Aldo-keto reductase (AKR) superfamily website and database: An update.

The aldo-keto reductase (AKR) superfamily is a large family of proteins found across the kingdoms of life. Shared features of the family include 1) structural similarities such as an (α/ß)8-barrel structure, disordered loop structure, cofactor binding site, and a catalytic tetrad, and 2) the ability to catalyze the nicotinamide adenine dinucleotide (phosphate) reduced (NAD(P)H)-dependent reduction of a carbonyl group. A criteria of family membership is that the protein must have a measured function, and thus, genomic sequences suggesting the transcription of potential AKR proteins are considered pseudo-members until evidence of a functionally expressed protein is available. Currently, over 200 confirmed AKR superfamily members are reported to exist. A systematic nomenclature for the AKR superfamily exists to facilitate family and subfamily designations of the member to be communicated easily. Specifically, protein names include the root "AKR", followed by the family represented by an Arabic number, the subfamily-if one exists-represented by a letter, and finally, the individual member represented by an Arabic number. The AKR superfamily database has been dedicated to tracking and reporting the current knowledge of the AKRs since 1997, and the website was last updated in 2003. Here, we present an updated version of the website and database that were released in 2023. The database contains genetic, functional, and structural data drawn from various sources, while the website provides alignment information and family tree structure derived from bioinformatics analyses.

Ocean to Tree: Leveraging Single-Molecule RNA-Seq to Repair Genome Gene Models and Improve Phylogenomic Analysis of Gene and Species Evolution.

Understanding gene evolution across genomes and organisms, including ctenophores, can provide unexpected biological insights. It enables powerful integrative approaches that leverage sequence diversity to advance biomedicine. Sequencing and bioinformatic tools can be inexpensive and user-friendly, but numerous options and coding can intimidate new users. Distinct challenges exist in working with data from diverse species but may go unrecognized by researchers accustomed to gold-standard genomes. Here, we provide a high-level workflow and detailed pipeline to enable animal collection, single-molecule sequencing, and phylogenomic analysis of gene and species evolution. As a demonstration, we focus on (1) PacBio RNA-seq of the genome-sequenced ctenophore Mnemiopsis leidyi, (2) diversity and evolution of the mechanosensitive ion channel Piezo in genetic models and basal-branching animals, and (3) associated challenges and solutions to working with diverse species and genomes, including gene model updating and repair using single-molecule RNA-seq. We provide a Python Jupyter Notebook version of our pipeline (GitHub Repository: Ctenophore-Ocean-To-Tree-2023 https://github.com/000generic/Ctenophore-Ocean-To-Tree-2023 ) that can be run for free in the Google Colab cloud to replicate our findings or modified for specific or greater use. Our protocol enables users to design new sequencing projects in ctenophores, marine invertebrates, or other novel organisms. It provides a simple, comprehensive platform that can ease new user entry into running their evolutionary sequence analyses.

DRIVERS OF HYPERFERREMIA IN CHILDREN LIVING ON RADIOLOGICALLY CONTAMINATED TERRITORIES AFTER THE CHNPP ACCIDENT IN UKRAINE. / ЧИННИКИ, ЯКІ ВПЛИВАЮТЬ НА МЕХАНІЗМИ ФОРМУВАННЯ ПІДВИЩЕНОЇ ЩІЛЬНОСТІ КІСТКОВОЇ ТКАНИНИ У ДІТЕЙ, ЖИТЕЛІВ РАДІОАКТИВНО ЗАБРУДНЕНИХ ТЕРИТОРІЙ, ПІСЛЯ АВАРІЇ НА ЧАЕС.

