Individual Phenotypes Research Articles

Novel genetic markers for chronic kidney disease in a geographically isolated population of Indigenous Australians: Individual and multiple phenotype genome-wide association study

BackgroundChronic kidney disease (CKD) is highly prevalent among Indigenous Australians, especially those in remote regions. The Tiwi population has been isolated from mainland Australia for millennia and exhibits unique genetic characteristics that distinguish them from other Indigenous and non-Indigenous populations. Notably, the rate of end-stage renal disease is up to 20 times greater in this population compared to non-Indigenous populations. Despite the identification of numerous genetic loci associated with kidney disease through GWAS, the Indigenous population such as Tiwi remains severely underrepresented and the increased prevalence of CKD in this population may be due to unique disease-causing alleles/genes.MethodsWe used albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) to estimate the prevalence of kidney disease in the Tiwi population (N = 492) in comparison to the UK Biobank (UKBB) (N = 134,724) database. We then performed an exploratory factor analysis to identify correlations among 10 CKD-related phenotypes and identify new multi-phenotype factors. We subsequently conducted a genome-wide association study (GWAS) on all single and multiple phenotype factors using mixed linear regression models, adjusted for age, sex, population stratification, and genetic relatedness between individuals.ResultsBased on ACR, 20.3% of the population was at severely increased risk of CKD progression and showed elevated levels of ACR compared to the UKBB population independent of HbA1c. A GWAS of ACR revealed novel association loci in the genes MEG3 (chr14:100812018:T:A), RAB36 (rs11704318), and TIAM2 (rs9689640). Additionally, multiple phenotypes GWAS of ACR, eGFR, urine albumin, and serum creatinine identified a novel variant that mapped to the gene MEIS2 (chr15:37218869:A:G). Most of the identified variants were found to be either absent or rare in the UKBB population.ConclusionsOur study highlights the Tiwi population’s predisposition towards elevated ACR, and the collection of novel genetic variants associated with kidney function. These associations may prove valuable in the early diagnosis and treatment of renal disease in this underrepresented population. Additionally, further research is needed to comprehensively validate the functions of the identified variants/genes.

Hybrid glycophorin GP (A-B) and anti-Ena antibody in a multiparous woman

Abstract The MNS system is a large, complex group of antigens, with 50 antigens at present. The major antigens of the system are carried on glycophorins A and B, which are important red cell sialoglycoproteins. Altered expression of MNS antigens is possible in cases where there is a formation of hybrid glycophorins. Some of these patients may make clinically significant antibodies which can be associated with hemolytic transfusion reactions (HTR) or hemolytic disease of the fetus and the newborn. This is a report of one such case with both these phenomena, in a multiparous woman. Incompatible cross-matches at the referral center caused the samples to be sent to this immunohematological laboratory where the serological profile was detailed. On sending the samples to a third blood group reference laboratory, gene sequencing was done and the antibody was identified. At this immunohematological laboratory, the phenotype was determined as M-N+. The patient’s sera showed panreactivity with all panel cells (3-cell and 11-cell). At blood group reference laboratory, the findings were as follows- GYP (A-B) hybrid gene consistent with hemi/homozygosity for GYP*JL was confirmed and the panreactive antibody was identified as anti - Ena. Rare, atypical phenotypes in the MNS system can result from mutations affecting the sialoglycoproteins the antigens are carried on. The subset of antigens expressed in individual phenotypes varies and these patients can develop antibodies against the antigens they lack. When they present with immunohematological challenges such as panreactivity and incompatibility, a combination of serology, molecular technologies, and family studies help solve the problem. Alternatives to transfusion are also useful options in managing such cases.

β-Actin G342D as a Cause of NK Cell Deficiency Impairing Lytic Synapse Termination.

NK cell deficiency (NKD) occurs when an individual's major clinical immunodeficiency derives from abnormal NK cells and is associated with several genetic etiologies. Three categories of β-actin-related diseases with over 60 ACTB (β-actin) variants have previously been identified, none with a distinct NK cell phenotype. An individual with mild developmental delay, macrothrombocytopenia, and susceptibility to infections, molluscum contagiosum virus, and EBV-associated lymphoma had functional NKD for over a decade. A de novo ACTB variant encoding G342D β-actin was identified and was consistent with the individual's developmental and platelet phenotype. This novel variant also was found to have direct impact in NK cells because its expression in the human NK cell line YTS (YTS-NKD) caused increased cell spreading in lytic immune synapses created on activating surfaces. YTS-NKD cells were able to degranulate and perform cytotoxicity, but they demonstrated defective serial killing because of prolonged conjugation to the killed target cell and thus were effectively unable to terminate lytic synapses. G342D β-actin results in a novel, to our knowledge, mechanism of functional NKD via increased synaptic spreading and defective lytic synapse termination with resulting impaired serial killing, leading to overall reductions in NK cell cytotoxicity.

