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A central topic in research at the intersection of development and evolution is the origin of novel traits. Despite progress on understanding how developmental mechanisms underlie patterns of diversity in the history of life, the problem of novelty continues to challenge researchers. Here we argue that research on evolutionary novelty and the closely associated phenomenon of co-option can be reframed fruitfully by: (1) specifying a conceptual model of mechanisms that underwrite character identity, (2) providing a richer and more empirically precise notion of co-option that goes beyond common appeals to “deep homology”, and (3) attending to the nature of experimental interventions that can determine whether and how the co-option of identity mechanisms can help to explain novel character origins. This reframing has the potential to channel future investigation to make substantive progress on the problem of evolutionary novelty. To illustrate this potential, we apply our reframing to two case studies: treehopper helmets and beetle horns. ispartof: Seminars In Cell & Developmental Biology pages:1-20 status: Published online

BackgroundThe addition of calcium to resuscitation fluids is a common practice in horses, but studies evaluating the effects of calcium supplementation are limited. In healthy horses, decreases in heart rate and changes in serum electrolyte concentrations have been reported.HypothesisCalcium gluconate administration at a rate of 0.4 mg/kg/min to eliminated endurance horses with metabolic problems will affect heart rate, gastrointestinal sounds, and serum electrolyte concentrations.AnimalsEndurance horses eliminated from the Tevis Cup 100-mile (160 km) endurance ride for metabolic problems and requiring IV fluid therapy were eligible.MethodsSixteen horses were randomly assigned to receive 0.4 mg/kg/min of calcium (23% calcium gluconate solution) over 1 hour diluted in 10 L of a non-calcium containing isotonic crystalloid (CAL group) or 10 L of a non-calcium containing isotonic crystalloid (CON group). Staff members administering the fluids were blinded to treatment group. Blood samples were collected and physical examinations performed before and after treatment. Heart rates were recorded every 15 min during fluid administration. Data were compared using 2-way analysis of variance (ANOVA) with repeated measures for continuous variables and Fisher's exact test for categorical variables.ResultsCalcium was associated with lower heart rates 45 min after starting the infusion (P = .002). Gastrointestinal sounds were less likely to improve in the calcium group compared with the control group (P = .005). An increase in plasma phosphorus concentration (P = .03) was associated with calcium administration.ConclusionsIntravenous calcium supplementation to endurance horses eliminated from competition after development of metabolic problems may decrease heart rate but impairs improvement in gastrointestinal sounds.

While infection and perceived infection risk can influence social and reproductive behavior in several taxa, relatively little is known about how infection specifically affects pair bond behaviors. Some pair bond maintenance behaviors may be costly to maintain during infection, and infection could promote avoidance behaviors within an established pair. Many species exhibiting pair bonds are part of larger social groups, and behavioral shifts in established pairs can result in altered extra-pair contact rates that could also shape disease transmission. Using captive zebra finches (Taeniopygia guttata), we examined how an immune challenge with lipopolysaccharide (LPS) influences activity, social behavior, and pair bond maintenance behaviors in established pairs and their healthy neighbors. We observed shifts in individual and pair maintenance behaviors in both immune-challenged pairs and healthy pairs exposed to a social cue of infection (sick conspecifics). Specifically, LPS-challenged birds decreased activity and social interaction attempts relative to control birds, consistent with LPS-induced sickness behavior. LPS-challenged birds also increased the frequency of clumping (perching together in bodily contact) between individuals within a pair. Healthy birds exposed to immune-challenged conspecifics decreased flight activity and increased self-preening, behaviors which could function to limit infection risk. Exploring how both infection and the perceived risk of infection shape behaviors within and among paired individuals will increase our understanding of the role of social behaviors in shaping disease dynamics.

The concept of teleonomy has been attracting renewed attention recently. This is based on the idea that teleonomy provides a useful conceptual replacement for teleology, and even that it constitutes an indispensable resource for thinking biologically about purposes. However, both these claims are open to question. We review the history of teleological thinking from Greek antiquity to the modern period to illuminate the tensions and ambiguities that emerged when forms of teleological reasoning interacted with major developments in biological thought. This sets the stage for an examination of Pittendrigh’s (Adaptation, natural selection, and behavior. In: Roe A, Simpson GG (eds) Behavior and evolution. Yale University Press, New Haven, pp 390–416, 1958) introduction of “teleonomy” and its early uptake in the work of prominent biologists. We then explore why teleonomy subsequently foundered and consider whether the term may yet have significance for discussions of goal-directedness in evolutionary biology and philosophy of science. This involves clarifying the relationship between teleonomy and teleological explanation, as well as asking how the concept of teleonomy impinges on research at the frontiers of evolutionary theory.

