Large Family Research Articles

The Power of Molecular Dynamics Simulations and Their Applications to Discover Cysteine Protease Inhibitors.

A large family of enzymes with the function of hydrolyzing peptide bonds, called peptidases or cysteine proteases (CPs), are divided into three categories according to the peptide chain involved. CPs catalyze the hydrolysis of amide, ester, thiol ester, and thioester peptide bonds. They can be divided into several groups, such as papain-like (CA), viral chymotrypsin-like CPs (CB), papain-like endopeptidases of RNA viruses (CC), legumain-type caspases (CD), and showing active residues of His, Glu/Asp, Gln, Cys (CE). The catalytic mechanism of CPs is the essential cysteine residue present in the active site. These mechanisms are often studied through computational methods that provide new information about the catalytic mechanism and identify inhibitors. The role of computational methods during drug design and development stages is increasing. Methods in Computer-Aided Drug Design (CADD) accelerate the discovery process, increase the chances of selecting more promising molecules for experimental studies, and can identify critical mechanisms involved in the pathophysiology and molecular pathways of action. Molecular dynamics (MD) simulations are essential in any drug discovery program due to their high capacity for simulating a physiological environment capable of unveiling significant inhibition mechanisms of new compounds against target proteins, especially CPs. Here, a brief approach will be shown on MD simulations and how the studies were applied to identify inhibitors or critical information against cysteine protease from several microorganisms, such as Trypanosoma cruzi (cruzain), Trypanosoma brucei (rhodesain), Plasmodium spp. (falcipain), and SARS-CoV-2 (Mpro). We hope the readers will gain new insights and use our study as a guide for potential compound identifications using MD simulations.

From the mono model to the family. 60 years of tractor DT-75. Little-known modifications

60 years ago, on December 30, 1963, serial production of the most famous and common tracked agricultural tractor DT-75 was started at the Volgograd Tractor Plant. The manufacture of a monomodel (general-purpose tractor DT-75) moved to the production of a large family of modifications and complete sets, the total number of which is approaching 30. The mass-production included basic general-purpose tractors DT-75, DT-75M, DT-75MV, DT-75N, DT-75D, their swamp DT-75B, DT-75BV, DT-75NB and steep DT-75K modifications. There are also peat DT-75DT and arable-tilled DT-75NP, DT-75DP tractors, produced in small batches. And tractors DT-75DA, DT-75BK, DT-75BR, remaining only in prototypes. These little-known tractors are described in this article.

Determinants of Smallholder Farmers’ Decisions to Use Multiple Climate-Smart Agricultural Technologies in North Wello Zone, Northern Ethiopia

Climate change presents significant challenges to agriculture in developing nations, affecting farmers’ livelihoods and food security. In Ethiopia, agriculture is crucial to the economy and the well-being of millions. This study focuses on analyzing the determinants that affect smallholder farmers’ adoption of climate-smart agriculture (CSA) technologies in the North Wello administrative zone, northern Ethiopia. Through multivariate and ordered probit econometric models, data from 411 rural household heads were analyzed. Results reveal the synergy among climate-smart agricultural practices in rainfed farming systems, essential for crafting a comprehensive CSA package within an agroecological framework. The multivariate probit estimation results show that education, membership in local organizations, farm size, tropical livestock unit (TLU), irrigated land ownership, plot number, steep slope, farmland distance to home, and access to a local media source are positive determinants for the decision to use the type and several climate-smart agricultural practices. Lack of credit, large family size, distance from extension services, and proximity to the nearest market were all associated with lower adoption of all CSA technologies. The findings suggest that blanket recommendations for climate-smart agricultural technologies for smallholder farmers can be avoided. The complementarities that exist between CSA technologies may require further investigation into how such complementarities have benefits in terms of improving land productivity and food security and reducing climate-related risks for smallholder farmers in Ethiopia and other contexts. Moreover, by emphasizing an agroecological framework, the study promotes environmentally sustainable and socially equitable agricultural practices that are economically viable, contributing to broader environmental sustainability and development goals.

