Notes

TRAFIC: statistical design and style along with examination plan for the sensible first cycle 1/2 Bayesian adaptable dosage escalation demo throughout rheumatism.
Drought alters allocation patterns of carbon (C) and nutrients in trees and eventually impairs tree functioning. Elevated soil nutrient availability might alter the response of trees to drought. We hypothesize that increased soil nutrient availability stimulates root metabolism and carbon allocation to belowground tissues under drought stress. To test this hypothesis, we subjected three-year-old Pinus sylvestris saplings in open-top cambers during two subsequent years to drought using three different water treatments (100%, 20% and 0% plant available water in the soil) and two soil nutrient regimes (ambient and nitrogen-phosphorus-potassium (N-P-K) fertilization corresponding to 5 g N/m2/yr) and released drought thereafter. We conducted a 15N and 13C labelling experiment during the peak of the first-year drought by injecting 15N labelled fertilizer in the soil and exposing the tree canopies to 13C labelled CO2. The abundance of the N and C isotopes in the roots, stem and needles was assessed during the following year. C uptake was slightly lower in drought stressed trees, and extreme drought inhibited largely the N uptake and transport. Carbon allocation to belowground tissues was decreased under drought, but not in combination with fertilization. Our results indicate a potential positive feedback loop, where fertilization improved the metabolism and functioning of the roots, stimulating C allocation to belowground tissues. This way, soil nutrients compensated for drought-induced loss of root functioning, mitigating drought stress of trees.
Evolutionary analyses of well-annotated HIV sequence data can provide insights into viral transmission patterns and associated factors. Here, we explored the transmission dynamics of the HIV-1 subtype B epidemic across the San Diego (US) - Tijuana (Mexico) border region to identify factors that could help guide public health policy.

HIV pol sequences were collected from people with HIV in San Diego County and from Tijuana between 1996-2018. A multistep phylogenetic approach was used to characterize the dynamics of spread. The contribution of geospatial factors and HIV risk group to the local dynamics were evaluated.

