Node features of chromosome structure networks and their connections to genome annotation.

The 3D conformations of chromosomes can encode biological significance, and the implications of such structures have been increasingly appreciated recently. Certain chromosome structural features, such as A/B compartmentalization, are frequently extracted from Hi-C pairwise genome contact information (physical association between different regions of the genome) and compared with linear annotations of the genome, such as histone modifications and lamina association. We investigate how additional properties of chromosome structure can be deduced using an abstract graph representation of the contact heatmap, and describe specific network properties that can have a strong connection with some of these biological annotations. We constructed chromosome structure networks (CSNs) from bulk Hi-C data and calculated a set of site-resolved (node-based) network properties. These properties are useful for characterizing certain aspects of chromosomal structure. We examined the ability of network properties to differentiate several scenarios, such as haploid vs diploid cells, partially inverted nuclei vs conventional architecture, depletion of chromosome architectural proteins, and structural changes during cell development. We also examined the connection between network properties and a series of other linear annotations, such as histone modifications and chromatin states including poised promoter and enhancer labels. We found that semi-local network properties exhibit greater capability in characterizing genome annotations compared to diffusive or ultra-local node features. For example, the local square clustering coefficient can be a strong classifier of lamina-associated domains. We demonstrated that network properties can be useful for highlighting large-scale chromosome structure differences that emerge in different biological situations.

Life outside the LINC complex - Do SUN proteins have LINC-independent functions?

Sad1 and UNC84 (SUN) and Klarsicht, ANC-1, and Syne homology (KASH) proteins interact at the nuclear periphery to form the linker of nucleoskeleton and cytoskeleton (LINC) complex, spanning the nuclear envelope (NE) and connecting the cytoskeleton with the nuclear interior. It is now well-documented that several cellular functions depend on LINC complex formation, including cell differentiation and migration. Intriguingly, recent studies suggest that SUN proteins participate in cellular processes where their association with KASH proteins may not be required. Building on this recent research, we elaborate on the hypothesis that SUN proteins may perform LINC-independent functions and discuss the modalities that may allow SUN proteins to function at the INM when they are not forming LINC complex.

Knockdown of LAP2α inhibits adipogenesis of human adipose-derived stem cells and ameliorates high-fat diet-induced obesity.

Adipogenesis, a pivotal cellular process involving the differentiation of mesenchymal stem cells (MSCs) to mature adipocytes, plays a significant role in various physiological functions. Dysregulation of adipogenesis is implicated in conditions such as obesity. However, the complete molecular understanding of adipogenesis remains elusive. This study aimed to uncover the novel role of lamina-associated polypeptide 2 alpha (LAP2α) in human adipose-derived stem cells (hASCs) adipogenesis and its impact on high-fat diet (HFD)-induced obesity and associated metabolic disturbances. LAP2α expression was assessed during the adipogenic differentiation of hASCs using RT-qPCR and western blotting. The functional role of LAP2α in adipogenesis was explored both in vitro and in vivo through loss- and gain-of-function studies. Moreover, mice with HFD-induced obesity received lentivirus injection to assess the effect of LAP2α knockdown on fat accumulation. Molecular mechanisms underlying LAP2α in adipogenic differentiation were investigated using RT-qPCR, Western blotting, immunofluorescence staining, and Oil Red O staining. LAP2α expression was upregulated during hASCs adipogenic differentiation. LAP2α knockdown hindered adipogenesis, while LAP2α overexpression promoted adipogenic differentiation. Notably, LAP2α deficiency resisted HFD-induced obesity, improved glucose intolerance, mitigated insulin resistance, and prevented fatty liver development. Mechanistically, LAP2α knockdown attenuated signal transducer and activator of transcription 3 (STAT3) activation by reducing the protein level of phosphorylated STAT3. A STAT3 activator (Colivelin) counteracted the negative impact of LAP2α deficiency on hASCs adipogenic differentiation. Taken together, our current study established LAP2α as a crucial regulator of hASCs adipogenic differentiation, unveiling a new therapeutic target for obesity prevention.

