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    Disciplines / Research questions

    Biology

    98 research topics · 322 questions

    Occurrence and prevention of neuronal death in cerebral ischemia3 questions

    1. Unresolved translational core of the ischemic cascade: cell-death programs, peri-infarct depolarizations, inflammation, and white-matter injury in human ischemic stroke

    2. Selective neuronal loss and microglial activation in the salvaged human ischaemic penumbra: therapeutic significance after reperfusion

    3. Causal molecular determinants of ischemic brain tissue fate: selective neuronal necrosis, infarction, or recovery, and the basis of selective vulnerability and inflammatory causality

    Can vaccines treat chronic brain diseases?3 questions

    1. Combined Aβ/tau active vaccination for Alzheimer's disease: from brain-pathology reduction to cognitive benefit, balanced immunogenicity, and human translation

    2. Mechanism of protection and epitope-display design rules of prion peptide-displaying polyomavirus-like-particle vaccination in scrapie-infected mice

    3. Safety, durability, strain breadth, therapeutic window, and human translation of structure-based conformational-epitope vaccines targeting misfolded alpha-synuclein

    The mystery of bird migration and navigation3 questions

    1. How is migratory direction encoded and inherited such that bi-axial (axis-reversed) orientation arises in the Eurasian blackcap?

    2. Completing the mechanistic picture of avian magnetoreception: radical-pair receptor identity, visual-magnetic integration, neural convergence, and the origin of fixed-direction responses

    3. In vivo magnetoreceptor role and geomagnetic-field sensitivity mechanism of songbird cryptochrome 4

    Do birds have language?3 questions

    1. Songbird recursive pattern learning: is the starling context-free-grammar capacity real, how far does it extend, and what mechanisms implement it?

    2. Receiver-side validation of meaning and the intentional status of production in the combinatorial call sequences of Campbell's monkeys

    3. Open questions on compositional syntax in Japanese tit call sequences: internal semantics of the ABC unit, receiver parsing mechanisms, and taxonomic distribution

    Physiological basis and biological indicators of tolerance to artificial cabin environments2 questions

    1. Causal attribution and countermeasure efficacy for vascular deconditioning during long-duration confinement in closed life-support habitats

    2. From correlates to causes: validating the health significance of microbiome and metabolome shifts during long-term isolation confinement (Green Star 180 CELSS)

    Is human parthenogenesis possible?2 questions

    1. Mechanism of the prolonged second cell cycle in human haploid parthenotes and the epigenetic programs of cleavage-stage human uniparental embryos

    2. From one-pronuclear IVF oocytes to validated homozygous human parthenogenetic embryonic stem cells: origin, diploidization, imprinting stability, and therapeutic proof

    Mechanisms of human tolerance to extreme natural environments1 questions

    1. Causal mechanisms of Tibetan-enriched structural variants underlying high-altitude adaptation: validating the pangenome's SV–trait associations, the synapse-pathway enrichment, and the SLC6A3 intronic VNTR

    Do human pheromones exist?2 questions

    1. Chemical fingerprints and reception mechanisms of human emotional chemosignals: identifying the molecules that communicate fear and disgust, how they are detected, and when the communication operates

    2. Menstrual synchrony: fact or artifact — settling the existence, mechanism, and adaptive significance of cycle coordination among cohabiting women

    How is human sex determined?3 questions

    1. Ubiquitin-dependent turnover of SRY variants and quantitative input-output mapping of the human SRY-SOX9 sex-determination switch

    2. Mechanism and incomplete penetrance of upstream SOX9 enhancer duplication in SRY-negative 46,XX testicular development

    3. Mechanism of attenuated Sox9-enhancer occupancy by the inherited SRY variant p.Met64Val and the modulated threshold of human sex determination

    How do humans regulate their own emotions?2 questions

    1. The intentionality boundary of emotion regulation: does the reappraisal advantage for emotions over moods generalize beyond self-report?

    2. What does ventral-striatum activity during instructed up-regulation of positive emotion represent, and do laboratory neural markers of positive-emotion up-regulation generalize to emotion regulation and affect in daily life?