During the fertilization process, the interaction between the sperm and the oocyte is mediated by a process known as acrosomal exocytosis (AE). Although the role of the sperm acrosome on fertilization has been studied extensively over the last 70 years, little is known about the molecular mechanisms that govern acrosomal function, particularly in species other than mice or humans. Even though subfertility due to acrosomal dysfunction is less common in large animals than in humans, the evaluation of sperm acrosomal function should be considered not only as a complementary but a routine test when individuals are selected for breeding potential. This certainly holds true for stallions, which might display lower levels of fertility in the face of "acceptable" sperm quality parameters determined by conventional sperm assays. Nowadays, the use of high throughput technologies such as flow cytometry or mass spectrometry-based proteomic analysis is commonplace in the research arena. Such techniques can also be implemented in clinical scenarios of males with "idiopathic" subfertility. The current review focuses on the sperm acrosome, with particular emphasis on the stallion. We aim to describe the physiological events that lead to the acrosome formation within the testis, the role of very specific acrosomal proteins during AE, the methods to study the occurrence of AE under in vitro conditions, and the potential use of molecular biology techniques to discover new markers of acrosomal function and subfertility associated with acrosomal dysfunction in stallions.

Intracytoplasmic Sperm Injection (ICSI) using frozen/thawed sperm is a common procedure to obtain embryos from fertile or subfertile mares and stallions. Stallion-associated factors that impact the efficiency of ICSI have been studied less than those associated with the mare. Three experiments were conducted: Experiment 1: the effect of freezing extender composition and cryoprotectant; Experiment 2: the effect of sperm exposure to seminal plasma prior to freezing (ejaculated vs. epididymal sperm; two-freeze/thaw cycles each); and Experiment 3: the effect of sperm morphologic feature used for fertilization (normal vs. cytoplasmic droplet vs. bent tail); on the blastocyst rate after ICSI. In Experiment 1, stallion sperm was cryopreserved using commercially available extenders containing: a) 2% egg-yolk + milk + 4% glycerol (MFR5); b) 2% egg-yolk + milk + 2% glycerol + 3% methyl formamide (CMMFR5); c) 20% egg-yolk + 4.75% glycerol (LE); or d) 20% egg-yolk + 2% glycerol + 3% methyl formamide (CMLE). Sperm from each of the treatment groups were used for Piezo-driven ICSI on in vitro-matured equine oocytes (n = 321). Extender CMLE resulted in a lower cleavage rate (35%) than the other treatment groups (MFR5: 74%, CMMFR5: 62%, LE: 68%; P 0.05). Extender MFR5 yielded a higher blastocyst rate per injected oocyte (21/82 [26%]) than the Groups LE (8/77 [10%]), CMLE (4/80 [5%]) or CMMFR5 (4/82 [5%]; P 0.05). Extender MFR5 also yielded a higher blastocyst rate per cleaved oocyte (34%) than Groups LE, CMLE or CMMFR5 (15%, 14%, 8%; respectively P 0.05). In Experiment 2, ejaculated (EJ) and epididymal (EPD) sperm from a fertile stallion which was initially cryopreserved in the CMLE extender, was thawed and re-cryopreserved in MFR5 extender for use in ICSI. Sperm from both groups (EJ vs. EPD) were used for ICSI on in vitro matured oocytes (n = 127). Differences were not detected for cleavage rate (EJ: 36/63 [57%] vs. EPD: 49/64 [77%]), blastocyst rate per injected oocyte (EJ: 11/63 [17%] vs. EPD: 11/64 [17%]), or blastocyst rate per cleaved oocyte (EJ: 31% vs. EPD: 22%) between treatment groups (P 0.05). In Experiment 3, morphologically normal sperm (N), or sperm with proximal droplets (PD) or bent tails (BT), were obtained from a single fertile stallion and were used for ICSI on in vitro matured oocytes (n = 75). No differences were detected among treatment groups for cleavage rate (N: 19/25 [77%] vs. PD: 20/25 [88%] vs. BT: 18/25 [72%]), blastocyst rate per injected oocyte (N: 6/25 [24%] vs. PD: 5/25 [20%] vs. BT: 2/25 [8%]), and blastocyst rate per cleaved oocyte (N: 32% vs. PD: 23% vs. BT: 11%; P 0.05). In conclusion, the current study indicates that freezing extender composition used for stallion sperm cryopreservation has an impact on the developmental competence of in vitro-matured equine oocytes after ICSI and in vitro culture. Furthermore, we were unable to detect differences on cleavage and blastocyst rates when performing ICSI when using: 1) ejaculated or epididymal sperm; or 2) sperm with different morphologic features. The results from the current study provide additional insight regarding stallion-related factors that should be considered when performing ICSI in horses.

Background: Next generation sequencing studies have revealed an ever-increasing number of causes for genetic disorders of central nervous system white matter. A substantial number of disorders are identifiable from their specific pattern of biochemical and/or imaging findings for which single gene testing may be indicated. Beyond this group, the causes of genetic white matter disorders are unclear and a broader approach to genomic testing is recommended. Aim: This study aimed to identify the genetic causes for a group of individuals with unclassified white matter disorders with suspected genetic aetiology and highlight the investigations required when the initial testing is non-diagnostic. Methods: Twenty-six individuals from 22 families with unclassified white matter disorders underwent deep phenotyping and genome sequencing performed on trio, or larger, family groups. Functional studies and transcriptomics were used to resolve variants of uncertain significance with potential clinical relevance. Results: Causative or candidate variants were identified in 15/22 (68.2%) families. Six of the 15 implicated genes had been previously associated with white matter disease (COL4A1, NDUFV1, SLC17A5, TUBB4A, BOLA3, DARS2). Patients with variants in the latter two presented with an atypical phenotype. The other nine genes had not been specifically associated with white matter disease at the time of diagnosis and included genes associated with monogenic syndromes, developmental disorders, and developmental and epileptic encephalopathies (STAG2, LSS, FIG4, GLS, PMPCA, SPTBN1, AGO2, SCN2A, SCN8A). Consequently, only 46% of the diagnoses would have been made via a current leukodystrophy gene panel test. Discussion: These results confirm the importance of broad genomic testing for patients with white matter disorders. The high diagnostic yield reflects the integration of deep phenotyping, whole genome sequencing, trio analysis, functional studies, and transcriptomic analyses. Conclusions: Genetic white matter disorders are genetically and phenotypically heterogeneous. Deep phenotyping together with a range of genomic technologies underpin the identification of causes of unclassified white matter disease. A molecular diagnosis is essential for prognostication, appropriate management, and accurate reproductive counseling.