Management of Extensive Buccosinusal and Bucconasal Communications After Maxillary Giant Cell Tumor Resection Using the Cortical Bone Lamina Technique: A Case Report.

Giant cell tumors are rare, locally aggressive non-odontogenic osteolytic tumors associated with high rates of local recurrence. Treatment modalities are subject to considerable controversy, with successful outcomes hinging on achieving complete tumor elimination through thorough curettage. A 78-year-old male referred in December 2023 for a persistent mucosal lesion in the right maxilla under a removable denture. Clinical examination revealed a well-defined erythematous nodular lesion measuring approximately 3 cm along its long axis, localized on ridge quadrant 1. Biopsy confirmed the diagnosis of giant cell tumor. Although complete resection with healthy margins may be justified for aggressive lesions, it often results in significant morbidity and requires immediate defect reconstruction. Some studies suggest favorable long-term outcomes with guided bone regeneration (GBR). The bone lamina technique uses a xenogeneic cortical bone membrane to maintain space and promote bone healing. This surgical approach promotes bone healing through the mechanical support and biological properties of the lamina. The purpose of this case report is to evaluate the efficacy of the bone lamina technique and its role in managing complications following giant cell tumor resection.

CRWN nuclear lamina components maintain the H3K27me3 landscape and promote successful reproduction in Arabidopsis.

Arabidopsis lamin analogs CROWDED NUCLEIs (CRWNs) are necessary to maintain nuclear structure, genome function, and proper plant growth. However, whether and how CRWNs impact reproduction and genome-wide epigenetic modifications is unknown. Here, we investigate the role of CRWNs during the development of gametophytes, seeds, and endosperm, using genomic and epigenomic profiling methods. We observed defects in crwn mutant seeds including seed abortion and reduced germination rate. Quadruple crwn null genotypes were rarely transmitted through gametophytes. Because defects in seeds often stem from abnormal endosperm development, we focused on crwn1 crwn2 (crwn1/2) endosperm. These mutant seeds exhibited enlarged chalazal endosperm cysts and increased expression of stress-related genes and the MADS-box transcription factor PHERES1 and its targets. Previously, it was shown that PHERES1 expression is regulated by H3K27me3 and that CRWN1 interacts with the PRC2 interactor PWO1. Thus, we tested whether crwn1/2 alters H3K27me3 patterns. We observed a mild loss of H3K27me3 at several hundred loci, which differed between endosperm and leaves. These data indicate that CRWNs are necessary to maintain the H3K27me3 landscape, with tissue-specific chromatin and transcriptional consequences.

Pervasive nuclear envelope ruptures precede ECM signaling and disease onset without activating cGAS-STING in Lamin-cardiomyopathy mice.

Nuclear envelope (NE) ruptures are emerging observations in Lamin-related dilated cardiomyopathy, an adult-onset disease caused by loss-of-function mutations in Lamin A/C, a nuclear lamina component. Here, we test a prevailing hypothesis that NE ruptures trigger the pathological cGAS-STING cytosolic DNA-sensing pathway using a mouse model of Lamin cardiomyopathy. The reduction of Lamin A/C in cardio-myocyte of adult mice causes pervasive NE ruptures in cardiomyocytes, preceding inflammatory transcription, fibrosis, and fatal dilated cardiomyopathy. NE ruptures are followed by DNA damage accumulation without causing immediate cardiomyocyte death. However, cGAS-STING-dependent inflammatory signaling remains inactive. Deleting cGas or Sting does not rescue cardiomyopathy in the mouse model. The lack of cGAS-STING activation is likely due to the near absence of cGAS expression in adult cardiomyocytes at baseline. Instead, extracellular matrix (ECM) signaling is activated and predicted to initiate pro-inflammatory communication from Lamin-reduced cardiomyocytes to fibroblasts. Our work nominates ECM signaling, not cGAS-STING, as a potential inflammatory contributor in Lamin cardiomyopathy.

