Vocal repertoire and individuality in the plains zebra (Equus quagga).

Acoustic signals are vital in animal communication, and quantifying them is fundamental for understanding animal behaviour and ecology. Vocalizations can be classified into acoustically and functionally or contextually distinct categories, but establishing these categories can be challenging. Newly developed methods, such as machine learning, can provide solutions for classification tasks. The plains zebra is known for its loud and specific vocalizations, yet limited knowledge exists on the structure and information content of its vocalzations. In this study, we employed both feature-based and spectrogram-based algorithms, incorporating supervised and unsupervised machine learning methods to enhance robustness in categorizing zebra vocalization types. Additionally, we implemented a permuted discriminant function analysis to examine the individual identity information contained in the identified vocalization types. The findings revealed at least four distinct vocalization types-the 'snort', the 'soft snort', the 'squeal' and the 'quagga quagga'-with individual differences observed mostly in snorts, and to a lesser extent in squeals. Analyses based on acoustic features outperformed those based on spectrograms, but each excelled in characterizing different vocalization types. We thus recommend the combined use of these two approaches. This study offers valuable insights into plains zebra vocalization, with implications for future comprehensive explorations in animal communication.

Studies on "Ascites sarcoma".

This review seeks to highlight and celebrate Professor Tomizo Yoshida's famous work on "Establishment and characterization of a rat ascites sarcoma, later named "Yoshida ascites sarcoma". Considering the tremendous contribution of this ascites tumor system to the subsequent promotion of research on cancer biology and cancer chemotherapy, his paper should be regarded as a monumental one in the cancer field. The research was carried out during 1943 and the results were submitted to this Journal in October 1944, when Japan was approaching a debilitating defeat in World War II in August 1945. In 1947, when "Research on Ascites sarcoma" was first comprehensively introduced to researchers in a special lecture at the Annual Meeting of the Japanese Society of Pathology, the whole audience was deeply impressed and was encouraged to resume scientific activity in Japan.

Autocatalysis, Autopoiesis, and the Opportunity Cost of Individuality.

Ever since Varela and Maturana proposed the concept of autopoiesis as the minimal requirement for life, there has been a focus on cellular systems that erect topological boundaries to separate themselves from their surrounding environment. Here, we reconsider whether the existence of such a spatial boundary is strictly necessary for self-producing entities. This work presents a novel computational model of a minimal autopoietic system inspired by dendrites and molecular dynamic simulations in three-dimensional space. A series of simulation experiments where the metabolic pathways of a particular autocatalytic set are successively inhibited until autocatalytic entities that could be considered autopoietic are produced. These entities maintain their distinctness in an environment containing multiple identical instances of the entities without the existence of a topological boundary. This gives rise to the concept of a metabolic boundary which manifests as emergent self-selection criteria for the processes of self-production without any need for unique identifiers. However, the adoption of such a boundary comes at a cost, as these autopoietic entities are less suited to their simulated environment than their autocatalytic counterparts. Finally, this work showcases a generalized metabolism-centered approach to the study of autopoiesis that can be applied to both physical and abstract systems alike.

Systematic mapping of organism-scale gene-regulatory networks in aging using population asynchrony.

In aging, physiologic networks decline in function at rates that differ between individuals, producing a wide distribution of lifespan. Though 70% of human lifespan variance remains unexplained by heritable factors, little is known about the intrinsic sources of physiologic heterogeneity in aging. To understand how complex physiologic networks generate lifespan variation, new methods are needed. Here, we present Asynch-seq, an approach that uses gene-expression heterogeneity within isogenic populations to study the processes generating lifespan variation. By collecting thousands of single-individual transcriptomes, we capture the Caenorhabditis elegans "pan-transcriptome"-a highly resolved atlas of non-genetic variation. We use our atlas to guide a large-scale perturbation screen that identifies the decoupling of total mRNA content between germline and soma as the largest source of physiologic heterogeneity in aging, driven by pleiotropic genes whose knockdown dramatically reduces lifespan variance. Our work demonstrates how systematic mapping of physiologic heterogeneity can be applied to reduce inter-individual disparities in aging.

