bluuebunny/crossref_metadata_2025 huggingface dataset:
CTNND1 affects trophoblast proliferation and specification during human embryo implantation
Authors: Qin Jiaying , Lv Bo , Yao Yao , Han Xuan , Xue Zhigang , Lin Chao-Po , Xue Jinfeng , Ji Yazhong
Published: November 2024

The placenta, serving as the crucial link between maternal and infant, plays a pivotal role in maintaining a healthy pregnancy. Placental dysplasia can lead to various complications, underscoring the importance of understanding trophoblast lineage development. During peri-implantation, the trophectoderm undergoes differentiation into cytotrophoblast, syncytiotrophoblast, and extravillous trophoblast. However, the specification and regulation of human trophoblast lineage during embryo implantation, particularly in the peri-implantation phase, remain to be explored. In this study, we employed a co-culture model of human endometrial cells and native embryos and analyzed the single-cell transcriptomic data of 491 human embryonic trophoblasts during E6 to E10 to identify the key regulatory factors and the lineage differentiation process during peri-implantation. Our data identified four cell subpopulations during the implantation, including a specific transitional state toward the differentiation in which the CTNND1, one crucial component of Wnt signaling pathway activated by cadherins, acted as a crucial factor. Knockdown of CTNND1 impacted the proliferative capacity of human trophoblast stem cells, leading to early extravillous trophoblast-like differentiation. Intriguingly, ablation of CTNND1 compromised the terminal differentiation of human trophoblast stem cells toward syncytiotrophoblast or extravillous trophoblast in vitro. These findings contribute valuable insights into trophoblast lineage dynamics and offer a reference for research on placental-related diseases.
Developmental programming: preconceptional and gestational exposure of sheep to biosolids on offspring ovarian dynamics
Authors: Halloran Katherine M , Zhou Yiran , Bellingham Michelle , Lea Richard G , Evans Neil P , Sinclair Kevin D , Smith Peter , Padmanabhan Vasantha
Published: November 2024

Developmental exposure to environmental chemicals perturbs establishment and maintenance of the ovarian reserve across the reproductive lifetime, leading to premature follicle depletion and ovarian aging. Considering humans are exposed to a complex mixture of environmental chemicals, real-life models assessing their cumulative impact on the ovarian reserve are needed. Biosolids are a source of a real-life mixture of environmental chemicals. While earlier studies demonstrated that grazing pregnant sheep on biosolids-treated pastures did not influence establishment of the ovarian reserve in fetal life, its impact on subsequent depletion of ovarian reserve during reproductive life of offspring is unknown. We hypothesized that developmental exposure to biosolids accelerates depletion of ovarian reserve. Ovaries were collected from F1 juveniles (9.5 weeks) and adults (2.5 years) born to F0 ewes grazed on control inorganic fertilizer pastures or biosolids-treated pastures from before conception and throughout gestation. The impact on follicular density, activation rate, and anti-Müllerian hormone (mediator of activation) expression by immunohistochemistry was determined. Activation rate was increased in F1 biosolids-treated pastures juveniles with a corresponding reduction in primordial follicle density. In contrast, activation rate and ovarian reserve were similar between control and F1 biosolids-treated pastures adults. The density of anti-Müllerian hormone-positive antral follicles was lower in biosolids-treated pastures juveniles, whereas anti-Müllerian hormone expression tended to be higher in antral follicles of biosolids-treated pastures adults, consistent with the changes in the ovarian reserve. These findings of detrimental effects of developmental exposure to biosolids during juvenile life that normalizes in adults is supportive of a shift in activation rate likely related to peripubertal hormonal changes.
Fertility and early embryonic development in a CD46-edited Gir heifer with reduced susceptibility to BVDV
Authors: Snider Alexandria P , Workman Aspen M , Heaton Michael P , Vander Ley Brian L , Krueger Alexandria C , Sonstegard Tad S
Published: November 2024

Bovine viral diarrhea virus (BVDV) infection during pregnancy is a significant contributor to reproductive failures in cattle. The bovine receptor for BVDV (CD46) was previously edited with a six amino acid substitution (G82QVLAL to A82LPTFS) and shown to have significantly reduced BVDV susceptibility in a Gir heifer calf. Since a role for CD46 has been proposed in mammalian fertilization, our objective was to assess the edited heifer’s fertilization rates, early embryonic development, and germline transmission conformation of the edit. Cumulus oocyte complexes were collected from the edited heifer and unedited females, fertilized with semen from an unedited bull and cultured until the blastocyst stage. Ultrasound examinations and serum progesterone concentration were also monitored to confirm estrous cyclicity in the CD46-edited heifer. Estrous cyclicity was normal with visualization of a corpus luteum and elevated progesterone concentrations. Fertilization rates and blastocyst development were not different in oocytes from edited and unedited controls. Genome sequence analysis of blastocysts confirmed germline transmission of either edited allele from the heifer. Subsequently, the CD46-edited heifer was artificially inseminated with semen from an unedited Gir bull and fertility status was confirmed with a diagnosed conception at Day 35 of gestation. Thus, a six amino acid substitution in CD46 did not negatively affect fertilization of edited oocytes or early embryonic development when fertilized with semen from an unedited bull. An edited bull is still needed to similarly evaluate reproductive function of sperm cells carrying this CD46 edit.
Exosomal ncRNAs in reproductive cancers
Authors: Kowalczyk Alicja , Wrzecińska Marcjanna , Gałęska Elżbieta , Czerniawska-Piątkowska Ewa , Camiña Mercedes , Araujo Jose P , Dobrzański Zbigniew
Published: November 2024