OBJECTIVE: assessment of clinical-hematological and metabolic-biochemical parameters of the of bone tissue and hormonal regulation depending on the serum iron content and radiation dose values in children living on radiologically contaminated territories after the ChNPP accident in Ukraine. MATERIALS AND METHODS: Children (n = 271) living on radiologically contaminated territories (RCT) of Ukraine were involved in the study. Three study groups were formed according to the serum iron level (SIL), namely group I with SIL 10.0-22.0 µmol/l (n = 92), group II with SIL 23.0-34.0 µmol/l (n = 144), and group III with SIL above 35.0 µmol/l (n = 35). Diseases in the family tree, bodyweight at birth, complaints on osalgia, bone fractures, jaw anomalies, dental caries, and obesity were accounted. Morphometric parameters of erythrocytes and hemogram elements were analyzed. Creatinine, alkaline phosphatase, calcium, total protein, iron, cholesterol, bilirubin, and transaminases were assayed in blood serum. The urine content of the 19 free amino acids, serum content of the free thyroxine (FT4), pituitary thyroid-stimulating hormone (TSH), and cortisol were assayed both with bone tissue density. Individual radiation doses were calculated. RESULTS: In 12.9 % of cases the SIL was > 35.0 µmol/l. Relatives with endocrine diseases were often present in the family tree of children with SIL > 23.0 µmol/l. There were increased urine content of the free amino acids (p < 0.05) and signs of protein degradation under high SIL. Contents of amino acids involved in collagen synthesis and antioxidant status (alanine, serine, glutamine, aspartic acid) and iron metabolism (arginine, leucine) were assayed at the highest levels (p < 0.05). Urinary levels of valine, lysine, and methionine, which are associated with iron metabolism, were decreased (p < 0.05). An inverse correlation (rs = -0.58; p < 0.01) was established between the serum TSH and cortisol levels regardless of the SIL. Serum TSH level directly correlated with urine content of amino acids involved in collagen synthesis. An inverse correlation (rs = -0.55; p < 0.001) was established between the serum TSH level and urine content of tyrosine that is essential for the thyroid hormone (triiodothyronine and thyroxine) synthesis.Cortisol was found having a negative effect on protein synthesis. Inverse correlation was established between the serum cortisol level and urine content of the free amino acids essential for collagen synthesis. There was no dependence of the average radiation dose values on the SIL. An inverse correlation was determined between the patient's radiation dose and SIL > 35.0 µmol/l (rs = -0.29; p < 0.05). CONCLUSIONS: The increased SIL in children living on RCT may occur due to both a genetic predisposition and the acquired factors driving protein and mineral metabolism of bone and their hormonal regulation.

Marine pyridoacridine, pyridoacridone and pyrroloacridine alkaloids.

The families of pyridoacridine, pyridoacridone, and pyrroloacridine alkaloids are fascinating classes of natural products that have attracted the attention of chemists for over 80 years. Since the first purification of a brightly colored molecule isolated from the sea anemone Calliactis parasitica in 1940, over 110 examples of these alkaloids have been reported from marine organisms. While the paucity of numbers of protons relative to carbons and nitrogens in these molecules presents challenges in structure solution, the chemist is rewarded by their bright pigmented colors and typically diverse biological activities. In the past, several authors have proposed biosynthetic relationships within the pyridoacridine family of alkaloids, formulating a family tree derived from the reaction of dopaminequinone and kynuramine to tie together over 75 alkaloids. Inclusion of two additional quinones, and one homologous diamine, building blocks, for which there is biomimetic synthesis support, is suggestive of a more expansive connected biogenesis that encompasses not only pyridoacridines, but also pyridoacridone, and pyrroloacridine alkaloids. This review covers the isolation, structure elucidation, and proposed biosynthesis and biogenesis of pyridoacridine, pyridoacridone and pyrroloacridine marine alkaloids published to the end of 2022. Biomimetic or bio-inspired syntheses of the compound classes are described and new biological activities reported since 2004 are updated.

First Evidence of Familial Transmission of Hereditary Gastrointestinal Polyposis Associated with Germline APC Variant in Jack Russell Terriers.

