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PLoS Genetics ◽  
2022 ◽  
Vol 18 (1) ◽  
pp. e1010003
Author(s):  
Karo Tanaka ◽  
Vanessa Besson ◽  
Manon Rivagorda ◽  
Franck Oury ◽  
Giovanna Marazzi ◽  
...  

The paternally expressed gene 3 (Pw1/Peg3) is a mammalian-specific parentally imprinted gene expressed in stem/progenitor cells of the brain and endocrine tissues. Here, we compared phenotypic characteristics in Pw1/Peg3 deficient male and female mice. Our findings indicate that Pw1/Peg3 is a key player for the determination of sexual dimorphism in metabolism and behavior. Mice carrying a paternally inherited Pw1/Peg3 mutant allele manifested postnatal deficits in GH/IGF dependent growth before weaning, sex steroid dependent masculinization during puberty, and insulin dependent fat accumulation in adulthood. As a result, Pw1/Peg3 deficient mice develop a sex-dependent global shift of body metabolism towards accelerated adiposity, diabetic-like insulin resistance, and fatty liver. Furthermore, Pw1/Peg3 deficient males displayed reduced social dominance and competitiveness concomitant with alterations in the vasopressinergic architecture in the brain. This study demonstrates that Pw1/Peg3 provides an epigenetic context that promotes male-specific characteristics through sex steroid pathways during postnatal development.


2022 ◽  
Author(s):  
Andrew D Letten

Mechanistic models of resource competition underpin numerous foundational concepts and theories in ecology, and continue to be employed widely to address diverse research questions. Nevertheless, current software tools present a comparatively steep barrier to entry. I introduce the R package rescomp to support the specification, simulation and visualisaton of a broad spectrum of consumer-resource interactions. rescomp is compatible with diverse model specifications, including an unlimited number of consumers and resources, different consumer functional responses (type I, II and III), different resource types (essential or substitutable) and supply dynamics (chemostats, logistic and/or pulsed), delayed consumer introductions, time dependent growth and consumption parameters, and instantaneous changes to consumer and/or resource densities. Several examples on implementing rescomp are provided. In addition, a wide variety of additional examples can be found in the package vignettes, including using rescomp to reproduce the results of several well known studies from the literature. rescomp provides users with an accessible tool to reproduce classic models in ecology, to specify models resembling a wide range of experimental designs, and to explore diverse novel model formulations.


2022 ◽  
Author(s):  
Christopher M Wintersinger ◽  
Dionis Minev ◽  
Anastasia Ershova ◽  
Hiroshi Sasaki ◽  
Gokul Gowri ◽  
...  

Living systems achieve robust self-assembly across length scales. Meanwhile, nanofabrication strategies such as DNA origami have enabled robust self-assembly of submicron-scale shapes.However, erroneous and missing linkages restrict the number of unique origami that can be practically combined into a single supershape. We introduce crisscross polymerization of DNA-origami slats for strictly seed-dependent growth of custom multi-micron shapes with user-defined nanoscale surface patterning. Using a library of ~2000 strands that can be combinatorially assembled to yield any of ~1e48 distinct DNA origami slats, we realize five-gigadalton structures composed of >1000 uniquely addressable slats, and periodic structures incorporating >10,000 slats. Thus crisscross growth provides a generalizable route for prototyping and scalable production of devices integrating thousands of unique components that each are sophisticated and molecularly precise.


Author(s):  
Ramon Hochstrasser ◽  
Hubert Hilbi

Legionella species are facultative intracellular pathogens, which cause a life-threatening pneumonia termed Legionnaires’ disease. Legionella pneumophila employs the Legionella quorum sensing (Lqs)-LvbR network to regulate virulence and motility, but its role for growth in media is ill-defined. Here we report that compared to the parental L. pneumophila strain JR32, a Δ lqsR mutant showed a reduced lag phase at 30°C and reached a higher cell density at 45°C, while the Δ lqsA , Δ lqsS and Δ lqsT mutants showed a longer lag phase and reached only a lower cell density. A Δ lvbR mutant resumed growth like the parental strain at 30°C, but exhibited a substantially reduced cell density at 45°C. Thus, LvbR is an important cell density regulator at elevated temperatures. Environmental and clinical L. pneumophila strains grew in AYE medium after distinct lag phases with similar rates at 30°C, reached different cell densities at the optimal growth temperature of 40°C, and no longer grew at 50°C. Legionella longbeachae reached a rather low cell density at 40°C and did not grow at and beyond 45°C. Genes encoding components of the Lqs-LvbR network were present in the genomes of the environmental and clinical L. pneumophila isolates, and upon growth at 30°C or 45°C the P lqsR , P lqsA , P lqsS and P lvbR promoters from strain JR32 were expressed in these strains with distinct patterns. Taken together, our results indicate that the Lqs-LvbR network governs the temperature-dependent growth onset and cell density of the L. pneumophila reference strain JR32, and possibly also of environmental and clinical L. pneumophila isolates. Importance Environmental bacteria of the genus Legionella are the causative agents of the severe pneumonia Legionnaires’ disease, the incidence of which is worldwide on the rise. Legionella pneumophila and Legionella longbeachae are the clinically most relevant species. The opportunistic pathogens are inhaled through contaminated aerosols and replicate in human lung macrophages with a similar mechanism as in their natural hosts, free-living amoebae. Given their prevalence in natural and technical water systems, an efficient control of Legionella spp. by physical, chemical or biological means will reduce the incidence of Legionnaires’ disease. Here we show that the Legionella quorum sensing (Lqs) system and the pleiotropic transcription factor LvbR govern the temperature-dependent growth onset and cell density of bacterial cultures. Hence, the growth of L. pneumophila in water systems is not only determined by the temperature and nutrient availability, but also by quorum sensing, i.e., density- and signaling molecule-dependent gene regulation.


