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Transcription initiation has long been considered a primary regulatory step in gene expression. Recent work, however, shows that downstream events, such as transcription elongation, can also play important roles.1-3 A well-characterized example from animals is promoter-proximal pausing, where transcriptionally engaged Pol II accumulates 30-50 bp downstream of the transcription start site (TSS) and is thought to enable rapid gene activation.2 Plants do not make widespread use of promoter-proximal pausing; however, in a phenomenon known as 3' pausing, a significant increase in Pol II is observed near the transcript end site (TES) of many genes.4-6 Previous work has shown that 3' pausing is promoted by the BORDER (BDR) family of negative transcription elongation factors. Here we show that BDR proteins play key roles in gene repression. Consistent with BDR proteins acting to slow or pause elongating Pol II, BDR-repressed genes are characterized by high levels of Pol II occupancy, yet low levels of mRNA. The BDR proteins physically interact with FPA,7 one of approximately two dozen genes collectively referred to as the autonomous floral-promotion pathway,8 which are necessary for the repression of the flowering time gene FLOWERING LOCUS C (FLC).9-11 In early-flowering strains, FLC expression is repressed by repressive histone modifications, such as histone H3 lysine 27 trimethylation (H3K27me3), thereby allowing the plants to flower early. These results suggest that the repression of transcription elongation by BDR proteins may allow for the temporary pausing of transcription or facilitate the long-term repression of genes by repressive histone modifications.

The co-occurrence of cancer and heart failure (HF) represents a significant clinical drawback as each disease interferes with the treatment of the other. In addition to shared risk factors, a growing body of experimental and clinical evidence reveals numerous commonalities in the biology underlying both pathologies. Inflammation emerges as a common hallmark for both diseases as it contributes to the initiation and progression of both HF and cancer. Under stress, malignant and cardiac cells change their metabolic preferences to survive, which makes these metabolic derangements a great basis to develop intersection strategies and therapies to combat both diseases. Furthermore, genetic predisposition and clonal haematopoiesis are common drivers for both conditions and they hold great clinical relevance in the context of personalized medicine. Additionally, altered angiogenesis is a common hallmark for failing hearts and tumours and represents a promising substrate to target in both diseases. Cardiac cells and malignant cells interact with their surrounding environment called stroma. This interaction mediates the progression of the two pathologies and understanding the structure and function of each stromal component may pave the way for innovative therapeutic strategies and improved outcomes in patients. The interdisciplinary collaboration between cardiologists and oncologists is essential to establish unified guidelines. To this aim, pre-clinical models that mimic the human situation, where both pathologies coexist, are needed to understand all the aspects of the bidirectional relationship between cancer and HF. Finally, adequately powered clinical studies, including patients from all ages, and men and women, with proper adjudication of both cancer and cardiovascular endpoints, are essential to accurately study these two pathologies at the same time.

BackgroundNational medical student surveys amidst the coronavirus disease 2019 (COVID-19)-driven subinternship cancellations have demonstrated the need for supplemental, standardized subspecialty medical education, mentorship, and career planning nationally. We have presented the first live, cross-institutional virtual medical student subspecialty training camp to deliver standardized neurosurgical educational content to medical students during the COVID-19 pandemic, and its results on medical student anxiety and perceptions of neurosurgery.MethodsThe online training camp used a video conferencing platform that was open to all medical students. A post-training camp survey was administered.ResultsA total of 305 medical students registered for the event from 107 unique U.S. medical schools. Of the 305 medical students, 108 reported intending to apply to neurosurgery residency in 2021. The top medical student objectives for the training camp were program networking and mentorship. Of the 305 participants, 121 (39.7%) completed the post-training survey. Of the respondents, 65.0% reported improved neurosurgical knowledge, 79.8% reported decreased anxiety about subinternships and interviews, 82.5% reported increased enthusiasm about neurosurgery, and 100% desired a future annual virtual training camp because of the increased accessibility and decreased cost. This was especially important for students at institutions without home subspecialty programs and those with financial burdens.ConclusionsCOVID-19-driven innovations in medical education have accelerated changes that may have long been necessary. This virtual structure improved resource usage and scalability compared with in-person training, maintained social distancing, and democratized access to standardized, specialized content not often available through traditional medical curricula. Even as a supplement to in-person events, the virtual training camp model could be implemented by national medical societies, which might significantly increase medical students' preparedness for, and education in, neurosurgery and other subspecialties.

