Similar Genetic Background Research Articles

Genetically Related Avian Influenza H7N9 Viruses Exhibit Different Pathogenicity in Mice

Avian influenza viruses can cross species barriers and adapt to mammals. The H7N9 subtype AIV that emerged in China in 2013 caused 1568 human infections, with a mortality rate of nearly 40%. We conducted a retrospective analysis of H7N9 viruses that were isolated in live poultry markets in 2013. We found that two avian-origin H7N9 isolates, A/chicken/Eastern China/JTC4/2013 and A/chicken/Eastern China/JTC11/2013, have a similar genetic background but exhibit different pathogenicity in mice. Whole-genome alignment of the two H7N9 viruses was carried out, and only six amino acid differences mapped in five genes, including the well-known virulence molecular marker PB2-E627K. Our retrospective analysis highlighted the importance of monitoring the adaptive mutations in avian influenza viruses with zoonotic potential.

Metagenomic analysis of ecological niche overlap and community collapse in microbiome dynamics.

Species utilizing the same resources often fail to coexist for extended periods of time. Such competitive exclusion mechanisms potentially underly microbiome dynamics, causing breakdowns of communities composed of species with similar genetic backgrounds of resource utilization. Although genes responsible for competitive exclusion among a small number of species have been investigated in pioneering studies, it remains a major challenge to integrate genomics and ecology for understanding stable coexistence in species-rich communities. Here, we examine whether community-scale analyses of functional gene redundancy can provide a useful platform for interpreting and predicting collapse of bacterial communities. Through 110-day time-series of experimental microbiome dynamics, we analyzed the metagenome-assembled genomes of co-occurring bacterial species. We then inferred ecological niche space based on the multivariate analysis of the genome compositions. The analysis allowed us to evaluate potential shifts in the level of niche overlap between species through time. We hypothesized that community-scale pressure of competitive exclusion could be evaluated by quantifying overlap of genetically determined resource-use profiles (metabolic pathway profiles) among coexisting species. We found that the degree of community compositional changes observed in the experimental microbiome was correlated with the magnitude of gene-repertoire overlaps among bacterial species, although the causation between the two variables deserves future extensive research. The metagenome-based analysis of genetic potential for competitive exclusion will help us forecast major events in microbiome dynamics such as sudden community collapse (i.e., dysbiosis).

Protein biomarkers for root length and root dry mass on chromosomes 4A and 7A in wheat

Improving the wheat (Triticum aestivum L.) root system is important for enhancing grain yield and climate resilience. Total root length (RL) and root dry mass (RM) significantly contribute to water and nutrient acquisition directly impacting grain yield and stress tolerance. This study used label-free quantitative proteomics to identify proteins associated with RL and RM in wheat near-isogenic lines (NILs). NIL pair 6 had 113 and NIL pair 9 had 30 differentially abundant proteins (DAPs). Three of identified DAPs located within the targeted genomic regions (GRs) of NIL pairs 6 (qDT.4A.1) and 9 (QHtscc.ksu-7A), showed consistent gene expressions at the protein and mRNA transcription (qRT-PCR) levels for asparagine synthetase (TraesCS4A02G109900), signal recognition particle 19 kDa protein (TraesCS7A02G333600) and 3,4-dihydroxy-2-butanone 4-phosphate synthase (TraesCS7A02G415600). This study discovered, for the first time, the involvement of these proteins as candidate biomarkers for increased RL and RM in wheat. However, further functional validation is required to ascertain their practical applicability in wheat root breeding. Significance of the studyClimate change has impacted global demand for wheat (Triticum aestivum L.). Root traits such as total root length (RL) and root dry mass (RM) are crucial for water and nutrient uptake and tolerance to abiotic stresses such as drought, salinity, and nutrient imbalance in wheat. Improving RL and RM could significantly enhance wheat grain yield and climate resilience. However, breeding for these traits has been limited by lack of appropriate root phenotyping methods, advanced genotypes, and the complex nature of the wheat genome. In this study, we used a semi-hydroponic root phenotyping system to collect accurate root data, near-isogenic lines (NILs; isolines with similar genetic backgrounds but contrasting target genomic regions (GRs)) and label-free quantitative proteomics to explore the molecular mechanisms underlying high RL and RM in wheat. We identified differentially abundant proteins (DAPs) and their molecular pathways in NIL pairs 6 (GR: qDT.4A.1) and 9 (GR: QHtscc.ksu-7A), providing a foundation for further molecular investigations. Furthermore, we identified three DAPs within the target GRs of the NIL pairs with differential expression at the transcript level, as confirmed by qRT-PCR analysis which could serve as candidate protein biomarkers for RL and RM improvement.