Many children, many blessings: Reinterpreting Psalm 127:5 in the Nigerian context

The idea of “many children, many blessings” in Ps 127:5 resonates with African traditional belief systems. However, in contemporary Nigeria, modernisation has introduced inescapable variables that make large families undesirable. In spite of this, many Nigerians still produce many children, apparently relying on the traditional belief that God determines one’s number of children, and possibly also on Ps 127:5. Applying the historical-critical and descriptive methods, the article assessed the relevance of Ps 127:5 in contemporary Nigeria and found that the text reflects the ancient Israelite context wherein parents depended on the number of their children in socio-economic terms, a situation which also resonates with the premodern African context. The modern Nigerian context, however, brought about changes in the pattern of parent-child interdependence such that now even peasant parents have to send their children to school and do all the manual work alone. In view of the high rate of unemployment, even many university graduates still have to depend on their parents. With this transition, large families come with implications such as hunger, poor health, and inadequate or lack of Western education for the children. Moreover, raising large families now has to contend with global issues such as overpopulation and family planning. To this end, a pastoral application of Ps 127:5 in Nigeria now has to respond to issues that come with large families.

Racial and Temporal Differences in Fertility-Education Trade-Offs Reveal the Effect of Economic Opportunities on Optimum Family Size in the United States.

Contemporary trends in low fertility can in part be explained by increasing incentives to invest in offspring's embodied capital over offspring quantity in environments where education is a salient source of social mobility. However, studies on this subject have often neglected to empirically examine heterogeneity, missing out on the opportunity to investigate how this relationship is impacted when individuals are excluded from meaningful participation in economic spheres. Using General Social Survey data from the United States, I examine changes in the relationship between number of siblings and college attendance for White and Black respondents throughout the 1900s. Results show that in the early 1900s, White individuals from larger families had a lower chance of completing four years of college education than those from smaller families, whereas the likelihood for Black individuals was more uniform across family sizes. These racial differences mostly converged in the later part of the century. These results may help explain variations in the timing of demographic transitions within different racial groups in the United States and suggest that the benefits of decreasing family size on educational outcomes may be conditional on the specific economic opportunities afforded to a family.

Glucose transporter-1 deficiency syndrome with extreme phenotypic variability in a five-generation family carrying a novel SLC2A1 variant.

Glucose transporter-1 (GLUT1) deficiency syndrome (GLUT1-DS) is a metabolic disorder due to reduced expression of GLUT1, a glucose transporter of the central nervous system. GLUT1-DS is caused by heterozygous SLC2A1 variants that mostly arise de novo. Here, we report a large family with heterogeneous phenotypes related to a novel SLC2A1 variant. We present clinical and genetic features of a five-generation family with GLUT1-DS. The 14 (nine living) affected members had heterogeneous phenotypes, including seizures (11/14), behavioral disturbances (5/14), mild intellectual disability (3/14), and/or gait disabilities (2/14). Brain magnetic resonance imaging revealed hippocampal sclerosis in the 8-year-old proband, who also had drug-responsive absences associated with attention-deficit/hyperactivity disorder. His 52-year-old father, who had focal epilepsy since childhood, developed paraparesis related to a reversible myelitis associated with hypoglycorrhachia. Molecular study detected a novel heterozygous missense variant (c.446C>T) in exon 4 of SLC2A1 (NM: 006516.2) that cosegregated with the illness. This variant causes an amino acid replacement (p.Pro149Leu) at the fourth transmembrane segment of GLUT1, an important domain located at its catalytic core. Our study illustrates the extremely heterogenous phenotypes in familial GLUT1-DS, ranging from milder classic phenotypes to more subtle neurological disorder including paraparesis. This novel SLC2A1 variant (c.446C>T) provides new insight into the pathophysiology of GLUT1-DS.