The diversity of social complexity in termites.

Sociality underpins major evolutionary transitions and significantly influences the structure and function of complex ecosystems. Social insects, seen as the pinnacle of sociality, have traits like obligate sterility that are considered 'master traits', used as single phenotypic measures of this complexity. However, evidence is mounting that completely aligning both phenotypic and evolutionary social complexity, and having obligate sterility central to both, is erroneous. We hypothesize that obligate and functional sterility are insufficient in explaining the diversity of phenotypic social complexity in social insects. To test this, we explore the relative importance of these sterility traits in an understudied but diverse taxon: the termites. We compile the largest termite social complexity dataset to date, using specimen and literature data. We find that although functional and obligate sterility explain a significant proportion of variance, neither trait is an adequate singular proxy for the phenotypic social complexity of termites. Further, we show both traits have only a weak association with the other social complexity traits within termites. These findings have ramifications for our general comprehension of the frameworks of phenotypic and evolutionary social complexity, and their relationship with sterility.

Responsiveness of functional performance and muscle strength, power, and size to resistance training: A systematic review.

There is a recent and growing interest in assessing differential responders to resistance training (RT) for diverse outcomes. Thus, the individual ability to respond to an intervention for a specific measurement, called responsiveness, remains to be better understood. Thus, the current study aimed to summarize the available information about the effects of RT on functional performance and muscle strength, power, and size in healthy adults, through the prevalence rate in different responsiveness classifications models. A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and was registered at the International Prospective Register of Systematic Reviews (PROSPERO, CRD42021265378). PubMed/MEDLINE, Scopus, and Embase databases were systematically searched in October 2023. A total of 13 studies were included, totaling 921 subjects. Only two studies presented a low risk of bias. Regarding the effectiveness of RT, the prevalence rate for non-responders ranged from 0% to 44% for muscle strength, from 0% to 84% for muscle size, and from 0% to 42% for functional performance, while for muscle power, the only study found showed a responsiveness rate of 37%. In conclusion, a wide range of differential responders is described for all variables investigated. However, the evidence summarized in this systematic review suggested some caution while interpreting the findings, since the body of evidence found seems to be incipient, and widely heterogeneous in methodological and statistical aspects.

Biological variation of PIVKA-II in blood serum of healthy subjects measured by automated electrochemiluminescent assay.

Background: Prothrombin/Protein Induced by Vitamin K Absence-II (PIVKA-II) is a candidate biomarker of hepatocellular cancer, recommended both for diagnostics and monitoring. The aim was to evaluate biological variation (BV) of serum PIVKA-II. Methods: Within-subject (CVI) and between-subject (CVG) BV estimates were assessed in 14 healthy volunteers in a 6-week protocol. Serum concentrations of PIVKA-II were measured by a Roche Elecsys PIVKA-II diagnostic kit (cobas e8000). Precision (CVA) was assessed from duplicate measurements of all volunteers' samples. Two methods were used for the estimation of CVI: SD-ANOVA and CV-ANOVA method. We calculated the index of individuality (II) and reference change value. The experiment was fully compliant with EFLM database checklist. Results: The CVI of PIVKA-II in healthy persons, as calculated by two statistical methods, were 8.2% (SD-ANOVA with CVA of 3.2%) and 9.4% (CV-ANOVA) with CVA of 2.7%). The CVG was 19.5% (SD-ANOVA), and respective II and RCV were 0.42 and 24.4%. Conclusions: CVI and CVG of PIVKA-II were 8.2% and 19.5%, respectively, with CVA below 4%. The low II and RCV below 25% enable the use of this biomarker both for diagnostics and monitoring. More data are needed before the introduction of PIVKA-II into clinical practice.

Biological variation in the estimated glomerular filtration rate of healthy individuals within 24 h calculated using 2021CKD-EPI equations.

