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Single-cell sequencing methods have emerged as powerful tools for identification of heterogeneous cell types within defined brain regions. Application of single-cell techniques to study the transcriptome of activated neurons can offer insight into molecular dynamics associated with differential neuronal responses to a given experience. Through evaluation of common whole-cell and single-nuclei RNA-sequencing (snRNA-seq) methods, here we show that snRNA-seq faithfully recapitulates transcriptional patterns associated with experience-driven induction of activity, including immediate early genes (IEGs) such as Fos , Arc and Egr1 . SnRNA-seq of mouse dentate granule cells reveals large-scale changes in the activated neuronal transcriptome after brief novel environment exposure, including induction of MAPK pathway genes. In addition, we observe a continuum of activation states, revealing a pseudotemporal pattern of activation from gene expression alone. In summary, snRNA-seq of activated neurons enables the examination of gene expression beyond IEGs, allowing for novel insights into neuronal activation patterns in vivo. The molecular dynamics associated with neuronal activation patterns in vivo are unclear. Lacar et al . perform single-nuclei RNA-sequencing of hippocampal neurons from mice exposed to a novel environment, and identify large-scale transcriptome changes in individual neurons associated with the experience.

Background Long interspersed element-1 (LINE-1, L1) is the major driver of mobile DNA activity in modern humans. When expressed, LINE-1 loci produce bicistronic transcripts encoding two proteins essential for retrotransposition, ORF1p and ORF2p. Many types of human cancers are characterized by L1 promoter hypomethylation, L1 transcription, L1 ORF1p protein expression, and somatic L1 retrotransposition. ORF2p encodes the endonuclease and reverse transcriptase activities required for L1 retrotransposition. Its expression is poorly characterized in human tissues and cell lines. Results We report mass spectrometry-based tumor proteome profiling studies wherein ORF2p eludes detection. To test whether ORF2p could be detected with specific reagents, we developed and validated five rabbit monoclonal antibodies with immunoreactivity for specific epitopes on the protein. These reagents readily detect ectopic ORF2p expressed from bicistronic L1 constructs. However, endogenous ORF2p is not detected in human tumor samples or cell lines by western blot, immunoprecipitation, or immunohistochemistry despite high levels of ORF1p expression. Moreover, we report endogenous ORF1p-associated interactomes, affinity isolated from colorectal cancers, wherein we similarly fail to detect ORF2p. These samples include primary tumors harboring hundreds of somatically acquired L1 insertions. The new data are available via ProteomeXchange with identifier PXD013743. Conclusions Although somatic retrotransposition provides unequivocal genetic evidence for the expression of ORF2p in human cancers, we are unable to directly measure its presence using several standard methods. Experimental systems have previously indicated an unequal stoichiometry between ORF1p and ORF2p, but in vivo, the expression of these two proteins may be more strikingly uncoupled. These findings are consistent with observations that ORF2p is not tolerable for cell growth.

Nature Communications 7: Article number: 11022 (2016); Published 19 April 2016; Updated 17 March 2017 An incorrect version of Supplementary Data 1, in which normalized counts were analysed instead of raw counts, resulting in a smaller number of differentially expressed genes, was inadvertently published with this article.

Nature Communications 7: Article number:11022 (2016); Published 19 April 2016; Updated 14 June 2016 In the original version of this Article, the middle names or initials of the authors Suguna Rani Krishnaswami, Jerika J. Barron, Martijn J.E. Kelder, Sarah L. Parylak, Apuã C.M. Paquola and Jennifer A. Erwin were omitted from the author information.

The biological factors responsible for differential chemoresponsiveness in oligodendroglial tumours with or without the -1p/-19q genotype are unknown, but tumour vascularity may contribute. We aimed to determine whether dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) could distinguish molecular subtypes of oligodendroglial tumour, and examined the relationship between relative cerebral blood volume (rCBV) and outcome following procarbazine, lomustine and vincristine (PCV) chemotherapy. Pretherapy rCBV was calculated and inter- and intraobserver variability assessed. Allelic imbalance in 1p36, 19q13, 17p13, 10p12-15, and 10q22-26 and p53 mutation (exons 5-8) were determined. rCBV was compared with genotype and clinicopathological characteristics (n=37) and outcome following PCV chemotherapy (n=33). 1p/19q loss was seen in 6/9 grade II oligodendrogliomas, 6/14 grade II oligoastrocytomas, 4/4 grade III oligodendrogliomas, and 3/10 grade III oligoastrocytomas. rCBV measurements had good inter- and intraobserver variability, but did not distinguish histology subtype or grade. Tumours with 1p/19q loss had higher rCBV values (Student's t-test P=0.001). Receiver operating characteristic analysis revealed a cut-off of 1.59 for identifying genotype (sensitivity 92%, specificity 76%). Tumours with high and low rCBV showed response to chemotherapy. The -1p/-19q genotype, but not rCBV, was strongly associated with response, progression-free and overall survival following PCV chemotherapy. Tumours with high rCBV and intact 1p/19q were associated with shorter progression-free and overall patient survival than those with intact 1p/19q and low rCBV or high rCBV and 1p/19q loss. rCBV identifies oligodendroglial tumours with 1p/19q loss, but does not predict chemosensitivity. The prognostic significance of rCBV may differ in oligodendroglial tumours with or without the -1p/-19q genotype.