An Innovative Use of Point-of-Care Ultrasound for Identification and Management of a Rare and Uncommon Perioperative Complication: Periorbital Emphysema Following Sinus Surgery in a Pediatric Patient.

Periorbital emphysema is a rare complication following functional endoscopic sinus surgery (FESS) with potential sight-threatening consequences. We present a case of an eight-year-old male who developed periorbital emphysema after FESS for allergic fungal sinusitis. Prompt diagnosis was made using point-of-care ultrasound (POCUS), facilitating timely intervention and conservative management. This case underscores the importance of perioperative imaging to identify lamina papyracea abnormalities, smooth extubation to prevent complications, and the innovative use of POCUS in diagnosing perioperative orbital emphysema and managing it conservatively while examining the eye at regular intervals. These findings highlight the significance of vigilance during FESS procedures and the utility of POCUS in diagnosing and managing rare perioperative complications.

Cutaneous Superficial Basal Cell Carcinoma is a Basal Cell Carcinoma In Situ: Electron Microscopy of a Case Series of Basal Cell Carcinomas.

Basal cell carcinoma (BCC) is the most common skin cancer. Skin cancers may present either as a non-invasive tumor or an invasive malignancy. The terminology of carcinoma in situ is used when the tumor is either just limited to epidermis or not present as single cells or nests in the dermis. However, currently the terminology superficial BCC is inappropriately used instead of BCC in situ when the skin cancer is limited to epidermis. In this study we compare the pathologic changes of superficial, nodular, and infiltrative BCCs using electron microscopy to identify the ultrastructural characteristics and validate the previously proposed terminology. Three cases of BCC (superficial BCC, nodular BCC, and infiltrative BCC) diagnosed by dermatopathologists at our institute were selected for review. Paraffin block tissues from these cases were sent for electron microscopy studies which demonstrated disruption of basal lamina in both nodular and infiltrative type of BCC, while it remains intact in BCC superficial type after extensive examination. Therefore, similar to other in situ skin cancers, there is no invasion of the neoplasm in superficial BCC into the dermis. Hence, the older term superficial BCC should be appropriately replaced with the newer terminology BCC in situ.

Crosstalk between mitotic reassembly and repair of the nuclear envelope.

In eukaryotic cells, the nuclear envelope (NE) is a membrane partition between the nucleus and the cytoplasm to compartmentalize nuclear contents. It plays an important role in facilitating nuclear functions including transcription, DNA replication and repair. In mammalian cells, the NE breaks down and then reforms during cell division, and in interphase it is restored shortly after the NE rupture induced by mechanical force. In this way, the partitioning effect is regulated through dynamic processes throughout the cell cycle. A failure in rebuilding the NE structure triggers the mixing of nuclear and cytoplasmic contents, leading to catastrophic consequences for the nuclear functions. Whereas the precise details of molecular mechanisms for NE reformation during cell division and NE restoration in interphase are still being investigated, here, we mostly focus on mammalian cells to describe key aspects that have been identified and to discuss the crosstalk between them.

Immediate implant placement in a dialysis patient. A case report.

Implant-supported rehabilitation in high-risk patients poses significant challenges for the dental team. The presence of comorbidities and increased infection risk can, for example, lead to a higher risk of implant loss. For the therapy to be completed with as few complications as possible, special anamnesis, detailed diagnostics, and a risk analysis based on those findings are indispensable. The aim of all considerations is to keep the risk of infection for the patient with a disease history to a minimum and to strive for an appropriate functional and esthetic therapeutic success. Particularly in the esthetic zone, in addition to the general health risks of the surgical procedure, esthetic aspects are increasingly taken into account in planning. The present article describes the implant-prosthetic replacement of a single anterior tooth in a dialysis patient. Several aspects (regular dialysis, missing buccal lamella, high smile line, functional risk) increased the risk of complications in this case.

A lineage-specific protein network at the trypanosome nuclear envelope.

