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Cassava ( Manihot esculenta Crantz) is an important root crop, which despite its drought tolerance suffers considerable yield losses under water deficit. One strategy to increase crop yields under water deficit is improving the crop's transpiration efficiency, which could be achieved by variety selection and potassium application. We assessed carbon isotope composition in bulk leaf material and extracted carbohydrates (soluble sugar, starch, and cellulose) of selected leaves one month after inducing water deficit to estimate transpiration efficiency and storage root biomass under varying conditions in a greenhouse experiment. A local and improved variety were grown in sand, supplied with nutrient solution with two potassium levels (1.44 vs. 0.04 mM K + ) and were subjected to water deficit five months after planting. Potassium application and selection of the improved variety both increased transpiration efficiency of the roots with 58% and 85% respectively. Only in the improved variety were 13 C ratios affected by potassium application (up to - 1.8‰ in δ 13 C of soluble sugar) and water deficit (up to + 0.6‰ in δ 13 C of starch and soluble sugar). These data revealed a shift in substrate away from transitory starch for cellulose synthesis in young leaves of the improved variety under potassium deficit. Bulk δ 13 C of leaves that had fully developed prior to water deficit were the best proxies for storage root biomass (r = - 0.62, r = - 0.70) and transpiration efficiency (r = - 0.68, r = - 0.58) for the local and improved variety respectively, making laborious extractions redundant. Results obtained from the youngest fully developed leaf, commonly used as a diagnostic leaf, were complicated by remobilized assimilates in the improved variety, making them less suitable for carbon isotope analysis. This study highlights the potential of carbon isotope composition to assess transpiration efficiency and yield, depending on the chosen sampling strategy as well as to unravel carbon allocation processes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Van Laere, Merckx, Hood-Nowotny and Dercon.)

Rationale: Cassava production faces challenges in a changing climate. Pulse labelling cassava with 13 C-CO 2 has the potential to elucidate carbon allocation mechanisms of cassava under drought stress and with potassium application. Understanding these mechanisms could guide efforts to mitigate effects of drought in cassava cropping systems., Methods: Forty-eight cassava plants received a nutrient solution high or low in potassium. Water deficit was imposed on half of the plants at bulk root initiation stage, after which they were labelled for 8 h with 13 C-CO 2 in a 15 m 3 growth chamber. Plants were harvested 8 h, 9 days and 24 days after labelling, and separated into leaves, stems and roots. δ 13 C values of the different parts were measured using an isotope ratio mass spectrometer, from which 13 C excess was calculated., Results: Water deficit decreased transpiration (P < 0.001) and increased carbon respiration (P < 0.05). Potassium application increased assimilate distribution to the roots (P < 0.05) at 9 days after labelling, more strongly for plants under water deficit. The opposite was found at 24 days (P < 0.05) with the legacy of water deficit additionally increasing assimilate distribution to roots (P < 0.05). Youngest, fully expanded leaves contained up to 47% of initial 13 C excess at 24 days after labelling., Conclusions: Pulse labelling proved to be successful in shedding light on carbon allocation in relation to water and potassium availability. This technique, once adapted to field conditions, could further be used to improve fertilizer recommendations or change agronomic practices to cope with plant stress., (© 2022 The Authors. Rapid Communications in Mass Spectrometry published by John Wiley & Sons Ltd.)

Dysregulation of kinase signaling pathways favors tumor cell survival and therapy resistance in cancer. Here, we reveal a posttranslational regulation of kinase signaling and nuclear receptor activity via deubiquitination in T cell acute lymphoblastic leukemia (T-ALL). We observed that the ubiquitin-specific protease 11 (USP11) is highly expressed and associates with poor prognosis in T-ALL. USP11 ablation inhibits leukemia progression in vivo, sparing normal hematopoiesis. USP11 forms a complex with USP7 to deubiquitinate the oncogenic lymphocyte cell-specific protein-tyrosine kinase (LCK) and enhance its activity. Impairment of LCK activity leads to increased glucocorticoid receptor (GR) expression and glucocorticoids sensitivity. Genetic knockout of USP7 improved the antileukemic efficacy of glucocorticoids in vivo. The transcriptional activation of GR target genes is orchestrated by the deubiquitinase activity and mediated via an increase in enhancer-promoter interaction intensity. Our data unveil how dysregulated deubiquitination controls leukemia survival and drug resistance, suggesting previously unidentified therapeutic combinations toward targeting leukemia.