Pharmaceutics ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 88
Author(s):  
Lital Cohen ◽  
Yehuda G. Assaraf ◽  
Yoav D. Livney

Prostate cancer (PC) is the most common cancer in men over 50 and the 4th most prevalent human malignancy. PC treatment may include surgery, androgen deprivation therapy, chemotherapy, and radiation therapy. However, the therapeutic efficacy of systemic chemotherapy is limited due to low drug solubility and insufficient tumor specificity, inflicting toxic side effects and frequently provoking the emergence of drug resistance. Towards the efficacious treatment of PC, we herein developed novel selectively PC-targeted nanoparticles (NPs) harboring a cytotoxic drug cargo. This delivery system is based upon PEGylated nanostructured lipid carriers (NLCs), decorated with a selective ligand, targeted to prostate-specific membrane antigen (PSMA). NPs loaded with cabazitaxel (CTX) displayed a remarkable loading capacity of 168 ± 3 mg drug/g SA-PEG, encapsulation efficiency of 67 ± 1%, and an average diameter of 159 ± 3 nm. The time-course of in vitro drug release from NPs revealed a substantial drug retention profile compared to the unencapsulated drug. These NPs were selectively internalized into target PC cells overexpressing PSMA, and displayed a dose-dependent growth inhibition compared to cells devoid of the PSMA receptor. Remarkably, these targeted NPs exhibited growth-inhibitory activity at pM CTX concentrations, being markedly more potent than the free drug. This selectively targeted nano-delivery platform bears the promise of enhanced efficacy and minimal untoward toxicity.


2021 ◽  
Author(s):  
Yasuhiro Kamimura ◽  
Kazuaki Tadokoro ◽  
Sho Furuichi ◽  
Ryuji Yukami

Density dependence is a fundamental concept for fish population dynamics. Although density-dependent growth and maturity among older juveniles and adults is important for regulating fish population size and for fisheries management, the mechanism of density dependence for marine fishes remains unclear. Here, we examined changes in Japanese sardine growth with increasing abundance beginning in the 2010s and how the current pattern of density-dependent growth differs from that of a previous stock-increase period from the 1970s to early 1980s. During the current period of increasing abundance, mean standard length has already dropped to the lowest level yet observed and growth has declined more sharply with increased abundance than in the 1970s and 1980s. Mesozooplankton biomass in July in the summer feeding grounds was also lower during the current period. Therefore, our results suggest that summer food availability in the western North Pacific controls the strength of density-dependent growth. A lower carrying capacity for Japanese sardine could account for the stronger density dependence of growth observed in the 2010s; this indicates that future Japanese sardine abundance might not increase as much as in the 1980s unless food availability improves.


mBio ◽  
2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Yi Lou ◽  
Jing Zhang ◽  
Guanghui Wang ◽  
Wenqin Fang ◽  
Shumin Wang ◽  
...  

Fusarium head blight (FHB), caused predominantly by Fusarium graminearum , is an economically devastating disease of a wide range of cereal crops. Our previous study identified F. graminearum Vps17, Vps5, Snx41, and Snx4 as PX domain-containing proteins that were involved in membrane trafficking mediating the fungal development and pathogenicity, but the identity and biological roles of the remaining members of this protein family remain unknown in this model phytopathogen.


2021 ◽  
Vol 22 (24) ◽  
pp. 13588
Author(s):  
Huachun Sheng ◽  
Shuangxi Zhang ◽  
Yanping Wei ◽  
Shaolin Chen

In plants, seedling growth is subtly controlled by multiple environmental factors and endogenous phytohormones. The cross-talk between sugars and brassinosteroid (BR) signaling is known to regulate plant growth; however, the molecular mechanisms that coordinate hormone-dependent growth responses with exogenous sucrose in plants are incompletely understood. Skotomorphogenesis is a plant growth stage with rapid elongation of the hypocotyls. In the present study, we found that low-concentration sugars could improve skotomorphogenesis in a manner dependent on BR biosynthesis and TOR activation. However, accumulation of BZR1 in bzr1-1D mutant plants partially rescued the defects of skotomorphogenesis induced by the TOR inhibitor AZD, and these etiolated seedlings displayed a normal phenotype like that of wild-type seedlings in response to both sucrose and non-sucrose treatments, thereby indicating that accumulated BZR1 sustained, at least partially, the sucrose-promoted growth of etiolated seedlings (skotomorphogenesis). Moreover, genetic evidence based on a phenotypic analysis of bin2-3bil1bil2 triple-mutant and gain-of-function bin2–1 mutant plant indicated that BIN2 inactivation was conducive to skotomorphogenesis in the dark. Subsequent biochemical and molecular analyses enabled us to confirm that sucrose reduced BIN2 levels via the TOR–S6K2 pathway in etiolated seedlings. Combined with a determination of the cellulose content, our results indicated that sucrose-induced BIN2 degradation led to the accumulation of BZR1 and the enhancement of cellulose synthesis, thereby promoting skotomorphogenesis, and that BIN2 is the converging node that integrates sugar and BR signaling.


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