Extracellular vesicles, particularly exosomes, play a pivotal role in the cellular mechanisms underlying cancer. This review explores the various functions of exosomes in the progression, growth, and metastasis of cancers affecting the male and female reproductive systems. Exosomes are identified as key mediators in intercellular communication, capable of transferring bioactive molecules such as microRNAs, proteins, and other nucleic acids that influence cancer cell behavior and tumor microenvironment interactions. It has been shown that non-coding RNAs transported by exosomes play an important role in tumor growth processes. Significant molecules that may serve as biomarkers in the development and progression of male reproductive cancers include miR-125a-5p, miR-21, miR-375, the miR-371 ~ 373 cluster, and miR-145-5p. For female reproductive cancers, significant microRNAs include miR-26a-5p, miR-148b, miR-205, and miRNA-423-3p. This review highlights the potential of these noncoding RNAs as biomarkers and prognostics in tumor diagnostics. Understanding the diverse roles of exosomes may hold promise for developing new therapeutic strategies and improving treatment outcomes for cancer patients.
Two-directional trafficking of the IFT25 protein in the developing mouse sperm flagella
Authors: Li Wei , Niu Changmin , Yap Yi Tian , Li Tao , Zheng Cheng , Goswami Mariska , Kandiraju Sanjana , Dhikhirullahi Opeyemi , Xu Jie , Zhang Jifeng , Kelly Christopher V , Zhang Zhibing
Published: November 2024

Intraflagellar transport 25 is a component of the intraflagellar transport 25-B complex. In mice, even though this intraflagellar transport component is not required for cilia formation in somatic cells, it is essential for sperm formation. However, the intracellular localization of this protein in male germ cells is not known given no reliable antibodies are available for histologic studies, and the dynamic trafficking in the developing sperm flagella is not clear. To examine localization of the protein in male germ cells and further investigate the mechanism of intraflagellar transport in sperm formation, particularly to look into the dynamic trafficking of the protein, we generated a mouse intraflagellar transport 25–green fluorescent protein knock-in mouse model using the clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeats associated protein 9 system, with the mouse intraflagellar transport 25 protein fused with a green fluorescent protein tag in the C-terminus. Three independent lines were analyzed. Western blotting using both anti-intraflagellar transport 25 and anti-green fluorescent protein antibodies showed that the intraflagellar transport 25–green fluorescent protein fusion protein was highly abundant only in the testis, which is consistent with the endogenous intraflagellar transport 25 protein. Examination of localization of the intraflagellar transport 25–green fluorescent protein in isolated germ cells revealed that the fusion protein was present in the cytoplasm of spermatocytes and round spermatids and a strong signal was present in the developing sperm flagellar. The homozygous knock-in mice had normal spermatogenesis, fertility and sperm parameters. Diffusion analysis of intraflagellar transport 25 within the developing flagellar revealed the presence of both mobile and immobile fractions as revealed by fluorescence recovery after photobleaching. Kymograph and fluorescence recovery after photobleaching analyses demonstrate the transport of intraflagellar transport 25–green fluorescent protein within the developing tail demonstrate no apparent preference for trafficking toward and away from the cell body. The speed of trafficking depends on the stage of sperm development, ranging from highly mobile unrestricted diffusion initially, mobile punctate structures in developing sperm, and immobile punctate structures in mature sperm. Our studies demonstrate that mouse intraflagellar transport 25 travels along the developing sperm flagella in two directions that might be essential for functional sperm formation.
Predictive value of residual active histologic lesions on renal flare in lupus nephritis patients with clinical remission
Authors: Hou Jinhua , Liang Dandan , Quan Songxia , Liu Zhangsuo , Liu Zhihong
Published: November 2024

Background

Renal flare in lupus nephritis (LN) is a crucial contributing factor to poor kidney outcomes. This study aimed at evaluating the predictive value of residual active histologic lesions on renal flare in proliferative LN patients with clinical remission.

Methods

We retrospectively enrolled LN patients with class III/IV ± V (biopsy 1) who had undergone a protocol repeat biopsy (biopsy 2) at 7.3 (IQR: 6.5, 8.4) months after induction therapy with clinical remission and experienced renal flare within 3 years or had been followed up for at least 3 years without renal flare after biopsy 2 with maintenance therapy from two kidney units in China.

Results

A total of 114 eligible patients were included, 28 (24.6%) of whom developed a renal flare. Activity index (AI) at biopsy 2 was significantly associated with LN flare (P < .0001). If AI > 1, the OR for LN flare was 23.1 (95%CI, 5.1–103.8, P < .001). For patients with partial clinical remission compared with those with complete clinical remission, the OR for LN flare was 3.0 (95%CI: 1.1–8.3, P = .029). Multivariate analysis showed that anti-dsDNA positivity, presence of cellular/fibrocellular crescent, and endocapillary hypercellularity at biopsy 2 were independent risk factors for LN flare. When residual active histologic lesions were added to clinical variables, the area under the curve of the prediction model for LN flare significantly increased and the misclassification rate significantly decreased.

