Biology subjects

Khan, I.

Publications and source records attributed to Khan, I..

44 records · Page 3Linked to original sources

bioRxiv2020

CARCASS SCAVENGING RELAXES CHEMICAL-DRIVEN FEMALE INTERFERENCE COMPETITION

Female-female nonsexual interference competition is rapidly emerging as a major fitness determinant of biased sex-ratio groups with high female density. How do females overcome such competition? We used adult flour beetle Tribolium castaneum to answer this question, where females from female-biased groups suppressed each others fecundity by secreting toxic quinones from their stink glands, revealing a chemical-driven interference competition. The added natal resource did not alleviate these fitness costs. Females also did not disperse more at high female-density. Hence, the competition was neither limited by the total resource availability nor the inability to avoid chemical interference. Instead, protein sequestered via scavenging of nutrient-rich carcasses relaxed the female competition, by increasing their fecundity and reducing the quinone content. Even infected carcasses were scavenged to extract fitness benefits, despite the infection-risk. Finally, individual stink gland components triggered carcass-scavenging to increase fecundity, indicating a potentially novel chemical feedback loop to reduce the competition.

ecology↗

bioRxiv2020

Regulation of polyphosphate glucokinase gene expression through co-transcriptional processing in Mycobacterium tuberculosis H37Rv

Transcription is the process that allows the simultaneous folding of RNA molecules, known as co-transcriptional folding. This folding determines the functional properties of RNA molecules and possibly having a critical role during the synthesis as well. This functioning includes the characterized properties of riboswitches and ribozymes as well, which is significant when the transcription rate is comparable to the cellular environment. This study aims to discover a novel non-coding region that is important in the genetic expression of Mycobacterium tuberculosis. In this work, we identified a novel non-coding element of polyphosphate glucokinase (ppgk) gene that undergoes cleavage activity during the transcriptional process in Mycobacterium tuberculosis. We revealed that cleavage occurs within the nascent RNA, and the resultant cleaved 3RNA fragment carries the Shine-Dalgarno (SD) sequence and expression platform. Site-specific mutations provide a strong correlation between the disruption of cleavage activity and expression of ppgk gene. We concluded that co-transcriptional processing at the noncoding region as the required mechanism for ppgk expression that remains constitutive within the bacterial environment. The underlying reason for ppgk mRNA processing and expression is correlated because the non-coding counterpart adopts a hairpin domain that sequesters ribosomal binding site. Thus, the mRNA processing at the immediate upstream of Shine-Dalgarno sequence is required to prevent this sequestration and subsequent expression as well. This study defines the molecular mechanism that is dependent on the transient but highly active structural features of the nascent RNA.

molecular biology↗

bioRxiv2019

The MEK1/2 pathway as a therapeutic target in high-grade serous ovarian carcinoma

RationaleHigh-grade serous ovarian carcinoma (HGSOC) is the deadliest of gynecological cancers due to high rate of recurrence and acquired chemoresistance. Mutation and activation of the RAS/MAPK pathway has been linked to cancer cell proliferation and therapeutic resistance in numerous cancers. While RAS mutations are not commonly observed in HGSOC, less is known about downstream pathway activation. We therefore sought to investigate the role of MEK1/2 signaling in ovarian cancer.\n\nMethodsMEK1/2 pathway activity was evaluated in clinical HGSOC tissue samples and ovarian cancer cell lines by using tissue microarray-based immunohistochemistry, immunoblotting, and RT-qPCR. OVCAR8 and PEO4 HGSOC cell lines were used to assess the effect of MEK1/2 inhibition on cell viability, proliferation rate, and stem-like characteristics. Xenografts were used in mice to investigate the effect of MEK1/2 inhibition on tumor growth in vivo. A drug washout experimental model was used to study the lasting effects of MEK1/2 inhibition therapy.\n\nResultsMEK1/2 signaling is active in a majority of HGSOC tissue samples and cell lines. MEK1/2 is further stimulated by cisplatin treatment, suggesting that MEK1/2 activation may play a role in chemotherapy resistance. The MEK1/2 inhibitor, trametinib, drastically inhibits MEK1/2 downstream signaling activity, causes prominent cell cycle arrest in the G1/0-phase in cell cultures, and reduces the rate of tumor growth in vivo, but does not induce cell death. Cells treated with trametinib display a high CD133+ fraction and increased expression of stemness-associated genes. Transient trametinib treatment causes long-term increases in a high ALDH1 activity subpopulation of cells that possess the capability of surviving and growing in non-adherent conditions.\n\nConclusionsMEK1/2 inhibition in HGSOC cells efficiently inhibits proliferation and tumor growth and therefore may be a promising approach to suppress ovarian cancer cell growth. MEK1/2 inhibition promotes stem-like properties, thus suggesting a possible mechanism of resistance and that a combination with CSC-targeting drugs should be considered.

