Estimating Amino Acid Requirements in Real-Time for Precision-Fed Pigs: The Challenge of Variability among Individuals

This study aimed to measure protein deposition (PD) in pigs fed with daily tailored diets where either dietary lysine (Lys) or threonine (Thr) were provided at independent levels (ignoring an ideal ratio). A total of 95 growing pigs (35 kg body weight (BW)) with electronic ear tags granting them access to automatic feeders were randomly assigned to treatments. The setup was an unbalanced 2 × 5 factorial arrangement with Lys and Thr provided at five levels (i.e., 60%, 80%, 100%, 120%, and 140% of the estimated individual requirements of Lys and Thr), resulting in 25 treatments for 21 days. The observed PD variation to Lys and Thr provisions was large, with Lys and Thr intake explaining only 11% of the variation. Cluster analysis discriminated pigs with low (167 g/d, n = 16), medium (191 g/d, n = 38), and high (213 g/d, n = 37) PD, but with a similar amino acid intake. Differences in PD were associated with differences in nutrient efficiency of utilization. Providing Lys and Thr in a factorial mode, ignoring an ideal ratio, did not decrease the variability in PD. Future research efforts should focus on identifying and investigating the sources of interindividual variability—a necessary step before final recommendations can be made for AA in precision-fed pigs.

Legume plant defenses and nutrients mediate indirect interactions between soil rhizobia and chewing herbivores

Soil bacteria that form mutualisms with plants, such as rhizobia, affects susceptibility of plants to herbivores and pathogens. Soil rhizobia also promote nitrogen fixation, which mediates host nutrient levels and defenses. However, whether aboveground herbivores affect the function of soil rhizobia remains poorly understood. We assessed reciprocal interactions between Sitona lineatus, a chewing herbivore, and pea (Pisum sativum) plants grown with or without rhizobia (Rhizobium leguminosarum biovar viciae). We also examined the underlying plant-defense and nutritional mechanisms of these interactions. In our experiments, soil rhizobia influenced feeding and herbivory by chewing herbivores. Leaf defoliation by S. lineatus was lower on plants treated with rhizobia, but these insects had similar amino acid levels compared to those on un-inoculated plants. Plants grown with soil rhizobia had increased expression of gene transcripts associated with phytohormone-mediated defense, which may explain decreased susceptibility to S. lineatus. Rhizobia also induced expression of gene transcripts associated with physical and antioxidant-related defense pathways in P. sativum. Conversely, S. lineatus feeding reduced the number of root nodules and nodule biomass, suggesting a disruption of the symbiosis between plants and rhizobia. Our study shows that aboveground herbivores can engage in mutually antagonistic interactions with soil microbes mediated through a multitude of plant-mediated pathways.

AID overexpression leads to aggressive murine CLL and non-Ig mutations that mirror human neoplasms.

Most cancers become more dangerous by the outgrowth of malignant subclones with additional DNA mutations that favor proliferation or survival. Using chronic lymphocytic leukemia (CLL), a disease exemplary of this process, and a model for neoplasms in general, we created transgenic mice overexpressing the enzyme, activation-induced deaminase (AID), whose normal function is to induce DNA mutations in B lymphocytes. AID allows normal B lymphocytes to develop more effective immunoglobulin (Ig)-mediated immunity, but also is able to mutate non-Ig genes, predisposing to cancer. In chronic lymphocytic leukemia (CLL), AID expression correlates with poor prognosis suggesting a role for this enzyme in disease progression. Nevertheless, direct experimental evidence identifying the specific genes that are mutated by AID and indicating that those genes are associated with disease progression is not available. To address this point, we overexpressed Aicda in a murine model of CLL (Em-TCL1). Analyses of TCL1/AID mice demonstrate a role for AID in disease kinetics, CLL-cell proliferation, and the development of cancer-related target mutations with canonical AID signatures in non-Igs genes. Notably, our mouse models can accumulate mutations in the same genes that are mutated in human cancers. Moreover, some of these mutations occur at homologous positions, leading to identical or chemically-similar amino acid substitutions as in human CLL and lymphoma.Together, these findings support a direct link between aberrant AID activity and CLL driver mutations that are then selected for their oncogenic effects, whereby AID promotes aggressiveness in CLL and other B-cell neoplasms.