Decoding Arabidopsis thaliana CPK/SnRK Superfamily Kinase Client Signaling Networks Using Peptide Library and Mass Spectrometry

Members of the calcium-dependent protein kinase (CDPK/CPK) and SNF-related protein kinase (SnRK) superfamilies are commonly found in plants and some protists. Our knowledge of client specificity of the members of this superfamily is fragmentary. As this family is represented by over 30 members in Arabidopsis thaliana, the identification of kinase-specific and overlapping client relationships is crucial to our understanding the nuances of this large family of kinases as directed towards signal transduction pathways. Herein, we used the kinase client (KiC) assay—a relative, quantitative, high-throughput mass spectrometry-based in vitro phosphorylation assay—to identify and characterize potential CPK/SnRK targets of Arabidopsis. Eight CPKs (1, 3, 6, 8, 17, 24, 28, and 32), four SnRKs (subclass 1 and 2), and PPCK1 and PPCK2 were screened against a synthetic peptide library that contains 2095 peptides and 2661 known phosphorylation sites. A total of 625 in vitro phosphorylation sites corresponding to 203 non-redundant proteins were identified. The most promiscuous kinase, CPK17, had 105 candidate target proteins, many of which had already been discovered. Sequence analysis of the identified phosphopeptides revealed four motifs: LxRxxS, RxxSxxR, RxxS, and LxxxxS, that were significantly enriched among CPK/SnRK clients. The results provide insight into both CPK- and SnRK-specific and overlapping signaling network architectures and recapitulate many known in vivo relationships validating this large-scale approach towards discovering kinase targets.

Beauville p-groups of wild type and groups of maximal class

AbstractLet G be a Beauville p-group. If G exhibits a ‘good behaviour’ with respect to taking powers, then every lift of a Beauville structure of $$G/\Phi (G)$$ G / Φ ( G ) is a Beauville structure of G. We say that G is a Beauville p-group of wild type if this lifting property fails to hold. Our goal in this paper is twofold: firstly, we fully determine the Beauville groups within two large families of p-groups of maximal class, namely metabelian groups and groups with a maximal subgroup of class at most 2; secondly, as a consequence of the previous result, we obtain infinitely many Beauville p-groups of wild type.

Economic Implications of Government Flood Control Policy: A Case of Rice in Japan

Japan’s susceptibility to and severity of floods have necessitated flood control policies by the government. “Overflowing flood control”, in which the floods due to torrential rains are systematically diverted to agricultural lands in the upper to middle reaches, is one of them. More information is needed on the public assessment of the overflowing flood control policy, and this research seeks to bridge this gap. Data evaluating rice affected by the policy were collected from a random nth-price auction using a developed online system. The sample consisted of 47 consumers living in the downstream areas of the Edogawa River, one of Japan’s first-class, or prime, rivers. Data on their attitudes toward the policy were collected with a questionnaire. Multiple ordered probit models are used for regression analysis. The results show that the sample respondents were willing to pay an average of JPY 1578 for 5 kg of rice, slightly higher than the national average rice production cost, and that 36% of the sample agreed with the flood control policy, which is positively associated with large families or owning many assets.

Non‐accessible localizations

AbstractIn a 2005 paper, Casacuberta, Scevenels, and Smith construct a homotopy idempotent functor on the category of simplicial sets with the property that whether it can be expressed as localization with respect to a map is independent of the ZFC axioms. We show that this construction can be carried out in homotopy type theory. More precisely, we give a general method of associating to a suitable (possibly large) family of maps, a reflective subuniverse of any universe . When specialized to an appropriate family, this produces a localization which when interpreted in the ‐topos of spaces agrees with the localization corresponding to . Our approach generalizes the approach of Casacuberta et al. (Adv. Math. 197 (2005), no. 1, 120–139) in two ways. First, by working in homotopy type theory, our construction can be interpreted in any ‐topos. Second, while the local objects produced by Casacuberta et al. are always 1‐types, our construction can produce ‐types, for any . This is new, even in the ‐topos of spaces. In addition, by making use of universes, our proof is very direct. Along the way, we prove many results about “small” types that are of independent interest. As an application, we give a new proof that separated localizations exist. We also give results that say when a localization with respect to a family of maps can be presented as localization with respect to a single map, and show that the simplicial model satisfies a strong form of the axiom of choice that implies that sets cover and that the law of excluded middle holds.

Legionella effector LnaB is a phosphoryl-AMPylase that impairs phosphosignalling.