The nuclear envelope (NE) separates translation and transcription and is the location of multiple functions, including chromatin organization and nucleocytoplasmic transport. The molecular basis for many of these functions have diverged between eukaryotic lineages. Trypanosoma brucei, a member of the early branching eukaryotic lineage Discoba, highlights many of these, including a distinct lamina and kinetochore composition. Here, we describe a cohort of proteins interacting with both the lamina and NPC, which we term lamina-associated proteins (LAPs). LAPs represent a diverse group of proteins, including two candidate NPC-anchoring pore membrane proteins (POMs) with architecture conserved with S. cerevisiae and H. sapiens, and additional peripheral components of the NPC. While many of the LAPs are Kinetoplastid specific, we also identified broadly conserved proteins, indicating an amalgam of divergence and conservation within the trypanosome NE proteome, highlighting the diversity of nuclear biology across the eukaryotes, increasing our understanding of eukaryotic and NPC evolution.

Analysis of the impact of intraventricular hemorrhage on the functional outcome of ruptured anterior cerebral artery aneurysm after clipping.

Background: Various clinical symptoms and variables have been suggested as potential indicators of outcomes in patients with subarachnoid hemorrhage (SAH) resulting from ruptured intracranial aneurysms. The detailed discussion of the consequences of intraventricular hemorrhage (IVH), frequently reported in cases of anterior communicating artery (ACoA) aneurysms, is still pending. The study aimed to assess the results of aneurysm surgery performed early versus delayed in patients with SAH, specifically focusing on the occurrence of IVH. Methods: This study involved patients with ACoA aneurysms who experienced SAH and underwent microsurgical clipping of the aneurysm. A retrospective review was conducted on the patients' medical records. The modified Rankin score was compared between two groups of patients based on the presence or absence of IVH. Results: Ninety-one participants (52 males and 39 females) were included in the study. The initial computed tomography scan showed that 20 patients (with a mean age of 51 ± 13.7 years) had IVH, while 71 patients (with a mean age of 45.8 ± 11.7 years) did not have any signs of IVH. The proportion of patients with poor functional outcomes after six months was 55% in the presence of IVH, compared to 25.4% in patients without IVH, indicating a significant difference in outcome between the two groups (P < 0.016). Conclusion: Patients with SAH having aneurysms located in the ACoA associated with the intraventricular hemorrhage had a poor functional outcome.

Temporal Protrusion of the Optic Disc Implicated in Central Visual Field Abnormalities in High Myopia: Two Case Reports.

Introduction: Severe central visual field defects are frequently observed in highly myopic eyes. This report details 2 cases of central visual field defects in individuals with high myopia, characterized by an unusual temporal protrusion of the optic disc, a feature not previously documented. Case Presentation: Two patients, a 54-year-old man and a 65-year-old woman, were diagnosed with high myopia in their left eyes, displaying an outward protrusion of the optic disc toward the macula. Swept-source optical coherence tomography revealed a focal lamina cribrosa defect at the temporal edge of the protruding optic disc, corresponding to the papillomacular bundle area of retinal nerve fibers, which exhibited thinning around the focal lamina cribrosa defect. Visual field examination indicated a central visual field defect in the affected eyes, which pattern corresponded to the papillomacular bundle responsible area. Conclusion: The emergence of a temporal protrusion in the optic disc may lead to a focal lamina cribrosa defect, resulting in a central visual field defect in highly myopic eyes. This distinctive optic disc feature may constitute a critical risk factor for a central visual field defect. Hence, optic disc protrusion in high myopia warrants attention, necessitating careful ophthalmic examinations for central visual field defects.

Photobiomodulation inhibits neuronal firing in the superficial but not deep layer of a rat spinal dorsal horn.

