Regulation of chromatin accessibility and gene expression in the developing hippocampal primordium by LIM-HD transcription factor LHX2.

In the mammalian cerebral cortex, the hippocampal primordium (Hcp) occupies a discrete position in the dorsal telencephalic neuroepithelium adjacent to the neocortical primordium (Ncp). We examined transcriptomic and chromatin-level features that distinguish the Hcp from the Ncp in the mouse during the early neurogenic period, embryonic day (E)12.5. ATAC-seq revealed that the Hcp was more accessible than the Ncp at this stage. Motif analysis of the differentially accessible loci in these tissues revealed LHX2 as a candidate transcription factor for modulating gene regulatory networks (GRNs). We analyzed LHX2 occupancy profiles and compared these with transcriptomic data from control and Lhx2 mutant Hcp and Ncp at E12.5. Our results revealed that LHX2 directly regulates distinct genes in the Hcp and Ncp within a set of common pathways that control fundamental aspects of development namely pluripotency, axon pathfinding, Wnt, and Hippo signaling. Loss of Lhx2 caused a decrease in accessibility, specifically in hippocampal chromatin, suggesting that this factor may play a unique role in hippocampal development. We identified 14 genes that were preferentially enriched in the Hcp, for which LHX2 regulates both chromatin accessibility and mRNA expression, which have not thus far been examined in hippocampal development. Together, these results provide mechanistic insight into how LHX2 function in the Hcp may contribute to the process by which the hippocampus acquires features distinct from the neocortex.

Dentate gyrus morphogenesis is regulated by ß-catenin function in hem-derived fimbrial glia.

The dentate gyrus, a gateway for input to the hippocampal formation, arises from progenitors in the medial telencephalic neuroepithelium adjacent to the cortical hem. Dentate progenitors navigate a complex migratory path guided by two cell populations that arise from the hem, the fimbrial glia and Cajal-Retzius (CR) cells. As the hem expresses multiple Wnt genes, we examined whether ß-catenin, which mediates canonical Wnt signaling and also participates in cell adhesion, is necessary for the development of hem-derived lineages. We report that, in mice, the fimbrial glial scaffold is disorganized and CR cells are mispositioned upon hem-specific disruption of ß-catenin. Consequently, the dentate migratory stream is severely affected, and the dentate gyrus fails to form. Using selective Cre drivers, we further determined that ß-catenin function is required in the fimbrial glial scaffold, but not in the CR cells, for guiding the dentate migration. Our findings highlight a primary requirement for ß-catenin for the organization of the fimbrial scaffold and a secondary role for this factor in dentate gyrus morphogenesis.

Post-cardiac Surgery Delirium: When the Details Matter!

How to cite this article: Suresh V, Magoon R. Post-cardiac Surgery Delirium: When the Details Matter! Indian J Crit Care Med 2024;28(2):185-187.

Optic Nerve Sheath Diameter in Hyponatremia: A Closer Look.

How to cite this article: Jose J, Suresh V, Magoon R. Optic Nerve Sheath Diameter in Hyponatremia: A Closer Look. Indian J Crit Care Med 2023;27(6):452.

A Clarion Call for a More Comprehensive Approach to Acute Respiratory Distress Syndrome Severity Categorization.

How to cite this article: Magoon R, Suresh V. A Clarion Call for a More Comprehensive Approach to Acute Respiratory Distress Syndrome Severity Categorization. Indian J Crit Care Med 2022;26(12):1308-1309.

Airborne Infections and Emergency Surgery: The COVID-19 Pandemic Perspective.

COVID-19 which emerged in Wuhan, China has rapidly spread all over the globe and the World Health Organisation has declared it a pandemic. COVID-19 disease severity shows variation depending on demographic characteristics like age, history of chronic illnesses such as cardio-vascular/renal/respiratory disease; pregnancy; immune-suppression; angiotensin converting enzyme inhibitor medication use; NSAID use etc but the pattern of disease spread is uniform - human to human through contact, droplets and fomites. Up to 3.5% of health care workers treating COVID-19 contact an infection themselves with 14.8% of these infections severe and 0.3% fatal. The situation has spread panic even among health care professionals and the cry for safe patient care practices are resonated world-wide. Surgeons, anesthesiologists and intensivists who very frequently perform endotracheal intubation, tracheostomy, non-invasive ventilation and manual ventilation before intubation are at a higher odds ratio of 6.6, 4.2, 3.1 and 2.8 respectively of contacting an infection themselves. Elective surgery is almost always deferred in fever/infection scenarios. A surgeon and an anesthesiologist can anytime encounter a situation where in a COVID-19 patient requires an emergency surgery. COVID-19 cases requiring surgery predispose anesthesiologists and surgeons to cross-infection threats. This paper discusses, the COVID-19 precautionary outlines which has to be followed in the operating room; personal protective strategies available at present; methods to raise psychological preparedness of medical professionals during a pandemic; conduct of anesthesia in COVID-19 cases/suspect cases; methods of decontamination after conducting a surgery for COVID-19 case in the operating room; and post-exposure prophylaxis for medical professionals.