Model-guided design of mammalian genetic programs.

Genetically engineering cells to perform customizable functions is an emerging frontier with numerous technological and translational applications. However, it remains challenging to systematically engineer mammalian cells to execute complex functions. To address this need, we developed a method enabling accurate genetic program design using high-performing genetic parts and predictive computational models. We built multifunctional proteins integrating both transcriptional and posttranslational control, validated models for describing these mechanisms, implemented digital and analog processing, and effectively linked genetic circuits with sensors for multi-input evaluations. The functional modularity and compositional versatility of these parts enable one to satisfy a given design objective via multiple synonymous programs. Our approach empowers bioengineers to predictively design mammalian cellular functions that perform as expected even at high levels of biological complexity.

Consecutive Hits of COVID-19 in India: The Mystery of Plummeting Cases and Current Scenario.

The novel coronavirus disease 2019 (COVID-19)-related pandemic has been in existence for almost 2 years now after its possible emergence from a wet market in the city of Wuhan of the Chinese mainland. Evidence of the emergence and transmission of this virus was attributed to bats and pangolins. The causative virus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has rapidly spread globally, affecting humans considerably with its current death toll to be over 4.7 million out of more than 233 confirmed cases as of September 2021. The virus is constantly mutating and continuously trying to establish itself in humans by increasing its transmissibility and virulence through its numerous emerging variants. Several countries have been facing multiple waves of COVID-19 outbreaks one after the other, putting the medical and healthcare establishments under tremendous stress. Although very few drugs and vaccines have been approved for emergency use, their production capabilities need to meet the needs of a huge global population. Currently, not even a quarter of the world population is vaccinated. The situation in India has worsened during the ongoing second wave with the involvement of virus variants with a rapid and huge surge in COVID-19 cases, where the scarcity of hospital infrastructure, antiviral agents, and oxygen has led to increased deaths. Recently, increased surveillance and monitoring, strengthening of medical facilities, campaigns of awareness programs, progressive vaccination drive, and high collaborative efforts have led to limiting the surge of COVID-19 cases in India to a low level. This review outlines the global status of the pandemic with special reference to the Indian scenario.

Constitutional LZTR1 mutation presenting with a unilateral vestibular schwannoma in a teenager.

Schwannomatosis is a rare neurofibromatosis clinically diagnosed by age-dependent criteria, with bilateral vestibular schwannoma and/or a constitutional NF2 mutation representing exclusion criteria. Following SMARCB1 germline mutations, constitutional mutations in LZTR1 were discovered. We report on the molecular investigation in a patient presenting at 14 years with a unilateral vestibular schwannoma, ultimately causing blindness and unilateral hearing loss, in the absence of other schwannomas or a positive family history. In DNA derived from frozen tumor tissue, a comprehensive NF2, SMARCB1 and LZTR1 analysis showed an NF2 truncating mutation c.1006_1021delins16; an LZTR1 mutation c.791+1G>A; and a partial 22q deletion including NF2, SMARCB1 and LZTR1. Sequence analysis on peripheral blood derived DNA showed the LZTR1 mutation to be constitutional, but the NF2 mutation and partial 22q deletion were not found, indicating them to be somatic events. RNA-based targeted analysis confirmed missplicing of LZTR1 intron 8, predicted to result in a premature stop codon. This LZTR1 mutation was paternally inherited. While isolated vestibular schwannoma or NF2 may be considered in a young individual with a unilateral vestibular schwannoma, this report suggests that LZTR1 -related schwannomatosis be added to this differential diagnosis.

Axillary lump: an unusual presentation of fat necrosis in the breast.

The clinical presentation of an axillary lump, in majority of cases, raises suspicion of an enlarged lymph node due to malignant causes. In this case report, we established a diagnosis of an axillary lump caused by fat necrosis. We present this case report with review of the literature to familiarize clinicians with this condition.

Susceptibility to astrocytoma and meningioma: influence of allelism at glutathione S-transferase (GSTT1 and GSTM1) and cytochrome P-450 (CYP2D6) loci.

We describe a case-control study to identify associations between polymorphism at the cytochrome P-450 (CYP2D6) and glutathione S-transferase (GSTT1 and GSTM1) loci and susceptibility to astrocytoma and meningioma. Accordingly, genotype frequencies in 112 astrocytoma and 50 meningioma patients were compared with frequencies in 577 controls. GSTM1 genotype frequencies in these groups were not different. Logistic regression analysis showed GSTT1 null and CYP2D6 poor metabolizer were risk factors in astrocytoma (odds ratio = 2.67 P = 0.0005 and odds ratio = 4.17 P = 0.0043, respectively) and meningioma (odds ratio = 4.52, P = 0.0001 and odds ratio = 4.90, P = 0.0132, respectively) when corrected for the other variables. No interactive effects between genotypes were identified. The data suggest polymorphism at loci encoding carcinogen-metabolizing enzymes influences susceptibility to astrocytoma and meningioma, possibly by determining effectiveness in the detoxification of environmental carcinogens.