Conclusions

Renal flare in LN patients with clinical remission is strongly associated with the residual active histologic lesions.
The sedoheptulose kinase CARKL controls T-cell cytokine outputs and migration by promoting metabolic reprogramming
Authors: Certo Michelangelo , Niven Jennifer , Haas Robert , Rudzinska Paula , Smith Joanne , Cucchi Danilo , Hombrebueno Jose R , Mauro Claudio
Published: November 2024

Background

Immunometabolism is a crucial determinant of immune cell function, influencing cellular activation and differentiation through metabolic pathways. The intricate interplay between metabolism and immune responses is highlighted by the distinct metabolic programs utilized by immune cells to support their functions. Of particular interest is the pentose phosphate pathway (PPP), a key metabolic pathway branching out of glycolysis that plays a pivotal role in generating NADPH and pentose sugars crucial for antioxidant defense and biosynthesis. The sedoheptulose kinase Carbohydrate Kinase-like protein (CARKL), an enzyme involved in the PPP, emerges as a critical regulator of cell metabolism and was previously shown to play a role in macrophage function.

Methods

This study delves into the impact of CARKL expression on T-cell functionality, revealing dynamic alterations in response to cellular activation. Notably, CARKL overexpression leads to significant metabolic shifts in T cells, affecting mitochondrial respiration, ATP production, and inflammatory cytokine profiles. Furthermore, CARKL modulation influences T-cell motility by regulating chemokine receptor expression, particularly compromising CXCR3 expression and impairing T-cell migration in response to specific chemokine signals.

Conclusions

These findings underscore the multifaceted role of CARKL as a metabolic regulator shaping T-cell responses. Overall, our data reveal the complex regulatory mechanisms orchestrated by CARKL in T-cell function, with implications for immune regulation. Further exploration of the molecular interactions between CARKL and metabolic reprogramming in T cells could provide valuable insights into immune regulation and potential therapeutic strategies.
Fertility Beliefs and Outcomes: the Role of Relationship Status and Attractiveness
Authors: Gong Yifan , Skura Tyler , Stinebrickner Ralph , Stinebrickner Todd
Published: November 2024

Unique data from the Berea Panel Study provide new evidence about fertility outcomes before age thirty and beliefs about these outcomes elicited soon after college graduation. Comparing outcomes and beliefs yields a measure of belief accuracy. Individuals who are unmarried and not in relationships at age twenty-four are extremely optimistic about the probability of having children, while married individuals have very accurate beliefs. Novel attractiveness measures are central for understanding fertility beliefs and outcomes for females, but not for males. Marriage is a mechanism that is relevant for understanding differences in beliefs, outcomes and misperceptions across relationship and attractiveness groups.
Support for a ban on characterizing flavours in cigarettes in the UK: a longitudinal online survey
Authors: Moodie Crawford , Best Catherine , Jones Daniel
Published: November 2024

Most European countries have banned flavoured cigarettes. No study has explored whether support for such a ban changes post-implementation. In the UK, a menthol cigarette ban came into force in May 2020. A longitudinal survey in the UK with adult smokers and ex-smokers explored support for the ban in 2019 (N = 3175) and 2022 (N = 3047). Support increased from 2019 (pre-ban) to 2022 (post-ban) for all participants (18.1% to 35.0%), with increased support evident for flavour cigarette smokers (20.7% to 34.5%), non-flavour cigarette smokers (13.5% to 18.1%), and ex-smokers (24.4% to 50.8%). Increased support for tobacco-related policies helps regulators defend policy decisions.
Weak integration allows novel fin shapes and spurs locomotor diversity in reef fishes
Authors: Satterfield Darien R , Yin Bernice , Jung Sky , Hodges-Lisk Samantha , Wainwright Dylan K , Burns Michael D , Wainwright Peter C
Published: November 2024

In functional systems composed of many traits, selection for specialized function can induce trait evolution by acting directly on individual components within the system, or indirectly through networks of trait integration. However, strong integration can also hinder diversification into regions of trait space that are not aligned with axes of covariation among traits. Thus, non-independence among traits may limit functional expansion. We explore this dynamic in the evolution of fin shapes in 106 species from 38 families of coral reef fishes, a polyphyletic assemblage that shows exceptional diversity in locomotor function. Despite expectations of a strong match between form and function, we find subtantial fin shape disparity across species that share a swimming mode. The evolution of fin shape is weakly integrated across the four functionally dominant fins in swimming and integration is weakened as derived swimming modes evolve. The weak integration among fins in the ancestral locomotor condition provides a primary axis of diversification while allowing for off-axis diversification via independent trait responses to selection. However, the evolution of novel locomotor modes coincides with a loss of integration among fins. Our study highlights the need for additional work on the functional consequences of fin shape in fishes.
A first look at the genome structure of hexaploid “Mitcham” peppermint (Mentha × piperita L.)
Authors: Talbot Samuel C , Pandelova Iovanna , Lange Bernd Markus , Vining Kelly J
Published: November 2024

