Phylogenomic analyses of ochrophytes (stramenopiles) with an emphasis on neglected lineages.

Ochrophyta is a photosynthetic lineage that crowns the phylogenetic tree of stramenopiles, one of the major eukaryotic supergroups. Due to their ecological impact as a major primary producer, ochrophytes are relatively well-studied compared to the rest of the stramenopiles, yet their evolutionary relationships remain poorly understood. This is in part due to a number of missing lineages in large-scale multigene analyses, and an apparently rapid radiation leading to many short internodes between ochrophyte subgroups in the tree. These short internodes are also found across deep-branching lineages of stramenopiles with limited phylogenetic signal, leaving many relationships controversial overall. We have addressed this issue with other deep-branching stramenopiles recently, and now examine whether contentious relationships within the ochrophytes may be resolved with the help of filling in missing lineages in an updated phylogenomic dataset of ochrophytes, along with exploring various gene filtering criteria to identify the most phylogenetically informative genes. We generated ten new transcriptomes from various culture collections and a single-cell isolation from an environmental sample, added these to an existing phylogenomic dataset, and examined the effects of selecting genes with high phylogenetic signal or low phylogenetic noise. For some previously contentious relationships, we find a variety of analyses and gene filtering criteria consistently unite previously unstable groupings with strong statistical support. For example, we recovered a robust grouping of Eustigmatophyceae with Raphidophyceae-Phaeophyceae-Xanthophyceae while Olisthodiscophyceae formed a sister-lineage to Pinguiophyceae. Selecting genes with high phylogenetic signal or data quality recovered more stable topologies. Overall, we find that adding under-represented groups across different lineages is still crucial in resolving phylogenetic relationships, and discrete gene properties affect lineages of stramenopiles differently. This is something which may be explored to further our understanding of the molecular evolution of stramenopiles.

Single-channel seizure detection with clinical confirmation of seizure locations using CHB-MIT dataset.

Introduction: Long-term electroencephalography (EEG) monitoring is advised to patients with refractory epilepsy who have a failure of anti-seizure medication and therapy. However, its real-life application is limited mainly due to the use of multiple EEG channels. We proposed a patient-specific deep learning-based single-channel seizure detection approach using the long-term scalp EEG recordings of the Children's Hospital Boston-Massachusetts Institute of Technology (CHB-MIT) dataset, in conjunction with neurologists' confirmation of spatial seizure characteristics of individual patients. Methods: We constructed 18-, 4-, and single-channel seizure detectors for 13 patients. Neurologists selected a specific channel among four channels, two close to the behind-the-ear and two at the forehead for each patient, after reviewing the patient's distinctive seizure locations with seizure re-annotation. Results: Our multi- and single-channel detectors achieved an average sensitivity of 97.05-100%, false alarm rate of 0.22-0.40/h, and latency of 2.1-3.4 s for identification of seizures in continuous EEG recordings. The results demonstrated that seizure detection performance of our single-channel approach was comparable to that of our multi-channel ones. Discussion: We suggest that our single-channel approach in conjunction with clinical designation of the most prominent seizure locations has a high potential for wearable seizure detection on long-term EEG recordings for patients with refractory epilepsy.

The telovelar approach for fourth ventricular tumors in children: is removal of the posterior arch of C1 necessary?

PURPOSE: Various surgical nuances of the telovelar approach have been suggested. The necessity of removing the posterior arch of C1 to accomplish optimal tumor exposure is still debated. Therefore, we report on our experience and technical details of the fourth ventricular tumor resection in a modified prone position without systematic removal of the posterior arch of C1. METHODS: A retrospective analysis of all pediatric patients, who underwent a fourth ventricular tumor resection in the modified prone position between 2012 and 2021, was performed. RESULTS: We identified 40 patients with a median age of 6 years and a M:F ratio of 25:15. A telovelar approach was performed in all cases. In 39/40 patients, the posterior arch of C1 was not removed. In the remaining patient, the reason for removing C1 was tumor extension below the level of C2 with ventral extension. Gross or near total resection could be achieved in 34/39 patients, and subtotal resection in 5/39 patients. In none of the patients, a limited exposure, sight of view, or range of motion caused by the posterior arch of C1 was encountered, necessitating an unplanned removal of the posterior arch of C1. Importantly, in none of the cases, the surgeon had the impression of a limited sight of view to the most rostral parts of the fourth ventricle, which necessitated a vermian incision. CONCLUSION: A telovelar approach without the removal of the posterior arch of C1 allows for an optimal exposure of the fourth ventricle provided that critical nuances in patient positioning are considered.

