Multiplex, multimodal mapping of variant effects in secreted proteins.

Despite widespread advances in DNA sequencing, the functional consequences of most genetic variants remain poorly understood. Multiplexed Assays of Variant Effect (MAVEs) can measure the function of variants at scale, and are beginning to address this problem. However, MAVEs cannot readily be applied to the ~10% of human genes encoding secreted proteins.

Beyond reductionism: Understanding motivational energization requires higher-order constructs.

We argue that the target article's computational/reductionistic approach to motivation is insufficient to explain the energization of human behavior, because such explanation requires broad consideration of "what people are trying to do." We illustrate what is gained by retaining (rather than jettisoning) higher-order motivation constructs and show that the authors' approach assumes, but fails to name, such constructs.

Physiologically Based Pharmacokinetic Modeling and Simulation to Support a Change in the FDA-Labeled Dosing Frequency of RHB-105 Low-Dose Rifabutin Triple Therapy for Helicobacter pylori Eradication.

Patient adherence is vital for Helicobacter pylori eradication. Simplifying therapy dosing schedules may promote patient adherence, enhance treatment success rates, and help mitigate the development of antibiotic resistance. We aimed to assess plasma and intragastric rifabutin, amoxicillin, and omeprazole concentrations comparing two dosing schedules of RHB-105 (every 8 h and a more flexible three-times daily schedule, at 8 a.

Making Community-Based Palliative Care Eligibility Determinations: Palliative Care Team Member Perspectives on Access to Information and Algorithm Use.

Background: Seriously ill older adults have high risk of mortality, symptom burden, and compromised functional status, and may benefit from community-based palliative care ("palliative care"). However, identifying potentially eligible individuals is challenging.

Objectives: Identify how a palliative care team makes eligibility determinations, including the use of a mortality risk algorithm.

Quantitative patterns of visual impairment and recovery in children with brain injury.

Brain injury can cause many distinct types of visual impairment in children, but these deficits are difficult to quantify due to co-morbid deficits in communication and cognition. Clinicians must instead rely on low-resolution, subjective judgements of simple reactions to handheld stimuli, which limits treatment potential. We have developed an interactive assessment program called the Visual Ladder, which uses gaze-based responses to intuitive, game-like tasks to address the lack of broad-spectrum quantified data on the visual abilities of children with brain injury.

The free will capacity: A uniquely human adaption.

Herein, I characterize free will (FW) is an evolved functional capacity within the mature human mind, which provides us with numerous adaptive benefits. The FW capacity was selected for because it enables us to respond effectively to momentary contingencies, via on-the-spot deliberation. But FW also extricates us from the present moment, enabling us to generate and decide between imagined long-term futures.

Diurnal temperature variation impacts energetics but not reproductive effort across seasons in a temperate dung beetle.

Temperature varies on multiple timescales and ectotherms must adjust to these changes to survive. These adjustments may lead to energetic trade-offs between self-maintenance and reproductive investment. However, we know little about how diurnal and seasonal temperature changes impact energy allocation.

Paenibacillus spp infection among infants with postinfectious hydrocephalus in Uganda: an observational case-control study.

Background: Paenibacillus thiaminolyticus is a cause of postinfectious hydrocephalus among Ugandan infants. To determine whether Paenibacillus spp is a pathogen in neonatal sepsis, meningitis, and postinfectious hydrocephalus, we aimed to complete three separate studies of Ugandan infants. The first study was on peripartum prevalence of Paenibacillus in mother-newborn pairs.

Neonatal Paenibacilliosis: Paenibacillus Infection as a Novel Cause of Sepsis in Term Neonates With High Risk of Sequelae in Uganda.

Background: Paenibacillus thiaminolyticus may be an underdiagnosed cause of neonatal sepsis.

Methods: We prospectively enrolled a cohort of 800 full-term neonates presenting with a clinical diagnosis of sepsis at 2 Ugandan hospitals. Quantitative polymerase chain reaction specific to P.

Physiologically-based pharmacokinetic modelling to predict intragastric rifabutin concentrations in the treatment of Helicobacter pylori infection.

Background: Sustained intragastric antibiotic exposure is important for Helicobacter pylori eradication, yet little is known about gastric pharmacology of commonly used H. pylori regimens. For rifabutin, differing intragastric concentrations based on dosing regimen may account for differences in reported eradication rates.

A trait-based framework for dung beetle functional ecology.

Traits are key for understanding the environmental responses and ecological roles of organisms. Trait approaches to functional ecology are well established for plants, whereas consistent frameworks for animal groups are less developed. Here we suggest a framework for the study of the functional ecology of animals from a trait-based response-effect approach, using dung beetles as model system.

Experimental increases in temperature mean and variance alter reproductive behaviours in the dung beetle .

Temperature profoundly impacts insect development, but plasticity of reproductive behaviours may mediate the impacts of temperature change on earlier life stages. Few studies have examined the potential for adult behavioural plasticity to buffer offspring from the warmer, more variable temperatures associated with climate change. We used a field manipulation to examine whether the dung beetle alters breeding behaviours in response to temperature changes and whether behavioural shifts protect offspring from temperature changes.

The relative influence of history, climate, topography and vegetation structure on local animal richness varies among taxa and spatial grains.