BackgroundNational medical student surveys amidst the coronavirus disease 2019 (COVID-19)-driven subinternship cancellations have demonstrated the need for supplemental, standardized subspecialty medical education, mentorship, and career planning nationally. We have presented the first live, cross-institutional virtual medical student subspecialty training camp to deliver standardized neurosurgical educational content to medical students during the COVID-19 pandemic, and its results on medical student anxiety and perceptions of neurosurgery.MethodsThe online training camp used a video conferencing platform that was open to all medical students. A post-training camp survey was administered.ResultsA total of 305 medical students registered for the event from 107 unique U.S. medical schools. Of the 305 medical students, 108 reported intending to apply to neurosurgery residency in 2021. The top medical student objectives for the training camp were program networking and mentorship. Of the 305 participants, 121 (39.7%) completed the post-training survey. Of the respondents, 65.0% reported improved neurosurgical knowledge, 79.8% reported decreased anxiety about subinternships and interviews, 82.5% reported increased enthusiasm about neurosurgery, and 100% desired a future annual virtual training camp because of the increased accessibility and decreased cost. This was especially important for students at institutions without home subspecialty programs and those with financial burdens.ConclusionsCOVID-19-driven innovations in medical education have accelerated changes that may have long been necessary. This virtual structure improved resource usage and scalability compared with in-person training, maintained social distancing, and democratized access to standardized, specialized content not often available through traditional medical curricula. Even as a supplement to in-person events, the virtual training camp model could be implemented by national medical societies, which might significantly increase medical students' preparedness for, and education in, neurosurgery and other subspecialties.

This position statement from the Heart Failure Association of the European Society of Cardiology Cardio-Oncology Study Group in collaboration with the International Cardio-Oncology Society presents practical, easy-to-use and evidence-based risk stratification tools for oncologists, haemato-oncologists and cardiologists to use in their clinical practice to risk stratify oncology patients prior to receiving cancer therapies known to cause heart failure or other serious cardiovascular toxicities. Baseline risk stratification proformas are presented for oncology patients prior to receiving the following cancer therapies: anthracycline chemotherapy, HER2-targeted therapies such as trastuzumab, vascular endothelial growth factor inhibitors, second and third generation multi-targeted kinase inhibitors for chronic myeloid leukaemia targeting BCR-ABL, multiple myeloma therapies (proteasome inhibitors and immunomodulatory drugs), RAF and MEK inhibitors or androgen deprivation therapies. Applying these risk stratification proformas will allow clinicians to stratify cancer patients into low, medium, high and very high risk of cardiovascular complications prior to starting treatment, with the aim of improving personalised approaches to minimise the risk of cardiovascular toxicity from cancer therapies.

Enzymatic hydrolysis of lactose is a crucial step to improve the efficiency and selectivity of membrane-based separations toward the recovery of milk oligosaccharides free from simple sugars. Response surface methodology was used to investigate the effects temperature (25.9 to 54.1 °C) and amount of enzyme (0.17 to 0.32% w/w) at 1, 2, and 4 h of reaction on the efficiency of lactose hydrolysis by Aspergillus oryzae β-galactosidase, preservation of major goat whey oligosaccharides, and on the de-novo formation of oligosaccharides. Lactose hydrolysis above 99% was achieved at 1, 2, and 4 h, not being significantly affected by temperature and amount of enzyme within the tested conditions. Formation of 4 Hexose (Hex) and 4 Hex 1 Hex and an increased de-novo formation of 2 Hex 1 N-Acetyl-Neuraminic Acid (NeuAc) and 2 Hex 1 N-Glycolylneuraminic acid (NeuGc) was observed in all treatments. Overall, processing conditions using temperatures ≤40 °C and enzyme concentration ≤0.25% resulted in higher preservation/formation of goat whey oligosaccharides.