Severe Neurological Manifestation Associated With Coronavirus Disease 2019 in Children During the Omicron Variant-Predominant Period.

BACKGROUND: The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to be more infectious and less severe than the other variants. Despite the increasing number of symptomatic patients, severe neurological complications in children with the Omicron variant have been reported rarely, unlike with wild-type or Delta variants. This study aimed to investigate severe neurological complications in children with Omicron variant infection. METHODS: We conducted a retrospective study of 17 pediatric patients with severe neurological manifestations associated with coronavirus disease 2019 in Korea during the Omicron variant prevalence, from January 1 to April 30, 2022. RESULTS: Among the 17 patients, 11 had pre-existing neurological disabilities and nine met the criteria for multisystem inflammatory syndrome in children (MIS-C). Four of the five vaccine-eligible patients (12 years and older) were unvaccinated. Severe neurological manifestations included acute necrotizing encephalopathy, acute fulminant cerebral edema, acute disseminated encephalomyelitis, basal ganglia encephalitis, unclassified severe encephalopathy/encephalitis, and refractory status dystonicus. Patients with MIS-C and underlying neurological disabilities had longer median hospital and intensive care unit stays compared with those without these conditions. Five patients survived with new neurological deficits at the one-year follow-up, and three died, all of whom had underlying neurological disabilities. CONCLUSIONS: This study shows that severe neurological complications in pediatric patients with the Omicron variant of SARS-CoV-2 occur infrequently but may lead to significant morbidity and mortality, especially among those with pre-existing neurological disabilities and unvaccinated individuals. Continued efforts are necessary to prevent and manage such complications in these vulnerable populations.

Abnormal Electroencephalogram Findings and Its Correlation With Clinical Features From Pediatric Patients in Psychiatric Clinic.

Objective: We aimed to evaluate the occurrence of electroencephalogram (EEG) abnormalities in pediatric patients attending an outpatient psychiatry clinic at a tertiary center. We examined the rates of abnormalities and specific findings based on demographics, specific diagnoses, and clinical severity. Methods: This study included pediatric patients who underwent EEG at the outpatient psychiatry clinic. Patient demographics, psychiatric diagnosis, intellectual disability, intelligent quotient (IQ) score, family history of psychiatric disorders, and Clinical Global Impression-Severity (CGI-S) score were obtained through retrospective electronic health record analysis. The rate of EEG abnormalities was calculated, and specific abnormal findings were reviewed. Relationships between the rate of EEG abnormalities and diagnosis, severity, IQ, and age at EEG examination were analyzed. Results: Of 319 patients who underwent EEG, 21.3% (68 patients) of patients exhibited abnormalities, including background abnormalities (14.7%, 47 patients), interictal epileptiform discharges (IEDs) (10.3%, 33 patients), and a slow posterior dominant rhythm (3.8%, 10 patients). The frontal region was the most commonly affected area. Neurodevelopmental disorders (NDDs) had the most frequent abnormalities (29.8%), followed by anxiety (16.7%), sleep (14.3%), mood (11.7%), psychotic (5%), and conduct disorders (0%). Disease severity did not correlate with the rate of EEG abnormalities. Adjusted for age, sex, severity, and family history, patients with EEG abnormalities exhibited lower IQ scores. Conclusion: EEG abnormalities were common in pediatric patients with psychiatric disorders, with background abnormalities detected as frequently as IEDs. Disease severity was not associated with EEG abnormality, while IQ scores showed a negative correlation.

Genomic analyses of Symbiomonas scintillans show no evidence for endosymbiotic bacteria but does reveal the presence of giant viruses.

