Efficacy and safety of echinocandin monotherapy and combination therapy for immunocompromised patients with systemic candidiasis: A systematic review and meta-analysis.

Background: Systemic candidiasis is caused by Candida invading the bloodstream. The efficacy and safety of echinocandins in monotherapy and combination therapy regimes have not been adequately compared in immunocompromised patients with Candidiasis, and thus this systematic review aims to do so.

Methods: A protocol was prepared a priori.

Structural basis for p50RhoGAP BCH domain-mediated regulation of Rho inactivation.

Spatiotemporal regulation of signaling cascades is crucial for various biological pathways, under the control of a range of scaffolding proteins. The BNIP-2 and Cdc42GAP Homology (BCH) domain is a highly conserved module that targets small GTPases and their regulators. Proteins bearing BCH domains are key for driving cell elongation, retraction, membrane protrusion, and other aspects of active morphogenesis during cell migration, myoblast differentiation, and neuritogenesis.

Online conferencing platform provides opportunity for reciprocal teaching.

The use of online platform to conduct teaching and learning activities has becoming a new norm for teachers and students during this COVID-19 outbreak. In this commentary, we share our experiences of using online conferencing platform to promote active and interactive learning among students. We also suggest approaches that teachers can use to design their teaching and learning activities by employing reciprocal teaching as a way to engage students online instead of using the platform for didactic teaching by the teacher.

Role of Kip2 during early mitosis - impact on spindle pole body separation and chromosome capture.

Mitotic spindle dynamics are regulated during the cell cycle by microtubule motor proteins. In , one such protein is Kip2p, a plus-end motor that regulates the polymerization and stability of cytoplasmic microtubules (cMTs). Kip2p levels are regulated during the cell cycle, and its overexpression leads to the formation of hyper-elongated cMTs.

Timely Endocytosis of Cytokinetic Enzymes Prevents Premature Spindle Breakage during Mitotic Exit.

Cytokinesis requires the spatio-temporal coordination of membrane deposition and primary septum (PS) formation at the division site to drive acto-myosin ring (AMR) constriction. It has been demonstrated that AMR constriction invariably occurs only after the mitotic spindle disassembly. It has also been established that Chitin Synthase II (Chs2p) neck localization precedes mitotic spindle disassembly during mitotic exit.

Simulating an investigative study of clinical cancer samples: use of tissue slides and PCR-based promoter-hypermethylation analysis.

Topics on the molecular basis underlying cancer are quite popular among students. Also, excellent textbooks abound that provide interesting materials for discussion during lectures and tutorials about major events leading to cancer formation and progression. However, much less is available for students to conduct experiments for the analysis of cancer samples in undergraduate modules where there is a limited time-frame.

Multi-step down-regulation of the secretory pathway in mitosis: a fresh perspective on protein trafficking.

The secretory pathway delivers proteins synthesized at the rough endoplasmic reticulum (RER) to various subcellular locations via the Golgi apparatus. Currently, efforts are focused on understanding the molecular machineries driving individual processes at the RER and Golgi that package, modify and transport proteins. However, studies are routinely performed using non-dividing cells.

CHFR: a key checkpoint component implicated in a wide range of cancers.

CHFR (Checkpoint with Forkhead-associated and RING finger domains) has been implicated in a checkpoint regulating entry into mitosis. However, the details underlying its roles and regulation are unclear due to conflicting lines of evidence supporting different notions of its functions. We provide here an overview of how CHFR is thought to contribute towards regulating mitotic entry and present possible explanations for contradictory observations published on the functions and regulation of CHFR.

Dependence of Chs2 ER export on dephosphorylation by cytoplasmic Cdc14 ensures that septum formation follows mitosis.

Cytokinesis, which leads to the physical separation of two dividing cells, is normally restrained until after nuclear division. In Saccharomyces cerevisiae, chitin synthase 2 (Chs2), which lays down the primary septum at the mother-daughter neck, also ensures proper actomyosin ring constriction during cytokinesis. During the metaphase-to-anaphase transition, phosphorylation of Chs2 by the mitotic cyclin-dependent kinase (Cdk1) retains Chs2 at the endoplasmic reticulum (ER), thereby preventing its translocation to the neck.

