Alternative models of funding curiosity-driven research.

Funding of curiosity-driven science is the lifeblood of scientific and technological innovation. Various models of funding allocation became institutionalized in the 20th century, shaping the present landscape of research funding. There are numerous reasons for scientists to be dissatisfied with current funding schemes, including the imbalance between funding for curiosity-driven and mission-directed research, regional and country disparities, path-dependency of who gets funded, gender and race disparities, low inter-reviewer reliability, and the trade-off between the effort and time spent on writing or reviewing proposals and doing research.

Automating the practice of science: Opportunities, challenges, and implications.

Automation transformed various aspects of our human civilization, revolutionizing industries and streamlining processes. In the domain of scientific inquiry, automated approaches emerged as powerful tools, holding promise for accelerating discovery, enhancing reproducibility, and overcoming the traditional impediments to scientific progress. This article evaluates the scope of automation within scientific practice and assesses recent approaches.

The present and future of peer review: Ideas, interventions, and evidence.

What is wrong with the peer review system? Is peer review sustainable? Useful? What other models exist? These are central yet contentious questions in today's academic discourse. This perspective critically discusses alternative models and revisions to the peer review system. The authors highlight possible changes to the peer review system, with the goal of fostering further dialog among the main stakeholders, including producers and consumers of scientific research.

Is Ockham's razor losing its edge? New perspectives on the principle of model parsimony.

The preference for simple explanations, known as the parsimony principle, has long guided the development of scientific theories, hypotheses, and models. Yet recent years have seen a number of successes in employing highly complex models for scientific inquiry (e.g.

The misalignment of incentives in academic publishing and implications for journal reform.

For most researchers, academic publishing serves two goals that are often misaligned-knowledge dissemination and establishing scientific credentials. While both goals can encourage research with significant depth and scope, the latter can also pressure scholars to maximize publication metrics. Commercial publishing companies have capitalized on the centrality of publishing to the scientific enterprises of knowledge dissemination and academic recognition to extract large profits from academia by leveraging unpaid services from reviewers, creating financial barriers to research dissemination, and imposing substantial fees for open access.

How should the advancement of large language models affect the practice of science?

Large language models (LLMs) are being increasingly incorporated into scientific workflows. However, we have yet to fully grasp the implications of this integration. How should the advancement of large language models affect the practice of science? For this opinion piece, we have invited four diverse groups of scientists to reflect on this query, sharing their perspectives and engaging in debate.

PgpP is a broadly conserved phosphatase required for phosphatidylglycerol lipid synthesis.

The cytoplasmic membrane of bacteria is composed of a phospholipid bilayer made up of a diverse set of lipids. Phosphatidylglycerol (PG) is one of the principal constituents and its production is essential for growth in many bacteria. All the enzymes required for PG biogenesis in have been identified and characterized decades ago.

Intraspecific Variation and Recent Loss of Ancient, Conserved Effector Genes in the Sudden Oak Death Pathogen .

Members of the genus are responsible for many important diseases in agricultural and natural ecosystems. causes devastating diseases of oak, and tanoak stands in US forests and larch in the UK. The four evolutionary lineages involved express different virulence phenotypes on plant hosts, and characterization of gene content is foundational to understanding the basis for these differences.

Predicting real-world navigation performance from a virtual navigation task in older adults.

Virtual reality environments presented on tablets and smartphones offer a novel way of measuring navigation skill and predicting real-world navigation problems. The extent to which such virtual tests are effective at predicting navigation in older populations remains unclear. We compared the performance of 20 older participants (54-74 years old) in wayfinding tasks in a real-world environment in London, UK, and in similar tasks designed in a mobile app-based test of navigation (Sea Hero Quest).

Alternative approaches for monitoring and evaluation of lymphatic filariasis following mass drug treatment with ivermectin, diethylcarbamazine and albendazole in East New Britain Province, Papua New Guinea.

Background: WHO recommends two annual rounds of mass drug administration (MDA) with ivermectin, diethylcarbamazine, and albendazole (IDA) for lymphatic filariasis (LF) elimination in treatment naïve areas that are not co-endemic for onchocerciasis such as Papua New Guinea (PNG). Whether two rounds of MDA are necessary or sufficient and the optimal sampling strategies and endpoints for stopping MDA remain undefined.

Methods And Findings: Two cross-sectional studies were conducted at baseline (N = 49 clusters or villages) and 12 months after mass drug administration (MDA) with IDA (N = 47 villages) to assess lymphatic filariasis (LF) by circulating filarial antigenemia (CFA) and microfilariae (Mf).

Minimization of the Bacillus subtilis divisome suggests FtsZ and SepF can form an active Z-ring, and reveals the amino acid transporter BraB as a new cell division influencing factor.

Bacterial cytokinesis begins with polymerization of the tubulin homologue FtsZ into a ring-like structure at midcell, the Z-ring, which recruits the late cell division proteins that synthesize the division septum. Assembly of FtsZ is carefully regulated and supported by a dozen conserved cell division proteins. Generally, these proteins are not essential, but removing more than one is in many cases lethal.

Wild-type bone marrow cells repopulate tissue resident macrophages and reverse the impacts of homozygous CSF1R mutation.