    Why does human immunodeficiency virus (HIV) infection lead to AIDS?3 questions

    1. In vivo contribution of the CARD8 inflammasome and parallel cell-death pathways to CD4+ T-cell depletion and chronic inflammation in pathogenic HIV/SIV infection

    2. Causal primacy of early IFNα avoidance in HIV elite control: low-inoculum initiation, cause-versus-consequence of controller immune features, and IFNα-lowering as therapy

    3. Causal role and mechanisms of microbial translocation in HIV-associated chronic immune activation

    How are microbial degradation pathways of synthetic compounds formed and evolved?3 questions

    1. How linuron catabolism assembles and disseminates in Variovorax: the IS1071 composite-transposon mechanism, transferability of novel catabolic plasmids, clade-1 predisposition, and the worldwide catabolic gene reservoir

    2. Functional completion and evolutionary reconstruction of the patchwork-assembled 2-chloronitrobenzene catabolism pathway in Pseudomonas stutzeri ZWLR2-1

    3. Redox control of bacterial evolvability: establishing the generality, mechanism, community consequences, and exploitable applications of NAD(P)H-dependent buffering of ROS-driven mutagenesis during novel-xenobiotic catabolism

    Is it possible to create artificial germ cells?3 questions

    1. Closing the developmental-competence gap of in vitro-generated oocytes: meiotic, epigenetic, and culture-condition fidelity in full in vitro oogenesis from pluripotent stem cells

    2. Functional role of the X-chromosome inactivation/reactivation cycle in female mouse germ cells: driver versus diagnostic mark of meiotic competence

    3. Molecular execution and functional requirement of the 3D genome reorganization at the transition to gametogenesis

    How can artificial cells be made?2 questions

    1. Integrating synthetic-cell compartment growth and division with genetic replication, autonomous fuel supply, and evolution: the open challenge to which self-reproducing inorganic colloidosomes pointed

    2. Genetically encoded inducible control of in vitro transcription–translation coupled DNA replication (TTcDR): breaking the ~4-fold induction limit toward coupling metabolic activity to replication

    How to promote peripheral nerve regeneration3 questions

    1. Causal scope and regulation of Schwann cell c-Jun in peripheral nerve repair: functional endpoints, the Sonic hedgehog loop, chronic-denervation atrophy, and integration with other repair-phenotype regulators

    2. Optimal timing, duration, and dosing of regulated GDNF expression for peripheral nerve repair without axonal entrapment

    3. Mechanisms of senescent Schwann cell formation and axonal inhibition in aging and chronically denervated peripheral nerves, and the safety of senolytic clearance for nerve repair

    How to perform in vivo examination of brain function1 questions

    1. Extending 110 μm multimode-fibre holographic endo-microscopy to high-speed, bend-tolerant, chronic deep-brain imaging in awake, freely moving animals

    How to prevent dormant tumor cells from being activated through immune intervention3 questions

    1. Immune induction versus immune constraint of pancreatic cancer dormancy: reconciling the adaptive-immunity requirement with Dec2-mediated immune evasion, and the maintain-versus-eradicate therapeutic strategy

    2. Awakening from and therapeutic eradication of immune-mediated metastatic dormancy in breast cancer: reactivation mechanisms, durability of CD39+PD-1+CD8+ T-cell control, and elimination of dormant disseminated cancer cells

    3. Causal immunological maintenance of tumor dormancy in early-stage breast cancer: do infiltrating T effector and T effector-memory cells keep disseminated dormant cells quiescent, and can dormancy-window immunotherapy prevent distant recurrence?

    The mystery of the origin of snakes4 questions

    1. The origin and early evolution of snakes: phylogenetic placement of Serpentes, Laurasian versus Gondwanan origins, and the rise of constriction

    2. Phylogenetic position, origin, radiation, and extinction of non-ophidian ophidiomorphs (dolichosaurs) and the stem-lineage context of snake origins

    3. The assembly of the snake skull and the drivers of the early snake radiation: sequence, polarity, and timing from the Mesozoic stem-snake fossil record

    4. The ecological and developmental origin of the snake body plan: ancestral ecology, coupled skull–body heterochronic evolution, and the mechanism of accelerated cranial development

    How large is the deep underground biosphere?7 questions

    1. Global prevalence and quantitative significance of the geologically mediated microbial dispersal loop in the deep biosphere

    2. Origins, in situ rates, and global extent of hydrogen and dark oxygen fueling high microbial productivity in ancient groundwaters

    3. Functional characterization of microbial life in ultradeep crystalline bedrock: active metabolism, energy sources, and drivers of community composition below 2 km (Otaniemi–Pyhäsalmi, Fennoscandian Shield)

    4. Quantifying the eukaryotic contribution to terrestrial deep-subsurface biomass and diversity: global extrapolation and natural baselines beyond mined fracture waters