The incidence of human papillomavirus (HPV)-positive oropharyngeal cancer, a disease affecting younger patients, is rapidly increasing. Cetuximab, an epidermal growth factor receptor inhibitor, has been proposed for treatment de-escalation in this setting to reduce the toxicity of standard cisplatin treatment, but no randomised evidence exists for the efficacy of this strategy. We did an open-label randomised controlled phase 3 trial at 32 head and neck treatment centres in Ireland, the Netherlands, and the UK, in patients aged 18 years or older with HPV-positive low-risk oropharyngeal cancer (non-smokers or lifetime smokers with a smoking history of <10 pack-years). Eligible patients were randomly assigned (1:1) to receive, in addition to radiotherapy (70 Gy in 35 fractions), either intravenous cisplatin (100 mg/m2 on days 1, 22, and 43 of radiotherapy) or intravenous cetuximab (400 mg/m2 loading dose followed by seven weekly infusions of 250 mg/m2). The primary outcome was overall severe (grade 3–5) toxicity events at 24 months from the end of treatment. The primary outcome was assessed by intention-to-treat and per-protocol analyses. This trial is registered with the ISRCTN registry, number ISRCTN33522080. Between Nov 12, 2012, and Oct 1, 2016, 334 patients were recruited (166 in the cisplatin group and 168 in the cetuximab group). Overall (acute and late) severe (grade 3–5) toxicity did not differ significantly between treatment groups at 24 months (mean number of events per patient 4·8 [95% CI 4·2–5·4] with cisplatin vs 4·8 [4·2–5·4] with cetuximab; p=0·98). At 24 months, overall all-grade toxicity did not differ significantly either (mean number of events per patient 29·2 [95% CI 27·3–31·0] with cisplatin vs 30·1 [28·3–31·9] with cetuximab; p=0·49). However, there was a significant difference between cisplatin and cetuximab in 2-year overall survival (97·5% vs 89·4%, hazard ratio 5·0 [95% CI 1·7–14·7]; p=0·001) and 2-year recurrence (6·0% vs 16·1%, 3·4 [1·6–7·2]; p=0·0007). Compared with the standard cisplatin regimen, cetuximab showed no benefit in terms of reduced toxicity, but instead showed significant detriment in terms of tumour control. Cisplatin and radiotherapy should be used as the standard of care for HPV-positive low-risk patients who are able to tolerate cisplatin. Cancer Research UK.

A woman underwent breast conservation surgery and axillary clearance for T1N1M0 breast carcinoma, followed by adjuvant chemotherapy, radiotherapy and hormone therapy. At 3-year follow-up she presented with lumbar back pain and developed bilateral lower limb weakness. MRI spine demonstrated an expansile lesion at L1 causing cauda equina compression. The mass, unusually, was centred on the spinous process; metastases typically involve pedicles. The patient underwent surgical decompression with complete resolution of neurological signs. Histology revealed Masson tumour (intravascular papillary endothelial hyperplasia), a benign vascular lesion. Pain recurrence 9 months later prompted imaging demonstrating recurrent mass. Preoperative embolisation and re-excision was undertaken for recurrent Masson tumour. Recurrence of these lesions is rare and it was felt residual disease was likely. Radiotherapy has been used in isolated cases; therefore, she was treated with adjuvant radiotherapy, the first reported case of radiation in management of extracranial Masson tumour, and remains well 3 years later.

Objectives: Squamous cell carcinoma of the tongue base has a poor prognosis, and treatment is accompanied by a number of major problems. In view of this, it is important to recognize which patients will benefit from treatment with curative intent and which treatment method to use. Methods: One hundred sixty-five patients with squamous cell carcinoma of the tongue base were identified on our database. Eighty-two patients were treated by radical irradiation, and 41 by surgery. A further 42 patients were considered unsuitable for curative treatment. Results: The 5-year cause-specific survival rate was 41% for those treated by irradiation, 58% for those treated by surgery, and 9% for untreated patients. There was no difference in the efficacy of treatment methods (p = .5362), but a highly significant difference was seen in survival rate between treated and untreated patients (p = .0028). The decision regarding administration of curative treatment was based on the extent of locoregional involvement at the primary site (p = .0139; odds ratio, 0.43) and in the neck (p = .0078; odds ratio, 0.23). No factors affected the decision to treat by irradiation or surgery. When the observed survival rate was calculated, there was no significant difference in 5-year survival rate between treated and untreated patients (p = .2762). Those with early (T1-2) disease at the primary site had an improved survival rate from 0.5 to 4 years compared with those who were untreated (T3-4; p = .0081; odds ratio, 2.2). In addition, those with early (T1-2) disease had a better survival rate than those with advanced cancers (p = .0139; odds ratio, 2.09). There was, however, no difference in survival rate at 5 years. Those with early disease compared with those with advanced disease were twice as likely to be alive at 2 years; however, all survival advantages had disappeared by 5 years. Conclusions: In terms of observed survival, treating tongue base squamous cell carcinoma that is locally advanced (T3-4) at presentation offers no survival advantage over palliation alone. Treating early disease (T1-2) doubles the survival rate for up to 4 years, but by 5 years this survival advantage is lost. The present study finds radiotherapy and surgery to be equivalent at controlling this disease.

Others, such as the Law Student Engagement Committee, were created during the trials and travails of the pandemic as SciTech leadership recognized the need for a focused approach to engage with the next generation as we shifted to a new way of working. [...]just this year, SciTech inaugurated two new committees-the Committee on Risk and Trust Management and the Committee on Law School and Interdisciplinary Education Outreach. The creation of these committees was inspired by the recognition that SciTech needs to be actively engaged with law school faculty and legal education and the importance of enterprise risk management in addressing potential problems and issues associated with new technologies. To the law students or recent graduates or technology experts with an interest in this space-I encourage you to take advantage of all the SciTech Section has to offer you as you begin your legal career. David Husband is co-chair of the Law Student Engagement Committee in ABAs SciTech Section and works as a senior counsel for the Board of Governors of the Federal Reserve System.