BACKGROUND AND AIMS: Use the MDRD (Modification of Diet in Renal Disease) and 2021 CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation void of race coefficients (CKD-EPICrea, CKD-EPICys-C, and CKD-EPICrea+Cys-C) to estimate the BV (Biological variation) of eGFR (estimated glomerular filtration rate) within 24 h in a healthy population to help explain future studies using eGFR in the context of a known BV. METHODS: Blood samples were collected from 30 healthy subjects at six time points within 24 h. Serum creatinine (S-Crea) and serum cystatin C (S-Cys-C) were measured, and the BV of eGFR was calculated. Outlier and variance homogeneity analyses were performed, followed by CV-ANOVA on trend-corrected data. RESULTS: The eGFR CVI for the four equations (MDRD, CKD-EPICrea, CKD-EPICys-C, and CKD-EPICrea+Cys-C) were 8.39% (7.50-9.51%), 3.90% (3.49-4.42%), 6.58% (5.88-7.46%), and 5.03% (4.50-5.71%), respectively. The corresponding II and RCVpos/neg values were 0.69, 0.48, 0.51, and 0.31, and (29.30%, - 22.66%), (12.69%, - 11.2 6%), (20.97%, - 17.33%), and (15.88%, - 13.70%), respectively; RCVpos /neg of eGFR was highest in the MDRD equation and lowest in the CKD-EPI Crea equation. Additionally, the RCVpos/neg values of the individual was highest in the MDRD equation and lowest in the CKD-EPICrea+Cys-C equation; they are (56.51%, - 36.11%) and (5.01%, - 4.77%), respectively. CONCLUSIONS: We present data on the 24 h BV eGFR of the 2021 CKD-EPI equations. The presence of BV has impact on the interpretation of GFR results, affecting CKD disease grading. The RCVpos/neg differences were large among the individuals. When using eGFRs based on the MDRD and CKD-EPI equations, it is necessary to combine RCVpos/neg values before interpreting the results.

The Commonality and Individuality of Human Brains When Performing Tasks.

It is imperative to study individual brain functioning toward understanding the neural bases responsible for individual behavioral and clinical traits. The complex and dynamic brain activity varies from area to area and from time to time across the entire brain, and BOLD-fMRI measures this spatiotemporal activity at large-scale systems level. We present a novel method to investigate task-evoked whole brain activity that varies not only from person to person but also from task trial to trial within each task type, offering a means of characterizing the individuality of human brains when performing tasks. For each task trial, the temporal correlation of task-evoked ideal time signal with the time signal of every point in the brain yields a full spatial map that characterizes the whole brain's functional co-activity (FC) relative to the task-evoked ideal response. For any two task trials, regardless of whether they are the same task or not, the spatial correlation of their corresponding two FC maps over the entire brain quantifies the similarity between these two maps, offering a means of investigating the variation in the whole brain activity trial to trial. The results demonstrated a substantially varied whole brain activity from trial to trial for each task category. The degree of this variation was task type-dependent and varied from subject to subject, showing a remarkable individuality of human brains when performing tasks. It demonstrates the potential of using the presented method to investigate the relationship of the whole brain activity with individual behavioral and clinical traits.

Temporal Interactions between Maintenance of Cerebral Cortex Thickness and Physical Activity from an Individual Person Micro-Longitudinal Perspective and Implications for Precision Medicine.

Maintenance of brain structure is essential for neurocognitive health. Precision medicine has interests in understanding how maintenance of an individual person's brain, including cerebral cortical structure, interacts with lifestyle factors like physical activity. Cortical structure, including cortical thickness, has recognized relationships with physical activity, but concepts of these relationships come from group, not individual, focused findings. Whether or how group-focused concepts apply to an individual person is fundamental to precision medicine interests but remains unclear. This issue was studied in a healthy man using concurrent micro-longitudinal tracking of magnetic resonance imaging-defined cortical thickness and accelerometer-defined steps/day over six months. These data permitted detailed examination of temporal relationships between thickness maintenance and physical activity at an individual level. Regression analyses revealed graded significant and trend-level temporal interactions between preceding activity vs. subsequent thickness maintenance and between preceding thickness maintenance vs. subsequent activity. Interactions were bidirectional, delayed/prolonged over days/weeks, positive, bilateral, directionally asymmetric, and limited in strength. These novel individual-focused findings in some ways are predicted, but in other ways remain unaddressed or undetected, by group-focused work. We suggest that individual-focused concepts of temporal interactions between maintenance of cortical structure and activity can provide needed new insight for personalized tailoring of physical activity, cortical, and neurocognitive health.