Comparable Evaluation of Nutritional Benefits of Lactobacillus plantarum and Bacillus toyonensis Probiotic Supplementation on Growth, Feed Utilization, Health, and Fecal Microbiota in Pre-Weaning Male Calves.

This study was conducted to investigate the impact of probiotic supplementation using Lactobacillus plantarum DSA 20174 and/or Bacillus toyonensis ATCC 55050 on growth performance, blood parameters, hematological measures, and fecal microbiota in pre-weaning Holstein calves. Thirty-two four-day-old male calves with a similar genetic background, weighing an average of 38.27 ± 0.12 kg, were randomly assigned to four groups. The groups consisted of a control group (CON) without supplementation, a group receiving B. toyonensis (BT) at 3 × 109 cfu/calf/day, a group receiving L. plantarum (LP) at 1 × 1010 cfu/calf/day, and a group receiving a combination of LP and BT (LP + BT) at half the dosage for each. The study found that calves supplemented with LP and LP + BT experienced significant improvements in average daily gain and final body weight compared to the control group. The LP + BT group showed the most positive effects on TDMI, starter intake, and CP intake. RBC counts tended to be higher in the probiotic groups, with the LP + BT group having the highest values. The LP + BT group also had higher total protein, albumin, globulin, and hematocrit concentrations. All probiotic groups showed higher serum IgG concentrations. Probiotic supplementation led to increased total bacterial count and decreased levels of E. coli, salmonella, and clostridium. The LP + BT group had a significant decrease in coliform count, while both LP and LP + BT groups had increased Lactobacillus populations. In conclusion, LP + BT probiotic supplement showed the most beneficial effects on growth, feed efficiency, blood constituents, and modulation of fecal microbiota composition.

Candidate genes for field resistance to cassava brown streak disease revealed through the analysis of multiple data sources.

Cassava (Manihot esculenta Crantz) is a food and industrial storage root crop with substantial potential to contribute to managing risk associated with climate change due to its inherent resilience and in providing a biodegradable option in manufacturing. In Africa, cassava production is challenged by two viral diseases, cassava brown streak disease (CBSD) and cassava mosaic disease. Here we detect quantitative trait loci (QTL) associated with CBSD in a biparental mapping population of a Tanzanian landrace, Nachinyaya and AR37-80, phenotyped in two locations over three years. The purpose was to use the information to ultimately facilitate either marker-assisted selection or adjust weightings in genomic selection to increase the efficiency of breeding. Results from this study were considered in relation to those from four other biparental populations, of similar genetic backgrounds, that were phenotyped and genotyped simultaneously. Further, we investigated the co-localization of QTL for CBSD resistance across populations and the genetic relationships of parents based on whole genome sequence information. Two QTL on chromosome 4 for resistance to CBSD foliar symptoms and one on each of chromosomes 11 and 18 for root necrosis were of interest. Of significance within the candidate genes underlying the QTL on chromosome 4 are Phenylalanine ammonia-lyase (PAL) and Cinnamoyl-CoA reductase (CCR) genes and three PEPR1-related kinases associated with the lignin pathway. In addition, a CCR gene was also underlying the root necrosis-resistant QTL on chromosome 11. Upregulation of key genes in the cassava lignification pathway from an earlier transcriptome study, including PAL and CCR, in a CBSD-resistant landrace compared to a susceptible landrace suggests a higher level of basal lignin deposition in the CBSD-resistant landrace. Earlier RNAscope® in situ hybridisation imaging experiments demonstrate that cassava brown streak virus (CBSV) is restricted to phloem vessels in CBSV-resistant varieties, and phloem unloading for replication in mesophyll cells is prevented. The results provide evidence for the involvement of the lignin pathway. In addition, five eukaryotic initiation factor (eIF) genes associated with plant virus resistance were found within the priority QTL regions.