Functional and Structural Variation among Sticholysins, Pore-Forming Proteins from the Sea Anemone Stichodactyla helianthus

Venoms constitute complex mixtures of many different molecules arising from evolution in processes driven by continuous prey–predator interactions. One of the most common compounds in these venomous cocktails are pore-forming proteins, a family of toxins whose activity relies on the disruption of the plasmatic membranes by forming pores. The venom of sea anemones, belonging to the oldest lineage of venomous animals, contains a large amount of a characteristic group of pore-forming proteins known as actinoporins. They bind specifically to sphingomyelin-containing membranes and suffer a conformational metamorphosis that drives them to make pores. This event usually leads cells to death by osmotic shock. Sticholysins are the actinoporins produced by Stichodactyla helianthus. Three different isotoxins are known: Sticholysins I, II, and III. They share very similar amino acid sequence and three-dimensional structure but display different behavior in terms of lytic activity and ability to interact with cholesterol, an important lipid component of vertebrate membranes. In addition, sticholysins can act in synergy when exerting their toxin action. The subtle, but important, molecular nuances that explain their different behavior are described and discussed throughout the text. Improving our knowledge about sticholysins behavior is important for eventually developing them into biotechnological tools.

Unique and Universal Proteins in Human Genome

<span>One of the major troubles with a comparative analysis between human and other species is that only similar amino acid sequences are selected for analysis. To find the connection among the species and find out the unique, the common and the universal proteins, the entire genome of 40 species are compared with the human genome which is utilized as reference genome. More than 11 billion pairwise alignments are performed using blastp. Several findings are introduced in this study, for example, we found 330 unique proteins in human genome and have insignificant hits in all tested genomes, the number of universal proteins in human genome and conserved in all tested species is 82, and there are 180 proteins common in vertebrates genomes, but have insignificant hits in the other tested species. In contrary to the previous studies which use selected set of the genes and do not consider the whole genomes, this study proves that the similarity between human and chimpanzee is only 94.8.</span>

Structure and function of secretory glochids and nectar composition in two Opuntioideae (Cactaceae) species

Cactaceae exhibit highly modified spines that are considered to be extrafloral nectaries (EFNs). Despite their ecological and taxonomical relevance in this family, little is known on their structure and function. We have described the anatomy, ontogenesis, and ultrastructure of the secretory glochids in two Opuntioideae species. Young cladodes of Brasiliopuntia brasiliensis (Willd.) A. Berger and Nopalea cochenillifera (L.) Salm-Dyck were processed for light and electron microscopy studies. The composition of the secretions was analyzed by high performance liquid chromatography. The secretory glochids were soft, massive, and barbed, as well as translucent. Hyaline droplets on the secretory glochid apex were collected by aggressive ants. The secretory glochids originated from the areolar meristem, beginning as small protuberances formed by protoderm and ground meristem. Mature secretory glochids consisted of a central multiseriate axis of ground cells covered by uniseriate epidermis with a continuous cuticle, and exhibited three regions: (i) dilated vascularized base with parenchyma cells exhibiting features associated to nectar secretion; (ii) elongated median region with juxtaposed fusiform non-lignified parenchyma cells; and (iii) tapered apical portion with immature fibers loosely arranged cells. The exudate was sucrose-dominant with a similar amino acid profile in both species. Our results shed light on the secretory activity of glochids in Cactaceae and their role in cactus–ant interactions.