The intensity paradox: A systematic review and meta-analysis of its impact on the cardiorespiratory fitness of older adults.

AIM: The present systematic review and meta-analysis aimed to compare the effect of moderate- versus high-intensity aerobic exercise on cardiorespiratory fitness (CRF) in older adults, taking into account the volume of exercise completed. METHODS: The databases MEDLINE (Ovid), EMBASE (Ovid), and CENTRAL (Cochrane Library) were searched to identify randomized controlled trials (RCTs). Two reviewers extracted data and assessed bias. Comprehensive Meta-Analysis software calculated overall effect size, intensity differences, and performed meta-regression analyses using pre-to-post intervention or change scores of peak oxygen uptake (V̇O2 peak). The review included 23 RCTs with 1332 older adults (intervention group: n = 932; control group: n = 400), divided into moderate-intensity (435 older adults) and high-intensity (476 older adults) groups. RESULTS: Meta-regression analysis showed a moderate, but not significant, relationship between exercise intensity and improvements in V̇O2 peak after accounting for the completed exercise volume (ß = 0.31, 95% CI = [-0.04; 0.67]). Additionally, studies comparing moderate- versus high-intensity revealed a small, but not significant, effect in favor of high-intensity (Hedges' g = 0.20, 95% CI = [-0.02; 0.41]). Finally, no significant differences in V̇O2 peak improvements were found across exercise groups employing various methods, modalities, and intensity monitoring strategies. CONCLUSION: Findings challenge the notion that high-intensity exercise is inherently superior and indicate that regular aerobic exercise, irrespective of the specific approach and intensity, provides the primary benefits to CRF in older adults. Future RCTs should prioritize valid and reliable methodologies for monitoring and reporting exercise volume and adherence among older adults.

Subjective experience of the environment determines serotoninergic antidepressant treatment outcome in male mice.

BACKGROUND: The effects of the selective serotonin reuptake inhibitors (SSRIs), the first-line antidepressant treatment, have been proposed to be affected, at least in part, by the living environment. Since the quality of the environment depends not only on its objective features, but also on the subjective experience, we hypothesized that the latter plays a key role in determining SSRI treatment outcome. METHODS: We chronically administered the SSRI fluoxetine to two groups of adult CD-1 male mice that reportedly show distinct subjective experiences of the environment measured as consistent and significantly different responses to the same emotional and social stimuli. These distinct socioemotional profiles were generated by rearing mice either in standard laboratory conditions (SN) or in a communal nest (CN) where three dams breed together their offspring, sharing caregiving behavior. RESULTS: At adulthood, CN mice displayed higher levels of agonistic and anxiety-like behaviors than SN mice, indicating that they experience the environment as more socially challenging and potentially dangerous. We then administered fluoxetine, which increased offensive and anxious response in SN, while producing opposite effects in CN mice. BDNF regulation was modified by the treatment accordingly. LIMITATIONS: Subjective experience in mice was assessed as behavioral response to the environment. CONCLUSIONS: These results show that the subjective experience of the environment determines fluoxetine outcome. In a translational perspective, our findings suggest considering not only the objective quality, but also the subjective appraisal, of the patient's living environment for developing effective personalized therapeutic approaches in psychiatry.

What if gastrointestinal complications in endurance athletes were gut injuries in response to a high consumption of ultra-processed foods? Please take care of your bugs if you want to improve endurance performance: a narrative review.

