bluuebunny/crossref_metadata_2025 huggingface dataset:
Statistical examination of shared loci in neuropsychiatric diseases using genome-wide association study summary statistics
Authors: Spargo Thomas P , Gilchrist Lachlan , Hunt Guy P , Dobson Richard JB , Proitsi Petroula , Al-Chalabi Ammar , Pain Oliver , Iacoangeli Alfredo
Published: September 2023

Continued methodological advances have enabled numerous statistical approaches for the analysis of summary statistics from genome-wide association studies. Genetic correlation analysis within specific regions enables a new strategy for identifying pleiotropy. Genomic regions with significant ‘local’ genetic correlations can be investigated further using state-of-the-art methodologies for statistical fine-mapping and variant colocalisation. We explored the utility of a genome-wide local genetic correlation analysis approach for identifying genetic overlaps between the candidate neuropsychiatric disorders, Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia, Parkinson’s disease, and schizophrenia. The correlation analysis identified several associations between traits, the majority of which were loci in the human leukocyte antigen region. Colocalisation analysis suggested that disease-implicated variants in these loci often differ between traits and, in one locus, indicated a shared causal variant between ALS and AD. Our study identified candidate loci that might play a role in multiple neuropsychiatric diseases and suggested the role of distinct mechanisms across diseases despite shared loci. The fine-mapping and colocalisation analysis protocol designed for this study has been implemented in a flexible analysis pipeline that produces HTML reports and is available at: https://github.com/ThomasPSpargo/COLOC-reporter.
The genetic and dietary landscape of the muscle insulin signalling network
Authors: van Gerwen Julian , Masson Stewart W. C. , Cutler Harry B. , Díaz-Vegas Alexis , Potter Meg , Stöckli Jacqueline , Madsen Søren , Nelson Marin E. , Humphrey Sean J. , James David E.
Published: September 2023

Metabolic disease is caused by a combination of genetic and environmental factors, yet few studies have examined how these factors influence signal transduction, a key mediator of metabolism. Using mass spectrometry-based phosphoproteomics, we quantified 23,126 phosphosites in skeletal muscle of five genetically distinct mouse strains in two dietary environments, with and without acute
in vivo
insulin stimulation. Almost half of the insulin-regulated phosphoproteome was modified by genetic background on an ordinary diet, and high-fat high-sugar feeding affected insulin signalling in a strain-dependent manner. Our data revealed coregulated subnetworks within the insulin signalling pathway, expanding our understanding of the pathway’s organisation. Furthermore, associating diverse signalling responses with insulin-stimulated glucose uptake uncovered regulators of muscle insulin responsiveness, including the regulatory phosphosite S469 on Pfkfb2, a key activator of glycolysis. Finally, we confirmed the role of glycolysis in modulating insulin action in insulin resistance. Our results underscore the significance of genetics in shaping global signalling responses and their adaptability to environmental changes, emphasizing the utility of studying biological diversity with phosphoproteomics to discover key regulatory mechanisms of complex traits.
Neural criticality from effective latent variables
Authors: Morrell Mia , Nemenman Ilya , Sederberg Audrey J.
Published: September 2023

Observations of power laws in neural activity data have raised the intriguing notion that brains may operate in a critical state. One example of this critical state is “avalanche criticality,” which has been observed in various systems, including cultured neurons, zebrafish, rodent cortex, and human EEG. More recently, power laws were also observed in neural populations in the mouse under an activity coarse-graining procedure, and they were explained as a consequence of the neural activity being coupled to multiple dynamical latent variables. An intriguing possibility is that avalanche criticality emerges due to a similar mechanism. Here, we determine the conditions under which dynamical latent variables give rise to avalanche criticality. We find that a single, quasi-static latent variable can generate critical avalanches, but multiple latent variables lead to critical behavior in a broader parameter range. We identify two regimes of avalanches, both critical but differing in the amount of information carried about the latent variable. Our results suggest that avalanche criticality arises in neural systems, in which there is an emergent dynamical variable or shared inputs creating an effective latent dynamical variable and when this variable can be inferred from the population activity.
Inhibition of Notch activity by phosphorylation of CSL in response to parasitization in Drosophila
Authors: Deichsel Sebastian , Frankenreiter Lisa , Fechner Johannes , Gahr Bernd M. , Zimmermann Mirjam , Mastel Helena , Preis Irina , Preiss Anette , Nagel Anja C.
Published: September 2023

Notch signaling activity regulates hematopoiesis in
Drosophila
and vertebrates alike. Parasitoid wasp infestation of
Drosophila
larvae, however, requires a rapid downregulation of Notch activity to allow the formation of encapsulation-active blood cells. Here we show that the
Drosophila
CSL transcription factor Suppressor of Hairless [Su(H)] is phosphorylated at Serine 269 in response to parasitoid wasp infestation. As this phosphorylation interferes with the DNA-binding of Su(H), it reversibly inhibits Notch activity. Accordingly, phospho-deficient