GENETIC PARAMETERS AND PRINCIPAL COMPONENT ANALYSIS FOR QUANTITATIVE TRAITS IN RICE (ORYZA SATIVA L.)

Conventional breeding is vital in improving yield-related traits and developing high-yielding cultivars. In the presented study, an evaluation of 15 F1 hybrids compared them to their six parental genotypes for genetic variation of various traits. The results showed that the analysis of variance revealed significant (P ≤ 0.01) differences among the cross combinations and parental cultivars and among the parents and crosses. The mean sum of squares of parents vs. crosses also indicated substantial (P ≤ 0.01) for all the characteristics. The general (GCA) and specific combining ability (SCA) variances were significant (P ≤ 0.01) for all traits studied in the F1 generation. Three varieties, namely, Sakha108, Giza179, and Sakha109, were highly significantly positive for grain yield plant-1, which means these varieties can benefit as good combiners to transfer the said trait in the breeding program. In SCA, seven crosses were negative in plant height and a negative value was desirable to avoid lodging and suitable for mechanical harvesting; however, positive significant values are preferable in the rest of the traits. The results indicated that the best crosses for grain yield plant-1 and plant height were Sakha105 × Sakha102, Sakha105 × Sakha108, and Sakha108 × Sakha109. Conducting cluster analysis also exhibited the genotypes dividing into four groups. The first group included rice genotypes Sakha109 and Sakha108 alone. These cultivars, produced from a common parent Sakha101, could have genetic relations for three quantitative traits (flag leaf area, 1000-grain weight, and panicle weight). The second group, comprising Sakha 102 and Sakha 106, has a very similar genetic background because both cultivars share a common parent, Giza 177. In addition, these two rice cultivars had at par number of tillers plant-1, 1000-grain weight, and panicles plant-1. The third group included only Giza 179 belonging to Indica-Japonica varieties. A fourth group has Sakha 105 produced by different parents.

Association of Helicobacter pylori Infection with Autoimmune Thyroid Disease in the Female Sex.

Helicobacter pylori infection has been associated with an increased risk of thyroid diseases (TDs), although scientific evidence is conflicting. In the present study the relationship between TDs, including both autoimmune (AI) and non-autoimmune TD, and H. pylori infection was investigated. Data from records of patients undergoing upper endoscopy and histologically evaluated for H. pylori infection were retrieved. In addition to demographic information, the features of gastritis based on non-targeted biopsies collected from the antrum, angulus, and corpus were analyzed. The presence of H. pylori infection and atrophy and/or metaplasia and/or dysplasia in at least one gastric specimen was defined as a long-lasting H. pylori infection and the presence of a chronic-active gastritis as a current infection. Hashimoto's and Graves' diseases were included in the AITD group, and thyroid nodules, goiter, iatrogenic thyroid hypo/hyper function, and thyroidectomy in the non-autoimmune TD group. A total of 8322 records from adult patients from Northern Sardinia, characterized by a similar genetic background, was analyzed. Participants were aged 18-93 years (females 5339, 64.1%), and more specifically, 562 (6.7%) had a diagnosis of AITD and 448 (5.4%) of non-autoimmune TD. A significant association between long-lasting H. pylori and AITD (OR 1.34; 95%CI 1.13-1.60) was found, irrespective of age, sex, body mass index, and smoking status, while it was not associated with non-autoimmune TD. Current H. pylori infection did not show significant ORs for AITD (OR 0.99; 95%CI 0.64-1.57) and non-autoimmune TD (OR 0.86; 95%CI 0.66-1.15). The association with long-lasting H. pylori infection was confirmed to be significant for both Hashimoto's thyroiditis and Graves' disease by multivariable regression analysis. Stratification according to sex revealed a significant association only for females (OR 1.39; 95%CI 1.12-1.72). Our results indicate that long-lasting H. pylori infection is associated with AITD in the female adult population of Northern Sardinia.