Acrosomal dysfunction has been considered as a cause of subfertility in males of different species, including stallions. A subset of subfertile stallions with acrosomal dysfunction is unique because they have normal sperm quality (motility, morphology, viability, and DNA quality). The current work aims to describe the clinical characteristics of subfertile stallions that were diagnosed with Impaired Acrosomal Exocytosis (IAE) by using two high throughput methods: flow cytometry and molecular genetic analysis, and to identify the prevalence of subfertility due to IAE in stallions evaluated at Texas AM University. Clinical data from 1,128 stallions evaluated during 17 years at a Veterinary Teaching Hospital was retrospectively analyzed. Only stallions with a history of subfertility not explained following a breeding soundness examination and/or conventional semen analysis, were included. For those stallions, the acrosomal exocytosis test (AE test), in which sperm is incubated at 37 °C for up to 2 h in the presence of the calcium ionophore A23187, was used to determine IAE. The difference in AE-Rate (AE-Diff) between each pair of fertile control stallion and subfertile stallion was categorized as: Normal: AE-Diff14%; Questionable: AE-Diff 15-29%; Abnormal: AE-Diff30%. In selected cases, blood or hair was procured for identification of the susceptibility genotype for IAE, A/A-A/A, in the FKBP6 gene, exon 5. Twenty-one (21) stallions (1.86% total population analyzed) had reduced fertility despite having acceptable sperm quality. Sperm from these stallions were subjected to the AE Test. Of these, 8 stallions had reduced sperm AE-rate, based on the AE Test (8/21; 38.1%). Subsequently, blood or hair samples from these 8 stallions which had either questionable (AE-Diff 15 - 29%; n = 5) or abnormal (AE-Diff30%; n = 3) responses to the AE Test were analyzed for the susceptibility genotype for IAE, A/A-A/A (FKBP6 gene, exon 5). Seven out of the eight (7/8) stallions carried this susceptibility genotype. All of these were Thoroughbreds. After 2 h of incubation, the viability in fertile stallion sperm was lower than in A/A-A/A stallions (4% vs. 25%, respectively; P 0.05), while the AE-rate was higher for fertile than for A/A-A/A stallions (85% vs. 56%, respectively; P 0.05). The use of two high throughput tests (i.e., flow cytometry and molecular genetic analysis) may complement each other in the diagnosis of IAE in breeding stallions. In this study, 5/7 subfertile stallions diagnosed with the IAE susceptibility genotype would have been diagnosed as normal with the AE Test. This study introduces a subset of stallions with the IAE genotype with fertility higher than has been previously reported (i.e.,15% per-cycle pregnancy rate), suggesting that IAE manifests as a broader range of subfertility.

PDF file - 515K, Members of the ErbB4 pathway. Genes found to be differentially expressed in one or more of the MCF-7 cell lines are shaded

Mouse mammary tumor virus (MMTV) is associated primarily with mammary carcinomas and lymphomas. The signal peptide of the MMTV envelope precursor is uniquely targeted to nucleoli of cells that harbor the virus, where it can function as a nuclear export factor for intron-containing transcripts. Antibodies to this signal peptide, which we refer to as p14, were previously shown to label nucleoli in a subset of human breast cancers. To look for additional cellular functions of p14, different mutants were ectopically expressed in the MCF-7 human breast cancer cell line. This approach identified motifs responsible for its nucleolar targeting, nucleocytoplasmic shuttling, target protein (B23, nucleophosmin) binding, and phosphorylation at serine 18 and 65 both in situ and in vitro. To test the role of these phosphorylation sites, we carried out in vivo tumorigenesis studies in severe combined immunodeficient mice. The findings show that the p14-Ser65Ala mutation is associated with impaired tumorigenicity, whereas the p14-Ser18Ala mutation is associated with enhanced tumorigenicity. Microarray analysis suggests that phosphorylation at serine 18 or at serine 65 is associated with transcriptional regulation of the L5 nucleolar ribosomal protein (a p14 target) and the Erb-B signal transduction pathway. Taken together, these results show that the phosphorylation status of p14 determines whether it functions as a pro-oncogenic or antioncogenic modulator. Mol Cancer Res; 10(8); 1077–86. ©2012 AACR.

