Use and Outcomes of Dexamethasone in the Management of Malignant Small Bowel Obstruction.

Objective: To describe rates of dexamethasone use in the nonoperative management of malignant small bowel obstruction (mSBO) and their outcomes.

Background: mSBO is common in patients with advanced abdominal-pelvic cancers. Management includes prioritizing quality of life and avoiding surgical intervention when possible.

The ZIKV NS5 Protein Aberrantly Alters the Tubulin Cytoskeleton, Induces the Accumulation of Autophagic p62 and Affects IFN Production: HDAC6 Has Emerged as an Anti-NS5/ZIKV Factor.

Zika virus (ZIKV) infection and pathogenesis are linked to the disruption of neurogenesis, congenital Zika syndrome and microcephaly by affecting neural progenitor cells. Nonstructural protein 5 (NS5) is the largest product encoded by ZIKV-RNA and is important for replication and immune evasion. Here, we studied the potential effects of NS5 on microtubules (MTs) and autophagy flux, together with the interplay of NS5 with histone deacetylase 6 (HDAC6).

HIV Infection: Shaping the Complex, Dynamic, and Interconnected Network of the Cytoskeleton.

HIV-1 has evolved a plethora of strategies to overcome the cytoskeletal barrier (i.e., actin and intermediate filaments (AFs and IFs) and microtubules (MTs)) to achieve the viral cycle.

TDP-43 Controls HIV-1 Viral Production and Virus Infectiveness.

The transactive response DNA-binding protein (TARDBP/TDP-43) is known to stabilize the anti-HIV-1 factor, histone deacetylase 6 (HDAC6). TDP-43 has been reported to determine cell permissivity to HIV-1 fusion and infection acting on tubulin-deacetylase HDAC6. Here, we studied the functional involvement of TDP-43 in the late stages of the HIV-1 viral cycle.

Nanomaterials to combat SARS-CoV-2: Strategies to prevent, diagnose and treat COVID-19.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the associated coronavirus disease 2019 (COVID-19), which severely affect the respiratory system and several organs and tissues, and may lead to death, have shown how science can respond when challenged by a global emergency, offering as a response a myriad of rapid technological developments. Development of vaccines at lightning speed is one of them. SARS-CoV-2 outbreaks have stressed healthcare systems, questioning patients care by using standard non-adapted therapies and diagnostic tools.

Depletion or cleavage of cohesin during anaphase differentially affects chromatin structure and segregation.

Chromosome segregation requires both the separation of sister chromatids and the sustained condensation of chromatids during anaphase. In yeast cells, cohesin is not only required for sister chromatid cohesion but also plays a major role determining the structure of individual chromatids in metaphase. Separase cleavage is thought to remove all cohesin complexes from chromosomes to initiate anaphase.

Contribution of the HIV-1 Envelope Glycoprotein to AIDS Pathogenesis and Clinical Progression.

In the absence of antiviral therapy, HIV-1 infection progresses to a wide spectrum of clinical manifestations that are the result of an entangled contribution of host, immune and viral factors. The contribution of these factors is not completely established. Several investigations have described the involvement of the immune system in the viral control.

Transactive Response DNA-Binding Protein (TARDBP/TDP-43) Regulates Cell Permissivity to HIV-1 Infection by Acting on HDAC6.

The transactive response DNA-binding protein (TARDBP/TDP-43) influences the processing of diverse transcripts, including that of histone deacetylase 6 (HDAC6). Here, we assessed TDP-43 activity in terms of regulating CD4+ T-cell permissivity to HIV-1 infection. We observed that overexpression of wt-TDP-43 increased both mRNA and protein levels of HDAC6, resulting in impaired HIV-1 infection independently of the viral envelope glycoprotein complex (Env) tropism.

FACT mediates cohesin function on chromatin.

Cohesin is a regulator of genome architecture with roles in sister chromatid cohesion and chromosome compaction. The recruitment and mobility of cohesin complexes on DNA is restricted by nucleosomes. Here, we show that the role of cohesin in chromosome organization requires the histone chaperone FACT ('facilitates chromatin transcription') in Saccharomyces cerevisiae.

Fanconi Anaemia-Like Mph1 Helicase Backs up Rad54 and Rad5 to Circumvent Replication Stress-Driven Chromosome Bridges.