cancer biology↗

bioRxiv2019

BASAL RESISTANCE AGAINST A PATHOGEN IS MORE BENEFICIAL THAN IMMUNE PRIMING RESPONSES IN FLOUR BEETLES

In insects, basal pathogen resistance and immune priming can evolve as mutually exclusive strategies, with distinct infection outcomes. However, the evolutionary drivers of such diverse immune functions remain poorly understood. Here, we addressed this key issue by systematically analyzing the differential fitness costs and benefits of priming vs. resistance evolution in Tribolium beetle populations infected with Bacillus thuringiensis. Surprisingly, resistant beetles had increased post-infection reproduction and a longer lifespan under both starving as well as fed conditions, with no other measurable costs. In contrast, priming reduced offspring early survival, development rate and reproduction. Priming did improve post-infection survival of offspring, but this added trans-generational benefit of immune priming might not compensate for its pervasive costs. Resistance was thus consistently more beneficial. Our work represents the first report of experimentally evolved trans-generational priming, and a detailed comparison of the complex fitness consequences of evolved priming vs resistance. HIGHLIGHTSO_LIDivergent costs and benefits of experimentally evolved immune priming vs resistance C_LIO_LIIncreased reproduction and lifespan in resistant populations C_LIO_LINo other hidden costs of resistance C_LIO_LIIn contrast, reduced juvenile fitness and reproduction in primed populations C_LIO_LIFirst evidence for experimentally evolved trans-generational immune priming C_LI

evolutionary biology↗

bioRxiv2018

Prokaryotic Diversity from Extreme Environments of Pakistan and its Potential Applications at Regional Levels

Extremophiles, the microorganisms thriving in extreme environments, provide valuable resources for practicing novel biotechnological processes. Pakistan homes a wide spectrum of extreme environments which harbor various biotechnologically significant microorganisms. This review gauges the structural and functional bacterial diversity of several extreme environments, emphasizing their potentials as a source of extremozymes, and in bioleaching, bioremediation, and bioenergy production at regional level. Further, this review highlights a panoramic account of the local natural conservatories of extremophiles. The inadequacies of current fragmental research are discussed with suggestions to quantitatively define the structural and functional diversity of unexplored extreme localities.

microbiology↗

bioRxiv2018

Pathogen susceptibility and fitness costs explain variation in immune priming across natural populations of flour beetles

In many insects, individuals primed with low doses of pathogens live longer after being exposed to the same pathogen later in life. Yet, our understanding of the evolutionary and ecological history of priming of immune response in natural insect populations is limited. Previous work demonstrated population-, sex- and- stage specific variation in the survival benefit of priming response in flour beetles (Tribolium castaneum) infected with their natural pathogen Bacillus thuringiensis. However, the evolutionary forces responsible for this natural variation remained unclear. Here, we tested whether the strength of the priming response (measured as the survival benefit after priming and subsequent infection relative to unprimed controls) was associated with multiple fitness parameters across 10 flour beetle populations. Our results suggest two major selective pressures that may explain the observed inter-population variation in priming: (A) Basal pathogen susceptibility - populations that were more susceptible to infection produced a stronger priming response, and (B) Reproductive success - populations where primed females produced more offspring had lower survival benefit, suggesting a trade-off between priming response and reproduction. Our work is the first empirical demonstration of multiple selective pressures that may govern the adaptive evolution of immune priming in the wild. We hope that this motivates further experiments to establish the role of pathogen-imposed selection and fitness costs in the evolution of priming in natural insect populations.

evolutionary biology↗

bioRxiv2017

Experimental Evolution Of Insect Immune Memory Vs. Pathogen Resistance

Under strong pathogen pressure, insects often evolve resistance to infection. Many insects are also protected via immune memory ( immune priming), whereby sub-lethal exposure to a pathogen enhances survival after secondary infection. To understand the evolution and consequences of these immune responses, we imposed strong pathogen selection on flour beetles (Tribolium castaneum), infecting them with Bacillus thuringiensis (Bt) for 11 generations. Populations injected first with heat-killed and then live Bt each generation evolved high basal resistance against multiple Bt strains. In contrast, all populations injected only with a high dose of live Bt evolved less effective but strain-specific priming response. Control populations injected with heat-killed Bt did not evolve priming; and in the ancestor, priming was effective only against a low Bt dose. Thus, pathogens can select for rapid modulation of insect priming ability, leading to divergent immune strategies (generalized resistance vs. specific immune priming) with distinct mechanisms and adaptive benefits.

evolutionary biology↗

bioRxiv2017

FEMALE CHEMICAL WARFARE DRIVES FITNESS EFFECTS OF GROUP SEX RATIO

In animals, skewed sex ratios can affect individual fitness either via sexual interactions (e.g. intersexual conflict or intrasexual mate competition) or non-sexual interactions (e.g. sex-specific resource competition). Because most analyses of sex ratio focus on sexual interactions, the relative importance of these mechanisms remains unclear. We addressed this problem using the flour beetle Tribolium castaneum, where male-biased sex ratios increase female fitness relative to unbiased or female-biased groups. Although flour beetles show both sexual and non-sexual (resource) competition, we found that sexual interactions did not explain female fitness. Instead, female fecundity was dramatically reduced even after a brief exposure to flour conditioned by other females. Earlier studies suggested that quinones (secreted toxins) might mediate density-dependent population growth in flour beetles. We identified ethyl- and methyl-benzoquinone (EBQ and MBQ) as the primary components of adult stink glands that regulate female fecundity. In female-biased groups (i.e. at high female density), females upregulated quinones and suppressed each others reproduction. In male-biased groups, low female density lead to low quinone levels, allowing higher fecundity. Thus, quinones serve both as indicators and mediators of female competition, resulting in the observed fitness decline in female-biased groups. Our results underscore the importance of non-sexual interference competition that may often underlie the fitness consequences of skewed sex ratios.

evolutionary biology↗