Spectral and photochemical diversity of tandem cysteine cyanobacterial phytochromes

The atypical trichromatic cyanobacterial phytochrome NpTP1 from Nostoc punctiforme ATCC 29133 is a linear tetrapyrrole (bilin)-binding photoreceptor protein that possesses tandem-cysteine residues responsible for shifting its light-sensing maximum to the violet spectral region. Using bioinformatics and phylogenetic analyses, here we established that tandem-cysteine cyanobacterial phytochromes (TCCPs) compose a well-supported monophyletic phytochrome lineage distinct from prototypical red/far-red cyanobacterial phytochromes. To investigate the light-sensing diversity of this family, we compared the spectroscopic properties of NpTP1 (here renamed NpTCCP) with those of three phylogenetically diverged TCCPs identified in the draft genomes of Tolypothrix sp. PCC7910, Scytonema sp. PCC10023, and Gloeocapsa sp. PCC7513. Recombinant photosensory core modules of ToTCCP, ScTCCP, and GlTCCP exhibited violet-blue–absorbing dark-states consistent with dual thioether-linked phycocyanobilin (PCB) chromophores. Photoexcitation generated singly-linked photoproduct mixtures with variable ratios of yellow-orange and red-absorbing species. The photoproduct ratio was strongly influenced by pH and by mutagenesis of TCCP- and phytochrome-specific signature residues. Our experiments support the conclusion that both photoproduct species possess protonated 15E bilin chromophores, but differ in the ionization state of the noncanonical “second” cysteine sulfhydryl group. We found that the ionization state of this and other residues influences subsequent conformational change and downstream signal transmission. We also show that tandem-cysteine phytochromes present in eukaryotes possess similar amino acid substitutions within their chromophore-binding pocket, which tune their spectral properties in an analogous fashion. Taken together, our findings provide a roadmap for tailoring the wavelength specificity of plant phytochromes to optimize plant performance in diverse natural and artificial light environments.

Biological functions and theranostic potential of HMGB family members in human cancers

The high mobility group box (HMGB) protein family consists of four members: HMGB1, 2, 3, and 4. They share similar amino acid sequences and identical functional regions, especially HMGB1, 2, and 3. The homology in structure may lead to similarity in function. In fact, though their targets may be different, they all possess the fundamental function of binding and distorting target DNAs. However, further research confirmed they are distributed differently in tissues and involved in various distinct physiological and pathological cellular processes, including cell proliferation, division, migration, and differentiation. Recently, the roles of HMGB family members in carcinogenesis has been widely investigated; however, systematic discussion on their functions and clinical values in malignant tumors is limited. In this review, we mainly review and summarize recent advances in knowledge of HMGB family members in terms of structure, distribution, biochemical cascades, and specific mechanisms regarding tumor progression. Importantly, the diagnostic, prognostic, and therapeutic value of these proteins in cancers is discussed. Finally, we envisage the orientation and challenges of this field in further studies.

Large Ankyrin repeat proteins are formed with similar and energetically favorable units

Ankyrin containing proteins are one of the most abundant repeat protein families present in all extant organisms. They are made with tandem copies of similar amino acid stretches that fold into elongated architectures. Here, we build and curated a dataset of 200 thousand proteins that contain 1,2 million Ankyrin regions and characterize the abundance, structure and energetics of the repetitive regions in natural proteins. We found that there is a continuous roughly exponential variety of array lengths with an exceptional frequency at 24 repeats. We describe that individual repeats are seldom interrupted with long insertions and accept few deletions, consistently with the know tertiary structures. We found that longer arrays are made up of repeats that are more similar to each other than shorter arrays, and display more favourable folding energy, hinting at their evolutionary origin. The array distributions show that there is a physical upper limit to the size of an array of Ankyrin repeats of about 120 copies, consistent with the limit found in nature. Analysis of the identity patterns within the arrays suggest that they may have originated by sequential copies of more than one Ankyrin unit.Author summaryRepeat proteins are coded in tandem copies of similar amino acid stretches. We built and curated a large dataset of Ankyrin containing proteins, one of the most abundant families of repeat proteins, and characterized the structure of the arrays formed by the repetitions. We found that large arrays are constructed with repetitions that are more similar to each other than shorter arrays. Also, the largest the array, the more energetically favourable its folding energy is. We speculate about the mechanistic origin of large arrays and hint into their evolutionary dynamics.