A comparative profile of urinary scent signals of two endangered Japanese populations of leopard cat

Two subspecies of mainland leopard cats (Prionailurus bengalensis), Iriomote cats (Prionailurus bengalensis iriomotensis), and Tsushima leopard cats (Prionailurus bengalensis euptilurus), are small, endangered felids that are endemic to the Japanese islands, Iriomote-jima and Tsushima, respectively. Both subspecies have an estimated population size of only about 100 individuals each. Therefore, it is crucial to expand our understanding of these subspecies to successfully conserve them. While their morphology, anatomy, ecology, pathology, and genetics are well studied, little is known about their physiology regulated in subspecies-specific manners. This study characterized their urinary volatile and nonvolatile organic compounds, with which individuals express their physiological status and territorial ownership. We found significantly higher levels of 3-mercapto-3-methyl-1-butanol and its structural analogs, which are scent signals of domestic cats, in the urinary headspace of Iriomote cats than in that of Tsushima leopard cats. There were no differences in the urinary levels of felinine, an amino acid that acts as a precursor of 3-mercapto-3-methyl-1-butanol, suggesting the variation of catalytic activities for decomposing felinine to 3-mercapto-3-methyl-1-butanol between subspecies. Both subspecies exhibited physiological proteinuria due to the secretion of carboxylesterase 5A, also known as cauxin, for the production of felinine. In conclusion, while the two endangered Japanese subspecies of mainland leopard cats share similar genetic backgrounds, urinary contents of metabolites vary between the subspecies. We suggest that after the separation into two subspecies, the regulation of the metabolic pathway for 3-mercapto-3-methyl-1-butanol production likely evolved differently in each subspecies in response to their specific environments.

Unraveling female communication through scent marks in the Norway rat

Chemical communication by females remains poorly understood, with most attention focused on female advertisement of sexual receptivity to males or mother-offspring communication. However, in social species, scents are likely to be important for mediating competition and cooperation between females determining individual reproductive success. Here, we explore chemical signaling by female laboratory rats (Rattus norvegicus) to test i) whether females target their deployment of scent information differentially according to their sexual receptivity and the genetic identity of both female and male conspecifics signaling in the local environment and ii) whether females are attracted to gain the same or different information from female scents compared to males. Consistent with targeting of scent information to colony members of similar genetic background, female rats increased scent marking in response to scents from females of the same strain. Females also suppressed scent marking in response to male scent from a genetically foreign strain while sexually receptive. Proteomic analysis of female scent deposits revealed a complex protein profile, contributed from several sources but dominated by clitoral gland secretion. In particular, female scent marks contained a series of clitoral-derived hydrolases and proteolytically truncated major urinary proteins (MUPs). Manipulated blends of clitoral secretion and urine from estrus females were strongly attractive to both sexes, while voided urine alone stimulated no interest. Our study reveals that information about female receptive status is shared between females as well as with males, while clitoral secretions containing a complex set of truncated MUPs and other proteins play a key role in female communication.

Major Histocompatibility Complex-B haplotype and ovarian graft response

Gonadal tissue transfer is considered one of the best methods to preserve genetic variability. Poultry hosts can receive a gonad from a donor of a different genetic background, sustain the growth of this graft, and produce gametes from it. Unfortunately, the host's strong immune response may significantly reduce the gonadal graft's ability to reach maturity. Our study aimed to evaluate the influence of MHC-B alleles in rejecting a gonadal graft of similar or different genetic backgrounds. In the first experiment, ovarian tissue was transplanted to chicks of similar genetic backgrounds, either Lohmann White (LW) with variable MHC-B or Barred Rock (BR) with fixed MHC-B. The sustained growth of donor ovarian tissues occurred in (4/7 hosts) BR (MHC-B matched) hosts only-one of these graft-positive-BR hens produced eggs derived from the donor ovary. No grafts were recovered when the host and the donor had an LW background (0/9; MHC-B mismatched). In the second experiment, ovarian transplantation was done between chicks of either similar or different genetic backgrounds (Brown Leghorn [BL], BR, and BL/BR F1). The 2 pure lines contained only one MHC-B allele, whereas the F1 heterozygotes had both. All host birds were given a daily dose of an immunosuppressant (mycophenolate mofetil) until maturity. The success rate was assessed by microsatellite genotype confirmation of donor-derived ovaries plus physiological and histological analyses of ovarian grafts. In this second experiment, 11 out of 43 ovarian hosts laid eggs. However, all fertilized eggs from these hens were derived from the remnant host ovarian tissue, not from the donor ovaries. A necropsy assessment was done on all 43 host birds. Ten donor grafts were recovered from hosts having matched (6 hosts) and mismatched (4 hosts) MHC-B, and none were functional. Interestingly, 6 of them were enclosed by a serous membrane capsule filled with fluid and had various tissue growth. In addition, clusters of immune cells were observed in all recovered donor grafts. Our results demonstrated that genetic background could greatly influence the success of gonadal transfer in chickens.