To improve performance and recovery faster, athletes are advised to eat more often than usual and consume higher doses of simple carbohydrates, during and after exercise. Sports energetic supplements contain food additives, such as artificial sweeteners, emulsifiers, acidity regulators, preservatives, and salts, which could be harmful to the gut microbiota and impair the intestinal barrier function. The intestinal barrier plays a critical function in bidirectionally regulation of the selective transfer of nutrients, water, and electrolytes, while preventing at the same time, the entrance of harmful substances (selective permeability). The gut microbiota helps to the host to regulate intestinal homeostasis through metabolic, protective, and immune functions. Globally, the gut health is essential to maintain systemic homeostasis in athletes, and to ensure proper digestion, metabolization, and substrate absorption. Gastrointestinal complaints are an important cause of underperformance and dropout during endurance events. These complications are directly related to the loss of gut equilibrium, mainly linked to microbiota dysbiosis and leaky gut. In summary, athletes must be cautious with the elevated intake of ultra-processed foods and specifically those contained on sports nutrition supplements. This review points out the specific nutritional interventions that should be implemented and/or discontinued depending on individual gut functionality.

Biological variation of serum neopterin concentrations in apparently healthy individuals.

OBJECTIVES: The aims of this study were to determine the biological variation (BV), reference change value (RCV), index of individuality (II), and quality specifications for serum neopterin concentrations; a measurand provided by clinical laboratories as an indicator of cellular immunity. METHODS: The study delivered serum samples collected for 10 consecutive weeks from 12 apparently healthy individuals (3 male, 9 female). Serum neopterin concentrations were measured using high-performance liquid chromatography with fluorometric detection. The data analysis was performed using an online statistical tool and addressed published criteria for estimation of biological variation. RESULTS: The mean neopterin concentration was 5.26 nmol/L. The within-subject biological variation (CVI) with 95 % confidence interval (CI) of neopterin serum concentrations was 11.54 % (9.98-13.59), and the between-subject biological variation (CVG) with 95 % CI was 43.27 % (30.52-73.67). The neopterin asymmetrical RCV was -24.9 %/+33.1 %, and the II was 0.27. The desirable quality specifications for neopterin were <5.77 % for precision, <11.20 % for bias, and <20.72 % for total allowable error (TEa). When analytical variation was used instead of CVI to calculate TEa, the desirable TEa was <18.39. CONCLUSIONS: This study determined BV data for neopterin, an indicator of cell-mediated immune response. Asymmetric RCV values, of 24.9 % decrease or a 33.1 % increase between consecutive measurements indicate significant change. The II of 0.27 indicates a high degree of individuality, therefore that it is appropriate to consider the use of personal reference data and significance of change rather than the reference interval as points of reference for the evaluation of neopterin serum concentrations.

Joseph E. Murray's Struggle to Transplant Kidneys: Failure, Individuality, and Plastic Surgery, 1950-1965.

This paper offers a historical analysis of the American plastic surgeon and Nobel laureate Joseph E. Murray's kidney transplantation. After succeeding in the first kidney transplantation between monozygotic twins in 1954, he transplanted kidneys between genetically distinct people after X-radiation and immunosuppressants. Amid these achievements, however, Murray encountered numerous failures, which he thought were closely intertwined with each patient's physiological and pathological individuality. As he appropriated his expertise in plastic surgery for kidney transplantation, this individuality became a major issue that he had to cope with in his efforts to avoid failures. To him, kidney transplantation could fail because of each individual's immunological barrier or constitutional singularity that could engender unexpected complications. Although he could neither explain nor control many of these failures, I argue that his unsuccessful work and patient individuality played multiple roles in shaping his operations as a plastic surgeon. They structured the path of his surgical research, made sense of it, defended him from criticism, and formed the way that he presented the results of his work with an immunological implication. Consequently, Murray, with little scientific training, articulated an important dimension of immunological tolerance relevant to clinical settings.

Ethics in infectious diseases: latent challenges. Part I.