Peppermint, Mentha × piperita L., is a hexaploid (2n = 6x = 72) and the predominant cultivar of commercial mint oil production in the US. This cultivar is threatened because of high susceptibility to the fungal disease verticillium wilt, caused by Verticillium dahliae. This report details the first draft polyploid chromosome-level genome assembly for this mint species. The “Mitcham” genome resource will broaden comparative studies of disease resistance, essential oil biosynthesis, and hybridization events within the genus Mentha. It will also be a valuable contribution to the body of phylogenetic studies involving Mentha and other genera that contain species with varying ploidy levels.
Risk of neurologic events after surgery for mitral valve insufficiency and concomitant Cox-maze IV procedure for atrial fibrillation. A nationwide register-based study
Authors: Albåge Anders , Vanky Farkas , Boano Gabriella , Holmgren Anders , Jidéus Lena , Johansson Birgitta , Kennebäck Göran , Nozohoor Shahab , Scherstén Henrik , Sjögren Johan , Wickbom Anders , Ivert Torbjörn
Published: November 2024

OBJECTIVES

Analysis of the long-term risks of ischaemic stroke and cerebral bleeding in patients with atrial fibrillation after mitral valve surgery and concomitant Cox-maze IV procedure.

METHODS

In total, 397 patients with symptomatic degenerative mitral valve insuffciency and atrial fibrillation, underwent mitral valve surgery and Cox-maze IV in Sweden between 2009 and 2017. In this retrospective nationwide analysis, patients were followed in national patient registers until 30 September 2022.

RESULTS

There were 4 deaths within 30 days (1.0%). Mean follow-up was 8.7 (0.1–13.4) years. Survival without ischaemic stroke or cerebral haemorrhage at 5 and 10 years were 90% and 74%, respectively. Nineteen patients experienced an ischaemic stroke, of which 4 were fatal. Five of 34 patients (14.7%) with a history of stroke preoperatively experienced ischaemic stroke during follow-up. The linearized rate of ischaemic stroke per patient-year was 0.6% and was similar regardless of left atrial appendage closure during surgery or whether a mechanical valve was inserted. The observed ischaemic stroke rate was lower than the predicted rate for all CHA2DS2-VASc score groups. Fourteen patients suffered cerebral bleeding, of which 3 were fatal. Patients who experienced cerebral bleeding were older and had higher mechanical valve implantation rate than those without cerebral bleeding.

CONCLUSIONS

Surgery for mitral valve insufficiency and concomitant Cox-maze IV can be performed with low perioperative risk. There is a low continuing risk of stroke long-term postoperatively that correlates with a higher CHA2DS2-VASc score. Patients with preoperative stroke are at increased risk of postoperative stroke despite atrial fibrillation surgery.
Palovarotene (Sohonos), a synthetic retinoid for reducing new heterotopic ossification in fibrodysplasia ossificans progressiva: history, present, and future
Authors: Hsiao Edward C , Pacifici Maurizio
Published: November 2024

Retinoids are metabolic derivatives of vitamin A and play crucial roles in the regulation of various tissues and organs during prenatal and postnatal development. Active retinoids, like all-trans-retinoic acid, are synthesized in the cytoplasm and subsequently interact with nuclear retinoic acid receptors (RARα, RARβ, and RARγ) to enhance transcription of specific genes. In the absence of retinoids, RARs can still bind to response elements of target genes but repress their transcription. Chondrogenic cell differentiation and cartilage maturation in the growth plate require the absence of retinoid signaling and transcriptional repression by unliganded RARs. This led to the hypothesis that synthetic retinoid agonists may be pharmacological agents to inhibit those cellular processes and counter the excessive formation of cartilage and bone in conditions like heterotopic ossification (HO). HO can be instigated by diverse culprits including trauma, invasive surgeries, inflammatory disorders, or genetic conditions. One such genetic disease is fibrodysplasia ossificans progressiva (FOP), a rare disorder driven by activating mutations in the ACVR1 gene. Patients with FOP have severe and progressive HO formation in soft tissues, leading to extensive permanent loss of mobility and increased mortality. Synthetic retinoid agonists selective for RARα or RARγ showed efficacy against injury-induced and genetic HO in mouse models. The RARγ agonists showed the highest effectiveness, with palovarotene being selected for clinical trials in patients with FOP. Post hoc analyses of phase II and phase III clinical trials showed that palovarotene has significant disease-modifying effects for FOP, but with significant risks such as premature growth plate closure in some younger subjects. This review provides an overview of retinoid and RAR roles in skeletal development and discusses the identification of palovarotene as a potential FOP therapy, the clinical data supporting its regulatory approval in some countries, and the potential applications of this drug for other relevant disorders besides FOP.
CDC73 c.1155-3A>G is a pathogenic variant that causes aberrant splicing, disrupted parafibromin expression, and hyperparathyroidism-jaw tumor syndrome
Authors: Needleman Leor , Chun Nicolette , Sitaraman Sathvika , Tan Marilyn , Sellmeyer Deborah E , Kebebew Electron , Annes Justin P
Published: November 2024