Thyroid hormone links environmental signals to DNA methylation.

Environmental conditions experienced within and across generations can impact individual phenotypes via so-called 'epigenetic' processes. Here we suggest that endocrine signalling acts as a 'sensor' linking environmental inputs to epigenetic modifications. We focus on thyroid hormone signalling and DNA methylation, but other mechanisms are likely to act in a similar manner. DNA methylation is one of the most important epigenetic mechanisms, which alters gene expression patterns by methylating cytosine bases via DNA methyltransferase enzymes. Thyroid hormone is mechanistically linked to DNA methylation, at least partly by regulating the activity of DNA methyltransferase 3a, which is the principal enzyme that mediates epigenetic responses to environmental change. Thyroid signalling is sensitive to natural and anthropogenic environmental impacts (e.g. light, temperature, endocrine-disrupting pollution), and here we propose that thyroid hormone acts as an environmental sensor to mediate epigenetic modifications. The nexus between thyroid hormone signalling and DNA methylation can integrate multiple environmental signals to modify phenotypes, and coordinate phenotypic plasticity at different time scales, such as within and across generations. These dynamics can have wide-ranging effects on health and fitness of animals, because they influence the time course of phenotypic adjustments and potentially the range of environmental stimuli that can elicit epigenetic responses. This article is part of the theme issue 'Endocrine responses to environmental variation: conceptual approaches and recent developments'.

Longitudinal stability of reward and relief drinking phenotypes in community and treatment-seeking individuals who engage in heavy drinking.

Precision medicine approaches aim to improve treatment outcomes by identifying which treatments work best for specific individual phenotypes. In the treatment of alcohol use disorder (AUD), precision medicine approaches have been proposed based on phenotypes characterized by individuals who drink primarily to enhance rewarding experiences (i.e., reward drinking) or those who drink primarily to relieve negative states (i.e., relief drinking). This study examined these phenotypes across treatment- and nontreatment-seeking individuals and the stability of the phenotypes over time. We used latent profile and latent transition analyses to identify and assess longitudinal stability (over 3 or 4 months) of reward and relief drinking subgroups within a nontreatment-seeking community sample that engaged in hazardous drinking (n = 189) and two treatment-seeking samples of individuals with AUD enrolled in two large clinical trials (n = 1726, n = 1383). We examined prospective associations with alcohol consumption and consequences at long-term follow-up (15 or 18 months). Results supported four subgroups: low reward/low relief, low reward/high relief, high reward/low relief, and high reward/high relief. The community sample contained more individuals classified within the high reward/low relief subgroup than treatment-seeking samples. Subgroups were generally more stable over time in the community sample than in the treatment-seeking samples. Alcohol consumption and consequences decreased over time for the treatment-seeking samples, with consequences and drinking frequency decreasing for the community sample. Participants classified within the high reward/high relief and low reward/high relief groups reported the most consequences and consumption at long-term follow-up. Reward and relief drinking phenotypes can be identified within community and treatment-seeking samples of individuals who drink heavily. The phenotypic subgroups appear to be stable over time in the absence of treatment, change somewhat during treatment, and provide utility in predicting alcohol consumption and consequences.

Myasthenia gravis concurrent with Parkinson's disease in a Spanish cohort. Causation or correlation?