MYCN is an oncogenic driver in neural crest-derived neuroblastoma and medulloblastoma. To better understand the early effects of MYCN activation in a neural-crest lineage context, we profiled the transcriptome of immortalized human retina pigment epithelial cells with inducible MYCN activation. Gene signatures associated with elevated MYC/MYCN activity were induced after 24 h of MYCN activation, which attenuated but sustained at later time points. Unexpectedly, MYCN activation was accompanied by reduced cell growth. Gene set enrichment analysis revealed a senescence-like signature with strong induction of p53 and p21 but in the absence of canonical hallmarks of senescence such as β-galactosidase positivity, suggesting incomplete cell fate commitment. When scrutinizing the putative drivers of this growth attenuation, differential gene expression analysis identified several regulators of nucleolar stress. This process was also reflected by phenotypic correlates such as cytoplasmic granule accrual and nucleolar coalescence. Hence, we propose that the induction of MYCN congests the translational machinery, causing nucleolar stress and driving cells into a transient pre-senescent state. Our findings shed new light on the early events induced by MYCN activation and may help unravelling which factors are required for cells to tolerate unscheduled MYCN overexpression during early malignant transformation., (© 2021. The Author(s).)

Reverse transcription quantitative PCR (RT-qPCR) is the gold standard method for gene expression analysis on mRNA level. To remove experimental variation, expression levels of the gene of interest are typically normalized to the expression level of stably expressed endogenous reference genes. Identifying suitable reference genes and determining the optimal number of reference genes should precede each quantification study. Popular reference genes are not necessarily stably expressed in the examined conditions, possibly leading to inaccurate results. Stably and universally expressed repetitive elements (ERE) have previously been shown to be an excellent alternative for normalization using classic reference genes in human and zebrafish samples. Here, we confirm that in mouse tissues, EREs are broadly applicable reference targets for RT-qPCR normalization, provided that the RNA samples undergo a thorough DNase treatment. We identified Orr1a0, Rltr2aiap, and Rltr13a3 as the most stably expressed mouse EREs across six different experimental conditions. Therefore, we propose this set of ERE reference targets as good candidates for normalization of RT-qPCR data in a plethora of conditions. The identification of widely applicable stable mouse RT-qPCR reference targets for normalization has great potential to facilitate future murine gene expression studies and improve the validity of RT-qPCR data.

Thomas Montanus (1617-1685), physician of the City of Bruges, is the author of a voluminous treatise on plague, published in 1669, and written after an epidemic of plague in Bruges in 1666. A translation in Dutch of the treatise will be published shortly. In this contribution some biographical data on Montanus are presented: his descendence, his education, his career and his professional experience with plague. On the other hand the structure of the plague treatise Qualitas loimodea sive pestis Brugana is briefly mentioned.

In a short historical perspective we restrain the meaning of the concept oenology to the importance of wine as a treatment of well defined internal diseases, with special attention to the 16th and 17th centuries and to the personality of Nonnius. Hippocrates was the first physician who ascertained the healing value of wine. He recommended white wine in cases of dropsy and red wine in order to stimulate hunger and to nourish the body. The opinion of the Ancients concerning wine remained almost unchanged during the Middle Ages. Eight chapters of Nonnius' "Diaeteticon" are dedicated to wine. The Antwerp scholar agrees with Galen, who teaches that "dark and sweet wines produce much blood, while white and light ones produce but little blood, so that the first ones are proper to feed the body and the other ones to get rid of liquids through the urine.' Nonnius further discusses honey-wine and 'mulsa' or hydromel. But it is not before the latest half century that oenology has made enormous progress due to the use of new techniques and as a result of the practice of oenotherapy by conscientious researchers, based upon serious scientific research. However, two fundamental remarks have to be made: the daily quantity shall not exceed four glasses, divided over the two principal meals, and wine shall always be drunk with food. Recent research proves that wine may be a helpful adjuvant, when the blood circulation is at stake.