Hand-Rearing Method for Infant Marmosets.

The common marmoset (Callithrix jacchus) is a small and highly social New World monkey with high reproduction rates, which has been proven to be a compelling non-human primate model for biomedical and neuroscience research. Some females give birth to triplets; however, the parents cannot raise all of them. To save these infants, we have developed a hand-rearing method for raising newborn marmosets. In this protocol, we describe the formula of the food, the time for feeding, the configuration of the temperature and humidity, as well as the adaptation of the hand-reared infants to the colony environment. This hand-rearing method significantly increases the survival rate of marmoset infants (without hand-rearing: 45%; with hand-rearing: 86%) and provides the opportunity to study the development of marmoset infants with similar genetic backgrounds raised in different postnatal environments. As the method is practical and easy to use, we anticipate that it could also be applied to other labs working with common marmosets.

Heterogeneous distribution of Cardinium in whitefly populations is associated with host nuclear genetic background.

Inherited bacterial symbionts are very common in arthropods, but infection frequency can vary widely among populations. Experiments and interpopulation comparisons suggest that host genetic background might be important in explaining this variation. Our extensive field investigation showed that the infection pattern of the facultative symbiont Cardinium was heterogeneous across geographical populations of the invasive whitefly Bemisia tabaci Mediterranean (MED) in China, with genetic nuclear differences evident in 2 of the populations: 1 with a low infection rate (SD line) and 1 with a high infection rate (HaN line). However, whether the heterogeneous frequency of Cardinium is associated with the host genetic background remains poorly understood. Here, we compared the fitness of the Cardinium-infected and uninfected sublines with similar nuclear genetic backgrounds from SD and HaN lines, respectively, and further determine whether host extranuclear or nuclear genotype influenced the Cardinium-host phenotype by performing 2 new introgression series of 6 generations between SD and HaN lines (i.e., Cardinium-infected females of SD were backcrossed with uninfected males of HaN, and vice versa). The results showed that Cardinium provides marginal fitness benefits in the SD line, whereas Cardinium provides strong fitness benefits in the HaN line. Further, both Cardinium and the Cardinium-host nuclear interaction influence the fecundity and pre-adult survival rate of B.tabaci, whereas the extranuclear genotype does not. In conclusion, our results provide evidence that Cardinium-mediated fitness effects were closely associated with the host genetic background, which provides a fundamental basis for understanding the mechanism underlying the heterogeneous distribution of Cardinium in B.tabaci MED populations across China.

Cultivar and Maternal Plant Environment Influence Cold Stratification Requirements and Germination Rates of Vitis Species

Open-pollinated seeds from grapevines in Parlier and Davis (in California) and Geneva (in New York) were collected in 2016, 2017, and 2018. Seeds were subjected to a series of cold stratification treatments of varying lengths and germinated in incubators to compare germination rates. Two V. vinifera cultivars (Chardonnay and Cabernet Sauvignon) and three other cultivars (V. labrusca hybrids) with a similar genetic background were compared across three locations to test for maternal environmental effects on germination rates under different cold stratification durations. Two interspecific hybrids (‘Salamander’ and ‘Sovereign Rose’) and three genotypes each from two species, V. riparia and V. cinerea, were evaluated to compare germination rate variability at different cold stratification durations among and within species and hybrids. Large variability in germination rates was evident among and within grape species, with some accessions requiring little to no cold stratification, and others requiring 10 to 12 weeks. These differences could be useful for breeding grapevines with high or low dormancy requirements. The maternal plant environment impacted the seed weight and total seed germination across years and locations.