Comorbidity between myasthenia gravis (MG) and other autoimmune diseases is well-documented. However, concurrent MG and Parkinson's disease (PD) have rarely been described. This concurrence has mostly been considered coincidental in cases reported to date. We characterized patients with concurrent MG and PD within a cohort of 631 MG patients by gender, age, MGFA class, quantitative MG score at diagnosis, UPDRS score at diagnosis, and the DaTSCAN uptake pattern, to determine the frequency and the phenotype of individuals with these two concurrent entities. Meta-analysis of cases in the literature was used for comparison with our series. Eighteen cases were identified in which the two diseases were concurrent. The major characteristics of the phenotype are male prevalence, late-onset MG, and frequent initial symptoms of dropped head and oculobulbar involvement. DAT confirmed reduced bilateral uptake in eleven patients and reduced unilateral uptake in the others. To our knowledge, this is the largest reported series of concurrent MG and PD. This concurrence is more common than expected (2.85%). Either MG or PD may appear first. We found no iatrogenic relationship for the order of appearance. The overlapping of symptoms sometimes leads physicians to overlook the second disease, instead viewing it as a deterioration of the first. This study describes patients with well-documented diagnoses of both MG and PD, thus providing further indications of a shared etiology of these two diseases. Prospective studies including genetic, immunological, and environmental analysis are necessary to identify possible common pathogenic mechanisms.

Microglia activity in the human basal ganglia is altered in alcohol use disorder and reversed with remission from alcohol.

Alcohol use disorder (AUD) is characterized by cycles of abuse, withdrawal, and relapse. Neuroadaptations in the basal ganglia are observed in AUD; specifically in the putamen, globus pallidus (GP), and ventral pallidum (VP). These regions are associated with habit formation, drug-seeking behaviors, and reward processing. While previous studies have shown the crucial role of glial cells in drug seeking, it remains unknown whether glial cells in the basal ganglia are altered in AUD. Glial cells in the putamen, GP, and VP were examined in human post-mortem tissue of AUD and alcohol remission cases. Immunohistochemistry was performed to analyze cell count, staining intensity, and morphology of microglia and astrocytes, using markers Iba-1 and GFAP. Morphological analysis revealed a significant decrease in microglia cell size and process retraction, indicating activation or a dystrophic microglia phenotype in individuals with AUD compared to controls. Microglia staining intensity was also higher in the GP and VP in AUD cases, whereas microglia staining intensity and cell size in remission cases were not different to control cases. In contrast, no astrocyte changes were observed in examined brain regions for both AUD and remission cases compared to controls. These results suggest alcohol exposure alters microglia, potentially contributing to dysfunctions in the basal ganglia that maintain addiction, and abstinence from alcohol may reverse microglia changes and associated dysfunctions. Overall, this study further characterizes AUD neuropathology and implicates microglia in the putamen, GP, and VP as a potential target for therapy.

Body Composition Indicators Jointly Predict Metabolic Unhealthy Phenotypes in Young and Middle-Aged Obese Individuals: A Cross-Sectional Quantitative Computed Tomography Study.

The main aim of this study is to analyze the relationship between body composition indices and metabolic unhealthy phenotypes in young and middle-aged obese patients and to assess their joint predictive ability. A cross-sectional study method was used to select 207 patients who were proposed to undergo weight loss surgery for morbid obesity from March to November 2022. Total adipose tissue (TAT), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), liver fat content (LFC), cross-sectional area (CSAmuscle), and intermuscular adipose tissue (CSAIMAT) of paraspinal muscles were measured using quantitative computed tomography. Participants were categorized into two groups: metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO). The receiver operating characteristic curve comprised body composition variables that correlated with MUO, and the area under the curve (AUC) was calculated to compare their prediction capacity for MUO. There were 71 patients with MHO (34.3%) and 136 patients with MUO (65.7%). The VAT, VAT/TAT ratio, LFC, and CSAmuscle was higher in MUO patients than in MHO (all P < 0.001), and SAT was lower than in MHO (P = 0.008). And all of these metrics were correlated with MUO (all P < 0.05). Inclusion of these body composition metrics in the ROC analysis showed that the AUC values for SAT, VAT, VAT/TAT ratio, LFC and CSAmuscle were 0.615, 0.663, 0.727, 0.694, 0.671, respectively, and the combination of the VAT/TAT ratio and the LFC had the ability to predict MUO best (AUC=0.746, P = 0.025). The combined use of VAT/TAT ratio and LFC is superior to the use of these two metrics alone in terms of their ability to predict the MUO, providing a more accurate approach to the management and prevention of obesity-related metabolic risk.

Sleep and memory complaints in long COVID: an insight into clustered psychological phenotypes.