Infectious diseases socially imply individual and community medical problems. Therefore, they require actions aimed at social processes that affect the well-being of the individuals without losing sight of social groups. Faced with this panorama, we ask ourselves: is there a direct relationship between ethics and infectious diseases? To elucidate an answer, let us remember the peak period of the COVID-19 pandemic when guidelines based on ethical principles were issued to facilitate medical decisions on allocating scarce resources in periods of maximum demand. In those moments, since there was no inclusive component of society, the decisions made produced massive criticism. The reactions demonstrated the need to analyze in detail the criteria that had been considered correct. Consequently, we affirm that bioethical principles are transcendental in medical decisions and must be examined, not only for the individual but also with a view to public health. Moreover, the acquired immunodeficiency syndrome (AIDS) epidemic has lived with us for decades, and it continues to show its tragic face in the form of new cases, chronic illnesses, and deaths. Joint United Nations Programme on HIV/AIDS brings us closer to a complex reality where the fight against disease and global health are interrelated with other problems, such as the need to reduce inequality, for which human rights, gender equality, social protection, and the development of research projects, where the ethics committees in research in community processes are constituents.

Las enfermedades infecciosas implican problemas médicos individuales y comunitarios, por lo que requieren acciones dirigidas a procesos sociales que incidan en el bienestar de los individuos, sin perder de vista a los grupos sociales. Nos preguntamos: ¿existe relación directa entre la ética y las enfermedades infecciosas? Para dilucidar una respuesta, recordemos el periodo más álgido de la pandemia por COVID-19, cuando se emitieron guías fundamentadas en principios éticos para facilitar las decisiones médicas en la asignación de recursos escasos en periodos de máxima demanda. Al no haber un componente inclusivo con la sociedad, las decisiones que se tomaron produjeron críticas masivas, que demostraron la necesidad de analizar a detalle los criterios que se habían considerado correctos. En consecuencia, afirmamos que los principios bioéticos son trascendentales en las decisiones médicas y deben ser examinados, no solo frente al individuo, sino de cara a la salud pública (bien común e individualidad). Por otra parte, la epidemia del SIDA (síndrome de inmunodeficiencia adquirida) convive con nosotros desde hace décadas. ONUSIDA (Programa Conjunto de las Naciones Unidas sobre el VIH/SIDA) nos acerca una realidad compleja, como es que la lucha contra la enfermedad y por la salud global se interrelaciona con otros problemas como la necesidad de reducer la desigualdad, por los derechos humanos, la igualdad de género, la protección social y el desarrollo de proyectos de investigación, donde los comités de Ética en investigación en procesos comunitarios son constituyentes.

Ethics in infectious diseases: latent challenges. Part I / Ética en enfermedades infecciosas: retos latentes. Parte I

Abstract Infectious diseases socially imply individual and community medical problems. Therefore, they require actions aimed at social processes that affect the well-being of the individuals without losing sight of social groups. Faced with this panorama, we ask ourselves: is there a direct relationship between ethics and infectious diseases? To elucidate an answer, let us remember the peak period of the COVID-19 pandemic when guidelines based on ethical principles were issued to facilitate medical decisions on allocating scarce resources in periods of maximum demand. In those moments, since there was no inclusive component of society, the decisions made produced massive criticism. The reactions demonstrated the need to analyze in detail the criteria that had been considered correct. Consequently, we affirm that bioethical principles are transcendental in medical decisions and must be examined, not only for the individual but also with a view to public health. Moreover, the acquired immunodeficiency syndrome (AIDS) epidemic has lived with us for decades, and it continues to show its tragic face in the form of new cases, chronic illnesses, and deaths. Joint United Nations Programme on HIV/AIDS brings us closer to a complex reality where the fight against disease and global health are interrelated with other problems, such as the need to reduce inequality, for which human rights, gender equality, social protection, and the development of research projects, where the ethics committees in research in community processes are constituents.