Jack Russell terriers (JRTs) with gastrointestinal (GI) neoplastic polyps have been recently reported to harbor an identical germline variant in the adenomatous polyposis coli (APC) gene, c.[462_463delinsTT], in the heterozygous state, which indicates that this disease is an autosomal dominant hereditary disorder. Many individual cases of this disease have been observed in clinical practice; however, familial transmission has not been demonstrated due to the difficulty in tracing the family members of household dogs, especially after the disease's onset in adulthood. Recently, we encountered two cases of GI polyposis in maternal half sisters. These two cases facilitated the identification of additional relatives spanning three generations, including parents, full and half siblings of the dam (aunt and uncle), littermate and non-littermate siblings, and a nephew. Genetic analysis revealed that 11 of the 14 examined JRTs in this family carried the heterozygous germline APC variant, and eight dogs with the variant already had a current and/or past medical history of GI neoplastic polyps. Some cases in the family showed significantly more severe disease phenotypes than those initially reported, suggesting that the severity of this disease can vary considerably among individuals. Moreover, familial aggregation of severe cases suggested that the genetic modifier involved in increasing severity may have been transmitted in this family in addition to the germline APC variant. Furthermore, in addition to this family, we reported two other families of JRTs affected by hereditary GI polyposis that consisted of five full and half siblings and a mother-daughter pair, respectively. These findings unequivocally establish the transgenerational transmission of hereditary GI polyposis associated with the germline APC variant in JRT lineages.

Addressing the feasibility of people of African descent finding living African relatives using direct-to-consumer genetic testing.

People of African descent use direct-to-consumer genomics services such as 23andMe and AncestryDNA for various family histories and health reasons, including identifying and interacting with the previously unknown living African genetic relatives. In this commentary, I argue that it is reasonable to consider that cousin pairs consisting of an African person and a descendant of an African person enslaved in the Americans during the Transatlantic Slave Trade (i.e., a person of African descent) have genealogical ancestors recent enough to be detected using autosomal DNA testing where the pair has shared ancestors in the range of 20-6 generations ago from the present.

Phylogenomics as an effective approach to untangle cross-species hybridization event: A case study in the family Nymphaeaceae.

Hybridization is common and considered as an important evolutionary force to increase intraspecific genetic diversity. Detecting hybridization events is crucial for understanding the evolutionary history of species and further improving molecular breeding. The studies on identifying hybridization events through the phylogenomic approach are still limited. We proposed the conception and method of identifying allopolyploidy events by phylogenomics. The reconciliation and summary of nuclear multi-labeled gene family trees were adopted to untangle hybridization events from next-generation data in our novel phylogenomic approach. Given horticulturalists' relatively clear cultivated crossbreeding history, the water lily family is a suitable case for examining recent allopolyploidy events. Here, we reconstructed and confirmed the well-resolved nuclear phylogeny for the Nymphaeales family in the context of geological time as a framework for identifying hybridization signals. We successfully identified two possible allopolyploidy events with the parental lineages for the hybrids in the family Nymphaeaceae based on summarization from multi-labeled gene family trees of Nymphaeales. The lineages where species Nymphaea colorata and Nymphaea caerulea are located may be the progenitors of horticultural cultivated species Nymphaea 'midnight' and Nymphaea 'Woods blue goddess'. The proposed hybridization hypothesis is also supported by horticultural breeding records. Our methodology can be widely applied to identify hybridization events and theoretically facilitate the genome breeding design of hybrid plants.

SpeciesRax: A Tool for Maximum Likelihood Species Tree Inference from Gene Family Trees under Duplication, Transfer, and Loss.

Species tree inference from gene family trees is becoming increasingly popular because it can account for discordance between the species tree and the corresponding gene family trees. In particular, methods that can account for multiple-copy gene families exhibit potential to leverage paralogy as informative signal. At present, there does not exist any widely adopted inference method for this purpose. Here, we present SpeciesRax, the first maximum likelihood method that can infer a rooted species tree from a set of gene family trees and can account for gene duplication, loss, and transfer events. By explicitly modeling events by which gene trees can depart from the species tree, SpeciesRax leverages the phylogenetic rooting signal in gene trees. SpeciesRax infers species tree branch lengths in units of expected substitutions per site and branch support values via paralogy-aware quartets extracted from the gene family trees. Using both empirical and simulated data sets we show that SpeciesRax is at least as accurate as the best competing methods while being one order of magnitude faster on large data sets at the same time. We used SpeciesRax to infer a biologically plausible rooted phylogeny of the vertebrates comprising 188 species from 31,612 gene families in 1 h using 40 cores. SpeciesRax is available under GNU GPL at https://github.com/BenoitMorel/GeneRax and on BioConda.