Su(H)
S269A

mutants are immune compromised. A screen for kinases involved in Su(H) phosphorylation identified Pkc53E, required for normal hematopoiesis as well as for parasitoid immune response. Genetic and molecular interactions support the specificity of the Su(H)-Pkc53E relationship. Moreover, phorbol ester treatment inhibits Su(H) activity in vivo and in human cell culture. We conclude that Pkc53E targets Su(H) during parasitic wasp infestation, inducing downregulation of Notch activity, thereby remodeling the blood cell population required for wasp egg encapsulation.
Cortical plasticity is associated with blood–brain barrier modulation
Authors: Swissa Evyatar , Monsonego Uri , Yang Lynn T , Schori Lior , Kamintsky Lyna , Mirloo Sheida , Burger Itamar , Uzzan Sarit , Patel Rishi , Sudmant Peter H , Prager Ofer , Kaufer Daniela , Friedman Alon
Published: September 2023

Brain microvessels possess the unique properties of a blood–brain barrier (BBB), tightly regulating the passage of molecules from the blood to the brain neuropil and vice versa. In models of brain injury, BBB dysfunction and the associated leakage of serum albumin to the neuropil have been shown to induce pathological plasticity, neuronal hyper-excitability, and seizures. The effect of neuronal activity on BBB function and whether it plays a role in plasticity in the healthy brain remain unclear. Here we show that neuronal activity induces modulation of microvascular permeability in the healthy brain and that it has a role in local network reorganization. Combining simultaneous electrophysiological recording and vascular imaging with transcriptomic analysis in rats, and functional and BBB-mapping MRI in human subjects, we show that prolonged stimulation of the limb induces a focal increase in BBB permeability in the corresponding somatosensory cortex that is associated with long-term synaptic plasticity. We further show that the increased microvascular permeability depends on neuronal activity and involves caveolae-mediated transcytosis and transforming growth factor β signaling. Our results reveal a role of BBB modulation in cortical plasticity in the healthy brain, highlighting the importance of neurovascular interactions for sensory experience and learning.
Synthetic analysis of trophic diversity and evolution in Enantiornithes with new insights from Bohaiornithidae
Authors: Miller Case Vincent , Bright Jen A , Wang Xiaoli , Zheng Xiaoting , Pittman Michael
Published: September 2023

Enantiornithines were the dominant birds of the Mesozoic, but understanding of their diet is still tenuous. We introduce new data on the enantiornithine family Bohaiornithidae, famous for their large size and powerfully built teeth and claws. In tandem with previously published data, we comment on the breadth of enantiornithine ecology and potential patterns in which it evolved. Body mass, jaw mechanical advantage, finite element analysis of the jaw, and traditional morphometrics of the claws and skull are compared between bohaiornithids and living birds. We find bohaiornithids to be more ecologically diverse than any other enantiornithine family: Bohaiornis and Parabohaiornis are similar to living plant-eating birds; Longusunguis resembles raptorial carnivores; Zhouornis is similar to both fruit-eating birds and generalist feeders; and Shenqiornis and Sulcavis plausibly ate fish, plants, or a mix of both. We predict the ancestral enantiornithine bird to have been a generalist which ate a wide variety of foods. However, more quantitative data from across the enantiornithine tree is needed to refine this prediction. By the Early Cretaceous, enantiornithine birds had diversified into a variety of ecological niches like crown birds after the K-Pg extinction, adding to the evidence that traits unique to crown birds cannot completely explain their ecological success.
Semaphorin7A patterns neural circuitry in the lateral line of the zebrafish
Authors: Dasgupta Agnik , Reagor Caleb C , Paik Sang Peter , Snow Lauren M , Jacobo Adrian , Hudspeth AJ
Published: September 2023

In a developing nervous system, axonal arbors often undergo complex rearrangements before neural circuits attain their final innervation topology. In the lateral line sensory system of the zebrafish, developing sensory axons reorganize their terminal arborization patterns to establish precise neural microcircuits around the mechanosensory hair cells. However, a quantitative understanding of the changes in the sensory arbor morphology and the regulators behind the microcircuit assembly remain enigmatic. Here, we report that Semaphorin7A (Sema7A) acts as an important mediator of these processes. Utilizing a semi-automated three-dimensional neurite tracing methodology and computational techniques, we have identified and quantitatively analyzed distinct topological features that shape the network in wild-type and Sema7A loss-of-function mutants. In contrast to those of wild-type animals, the sensory axons in Sema7A mutants display aberrant arborizations with disorganized network topology and diminished contacts to hair cells. Moreover, ectopic expression of a secreted form of Sema7A by non-hair cells induces chemotropic guidance of sensory axons. Our findings propose that Sema7A likely functions both as a juxtracrine and as a secreted cue to pattern neural circuitry during sensory organ development.
Synthetic Eco-Evolutionary Dynamics in Simple Molecular Environment
Authors: Casiraghi Luca , Mambretti Francesco , Tovo Anna , Paraboschi Elvezia Maria , Suweis Samir , Bellini Tommaso
Published: September 2023

