Faculty reviews最新文献

Penile prosthesis surgery represents the end-stage treatment for erectile dysfunction. It is conventionally used only in cases of erectile dysfunction refractory to pharmacological treatments or vacuum constriction devices. Contemporary literature suggests that penile prothesis surgery is associated with a high satisfaction rate and a low complication profile. However, it must be appreciated that the complications of surgery can have devastating consequences on a patient's quality of life and satisfaction and include infection, prosthesis malfunction, penile corporal perforation and penile length loss. Several factors - such as appropriate patient selection, methodical preoperative assessment and patient optimization, specific intraoperative protocols and postoperative recommendations - can reduce the risk of surgical complications. This narrative review discusses the diagnosis and management of both intraoperative and postoperative complications of penile prosthesis surgery.

Maintenance of a functional proteome is achieved through the mechanism of proteostasis that involves precise coordination between molecular machineries assisting a protein from its conception to demise. Although each organelle within a cell has its own set of proteostasis machinery, inter-organellar communication and cell non-autonomous signaling bring forth the multidimensional nature of the proteostasis network. Exposure to extrinsic and intrinsic stressors can challenge the proteostasis network, leading to the accumulation of aberrant proteins or a decline in the proteostasis components, as seen during aging and in several diseases. Here, we summarize recent advances in understanding the role of proteostasis and its regulation in aging and disease, including monogenetic and infectious diseases. We highlight some of the emerging as well as unresolved questions in proteostasis that need to be addressed to overcome pathologies associated with damaged proteins and to promote healthy aging.

Tic disorders and Tourette syndrome are the most common movement disorders in children and are characterized by movements or vocalizations. Clinically, Tourette syndrome is frequently associated with comorbid psychiatric symptoms. Although dysfunction of cortical-striatal-thalamic-cortical circuits with aberrant neurotransmitter function has been considered the proximate cause of tics, the mechanism underlying this association is unclear. Recently, many studies have been conducted to elucidate the epidemiology, clinical course, comorbid symptoms, and pathophysiology of tic disorders by using laboratory studies, neuroimaging, electrophysiological testing, environmental exposure, and genetic testing. In addition, many researchers have focused on treatment for tics, including behavioral therapy, pharmacological treatment, and surgical treatment. Here, we provide an overview of recent progress on Tourette syndrome.

Interleukin-4 (IL-4) is a four-α-helical bundle type I cytokine with broad pleiotropic actions on multiple lineages. Major actions of IL-4 were initially discovered for B and T cells, but this cytokine acts on more than a dozen different target cells spanning the innate and adaptive immune systems and is produced by multiple different cellular sources. While IL-4 was discovered just under 40 years ago in 1982, the interest in and discoveries related to this cytokine continue to markedly expand. There are important new advances related to its biological actions and to its mechanisms of signaling, including critical genes and downstream targets in a range of cell types. IL-4 is critical not only for careful control of immunoglobulin production but also related to inflammation, fibrosis, allergic reactions, and antitumor activity, with actions of IL-4 occurring through two different types of receptors, one of which is also used by IL-13, a closely related cytokine with partially overlapping actions. In this review, we cover critical older information but also highlight newer advances. An area of evolving interest relates to the therapeutic blockade of IL-4 signaling pathway to treat atopic dermatitis and asthma. Thus, this cytokine is historically important, and research in this area has both elucidated major biological pathways and led to therapeutic advances for diseases that affect millions of individuals.

Cerebral toxoplasmosis and cerebral malaria are two important neurological diseases caused by protozoan parasites. In this review, we discuss recent findings regarding the innate immune responses of microglia and astrocytes to Toxoplasma and Plasmodium infection. In both infections, these tissue-resident glial cells perform a sentinel function mediated by alarmin crosstalk that licenses adaptive type 1 immunity in the central nervous system. Divergent protective or pathogenic effects of type 1 activation of these astrocytes and microglia are revealed depending on the inherent lytic potential of the protozoan parasite.