This study evaluated clinical features of individuals with long COVID (5-8 months after diagnosis) who reported sleep and memory problems (62 cases) compared to those without (52 controls). Both groups had a similar mean age (41 vs. 39 years). Around 86% of the participants were non-hospitalized at the time of infection, and none of them were vaccinated at that point. Subsequently, both cases and controls received the vaccine; however, the vaccination rates differed significantly between the groups (30.7% vs. 51.0%). Cases and controls had similar rates of symptoms at acute COVID phase. However, cases were more likely to experience coryza, dyspnea, headache, and nausea/vomiting during long COVID. Regarding new-onset symptoms in long COVID, 12.9% of cases had dyspnea, and 14.5% experienced nausea/vomiting, whereas in the control group there were only 1.9% and 0.0%, respectively. Cases also had a significantly higher prevalence of persistent headache (22.6% vs. 7.7%), and dyspnea (12.9% vs. 0.0). In addition, cases also showed an increased rate of mental health complaints: disability in daily activities (45.2% vs. 9.6%; P<0.001); concentration/sustained attention difficulties (74.2% vs. 9.6%; P<0.001); anxiety-Generalized Anxiety Disorder 2-item scale (GAD-2) ≥ 3 (66.1% vs. 34.6%; P=0.0013); and "post-COVID sadness" (82.3% vs. 40.4%; P<0.001). We observed a significant correlation between sadness and anxiety in cases, which was not observed in controls (P=0.0212; Spearman correlation test). Furthermore, the frequency of concomitant sadness and anxiety was markedly higher in cases compared to controls (59.7% vs. 19.2%) (P<0.0001; Mann-Whitney test). These findings highlight a noteworthy association between sadness and anxiety specifically in cases. In conclusion, our data identified concurrent psychological phenotypes in individuals experiencing sleep and memory disturbances during long COVID. This strengthens the existing evidence that SARS-CoV-2 causes widespread brain pathology with interconnected phenotypic clusters. This finding highlights the need for comprehensive medical attention to address these complex issues, as well as major investments in testing strategies capable of preventing the development of long COVID sequelae, such as vaccination.

Tibia-first, gap-balanced patient-specific alignment technique achieves well-balanced gaps in 90% of cases by rebuilding bony anatomy within boundaries.

Patient-specific alignment (PSA) techniquetries to achieve balanced gaps and simultaneously rebuild the individual bony phenotype. The hypothesis was: PSA technique achieves balanced knees in a high percentage with more anatomical resections than adjusted mechanical alignment (AMA). Three hundred sixty-seven patients underwent navigated total knee arthroplasty (TKA) with a tibia-first gap-balanced PSA technique. Resection boundaries for medial proximal tibia angle (MPTA) of 86-92°, mechanical lateral distal femoral angle (mLDFA) of 86-92°, and hip-knee-ankle angle (HKA) of 175-185° were defined. Preoperative and intraoperative parameters of HKA, MPTA, mLDFA, and gap widths were recorded. Depending on the coronal deformity, the patients were divided into three groups: varus HKA < 178°; straight 178-182° and valgus HKA > 182°. The stability was analysed by assessing the difference between medial and lateral extension and flexion gaps as well as between flexion and extension gaps. All PSA measurements were compared with data from a previously published AMA series. PSA achieved balanced gaps in extension, flexion and between flexion/extension in over 90% of cases, being similar to AMA. In PSA, MPTA and mLDFA were restored within 1°, except in extreme varus (MPTA difference 2°) and valgus knees (mLDFA difference 3°). This was caused by the defined boundaries of the alignment technique. This individualised reconstruction led to significantly more anatomical resections of all tibia and femur resections. A tibia-first, gap-balanced PSA technique achieves balanced joints in more than 90% of cases. By maintaining preoperative MPTA and mLDFA to a high extent, far more anatomical resections, compared to AMA were performed. Future studies need to be conducted to investigate whether those promising intraoperative results correlate with postoperative patient outcomes and whether patients outside the 5° corridor have higher failure rates. Level III, retrospective cohort study.

Heat shocks during egg incubation led to developmental, morphological, and behavioral differences in Arctic charr (Salvelinus alpinus).