Germline and somatic pathogenic variants in the CDC73 gene, encoding the nuclear protein parafibromin, increase the risk for parathyroid carcinoma and cause hereditary primary hyperparathyroidism (PHPT) syndromes known as familial isolated hyperparathyroidism (FIHP) and hyperparathyroidism-jaw tumor syndrome (HPT-JT). The identification of pathogenic germline variants in PHPT-susceptibility genes can influence surgical planning for parathyroidectomy, guide screening for potential syndromic manifestations, and identify/exonerate at-risk family members. Numerous types of pathogenic germline variants have been described for CDC73-related conditions, including deletion, truncating, missense, and splice site mutations. Here, we report identification of a non-coding germline CDC73 variant (CDC73 c.1155-3A > G), previously categorized as a variant of uncertain significance (VUS), in a family with HPT-JT. This variant, found in two family members with PHPT, altered CDC73 splicing in peripheral blood cells and disrupted parafibromin immunostaining in associated parathyroid adenomas, strongly evidencing its pathogenicity. Sestamibi scintigraphy yielded nondiagnostic localization results for both patients’ parathyroid adenomas, consistent with prior studies suggesting lower sensitivity for small or cystic lesions. Our findings demonstrate key aspects of CDC73-related disorders, highlight the diagnostic value of RNA testing, and exemplify the importance of obtaining a thorough, three-generational family history.
Fracture characteristics of human cortical bone influenced by the duration of in vitro glycation
Authors: Lin Mei-Chun , Sihota Praveer , Kolibová Sofie Dragoun , Fiedler Imke A K , Krug Johannes , Wölfel Eva M , Moritz Manuela , Riedner Maria , Ondruschka Benjamin , Citak Mustafa , Klebig Felix , von Brackel Felix N , Qwamizadeh Mahan , Jähn-Rickert Katharina , Busse Björn
Published: November 2024

Advanced glycation end products (AGEs) accumulate in various tissues, including bone, due to aging and conditions like diabetes mellitus. To investigate the effects of AGEs on bone material quality and biomechanical properties, an in vitro study utilizing human tibial cortex, sectioned into 90 beams, and randomly assigned to three mechanical test groups was performed. Each test group included ribose (c = 0.6 M) treatment at 7-, 14-, and 21-d, alongside control groups (n = 5 per group). Fluorescent AGE (fAGE) and carboxymethyl-lysine (CML) levels were assessed through fluorometric analysis and mass spectrometry, while bone matrix composition was characterized using Fourier-transform infrared and Raman spectroscopy. Mechanical properties were determined through nanoindentation and three-point bending tests on non-notched and notched specimens. The results showed significant increases in fAGEs levels at 7-, 14-, and 21-d compared to controls (119%, 311%, 404%; p = .008, p < .0001, p < .0001, respectively), CML levels also rose substantially compared to controls (383%, 503%, 647%, p < .0001, p < .0001, p < .0001, respectively). Analysis of bone matrix composition showed greater sugars/Amide I ratio at 21-d glycation compared to controls, 7-d, and 14-d (p = .001, .011, .006, respectively); and higher carbonate-to-phosphate ratios in the ribose treatment group compared with controls (p < .05) in the interstitial bone area. Mechanical testing of notched specimens exhibited a higher yield force, pre-yield toughness, and maximum force at 14-d glycation compared to controls and to both 7-d and 21-d glycation (p < .05). Nanoindentation showed that the hardness was lower at 7-d glycation compared to the controls and 21-d glycation (p < .05). In conclusion, the study found altered mechanical properties at 7 and 14 d of glycation, which then returned to control levels at 21 d, indicating a dynamic relationship between glycation duration and mechanical characteristics that deserves further exploration.
Unusual PHEX variants implicate uncommon genetic mechanisms for X-linked hypophosphatemic rickets
Authors: Alzoebie Lama , Li Dong , Wang Xiang , Weber David R , Levine Michael A
Published: November 2024

X-linked hypophosphatemic rickets (XLH), the most common form of hereditary rickets, is characterized by renal phosphate wasting and abnormal vitamin D metabolism due to elevated circulating levels of the phosphatonin fibroblast growth factor 23 (FGF23). Dominant inactivating variants of the phosphate regulating endopeptidase homolog, X-linked (PHEX), gene are present in patients with XLH, and more than half of affected patients carry de novo variants. We report on 3 families in whom affected members had highly unusual PHEX pathogenic variants. In 1 family we identified a previously described deep intronic PHEX variant (c.1768 + 173A>G) in the proband and her affected son. This variant is also near a previously reported PHEX variant (c.1768 + 177_1768 + 180dupGTAA) and is predicted to affect splicing by SpliceAI (delta score: 0.95) through creation of a new donor splice site. In a second proband we identified 2 pathogenic de novo and novel PHEX variants, c.2083delT (p.Ser695Profs*45) and c.2085delC (p.Tyr696Thrfs*44), that were present on different alleles, consistent with mosaicism for 3 PHEX alleles. The third proband also carried 2 PHEX variants (c.755 T>C [p.Phe252Ser] and c.759G>A [p.Met253Ile]), but in this case both variants were present on the same PHEX allele. These studies expand the molecular catalog of pathogenic PHEX variants in XLH and emphasize the importance of deep intronic sequencing and comprehensive family studies. Conventional approaches to genetic diagnosis may not be adequate to identify or characterize the disease-causing variants in the PHEX gene in some patients with likely XLH.
Elastic frequency controllable envelope inversion
Authors: Du Qiu , Gao Zhaoqi , Gao Jinghuai
Published: November 2024