Symbiomonas scintillans Guillou et Chrétiennot-Dinet, 1999 is a tiny (1.4 µm) heterotrophic microbial eukaryote. The genus was named based on the presence of endosymbiotic bacteria in its endoplasmic reticulum, however, like most such endosymbionts neither the identity nor functional association with its host were known. We generated both amplification-free shotgun metagenomics and whole genome amplification sequencing data from S. scintillans strains RCC257 and RCC24, but were unable to detect any sequences from known lineages of endosymbiotic bacteria. The absence of endobacteria was further verified with FISH analyses. Instead, numerous contigs in assemblies from both RCC24 and RCC257 were closely related to prasinoviruses infecting the green algae Ostreococcus lucimarinus, Bathycoccus prasinos, and Micromonas pusilla (OlV, BpV, and MpV, respectively). Using the BpV genome as a reference, we assembled a near-complete 190 kbp draft genome encoding all hallmark prasinovirus genes, as well as two additional incomplete assemblies of closely related but distinct viruses from RCC257, and three similar draft viral genomes from RCC24, which we collectively call SsVs. A multi-gene tree showed the three SsV genome types branched within highly supported clades with each of BpV2, OlVs, and MpVs, respectively. Interestingly, transmission electron microscopy also revealed a 190 nm virus-like particle similar the morphology and size of the endosymbiont originally reported in S. scintillans. Overall, we conclude that S. scintillans currently does not harbour an endosymbiotic bacterium, but is associated with giant viruses.

SYNGAP1-related developmental and epileptic encephalopathy: Genotypic and phenotypic characteristics and longitudinal insights.

The clinical and genetic characteristics of SYNGAP1 mutations in Korean pediatric patients are not well understood. We retrospectively analyzed 13 individuals with SYNGAP1 mutations from a longitudinal aspect. Clinical data, genetic profiles, and electroencephalography (EEG) patterns were examined. Genotypic analyses included gene panels and whole-exome sequencing. All patients exhibited global developmental delay from early infancy, with motor development eventually reaching independent ambulation by 3 years of age. Language developmental delay varied significantly from nonverbal to simple sentences, which plateaued in all patients. Patients with the best language outcomes typically managed 2-3-word sentences, corresponding to a developmental age of 2-3 years. Epilepsy developed in 77% of patients, with onset consistently following developmental delays at a median age of 31 months. Longitudinal EEG data revealed a shift from occipital to frontal epileptiform discharges with age, suggesting a correlation with synaptic maturation. These findings suggest that the critical developmental plateau occurs between the ages of 2 and 5 years and is potentially influenced by epilepsy. By analyzing longitudinal data, our study contributes to a deeper understanding of SYNGAP1-related DEE, provides potential EEG biomarkers, and underlines the importance of early diagnosis and intervention to address this complex disorder.

Multi-Dynamic-Multi-Echo-based MRI for the Pre-Surgical Determination of Sellar Tumor Consistency: a Quantitative Approach for Predicting Lesion Resectability.

PURPOSE: Pre-surgical information about tumor consistency could facilitate neurosurgical planning. This study used multi-dynamic-multi-echo (MDME)-based relaxometry for the quantitative determination of pituitary tumor consistency, with the aim of predicting lesion resectability. METHODS: Seventy-two patients with suspected pituitary adenomas, who underwent preoperative 3 T MRI between January 2020 and January 2022, were included in this prospective study. Lesion-specific T1-/T2-relaxation times (T1R/T2R) and proton density (PD) metrics were determined. During surgery, data about tumor resectability were collected. A Receiver Operating Characteristic (ROC) curve analysis was performed to investigate the diagnostic performance (sensitivity/specificity) for discriminating between easy- and hard-to-remove by aspiration (eRAsp and hRAsp) lesions. A Mann-Whitney-U-test was done for group comparison. RESULTS: A total of 65 participants (mean age, 54 years ± 15, 33 women) were enrolled in the quantitative analysis. Twenty-four lesions were classified as hRAsp, while 41 lesions were assessed as eRAsp. There were significant differences in T1R (hRAsp: 1221.0 ms ± 211.9; eRAsp: 1500.2 ms ±â€¯496.4; p = 0.003) and T2R (hRAsp: 88.8 ms ± 14.5; eRAsp: 137.2 ms ± 166.6; p = 0.03) between both groups. The ROC analysis revealed an area under the curve of 0.72 (95% CI: 0.60-0.85) at p = 0.003 for T1R (cutoff value: 1248 ms; sensitivity/specificity: 78%/58%) and 0.66 (95% CI: 0.53-0.79) at p = 0.03 for T2R (cutoff value: 110 ms; sensitivity/specificity: 39%/96%). CONCLUSION: MDME-based relaxometry enables a non-invasive, pre-surgical characterization of lesion consistency and, therefore, provides a modality with which to predict tumor resectability.

Risk factors for unfavorable outcome after spontaneous intracerebral hemorrhage in elderly patients.