XLS file - 23K, 142 genes which are transcriptionally regulated (up, down) by the PKC- vs CK2- mutant p14s

PDF file - 69K, Supplemental Table 1 Primers used to construct plasmids expressing point mutations in the p14 sequence Supplemental Table 2 Primers used to construct plasmids expressing deletions in the p14 sequence

An incomplete science begets imperfect models. Nevertheless, the target article advocates for jettisoning deep learning models with some competency in object recognition for toy models evaluated against a checklist of laboratory findings; an approach which evokes Alan Newell's 20 questions critique. We believe their approach risks incoherency and neglects the most basic test; can the model perform its intended task.

Contemporary models of categorization typically tend to sidestep the problem of how information is initially encoded during decision making. Instead, a focus of this work has been to investigate how, through selective attention, stimulus representations are "contorted" such that behaviorally relevant dimensions are accentuated (or "stretched"), and the representations of irrelevant dimensions are ignored (or "compressed"). In high-dimensional real-world environments, it is computationally infeasible to sample all available information, and human decision makers selectively sample information from sources expected to provide relevant information. To address these and other shortcomings, we develop an active sampling model, Sampling Emergent Attention (SEA), which sequentially and strategically samples information sources until the expected cost of information exceeds the expected benefit. The model specifies the interplay of two components, one involved in determining the expected utility of different information sources and the other in representing knowledge and beliefs about the environment. These two components interact such that knowledge of the world guides information sampling, and what is sampled updates knowledge. Like human decision makers, the model displays strategic sampling behavior, such as terminating information search when sufficient information has been sampled and adaptively adjusting the search path in response to previously sampled information. The model also shows human-like failure modes. For example, when information exploitation is prioritized over exploration, the bidirectional influences between information sampling and learning can lead to the development of beliefs that systematically differ from reality. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Replay can consolidate memories through offline neural reactivation related to past experiences. Category knowledge is learned across multiple experiences, and its subsequent generalization is promoted by consolidation and replay during rest and sleep. However, aspects of replay are difficult to determine from neuroimaging studies. We provided insights into category knowledge replay by simulating these processes in a neural network which approximated the roles of the human ventral visual stream and hippocampus. Generative replay, akin to imagining new category instances, facilitated generalization to new experiences. Consolidation-related replay may therefore help to prepare us for the future as much as remember the past. Generative replay was more effective in later network layers functionally similar to the lateral occipital cortex than layers corresponding to early visual cortex, drawing a distinction between neural replay and its relevance to consolidation. Category replay was most beneficial for newly acquired knowledge, suggesting replay helps us adapt to changes in our environment. Finally, we present a novel mechanism for the observation that the brain selectively consolidates weaker information, namely a reinforcement learning process in which categories were replayed according to their contribution to network performance. This reinforces the idea of consolidation-related replay as an active rather than passive process.

Background The US is experiencing an opioid crisis, substantially worsened by the pandemic. Pharmacists play a critical role in expanding access to care through harm reduction efforts and medications to treat opioid use disorder (mOUD), yet lack necessary education and resources. Academic detailing is a one-on-one technique, which can effectively address educational gaps. Objective The purpose was to assess needs and equip pharmacy staff to address the health of people with substance use disorders (SUD). Practice description Community pharmacists provide ongoing care for patients with SUD. Practice innovation Based on needs’ assessment findings, an academic detailing program was designed to provide education and resources for community pharmacies. The project sought to assess current practice and needs and address pharmacists' skills in managing patients with opioid use disorder (OUD) and/or at risk for overdose (OD). Visits were scheduled in high-risk regions. Coaching and materials were provided. Evaluation methods Detailers completed visits reports. Discrete variables were reported using descriptive statistics. Associations between discrete variables were detected with Chi-square or Fisher’s exact test. Results Detailers visited 136 pharmacies. Most stocked naloxone (86.8%), mOUD (94.9%) and would sell syringes (64%) per state law. Fifty-seven percent of pharmacies provided all of these services. However, additional education and resources were needed. Only 27.9% had naloxone signage and/or handouts; 22.1% had supplemental materials; and 25% had referral information. When asked to explain barriers, frequently cited themes included providing resources/help, financial issues, stigma, and transportation. Conclusion Pharmacists routinely care for patients at risk for OD and diagnosed with OUD. Academic detailing is a well-received strategy to disseminate education and materials, while gathering information about pharmacist needs and barriers. However, there remains room for expansion of services and opportunities for improved care. Further efforts should incorporate ongoing training and access to materials with visual cues, as well as referral and cost savings information.

Complex behavior is supported by the coordination of multiple brain regions. We propose coordination is achieved by a controller-peripheral architecture in which peripherals (e.g., the ventral visual stream) aim to supply needed inputs to their controllers (e.g., the hippocampus and prefrontal cortex) while expending minimal resources. We developed a formal model within this frame-work to address how multiple brain regions coordinate to support rapid learning from a few example images. The model captured how higher-level activity in the controller shaped lower-level visual representations, affecting their precision and sparsity in a manner that paralleled brain measures. Alternative models optimized by gradient descent irrespective of architectural constraints could not account for human behavior or brain responses, and, typical of standard deep learning approaches, were unstable trial-by-trial learners.