Thrombocytopoiesis is a complex process beginning at the level of hematopoietic stem cells, which ultimately generate megakaryocytes, large marrow cells with a distinctive morphology, and then, through a process of terminal maturation, megakaryocytes shed thousands of platelets into the circulation. This process is controlled by intrinsic and extrinsic factors. Emerging data indicate that an important intrinsic control on the late stages of thrombopoiesis is exerted by integrins, a family of transmembrane receptors composed of one α and one β subunit. One β subunit expressed by megakaryocytes is the β1 integrin, the role of which in the regulation of platelet formation is beginning to be clarified. Here, we review recent data indicating that activation of β1 integrin by outside-in and inside-out signaling regulates the interaction of megakaryocytes with the endosteal niche, which triggers their maturation, while its inactivation by galactosylation determines the migration of these cells to the perivascular niche, where they complete their terminal maturation and release platelets in the bloodstream. Furthermore, β1 integrin mediates the activation of transforming growth factor β (TGF-β), a protein produced by megakaryocytes that may act in an autocrine fashion to halt their maturation and affect the composition of their surrounding extracellular matrix. These findings suggest that β1 integrin could be a therapeutic target for inherited and acquired disorders of platelet production.

Testicular germ cell tumours (TGCTs) are the most common solid tumours in young men and have an excellent overall cure rate and prognosis. In most patients, localised disease is cured by surgery alone, and a minority of patients receive short-course adjuvant chemotherapy to reduce the risk of further relapse. Also, in about 80% of patients, metastatic disease can be cured by systemic cisplatin-based chemotherapy. Unfortunately, for a proportion of patients, the disease exhibits platinum resistance and relapse occurs. Despite further lines of systemic treatment, cure can be difficult to achieve in these patients and ultimately about 20% of them will die from disease progression. Addressing the mechanisms underpinning platinum resistance is critical to improving the survival and chances of cure for these patients. This review describes the latest advances in TGCT research, focusing on the identification of novel biomarkers, genetic characteristics and exploring novel treatments.

The sexually transmitted infection (STI) gonorrhoea remains a major global public health concern. The World Health Organization (WHO) estimates that 87 million new cases in individuals who were 15 to 49 years of age occurred in 2016. The growing number of gonorrhoea cases is concerning given the rise in gonococci developing antimicrobial resistance (AMR). Therefore, a global action plan is needed to facilitate surveillance. Indeed, the WHO has made surveillance leading to the elimination of STIs (including gonorrhoea) a global health priority. The availability of whole genome sequence data offers new opportunities to combat gonorrhoea. This can be through (i) enhanced surveillance of the global prevalence of AMR, (ii) improved understanding of the population biology of the gonococcus, and (iii) opportunities to mine sequence data in the search for vaccine candidates. Here, we review the current status in Neisseria gonorrhoeae genomics. In particular, we explore how genomics continues to advance our understanding of this complex pathogen.

While the human genome represents the most accurate vertebrate reference assembly to date, it still contains numerous gaps, including centromeric and other large repeat-containing regions - often termed the "dark side" of the genome - many of which are of fundamental biological importance. Miga et al.^1,2 present the first gapless assembly of the human X chromosome, with the help of ultra-long-read nanopore reads generated for the haploid complete hydatidiform mole (CHM13) genome. They reconstruct the ~3.1 megabase centromeric satellite DNA array and map DNA methylation patterns across complex tandem repeats and satellite arrays. This Telomere-to-Telomere assembly provides a superior human X chromosome reference enabling future sex-determination and X-linked disease research, and provides a path towards finishing the entire human genome sequence.

Cryo electron microscopy (cryoEM) is a fast-growing technique for structure determination. Two recent papers report the first atomic resolution structure of a protein obtained by averaging images of frozen-hydrated biomolecules. They both describe maps of symmetric apoferritin assemblies, a common test specimen, in unprecedented detail. New instrument improvements, different in the two studies, have contributed better images, and image analysis can extract structural information sufficient to resolve individual atomic positions. While true atomic resolution maps will not be routine for most proteins, the studies suggest structures determined by cryoEM will continue to improve, increasing their impact on biology and medicine.