Phylogeographic analyses of the 2,034 sequences revealed an important contribution of local transmission in sustaining the epidemic, as well as a complex viral migration network across the region. Geospatial viral dispersal between San Diego communities occurred predominantly among men-who-have-sex with-men with central San Diego being the main source (34.9%) and recipient (39.5%) of migrati efforts will be more effective. Combined, this work shows that epidemiological information gleaned from pathogen genomes can uncover mechanisms that underlie sustained spread and, in turn, can be a building block of public health decision making.Sheath senescence is an important part of bamboo shoot development during the fast growth stage. However, no information has been reported about this distinctive process until now. Using multiple approaches, we found that sheath senescence is a complex process that occurs sequentially with chloroplast corruption, chlorophyll degradation and water loss. Reactive oxygen species (ROS), salicylic acid and abscisic acid also accumulate in the senescing sheath. Transcriptome analysis showed that NAC and WRKY transcription factors, such as NAC2 and WRKY75, as well as their possible downstream target genes, such as those involved in ROS production, proteolysis and nutrition recycling, constitute the gene network of the bamboo sheath senescence process. Furthermore, the initiation of sheath senescence might be triggered by hexokinase genes, such as HXK6, which is localized to the mitochondrion and could promote leaf senescence when overexpressed in Arabidopsis. Sheath senescence occurs after the growth decrease of the internodes, which provides assimilates. The slowing of internode growth possibly results in sugar accumulation, such as glucose, in the sheath, which finally upregulates hexokinase genes and initiates sheath senescence. These findings reveal that sheath senescence is a multilevel regulation process and has a close link to the corresponding internode growth, which provides new insights into the shoot development of bamboo during the fast growth stage.Condensing enzymes catalyze the committed reaction of fatty acid elongation and determine the chain length of fatty acids accepted and produced by the elongation complex. While necessary for the elongation of very-long-chain fatty acids (VLCFAs), identified plant condensing enzymes cannot efficiently produce VLCFAs longer than 28 carbons, which are precursors for the most abundant cuticular waxes of most plant species that have been surveyed. The eceriferum2 (cer2) mutant of Arabidopsis thaliana has a severe wax-deficient phenotype and specifically lacks waxes longer than 28 carbons, but the CER2 protein does not share sequence similarity with condensing enzymes. Instead, CER2 is homologous to BAHD acyltransferases. Heterologous expression in yeast previously demonstrated that CER2, and a small clade of BAHD acyltransferases with high sequence identity to CER2, can extend the chain-length specificity of the condensing enzyme CER6. This biochemical function is distinct from that of the broader BAHD acyltransferase family. The product specificity and physiological functions of individual CER2-LIKE proteins are unique. Here, we demonstrate that CER2 physically interacts with the fatty acid elongase. We cloned chimeric CER2-LIKE proteins and expressed these in yeast cells to identify the features that define the substrate specificities of CER2-LIKEs. We generated homology-based structural models to compare CER2-LIKEs and BAHD acyltransferases. In addition, based on the current phylogenetic analysis of the CER2-LIKE clade, we describe two further Arabidopsis CER2-LIKE genes, CER2-LIKE3 and CER2-LIKE4. We used yeast expression and mutant analysis to characterize these genes. Collectively, these results expand our knowledge of the functions of CER2-LIKEs, the BAHD acyltransferase family and cuticular wax metabolism.Primordial germ cells (PGCs) are the founding population of the germ cell lineage that undergo a multistep process to generate spermatozoa or oocytes. Establishing an appropriate culture system for PGCs is a key challenge in reproductive biology. By a chemical screening using mouse PGC-like cells (mPGCLCs), which were induced from mouse embryonic stem cells, we reported previously that forskolin and rolipram synergistically enhanced the proliferation/survival of mPGCLCs with an average expansion rate of ~20-fold. In the present study, we evaluated other chemicals or cytokines to see whether they would improve the current mPGCLC culture system. Among the chemicals and cytokines examined, in the presence of forskolin and rolipram, cyclosporin A (CsA) and fibroblast growth factors (FGFs FGF2 and FGF10) effectively enhanced the expansion of mPGCLCs in vitro (~50-fold on average). During the expansion by CsA or FGFs, mPGCLCs comprehensively erased their DNA methylation to acquire a profile equivalent to that of gonadal germ cells in vivo, while maintaining their highly motile phenotype as well as their transcriptional properties as sexually uncommitted PGCs. Importantly, these mPGCLCs robustly contributed to spermatogenesis and produced fertile offspring. Furthermore, mouse PGCs (mPGCs) cultured with CsA ex vivo showed transcriptomes and DNA methylomes similar to those of cultured mPGCLCs. The improved culture system for mPGCLCs/mPGCs would be instructive for addressing key questions in PGC biology, including the mechanisms for germ cell migration, epigenetic reprogramming, and sex determination of the germline.Plants possess a regeneration capacity that enables them to survive after wounding. For example, detached Arabidopsis thaliana leaves are able to form adventitious roots from their cutting sites even in the absence of exogenous hormone supplements, as process termed de novo root regeneration (DNRR). Wounding rapidly induces auxin biosynthesis at the cutting sites and then elicits a signaling cascade to promote cell fate transitions and finally generate the adventitious roots. However, rooting rates in older plants are much lower than in younger leaf explants. In this review, we highlight the recent breakthroughs in the understanding of DNRR decay in older plants from at least two independent signaling routes (i) via the accumulation of EIN3 protein in older plants, which directly suppresses expression of WUSCHEL RELATED HOMEOBOX (WOX) genes to inhibit rooting; (ii) the miR156-SPLs-AP2/ERFs pathway, which modulates root regeneration by reducing auxin biosynthesis.Conspicuous color is a common trait of foliar galls, but their relationship with gall-inducing insects is unknown. Red and green galls were taken from sunny or shady parts of peach species Prunus persica (L.) Batsch. f. rubro-plena Schneid with peach aphid Tuberocephalus momonis (Matsumura) infestation. We found that the loss of photosynthetic pigments was associated with the conspicuous coloration of green gall tissues. The concentrations of anthocyanins significantly increased following ultraviolet (UV) irradiation of green gall tissues, suggesting that accumulation of anthocyanins in red galls is related to ultraviolet B and C (UVB and UVC) radiation. The expression of structural genes related to the biosynthesis of chlorogenic acid and malic acid benzoate was increased in all gall tissues and negatively correlated with the expression profiles of certain genes associated with photosynthetic biosynthesis, indicating that the increased transcript levels of the phenylpropanoid pathway might cause loss of photosynthetic efficiency in the gall tissues. Transcriptome and quantitative reverse transcription PCR analyses revealed that MYB transcription factors that up-regulate the biosynthesis of anthocyanins in red gall tissues might be activated by both UVB and UVC exposure. Comet assays suggest that green and red gall tissues have similar DNA damage following UV irradiation. R-848 cost No obvious effect of the up-regulated compounds on the growth of the peach aphid was observed. Interestingly, peach aphids under leaves painted with anthocyanins had lower mortality following UV irradiation than those in controls. These results suggest that the anthocyanins in red gall tissues have a defensive function for the peach aphid, protecting it against UV radiation.Hydraulic capacitance and carbohydrate storage are two drought adaptation strategies of woody angiosperms. However, we currently lack information on their associations and how they are associated with species' degree of isohydry. We measured total stem xylem nonstructural carbohydrate (NSC) concentration in the dry and wet seasons, xylem hydraulic capacitance, native leaf water potentials, pressure-volume curve parameters and photosynthetic performance in 24 woody understory species differing in their degree of isohydry. We found a trade-off between xylem water and carbohydrate storage both in storage capacitance and along a spectrum of isohydry. Species with higher hydraulic capacitance had lower native NSC storage. The less isohydric species tended to show greater NSC depletion in the dry season and have more drought-tolerant leaves. In contrast, the more isohydric species had higher hydraulic capacitance, which may enhance their drought avoidance capacity. In these species, leaf flushing in the wet season and higher photosynthetic rates in the dry season resulted in accumulation rather than depletion of NSC in the dry season.
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