Resumen Las enfermedades infecciosas implican problemas médicos individuales y comunitarios, por lo que requieren acciones dirigidas a procesos sociales que incidan en el bienestar de los individuos, sin perder de vista a los grupos sociales. Nos preguntamos: ¿existe relación directa entre la ética y las enfermedades infecciosas? Para dilucidar una respuesta, recordemos el periodo más álgido de la pandemia por COVID-19, cuando se emitieron guías fundamentadas en principios éticos para facilitar las decisiones médicas en la asignación de recursos escasos en periodos de máxima demanda. Al no haber un componente inclusivo con la sociedad, las decisiones que se tomaron produjeron críticas masivas, que demostraron la necesidad de analizar a detalle los criterios que se habían considerado correctos. En consecuencia, afirmamos que los principios bioéticos son trascendentales en las decisiones médicas y deben ser examinados, no solo frente al individuo, sino de cara a la salud pública (bien común e individualidad). Por otra parte, la epidemia del SIDA (síndrome de inmunodeficiencia adquirida) convive con nosotros desde hace décadas. ONUSIDA (Programa Conjunto de las Naciones Unidas sobre el VIH/SIDA) nos acerca una realidad compleja, como es que la lucha contra la enfermedad y por la salud global se interrelaciona con otros problemas como la necesidad de reducer la desigualdad, por los derechos humanos, la igualdad de género, la protección social y el desarrollo de proyectos de investigación, donde los comités de Ética en investigación en procesos comunitarios son constituyentes.

Biological Variation in Biochemistry Analytes in Laboratory Guinea Pigs (Cavia porcellus).

Biological variation (BV) describes the physiological random fluctuation around a homeostatic set point, which is a characteristic of all blood measurands (analytes). That variation may impact the clinical relevance of the changes that are observed in the serial results for an individual. Biological variation is represented mathematically by the coefficient of variation (CV) and occurs within each individual (CVI) and between individuals in a population (CVG). Biological variation data can be used to assess whether population-based reference or subject-based reference intervals should be used for the interpretation of laboratory results through the calculation of the index of individuality (IoI). This study aimed to determine the biological variations, calculate the IoI and reference change values (RCV) of clinical chemistry analytes in an outbred strain colony of Hartley guinea pigs (GPs), and set the quality specifications for clinical chemistry analytes. Blood was collected from 16 healthy adult laboratory colony GPs via jugular venipuncture at weekly intervals over six weeks. All the samples were frozen and analyzed in a single run. Analytical, CVI, and CVG biological variations, together with the IoI and RCV, were calculated for each measurand. Based on the estimated BV, the calculated IoI was low for glucose, so individual reference intervals (RCV) should be used. The majority of the measurands should be interpreted using both population-based and subject-based reference intervals as the IoIs were intermediate.

Evolutionary consequences of nascent multicellular life cycles.

A key step in the evolutionary transition to multicellularity is the origin of multicellular groups as biological individuals capable of adaptation. Comparative work, supported by theory, suggests clonal development should facilitate this transition, although this hypothesis has never been tested in a single model system. We evolved 20 replicate populations of otherwise isogenic clonally reproducing 'snowflake' yeast (Δace2/∆ace2) and aggregative 'floc' yeast (GAL1p::FLO1 /GAL1p::FLO1) with daily selection for rapid growth in liquid media, which favors faster cell division, followed by selection for rapid sedimentation, which favors larger multicellular groups. While both genotypes adapted to this regime, growing faster and having higher survival during the group-selection phase, there was a stark difference in evolutionary dynamics. Aggregative floc yeast obtained nearly all their increased fitness from faster growth, not improved group survival; indicating that selection acted primarily at the level of cells. In contrast, clonal snowflake yeast mainly benefited from higher group-dependent fitness, indicating a shift in the level of Darwinian individuality from cells to groups. Through genome sequencing and mathematical modeling, we show that the genetic bottlenecks in a clonal life cycle also drive much higher rates of genetic drift-a result with complex implications for this evolutionary transition. Our results highlight the central role that early multicellular life cycles play in the process of multicellular adaptation.