Whether supervised or unsupervised, human and machine learning is usually characterised as event-based. However, learning may also proceed by systems alignment in which mappings are inferred between systems, such as visual and linguistic systems. Systems alignment is possible because items that share similar visual contexts, such as a car and a truck, will also tend to share similar linguistic contexts. Because of the mirrored similarity relationships, the visual and linguistic systems and can be aligned at some later time absent either input. We considered whether children's early concepts are learned by systems alignment. We found that children's early concepts are close to optimal for inferring novel concepts through system alignment. Structurally, children's early concepts are distinguished by their dense semantic neighbourhoods. Artificial agents using these structural features were highly effective, including in domains that exclude children's early concepts. For children, system alignment and event-based learning appear complementary. Artificial systems can benefit from incorporating these developmental principles.

Regulation of mRNA degradation is critical for a diverse array of cellular processes and developmental cell fate decisions. Many methods for determining mRNA half-lives rely on transcriptional inhibition or metabolic labelling. Here, we use a non-invasive method for estimating half-lives for hundreds of mRNAs in the early Drosophila embryo. This approach uses the intronic and exonic reads from a total RNA-seq time series and Gaussian process regression to model the dynamics of premature and mature mRNAs. We show how regulation of mRNA stability is used to establish a range of mature mRNA dynamics during embryogenesis, despite shared transcription profiles. Using single-molecule imaging, we provide evidence that, for the mRNAs tested, there is a correlation between short half-life and mRNA association with P-bodies. Moreover, we detect an enrichment of mRNA 3′ ends in P-bodies in the early embryo, consistent with 5′ to 3′ degradation occurring in P-bodies for at least a subset of mRNAs. We discuss our findings in relation to recently published data suggesting that the primary function of P-bodies in other biological contexts is mRNA storage.

How can words shape meaning? Shared labels highlight commonalities between concepts whereas contrasting labels make differences apparent. To address such findings, we propose a deep learning accoun...

Climate change, overfishing, and other anthropogenic drivers are forcing marine resource users and decision makers to adapt—often rapidly. In this article we introduce the concept of pathways to rapid adaptation to crisis events to bring attention to the double-edged role that institutions play in simultaneously enabling and constraining swift responses to emerging crises. To develop this concept, we draw on empirical evidence from a case study of the iconic Maine lobster (Homarus americanus) industry. In the Gulf of Maine, the availability of Atlantic herring (Clupea harengus) stock, a key source of bait in the Maine lobster industry, declined sharply. We investigate the patterns of bait use in the fishery over an 18-year period (2002–2019) and how the lobster industry was able to abruptly adapt to the decline of locally-sourced herring in 2019 that came to be called the bait crisis. We found that adaptation strategies to the crisis were diverse, largely uncoordinated, and imperfectly aligned, but ultimately led to a system-level shift towards a more diverse and globalized bait supply. This shift was enabled by existing institutions and hastened an evolution in the bait system that was already underway, as opposed to leading to system transformation. We suggest that further attention to raceways may be useful in understanding how and, in particular, why marine resource users and coastal communities adapt in particular ways in the face of shocks and crises. Supplementary Information The online version contains supplementary material available at 10.1007/s13280-021-01617-8.

Adults in the United States are increasingly following ‘popular’ diet patterns that restrict food groups, macronutrients, or eating time. However, the intake of food groups associated with these diet patterns has not been well characterized. The objectives of this study were to (1) characterize the mean intake of food groups among consumers of popular diet patterns in the US, and (2) model the effect of targeted food substitutions on the intake of food groups. Data were acquired from the National Health and Nutrition Examination Survey, 2005–2018 (n = 34,411). A diet model was developed to assess the effects of replacing one serving each of foods highest in added sugar, sodium, saturated fat, and refined grains with healthy alternatives on the intake of key food groups for each diet pattern. Modeled replacement resulted in increased intake of fruit and whole grains and decreased intake of dairy for most diet patterns, while the effects on the intake of vegetables, protein foods, and oils were variable across diet patterns. The complexity of the natural eating environment, in which many people consume mixed dishes that include both healthy and less healthy ingredients, produces a challenge for health professionals when providing dietary counseling. Nevertheless, this substitution approach may help improve adherence to dietary guidelines, especially if used as a steppingstone for further dietary improvement.

The innate immune system is critical for host survival of infection. Infection models in organisms like Drosophila melanogaster are key for understanding evolution and dynamics of innate immunity. However, current toolsets for fly infection studies are limited in their throughput and their ability to generate longitudinal measurements of infection progression in single animals. Here we report a novel bioluminescent imaging strategy enabling non-invasive characterization of pathogen load over time. We demonstrate that photon flux from autobioluminescent reporter bacteria can be used to monitor relative pathogen loads in individual animals. Escherichia coli expressing the ilux operon were imaged in whole, living flies at relevant concentrations for immune study. Because animal sacrifice was not necessary to estimate pathogen load, stochastic responses to infection were characterized in individuals over time for the first time. The high temporal resolution of bioluminescence imaging also enabled visualization of the fine dynamics of microbial clearance on the hours time-scale. Overall, this non-invasive imaging strategy provides a simple and scalable platform to observe changes in pathogen load in vivo over time.