Temperature variation is affecting fish biodiversity worldwide, causing changes in geographic distribution, phenotypic structure, and even species extinction. Incubation is a critical stage for stenothermic species, which are vulnerable to large temperature fluctuations, and its effects on the phenotype at later developmental stages are understudied, despite the fact that the phenotype being essential for organism ecology and evolution. In this study, we tested the effects of heat shocks during the embryonic period on the phenotype of Arctic charr (Salvelinus alpinus). We repeatedly quantified multiple phenotypic traits, including morphology, development, and behavior, over a period of 4 months, from hatching to juvenile stage in individuals that had experienced heat shocks (+ 5°C on 24 h, seven times) during their embryonic stage and those that had not. We found that heat shocks led to smaller body size at hatching and a lower sociability. Interestingly, these effects weakened throughout the development of individuals and even reversed in the case of body size. We also found an accelerated growth rate and a higher body condition in the presence of heat shocks. Our study provides evidence that heat shocks experienced during incubation can have long-lasting effects on an individual's phenotype. This highlights the importance of the incubation phase for the development of ectothermic organisms and suggests that temperature fluctuations may have significant ecological and evolutionary implications for Arctic charr. Given the predicted increase in extreme events and the unpredictability of temperature fluctuations, it is critical to further investigate their effects on development by examining fluctuations that vary in frequency and intensity.

Clinical phenotypic spectrum of CTNNB1 neurodevelopmental disorder.

Pathogenic heterozygous loss of function variants in CTNNB1 are associated with CTNNB1 neurodevelopmental disorder. We report the clinical phenotype of individuals with CTNNB1 neurodevelopmental disorder using both caregiver-reported data (medical history, adaptive function, quality of life, and behavior issues) and in-person clinical assessments (neurological, motor, and cognitive function) in 32 individuals with likely pathogenic or pathogenic CTNNB1 variants. Most individuals had truncal hypotonia, muscle weakness, hypertonia, dystonia, microcephaly, and many had a history of tethered cord. Visual problems included strabismus, hyperopia, and familial exudative vitreoretinopathy. Half of individuals walked without an assistive device. The mean Gross Motor Functional Measure-66 score was 56.6 (SD = 14.8). Average time to complete Nine-Hole Peg Test was slower than norms. Mean general conceptual ability composite scores from Differential Ability Scales Second Edition were very low (M = 58.3, SD = 11.3). Fifty-five percent of individuals had low adaptive functioning based on the Vineland Adaptive Behavioral Scales. Based upon the Child Behavior Checklist total problems score, the majority (65%) of individuals had behavioral challenges. The mean overall Quality of Life Inventory-Disability score was 81.7 (SD = 11.9). These data provide a detailed characterization of clinical features in individuals with CTNNB1 neurodevelopmental disorder.

Congenital Hyperinsulinism in Humans and Insulin Secretory Dysfunction in Mice Caused by Biallelic DNAJC3 Variants.

The BiP co-chaperone DNAJC3 protects cells during ER stress. In mice, the deficiency of DNAJC3 leads to beta-cell apoptosis and the gradual onset of hyperglycemia. In humans, biallelic DNAJC3 variants cause a multisystem disease, including early-onset diabetes mellitus. Recently, hyperinsulinemic hypoglycemia (HH) has been recognized as part of this syndrome. This report presents a case study of an individual with HH caused by DNAJC3 variants and provides an overview of the metabolic phenotype of individuals with HH and DNAJC3 variants. The study demonstrates that HH may be a primary symptom of DNAJC3 deficiency and can persist until adolescence. Additionally, glycemia and insulin release were analyzed in young DNACJ3 knockout (K.O.) mice, which are equivalent to human infants. In the youngest experimentally accessible age group of 4-week-old mice, the in vivo glycemic phenotype was already dominated by a reduced total insulin secretion capacity. However, on a cellular level, the degree of insulin release of DNAJC3 K.O. islets was higher during periods of increased synthetic activity (high-glucose stimulation). We propose that calcium leakage from the ER into the cytosol, due to disrupted DNAJC3-controlled gating of the Sec61 channel, is the most likely mechanism for HH. This is the first genetic mechanism explaining HH solely by the disruption of intracellular calcium homeostasis. Clinicians should screen for HH in DNAJC3 deficiency and consider DNAJC3 variants in the differential diagnosis of congenital hyperinsulinism.

