The COVID-19 pfizer BioNTech mRNA vaccine and the frequency of seizures.

OBJECTIVE: A nationwide vaccination operation against Coronavirus disease 2019 (COVID-19) using the BNT162b2 mRNA vaccine commenced in Israel in December 2020. People older than 60 were prioritized, and most were vaccinated shortly after. Seizures are not infrequently attributed to the vaccine despite a lack of supporting evidence. People with epilepsy (PWE) are often reluctant to get the vaccine due to concerns of seizure aggravation. We aim to examine the effect of the vaccine effort on the frequency of both new-onset seizures and recurrent seizures in PWE. METHODS: All adults who presented to the emergency department (ED) of Tel Aviv Sourasky Medical Center between January 1st and May 31st, 2017-2021, and were diagnosed with seizures were included. Demographic, clinical, and vaccination status parameters were collected using MDClone, a data acquisition tool. Vaccination rates in the general population were obtained from official governmental publications. Statistics included a sub-analysis of patients with the highest vaccination rate, people older than 60. RESULTS: 1675 cases were included. The numbers of ED visits and hospital admissions due to seizures in 2021 were comparable to preceding years after adjusting for the total number of ED visits at the same time. Out of 339 cases in 2021, 134 patients older than 60 years old presented to the ED (39.5%) compared to 124-151 in 2017-2019 (37-44%) and 103 in 2020 (33%). The vaccination rate among patients hospitalized due to seizures was similar to the general population of the same age group during the same period in Israel. There was no temporal relation between vaccination and hospitalization due to a seizure. SIGNIFICANCE: Despite very high vaccination rates in the general population in Israel and especially among people older than 60 years, no increase was observed in ED presentations due to seizures. No temporal relation was observed between vaccination and hospitalization due to a seizure. We conclude that the mass vaccination with the Pfizer BioNTech mRNA vaccine is not associated with increased seizure propensity.

The flowering hormone florigen accelerates secondary cell wall biogenesis to harmonize vascular maturation with reproductive development.

Florigen, a proteinaceous hormone, functions as a universal long-range promoter of flowering and concurrently as a generic growth-attenuating hormone across leaf and stem meristems. In flowering plants, the transition from the vegetative phase to the reproductive phase entails the orchestration of new growth coordinates and a global redistribution of resources, signals, and mechanical loads among organs. However, the ultimate cellular processes governing the adaptation of the shoot system to reproduction remain unknown. We hypothesized that if the mechanism for floral induction is universal, then the cellular metabolic mechanisms underlying the conditioning of the shoot system for reproduction would also be universal and may be best regulated by florigen itself. To understand the cellular basis for the vegetative functions of florigen, we explored the radial expansion of tomato stems. RNA-Seq and complementary genetic and histological studies revealed that florigen of endogenous, mobile, or induced origins accelerates the transcription network navigating secondary cell wall biogenesis as a unit, promoting vascular maturation and thereby adapting the shoot system to the developmental needs of the ensuing reproductive phase it had originally set into motion. We then demonstrated that a remarkably stable and broadly distributed florigen promotes MADS and MIF genes, which in turn regulate the rate of vascular maturation and radial expansion of stems irrespective of flowering or florigen level. The dual acceleration of flowering and vascular maturation by florigen provides a paradigm for coordinated regulation of independent global developmental programs.

A cytokinin-activating enzyme promotes tuber formation in tomato.