Gender differences in phenotypic expressions of metabolic syndrome in ZSF rats

Aims: The focus of our laboratory has been to examine the mechanisms of insulin resistance and renal injury in metabolic syndrome. ZSF rats represent a transgenic murine model of human metabolic syndrome and spontaneously develop obesity, hyperglycemia, hypertension, progressive proteinuria, azotemia and severe hyperlipidemia. The renal and metabolic abnormalities in ZSF rats were first characterized and published from our laboratory (J Am Soc Neph 2007). However only male rats were examined in that study. Despite a totally similar genetic background, there could be significant gender differences in the expression of phenotypic characteristics of disease states. We examined the differences in the general and metabolic features of male and female rat models of metabolic syndrome. Methods: We studied male and female ZSF rats, an established model of metabolic syndrome. Obese ZSF (ZDFxSHHF-fa/facp) model was developed by crossing lean female Zucker Diabetic Fatty (ZDF ./fa) and lean male Spontaneously Hypertensive Heart Failure (SHHF/Mcc-facp, ./fa) rats. Male and female CD rats were used as controls. Rats were monitored from the 8th week of life and were fed normal rat chow (CD rats) or high calorie, high fat diet (Purina 5008) in the case of ZSF rats. The present report pertains to data obtained between 15-20 weeks of age. Blood pressure was measured by tail cuff plethysmography (Non-Invasive Blood Pressure measurements using the Kent CODA system). Blood and urine were examined for glucose (Ascensia Contour glucometer) and protein levels. Body weights were measured every week. Results: Our results show that at 20 weeks, males were heavier than the females in both ZSF (545±26g vs. 401±42g p<0.05) and CD (608±73g vs. 301±22g p<0.05) strains of rats. ZSF female rats were heavier than CD female rats. Male ZSF rats were fatter than male CD rats although the latter appear larger (no statistical difference in weights). There were no statistically significant differences in the BP amongst the four groups, which were all in the normal range. Blood glucose level were elevated in ZSF compared to CD rats. Male ZSF rats had higher glucose levels (342±36 mg/dl) compared to female ZSF rats (95±16mg/dl, p<0.05). Urine glucose levels were higher in male ZSF rats while urine protein levels were higher in female ZSF rats compared to the other three groups. Conclusions: Although the male and female ZSF rats shared the same general genetic material, at 20 weeks of age they exhibited significant differences in various manifestations of metabolic syndrome with male ZSF rats exhibiting more advanced featues. These observations underscore the impact of gender and implied physiological factors in influencing the physical manifestations of a disease state. Private Research Endowment This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Female Mice Are Less Susceptible to the Effects of Diet-Induced Obesity on Sleep and Sleep-Disordered Breathing

Diet-induced obesity (DIO) in male mice is a well-established model of sleep-disordered breathing (SDB). Male DIO mice manifest obesity hypoventilation, increased apnea severity, and sleep fragmentation. The effects of DIO on breathing during sleep and sleep architecture in females have been insufficiently investigated. In this study, we aimed to compare the breathing and sleep patterns of lean and obese female mice of similar genetic background. We hypothesized that female mice are less susceptible to the detrimental effects of DIO on sleep and SDB compared to males. Full-polysomnographies were performed in 15 lean female C57BL/6J and 14 female DIO-C57BL/6J mice using a whole-body plethysmography chamber. Arousals from sleep and apneas were manually scored. Ventilatory response to an arousal was calculated as ratio of the peak minute ventilation (V E ) during each arousal relative to the baseline V E (from 2.5s to 5s preceding the arousal). Breathing stability was measured using Poincaré plots of V E . Mice were acutely exposed to 8% CO 2 to measure the hypercapnic ventilatory response (HCVR). An additional 10 mice (5 each/group) underwent 24-h metabolic studies. We found that obesity was associated with hypometabolism, indicated by reduced oxygen consumption (VO 2 ) and CO 2 production in DIO mice. VE in 8% CO 2 and HCVR were significantly suppressed suggesting a decreased CO 2 sensitivity in obese animals. NREM sleep duration was reduced, but REM sleep was preserved. Arousal frequency was similar between groups (~78 events/h). DIO mice hypoventilated during NREM sleep. However, apnea severity was 4-fold augmented in lean females compared to DIO mice (14.7±3.9 vs 74.2±11.9 events/h; P<0.001). Breathing stability during sleep was significantly increased in lean mice. Ventilatory response to an arousal was higher in lean females, but it was attributed to an overall increased V E during arousal and at baseline. Our results suggest potential sex differences in the effects of DIO on breathing during sleep and sleep architecture. DIO in females appears to be less detrimental regarding SDB severity. The mechanisms underlying the augmented SDB severity in lean females are unknown, but an exacerbated CO2 responsiveness during sleep could play an important role. American Heart Association Postdoctoral Fellowship Award 828142 (to L.J.K.), NHLBI grant NIH R01 HL128970, R01 HL133100, and R01 HL13892 (to V.Y.P.), American Academy of Sleep Medicine Foundation 238-BS-20, and American Thoracic Society Unrestricted Award (to L.V.P.) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Genetic and Epigenetic Study of Monozygotic Twins Affected by Parkinson’s Disease