Although elastic full waveform inversion is considered a high-resolution seismic inversion method, it is sensitive to the initial model. When the initial model lacks long-wavelength components, the inversion results may be inaccurate. This limitation frequently results in cycle-skipping during the inversion process. Elastic envelope inversion (EEI) is an effective way to build initial models as input for EFWI. However, EEI ignores the difference in sensitivity of different frequency data to the cycle-skipping problem, which limits its performance. This paper introduces the elastic frequency controllable envelope (EFCE), a novel type of envelope with frequency-selection characteristics tailored for elastic data. Moreover, to enhance the utilization of weak reflected information, a modified version of EFCE named residual-modification-aided EFCE (RMAEFCE) is proposed. Building on RMAEFCE, we define a novel objective function and subsequently propose an innovative EFWI approach called RMAEFCE inversion (RMAEFCEI), with the aim of building accurate long-wavelength velocity models that include both P-wave and S-wave. Numerical experiments carried out using the Marmousi model show that our approach markedly outperforms EEI, effectively mitigating the cycle-skipping issue. When employing the initial models established by RMAEFCEI, EFWI can output satisfactory final models. In addition, RMAEFCEI can build acceptable long-wavelength velocity models even with an inaccurate wavelet, indicating that it is more robust to wavelet error.
Management of honey bee (Hymenoptera: Apidae) colonies under yellow-legged hornet (Hymenoptera: Vespidae) pressure
Authors: Diéguez-Antón Ana , Rodríguez-Flores María Shantal , Ordoñez Dios María Esther , Bunker Sarah , Nave Anabela , Godinho Joana , Casaca João Diogo , Guedes Helena , Seijo María Carmen
Published: November 2024

The yellow-legged hornet, Vespa velutina nigrithorax du Buysson, 1905, is a common predator of the honey bee, Apis mellifera, Linnaeus. It has become an invasive species in several territories around the world, constituting a major threat to beekeeping in those areas. Management strategies are based on destroying the hornets’ nests, trapping adults, or physical interventions to protect honey bee colonies. However, there is a lack of information on how beekeepers should manage their colonies when the yellow-legged hornet is present. Here we present an overview of the life cycle and identification of the yellow-legged hornet, and common control methods used in apiaries. Moreover, we highlight the importance of management techniques for improving honey bee colony survival, including recommendations for beekeepers to achieve better colony health and strength. Essential for such management is close attention to colony food reserves and the provision of extra food when honey bee foraging is stopped by yellow-legged hornets predating foragers in front of the hive. Weak or diseased honey bee colonies succumb easily to the predator; therefore colony strength is key to survival. Although more research is needed to improve control strategies of this invasive species, this manuscript is a useful guide for honey bee colony management in invaded areas.
An experimental calculation method for stress intensity factors of three-dimensional surface cracks
Authors: Qi Cong , Pi Ai-guo
Published: November 2024

Stress intensity factors (SIFs) are important parameters for evaluating structural reliability. This work combines CT in situ uniaxial compression experiment to study the main crack propagation trajectories of the reactive powder concrete (RPC) specimens. The three-dimensional (3D) displacement fields of RPC specimens with 3D surface cracks were analyzed using a 3D digital image correlation (3D-DIC) method. The 3D-DIC method was used to calculate the 3D surface crack SIFs of RPC specimens at different inclination angles, and the influence of crack inclination angles on SIFs was analyzed. The study found that the distribution pattern of SIFs calculated by the 3D-DIC method is consistent with the results obtained by the numerical method.
Mucinous adenocarcinoma of the appendix presenting as acute appendicitis: a case report
Authors: Al Salkhadi Asham , Al Salkhadi Mohammad Ajwad , Hasan Ayham
Published: November 2024

Mucinous adenocarcinoma of the appendix (MAA) is a rare primary malignancy with an incidence of 0.01–0.2% and often presents as acute appendicitis. We present a case of a 61-year-old male who initially presented with right iliac fossa pain, worsening over 3 days, accompanied by appetite loss but no other symptoms. The patient’s history included a splenectomy and epilepsy. Physical examination and computed tomography scan suggested a picture of acute appendicitis. He underwent an emergency laparoscopic appendectomy that was converted to open right hemicolectomy due to the mass’s adherence to the cecum. The mass, at the cecum, originating from the appendix, measured 10 × 7 × 7 cm. Pathology confirmed a moderately differentiated MAA. Accurate diagnosis requires a combination of imaging and histopathology. The patient recovered well and was discharged on Day 6 postoperatively. We aim to highlight the importance of distinguishing MAA from acute appendicitis and the need for careful preoperative evaluation.
Selective recognition of RNA G-quadruplex in vitro and in cells by L-aptamer–D-oligonucleotide conjugate
Authors: Zhao Haizhou , Lau Hill Lam , Zhang Kun , Kwok Chun Kit
Published: November 2024