The understanding of eco-evolutionary dynamics, and in particular the mechanism of emergence of species, is still fragmentary and in need of test bench model systems. To this aim we developed a variant of SELEX in-vitro selection to study the evolution of a population of ∼ 10
15
single-strand DNA oligonucleotide ‘individuals’. We begin with a seed of random sequences which we select via affinity capture from ∼ 10
12
DNA oligomers of fixed sequence (‘resources’) over which they compete. At each cycle (‘generation’), the ecosystem is replenished via PCR amplification of survivors. Massive parallel sequencing indicates that across generations the variety of sequences (‘species’) drastically decreases, while some of them become populous and dominate the ecosystem. The simplicity of our approach, in which survival is granted by hybridization, enables a quantitative investigation of fitness through a statistical analysis of binding energies. We find that the strength of individual-resource binding dominates the selection in the first generations, while inter and intra-individual interactions becomes important in later stages, in parallel with the emergence of prototypical forms of mutualism and parasitism.
14-3-3 protein augments the protein stability of phosphorylated spastin and promotes the recovery of spinal cord injury through its agonist intervention
Authors: Liu Qiuling , Yang Hua , Luo Jianxian , Peng Cheng , Wang Ke , Zhang Guowei , Lin Hongsheng , Ji Zhisheng
Published: September 2023

Axon regeneration is abortive in the central nervous system following injury. Orchestrating microtubule dynamics has emerged as a promising approach to improve axonal regeneration. The microtubule severing enzyme spastin is essential for axonal development and regeneration through remodeling of microtubule arrangement. To date, however, little is known regarding the mechanisms underlying spastin action in neural regeneration after spinal cord injury. Here, we use glutathione transferase pulldown and immunoprecipitation assays to demonstrate that 14-3-3 interacts with spastin, both in vivo and in vitro, via spastin Ser233 phosphorylation. Moreover, we show that 14-3-3 protects spastin from degradation by inhibiting the ubiquitination pathway and upregulates the spastin-dependent severing ability. Furthermore, the 14-3-3 agonist Fusicoccin (FC-A) promotes neurite outgrowth and regeneration in vitro which needs spastin activation. Western blot and immunofluorescence results revealed that 14-3-3 protein is upregulated in the neuronal compartment after spinal cord injury in vivo. In addition, administration of FC-A not only promotes locomotor recovery, but also nerve regeneration following spinal cord injury in both contusion and lateral hemisection models; however, the application of spastin inhibitor spastazoline successfully reverses these phenomena. Taken together, these results indicate that 14-3-3 is a molecular switch that regulates spastin protein levels, and the small molecule 14-3-3 agonist FC-A effectively mediates the recovery of spinal cord injury in mice which requires spastin participation.
Oxygen isotopes in orangutan teeth reveal recent and ancient climate variation
Authors: Smith Tanya M , Arora Manish , Austin Christine , Nunes Ávila Janaína , Duval Mathieu , Lim Tze Tshen , Piper Philip J , Vaiglova Petra , de Vos John , Williams Ian S , Zhao Jian-xin , Green Daniel R
Published: September 2023

Studies of climate variation commonly rely on chemical and isotopic changes recorded in sequentially produced growth layers, such as in corals, shells, and tree rings, as well as in accretionary deposits—ice and sediment cores, and speleothems. Oxygen isotopic compositions (δ18O) of tooth enamel are a direct method of reconstructing environmental variation experienced by an individual animal. Here, we utilize long-forming orangutan dentitions (Pongo spp.) to probe recent and ancient rainfall trends on a weekly basis over ~3–11 years per individual. We first demonstrate the lack of any consistent isotopic enrichment effect during exclusive nursing, supporting the use of primate first molar teeth as environmental proxies. Comparisons of δ18O values (n=2016) in twelve molars from six modern Bornean and Sumatran orangutans reveal a high degree of overlap, with more consistent annual and bimodal rainfall patterns in the Sumatran individuals. Comparisons with fossil orangutan δ18O values (n=955 measurements from six molars) reveal similarities between modern and late Pleistocene fossil Sumatran individuals, but differences between modern and late Pleistocene/early Holocene Bornean orangutans. These suggest drier and more open environments with reduced monsoon intensity during this earlier period in northern Borneo, consistent with other Niah Caves studies and long-term speleothem δ18O records in the broader region. This approach can be extended to test hypotheses about the paleoenvironments that early humans encountered in southeast Asia.
Gradient organisation of functional connectivity within resting state networks is present from 25 weeks gestation in the human fetal brain
Authors: Moore Jucha Willers , Wilson Siân , Oldehinkel Marianne , Cordero-Grande Lucilio , Uus Alena , Kyriakopoulou Vanessa , Duff Eugene P , O’Muircheartaigh Jonathan , Rutherford Mary A , Andreae Laura C , Hajnal Joseph V , Edwards A David , Beckmann Christian F , Arichi Tomoki , Karolis Vyacheslav R
Published: September 2023