GeneRax: A Tool for Species-Tree-Aware Maximum Likelihood-Based Gene Family Tree Inference under Gene Duplication, Transfer, and Loss.

Inferring phylogenetic trees for individual homologous gene families is difficult because alignments are often too short, and thus contain insufficient signal, while substitution models inevitably fail to capture the complexity of the evolutionary processes. To overcome these challenges, species-tree-aware methods also leverage information from a putative species tree. However, only few methods are available that implement a full likelihood framework or account for horizontal gene transfers. Furthermore, these methods often require expensive data preprocessing (e.g., computing bootstrap trees) and rely on approximations and heuristics that limit the degree of tree space exploration. Here, we present GeneRax, the first maximum likelihood species-tree-aware phylogenetic inference software. It simultaneously accounts for substitutions at the sequence level as well as gene level events, such as duplication, transfer, and loss relying on established maximum likelihood optimization algorithms. GeneRax can infer rooted phylogenetic trees for multiple gene families, directly from the per-gene sequence alignments and a rooted, yet undated, species tree. We show that compared with competing tools, on simulated data GeneRax infers trees that are the closest to the true tree in 90% of the simulations in terms of relative Robinson-Foulds distance. On empirical data sets, GeneRax is the fastest among all tested methods when starting from aligned sequences, and it infers trees with the highest likelihood score, based on our model. GeneRax completed tree inferences and reconciliations for 1,099 Cyanobacteria families in 8 min on 512 CPU cores. Thus, its parallelization scheme enables large-scale analyses. GeneRax is available under GNU GPL at https://github.com/BenoitMorel/GeneRax (last accessed June 17, 2020).

Longevity Relatives Count score identifies heritable longevity carriers and suggests case improvement in genetic studies.

Loci associated with longevity are likely to harbor genes coding for key players of molecular pathways involved in a lifelong decreased mortality and decreased/compressed morbidity. However, identifying such loci is challenging. One of the most plausible reasons is the uncertainty in defining long-lived cases with the heritable longevity trait among long-living phenocopies. To avoid phenocopies, family selection scores have been constructed, but these have not yet been adopted as state of the art in longevity research. Here, we aim to identify individuals with the heritable longevity trait by using current insights and a novel family score based on these insights. We use a unique dataset connecting living study participants to their deceased ancestors covering 37,825 persons from 1,326 five-generational families, living between 1788 and 2019. Our main finding suggests that longevity is transmitted for at least two subsequent generations only when at least 20% of all relatives are long-lived. This proves the importance of family data to avoid phenocopies in genetic studies.

Fabry pedigree analysis: A successful program for targeted genetic approach.

BACKGROUND: Fabry disease (FD) is an X-linked disorder of glycosphingolipid catabolism caused by a deficiency of the lysosomal enzyme alpha-galactosidase A (GLA). FD is still an underdiagnosed disorder worldwide. Moreover, there is delay between symptom onset and Fabry diagnosis of at least 10 years. Family screening offers an important benefit for detection of new patients. The aim of this work is to present the approach along with the results of a targeted genetic strategy for pedigree analysis for FD in Argentina. METHODS: By this strategy as soon as a new index Fabry patient is diagnosed, the pedigree group contacts the physician and a meeting is arranged with the physician and the family to build the family tree. RESULTS: Pedigree analysis was carried out for full in 31 families. In the work period, we have tested 1,462 relatives, and 501 were diagnosed FD. The proportion of positive detection was 33%. CONCLUSION: The targeted family screening approach is successful to detect undiagnosed Fabry patients. By this approach, the highest ratio index to pedigree ever reported for FD pedigree analysis of 1:15 was obtained.

f-treeGC: a questionnaire-based family tree-creation software for genetic counseling and genome cohort studies.