    5. Size and burial dynamics of the global marine subseafloor bacterial endospore pool

    6. Live-cell validity and lineage generality of the nonlinear cell size-to-carbon-mass scaling of small prokaryotes

    7. Direct determination of cell size, carbon content, and carbon density of indigenous deep-subseafloor microbial cells

    The patterns and significance of physiological hypoxia3 questions

    1. Causal role of physiological local oxygen-tension differences in the bone marrow for hematopoietic stem cell maintenance, quiescence, activation, and lineage choice in vivo

    2. Unresolved mechanisms and generality of HIF-2α-driven pseudohypoxic maintenance of cell stemness at physiological oxygen (open questions from Hammarlund, von Stedingk and Påhlman, 2018)

    3. Shared versus parallel origins of the hypoxia-harnessing solutions to oxygen-sensitive tissue renewal across animals, plants, and algae, and the obligatory hypoxia dependence of invertebrate stemness

    What is the impact of biological rhythms on the growth of plants and animals and on human diseases?2 questions

    1. Molecular pathways from cardiomyocyte BMAL1 loss to coordinated suppression of mitochondrial oxidative-metabolism genes and TCA-cycle/electron-transport uncoupling in the heart

    2. How the intestinal epithelial circadian clock and colonic inflammation shape microbiome and regulatory T cell rhythmicity: mechanisms, extrinsic cues, and functional consequences

    The efficient utilization of pentoses in biorefining1 questions

    1. Simultaneous glucose-xylose co-utilization by xylose-isomerase Saccharomyces cerevisiae: chromosomal integration optimization, in-vivo xylose isomerase activity, and relief of glucose-linked transcriptional inhibition

    Before fertilization, is there competition among sperm, sperm selection, and attraction of sperm by the egg?3 questions

    1. Mechanism and natural-population reality of genetically loaded sperm competition for compatible genes in the Gouldian finch (Erythrura gouldiae)

    2. Mechanistic and evolutionary basis of egg-chemoattractant-mediated gamete-level mate choice in the mussel Mytilus galloprovincialis

    3. Molecular basis of egg-driven sperm selection against related sperm in house mice

    What are the significance and mechanisms of sleep2 questions

    1. Mechanisms of sleep-wake recalibration of homeostatic and associative synaptic plasticity in the human cortex

    2. Stage-resolved mechanism of tuning for criticality during sleep: the functional division between REM and slow-wave sleep and the brain's means of monitoring the critical boundary

    The mystery of sleep2 questions

    1. The function of REM sleep and dreaming: untested causal predictions of the defensive activation theory

    2. Divergent evolution of sleep homeostasis in Drosophila: mechanisms, deep-sleep function, and generality of the circadian-primacy model

    How do host cells recognize viruses and produce type I interferons to resist viruses? How do viruses disrupt the host interferon response?3 questions

    1. Mechanisms by which the hepatitis E virus capsid protein ORF2 evades cell-intrinsic antiviral responses, beyond TBK1 sequestration, to enable persistent replication

    2. Mechanisms governing IFN-independent intrinsic OASL and interferon-stimulated-gene expression at steady state and the consequences of responder-cell frequency for antiviral defense and interferonopathy

    3. Mechanism and physiological role of the KSHV-encoded IPS-1 homologue (v-IPS-1) in blocking type I interferon induction during lytic replication

    Glycan metabolism in glycoproteins and the relationship between structural abnormalities and disease formation3 questions

    1. Muscle-directed therapy in phosphoglucomutase 1 deficiency (PGM1-CDG): efficacy of D-galactose for muscle energy metabolism and exercise capacity, the mechanism of impaired muscle glycogen synthesis, and prediction of severity from residual enzyme activity

    2. MAN1B1-CDG pathomechanism: brain glycoprotein targets of aberrant hybrid-type N-glycosylation, Golgi/ERAD disturbance, substrate-specific glycan variability, and the diagnostic limits of the intact-transferrin assay

    3. Mechanistic dissection and therapeutic validation of the galectin-4–core 1 O-glycan signaling axis in metastatic prostate cancer

    Do glycans in glyco-complexes contain a large amount of biological information?3 questions

    1. Molecular readers and site-specific rules by which N-glycan structures govern the spatial arrangement of Kv3.1 and E-cadherin in the plasma membrane

    2. Does protein structure causally encode site-specific glycosylation? Mechanistic basis, prospective validation, and generality of the glycoimpact framework

    3. Fidelity of glycan-code synthesis in a realistic Golgi: extending optimal information coding to the branched N-glycosylation network, molecular noise, and self-assembled cisternae