Background: Genetic and epigenetic modifiers of age at onset of Parkinson’s disease (PD) are largely unknown. It remains unclear whether DNA methylation (DNAm) age acceleration is linked to age at onset in PD patients of different ethnicities with a similar genetic background. We aim to characterize the clinical, genomic and epigenomic features of three pairs of Chinese monozygotic twins discordant for PD onset by up to 10 years. Methods: We conducted whole genome sequencing, multiplex ligation-dependent probe amplification and genome-wide DNAm array to evaluate the three pairs of Chinese monozygotic twins discordant for age at onset of PD (families A–C). Results: We identified two heterozygous PRKN mutations (exon 2–4 deletion and p.Met1Thr) in PD affected members of one family. Somatic mutation analyses of investigated families did not reveal any variants that could explain the phenotypic discordance in the twin pairs. Of note, our epigenetic study revealed that the twins with earlier-onset had a trend of faster DNAm age acceleration than the later-onset/asymptomatic twins, but without statistical significance. Conclusion: The link between DNAm age acceleration and PD onset in Chinese patients should be interpreted with cautious, and need to be further verified in an extended PD cohort with similar genetic background.

Effects of milk-derived bioactive peptide VPP on diarrhea of pre-weaning calves.

A well-known milk-derived bioactive tripeptide, VPP (Val-Pro-Pro) has good anti-inflammatory, anti-hypertension, and anti-hydrolysis properties. However, whether VPP can alleviate calf intestinal inflammation is unclear. In this experiment, the effects of VPP on growth, diarrhea incidence, serum biochemical indices, short-chain fatty acids, and fecal microorganisms were examined in pre-weaning Holstein calves. Eighteen calves with similar birth date, body weight, and genetic background were randomly assigned equally to two groups (n = 9). The control group was given 50 mL of phosphate buffer saline before morning feeding, whereas the VPP group received 50 mL of VPP solution (100 mg/kg body weight/d). The study lasted for 17 days, with the first 3 days used for adaptation. Initial and final body weights were determined, and daily dry matter intake and fecal score were recorded throughout the study. Serum hormone levels and antioxidant and immune indices were measured on day 14. Fecal microorganisms were collected on days 0, 7, and 14, and 16S rDNA sequencing was performed. Oral administration of VPP did not significantly affect calf average daily feed intake and body weight, but the growth rate in body weight was significantly higher in the VPP group than in the control group on day 7 (P < 0.05). Compared with the control, VPP significantly decreased serum TNF-α and IL-6 contents (P < 0.05), and concentrations of nitric oxide and IL-1β also decreased but not significantly (0.05 < P < 0.1). After seven days of VPP, relative abundances of g_Lachnoclostridium, uncultured_bacterium_, and g_Streptococcus in fecal samples increased significantly (P < 0.05). Compared with the control, VPP significantly increased concentrations of the fecal short-chain fatty acids n-butyric acid and isovaleric acid (P < 0.05). In conclusion, VPP can relieve intestinal inflammation and alleviate the degree of diarrhea in pre-weaning calves.