BACKGROUND: Dedicated storage organs in the form of tubers are evolutionary novelties that share a common function but originate in diverse species from different organs. Tubers in potato, Solanum tuberosum, are derived from the swollen tips of specialized basal lateral juvenile shoots, called stolons. Lateral buds of tomato, Solanum lycopersicum, a potato sibling species, only form regular shoots. The evo-devo mechanisms restricting tuber formation to basal juvenile axillary meristems of potato while completely inhibiting it in tomato meristems are not currently understood. RESULTS: Ectopic expression of tomato LONELY GUY (LOG1), a cytokinin (CK) biosynthesis gene, imparts potential to the outgrowing juvenile tomato buds to generate, de novo, aerial minitubers (TMTs). TMTs are morphologically, developmentally, and metabolically homologous to aerial potato tubers and display a unique transcriptome with altered hormonal signaling networks. The new hormonal balance stimulates ectopic branching of dormant axillary meristems and loss of apical dominance without disruption of polar auxin transport and obviates the need for specific branching genes. miR156, a master regulator of juvenility, extends tuber-forming potential to distal axillary buds in both wild-type potato and tomato primed by LOG1 signaling. CONCLUSIONS: Ubiquitous activation of TLOG1 uncovered a developmentally suppressed tuber-forming potential within tomato axillary meristems. Other meristems in other plants may also carry hidden, suppressed organogenesis potentials. The unlocking of this potential by the activity of a single gene represents a prime example of an evolutionary novelty in the making and suggests that CKs may function as universal regulators of storage-organ formation in plants.

Sp1 phosphorylation is involved in myelin basic protein gene transcription.

Myelin basic protein (MBP), which helps form compact myelin sheets, is a major protein expressed during oligodendrocyte (OL) differentiation. Myelin basic protein expression is regulated mainly at the transcriptional level. Previous studies showed that the transcription factor Sp1 can activate the MBP promoter. Data from the laboratory also indicate that Sp1 is expressed highly in both growing and differentiated cells. Because this is true, we wanted to understand how Sp1 activity is regulated such that it increases MBP gene transcription only in differentiating cells. Phosphorylation is one major way to regulate transcription factor activity. Our results show that there is more Sp1 binding to the MBP promoter in differentiating OLs. Sp1 is also more phosphorylated in differentiating OLs than in precursor cells. Using inhibitors of different pathways, we found that the protein kinase C (PKC) modulator phorbol 12-myristate 13-acetate (PMA) can increase Sp1 phosphorylation when the cells are treated for 1 hr and can decrease Sp1 phosphorylation with long treatment (12 hr). The increased phosphorylation of Sp1 induced by PMA in short treatments could be abolished by the extracellular signal-regulated kinases (ERK) pathway inhibitor PD98059. This indicates that PKC phosphorylates Sp1 through the ERK pathway. Mutation of Sp1 threonines 453 and 739, which are phosphorylated by ERK, decreased MBP transcriptional activity. Furthermore, we found that PKC regulates Sp1 phosphorylation only in differentiating OLs. In conclusion, our results indicate that, in OLs, Sp1 phosphorylation can be regulated by PKC-ERK pathways. This phosphorylation is important for MBP transcription and oligodendrocyte differentiation.

Galectin-4 is involved in p27-mediated activation of the myelin basic protein promoter.

Our previous studies have found that expression of p27 in oligodendrocytes enhances myelin basic protein (MBP) gene expression through a mechanism that involves the transcription factor Sp1. In this study we show that this activation only requires the N-terminal 45 amino acids of p27 containing a functional cyclin-binding motif. In an effort to identify other cofactors that are involved in the p27-mediated activation of MBP gene expression, a yeast two-hybrid assay was performed using an N-terminal truncated p27 and a mouse embryo cDNA library. Galectin-4 was found to interact with p27 in the yeast two-hybrid assay. This novel interaction was also confirmed using a glutathione-S-transferase interaction assay and immunoprecipitation assays. Expression of galectin-4 in primary oligodendrocytes was confirmed by western blot. Additionally, the MBP promoter could be activated by expression of galectin-4 in CG4 oligodendrocytes, similar to the effects of increased p27 levels. We also show that Sp1 and galectin-4 interact in cells, while a complex of all three proteins could not be found. We conclude that galectin-4 is involved in the p27-mediated activation of the MBP gene, possibly through modulation of the glycosylation status of the transcription factor Sp1.