Before we comment the subject of this lecture, we attract the reader's attention towards two remarks. We first want to point out that, although Vesalius is rightly considered as "the father of anatomy", in physiological matters--such as e.g. the physiology of the nervous system--he remained a faithful follower of Galen. A second preliminary remark explains why the books Vesalius devoted to the nervous system, namely the fourth and seventh books, as well as a part of the third book, don't belong to the best parts of the Fabrica, when we compare them with his Osteology and his Myology. We should not forget that some technical discoveries such as keeping brain-tissue in alcohol in order to harden it and colouring methods of Weigert, Marchi and Nissl, that made a refined macro- and microscopic examination of the nervous system possible, were only invented in the 19th century. The fourth book considers the peripheral nervous system. According to Vesalius, there are seven pairs of brain-nerves. His first pair corresponds to our Nervous opticus; his second pair concerns our Nervi oculomotorius, trochlearis and abducens; this third pair embraces a great part of our Nervus trigeminus; his fourth pair corresponds to our Nervus maxillaris; his fifth pair includes our Nervi facialis and acusticus; his sixth pair includes our Nervi vagus and accessorius; his seventh pair our Nervi hypoglossus and pharyngeus. Vesalius counts thirty pairs of spinal nerves. His description of the Plexus brachialis and the Plexus ischiadicus is closely related to the modern views in these matters. However, his teleologic views about them are remarkable, e.g. about the course of the Nervi recurrentes. The seventh book covers the brain. He successively and truly describes the cerebral membranes, the Ventriculi, the Cerebrum; his description relies on a series of horizontal slices. He also describes the brain-stem and the Cerebellum. Vesalius, who had doubts about the existence of the Plexus reticularis in Man, gives a tendentious description of the Infundibulum based on a false physiological theory about the secretion of "pituita", which he considers as the sluggish refuse of the ventricular system. A chapter of the third book is devoted to the blood circulation in the nervous system, with the unavoidable errors derived from Vesalius' galenic theories about blood distribution. We should point out the fact that Vesalius emphasizes quite rightly the metameric blood circulation of the spine. Finally, we should also emphasize the beauty of the images concerning the nervous system in Vesalius' works.

The poem Syphilis sive morbus gallicus was published by Fracastor in 1530. It is written in excellent Latin and gives a valuable description of the symptomatology of this venereal disease, that had appeared in Europe some years before. In his De morbis contagiosis, printed in Venice in 1546, Fracastor describes the cause of syphilis and appears as a precursor of bacteriology. Fracastor was born in 1483 within a well-known medical family. He studied the Fine Arts, Mathematics and Medicine in Padova. He made himself famous not only as a physician, but also as an astronomer, a naturalist, a poet and a philosopher. He acted as arbitrator between two of his fellow-physicians--Gaioni and Fumanelli--who couldn't come to an agreement as to the "nature" of wine. He communicated his reasons and conclusions in his treaty De vini temperatura sententia, published in 1534. Leaning on a rather scholastic reasoning, he takes the side of Fumanelli, who considers wine as being a "dry" remedy. What may be of interest for the modern reader, are the passages where Fracastor, as an excellent oenologist, enumerates the different wines and describes the indications for wine as a medicine. Remarkable are also the passages in which he, be it rather reluctantly, dares to contradict the Ancients.

Neurology and psychiatry differ from the other branches of medicine by their narrow implication with the nervous system. However, owing to the quantitative importance of neuroses in daily practice, an unbridgeable gap might appear between psychiatry, concerning the mind, and neurology, concerning the body. That gap cannot be justified, because the most psychogenic mental disease is associated with organic components and, on the other side, the most organic mental disorder is associated with psychological components; failing to appreciate purely psychical disturbances as preliminary symptoms of certain organic brain-disorders may have a fatal issue for the patient. Only the organic investigation, in the broadest sense of the term, of the nervous system may, in our time, allow an always closer approach to the background of psychiatric diseases that were considered, in earlier times, as purely psychogenic. The author chose Alzheimer's disease as an instance of the necessary intercourse between psychiatry and neurology. The author discusses the epidemiology, the symptomatology, the anatomopathology, the biochemistry and the therapy of this disease. In comparison with the course of things concerning Parkinson's disease, we may be sure that our knowledge concerning Alzheimer's disease will depend upon a narrow collaboration between psychiatry and the different branches of neurology.

The author reports a new case of chronic progressive bulbo-pontine paralysis with deafness. This case differed from other cases previously published on the basis of the later age of onset of labio-glosso-laryn-geal paralysis, by the absence of any vestibular changes despite bilateral involvement of the acoustic centres and above all by the normality of deep tendon reflexes. The author feels that chronic progressive vulvo-pontine paralysis with deafness is a specific individual condition, worthy of consideration as an autonomic clinical entity.