BACKGROUND: Spontaneous intracerebral hemorrhage (SICH) of the elderly is a devastating form of stroke with a high morbidity and economic burden. There is still a limited understanding of the risk factors for an unfavorable outcome where a surgical therapy may be less meaningful. Thus, the aim of this study is to identify factors associated with unfavorable outcome and time to death in surgically treated elderly patients with SICH. METHODS: We performed a single-center retrospective study of 70 patients (age > 60 years) with SICH operated between 2008 and 2020. Functional outcome was assessed by modified Rankin Scale. Various clinical and neuroradiological variables including type of neurosurgical treatment, anatomical location of hemorrhage, volumetry and distribution of hemorrhage were assessed. Univariate and multivariate logistic regression models were performed. Length of stay (LOS) and hospital costs are presented. RESULTS: The overall mortality (mean follow-up time of 22 months) in this study was 32/70 patients (45.71%), 30-days mortality was 8/70 (11.42%), and 12-months mortality was 22/70 (31.43%). Average LOS was 73.5 days with a median of 58, 766 € estimated in hospital costs per patient. Multivariate analysis for 12-months mortality was significant for intraventricular hemorrhage (IVH) (p = 0.007, HR = 1.021, 95% CI = 1.006 - 1.037). ROC analysis for 12-months mortality for IVH volume >= 7 cm3 presented an are under the curve of 0.658. CONCLUSIONS: We identified IVH volume > 7 cm3 as an independent prognostic risk factor for mortality in elderly patients after SICH. This may help clinicians in decision-making for this critical and growing subgroup of patients.

An evaluation of physical and augmented patient-specific intracranial aneurysm simulators on microsurgical clipping performance and skills: a randomized controlled study.

OBJECTIVE: In the era of flow diversion, there is an increasing demand to train neurosurgeons outside the operating room in safely performing clipping of unruptured intracranial aneurysms. This study introduces a clip training simulation platform for residents and aspiring cerebrovascular neurosurgeons, with the aim to visualize peri-aneurysm anatomy and train virtual clipping applications on the matching physical aneurysm cases. METHODS: Novel, cost-efficient techniques allow the fabrication of realistic aneurysm phantom models and the additional integration of holographic augmented reality (AR) simulations. Specialists preselected suitable and unsuitable clips for each of the 5 patient-specific models, which were then used in a standardized protocol involving 9 resident participants. Participants underwent four sessions of clip applications on the models, receiving no interim training (control), a video review session (video), or a video review session and holographic clip simulation training (video + AR) between sessions 2 and 3. The study evaluated objective microsurgical skills, which included clip selection, number of clip applications, active simulation time, wrist tremor analysis during simulations, and occlusion efficacy. Aneurysm occlusions of the reference sessions were assessed by indocyanine green videoangiography, as well as conventional and photon-counting CT scans. RESULTS: A total of 180 clipping procedures were performed without technical complications. The measurements of the active simulation times showed a 39% improvement for all participants. A median of 2 clip application attempts per case was required during the final session, with significant improvement observed in experienced residents (postgraduate year 5 or 6). Wrist tremor improved by 29% overall. The objectively assessed aneurysm occlusion rate (Raymond-Roy class 1) improved from 76% to 80% overall, even reaching 93% in the extensively trained cohort (video + AR) (p = 0.046). CONCLUSIONS: The authors introduce a newly developed simulator training platform combining physical and holographic aneurysm clipping simulators. The development of exchangeable, aneurysm-comprising housings allows objective radio-anatomical evaluation through conventional and photon-counting CT scans. Measurable performance metrics serve to objectively document improvements in microsurgical skills and surgical confidence. Moreover, the different training levels enable a training program tailored to the cerebrovascular trainees' levels of experience and needs.

Serine synthesis pathway upregulated by E-cadherin is essential for the proliferation and metastasis of breast cancers.

The loss of E-cadherin (E-cad), an epithelial cell adhesion molecule, has been implicated in the epithelial-mesenchymal transition (EMT), promoting invasion and migration of cancer cells and, consequently, metastasis. However, recent studies have demonstrated that E-cad supports the survival and proliferation of metastatic cancer cells, suggesting that our understanding of E-cad in metastasis is far from comprehensive. Here, we report that E-cad upregulates the de novo serine synthesis pathway (SSP) in breast cancer cells. The SSP provides metabolic precursors for biosynthesis and resistance to oxidative stress, critically beneficial for E-cad-positive breast cancer cells to achieve faster tumor growth and more metastases. Inhibition of PHGDH, a rate-limiting enzyme in the SSP, significantly and specifically hampered the proliferation of E-cad-positive breast cancer cells and rendered them vulnerable to oxidative stress, inhibiting their metastatic potential. Our findings reveal that E-cad adhesion molecule significantly reprograms cellular metabolism, promoting tumor growth and metastasis of breast cancers.