RNA Guanine-quadruplexes (rG4s) are important nucleic acid structures that govern vital biological processes. Although numerous tools have been developed to target rG4s, few specific tools are capable of discerning individual rG4 of interest. Herein, we design and synthesize the first L-aptamer–antisense oligonucleotide (ASO) conjugate, L-Apt.4–1c-ASO15nt(APP), with a focus on recognizing the amyloid precursor protein (APP) rG4 region as an example. The L-aptamer module binds with the rG4 structure, whereas ASO hybridizes with flanking sequences. Together, these two modules enhance the precise recognition of APP rG4. We demonstrate that the L-Apt.4–1c-ASO15nt(APP) conjugate can interact with the APP rG4 region with sub-nanomolar binding affinity, and distinguish APP rG4 from other G4s and non-G4s in vitro and in cells. We also show that L-Apt.4–1c-ASO15nt(APP) can inhibit APP protein expression. Notably, we investigate the inhibitory mechanism of this newly developed tool, and reveal that it controls gene expression by hindering DHX36 protein from unraveling the rG4, as well as by promoting translational inhibition and RNase H-mediated mRNA knockdown activity. Our novel L-aptamer–ASO conjugate tool not only enables the specific recognition of rG4 region of interest, but also allows efficient gene control via targeting rG4-containing transcripts in cells.
Neuroimmune-competent human brain organoid model of diffuse midline glioma
Authors: Sarnow Katharina , Majercak Emma , Qurbonov Qurbonali , Cruzeiro Gustavo A V , Jeong Daeun , Haque Ishraq A , Khalil Andrew , Baird Lissa C , Filbin Mariella G , Tang Xin
Published: November 2024

Background

Pediatric high-grade gliomas, such as diffuse midline glioma (DMG), have a poor prognosis and lack curative treatments. Current research models of DMG primarily rely on human DMG cell lines cultured in vitro or xenografted into the brains of immunodeficient mice. However, these models are insufficient to recapitulate the complex cell-cell interactions between DMG and the tumor-immune microenvironment (TIME), therefore fall short of accurately reflecting how efficacious therapeutic agents or combinations will be in the clinical setting.

Methods

To address these challenges, we developed a neuroimmune-competent brain/tumor fusion organoid model system consisting entirely of human cells to investigate the interactions between DMG cells and the primary innate immune cells of the brain, microglia, in the TIME at both cellular and subcellular levels. We generated microglia-containing brain organoids (MiCBOs) that carry morphologically mature, motile microglia and multiple subtypes of neurons to mimic the brain tumor microenvironment. These organoids were then fused with H3K27M mutant, TP53P27R/K132R DMG tumor spheroids to create the MiCBO-tumor fusion (MiCBO-TF) model.

Results

We utilized live imaging methods to simultaneously track the mobility of microglial cell bodies and the motility of their process, as well as the behavior of tumor cells within a human brain tissue environment. Our MiCBO-TF model faithfully recapitulated the diffuse infiltration pattern of DMG into brain tissue and revealed that microglial mobility and interactions with tumor cells are highly influenced by external factors and the surrounding tissue environment.

Conclusions

The MiCBO-TF model represents a powerful platform for both mechanistic investigations and the development of precision medicine approaches for DMG.
Introduction: Towards a Multifaceted History of Archaeology
Authors: Díaz-Andreu Margarita , Coltofean Laura
Published: November 2024

This introductory chapter sets out the basis for the handbook and for a new history of archaeology, while at the same time tracing the major lines behind the book. It first provides an overview of how historians of archaeology have argued for the need to know about the discipline’s past. The chapter then summarizes major methods and methodologies used by historians of archaeology. This summary includes a survey of works written by archaeologists and other learned individuals, the search for distinct types of documents in archives, and oral history. Finally, the chapter introduces the concept of this volume, its background, and its rationale, before presenting an overview of each of the parts and chapters into which the handbook has been subdivided.
A History of Archaeology and the Hard Sciences
Authors: Delley Géraldine
Published: November 2024

“Hard sciences” is a popular expression that appeared around the 1960s and usually includes the natural (biology, geology, physics, chemistry) and formal (mathematics, computer) sciences. The natural and hard sciences have occupied an increasingly important place in archaeology since the 1960s, to the extent that some of them—such as biology with DNA and genetics research—have felt it legitimate to appropriate archaeological topics. For their part, archaeologists have begun to speak of a “natural science turn.” The history of these interactions, however, cannot be summed up by the debates that took place in the second half of the twentieth century. Their origins go back to the nineteenth century, when archaeology—especially prehistoric archaeology—emerged as a discipline focusing on the history of humankind as both a natural and a cultural phenomenon. This chapter explores the interactions between archaeology and the hard and natural sciences from the nineteenth to the twenty-first centuries, taking central Europe as a case study. It follows four directions: the definition of disciplinary boundaries, the heuristic expectations of archaeologists regarding the natural and hard sciences, the political dimension related to the development of such collaborations, and the complexity of the epistemological issues emerging from those intensive interactions.
Archaeology as Leisure
Authors: Díaz-Andreu Margarita
Published: November 2024

This chapter offers a critical overview of the history of archaeological tourism, looking at its precedents and development over the last two centuries. The reasons that led first the wealthy and then the public to take an interest in antiquities are explained, as well as why governments were interested in promoting it. The chapter assesses practices and institutions that support this leisure activity, looking at a wide range of elements—from museums, archaeological sites open to the public, and events held in them to material culture, such as guidebooks and souvenirs. The chapter explains geographical expansion of archaeological tourism as well as its political, social, and economic context. In the most recent period, issues under discussion include gentrification, mass tourism, local communities, Indigenous rights, and the impact of neoliberalism on archaeological tourism.
Archives, Oral History, and Histories of Archaeology
Authors: Wolfhechel Jensen Ola
Published: November 2024