BACKGROUND: The Tohoku Medical Megabank project aims to create a next-generation personalized healthcare system by conducting large-scale genome-cohort studies involving three generations of local residents in the areas affected by the Great East Japan Earthquake. We collected medical and genomic information for developing a biobank to be used for this healthcare system. We designed a questionnaire-based pedigree-creation software program named "f-treeGC," which enables even less experienced medical practitioners to accurately and rapidly collect family health history and create pedigree charts. RESULTS: f-treeGC may be run on Adobe AIR. Pedigree charts are created in the following manner: 1) At system startup, the client is prompted to provide required information on the presence or absence of children; f-treeGC is capable of creating a pedigree up to three generations. 2) An interviewer fills out a multiple-choice questionnaire on genealogical information. 3) The information requested includes name, age, gender, general status, infertility status, pregnancy status, fetal status, and physical features or health conditions of individuals over three generations. In addition, information regarding the client and the proband, and birth order information, including multiple gestation, custody, multiple individuals, donor or surrogate, adoption, and consanguinity may be included. 4) f-treeGC shows only marriages between first cousins via the overlay function. 5) f-treeGC automatically creates a pedigree chart, and the chart-creation process is visible for inspection on the screen in real time. 6) The genealogical data may be saved as a file in the original format. The created/modified date and time may be changed as required, and the file may be password-protected and/or saved in read-only format. To enable sorting or searching from the database, the file name automatically contains the terms typed into the entry fields, including physical features or health conditions, by default. 7) Alternatively, family histories are collected using a completed foldable interview paper sheet named "f-sheet", which is identical to the questionnaire in f-treeGC. CONCLUSIONS: We developed a questionnaire-based family tree-creation software, named f-treeGC, which is fully compliant with international recommendations for standardized human pedigree nomenclature. The present software simplifies the process of collecting family histories and pedigrees, and has a variety of uses, from genome cohort studies or primary care to genetic counseling.

Examination of Huntington's disease with atypical clinical features in a Bangladeshi family tree.

Atypical manifestation of Huntington's disease (HD) could inform ongoing research into HD genetic modifiers not present in the primarily European populations studied to date. This work demonstrates that expanding HD genetic testing into under-resourced healthcare settings can benefit both local communities and ongoing research into HD etiology and new therapies.

The Infant Feeding Genogram: a tool for exploring family infant feeding history and identifying support needs.

BACKGROUND: Family culture and beliefs are passed through the generations within families and influence what constitutes appropriate infant care. This includes infant feeding decisions where a family history and support network congruent with women's infant feeding intentions has been shown to be important to women's breastfeeding experience. This is reflected in breastfeeding rates where women who were not breastfed themselves are less likely to initiate and continue with breastfeeding. Given the importance of family infant feeding history in the initiation and duration of breastfeeding, and the limited ability of some families to provide support; it is unclear why infant feeding family history and support networks are not explored during pregnancy. METHODS: The Infant Feeding Genogram was adapted from a simple pictorial device that is widely used in psychotherapy and genetic counselling. This tool was developed as part of a study investigating the experience of women when they were the first to breastfeed in their family. Fourteen Scottish participants completed their Infant Feeding Genogram as part of a semi-structured interview. The tool was adapted alongside their narratives to give a visual representation of each participant's family infant feeding history. RESULTS: The utility of the genogram is illustrated through two contrasting case examples with very different family feeding histories. The genogram showed family structures, patterns of infant feeding over time, and supportive or conflicting relationships. In the research setting it assisted women to explore their infant feeding history, identify challenges and sources of support and build rapport with the interviewer. CONCLUSIONS: The infant feeding genogram is proposed as a time efficient tool that could assist health professionals and other breastfeeding workers to support women and their families and by stimulating discussion around breastfeeding, Bby identifying strengths or possible deficits in social support for each individual, the tool could inform tailored support and care interventions. The effectiveness and acceptability of the Infant Feeding Genogram requires testing in the clinical environment. However, its successful application in other clinical contexts, combined with the interest in genealogy in popular culture, mean this is likely to be an acceptable, family friendly way to develop more effective breastfeeding conversations.