AMPylation is a posttranslational modification that generally modifies amino acid side chains of proteins with adenosine monophosphate (AMP)1,2. Here we report that with ATP as the ligand and actin as the host activator, the effector protein LnaB of Legionella pneumophila exhibits AMPylase activity toward the phosphoryl group of phosphoribose on PRR42-Ub that is generated by the SidE family effectors and deubiquitinases DupA/B in an E1/E2-independent ubiquitination process3-7. The product of LnaB is further hydrolyzed by an ADP-ribosyl hydrolase, MavL, to be Ub, thereby preventing accumulation of PRR42-Ub and ADPRR42-Ub and protecting the canonical ubiquitination in host cells. LnaB represents a large family of AMPylases adopting a common structural fold, which is distinct from those of the previously known AMPylases, in bacterial pathogens of more than 20 species. Moreover, LnaB also exhibits robust phosphoryl AMPylase activity toward phosphorylated residues and produces unique ADPylation modification in proteins. During infection, LnaB AMPylates the conserved phosphorylated tyrosine residues in the activation loop of the Src family kinases8,9, which dampens the host downstream phosphorylation signaling. Structural studies revealed the actin-dependent activation and catalytic mechanisms of the LnaB family of AMPylases. This study presents an unprecedented regulation and molecular mechanism in bacterial pathogenesis and protein phosphorylation.

A recurrent de novo missense mutation in COL1A1 causes osteogenesis imperfecta type II and preterm delivery in Normande cattle

BackgroundNine male and eight female calves born to a Normande artificial insemination bull named “Ly” were referred to the French National Observatory of Bovine Abnormalities for multiple fractures, shortened gestation, and stillbirth or perinatal mortality.ResultsUsing Illumina BovineSNP50 array genotypes from affected calves and 84 half-sib controls, the associated locus was mapped to a 6.5-Mb interval on chromosome 19, assuming autosomal inheritance with germline mosaicism. Subsequent comparison of the whole-genome sequences of one case and 5116 control genomes, followed by genotyping in the affected pedigree, identified a de novo missense substitution within the NC1 domain of the COL1A1 gene (Chr19 g.36,473,965G > A; p.D1412N) as unique candidate variant. Interestingly, the affected residue was completely conserved among 243 vertebrate orthologs, and the same substitution in humans has been reported to cause type II osteogenesis imperfecta (OI), a connective tissue disorder that is characterized primarily by bone deformity and fragility. Moreover, three COL1A1 mutations have been described to cause the same syndrome in cattle. Necropsy, computed tomography, radiology, and histology confirmed the diagnosis of type II OI, further supporting the causality of this variant. In addition, a detailed analysis of gestation length and perinatal mortality in 1387 offspring of Ly and more than 160,000 progeny of 63 control bulls allowed us to statistically confirm in a large pedigree the association between type II OI and preterm delivery, which is probably due to premature rupture of fetal membranes and has been reported in several isolated cases of type II OI in humans and cattle. Finally, analysis of perinatal mortality rates and segregation distortion supported a low level of germ cell mosaicism in Ly, with an estimate of 4.5% to 7.7% of mutant sperm and thus 63 to 107 affected calves born. These numbers contrast with the 17 cases reported and raise concerns about the underreporting of congenital defects to heredo-surveillance platforms, even for textbook genetic syndromes.ConclusionsIn conclusion, we describe a large animal model for a recurrent substitution in COL1A1 that is responsible for type II OI in humans. More generally, this study highlights the utility of such datasets and large half-sib families available in livestock species to characterize sporadic genetic defects.

