Protein-DNA Interactions Regulate Human Papillomavirus DNA Replication, Transcription, and Oncogenesis.

Human papillomavirus (HPV) is a group of alpha papillomaviruses that cause various illnesses, including cancer. There are more than 160 types of HPV, with many being "high-risk" types that have been clinically linked to cervical and other types of cancer. "Low-risk" types of HPV cause less severe conditions, such as genital warts.

Aberrant calcium channel splicing drives defects in cortical differentiation in Timothy syndrome.

The syndromic autism spectrum disorder (ASD) Timothy syndrome (TS) is caused by a point mutation in the alternatively spliced exon 8A of the calcium channel Ca1.2. Using mouse brain and human induced pluripotent stem cells (iPSCs), we provide evidence that the TS mutation prevents a normal developmental switch in Ca1.

Orai1 inhibitor STIM2β regulates myogenesis by controlling SOCE dependent transcriptional factors.

Store-operated Ca entry (SOCE), the fundamental Ca signaling mechanism in myogenesis, is mediated by stromal interaction molecule (STIM), which senses the depletion of endoplasmic reticulum Ca stores and induces Ca influx by activating Orai channels in the plasma membrane. Recently, STIM2β, an eight-residue-inserted splice variant of STIM2, was found to act as an inhibitor of SOCE. Although a previous study demonstrated an increase in STIM2β splicing during in vitro differentiation of skeletal muscle, the underlying mechanism and detailed function of STIM2β in myogenesis remain unclear.

Alternative splicing converts STIM2 from an activator to an inhibitor of store-operated calcium channels.

Store-operated calcium entry (SOCE) regulates a wide variety of essential cellular functions. SOCE is mediated by STIM1 and STIM2, which sense depletion of ER Ca(2+) stores and activate Orai channels in the plasma membrane. Although the amplitude and dynamics of SOCE are considered important determinants of Ca(2+)-dependent responses, the underlying modulatory mechanisms are unclear.

State-dependent signaling by Cav1.2 regulates hair follicle stem cell function.

The signals regulating stem cell activation during tissue regeneration remain poorly understood. We investigated the baldness associated with mutations in the voltage-gated calcium channel (VGCC) Cav1.2 underlying Timothy syndrome (TS).

Using light to control signaling cascades in live neurons.

Understanding the complexity of neuronal biology requires the manipulation of cellular processes with high specificity and spatio-temporal precision. The recent development of synthetic photo-activatable proteins designed using the light-oxygen-voltage and phytochrome domains provides a new set of tools for genetically targeted optical control of cell signaling. Their modular design, functional diversity, precisely controlled activity and in vivo applicability offer many advantages for investigating neuronal function.

Prion metal interaction: is prion pathogenesis a cause or a consequence of metal imbalance?

Functional role of cellular prion protein (PrPc) has been hypothesized to be in metal homeostasis and providing cells with a superoxide dismutase (SOD)-like activity to escape damage by reactive oxygen species (ROS). PrPc interacts with a range of divalent metal ions and undergoes Cu2+ as well as Zn2+-associated endocytosis, thereby maintaining homeostasis of these and other metal ions. Conformational change to a beta-sheet rich, protease resistant entity, reminiscent of the disease-associated scrapie form called PrPsc, has been found to be induced by interaction of PrPc with metal ions like Cu2+, Zn2+, Mn2+ and Fe2+.

An atypical presentation of obsessive compulsive disorder with difficulty in hearing.

Obsessive compulsive disorder (OCD) is a common psychiatric disorder which is easily recognized. However, sometimes patients of OCD present in such an atypical or bizarre way that their problem comes to notice as being a psychiatric disorder after multiple consultations in different specialties. We are reporting a case of a man who had first sought opinion in the Department of Ear, Nose and Throat (ENT) for hearing impairment.

Formation of amyloid fibrils by bovine carbonic anhydrase.

Amyloids are typically characterized by extensive aggregation of proteins where the participating polypeptides are involved in formation of intermolecular cross beta-sheet structures. Alternate structure attainment and amyloid formation has been hypothesized to be a generic property of a polypeptide, the propensities of which vary widely depending on the polypeptide involved and the physicochemical conditions it encounters. Many proteins that exist in the normal form in-vivo have been shown to form amyloid when incubated in partially denaturing conditions.