Phylogenomic position of genetically diverse phagotrophic stramenopile flagellates in the sediment-associated MAST-6 lineage and a potentially halotolerant placididean.

Unlike morphologically conspicuous ochrophytes, many flagellates belonging to basally branching stramenopiles are small and often overlooked. As a result, many of these lineages are known only through molecular surveys and identified as MArine STramenopiles (MAST), and remain largely uncharacterized at the cellular or genomic level. These likely phagotrophic flagellates are not only phylogenetically diverse, but also extremely abundant in some environments, making their characterization all the more important. MAST-6 is one example of a phylogenetically distinct group that has been known to be associated with sediments, but little else is known about it. Indeed, until the present study, only a single species from this group, Pseudophyllomitus vesiculosus (Pseudophyllomitidae), has been both formally described and associated with genomic information. Here, we describe four new species including two new genera of sediment-dwelling MAST-6, Vomastramonas tehuelche gen. et sp. nov., Mastreximonas tlaamin gen. et sp. nov., one undescribed Pseudophyllomitus sp., BSC2, and a new species belonging to Placididea, the potentially halotolerant Haloplacidia sinai sp. nov. We also provide two additional bikosian transcriptomes from a public culture collection, to allow for better phylogenetic reconstructions of deep-branching stramenopiles. With the SSU rRNA sequences of the new MAST-6 species, we investigate the phylogenetic diversity of the MAST-6 group and show a high relative abundance of MAST-6 related to M. tlaamin in samples across various depths and geographical locations. Using the new MAST-6 species, we also update the phylogenomic tree of stramenopiles, particularly focusing on the paraphyly of Bigyra.

Biosynthesis of chlorophyll c in a dinoflagellate and heterologous production in planta.

Chlorophyll c is a key photosynthetic pigment that has been used historically to classify eukaryotic algae. Despite its importance in global photosynthetic productivity, the pathway for its biosynthesis has remained elusive. Here we define the CHLOROPHYLL C SYNTHASE (CHLCS) discovered through investigation of a dinoflagellate mutant deficient in chlorophyll c. CHLCSs are proteins with chlorophyll a/b binding and 2-oxoglutarate-Fe(II) dioxygenase (2OGD) domains found in peridinin-containing dinoflagellates; other chlorophyll c-containing algae utilize enzymes with only the 2OGD domain or an unknown synthase to produce chlorophyll c. 2OGD-containing synthases across dinoflagellate, diatom, cryptophyte, and haptophyte lineages form a monophyletic group, 8 members of which were also shown to produce chlorophyll c. Chlorophyll c1 to c2 ratios in marine algae are dictated in part by chlorophyll c synthases. CHLCS heterologously expressed in planta results in the accumulation of chlorophyll c1 and c2, demonstrating a path to augment plant pigment composition with algal counterparts.

Radiosurgery as a Stand-Alone Treatment Option for Cerebral Dural Arteriovenous Fistulas: the Vienna Series.

BACKGROUND: Gamma Knife radiosurgery (GKRS) has been demonstrated to be an effective and safe treatment method for dural arteriovenous fistulas (DAVFs). However, only few studies, mostly with limited patient numbers, have evaluated radiosurgery as a sole and upfront treatment option for DAVFs. METHODS: Thirty-three DAVF patients treated with GKRS as a stand-alone management at our institution between January 1992 and January 2020 were included in this study. Obliteration rates, time to obliteration, neurologic outcome, and complications were evaluated retrospectively. RESULTS: Complete overall obliteration was achieved in 20/28 (71%) patients. The postradiosurgery actuarial rates of obliteration at 2, 5, and 10 years were 53, 71, and 85%, respectively. No difference in time to obliteration between carotid-cavernous fistulas (CCFs; 14/28, 50%, 17 months; 95% confidence interval [CI]: 7.4-27.2) and non-CCFs (NCCFs; 14/28, 50%, 37 months; 95% CI: 34.7-38.5; p = 0.111) were found. Overall, the neurologic outcome in our series was highly favorable at the time of the last follow-up. A complete resolution of symptoms was seen in two-thirds (20/30, 67%) of patients. One patient with multiple DAVFs suffered from an intracranial hemorrhage of the untreated lesion and died during the follow-up period, resulting in a yearly bleeding risk of 0.5%. No complications after radiosurgery were observed in our series. CONCLUSION: Our results show that GKRS is a safe and effective stand-alone management option for selected DAVF patients.