Odorant receptor co-receptors affect expression of tuning receptors in Drosophila

Insects detect odorants using two large families of heteromeric receptors, the Odorant Receptors (ORs) and Ionotropic Receptors (IRs). Most OR and IR genes encode odorant-binding “tuning” subunits, whereas four (Orco, Ir8a, Ir25a, and Ir76b) encode co-receptor subunits required for receptor function. Olfactory neurons are thought to degenerate in the absence of Orco in ants and bees, and limited data suggest this may happen to some olfactory neurons in Drosophila fruit flies as well. Here, we thoroughly examined the role of co-receptors on olfactory neuron survival in Drosophila. Leveraging knowledge that olfactory neuron classes are defined by the expression of different tuning receptors, we used tuning receptor expression in antennal transcriptomes as a proxy for the survival of distinct olfactory neuron classes. Consistent with olfactory neuron degeneration, expression of many OR-family tuning receptors is decreased in Orco mutants relative to controls, and transcript loss is progressive with age. The effects of Orco are highly receptor-dependent, with expression of some receptor transcripts nearly eliminated and others unaffected. Surprisingly, further studies revealed that olfactory neuron classes with reduced tuning receptor expression generally survive in Orco mutant flies. Furthermore, there is little apoptosis or neuronal loss in the antenna of these flies. We went on to investigate the effects of IR family co-receptor mutants using similar approaches and found that expression of IR tuning receptors is decreased in the absence of Ir8a and Ir25a, but not Ir76b. As in Orco mutants, Ir8a-dependent olfactory neurons mostly endure despite near-absent expression of associated tuning receptors. Finally, we used differential expression analysis to identify other antennal genes whose expression is changed in IR and OR co-receptor mutants. Taken together, our data indicate that odorant co-receptors are necessary for maintaining expression of many tuning receptors at the mRNA level. Further, most Drosophila olfactory neurons persist in OR and IR co-receptor mutants, suggesting that the impact of co-receptors on neuronal survival may vary across insect species.

Co-Removal of Perfluorooctanoic Acid and Nitrate from Water by Coupling Pd Catalysis with Enzymatic Biotransformation.

PFAS (poly- and per-fluorinated alkyl substances) represent a large family of recalcitrant organic compounds that are widely used and pose serious threats to human and ecosystem health. Here, palladium (Pd0)-catalyzed defluorination and microbiological mineralization were combined in a denitrifying H2-based membrane biofilm reactor to remove co-occurring perfluorooctanoic acid (PFOA) and nitrate. The combined process, i.e., Pd-biofilm, enabled continuous removal of ∼4 mmol/L nitrate and ∼1 mg/L PFOA, with 81% defluorination of PFOA. Metagenome analysis identified bacteria likely responsible for biodegradation of partially defluorinated PFOA: Dechloromonas sp. CZR5, Kaistella koreensis, Ochrobacterum anthropic, and Azospira sp. I13. High-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and metagenome analyses revealed that the presence of nitrate promoted microbiological oxidation of partially defluorinated PFOA. Taken together, the results point to PFOA-oxidation pathways that began with PFOA adsorption to Pd0, which enabled catalytic generation of partially or fully defluorinated fatty acids and stepwise oxidation and defluorination by the bacteria. This study documents how combining catalysis and microbiological transformation enables the simultaneous removal of PFOA and nitrate.

Multiscale Modeling of Physical Properties of Nanoporous Frameworks: Predicting Mechanical, Thermal, and Adsorption Behavior.

ConspectusNanoporous frameworks are a large and diverse family of supramolecular materials, whose chemical building units (organic, inorganic, or both) are assembled into a 3D architecture with well-defined connectivity and topology, featuring intrinsic porosity. These materials play a key role in various industrial processes and applications, such as energy production and conversion, fluid separation, gas storage, water harvesting, and many more. The performance and suitability of nanoporous materials for each specific application are directly related to both their physical and chemical properties, and their determination is crucial for process engineering and optimization of performances. In this Account, we focus on some recent developments in the multiscale modeling of physical properties of nanoporous frameworks, highlighting the latest advances in three specific areas: mechanical properties, thermal properties, and adsorption.In the study of the mechanical behavior of nanoporous materials, the past few years have seen a rapid acceleration of research. For example, computational resources have been pooled to create a public large-scale database of elastic constants as part of the Materials Project initiative to accelerate innovation in materials research: those can serve as a basis for data-based discovery of materials with targeted properties, as well as the training of machine learning predictor models.The large-scale prediction of thermal behavior, in comparison, is not yet routinely performed at such a large scale. Tentative databases have been assembled at the DFT level on specific families of materials, such as zeolites, but prediction at larger scale currently requires the use of transferable classical force fields, whose accuracy can be limited.Finally, adsorption is naturally one of the most studied physical properties of nanoporous frameworks, as fluid separation or storage is often the primary target for these materials. We highlight the recent achievements and open challenges for adsorption prediction at a large scale, focusing in particular on the accuracy of computational models and the reliability of comparisons with experimental data available. We detail some recent methodological improvements in the prediction of adsorption-related properties: in particular, we describe the recent research efforts to go beyond the study of thermodynamic quantities (uptake, adsorption enthalpy, and thermodynamic selectivity) and predict transport properties using data-based methods and high-throughput computational schemes. Finally, we stress the importance of data-based methods of addressing all sources of uncertainty.The Account concludes with some perspectives about the latest developments and open questions in data-based approaches and the integration of computational and experimental data together in the materials discovery loop.