During the third trimester of human gestation, the structure and function of the fetal brain is developing rapidly, laying the foundation for its connectivity framework across the lifespan. During this juncture, resting state functional MRI can be used to identify resting state networks (RSNs) which mature across gestation to resemble canonical RSNs at full term. However, the emergence of finer grain organisation of connectivity within these RSNs in the fetal brain is unknown. Using in-utero resting state fMRI, we performed connectopic mapping analysis to explore the presence of gradients in functional connectivity organisation of 11 cortical RSNs, known as connectopic maps in fetuses aged 25-37 weeks gestation (GW). We hypothesised that, if present, development of connectopic maps would be network specific in the third trimester of gestation, such that this property would be present within the earlier maturing primary sensory and motor networks before those associated with higher association function. In keeping with this, we found smooth connectopic maps in all of the studied RSNs from 25 GW, with the most spatially consistency across gestational age in the primary sensory and motor networks. Voxel-wise permutation testing of the connectopic maps identified local clusters of voxels within networks that significantly covaried with age, specifically in multisensory processing areas, suggesting multisensory processing may be developing during this period. Our analysis shows that functional gradient organisation is already established in the fetal brain and develops throughout gestation, which has strong implications for understanding how cortical organisation subserves the emergence of behaviour in the ensuing period.
Stratification of enterochromaffin cells by single-cell expression analysis
Authors: Song Yan , Fothergill Linda J , Lee Kari S , Liu Brandon Y , Koo Ada , Perelis Mark , Diwakarla Shanti , Callaghan Brid , Huang Jie , Wykosky Jill , Furness John B , Yeo Gene W
Published: September 2023

Dynamic interactions between gut mucosal cells and the external environment are essential to maintain gut homeostasis. Enterochromaffin (EC) cells transduce both chemical and mechanical signals and produce 5-hydroxytryptamine (5-HT) to mediate disparate physiological responses. However, the molecular and cellular basis for functional diversity of ECs remains to be adequately defined. Here, we integrated single-cell transcriptomics with spatial image analysis to identify fourteen EC clusters that are topographically organized along the gut. Subtypes predicted to be sensitive to the chemical environment and mechanical forces were identified that express distinct transcription factors and hormones. A

Piezo2
+

population in the distal colon was endowed with a distinctive neuronal signature. Using a combination of genetic, chemogenetic and pharmacological approaches, we demonstrated

Piezo2
+

ECs are required for normal colon motility. Our study constructs a molecular map for ECs and offers a framework for deconvoluting EC cells with pleiotropic functions.
Risk factors for adverse pregnancy outcomes in Chinese women: a meta-analysis
Authors: Huang Yiping , Xu Junbi , Peng Bin , Zhang Weiying
Published: September 2023

Objective

This study examined the associated risk factors of adverse pregnancy outcomes among Chinese females and furnished some fundamental principles and recommendations for enhanced prevention of adverse pregnancy and preservation of women’s well-being.

Methods

A systematic review was conducted by retrieving the MEDLINE (The National Library of Medicine), Embase, PubMed, and Cochrane databases. The relevant risk factors for adverse pregnancy in Chinese women were retrieved from May 2017 to April 2023. Use Review Manager for data analysis. Calculate the merge effect based on data attributes using mean difference (MD) or odds ratio (or) and 95% confidence interval (CI). The meta-analysis was registered at INPLASY (International Platform of Registered Systematic Review and Meta-analysis Protocols, 202340090).

Results

A total of 15 articles were included, with a total of 946,818 Chinese pregnant women. Moreover, all the literature was scored by the NOS (Newcastle-Ottawa Scale), and all literatures were ≥7 points, which were evaluated as high quality. There are seven risk factors related to adverse pregnancy in Chinese women: parity, pregnancy frequency, education level, smoking, gestational diabetes, gestational weeks, and age. Moreover, the main risk factors for adverse pregnancy are pregnancy frequency, education level, gestational diabetes mellitus, and age.

Conclusion

The pregnancy frequency, education level, gestational diabetes mellitus, and age were significantly associated with the adverse pregnancy in Chinese women, whereas gestational weeks, smoking, and parity had no significant effect on adverse pregnancy.
Biosynthesis of Graphene Oxide Nanoparticles from Coconut Fronds
Authors: Kaviyarasan G. , Rahale C. Sharmila , Shanmugasundaram R. , Palaniselvam V. , Saranya N.
Published: September 2023

To address the ecofriendly approach for the nano graphene oxide (nGO) synthesis, “Wealth from waste” idea utilized in this study. The synthesis process involves the controlled reduction and manipulation of nGO sheets to achieve nano-scale dimensions, resulting in nGO with improved structural integrity and enhanced surface area. Characterization of the synthesized nGO is conducted using advanced analytical tools, including Transmission Electron Microscopy (TEM), X-ray Diffraction (XRD), UV-Visible spectroscopy (UV-VIS) and Particle Size Analyser (PSA). The PSA analysis revealed, a predominantly monodisperse distribution with a peak size of approximately 314 nanometers with indicative of good dispersion uniformity. The UV-Visible spectroscopy displayed a significant absorption peak at 234 nanometers, elucidating the material’s optical characteristics. TEM images unveiled the structural features such as wrinkles, folds and nanoscale dimensions. The XRD diffractogram suggested the presence of both GO and rGO phases with unique intensity peaks at 10.33° and 32.35° shown the interlayer spacing of 3.72 and 1.11 nm respectively. These analyses provide valuable insights into the morphology, size and crystallinity present in the nGO, aiding in its structural elucidation. These findings affirm the successful conversion of coconut fronds waste into GO nanoparticles and open avenues for sustainable nanomaterial production. The unique properties of GO are utilized for water purification, oil spill cleanup, energy storage, sensors, composite materials, photodetectors, anticorrosive coatings, and so on. The biosynthesis of nano graphene oxide particles offers exciting opportunities for the development of next-generation materials with enhanced performance characteristics.
Characterization of Recycled Aggregates of Concrete and Bricks in the Central Region of Burkina Faso
Authors: Sawadogo Boukari , Gouba Bernard
Published: September 2023