FANCA c.3624C>T (p.Ser1208=) is a hypomorphic splice variant associated with delayed onset of Fanconi anemia

AbstractFanconi anemia (FA) is a hereditary, DNA repair deficiency disorder caused by pathogenic variants in any 1 of 22 known genes (FANCA-FANCW). Variants in FANCA account for nearly two-thirds of all patients with FA. Clinical presentation of FA can be heterogeneous and include congenital abnormalities, progressive bone marrow failure, and predisposition to cancer. Here, we describe a relatively mild disease manifestation among 6 individuals diagnosed with FA, each compound heterozygous for 1 established pathogenic FANCA variant and 1 FANCA exon 36 variant, c.3624C>T. These individuals had delayed onset of hematological abnormalities, increased survival, reduced incidence of cancer, and improved fertility. Although predicted to encode a synonymous change (p.Ser1208=), the c.3624C>T variant causes a splicing error resulting in a FANCA transcript missing the last 4 base pairs of exon 36. Deep sequencing and quantitative reverse transcription polymerase chain reaction analysis revealed that 6% to 10% of the FANCA transcripts included the canonical splice product, which generated wild-type FANCA protein. Consistently, functional analysis of cell lines from the studied individuals revealed presence of residual FANCD2 ubiquitination and FANCD2 foci formation, better cell survival, and decreased late S/G2 accumulation in response to DNA interstrand cross-linking agent, indicating presence of residual activity of the FA repair pathway. Thus, the c.3624C>T variant is a hypomorphic allele, which contributes to delayed manifestation of FA disease phenotypes in individuals with at least 1 c.3624C>T allele.

MAFLD: an ideal framework for understanding disease phenotype in individuals of normal weight.

The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) is significant, impacting almost one-third of the global population. MAFLD constitutes a primary cause of end-stage liver disease, liver cancer and the need for liver transplantation. Moreover, it has a strong association with increased mortality rates due to various extrahepatic complications, notably cardiometabolic diseases. While MAFLD is typically correlated with obesity, not all individuals with obesity develop the disease and a significant percentage of MAFLD occurs in patients without obesity, termed lean MAFLD. The clinical features, progression and underlying physiological mechanisms of patients with lean MAFLD remain inadequately characterized. The present review aims to provide a comprehensive summary of current knowledge on lean MAFLD and offer a perspective on defining MAFLD in individuals with normal weight. Key to this process is the concept of metabolic health and flexibility, which links states of dysmetabolism to the development of lean MAFLD. This perspective offers a more nuanced understanding of MAFLD and its underlying mechanisms and highlights the importance of considering the broader metabolic context in which the disease occurs. It also bridges the knowledge gap and offers insights that can inform clinical practice.

Clinical Benefits of Targeting Treatable Traits in Asthma and Chronic Obstructive Pulmonary Disease.

Asthma and chronic obstructive pulmonary disease (COPD) have long been debated regarding their similarities and differences in clinical presentation and pathology. There has also been a discussion about how common therapeutics should be used differently for each disease. Traditionally, a "one size fits all" stepwise treatment has been chosen based on the severity of each case after categorizing the diseases, such as asthma or COPD. However, recently, the need for a precise approach for the treatment of individual patients beyond the disease category has been emphasized, especially in severe cases. To achieve precise personalized therapy, it has become necessary to focus on the individual phenotypes and underlying causal molecular mechanisms (endotypes) and to identify key therapeutic targets, which are called treatable traits. This review discusses the evidence for the importance of identifying treatable traits and therapeutic strategies based on the broader perspective of chronic obstructive airway disease rather than on individual diseases such as asthma or COPD.

Intermittent fasting modulates human gut microbiota diversity in a phenotype-dependent manner: a systematic review.

Cumulative evidence suggests that intermittent fasting (IF) has beneficial effects on human metabolic health. It has been indicated that its impact on the gut microbiota may mediate these beneficial effects. As a result, we hypothesized that IF may impact the human gut microbiota. A systematic review was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) protocol using the PubMed, Scopus, and CINAHL databases. We registered our systematic review protocol in PROSPERO under registration number CRD42021270050. Human intervention studies published until April 30, 2023, were included. The quality of the included studies was assessed using National Institutes of Health (NIH) quality assessment study tools for intervention studies. The search in the database returned 166 studies, of which 13 matched all criteria for the final qualitative analysis. The body of evidence suggests that IF modulates human gut microbiota alpha and beta diversity in lean (relatively healthy) and relatively healthy overweight/obese individuals but not in individuals with metabolic syndrome. Furthermore, IF also alters human gut microbiota composition in all phenotypes. Of interest, the gut microbiota taxa or microbial metabolites after an IF intervention are associated with metabolic markers. According to this review, IF influences the diversity and taxonomic levels of the human gut microbiota. Individual metabolic phenotypes may alter the effect of IF on the diversity and taxonomic levels of the gut microbiota.

Auto-LIA: The Automated Vision-Based Leaf Inclination Angle Measurement System Improves Monitoring of Plant Physiology.

