unable to grow aerobically. No role was found for the Qox oxidase, nor was a qoxB::lacZ transcriptional fusion expressed under a variety of conditions. These are the first molecular studies to characterize the quinol oxidases of R. sphaeroides 2.4.1T.