Given the pervasiveness of gene sharing in evolution and the extent of homology across the tree of life, why is everything not homologous with everything else? The continuity and overlapping genetic contributions to diverse traits across lineages seem to imply that no discrete determination of homology is possible. Although some argue that the widespread overlap in parts and processes should be acknowledged as "partial" homology, this threatens a broad base of presumed comparative morphological knowledge accepted by most biologists. Following a long scientific tradition, we advocate a strategy of "theoretical articulation" that introduces further distinctions to existing concepts to produce increased contrastive resolution among the labels used to represent biological phenomena. We pursue this strategy by drawing on successful patterns of reasoning from serial homology at the level of gene sequences to generate an enriched characterization of serial homology as a hierarchical, phylogenetic concept. Specifically, we propose that the concept of serial homology should be applied primarily to repeated but developmentally individualized body parts, such as cell types, differentiated body segments, or epidermal appendages. For these characters, a phylogenetic history can be reconstructed, similar to families of paralogous genes, endowing the notion of serial homology with a hierarchical, phylogenetic interpretation. On this basis, we propose a five-fold theoretical classification that permits a more fine-grained mapping of diverse trait-types. This facilitates answering the question of why everything is not homologous with everything else, as well as how novelty is possible given that any new character possesses evolutionary precursors. We illustrate the fecundity of our account by reference to debates over insect wing serial homologs and vertebrate paired appendages.

The current study determined the effect of the egg-yolk (phospholipid source) level (egg yolk [20% EY] vs. skim-milk + egg yolk [SM + 2% EY]), cryoprotectant (glycerol [Gly] vs. glycerol + methylformamide [Gly + MF]), and pre-freeze cooling rate (-0.1 vs. -1 vs. -5 °C/min) on post-thaw stallion sperm quality. In Experiment 1, ejaculates (n = 27) from 9 stallions (3 ejaculates each) with varied sperm quality (High, Average, or Low) were frozen in EY-Gly, SMEY-Gly, EY-Gly + MF, or SMEY-Gly + MF extenders. Sperm in each group were cooled from 22° to 5°C using either -0.1 °C/min or -1 °C/min linear cooling rates prior to freezing. In Experiment 2, ejaculates (n = 24) from 12 stallions (2 ejaculates each) with High or Average sperm quality were frozen in EY-Gly, EY-Gly + MF, or in BotuCrio (BC) extenders. Sperm in each group were cooled from 22° to 5°C using either -1 or -5 °C/min linear cooling rates prior to freezing. In Experiment 1, for stallions with High or Average sperm quality, either cooling rate generally resulted in lower sperm quality for the SMEY-based extenders than for the EY-based extenders (P 0.05). Stallions with Low sperm quality were unaffected by any experimental treatment (P 0.05). In Experiment 2, a -5 °C/min cooling rate yielded lower sperm quality in BC than in EY-Gly or EY-Gly + MF groups (P 0.05); however, a -1 °C/min cooling rate yielded similar sperm quality among these treatments (P 0.05). In summary, the phospholipid level in the freezing extender and the pre-freeze cooling rate, but not the penetrating cryoprotectant, affected the post-thaw quality of stallion sperm.

While a large number of studies have investigated seafood consumption in various markets, surprisingly little is known about the types of seafood sold in retail outlets or their product forms in th...

Diet sustainability analyses inform policymaking decisions and provide clinicians and consumers with evidence-based information to make dietary changes. In the United States, the Food Commodity Intake Database (FCID) provides a crosswalk for integrating nationally representative data on food intake from the National Health and Nutrition Examination Survey (NHANES) with data on sustainability outcomes from other publicly available databases. However, FCID has not been updated since 2010 and does not link with contemporary NHANES data, which limits further advancements in sustainability research. This study fills this research gap by establishing novel linkages between FCID and NHANES 2011–2018, comparing daily per capita food intake with and without these linkages, and making these data publicly available for use by other researchers. To update FCID, two investigators independently established novel data linkages, a third investigator resolved discrepancies, and a fourth investigator audited linkages for accuracy. Dietary data were acquired from nearly 45,000 adults from 2001 to 2018, and food intake was compared between updated vs. non-updated FCID versions. Total food intake from 2011 to 2018 was 5–23% higher using the updated FCID compared to the non-updated version, and intake was over 100% higher in some years for some food categories including poultry, eggs, legumes, starchy vegetables, and tropical oils (P < 0.001 for all comparisons). Further efforts may be needed to create new food composition data to reflect new products and reformulations that enter the food supply over time. This study removes a barrier to further diet sustainability analyses by establishing a data crosswalk between contemporary NHANES and other publicly available databases on agricultural resource use, environmental impacts, and consumer food expenditures.