Adaptation to existence outside the womb is a key event in the life of a mammal. The absence of macrophages in rats with a homozygous mutation in the colony-stimulating factor 1 receptor (Csf1r) gene (Csf1rko) severely compromises pre-weaning somatic growth and maturation of organ function. Transfer of wild-type bone marrow cells (BMT) at weaning rescues tissue macrophage populations permitting normal development and long-term survival.

Repression of CADM1 transcription by HPV type 18 is mediated by three-dimensional rearrangement of promoter-enhancer interactions.

Upon infection, human papillomavirus (HPV) manipulates host cell gene expression to create an environment that is supportive of a productive and persistent infection. The virus-induced changes to the host cell's transcriptome are thought to contribute to carcinogenesis. Here, we show by RNA-sequencing that oncogenic HPV18 episome replication in primary human foreskin keratinocytes (HFKs) drives host transcriptional changes that are consistent between multiple HFK donors.

Hatching of whipworm eggs induced by bacterial contact is serine-protease dependent.

Whipworms (Trichuris spp) are ubiquitous parasites of humans and domestic and wild mammals that cause chronic disease, considerably impacting human and animal health. Egg hatching is a critical phase in the whipworm life cycle that marks the initiation of infection, with newly hatched larvae rapidly migrating to and invading host intestinal epithelial cells. Hatching is triggered by the host microbiota; however, the physical and chemical interactions between bacteria and whipworm eggs, as well as the bacterial and larval responses that result in the disintegration of the polar plug and larval eclosion, are not completely understood.

Site-selective photo-crosslinking for the characterisation of transient ubiquitin-like protein-protein interactions.

Non-covalent protein-protein interactions are one of the most fundamental building blocks in cellular signalling pathways. Despite this, they have been historically hard to identify using conventional methods due to their often weak and transient nature. Using genetic code expansion and incorporation of commercially available unnatural amino acids, we have developed a highly accessible method whereby interactions between biotinylated ubiquitin-like protein (UBL) probes and their binding partners can be stabilised using ultraviolet (UV) light-induced crosslinks.

Comparison of behind-the-ear vs. off-the-ear speech processors in cochlear implants: A systematic review and narrative synthesis.

Background: Cochlear implants (CI) with off-the-ear (OTE) and behind-the-ear (BTE) speech processors differ in user experience and audiological performance, impacting speech perception, comfort, and satisfaction.

Objectives: This systematic review explores audiological outcomes (speech perception in quiet and noise) and non-audiological factors (device handling, comfort, cosmetics, overall satisfaction) of OTE and BTE speech processors in CI recipients.

Methods: We conducted a systematic review following PRISMA-S guidelines, examining Medline, Embase, Cochrane Library, Scopus, and ProQuest Dissertations and Theses.

Using machine learning to forecast peak health care service demand in real-time during the 2022-23 winter season: A pilot in England, UK.

During winter months, there is increased pressure on health care systems in temperature climates due to seasonal increases in respiratory illnesses. Providing real-time short-term forecasts of the demand for health care services helps managers plan their services. During the Winter of 2022-23 we piloted a new forecasting pipeline, using existing surveillance indicators which are sensitive to increases in respiratory syncytial virus (RSV).

"Energetics of the outer retina II: Calculation of a spatio-temporal energy budget in retinal pigment epithelium and photoreceptor cells based on quantification of cellular processes".

The outer retina (OR) is highly energy demanding. Impaired energy metabolism combined with high demands are expected to cause energy insufficiencies that make the OR susceptible to complex blinding diseases such as age-related macular degeneration (AMD). Here, anatomical, physiological and quantitative molecular data were used to calculate the ATP expenditure of the main energy-consuming processes in three cell types of the OR for the night and two different periods during the day.

The metabolite transporters of C4 photosynthesis.

C4 photosynthesis is a highly efficient form of photosynthesis that utilises a biochemical pump to concentrate CO2 around rubisco. Although variation in the implementation of this biochemical pump exists between species, each variant of the C4 pathway is critically dependent on metabolite transport between organelles and between cells. Here we review our understanding of metabolite transport in C4 photosynthesis.

Carbonyl Reductase 1: a novel regulator of blood pressure in Down Syndrome.

Approximately one in every 800 children is born with the severe aneuploid condition of Down Syndrome, a trisomy of chromosome 21. Low blood pressure (hypotension) is a common condition associated with DS and can have a significant impact on exercise tolerance and quality of life. Little is known about the factors driving this hypotensive phenotype and therefore therapeutic interventions are limited.

Characterisation of RNA guanine-7 methyltransferase (RNMT) using a small molecule approach.

The maturation of the RNA cap involving guanosine N-7 methylation, catalyzed by the HsRNMT (RNA guanine-7 methyltransferase)-RAM (RNA guanine-N7 methyltransferase activating subunit) complex, is currently under investigation as a novel strategy to combat PIK3CA mutant breast cancer. However, the development of effective drugs is hindered by a limited understanding of the enzyme's mechanism and a lack of small molecule inhibitors. Following the elucidation of the HsRNMT-RAM molecular mechanism, we report the biophysical characterization of two small molecule hits.

The design of a striking dummy and the theoretical foundations of martial arts strikes.

The aim of the research was to develop the design of a striking dummy and the theoretical foundations of martial arts strikes and to test its effectiveness in a pedagogical experiment. This paper presents the design of a striking dummy and the foundational theories behind martial arts strikes. We used modern microelectronics, including a diverse range of sensors, for executing a multitude of electromechanical measurements.