Plant sensors are commonly used in agricultural production, landscaping, and other fields to monitor plant growth and environmental parameters. As an important basic parameter in plant monitoring, leaf inclination angle (LIA) not only influences light absorption and pesticide loss but also contributes to genetic analysis and other plant phenotypic data collection. The measurements of LIA provide a basis for crop research as well as agricultural management, such as water loss, pesticide absorption, and illumination radiation. On the one hand, existing efficient solutions, represented by light detection and ranging (LiDAR), can provide the average leaf angle distribution of a plot. On the other hand, the labor-intensive schemes represented by hand measurements can show high accuracy. However, the existing methods suffer from low automation and weak leaf-plant correlation, limiting the application of individual plant leaf phenotypes. To improve the efficiency of LIA measurement and provide the correlation between leaf and plant, we design an image-phenotype-based noninvasive and efficient optical sensor measurement system, which combines multi-processes implemented via computer vision technologies and RGB images collected by physical sensing devices. Specifically, we utilize object detection to associate leaves with plants and adopt 3-dimensional reconstruction techniques to recover the spatial information of leaves in computational space. Then, we propose a spatial continuity-based segmentation algorithm combined with a graphical operation to implement the extraction of leaf key points. Finally, we seek the connection between the computational space and the actual physical space and put forward a method of leaf transformation to realize the localization and recovery of the LIA in physical space. Overall, our solution is characterized by noninvasiveness, full-process automation, and strong leaf-plant correlation, which enables efficient measurements at low cost. In this study, we validate Auto-LIA for practicality and compare the accuracy with the best solution that is acquired with an expensive and invasive LiDAR device. Our solution demonstrates its competitiveness and usability at a much lower equipment cost, with an accuracy of only 2. 5° less than that of the widely used LiDAR. As an intelligent processing system for plant sensor signals, Auto-LIA provides fully automated measurement of LIA, improving the monitoring of plant physiological information for plant protection. We make our code and data publicly available at http://autolia.samlab.cn.

Lovers, not fighters: docility influences reproductive fitness, but not survival, in male Cape ground squirrels, Xerus inauris

Over their lifetime, individuals may use different behavioural strategies to maximize their fitness. Some behavioural traits may be consistent among individuals over time (i.e., ‘personality’ traits) resulting in an individual behavioural phenotype with different associated costs and benefits. Understanding how behavioural traits are linked to lifetime fitness requires tracking individuals over their lifetime. Here, we leverage a long-term study on a multi-year living species (maximum lifespan ~ 10 years) to examine how docility (an individual’s reaction to trapping and handling) may contribute to how males are able to maximize their lifetime fitness. Cape ground squirrels are burrowing mammals that live in social groups, and although males lack physical aggression and territoriality, they vary in docility. Males face high predation risk and high reproductive competition and employ either of two reproductive tactics (‘natal’ or ‘band’) which are not associated with different docility personalities. We found that although more docile individuals sired more offspring on an annual basis, docility did not affect an individual’s long-term (lifetime) reproductive output. Survival was not associated with docility or body condition, but annual survival was influenced by rainfall. Our findings suggest that although docility may represent a behavioural strategy to maximize fitness by possibly playing a role in female-male associations or female mate-choice, variations in docility within our study population is likely maintained by other environmental drivers. However, individual variations in behaviours may still contribute as part of the ‘tool kit’ individuals use to maximize their lifetime fitness.

Group phenotypic composition drives task performances in ants.

Differences in individual behaviour within a group can give rise to functional dissimilarities between groups, particularly in social animals. However, how individual behavioural phenotypes translate into the group phenotype remains unclear. Here, we investigate whether individual behavioural type affects group performance in a eusocial species, the ant Aphaenogaster senilis. We measured individual behavioural traits and created groups of workers with similar behavioural type, either high-exploratory or low-exploratory workers. We tested these groups in four different, ecologically relevant, tasks: reaction to an intruder, prey retrieval from a maze, nest relocation and tool use. We show that, compared to groups of low-exploratory workers, groups of high-exploratory workers were more aggressive towards intruders, more efficient in collecting prey, faster in nest relocation and more likely to perform tool use. Our results demonstrate a strong link between individual and collective behaviour in ants. This supports the 'behavioural type hypothesis' for group dynamics, which suggests that an individual's behaviour in a social environment reflects its own behavioural type. The average behavioural phenotype of a group can therefore be predicted from the behavioural types of individual group members.