Photobiomodulation (PBM) has attracted attention as a treatment for chronic pain. Previous studies have reported that PBM of the sciatic nerve inhibits neuronal firing in the superficial layers (lamina I-II) of the spinal dorsal horn of rats, which is evoked by mechanical stimulation that corresponds to noxious stimuli. However, the effects of PBM on the deep layers (lamina III-IV) of the spinal dorsal horn, which receive inputs from innocuous stimuli, remain poorly understood. In this study, we examined the effect of PBM of the sciatic nerve on firing in the deep layers of the spinal dorsal horn evoked by mechanical stimulation. Before and after PBM, mechanical stimulation was administered to the cutaneous receptive field using 0.6-26.0 g von Frey filaments (vFFs), and vFF-evoked firing in the deep layers of the spinal dorsal horn was recorded. The vFF-evoked firing frequencies were not altered after the PBM for any of the vFFs. The inhibition rate for 26.0 g vFF-evoked firing was approximately 13 % in the deep layers and 70 % in the superficial layers. This suggests that PBM selectively inhibits the transmission of pain information without affecting the sense of touch. PBM has the potential to alleviate pain while preserving the sense of touch.

Features Associated with Visible Lamina Cribrosa Pores in Individuals of African Ancestry with Glaucoma: Primary Open-Angle African Ancestry Glaucoma Genetics (POAAGG) Study.

There are scarce data regarding the rate of the occurrence of primary open-angle glaucoma (POAG) and visible lamina cribrosa pores (LCPs) in the eyes of individuals with African ancestry; the potential impact of these features on disease burden remains unknown. We recruited subjects with POAG to the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study. Through regression models, we evaluated the association between the presence of LCPs and various phenotypic features. In a multivariable analysis of 1187 glaucomatous eyes, LCPs were found to be more likely to be present in eyes with cup-to-disc ratios (CDR) of ≥0.9 (adjusted risk ratio (aRR) 1.11, 95%CI: 1.04-1.19, p = 0.005), eyes with cylindrical-shaped (aRR 1.22, 95%CI: 1.11-1.33) and bean pot (aRR 1.24, 95%CI: 1.13-1.36) cups versus conical cups (p < 0.0001), moderate cup depth (aRR 1.24, 95%CI: 1.06-1.46) and deep cups (aRR 1.27, 95%CI: 1.07-1.50) compared to shallow cups (p = 0.01), and the nasalization of central retinal vessels (aRR 1.33, 95%CI: 1.23-1.44), p < 0.0001). Eyes with LCPs were more likely to have a higher degree of African ancestry (q0), determined by means of SNP analysis (aRR 0.96, 95%CI: 0.93-0.99, p = 0.005 for per 0.1 increase in q0). Our large cohort of POAG cases of people with African ancestry showed that LCPs may be an important risk factor in identifying severe disease, potentially warranting closer monitoring by physicians.

Acquired Simple Bone Cyst Associated With Lumbar Spinal Canal Stenosis Progression: A Case Report.

A simple bone cyst (SBC) in the posterior lumbar bone structure is very rare. Here, we report a case of SBC at the L5 lumbar lamina with venous obstruction associated with ligamentum flavum thickening. A 59-year-old woman presented with intermittent claudication due to low back pain and bilateral sciatica. A lumbar MRI showed L4-5 lumbar spinal canal stenosis and a T2-weighted image hyperintense lesion in the L5 lamina. Imaging four years earlier showed no lesions in the L5 lamina. Her symptoms improved after lumbar decompression surgery. The L5 lamina lesion was SBC, leading to a diagnosis of venous infarction. The involvement of neovascularization in the mechanism of degenerative hypertrophy in the ligamentum flavum was suggested. In this case, increased venous perfusion and venous obstruction were involved in the formation of the bone cyst.

Feasibility of C2 Lamina Screw Placement in a New Zealand Cohort: Computed Tomography Analysis According to Ethnicity and Gender.