The North American Society for Pediatric and Adolescent Gynecology Fellowship Family Tree.

STUDY OBJECTIVE: To create a family tree to chronicle the proliferation of our specialty through fellowships (formal and informal) within the pediatric and adolescent gynecology practice and among the membership of the North American Society for Pediatric and Adolescent Gynecology (NASPAG). This historical project was undertaken as a way to demonstrate NASPAG's rich sense of heritage and community. The tree is meant to be a dynamic project, a living document, changing and expanding as this field of medicine grows, and offers a form of institutional memory for NASPAG. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTIONS: Questionnaires were sent out to all current NASPAG members via e-mail (and the list-serve) and were available at the 2014 NASPAG Annual Clinical and Research Meeting. Data from the questionnaires were recorded within GRAMPS 3.4.8, software used to create a family tree. MAIN OUTCOME MEASURES AND RESULTS: The result of the project was an elegant and intricate tree, containing 379 "family members" including physicians who specialize in pediatric and adolescent gynecology, adolescent medicine, reproductive endocrinology and infertility, and pediatric endocrinology. CONCLUSION: The family tree, which shows how one mentor might train multiple trainees and how past trainees later become mentors, highlights the value of physicians who take on supervisory and educational roles and the existence of comprehensive and inspirational training programs.

Clinical features analysis of familial spontaneous pneumothorax / 中华胸心血管外科杂志

Objective To summarize and analyze the clinical features of familial spontaneous pneumothorax.Methods During April 2001 to March 2013,the clinical data of 65 familial spontaneous pneumothorax from 21 families were retrospected and summarized.Contrasting with previous literature,the clinical features of familial spontaneous pneumothorax were analyzed.Results Patients in one family vary from 2 to 6,average 3.1.Families in which patients distribute in one generation,two generations and three generations were 19.0％,61.9％ and 19.0％ respectively.Male/female ratio of patients was.Mean onset age was 36.2 ± 12.2 ; Body mass index (BMI) of male and female patients were 24.0 ± 2.6 and 22.6 ± 3.0.32.7％ patients suffered bilateral pneumothorax.The recurrence rate after non-operative treatment was 50.0％.Conclusion Compared with sporadic spontaneous pneumothorax,Familial spontaneous pneumothorax has the following features:The incidence in man and woman was more similar; The onset age was older; Lanky body is less common; More were bilateral pneumothorax; Multiple pulmonary bullae are more common; Patients with non-surgical treatment have a higher recurrence rate.

GRFT - Genetic Records Family Tree Web Applet.

Current software for storing and displaying records of genetic crosses does not provide an easy way to determine the lineage of an individual. The genetic records family tree (GRFT) applet processes records of genetic crosses and allows researchers to quickly visualize lineages using a family tree construct and to access other information from these records using any Internet browser. Users select from three display features: (1) a family tree view which displays a color-coded family tree for an individual, (2) a sequential list of crosses, and (3) a list of crosses matching user-defined search criteria. Each feature contains options to specify the number of records shown and the latter two contain an option to filter results by the owner of the cross. The family tree feature is interactive, displaying a popup box with genetic information when the user mouses over an individual and allowing the user to draw a new tree by clicking on any individual in the current tree. The applet is written in JavaScript and reads genetic records from a tab-delimited text file on the server, so it is cross-platform, can be accessed by anyone with an Internet connection, and supports almost instantaneous generation of new trees and table lists. Researchers can use the tool with their own genetic cross records for any sexually reproducing organism. No additional software is required and with only minor modifications to the script, researchers can add their own custom columns. GRFT's speed, versatility, and low overhead make it an effective and innovative visualization method for genetic records. A sample tool is available at http://stanford.edu/walbot/grft-sample.html.