    The reasons for the formation of endemic species and their biogeographical significance2 questions

    1. Long-term climatic stability versus present-day precipitation as explanations of plant palaeo- and neoendemism in the Baetic–Rifan Mediterranean hotspot

    2. Are ecological and evolutionary centres of endemism a general feature of West Palearctic refugial hotspots? Generalizing the functional dichotomy of Italian butterfly endemism and its differential response to climate change

    Can the study of immunoreceptor editing verify the possibility of a "reverse central dogma"?2 questions

    1. Reverse information flow in antibody somatic hypermutation: DNA-templated repair versus RNA editing and reverse transcription in the origin of A/T mutations and strand-biased signatures

    2. Physiological prevalence and tolerance function of RAG-mediated receptor editing and revision in mature peripheral B cells

    Why is it difficult to develop a universal flu vaccine? Can humans have a single effective flu vaccine?3 questions

    1. How single founder mutations, redundant affinity maturation, and IGHV1-69 F54 polymorphism generate broadly neutralizing anti-influenza-stem antibodies: mechanism, population-level precursor frequencies, and designed elicitation (open questions arising from Pappas et al., Nature 2014)

    2. Overcoming the epistatic constraints on CR9114-like breadth evolution: routes to and elicitation of cross-group influenza HA stem broadly neutralizing antibodies

    3. Protective efficacy, cross-group breadth, and regimen determinants of influenza HA-stem immunogen vaccines in humans

    What is the molecular genetic basis of phenotypic differences in identical twins?1 questions

    1. Quantifying the zygotic, environmental, developmental-timing, and stochastic sources of DNA methylation discordance in monozygotic and dizygotic twins and their contribution to phenotype

    Microbial-synthesized polymers—application in biomaterials2 questions

    1. Raising pendant-hydroxyl content in biosynthetic PHA scaffolds: increasing 2,3-dihydroxybutyrate incorporation in PHBVDB and establishing its composition–property–biological-performance map

    2. Non-monotonic mechanical ageing of poly(3-hydroxybutyrate)/oligomeric mcl-PHA blends: rigid amorphous fraction partitioning and the microstructural origin of the aged 90/10 vs 95/5 anomaly

    Reconstruction of microbial cell networks2 questions

    1. Scalable, validated coupling of strain-resolved gut microbial community metabolic models with human host metabolic reconstructions for predictive host–microbiome simulation

    2. Biologically informed gap filling for genome-scale metabolic network reconstruction: identifying alternative pathways and integrating thermodynamic and heterogeneous functional-genomics evidence (the MIRAGE open problem)

    Why do plant leaves display colorful patterns?7 questions

    1. Does a resistance–tolerance trade-off maintain red–green leaf colour polymorphism? Direct tests of the defence–photosynthesis balance

    2. The functional significance of transient leaf mottling in Erythronium dens-canis: adaptive role, developmental mechanism, and cost–benefit balance

    3. The adaptive value of autumn leaf colouration: discriminating herbivore signalling from photoprotection

    4. Adaptive function and mechanistic determinants of photonic helicoidal cell walls in iridescent blue leaves

    5. Functional significance of extreme foliar anthocyanin pigmentation: decomposing the photoprotective mechanism of black leaves and explaining the rarity of black-leafed vascular plants

    6. Why red young leaves lack mechanical defence: causal mechanisms and selective agents of the pigmentation–mechanical-defence trade-off during leaf expansion

    7. Causal drivers of the continental-scale difference in red autumn colouration among Northern Hemisphere deciduous woody floras

    Why do the leaf arrangement sequences differ among plant species?5 questions

    1. Phyllotaxis and light capture: does the near-equivalence of Fibonacci-like divergence angles survive realistic light regimes, carbon gain, and fitness?

    2. Empirical validation of the adaptive cost explanation of the golden angle in phyllotaxis: the physiological cost mechanism, quantitative genetics, and variance structure of the divergence angle

    3. The molecular mechanism of the MONOPTEROS–PIN1 feedback module: how MP-dependent auxin signaling reorients PIN1 polarity non-cell-autonomously to pattern phyllotaxis, and how the module is modulated across species

    4. The biological basis of primordial age-dependent inhibitory power in the EDC2 phyllotaxis model: mechanisms, species-specific parameters, and empirical tests of orixate pattern formation

    5. Molecular mechanism setting the rotation angle of apical stem cell division planes in bryophytes and the origin of moss spiral phyllotaxis

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