Aggregates used in the construction of civil engineering works have an impact on the properties of concrete. For several years the central region is famous because of the effects of extraction of natural aggregates on the environment. We conducted laboratory tests on several recycled aggregates of concrete and bricks to determine their mechanical properties. This choice was guided by a concern to identify and analyze the characteristics of natural and recycled aggregates of concretes that impact the properties of concrete on the one hand  and to show the importance of increased use of recycled aggregates in concrete production to better preserve the environment and move towards sustainable development moreover. To better understand the qualities of these aggregates, it is necessary for us to carry out experimental tests in the laboratory.

The objective also guided the choice of the different types of recycled aggregates selected for the measurement of mechanical properties in the central region: Crushed Natural Gravel, Rolled Natural Gravel, Crushed Recycled Gravel, Recycled Spinning Gravel, Alluvionary Natural Sands, Recycled Brick Sands.

The results show that recycled aggregates of concrete and bricks in the central region can be used for high-quality concretes on the one hand and reduce the impact of artisanal extraction of non-recycled aggregates on the environment on the other hand.

In short, we retain that the characteristics of recycled aggregates are a function of the rate of mortar gangues glued to the mother aggregates.
Prevalence of Mycobacterium tuberculosis among HIV Patients Attending Federal Medical Centre Asaba, Delta State, Nigeria
Authors: Onyeka Odiase, Edgar , Mitsan Olley , Ugbomoiko Daniel Ohilebo , Erameh Theophilus Ogie , Gambo Ezekiel Dauda , Kanwulia Ofili Sandra , Ibrahim Muhammad Adamu , Ntasin Paul Yiran
Published: September 2023

Aim: The study aimed to ascertain the prevalence of tuberculosis among HIV-positive patients at the Federal Medical Center Asaba in Delta State, Nigeria.

Study Design: This study engaged a cross-sectional study design to prevalence of Mycobacterium Tuberculosis among HIV Patients Attending Federal Medical Centre Asaba, Delta State.

Place and Duration of the Study: The study was conducted in Federal Medical Center. Data collection spanned a specific duration from November, 2022 to January, 2023.

Methodology: A total of 188 samples were obtained from known HIV patients. The patients were selected by random sampling technique. The samples were analysed using GeneXpert machine (GX2.1 model) with the nuclei acid amplification (NAA) of DNA mycobacterium tuberculosis complex (MTBC) and resistance to rifampicin. Demographic data of participants were obtained through questionnaires.

Results: Out of 188 samples from HIV patients analyzed, MTB was detected in 13 (8.7%) patients with the highest prevalence recorded among male subjects 6(12%). Age group 19-29 was the most prevalent of MTB among the test subjects.

Conclusion: Mycobacterium tuberculosis is widespread among HIV patients in Asaba, Delta state, according to these data. As a result, patients must be encouraged to adhere to treatment and preventive measures.
Insights into the catalytic mechanism of Grimontia hollisae collagenase through structural and mutational analyses
Authors: Ueshima Saori , Yasumoto Mizuki , Kitagawa Yuto , Akazawa Kaho , Takita Teisuke , Tanaka Keisuke , Hattori Shunji , Mizutani Kimihiko , Mikami Bunzo , Yasukawa Kiyoshi
Published: September 2023

Grimontia hollisae collagenase (Ghcol) exhibits high collagen‐degrading activity. To explore its catalytic mechanism, its substrate (Gly‐Pro‐Hyp‐Gly‐Pro‐Hyp, GPOGPO)‐complexed crystal structure was determined at 2.0 Å resolution. A water molecule was observed near the active‐site zinc ion. Since this water was not observed in the product (GPO)‐complexed Ghcol, it was hypothesized that the GPOGPO‐complexed Ghcol structure reflects a Michaelis complex, providing a structural basis for understanding the catalytic mechanism. Analyses of the active‐site geometry and site‐directed mutagenesis of the active‐site tyrosine residues revealed that Glu493 and Tyr564 were essential for catalysis, suggesting that Glu493 functions as an acid and base catalyst while Tyr564 stabilizes the tetrahedral complex in the transition state. These results shed light on the catalytic mechanism of bacterial collagenase.
Suffix Order Restrictions in Bantu
Authors: Gibson Hannah , Kula Nancy C. , Marten Lutz , Taji Julius
Published: September 2023

