Dual role for transactivator protein C in activation of mom promoter of bacteriophage Mu

Transactivator C protein of bacteriophage Mu activates the mom gene of the phage by an unusual mechanism. DNA binding by C to its site results in unwinding of the neighboring sequences, realigning the out-of-phase promoter elements to facilitate RNA polymerase (RNAP) binding. High level stimulation of a C-independent constitutive promoter mutant (where RNAP is already bound) by the transactivator suggested an additional mechanism of transcription activation at a step after RNAP recruitment. In this study, we have investigated the various steps of promoter-polymerase interactions during transcription initiation by using both the promoter mutant and a positive control (pc) mutant of C protein. The transactivator does not influence formation of the open complex or its stability after facilitating the RNAP binding. However, at a subsequent step, the protein exerts an important role, enhancing the promoter clearance by increasing the productive RNAP.promoter complex. The pc mutant of the transactivator C is compromised at this step, supporting the additional downstream role for C in mom transcription activation. We suggest that this unusual multistep activation of Pmom has evolved to ensure irreversibility of the switch during the late lytic cycle of the phage

Bacteriophage Mu C protein is a new member of unusual leucine zipper-HTH class of proteins

Transcription activator protein C of bacteriophage Mu activates transcription of the late genes, including mom, during the lytic cycle of the phage. C binding to its site leads to the alteration in DNA topology of the promoter elements resulting in RNA polymerase (RNAP) recruitment. At the next step, the transactivator enhances promoter clearance of RNAP from Pmom. The C protein binds DNA with a very high affinity using a carboxylterminal helix turn helix (HTH) motif which has similarity with the HTH from paired domain of Drosophila prd protein. Previous studies established that the protein is dimeric in free and DNA bound forms. We describe now the unique dimerization interface of the protein. Two heptad repeats of hydrophobic amino acids found in the protein were considered to be the candidates for dimerization region. Site-directed mutational analysis revealed that the amino-terminal coiled coil region is not the dimerization determinant. In contrast, similar mutagenesis studies indicated a role for the leucine zipper motif, located in the middle region of the protein, in dimerization. Mixed oligomerization assays confirmed the importance of leucine zipper in C dimer formation establishing the presence of an uncommon zipper-HTH domain in the transactivator

An atypical manifestation of lateral medullary syndrome

Lateral medullary syndrome is a common brainstem stroke associated with a classical triad of Horner's Syndrome, ipsilateral ataxia and hypalgesia and thermoanasthesia of ipsilateral face.We report a case of a 49-year-old diabetic, non-hypertensive, postmenopausal female who presented with symptoms involving the left dorsal medulla along with right sided hemiparesis and left UMN-type facial palsy. Contralateral hemiparesis was explained by caudal extension of infarct involving the pyramids before decussation at the medulla, known as Babinski-Nageotte Syndrome. UMN-type facial palsy was attributed to involvement of hypothetical supranuclear aberrant corticobulbar fibres of facial nerve which descend down in the contralateral ventromedial medulla, decussate at level of upper medulla and then ascend in the dorsolateral medulla to reach the facial nerve nucleus. Association of these two entities with Wallenberg's Syndrome have been reported separately in literature, but not together as in this case. © The Author(s) 2019

Eye of the tiger sign in neurodegeneration with brain iron accumulation: a case report

Neurodegeneration with brain iron accumulation (NBIA) is a rare autosomal recessive disorder characterized by abnormal accumulation of ferritin in globus pallidus of brain. Magnetic resonance imaging (MRI) of brain demonstrates a characteristic ‘eye-of-the-tiger’ sign. We describe a case of NBIA in a child with classical clinical and MRI of brain features

Leptospirosis complicated with meningoencephalitis and pancreatitis – A case report

In severe leptospirosis multi organ involvement is common. Pancreatitis and meningo encephalitis are two\ud uncommon manifestations of leptospirosis. Our patient presented with fever, jaundice, altered sensorium and\ud subsequently developed severe pain abdomen. He was finally diagnosed as having icteic leptospirosis\ud complicated with pancreatitis and meningoencephalitis. Simultaneous presence of these two complications in a\ud patient of leptospirosis probably not been documented before

Cerebral infarction: an unusual manifestation of viper snake bite

Snake envenomation causes significant mortality and morbidity. Viper bite usually present with local cellulites, renal failure and bleeding disorders. Thrombotic manifestation of snake bite is rarely reported and early administration of Anti-Snake Venom Serum (ASV) also reduces the risk of thrombotic complications. Cerebral infarction in case of viper bite may be due to hypotension, hypercoagulability or direct action of venom on vessel wall. We report a rare case of viper bite, presented with renal failure and cerebral infarction in spite of early ASV institution. The thrombotic manifestation in this case was possibly due to disseminated intravascular coagulation

Pelvic Exenteration: Experience from a Rural Cancer Center in Developing World

Background. Pelvic exenteration (PE) is a morbid procedure. Ours is a rural based cancer center limited trained surgical oncology staff. Hence, this audit was planned to evaluate morbidity and outcomes of all patients undergoing PE at our center. Methods. This is a IRB approved retrospective audit of all patients who underwent PE at our center from January 2010 to August 2013. The toxicity grades were retrospectively assigned according to the CTCAE version 4.02 criteria. Chi-square test was done to identify factors affecting grades 3–5 morbidity. Kaplan Meier survival analysis has been used for estimation of median PFS and OS. Results. 34 patients were identified, with the median age of 52 years (28–73 years). Total, anterior, posterior, and modified posterior exenterations were performed in 4 (11.8%), 5 (14.7%), 14 (41.2%), and 11 (32.4%) patients, respectively. The median time for surgery was 5.5 hours (3–8 hours). The median blood loss was 500 mL (200–4000 mL). CTCAE version 4.02 grades 3-4 toxicity was seen in nine patients (25.7%). The median estimated progression free survival was 31.76 months (25.13–38.40 months). The 2-year overall survival was 97.14%. Conclusion. PE related grades 3–5 morbidity of 25.7% and mortality of 2.9% at our resource limited center are encouraging