Concomitant radiosurgical and targeted oncological treatment improves the outcome of patients with brain metastases from gastrointestinal cancer.

BACKGROUND: So far, only limited studies exist that evaluate patients with brain metastases (BM) from GI cancer and associated primary cancers who were treated by Gamma Knife Radiosurgery (GKRS) and concomitant immunotherapy (IT) or targeted therapy (TT). METHODS: Survival after GKRS was compared to the general and specific Graded Prognostic Assessment (GPA) and Score Index for Radiosurgery (SIR). Further, the influence of age, sex, Karnofsky Performance Status Scale (KPS), extracranial metastases (ECM) status at BM diagnosis, number of BM, the Recursive Partitioning Analysis (RPA) classes, GKRS1 treatment mode and concomitant treatment with IT or TT on the survival after GKRS was analyzed. Moreover, complication rates after concomitant GKRS and mainly TT treatment are reported. RESULTS: Multivariate Cox regression analysis revealed IT or TT at or after the first Gamma Knife Radiosurgery (GKRS1) treatment as the only significant predictor for overall survival after GKRS1, even after adjusting for sex, KPS group, age group, number of BM at GKRS1, RPA class, ECM status at BM diagnosis and GKRS treatment mode. Concomitant treatment with IT or TT did not increase the rate of adverse radiation effects. There was no significant difference in local BM progression after GKRS between patients who received IT or TT and patients without IT or TT. CONCLUSION: Good local tumor control rates and low rates of side effects demonstrate the safety and efficacy of GKRS in patients with BM from GI cancers. The concomitant radiosurgical and targeted oncological treatment significantly improves the survival after GKRS without increasing the rate of adverse radiation effects. To provide local tumor control, radiosurgery remains of utmost importance in modern GI BM management.

Hereditary Leiomyomatosis and Renal Cell Cancer: A Case Report of Pilar Leiomyomatosis with History of Kidney Cancer and Review of the Literature.

Pilar leiomyoma or piloleiomyoma is a benign neoplasm of the smooth muscle arising from the arrector pili muscle. It manifests as brown to red firm papulonodules with sites of predilection being the face, trunk, and extensor surfaces of the extremities. Histologically, the lesions exhibit ill-defined dermal tumors with interlacing fascicles of spindle cells. Some genodermatoses are characterized by the development of visceral tumors and cutaneous leiomyomatosis such as Reed's syndrome, and hereditary leiomyomatosis and renal cell cancer (HLRCC). A 55-year-old male presented with reddish-brown papules and nodules on the face and upper back, accompanied by sharp episodic pain on the face. He had undergone nephrectomy for renal cancer 9 years ago, and his younger brother had similar cutaneous manifestation. Histopathologic findings were consistent with pilar leiomyoma, showing bundles of smooth muscle tumors in the dermis. Based on the clinical information including clinical features, past medical history, and family history, HLRCC was highly suspected. To confirm the diagnosis, whole exome sequencing was performed using peripheral blood, which revealed a novel point mutation (c.739G>A, p.Glu247Lys) in the fumarate hydratase (FH) gene. We describe a confirmed case of HLRCC, which is a genetic disorder with a potential to cause visceral cancers, which dermatologists might overlook as a benign condition.

The Site of Origin of Medulloblastoma: Surgical Observations Correlated to Molecular Groups.

Developmental gene expression data from medulloblastoma (MB) suggest that WNT-MB originates from the region of the embryonic lower rhombic lip (LRL), whereas SHH-MB and non-WNT/non-SHH MB arise from cerebellar precursor matrix regions. This study aimed to analyze detailed intraoperative data with regard to the site of origin (STO) and compare these findings with the hypothesized regions of origin associated with the molecular group. A review of the institutional database identified 58 out of 72 pediatric patients who were operated for an MB at our department between 1996 and 2020 that had a detailed operative report and a surgical video as well as clinical and genetic classification data available for analysis. The STO was assessed based on intraoperative findings. Using the intraoperatively defined STO, "correct" prediction of molecular groups was feasible in 20% of WNT-MB, 60% of SHH-MB and 71% of non-WNT/non-SHH MB. The positive predictive values of the neurosurgical inspection to detect the molecular group were 0.21 (95% CI 0.08-0.48) for WNT-MB, 0.86 (95% CI 0.49-0.97) for SHH-MB and 0.73 (95% CI 0.57-0.85) for non-WNT/non-SHH MB. The present study demonstrated a limited predictive value of the intraoperatively observed STO for the prediction of the molecular group of MB.

