The mystery to cellular youth may remain in maintaining a small nucleolus.

• Nucleolus is a spherical structure seen in the nucleus of a cell, that helps in the production and assembly of cellular ribosomes. Nucleolus is the place where the ribosomal RNA genes are transcribed as well as it houses the ribosomal DNA (rDNA).
• rDNA is susceptible to genomic instability.
• In all organisms from yeast to humans, nucleoli expands during aging process.
• Recently Gutierrez and Tyler hypothesised that keeping nucleoli small could delay the aging process.
• For testing their hypothesis they engineered an artificial way to secure rDNA to the membrane surrounding the nucleus of yeast cells so they could control when it was anchored and when it was not.
• The research group discovered that fastening the nucleolus was enough to keep them compact as well as the small nucleoli delayed aging process.
• They observed that the yeast nucleoli did not expand at the same rate during the entire lifespan. Nucleoli remained small for most of the yeast’s life. But once when a nucleolar size threshold was reached, they found out that it grow quickly and become larger in size.
• After attaining that threshold size, lot of changes happened to the nucleoli including (a) biophysical properties of nucleoli got changed and (b) proteins started entering the nucleoli including Rad52 (homologous recombinational repair protein), which is otherwise normally excluded .
• Such changes of nucleoli triggers rDNA instability due to aberrant recombination and it was observed that after such changes cells survived for only five more cell divisions.
• They confirmed from their studies that the nucleolar expansion beyond the specific size threshold is a ‘mortality timer’.

As aging is an associated risk factor for various health conditions including cardiovascular diseases, malignancies and neurodegenerative diseases, this finding may help in developing a therapeutic strategy that can delay the onset of aging or the onset of such diseases.

Blood Test to detect Alzheimer Disease

• Presently, a precise diagnosis of Alzheimer disease requires either a sample of CSF or a PET CT imaging of brain. Such type of diagnostics cannot be performed in primary care clinics.
• Palmqvist and co-workers from Sweden have developed a blood test that can recognize Alzheimer’s disease in older adults with nearly 90 % precision.
• Palmqvist and colleagues found out that the amyloid probability score 2 (APS2) had high diagnostic precision in recognizing alzheimer disease among individuals with cognitive symptoms in primary and secondary care.
• This new test measures the ratio of certain key biomarkers of this disease in the blood. i.e. the ratio of plasma phosphorylated tau 217 (p-tau217) relative to non–p-tau217 (expressed as percentage of p-tau217) combined with the amyloid-β 42 and amyloid-β 40 plasma ratio.

This test will speed up the diagnosis of Alzheimer disease. More clinical studies are warranted to confirm how this test can influence clinical care of patients and in near future we hope this test will get an FDA approval as well.

HIV Prevention

• A pre-exposure prophylaxis for HIV infection has came out.
• Pre-exposure prophylaxis is common, and has generally involved use of a combination pill called Truvada, taken daily or a new drug, lenacapavir, an injection that was given twice in a year, was found to be even more efficient, as the drug is long-acting:
• Bekker and colleagues in their study involving 5,338 women in South Africa and Uganda were randomly assigned to receive Truvada or lenacapavir.
• Participants were assigned in a 2:2:1 ratio to receive subcutaneous lenacapavir every 26 weeks, daily oral emtricitabine-tenofovir alafenamide, or daily oral emtricitabine-tenofovir disoproxil fumarate (active control); all participants also received the alternate subcutaneous or oral placebo.
• Those women in the lenacapavir arm didn’t developed HIV as compared to about two of every 100 people treated for a year with the other drugs developed HIV.

Stem cell treatment restores vision

• Absence or insufficient number of Corneal limbal epithelial stem cells in patients lead to a condition called limbal stem-cell deficiency (LSCD).
• LSCD leads to the encircling of the corneal surface by fibrotic conjunctival tissue and a resultant loss of vision or in serious cases, blindness.
• Thus LSCD lead to severe consequences for vision and is difficult to treat.
• Most of the attempts to replace cornea by corneal transplantation from appropriate donors to patients failed due to immune rejections.
• Recently Soma and colleagues reported the use of corneal epithelial cell sheets developed from human iPSCs can treat LSCD.
• In this clinical study, they transplanted an allogeneic human iPSC derived corneal epithelial cell sheets onto four eyes of four patients (ages between 39 and 72) with LSCD.
• The study demonstrated a restored vision, and the beneficial effects remain after four to five years of follow-up.

iPSC derived corneal epithelial cell sheet transplantation for LSCD was safe and efficacious in 4 of those patients in the clinical trial. Clinical trial with large patient cohort is warranted to further investigate the efficacy of the procedure. This study opens up the possibility of using iPSC derived cells for treating other eye diseases including corneal endothelial disease as well as retinitis pigmentosa

Reason for Female biased autoimmunity cracked

• Autoimmune diseases strangely affect females more than males. i.e. women accounts for 78% of all autoimmune diseases . The reason for this incidence was unknown till recently.
• Dou and co-workers found out that in females the XX sex chromosome complement is strongly related with vulnerability to autoimmunity.
• Normally in females, one X chromosome is silenced throughout the body’s cells. i.e. to achieve gene dosage compensation, Xist long non-coding RNA (lncRNA) is expressed only in females to randomly inactivate one of the two X chromosomes. Dou and colleagues suggests that a protein that silences the X chromosome may trigger the autoimmune diseases.
• They showed that male mouse model expressing transgenic Xist developed more severe multi organ pathology in a pristane induced lupus model than wild type male animals.
• Xist expression in males reprogrammed T and B cell populations and chromatin states to more resemble wild-type females.
• They also showed that human patients with autoimmune diseases displayed significant autoantibodies to multiple components of XIST ribonucleoprotein.
• Thus Dou and colleagues showed that a sex-specific lncRNA scaffolds ubiquitous ribonucleoprotein components drive sex-biased immunity.

Even though this study throws light to the mechanisms linked with X chromosome inactivation and autoimmune diseases, more research is needed to understand its implications.

Treatment for multiple food allergies

• Food allergy affects children and adults 8% and 10% respectively in the US.
• A large percentage (30% - 86%) of those affected with food allergies are allergic to multiple foods.
• Current management for food allergies are food avoidance and emergency treatment, if accidental exposure occurs.
• Only one FDA approved oral immunotherapy product for peanut allergy is AR10, but unfortunately associated with adverse reactions.
• A monoclonal antibody Omalizumab, approved by FDA for use in patients above 1 year of age, binds to IgE has shown promise for the treatment of multiple food allergies in clinical trials.
• However, the drug, injected every two or four weeks, does not cure food allergies, and patients must continue to avoid foods with allergens in them.