Enzymatic hydrolysis of lactose is a crucial step to improve the efficiency and selectivity of membrane-based separations toward the recovery of milk oligosaccharides free from simple sugars. Response surface methodology was used to investigate the effects temperature (25.9 to 54.1 °C) and amount of enzyme (0.17 to 0.32% w/w) at 1, 2, and 4 h of reaction on the efficiency of lactose hydrolysis by Aspergillus oryzae β-galactosidase, preservation of major goat whey oligosaccharides, and on the de-novo formation of oligosaccharides. Lactose hydrolysis above 99% was achieved at 1, 2, and 4 h, not being significantly affected by temperature and amount of enzyme within the tested conditions. Formation of 4 Hexose (Hex) and 4 Hex 1 Hex and an increased de-novo formation of 2 Hex 1 N-Acetyl-Neuraminic Acid (NeuAc) and 2 Hex 1 N-Glycolylneuraminic acid (NeuGc) was observed in all treatments. Overall, processing conditions using temperatures ≤40 °C and enzyme concentration ≤0.25% resulted in higher preservation/formation of goat whey oligosaccharides.

The 13th Banff Conference on Allograft Pathology was held in Vancouver, British Columbia, Canada from October 5 to 10, 2015. The cardiac session was devoted to current diagnostic issues in heart transplantation with a focus on antibody-mediated rejection (AMR) and small vessel arteriopathy. Specific topics included the strengths and limitations of the current rejection grading system, the central role of microvascular injury in AMR and approaches to semiquantitative assessment of histopathologic and immunophenotypic indicators, the role of AMR in the development of cardiac allograft vasculopathy, the important role of serologic antibody detection in the management of transplant recipients, and the potential application of new molecular approaches to the elucidation of the pathophysiology of AMR and potential for improving the current diagnostic system. Herein we summarize the key points from the presentations, the comprehensive, open and wide-ranging multidisciplinary discussion that was generated, and considerations for future endeavors.

Larval Drosophila offer a study case for behavioral neurogenetics that is simple enough to be experimentally tractable, yet complex enough to be worth the effort. We provide a detailed, hands-on manual for Pavlovian odor-reward learning in these animals. Given the versatility of Drosophila for genetic analyses, combined with the evolutionarily shared genetic heritage with humans, the paradigm has utility not only in behavioral neurogenetics and experimental psychology, but for translational biomedicine as well. Together with the upcoming total synaptic connectome of the Drosophila nervous system and the possibilities of single-cell-specific transgene expression, it offers enticing opportunities for research. Indeed, the paradigm has already been adopted by a number of labs and is robust enough to be used for teaching in classroom settings. This has given rise to a demand for a detailed, hands-on manual directed at newcomers and/or at laboratory novices, and this is what we here provide. The paradigm and the present manual have a unique set of features: The paradigm is cheap, easy, and robust;The manual is detailed enough for newcomers or laboratory novices;It briefly covers the essential scientific context;It includes sheets for scoring, data analysis, and display;It is multilingual: in addition to an English version we provide German, French, Japanese, Spanish and Italian language versions as well.The present manual can thus foster science education at an earlier age and enable research by a broader community than has been the case to date.

