The minimal SUF system is not required for Fe-S cluster biogenesis in the methanogenic archaeon Methanosarcina acetivorans.

Iron-sulfur (Fe-S) proteins are essential for the ability of methanogens to carry out methanogenesis and biological nitrogen fixation (diazotrophy). Nonetheless, the factors involved in Fe-S cluster biogenesis in methanogens remain largely unknown. The minimal SUF Fe-S cluster biogenesis system (i.e., SufBC) is postulated to serve as the primary system in methanogens. Here, the role of SufBC in Methanosarcina acetivorans, which contains two sufCB gene clusters, was investigated. The CRISPRi-dCas9 and CRISPR-Cas9 systems were utilized to repress or delete sufC1B1 and sufC2B2, respectively. Neither the dual repression of sufC1B1 and sufC2B2 nor the deletion of both sufC1B1 and sufC2B2 affected the growth of M. acetivorans under any conditions tested, including diazotrophy. Interestingly, deletion of only sufC1B1 led to a delayed-growth phenotype under all growth conditions, suggesting that the deletion of sufC2B2 acts as a suppressor mutation in the absence of sufC1B1. In addition, the deletion of sufC1B1 and/or sufC2B2 did not affect the total Fe-S cluster content in M. acetivorans cells. Overall, these results reveal that the minimal SUF system is not required for Fe-S cluster biogenesis in M. acetivorans and challenge the universal role of SufBC in Fe-S cluster biogenesis in methanogens.

Pituitary metastases: a case series and scoping review.

PURPOSE: To understand the natural history and optimal treatment strategy for pituitary gland metastasis. METHODS: We performed both a retrospective chart review of patients treated at our institution and a scoping review of the topic. RESULTS: The retrospective review identified seven patients with an average age of 59.6 years. Primary histologies included breast cancer (4), melanoma (1), renal cell carcinoma (1), and sarcoma (1). Two patients had anterior pituitary endocrine dysfunction, one of whom was the only patient with visual symptoms. All patients were treated with radiosurgery and two also underwent surgical resection. Overall survival ranged from 6.5 to 117 months. Literature review identified 166 patients from 71 studies. The most common primary cancer was lung (27.7%), followed by breast (18.7%) and renal (14.5%) cancer. 107 presented with endocrine dysfunction, including 41 cases of diabetes insipidus and 55 cases of hypopituitarism. 110 presented with visual compromise. 107 patients received radiotherapy, 96 underwent surgical resection and 44 received systemic chemotherapy/immunotherapy. Surgery was significantly associated with an increased likelihood of vision improvement and a decreased likelihood of endocrine normalization. Radiographic regression predicted visual improvement. Median overall survival was 9.9 months (range: 0.2-96). CONCLUSIONS: This scoping review showed that both radiosurgery and surgical resection have been frequently used to treat pituitary metastases with good response. Vision improvement is more likely to happen following surgical resection, likely at the expense of endocrine dysfunction. Despite treatment and radiographic response, patient survival remains less than a year.

Concomitant Rupture of an Intracranial Aneurysm and a Dural Arteriovenous Fistula: Clinical Image.

A patient in his 50s presented with postcoital severe headache. Computed tomography revealed a subarachnoid hemorrhage but also a subdural hematoma at the left convexity. Computed tomography angiography revealed a large irregular anterior communicating artery aneurysm but also cortical serpiginous vessels suggestive of a vascular malformation adjacent to the subdural hematoma in the left convexity. Digital subtraction angiography confirmed the ruptured aneurysm but also revealed a Borden 3 type dural arteriovenous fistula on the left convexity. The fistula had arterial supply mostly from middle meningeal artery branches and venous drainage directly to a left cortical vein adjacent to superior sagittal sinus. Ruptured aneurysm was treated with coiling. The ruptured fistula was treated in the same session with transarterial Onyx embolization. The patient had a favorable outcome. Our case is an important reminder for all clinicians treating patients with intracranial hemorrhages on the necessity of fully reviewing all available preoperative imaging.

Antimicrobial peptides: A promising tool to combat multidrug resistance in SARS CoV2 era.

COVID-19 (Coronavirus Disease 2019), a life-threatening viral infection, is caused by a highly pathogenic virus named SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2). Currently, no treatment is available for COVID-19; hence there is an urgent need to find effective therapeutic drugs to combat COVID-19 pandemic. Considering the fact that the world is facing a major issue of antimicrobial drug resistance, naturally occurring compounds have the potential to achieve this goal. Antimicrobial peptides (AMPs) are naturally occurring antimicrobial agents which are effective against a wide variety of microbial infections. Therefore, the use of AMPs is an attractive therapeutic strategy for the treatment of SARS-CoV-2 infection. This review sheds light on the potential of antimicrobial peptides as antiviral agents followed by a comprehensive description of effective antiviral peptides derived from various natural sources found to be effective against SARS-CoV and other respiratory viruses. It also highlights the mechanisms of action of antiviral peptides with special emphasis on their effectiveness against SARS-CoV-2 infection.

Clinical, Prognostic and Therapeutic Significance of Heat Shock Proteins in Cancer.

BACKGROUND: Heat Shock Proteins (HSPs) constitute a group of proteins that play a crucial role in the process of protein folding. HSPs are also known to modulate a number of key apoptotic factors. High expression of these proteins is reported in an array of cancers, such as breast, prostate, colorectal, lung, ovarian, gastric, oral and esophageal cancer. Ample amount of investigations were carried out on a variety of cancers suggesting HSPs as a promising hallmark in cancers. Their expression profile in several tumors elucidates that they help in proliferation, invasion, metastasis and death of cancerous cells. Detection of the levels of heat shock proteins and their specific antibodies in the sera of diseased individuals can play an important role in cancer diagnosis. OBJECTIVES: This review will present and summarize latest research being carried out on heat shock proteins. It will also highlight the clinical and prognostic features of HSP27, HSP60, HSP70, HSP90 and HSP110, and will discuss future implications of HSPs in the diagnosis and prognosis of cancer. Furthermore, the role of heat shock proteins as a therapeutic target in cancer will be discussed. In addition, the review article will report various studies, where HSPs have been targeted for their therapeutic potential. CONCLUSION: In summary, multiple experimental investigations have been successful in suggesting the role of heat shock protein as a clinical biomarker and therapeutic target in cancer. HSPs are associated with a number of cancer hallmarks such as cell proliferation, invasion and metastasis. Inhibition of HSPs has resulted in successful therapeutic outcome in cancer. It has served as a novel anti-cancer therapy for the treatment of several cancer forms. However, more experimental studies are required to elucidate the reliability and efficacy of heat shock proteins in combination with other conventional markers for cancer diagnosis and prognosis. Novel and effective interventions through HSP inhibition are expected to decrease the burden of cancer in the near future.