Bantu languages typically have a rich and complex verb structure, where a range of derivational suffixes can be distinguished. Focusing on the interaction of applicative, causative, reciprocal and passive suffixes, different theoretical and analytical models have been used to explain the order of these suffixes. Work over the past 40 years has shown that the phonological shape of the suffixes, a morphological template determining suffix ordering, semantic scope and syntactic derivation all play a role in understanding suffix order in Bantu. In addition, research in this area has shown rich variation between different Bantu languages, including specific developments and restrictions on morphological processes and the interaction of derivational and inflectional suffixes. The area of suffix order restrictions has become a central topic in Bantu linguistics and in studies of the interaction between phonology, morphology, syntax and semantics more broadly.
Anaphoric Islands
Authors: Ward Gregory , Sproat Richard
Published: September 2023

Following Postal, alternative grammar‐based explanations of so‐called inbound and outbound anaphora were offered including more general notions of Lexical Integrity, all of which assumed that both inbound and outbound anaphora were categorically disallowed. However, it was soon observed that judgements of ‘outbound anaphora’ were gradient and context‐sensitive. Such counter‐examples were relegated to some (undefined) mechanism of ‘pragmatic amnestying’, inexplicably unavailable for ‘inbound anaphora’, which remains ill‐formed in any context. A general prohibition on pronouns occurring within words does seem to be operative in English (though, crucially, not in other languages) but outbound anaphora, as was first argued in Ward et al., is in fact grammatically unrestricted. As with anaphora in general, its felicity is shown to be a function of the accessibility of the referent, that is, the discourse entity to which an anaphor is used to refer. Subsequent work identified a number of formal and functional factors that increase the accessibility of discourse entities and therefore the felicity of anaphors being used to reference those entities. This analysis is supported by a corpus of naturally occurring tokens of outbound anaphora as well as a series of psycholinguistic studies that reveal that topicality and contrast facilitate comprehension of anaphors with word‐internal antecedents. One direct consequence of this work is that references to grammatical constraints on outbound anaphora have all but disappeared from the literature.
Back‐Formations and Subtractive Morphology
Authors: Köhnlein Björn
Published: September 2023

After a brief introduction to the concepts of back‐formation and subtractive morphology, this entry discusses subtractive morphology in German dialects, focusing on relevant descriptive generalizations and their impact on theories of morphology. The entry first describes the most widely discussed German subtraction pattern, where certain word‐final consonants that are present in monosyllabic singulars are absent in corresponding plural forms; some dialects also show subtraction in datives. One largely overlooked aspect of consonant subtraction is the fact that it predictably interacts with overt phonological processes in relevant dialects. It then considers another, less often treated type of subtractive morphology in German dialects, namely vowel shortening in plural forms, which is sometimes even attested in combination with consonant deletion. Lastly, it discusses the theoretical relevance of the patterns and evaluate existing approaches to the relevant facts in the light of the full dataset introduced in this entry.
Blocking Effects
Authors: Embick David , Benz Johanna , Paparounas Lefteris
Published: September 2023

This entry provides an overview and synthesis of grammatical approaches toblocking effects: informally, cases in which the ungrammaticality of one word (or phrase) is attributed to the existence of another. The primary focus concerns the scope of competition for grammaticality. While discussions of blocking are often directed at particular parts of the grammar (e.g. derivational morphology) the larger set of questions raised by (putative) blocking effects has the potential to distinguish predictions made by major theoretical movements like the Minimalist Program and Optimality Theory, precisely because of the different roles they attribute to competition. This review of theories of blocking is oriented towards larger questions of this type. It also examines the apparent absence of blocking: cases in which it looks as if one form should (all else being equal) block another, yet both exist. Observations to this effect appear in early and influential accounts of blocking, where they have underappreciated theoretical consequences concerning how the ‘paradigm space' associated with words and phrases is structured. A key theme throughout the entry is whether the phenomena that have been described as blocking effects are derivative of one grammatical (or extragrammatical) mechanism, or several. While the authors conclude that the latter view is correct, part of their argument is that the focus on unity is less important than the question of what evidence for (or against) competition in a given domain would look like in the first place.
Circumfixation
Authors: Marušič Franc Lanko
Published: September 2023

Circumfixation is a morphological operation as a result of which an affix appears to surround or circumscribe the stem. There are three possible arrangements of the affixal element and the stem in which the stem is circumscribed by the affix: a single affix can appear simultaneously on both sides of the stem, which is what I call amonomorphic circumfix, two independent affixes can be placed each on a different side of the stem, or else an affix could be alternating between a suffix and a prefix, by which it would in a sense also circumscribe the stem, it just would not do so simultaneously. The last‐mentioned option results inmobile affixes, which are covered in more detail in ‘Metathesis’ in this volume. This entry goes over various possible attestations of these three patterns and argues the only possible type of circumfixes are bimorphic circumfixes. It further claims that even the bimorphic circumfixes are (most likely) bimorphemic. Theoretical and processing reasons are presented that favour this restriction.
Category Change without Overt Marking
Authors: Don Jan
Published: September 2023