Genome-wide identification and expression analysis of Ubiquitin-specific protease gene family in maize (Zea mays L.)

BackgroundUbiquitin-specific proteases (UBPs) are a large family of deubiquitinating enzymes (DUBs). They are widespread in plants and are critical for plant growth, development, and response to external stresses. However, there are few studies on the functional characteristics of the UBP gene family in the important staple crop, maize (Zea mays L.).ResultsIn this study, we performed a bioinformatic analysis of the entire maize genome and identified 45 UBP genes. Phylogenetic analysis indicated that 45 ZmUBP genes can be divided into 15 subfamilies. Analysis of evolutionary patterns and divergence levels indicated that ZmUBP genes were present before the isolation of dicotyledons, were highly conserved and subjected to purifying selection during evolution. Most ZmUBP genes exhibited different expression levels in different tissues and developmental stages. Based on transcriptome data and promoter element analysis, we selected eight ZmUBP genes whose promoters contained a large number of plant hormones and stress response elements and were up-regulated under different abiotic stresses for RT-qPCR analysis, results showed that these genes responded to abiotic stresses and phytohormones to varying degrees, indicating that they play important roles in plant growth and stress response.ConclusionsIn this study, the structure, location and evolutionary relationship of maize UBP gene family members were analyzed for the first time, and the ZmUBP genes that may be involved in stress response and plant growth were identified by combining promoter element analysis, transcriptome data and RT-qPCR analysis. This study informs research on the involvement of maize deubiquitination in stress response.

Sociodemographic and Contextual Determinants of Men’s Fertility Desires in Northern Nigeria: An Analysis of the 2018 Demographic and Health Survey

Nigeria has a high fertility rate, averaging 5.1 children per woman. The desire for large families, especially by men from the northern region, is a crucial driver of the country’s high total fertility rate. There is, however, a shortage of evidence on the sociodemographic determinants of men’s fertility desires despite being essential stakeholders in fertility decisions in the family. This study, therefore, estimates men’s desired family sizes and the sociodemographic and contextual factors influencing their desires in the northern region of Nigeria. Data from the men’s recoded 2018 Nigeria Demographic and Health Survey dataset were used with a sample of 7,822 men. The chi-square test and ordinal logistic regression analysis were used to test the association and estimate the relationship between the outcome and predictor variables. The findings revealed that 71% of men desired to have at least six children, which was high irrespective of sociodemographic characteristics. However, the desire for six or more children was lower (65%) among the youngest cohort than among the oldest (80%). Being a Muslim (AOR = 4.50, 95% CI [3.86, 5.24], p < .05), having two or more wives (AOR = 2.41, 95% CI [1.68, 3.45], p < .05), having 3–5 (AOR = 2.28, 95% CI [1.89, 2.76], p < .05) and six or more (AOR = 6.03, 95% CI [4.48, 8.13], p < .05) living children, and living in the northeast (AOR = 2.03, 95% CI [1.75, 2.37], p < .05) and northwest (AOR = 1.44, 95% CI [1.20, 1.72], p < .05) zones were the most significant predictors of high fertility desire by men. Policymakers should target these categories of men in fertility and family planning programs to promote lowering and slowing the rate of fertility and population growth.