This paper describes a centrifuge study undertaken to investigate how sand gradation affects the system-level performance of embankments subjected to strong shaking. Current analysis and design practices are primarily based on knowledge from case history records of liquefaction, with the majority of those from sites consisting of clean, poorly graded sands. The narrow range of gradation characteristics represented in the case history database poses a challenge during the analysis of embankment structures traditionally constructed with, or founded on, more broadly graded soils. The tests herein were designed to elucidate how embankments uniformly constructed with a well graded and poorly graded sand perform differently during earthquake shaking. A centrifuge experiment test program was developed and conducted using the 9-m-radius centrifuge at the UC Davis Center for Geotechnical Modeling. The experiment design consisted of two submerged 10-degree embankments positioned side-by-side in the same rigid model container, with one embankment constructed with poorly graded sand and the other with well graded sand. The embankments were dry pluviated to the same relative density, but the absolute densities of the sands were different. The embankments were identically instrumented with dense arrays of in-situ sensors beneath the level ground above the slope and in the mid-slope to measure the dynamic response during liquefaction. Results showed that embankments constructed at equal relative densities would both liquefy (i.e., ru reach 1.0), but deformations were less severe for the embankments constructed with the well graded sand. Greater resistance to the generation and faster dissipation of excess porewater pressures, coupled with stronger dilatancy of the well graded sand increased embankment stability, curtailing liquefaction-induced deformations.

Purpose To define the effect of sperm agglutination, associated with incubation under capacitating conditions, on accuracy of membrane assessment via flow cytometry and to develop methods to mitigate that effect. Methods Sperm motility was measured by CASA. Sperm were stained with PI-PSA or a novel method, LD-PSA, using fixable live/dead stain and cell dissociation treatment, before flow-cytometric analysis. Using LD-PSA, acrosome reaction and plasma membrane status were determined in equine sperm treated with 10 μm A23187 for 10 min, followed by 0, 1, or 2 h incubation in capacitating conditions. Results Using PI-PSA, measured membrane integrity (MI; live sperm) was dramatically lower than was total motility (TMOT), indicating spurious results (“zombie sperm”). Sperm aggregates were largely of motile sperm. Loss of motility after A23187 treatment was associated with disaggregation and increased MI. On disaggregation using LD-PSA, MI rose, and MI then corresponded with TMOT. In equine sperm incubated after A23187 treatment, as the percentage of live acrosome-reacted sperm increased, TMOT decreased to near 0. Conclusion Flow cytometry assesses only individualized sperm; thus, agglutination of viable sperm alters recorded membrane integrity. As viable sperm become immotile, they individualize; therefore, factors that decrease motility, such as A23187, result in increased measured MI. Disaggregation before assessment allows more accurate determination of sperm membrane status; in this case we documented a mismatch between motility and live acrosome-reacted equine sperm that may relate to the poor repeatability of A23187 treatment for equine IVF. These findings are of profound value to future studies on sperm capacitation.

Transmission of livestock-associated Staphylococcus aureus clonal complex 9 (LA-SA CC9) between pigs raised on industrial hog operations (IHOs) and humans in the United States is poorly understood. We analyzed whole-genome sequences from 32 international S. aureus CC9 isolates and 49 LA-SA CC9 isolates from IHO pigs and humans who work on or live near IHOs in 10 pig-producing counties in North Carolina, USA. Bioinformatic analysis of sequence data from the 81 isolates demonstrated 3 major LA-SA CC9 clades. North Carolina isolates all fell within a single clade (C3). High-resolution phylogenetic analysis of C3 revealed 2 subclades of intermingled IHO pig and human isolates differing by 0–34 single-nucleotide polymorphisms. Our findings suggest that LA-SA CC9 from pigs and humans share a common source and provide evidence of transmission of antimicrobial-resistant LA-SA CC9 between IHO pigs and humans who work on or live near IHOs in North Carolina.

Under in vitro conditions, stallion sperm might preferentially use energy substrates that primarily undergo mitochondrial metabolism. The present study sought to determine the effects of glucose, pyruvate, lactate, or their combinations on the quality of stallion sperm subjected to cooled storage at different temperatures, when using a skim milk-based semen extender. In Experiment 1, no substrate (Control), glucose (40 mM; Glu-40), pyruvate (2 mM, 19.8 mM; Pyr-2, Pyr-19), lactate (2 mM, 19.8 mM; Lac-2, Lac-19, respectively), or their combinations (G/P/L-2 or G/P/L-19, respectively) were added to a milk-based extender and their effects were determined on motion characteristics, viability/acrosomal intactness (VAI), lipid peroxidation status (VLPP), and DNA integrity (COMPα-t) of sperm incubated for 1 h at 37 °C, or sperm stored for 24 h at either 10 or 20 °C. At any period and temperature tested, Glu-40, G/P/L-2, and G/P-L-19 resulted in similar motion characteristics (P > 0.05) but were higher than that of other treatment groups (P

Philosophical discussions of information and specificity in biology are now commonplace, but no consensus exists about whether the privileging of genetic causation in investigation and explanation is justified. However, little effort has been expended on understanding practices when scientists experimentally measure information or causal specificity. An example of this type of practice—measuring positional information in gene expression during pattern formation in embryogenesis—shows that biologists are unconcerned with comparing the amount of information in genes with that of other factors. Instead, they focus on whether the measured causal specificity explains the phenomenon under scrutiny.

Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Medtronic Background An absorbable antibacterial envelope (TYRX), which stabilizes cardiac implantable electronic devices (CIEDs) was shown to significantly reduce infections in a large randomized controlled trial (WRAP-IT). A 3rd generation envelope (T3) is being developed to improve the implanter experience and enable smoother device insertion with a redesigned, multifilament mesh, an enhanced form factor, and identical polymer coating and antibiotic concentrations as the currently available 2nd generation envelope (T2). Purpose To compare drug elution profiles of T3 vs T2 and evaluate the efficacy of T3 against bacteria commonly known to be associated with CIED infections. Methods The T3 drug elution profile was assessed in vitro by evaluating the amount of each drug, minocycline and rifampin, released at a given timepoint using an accelerated dissolution method. For comparative analysis with T2, elution curve equivalency was based on similarity factor values (f2) of ≥50 per FDA guidance. An in vivo elution study was also conducted (per the Principles of Laboratory Animal Care [NIH Publication no. 85-23 revised 1985]) to ensure drug concentrations met the minimal inhibitory concentration (MIC) through 7 days. Substantial equivalence was defined as rifampin and minocycline concentrations above MIC at 2hr post-implant and sustained through 7 days. In a further animal model, 12 pockets were created in 6 rabbits, for CIED insertion with and without T3 envelopes, to evaluate efficacy against gram+ and gram- bacteria. At day 7, implant sites were evaluated for signs of infection via macroscopic observations and microbial recovery procedures. A Fisher’s Exact Test was used for comparisons. Results The T3 envelope showed a similar elution profile to T2 in vitro (Figure) with f2 >50 (range 76-84). In the in vivo assessment, the T3 envelope eluted both antibiotics above the MIC at 2hr post-implant with sustained elution through 7 days, consistent with historical T2 performance. Further bacterial challenge studies in vivo showed a statistically significant reduction (p Conclusion The 3rd generation absorbable antibacterial envelope demonstrated equivalent pre-clinical performance compared to the 2nd generation envelope as antibiotic elution curves were equivalent, elution was sustained at concentrations above MIC for 7 days, and infection rates were significantly reduced compared to no envelope. These results suggest equivalent clinical performance could be expected with the newly designed envelope.

Fluorogenic bioorthogonal reactions enable biomolecule visualization in real time. These reactions comprise reporters that “light up” upon reaction with complementary partners. While the spectrum of fluorogenic chemistries is expanding, few transformations are compatible with live cells due to cross-reactivities or insufficient signal turn-on. To address the need for more suitable transformations for cellular imaging, we developed a fluorogenic reaction featuring cyclopropenone reporters and phosphines. The transformation involves regioselective activation and cyclization of cyclopropenones to form coumarin products. With optimal probes, the reaction provides >1,600-fold signal turn-on, one of the highest fluorescence enhancements reported to date. The bioorthogonal motifs were evaluated in vitro and in cells. The reaction was also found to be compatible with other common fluorogenic transformations, enabling multi-component imaging. Two cellular targets were visualized simultaneously, a first for fluorogenic bioorthogonal chemistries. Collectively, these data suggest that the cyclopropenone-phosphine reaction will bolster efforts to track biomolecule targets in their native settings

The innate immune system is critical for infection survival.

Optimum management of hip displacement in children with cerebral palsy (CP) is facilitated by an approach that focuses on anticipatory and preventive measures. Hip surveillance programs for children with CP were developed at the beginning of the new millennium, with the purpose of identifying hip displacement sufficiently early to permit a choice of effective management options. In the early years, hip surveillance was guided by epidemiological analysis of population-based studies of prevalence. In Australia, a National Hip Surveillance in CP Working Group was first convened in 2005. This resulted in a 2008 Consensus Statement of recommendations published and endorsed by Australasian Academy of Cerebral Palsy and Developmental Medicine (AusACPDM). The group undertook that the recommendations should be reviewed every 5 years to ensure currency and congruency with the emerging evidence base. As new evidence became available, hip surveillance guidelines developed, with the most recent 2020 Australian Hip Surveillance Guidelines endorsed by the AusACPDM. Implementing comprehensive hip surveillance programs has now been shown to improve the natural history of hip dislocations and improve quality of life. Standardised hip surveillance programs can also facilitate planning for multicentre research through harmonisation of data collection. This, in turn, can help with the identification of robust new evidence that is based on large cohort or population studies. Here a review of evidence informing the updated 2020 Hip Surveillance Guidelines is presented.

Regulation of mRNA degradation is critical for a diverse array of cellular processes and developmental cell fate decisions. Many methods for determining mRNA half-lives rely on transcriptional inhibition or metabolic labelling. Here we use a non-invasive method for estimating half-lives for hundreds of mRNAs in the early Drosophila embryo. This approach uses the intronic and exonic reads from a total RNA-seq time series and Gaussian process regression to model the dynamics of premature and mature mRNAs. We show how regulation of mRNA stability is used to establish a range of mature mRNA dynamics during embryogenesis, despite shared transcription profiles. Using single molecule imaging we provide evidence that, for the mRNAs tested, there is a correlation between short half-life and mRNA association with P-bodies. Moreover, we detect an enrichment of mRNA 3’ ends in P-bodies in the early embryo, consistent with 5’ to 3’ degradation occurring in P-bodies for at least a subset of mRNAs. We discuss our findings in relation to recently published data suggesting that the primary function of P-bodies in other biological contexts is mRNA storage.