Understanding the spatial scales at which environmental factors drive species richness patterns is a major challenge in ecology. Due to the trade-off between spatial grain and extent, studies tend to focus on a single spatial scale, and the effects of multiple environmental variables operating across spatial scales on the pattern of local species richness have rarely been investigated. Here, we related variation in local species richness of ground beetles, landbirds and small mammals to variation in vegetation structure and topography, regional climate, biome diversity and glaciation history for 27 sites across the USA at two different spatial grains.

Cytomegalovirus infections in infants in Uganda: Newborn-mother pairs, neonates with sepsis, and infants with hydrocephalus.

Objectives: To estimate the prevalence of cytomegalovirus (CMV) infections among newborn-mother pairs, neonates with sepsis, and infants with hydrocephalus in Uganda.

Design And Methods: Three populations-newborn-mother pairs, neonates with sepsis, and infants (≤3 months) with nonpostinfectious (NPIH) or postinfectious (PIH) hydrocephalus-were evaluated for CMV infection at 3 medical centers in Uganda. Quantitative PCR (qPCR) was used to characterize the prevalence of CMV.

Pitfalls of Physician-Directed Treatment of Helicobacter pylori: Results from Two Phase 3 Clinical Trials and Real-World Prescribing Data.

Background: Helicobacter pylori (H. pylori) infects ~ 35% of Americans and can lead to serious sequelae if left untreated. Growing evidence indicates that clarithromycin-based therapies (CBT) are becoming increasingly ineffective for treating H.

Vaginal microbiome topic modeling of laboring Ugandan women with and without fever.

The composition of the maternal vaginal microbiome influences the duration of pregnancy, onset of labor, and even neonatal outcomes. Maternal microbiome research in sub-Saharan Africa has focused on non-pregnant and postpartum composition of the vaginal microbiome. Here we aimed to illustrate the relationship between the vaginal microbiome of 99 laboring Ugandan women and intrapartum fever using routine microbiology and 16S ribosomal RNA gene sequencing from two hypervariable regions (V1-V2 and V3-V4).

The complete mitochondrial genome of the strawberry aphid Cockerell, 1901 (Hemiptera: Aphididae) from California, USA.

The aphid Cockerell, 1901 is an agricultural pest and known vector of strawberry viruses. To better understand its biology and systematics, we performed a genomic analysis on collected from Quinalt strawberry plants from Pacific Grove, Monterey county, California, USA using Oxford Nanopore and Illumina sequencing. The resulting data were used to assemble the aphids complete mitogenome.

The Glow Still Shows: Effects of Facial Masking on Perceptions of Duchenne Versus Social Smiles.

Facial expressions of emotion have important communicative functions. It is likely that mask-wearing during pandemics disrupts these functions, especially for expressions defined by activity in the lower half of the face. We tested this by asking participants to rate both Duchenne smiles (DSs; defined by the mouth and eyes) and non-Duchenne or "social" smiles (SSs; defined by the mouth alone), within masked and unmasked target faces.

Dung beetles show metabolic plasticity as pupae and smaller adult body size in response to increased temperature mean and variance.

Though organisms may use thermal plasticity to cope with novel temperature regimes, our understanding of plastic responses is limited. Research on thermal plasticity has traditionally focused on the response of organisms to shifts in mean temperatures. However, increased temperature variation can have a greater impact on organismal performance than mean temperature alone.

Duchenne Smiles as Honest Signals of Chronic Positive Mood.

Chronic positive mood (CPM) has been shown to confer a wide variety of social, functional, and health benefits. Some researchers have argued that humans evolved to feel CPM, which explains why most people report better than neutral mood (the "positivity offset bias") and why particularly happy people have particularly good outcomes. Here, we argue that the Duchenne smile evolved as an honest signal of high levels of CPM, alerting others to the psychological fitness of the smiler.

Global progress in incorporating climate adaptation into land protection for biodiversity since Aichi targets.

Climate adaptation strategies are being developed and implemented to protect biodiversity from the impacts of climate change. A well-established strategy involves the identification and addition of new areas for conservation, and most countries agreed in 2010 to expand the global protected area (PA) network to 17% by 2020 (Aichi Biodiversity Target 11). Although great efforts to expand the global PA network have been made, the potential of newly established PAs to conserve biodiversity under future climate change remains unclear at the global scale.

Autoantigen presentation by splenic dendritic cells is required for RBC-specific autoimmunity.

Background: Failure of humoral tolerance to red blood cell (RBC) antigens may lead to autoimmune hemolytic anemia (AIHA), a severe and sometimes fatal disease. Previous studies have shown that although tolerance is robust in HOD mice, autoantibodies are generated upon adoptive transfer of OTII CD4 T cells, which are specific for an epitope contained within the HOD antigen. These data imply that antigen-presenting cells (APCs) are presenting RBC-derived autoantigen(s) and are capable of driving T-cell activation.

Different amplitudes of temperature fluctuation induce distinct transcriptomic and metabolomic responses in the dung beetle .

Most studies exploring molecular and physiological responses to temperature have focused on constant temperature treatments. To gain a better understanding of the impact of fluctuating temperatures, we investigated the effects of increased temperature variation on dung beetles across levels of biological organization. Specifically, we hypothesized that increased temperature variation is energetically demanding.