Category change without overt marking is often called conversion or zero‐derivation. In discussing a few landmarks in the research on conversion, this article presents the arguments for and against the idea that conversion is a separate grammatical process, or that it is performed through zero affixes. The empirical evidence supports the idea that, within certain limits, conversion does not exist as a separate process or means to derive words, but rather that it is an epiphenomenon resulting from uncategorized elements in the lexicon that can be freely inserted into syntactic environments that define the category of the inserted element.
Defectiveness
Authors: Sims Andrea D.
Published: September 2023

Morphological defectiveness is a situation in which an inflected or derived word is expected in a language but no word with that meaning exists. It is thus a kind of absolute ungrammaticality or ineffability. In the context of the productive nature of morphology, gaps in inflectional and derivational paradigms seem anomalous – situations in which the grammar fails. Investigating the absence of a morphological form raises definitional and methodological issues, but the diverse causes of gaps allow insight into various aspects of morphological structure. Structural causes include phonotactic ill‐formedness, indeterminate allomorphy, anti‐allomorphy effects (lexical conservatism), and homophony avoidance, among others. Gaps also can arise in the context of lexicalization, inflectional loss and borrowing. At the same time, structural properties that the defective words in a language have in common often are also shared with non‐defective words. This raises the question of why defectiveness occurs instead of a structural repair or some other gap‐filling form. The frequent inadequacy of structural factors for predicting which words are defective suggests the need for a closer examination of the causes of defectiveness, in particular attention to mechanistic explanation. This includes processes involved in learning and change.
Deponency
Authors: Grestenberger Laura
Published: September 2023

The terms ‘deponency’ and ‘deponents’ originally referred to a particular class of Latin verbs, which take passive (‘non‐active’) morphology but are syntactically active. The term has been extended to verbs in other languages with seemingly aberrant voice morphology, and eventually to other kinds of perceived mismatches between morphology and syntax. Deponency has therefore become a useful tool for testing assumptions regarding the lexicon–(morpho)syntax interface. This entry uses deponency in Latin as a case study for various issues and discusses the behaviour of Latin deponents in finite and non‐finite contexts, in primary and secondary verbs, and from various theoretical perspectives.
Endoclisis and Mesoclisis
Authors: Crysmann Berthold , Luís Ana R.
Published: September 2023

Most clitics tend to be placed at the edge of a host, either as proclitics, to the left, or as enclitics, to the right. More rarely, however, clitics may also appear within the host word and these cases are referred to in the literature, rather interchangeably, as either mesoclitics (from Lat. meso ‘middle’) or endoclitics (from Greek endo ‘inside’). The idea that clitics may interrupt existing words has attracted much suspicion over the years and is almost uncontroversially regarded as a threat to lexical integrity. However, as is the case for clitics in general, endoclitics/mesoclitics also do not represent a uniform category. It is therefore essential not to draw conclusions before understanding what the properties of each case are, how they impact on the host word and whether they attach syntactically or morphologically. In this entry we try to shed light on the phenomenon of endoclisis/mesoclisis by examining two sets of word‐internal clitics, namely mesoclitics in European Portuguese and endoclitics in Udi. These two case studies provide us with extremely challenging and at times conflicting evidence as to the syntactic versus morphological nature of the phenomenon. But we hope to show that a careful evaluation of available diagnostic criteria is of utmost importance when drawing conclusions about the nature of the morphology‐syntax interface. Section 1 offers a general discussion of clitics. Section 2 deals with mesoclitics in European Portuguese and Section 3 with endoclitics in Udi. For each case study, we start with a description of the grammatical properties by applying well‐established criteria developed for the clitic‐affix distinction; having established the mixed nature of both the European Portuguese and Udi clitic systems, we then offer a brief discussion of existing analyses. The conclusion in Section 4 presents a summary of our findings.
Exocentric Compounds
Authors: Olsen Susan
Published: September 2023

We begin with the patterns of exocentric compounds in the Indo‐European daughter languages and trace their development to the present. In Germanic, their strength diminished as a result of diachronic changes leading to the integration of many forms into endocentric suffixation patterns. Consequently, the term exocentric compound has undergone a modification as it has come to identify the forms that resisted the trend to endocentricity. A different type of diachronic change resulted in the demise of one of the original patterns in Latin, setting the stage for the emergence in Romance of an innovative exocentric pattern to fill the gap.
Expletive Insertion
Authors: Bye Patrik
Published: September 2023

Expletive insertion entails the insertion of an expletive, such asfuckin, inside another word, for exampleabso‐fuckin‐lutely. The only unassailable phonological generalization is that the expletive is inserted before a foot. However, there is also a gradient aspect since the relative acceptability of the resulting form depends on the rhythmic quality of the entire expression. This includes whether the expletive is preceded by a foot, the number of syllables in each foot and whether the initial foot bears an accent. This entry argues that this reflects the expressive function of expletive insertion, which is to create an extended domain for an emphatic rhythmic performance. While expletive insertion has a rule‐governed aspect, its expressiveness derives in part from a deviance from linguistic givens, with attendant processing costs. Expletive insertion thus provides an argument for the importance of norms in expressive language use in addition to rules.
Honorificity
Authors: Yamada Akitaka
Published: September 2023