Use of selective phenotyping and genotyping to identify rare blood donors in Canada

The distribution of rare and specific red cell phenotypes varies between races and ethnicities. Therefore, the most compatible red cell units for patients with haemoglobinopathies and other rare blood requirements are most likely to be found in donors from similar genetic backgrounds. Our blood service introduced a voluntary question asking donors to provide their racial background/ethnicity. Results triggered additional phenotyping and/or genotyping. We analysed the results of additional testing performed between January 2021 and June 2022, and rare donors were added to the Rare Blood Donor database. We determined the incidence of various rare phenotypes and blood group alleles based on donor race/ethnicity. Over 95% of donors answered the voluntary question; 715 samples were tested, and 25 donors were added to the Rare Blood Donor database, including five k-, four U-, two Jk(a-b-) and two D- - phenotypes. Asking donors about their race/ethnicity was well received by donors, and the resulting selective testing enabled us to identify individuals with a higher likelihood of being rare blood donors, support patients with rare blood requirements and better understand the incidence of common and rare alleles and red blood cell phenotypes in the Canadian donor population.

Emergence of OXA-484-Producing Klebsiella variicola in China.

The frequent and inappropriate use of antibiotics has caused a dramatic rise in the number, species, and degree of multi-drug resistant bacteria, making them more prevalent and difficult to treat. In this context, the aim of the present study was to characterize the OXA-484-producing strains isolated from a perianal swab of a patient by using whole-genome analysis. In this study, carbapenemase-producing Klebsiella variicola was identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), average nucleotide identity (ANI) and PCR. S1 nuclease pulsed-field gel electrophoresis (S1-PFGE) and Southern blotting were utilized to characterize the plasmid profiles of K. variicola 4717. In particular, WGS was performed to obtain genomic information on this clinical isolate, and assemble all the plasmids of the bla OXA-484-harboring strain. The antimicrobial susceptibility pattern of K. variicola 4717 revealed that it was resistant to a range of antibiotics, including aztreonam, imipenem, meropenem, ceftriaxone, cefotaxime, ceftazidime, levofloxacin, ciprofloxacin, piperacillin-tazobactam, methylene-sulfamer oxazole, amoxicillin-clavulanic acid, cefepime, and tigecycline. Its susceptibility to chloromycin was intermediate, while it was still susceptible to amikacin, gentamicin, fosfomycin, and polymyxin B. The presence of two companion plasmids, p4717_1 and p4717_2, together with a plasmid carrying the bla OXA-484 gene was observed. An in-depth investigation of p4717-OXA-484 uncovered that it is an IncX3-type plasmid and shares a similar segment encoded by IS26. Given the similar genetic background, it was conceivable that bla OXA-484 could have developed from bla OXA-181 through a series of mutations. Herein, we described the first genome sequence of K. variicola strain harbouring the class D β-actamase bla OXA-484 in an Inc-X3-type plasmid. Our work also uncovered the genetic characterization of K. variicola 4717 and the importance of initiating antimicrobial detection promptly.

Comparison of the Prevalence of Type 2 Diabetes Mellitus in Asian Indians Living in the United States and India: Does Location Matter?

Type 2 diabetes mellitus (T2DM) has affected many people worldwide. One population that is greatly affected by T2DM is the Asian Indian population. The relative effects of genetics and environment on the development of diabetes in adults are not completely understood. We conducted an analysis to determine if location, through the environment and different diets, affects T2DM inheritance in Asian Indians. We hypothesised that the prevalence of T2DM depended on location. We analysed previously collected data on T2DM in the individual states of India and the U.S. and used this information to compare the prevalence of T2DM in Asian Indians living in these two countries. A total of 1,117,465,226 individuals were surveyed in India. Of these, 108,295,674 individuals had T2DM. Similarly, of the 1,704,846 individuals in the US, 298,107 had T2DM. The prevalence of T2DM was 17.49% in Asian Indians living in the US compared to 9.69% for Indians living in India (P < 0.00001). In individuals with similar genetic backgrounds, environmental factors significantly influence the development of T2DM.