Unrestrained spindle elongation during recovery from spindle checkpoint activation in cdc15-2 cells results in mis-segregation of chromosomes.

During normal metaphase in Saccharomyces cerevisiae, chromosomes are captured at the kinetochores by microtubules emanating from the spindle pole bodies at opposite poles of the dividing cell. The balance of forces between the cohesins holding the replicated chromosomes together and the pulling force from the microtubules at the kinetochores result in the biorientation of the sister chromatids before chromosome segregation. The absence of kinetochore-microtubule interactions or loss of cohesion between the sister chromatids triggers the spindle checkpoint which arrests cells in metaphase.

Safeguarding entry into mitosis: the antephase checkpoint.

Maintenance of genomic stability is needed for cells to survive many rounds of division throughout their lifetime. Key to the proper inheritance of intact genome is the tight temporal and spatial coordination of cell cycle events. Moreover, checkpoints are present that function to monitor the proper execution of cell cycle processes.

Retention of Chs2p in the ER requires N-terminal CDK1-phosphorylation sites.

In budding yeast, the secretory pathway is constitutively transporting cargoes such as invertase and alpha-factor throughout the cell division cycle. However, chitin synthase 2 (Chs2p), another cargo of the secretory pathway, is retained at the endoplasmic reticulum (ER) during mitosis when the mitotic kinase activity is high. Chs2p is exported from the ER to the mother-daughter neck only upon mitotic kinase destruction, indicating that the mitotic kinase activity is critical for the ER retention of Chs2p.

Exit from mitosis triggers Chs2p transport from the endoplasmic reticulum to mother-daughter neck via the secretory pathway in budding yeast.

Budding yeast chitin synthase 2 (Chs2p), which lays down the primary septum, localizes to the mother-daughter neck in telophase. However, the mechanism underlying the timely neck localization of Chs2p is not known. Recently, it was found that a component of the exocyst complex, Sec3p-green fluorescent protein, arrives at the neck upon mitotic exit.

Severing all ties between mother and daughter: cell separation in budding yeast.

At the end of nuclear division in the budding yeast, acto-myosin ring contraction and cytokinesis occur between mother and daughter cells. This is followed by cell separation, after which mother and daughter cells go their separate ways. While cell separation may be the last event that takes place between the two cells, it is nonetheless under tight regulation which ensures that both cells are viable upon separation.

Identification of a subunit of a novel Kleisin-beta/SMC complex as a potential substrate of protein phosphatase 2A.

Protein phosphatase 2A (PP2A) holoenzymes consist of a catalytic C subunit, a scaffolding A subunit, and one of several regulatory B subunits that recruit the AC dimer to substrates. PP2A is required for chromosome segregation, but PP2A's substrates in this process remain unknown. To identify PP2A substrates, we carried out a two-hybrid screen with the regulatory B/PR55 subunit.

Inactivation of mitotic kinase triggers translocation of MEN components to mother-daughter neck in yeast.

Chromosome segregation, mitotic exit, and cytokinesis are executed in this order during mitosis. Although a scheme coordinating sister chromatid separation and initiation of mitotic exit has been proposed, the mechanism that temporally links the onset of cytokinesis to mitotic exit is not known. Exit from mitosis is regulated by the mitotic exit network (MEN), which includes a GTPase (Tem1) and various kinases (Cdc15, Cdc5, Dbf2, and Dbf20).

MEN, destruction and separation: mechanistic links between mitotic exit and cytokinesis in budding yeast.

Cellular events must be executed in a certain sequence during the cell division in order to maintain genome integrity and hence ensure a cell's survival. In M phase, for instance, chromosome segregation always precedes mitotic exit (characterized by mitotic kinase inactivation via cyclin destruction); this is then followed by cytokinesis. How do cells impose this strict order? Recent findings in budding yeast have suggested a mechanism whereby partitioning of chromosomes into the daughter cell is a prerequisite for the activation of mitotic exit network (MEN).