Structure-Based Insight on the Mechanism of N-Glycosylation Inhibition by Tunicamycin.

N-glycosylation, a common post-translational modification, is widely acknowledged to have a significant effect on protein stability and folding. N-glycosylation is a complex process that occurs in the endoplasmic reticulum (ER) and requires the participation of multiple enzymes. GlcNAc-1-P-transferase (GPT) is essential for initiating N-glycosylation in the ER. Tunicamycin is a natural product that inhibits N-glycosylation and produces ER stress, and thus it is utilized in research. The molecular mechanism by which GPT triggers N-glycosylation is discussed in this review based on the GPT structure. Based on the structure of the GPT-tunicamycin complex, we also discuss how tunicamycin reduces GPT activity, which prevents N-glycosylation. This review will be highly useful for understanding the role of GPT in the N-glycosylation of proteins, as well as presents a potential for considering tunicamycin as an antibiotic treatment.

Broad spectrum of phenotype and genotype in Korean α-dystroglycan related muscular dystrophy presenting to a tertiary pediatric neuromuscular center.

α-Dystroglycanopathies are a clinically and genetically heterogeneous group of muscular dystrophies associated with the defective glycosylation of α-dystroglycan (α-DG). Eighteen genes associated with α-dystroglycanopathies have been identified, and the relative prevalence of genetic subtypes varies with ethnicity. Here, we investigated the clinical and genetic characteristics of α-DG-related muscular dystrophy in the Korean pediatric population. We analyzed the clinical characteristics and variant profiles of 42 patients with α-DG-related muscular dystrophies diagnosed by either reduced glycosylation of α-DG and/or genetic confirmation. Genotype-phenotype correlations were explored by a retrospective medical record review. The muscle-eye-brain disease/Fukuyama congenital muscular dystrophy was the most common phenotype (28/42, 66.7%). Homozygous or compound heterozygous variants were detected in 37 patients belonging to 34 unrelated families (37/42; 88.1%). Pathogenic variants were identified in FKTN (n = 24), POMGNT1 (n = 4), GMPPB (n = 4), FKRP (n = 2), POMT1 (n = 2), and ISPD (n = 1). Compound heterozygous retrotransposal insertions and deep-intronic variants in FKTN were the most common genotypes and were associated with severe phenotypes. This study suggests that α-DG-related muscular dystrophy has a wide range of genotypes and phenotypes according to ethnicity. A stratified genetic test according to ethnicity should be considered to diagnose α-DG-related muscular dystrophy.

Phylogenomics of novel ploeotid taxa contribute to the backbone of the euglenid tree.

Euglenids are a diverse group of flagellates that inhabit most environments and exhibit many different nutritional modes. The most prominent euglenids are phototrophs, but phagotrophs constitute the majority of phylogenetic diversity of euglenids. They are pivotal to our understanding of euglenid evolution, yet we are only starting to understand relationships amongst phagotrophs, with the backbone of the tree being most elusive. Ploeotids make up most of this backbone diversity-yet despite their morphological similarities, SSU rDNA analyses and multigene analyses show that they are non-monophyletic. As more ploeotid diversity is sampled, known taxa have coalesced into some subgroups (e.g. Alistosa), but the relationships amongst these are not always supported and some taxa remain unsampled for multigene phylogenetics. Here, we used light microscopy and single-cell transcriptomics to characterize five ploeotid euglenids and place them into a multigene phylogenetic framework. Our analyses place Decastava in Alistosa; while Hemiolia branches with Liburna, establishing the novel clade Karavia. We describe Hemiolia limna, a freshwater-dwelling species in an otherwise marine clade. Intriguingly, two undescribed ploeotids are found to occupy pivotal positions in the tree: Chelandium granulatum nov. gen. nov. sp. branches as sister to Olkasia, and Gaulosia striata nov. gen. nov. sp. remains an orphan taxon.