An siRNA-guided ARGONAUTE protein directs RNA polymerase V to initiate DNA methylation

In mammals and plants, cytosine DNA methylation is essential for the epigenetic repression of transposable elements and foreign DNA. In plants, DNA methylation is guided by small interfering RNAs (siRNAs) in a self-reinforcing cycle termed RNA-directed DNA methylation (RdDM). RdDM requires the specialized RNA polymerase V (Pol V), and the key unanswered question is how Pol V is first recruited to new target sites without pre-existing DNA methylation. We find that Pol V follows and is dependent on the recruitment of an AGO4-clade ARGONAUTE protein, and any siRNA can guide the ARGONAUTE protein to the new target locus independent of pre-existing DNA methylation. These findings reject long-standing models of RdDM initiation and instead demonstrate that siRNA-guided ARGONAUTE targeting is necessary, sufficient and first to target Pol V recruitment and trigger the cycle of RdDM at a transcribed target locus, thereby establishing epigenetic silencing.

To be or not to be three: a clinical narrative, an unanswered question

The psychoanalytic literature deals with parenthood as a developmental stage but barely addresses the couple's preconception of fertility intentions. The author reviews the available literature from social research and psychoanalytic writing. Working with a couple over family of origin conflicts, she uncovers the hidden conflict over the wish to have or not have a child, reveals unconscious fantasies about the potential child, and deals with conflict in the otherwise compatible couple relationship itself. The author offers this clinical vignette to extend psychoanalytic understanding of the unconscious fantasies involved. She concludes with a discussion of transference towards the couple therapist as an infection to be avoided, an annoying parent to speed away from, and a disturbing child about whom the couple was ambivalent.

Control of low flow regions in the cortical vasculature determines optimal arterio-venous ratios

The energy demands of neurons are met by a constant supply of glucose and oxygen via the cerebral vasculature. The cerebral cortex is perfused by dense, parallel arterioles and venules, consistently in imbalanced ratios. Whether and how arteriole–venule arrangement and ratio affect the efficiency of energy delivery to the cortex has remained an unanswered question. Here, we show by mathematical modeling and analysis of the mapped mouse sensory cortex that the perfusive efficiency of the network is predicted to be limited by low-flow regions produced between pairs of arterioles or pairs of venules. Increasing either arteriole or venule density decreases the size of these low-flow regions, but increases their number, setting an optimal ratio between arterioles and venules that matches closely that observed across mammalian cortical vasculature. Low-flow regions are reshaped in complex ways by changes in vascular conductance, creating geometric challenges for matching cortical perfusion with neuronal activity.

An siRNA-guided Argonaute protein directs RNA Polymerase V to initiate DNA methylation

In mammals and plants, cytosine DNA methylation is essential for the epigenetic repression of transposable elements and foreign DNA. In plants, DNA methylation is guided by small interfering RNAs (siRNAs) in a self-reinforcing cycle termed RNA-directed DNA methylation (RdDM). RdDM requires the specialized RNA Polymerase V (Pol V), and the key unanswered question is how Pol V is first recruited to new target sites without preexisting DNA methylation. We find that Pol V follows and is dependent upon the recruitment of an AGO4-clade ARGONAUTE protein, and any siRNA can guide the ARGONAUTE protein to the new target locus independent of preexisting DNA methylation. These findings reject long-standing models of RdDM initiation and instead demonstrate that siRNA-guided ARGONAUTE targeting is necessary, sufficient and first to target Pol V recruitment and trigger the cycle of RdDM at a transcribed target locus, thereby establishing epigenetic silencing.

Dengue in COVID 19 pandemic year 2020- Enquiry into the unanswered question of 2020?

India along with the world is facing one of the worst pandemic in recent times with COVID-19. Emergence of SARS-CoV-2 in dengue virus (DENV)–endemic areas has raised concern regarding coinfection with the two viruses Difficulty in distinguishing dengue and COVID-19, particularly during the acute stage, can engender inaccurate diagnoses. To study the trends in Dengue infections during the COVID 19 pandemic and previous 2 years.A retrospective study considering all the Dengue serology tests over the period of 3 years was considered. Dengue serology tests by Dengue Rapid card, COVID RT PCR, COVID 19 IgM & IgG.Spiking of cases in alternate year in Karnataka.2250, 5070,2284 samples processed fro Dengue in 2018,2019 & 2020. The positive percentage was 10.3% in the year 2019. Dengue NS1 & IgM positive cases were more as the cases seeked support of healthcare at the initial phase of fever. Environmental factors did not have a significant role to play in the state. Study on cellular & immunolgical mechanisms of COVID 19 virus will lead to improved diagnsotic modalities and correct interpretation of test results preventing fatal outcomes. Encouraging vaccination for COVID-19 will reduce fatal outcomes.

Quantum battles in attoscience: tunnelling

What is the nature of tunnelling? This yet unanswered question is as pertinent today as it was at the dawn of quantum mechanics. This article presents a cross section of current perspectives on the interpretation, computational modelling, and numerical investigation of tunnelling processes in attosecond physics as debated in the Quantum Battles in Attoscience virtual workshop 2020. Graphic abstract

CDK4/6 inhibitor-induced colitis: a case report and review of the literature

A 72-year-old woman with metastatic ER/PR-positive breast cancer who had been on ribociclib and letrozole for 1 year developed severe life-threatening colitis. She presented to emergency department with features of acute abdomen and diarrhoea. The diagnosis of colitis was confirmed radiologically as well as by histopathological examination of the biopsy specimen and the patient clinically improved after withholding ribociclib and receiving corticosteroids compatible with ribociclib-induced colitis. The mechanism of injury in CDK 4/6 inhibitor-induced colitis is unknown but may be related to recruitment of inflammatory cells. Whether the development of colitis is associated with tumour response is an interesting and unanswered question.