The goal of this chapter is to critically assess the nature of archives and oral history, how they are created, their possibilities and restraints in historical studies, and to present examples of theories and methods on how to use and evaluate them. The chapter also includes examples of the use of archives and oral histories in contemporary research, possible strategies for enrolling them in writing histories of archaeology in the future, and reflections on the impact of the digital development that we have witnessed in recent decades. Most information concerning archaeological achievements is not published but stored in various archives and in the minds of archaeologists as personal or collective memories. As the subject of archaeology’s history has become more specialized, the awareness of the potential of these sources has increased. This specialization has revealed long-forgotten and even neglected archaeologists, ideas, and practices and triggered interest in new issues that are important for our understanding of the discipline’s past.
The Origins and Growth of Archaeology and Education
Authors: Corbishley Mike
Published: November 2024

This chapter discusses archaeology in education. Archaeology in education is more than just about interesting the younger generation in digging and in visiting important sites and monuments across the world. It must start with the ways in which societies view the importance of the remains of their past. Archaeologists and historians, across the world, try to influence their own governments to protect their physical heritage and to try to change attitudes about the past held by the general public. Influencing governments is an important method of instilling in school students and their teachers a sense of respect for the past and of responsibility for preserving it and learning about it. This often takes the form of encouraging the inclusion of archaeology and the use of evidence-based teaching in the curriculum, especially but not exclusively in the history curriculum. Archaeological and heritage organizations and museums have been in the forefront of providing information and activities for the public and teaching for adults.
Sacred Archaeology in the Nineteenth and Twentieth Century
Authors: Effros Bonnie
Published: November 2024

This chapter analyzes the deployment of archaeology to reclaim, verify, or dismiss biblical or subsequent religious phenomena in Judeo-Christian faith traditions. Although scholars have studied the history of archaeology against the backdrop of nationalism, imperialism, and colonialism, the role of religious beliefs has not received sufficient attention. The chapter explores how archaeological activities have helped control the sacred through the discovery of holy places or objects, confirm or supplement religious narratives found in biblical, canonical, and hagiographical works, and stake claims to historical territories by identifying places described in religious texts. Although this reinvigoration of religious orthodoxy often accompanied nationalistic, imperial, and colonial initiatives before World War II, it became more isolated from scientific archaeology in the postwar period. Today, heritage sites are among the most promising spaces for meaningful dialogue between spiritual belief and archaeological practice. While the current chapter is limited to Judeo-Christian traditions, these ideas have relevance to other religions.
Archaeology, Nationalism, Imperialism, Colonialism, and the Postcolonial Turn
Authors: Díaz-Andreu Margarita
Published: November 2024

This chapter explores the relationship between professional archaeology and nationalism as a political ideology from the late eighteenth century up to the present. The influence on the discipline of the changes in nationalism throughout the nineteenth century is assessed, while also paying attention to how archaeologists contributed to the continuous remodeling of the nationalist discourse. The expansion of the chronological focus of archaeology from classical archaeology to the archaeology of other periods, such as prehistory and the Middle Ages, is examined with reference to the changes taking place in nationalism. The implications of the connection between nationalism and new imperialism for the study of past remains are also explored, looking at how archaeology became a tool of imperialism in the formal, informal, and internal colonies. The chapter then moves on to analyze the profound effects of decolonization on the study of the past in many parts of the world from World War II to the present day.
The History of Conflict Archaeology
Authors: McMillan Sophie M. , Pollard Tony
Published: November 2024

The chapter acknowledges the wide range of themes and approaches that sit beneath the overarching umbrella of conflict archaeology. These include battlefield archaeology, which, as this chapter proposes, is a distinct subfield of conflict archaeology rather than a less nuanced precursor to conflict archaeology as some practitioners have implied. Over recent decades, conflict archaeology has been among the fastest growing subdisciplines within the wider archaeological academy. It does however have a deeper history, and this chapter traces its evolution in Europe and the United States over the last century and more, identifying key landmarks and providing summary case studies where appropriate. The Western focus of the chapter is primarily due to space constraints; wherever possible, references have been made to non-Western contributions.
“Genius,” “Precursors,” and “Great (White) Men” in the History of Archaeology
Authors: Moro Abadía Oscar , Lewis-Sing Emma
Published: November 2024

This chapter refers to a number of critical works on the concepts of “genius,” “precursor,” and “great (white) men.” In the past, archaeologists regarded the history of their science as a story of the heroic discoverers who had greatly contributed to the understanding of the past. As a result, disciplinary historiographical accounts adopted the form of discovery stories. The practice of celebrating past glories of science has a number of pernicious effects for the history of science. In particular, historians have typically overemphasized the importance of the so-called precursors and overlooked the contribution of those scholars who have been excluded from the Pantheon of great scientists. To illustrate this problem, this chapter focuses on André Leroi-Gourhan and Annette Laming-Emperaire. Both made significant contributions to the study of cave art. Yet, while Leroi-Gourhan is celebrated as a “pioneer” of structuralism, Laming-Emperaire’s contributions are typically overlooked in archaeological histories.