Modeling of host PDZ-dependent interactions with SARS-CoV-2 Envelope protein and changes in PDZ proteins expression in macrophages and dendritic cells.

PDZ (PSD-95/Dlg/ZO-1) domain-containing proteins constitute a large family of scaffolds involved in a wide range of cellular tasks, and mainly studied in polarity functions. Diverse host PDZ proteins can be targeted by viral pathogens which express proteins containing PDZ-binding motifs (PDZbm). Previously, we have identified host PDZ-based interactions with the SARS-CoV-2 E protein (2E) in human monocytes. Here, we deepen the study of these interactions by docking and molecular dynamics analyses to identify the most favorable PDZ-PDZbm interaction of seven host PDZ proteins with the PDZbm of 2E. In addition, we analyzed changes in the expression of three of the PDZ proteins identified as 2E interactors in monocytes (syntenin, ZO-2, and IL-16), in human monocyte-derived macrophages (MΦ) and in dendritic cells (DCs) upon stimulation. Our results suggest that these PDZ proteins may have important functions in professional antigen-presenting cells (APCs), and their targeting by the PDZbm of 2E, a central virulence determinant of SARS-CoV-2, support the hypothesis that such PDZ-dependent interaction in immune cells may constitute a viral evasion mechanism. Inhibitor design based on the PDZbm of 2E in the development of drugs against a variety of diseases is discussed.

Matreex: compact and interactive visualisation for scalable studies of large gene families.

Studying gene family evolution strongly benefits from insightful visualisations. However, the ever-growing number of sequenced genomes is leading to increasingly larger gene families, which challenges existing gene tree visualisations. Indeed, most of them present users with a dilemma: display complete but intractable gene trees, or collapse subtrees, thereby hiding their children's information. Here, we introduce Matreex, a new dynamic tool to scale-up the visualisation of gene families. Matreex's key idea is to use "phylogenetic" profiles, which are dense representations of gene repertoires, to minimise the information loss when collapsing subtrees. We illustrate Matreex's usefulness with three biological applications. First, we demonstrate on the MutS family the power of combining gene trees and phylogenetic profiles to delve into precise evolutionary analyses of large multi-copy gene families. Secondly, by displaying 22 intraflagellar transport gene families across 622 species cumulating 5'500 representatives, we show how Matreex can be used to automate large-scale analyses of gene presence-absence. Notably, we report for the first time the complete loss of intraflagellar transport in the myxozoan Thelohanellus kitauei. Finally, using the textbook example of visual opsins, we show Matreex's potential to create easily interpretable figures for teaching and outreach. Matreex is available from the Python Package Index (pip install matreex) with the source code and documentation available at https://github.com/DessimozLab/matreex.

The hydrates of chlorogenic acid in its aqueous solution and in stored food products

AbstractChlorogenic acids (CQAs), a large family of naturally occurring esters of quinic acid with one, two or even three cinnamic acids moieties and/or moieties of cinnamic acids derivatives, supplied to human organisms mainly with coffee, tea, fruit and vegetables, have been among the most frequently studied polyphenols. Of these, caffeic acid esters predominate, and 5-O-caffeoylquinic acid (5-CQA) is their main and most widespread representative. Recently performed studies have shown that after removing water from the aqueous solution of 5-CQA, its dry residue contains two hydrates of this compound, each consisting of two 5-CQA molecules and two molecules of H2O (2 × 5-CQA*2xH2O). The results presented in the paper not only define the characteristic features of 5-CQA but, more importantly, offer solid evidence that 5-CQA hydrates begin to form already in the aqueous solution of 5-CQA immediately after the dissolution of this compound and that the analogous process can occur in food products containing 5-CQA during their storage. Moreover, the performed experiments indicate the validity of the hypothesis that 5-CQA hydrates are formed by active collisions of 5-CQA molecules with monomeric/dimeric water molecules existing in trace amount in strongly associated aqueous systems. The presence of 5-CQA hydrates in liquid food products may have a significant impact on the assessment of some of their physicochemical properties as well as their biochemical activity.