BACKGROUND: Previous analyses have suggested variations in cervical spine canal morphology according to ethnicity, possibly in part due to variations in the posterior elements. The potential for these variations to affect the placement of instrumentation is uncertain. The aim of this study was to report on the feasibility of C2 lamina screw insertion in a New Zealand cohort including analysis of Maori, the indigenous people of New Zealand. METHODS: A trauma computed tomography database was accessed to identify suitable images. On axial images, where the isthmus was at its widest, the outer diameter (OD) and inner diameter (ID) of the lamina were measured. Screw length was measured from a proposed entry point to the contralateral junction of the lamina and lateral mass. The spinolaminar angle was measured as the angle subtended by the screw trajectory and midsagittal plane. A 5.5-mm OD was accepted as a threshold for the feasibility of lamina screw placement. RESULTS: One hundred eighty-seven images were assessed: 115 New Zealand European and 72 Maori. The mean age of the cohort was 41.9 years (SD 19.6), and most patients (64%) were men. For the entire cohort, mean OD was 6.6 and 6.8 mm on the right and left, respectively; the mean inner diameter was 3.5 and 3.8 mm; mean screw length was 31.5 and 31.5 mm; and mean spinolaminar angle was 46.0° and 46.1°. C2 lamina screw placement was feasible in a majority of patients. Considering only Maori patients, placement was feasible in 96% of right and 94% of left laminae in men but 72% of right and 72% of left laminae in women. CONCLUSIONS: In a majority of patients, C2 lamina screw placement is feasible. However, advanced imaging must be carefully assessed preoperatively because data suggest that Maori women may not necessarily have optimal anatomy.Clinical RelevanceCare needs to be taken when assessing and planning surgery inpatients of different ethnicities because variations may exist in the morphology of the posterior elements of C2, leading to variation in optimal fixation strategy.Level of Evidence3.

Leaf unfolding and lamina biomechanics inSyngonium podophyllumandPilea peperomioides.

In nature, leaves and their laminae vary in shape, appearance and unfolding behaviour. We investigated peltate leaves of two model species with peltate leaves and highly different morphology (Syngonium podophyllumandPilea peperomioides) and two distinct unfolding patterns via time-lapse recordings: we observed successive unfolding of leaf halves inS. podophyllumand simultaneous unfolding inP. peperomioides.Furthermore, we gathered relevant morphological and biomechanical data in juvenile (unfolding) and adult (fully unfolded) leaves of both species by measuring the thickness and the tensile modulus of both lamina and veins as a measure of their stiffness. InS. podophyllum, lamina and veins stiffen after unfolding, which may facilitate unfolding in the less stiff juvenile lamina. Secondary venation highly contributes to stiffness in the adult lamina ofS. podophyllum, while the lamina itself withstands tensile loads best in direction parallel to secondary veins. In contrast, the leaf ofP. peperomioideshas a higher lamina thickness and small, non-prominent venation and is equally stiff in every region and direction, although, as is the case inS. podophyllum, thickness and stiffness increase during ontogeny of leaves from juvenile to adult. It could be shown that (changes in) lamina thickness and stiffness can be well correlated with the unfolding processes of both model plants, so that we conclude that functional lamina morphology in juvenile and adult leaf stages and the ontogenetic transition while unfolding is highly dependent on biomechanical characteristics, though other factors are also taken into consideration and discussed.

Application of Slice Culture System for Successional Dental Lamina in Diphyodont Mammals.

Replacement teeth develop from the successional dental lamina (SDL). Understanding how SDL transitions from quiescence to initiation is crucial for preserving dental lamina stem cells in the jawbone microenvironment and for complete tooth regeneration. Miniature pigs are good models for studying human tooth replacement because of their similarities to humans. However, the molecular mechanisms and cellular composition that initiate SDL development remain unclear. One possible reason for this is the limitations of the current methods for culturing SDL in vitro, such as the inability to directly observe tooth morphological changes during culture and low tissue viability. This study aimed to improve the in vitro culture method for SDL. Using a McIlwain Tissue Chopper, we obtained mandibular slices containing deciduous canine and SDL of permanent canine. The slices were approximately 500 µm thick and were cultured on a Transwell membrane supported with metal grids over medium. The SDL developed into the bud stage on the second day and entered the cap stage on the fifth day in vitro. The expression of proliferation markers, cell death markers, and key odontogenetic genes in vitro was similar to that observed in vivo. In conclusion, we successfully applied a slice culture system to the SDL of miniature pigs. This slice culture method allowed us to directly visualize SDL initiation and further elucidate the molecular mechanisms underlying the initiation of permanent tooth development.