The 13th Banff Conference on Allograft Pathology was held in Vancouver, British Columbia, Canada from October 5 to 10, 2015. The cardiac session was devoted to current diagnostic issues in heart transplantation with a focus on antibody-mediated rejection (AMR) and small vessel arteriopathy. Specific topics included the strengths and limitations of the current rejection grading system, the central role of microvascular injury in AMR and approaches to semiquantitative assessment of histopathologic and immunophenotypic indicators, the role of AMR in the development of cardiac allograft vasculopathy, the important role of serologic antibody detection in the management of transplant recipients, and the potential application of new molecular approaches to the elucidation of the pathophysiology of AMR and potential for improving the current diagnostic system. Herein we summarize the key points from the presentations, the comprehensive, open and wide-ranging multidisciplinary discussion that was generated, and considerations for future endeavors.

Larval Drosophila offer a study case for behavioral neurogenetics that is simple enough to be experimentally tractable, yet complex enough to be worth the effort. We provide a detailed, hands-on manual for Pavlovian odor-reward learning in these animals. Given the versatility of Drosophila for genetic analyses, combined with the evolutionarily shared genetic heritage with humans, the paradigm has utility not only in behavioral neurogenetics and experimental psychology, but for translational biomedicine as well. Together with the upcoming total synaptic connectome of the Drosophila nervous system and the possibilities of single-cell-specific transgene expression, it offers enticing opportunities for research. Indeed, the paradigm has already been adopted by a number of labs and is robust enough to be used for teaching in classroom settings. This has given rise to a demand for a detailed, hands-on manual directed at newcomers and/or at laboratory novices, and this is what we here provide. The paradigm and the present manual have a unique set of features: The paradigm is cheap, easy, and robust;The manual is detailed enough for newcomers or laboratory novices;It briefly covers the essential scientific context;It includes sheets for scoring, data analysis, and display;It is multilingual: in addition to an English version we provide German, French, Japanese, Spanish and Italian language versions as well.The present manual can thus foster science education at an earlier age and enable research by a broader community than has been the case to date.

This article questions dominant understandings of “China,” “Islam,” and the relationship between the two. It does so by uncovering an alternative understanding of China, one held by a group of people living within the Qing Empire and, later, the Republic of China: the Turki-speaking Muslims of Altishahr, known today as Uyghurs. Turki manuscript sources depict China as a distant and distasteful power, as a khanate in the Inner Asian tradition, and as a city synonymous with its ruler, characterized above all else by its rejection of Islam, yet vulnerable to conversion by charismatic Sufis. This notion of China, it is argued, is no more culturally determined than the predominant understanding of China that undergirds most scholarly studies of China, and no less enlightening. And yet Altishahri and other Islamic perspectives have been excluded from our notion of China, largely through a dependence on the concept of “syncretism.” As an alternative to the syncretism approach to cultural interchange, the article advocates for a greater focus on overlapping networks of shared meaning. Applied to the Altishahri case, this approach gives a sense of what is lost in the privileging of Islam and China as dominant categories, and shows the distortions involved in bounding these categories. Keywords: Islam, China, syncretism, Uyghur

This article questions dominant understandings of “China,” “Islam,” and the relationship between the two. It does so by uncovering an alternative understanding of China, one held by a group of people living within the Qing Empire and, later, the Republic of China: the Turki-speaking Muslims of Altishahr, known today as Uyghurs. Turki manuscript sources depict China as a distant and distasteful power, as a khanate in the Inner Asian tradition, and as a city synonymous with its ruler, characterized above all else by its rejection of Islam, yet vulnerable to conversion by charismatic Sufis. This notion of China, it is argued, is no more culturally determined than the predominant understanding of China that undergirds most scholarly studies of China, and no less enlightening. And yet Altishahri and other Islamic perspectives have been excluded from our notion of China, largely through a dependence on the concept of “syncretism.” As an alternative to the syncretism approach to cultural interchange, the article advocates for a greater focus on overlapping networks of shared meaning. Applied to the Altishahri case, this approach gives a sense of what is lost in the privileging of Islam and China as dominant categories, and shows the distortions involved in bounding these categories. Keywords: Islam, China, syncretism, Uyghur