This is a survey entry on grammatical devices encoding Honorificity. Rather than presenting a particular theory or an analysis, this entry synthesizes the research that has been done on Honorificity, and explores specific empirical data sets worthy of attention from researchers working on morphology and morphosyntax in general. With this goal in mind, this entry is organized according to the positions of such grammatical devices. Section 2 examines Honorificity in and around the nominal domain, such as pronouns, common nouns and other nominal derivational morphologies. Section 3 explores the Honorificity expressed in and around the verbal domain, such as subject and object honorifics. Finally, Section 4 investigates Honorificity found in the clause periphery, such as addressee honorifics, and other discourse‐oriented expressions.
Morphology in Sign Languages
Authors: Pfau Roland , Steinbach Markus
Published: September 2023

Sign languages show the same range of morphological processes as spoken languages. Linguistic research on many different sign languages has identified various kinds of inflectional and derivational processes. At the same time, morphological processes in sign languages are subject to modality‐specific properties not found in spoken languages. The impact of the visual–spatial modality makes sign languages typologically more uniform than spoken languages. Three modality‐specific properties are especially relevant for the discussion of sign language morphology: (i) the simultaneous realization of morphosyntactic features; (ii) the interaction of morphology with phonology in the overt realization of these features; and (iii) the impact of gestures on morphological processes. This entry does not provide a comprehensive survey of all morphological phenomena attested in sign languages. It discusses instead three prominent and well‐investigated inflectional processes – agreement, classifiers and nominal plural – and shows how different generative theories (minimalist program, Distributed Morphology, and Optimality Theory) can account for the modality‐independent as well as for the modality‐specific properties of inflection in sign languages. Still, we also point out that classical generative theories developed for spoken languages probably need to be supplemented by a gestural component to account for the impact of gestures on sign language morphology. The main goal of this entry is to exemplify how far morphological processes in sign languages can contribute to a broader understanding of morphological typology and theory.
Multiple and Cumulative Exponence
Authors: Fenger Paula
Published: September 2023

This entry discusses various issues related to how features (meaning) can be expressed in morphemes (form). In particular, it focuses on multiple exponence, a one‐to‐many mapping between form and meaning, and the reverse pattern of cumulative exponence, a many‐to‐one mapping. The entry starts with describing what multiple and cumulative exponence is, and provides an overview of the types of patterns that are found cross‐linguistically. The remainder of the entry discusses two issues related to both types of exponence. The first issue relates to cumulative exponence, and where the formation of a single morpheme expressing multiple features should be modelled: in the syntax or the morphology. The main empirical focus is on cumulative patterns of subject and object agreement from a cross‐linguistic perspective, which provide a rich testing ground for where to form a cumulative marker. The last section focuses on several issues related to multiple exponence. In particular, the section focuses on what empirically should be regarded as multiple exponence, and what should be excluded, if we take into account several diagnostics regarding wordhood. Most theories of multiple exponence exclude cases where a single feature is expressed multiple times on different words (for example with negative concord), and only include cases where a single feature is expressed many times word‐internally. However, determining what counts as word‐internal multiple exponence becomes more difficult in languages where wordhood diagnostics are divergent, which then raises questions on what the empirical landscape of multiple exponence might look like.
Multiscale spatial relationship‐based model for predicting bladder wall dose in pelvic radiotherapy
Authors: Gao Xiang , Ge Lei , Gao Junfeng , Cao Zheng
Published: September 2023

Purpose

This research aimed to develop a prediction model to assess bladder wall dosimetry during radiotherapy for patients with pelvic tumors, thereby facilitating the refinement and evaluation of radiotherapy treatment plans to mitigate bladder toxicity.

Methods

Radiotherapy treatment plans of 49 rectal cancer patients and 45 gynecologic cancer patients were collected, and multiple linear regression analyses were used to generate prediction models for bladder wall dose parameters (, ). These models were based on the multiscale spatial relationship between the planning target volume (PTV) and the bladder or bladder wall. The proportion of bladder or bladder wall volume overlapped by the different distance expansions of the PTV was used as an indicator of the multiscale spatial relationship. The accuracy of these models was verified in a cohort of 12 new patients, with further refinement of radiotherapy treatment plans using the predicted values as optimization parameters. Model accuracy was assessed using root mean square error (RMSE) and mean percentage error (MPE).

Results

Models derived from individual disease data outperformed those derived from combined datasets. Predicted bladder wall dose parameters were accurate, with the majority of initial calculated values for new patients falling within the 95% confidence interval of the model predictions. There was a robust correlation between the predicted and actual dose metrics, with a correlation coefficient of 0.943. Using the predicted values to optimize treatment plans significantly reduced bladder wall dose (p0.001), with bladder wall and decreasing by 2.27±0.80 Gy (5.8%±1.8%) and 2.96±2.05 cm3 (7.9%±5.4%), respectively.

Conclusion

The formulated prediction model provides a valuable tool for predicting and minimizing bladder wall dose and for optimizing and evaluating radiotherapy treatment plans for pelvic tumor patients. This approach holds promise for reducing bladder toxicity and potentially improving patient outcomes.