Homologous recombination (HR) is a preferred mechanism to deal with DNA replication impairments. However, HR synapsis gives rise to joint molecules (JMs) between the nascent sister chromatids, challenging chromosome segregation in anaphase. Joint molecules are resolved by the actions of several structure-selective endonucleases (SSEs), helicases and topoisomerases.

Lawsone, Juglone, and β-Lapachone Derivatives with Enhanced Mitochondrial-Based Toxicity.

Naphthoquinones are among the most active natural products obtained from plants and microorganisms. Naphthoquinones exert their biological activities through pleiotropic mechanisms that include reactivity against cell nucleophiles, generation of reactive oxygen species (ROS), and inhibition of proteins. Here, we report a mechanistic antiproliferative study performed in the yeast Saccharomyces cerevisiae for several derivatives of three important natural naphthoquinones: lawsone, juglone, and β-lapachone.

Morphological study of Socorro Island Merino sheep and its crosses with hair breeds.

A study was conducted with the objective to characterize the morphology of Socorro Island Merino sheep. A total of 67 sheep, 62 females, 26 purebred and 36 crossbred with hair breeds, and five males were scored for 10 body measurements in addition to live weight, and four racial and seven functional indices were calculated. The influence of sex and crossbreeding on the body measurements and indices was analyzed by one-way analysis of variance, and morphological harmony was determined using Spearman correlation.

Physical Proximity of Sister Chromatids Promotes Top2-Dependent Intertwining.

Sister chromatid intertwines (SCIs), or catenanes, are topological links between replicated chromatids that interfere with chromosome segregation. The formation of SCIs is thought to be a consequence of fork swiveling during DNA replication, and their removal is thought to occur because of the intrinsic feature of type II topoisomerases (Top2) to simplify DNA topology. Here, we report that SCIs are also formed independently of DNA replication during G/M by Top2-dependent concatenation of cohesed chromatids due to their physical proximity.

Cdc14 phosphatase: warning, no delay allowed for chromosome segregation!

Cycling events in nature start and end to restart again and again. In the cell cycle, whose purpose is to become two where there was only one, cyclin-dependent kinases (CDKs) are the beginning and, therefore, phosphatases must play a role in the ending. Since CDKs are drivers of the cell cycle and cancer cells uncontrollably divide, much attention has been put into knocking down CDK activity.

Overexpression of penicillin V acylase from Streptomyces lavendulae and elucidation of its catalytic residues.

The pva gene from Streptomyces lavendulae ATCC 13664, encoding a novel penicillin V acylase (SlPVA), has been isolated and characterized. The gene encodes an inactive precursor protein containing a secretion signal peptide that is activated by two internal autoproteolytic cleavages that release a 25-amino-acid linker peptide and two large domains of 18.79 kDa (alpha-subunit) and 60.

Mus81-Mms4 and Yen1 resolve a novel anaphase bridge formed by noncanonical Holliday junctions.

Downregulation of separase, condensin, Smc5/6, topoisomerase II and Cdc14 in Saccharomyces cerevisiae yields anaphase bridges formed by unresolved sister chromatids (SCBs). Here we report that the overlapping actions of the structure-selective endonucleases (SSEs) Mus81-Mms4/EME1 and Yen1/GEN1, but not Slx1-Slx4, are also essential to prevent the formation of spontaneous SCBs that depend on the homologous recombination pathway. We further show that the frequency of SCBs is boosted after mild replication stress and that they contain joint molecules enriched in non-canonical forms of the Holliday junction (HJ), including nicked-HJ (nHJ).

Yeast cytotoxic sensitivity to the antitumour agent β-lapachone depends mainly on oxidative stress and is largely independent of microtubule- or topoisomerase-mediated DNA damage.

β-Lapachone (β-lap) is a promising antitumour drug currently undergoing clinical trials. Although it is known that β-lap generates reactive oxygen species (ROS), its actual mechanism of action is still controversial. Especially important is to determine whether concomitant DNA or microtubule damage is the key target of its antitumour properties and whether DNA damage is mediated by topoisomerases as previously suggested.

Obesity delays functional recovery in trauma patients.

Background: Obesity is known to complicate trauma hospital stays. We hypothesize that obesity delays functional recovery in trauma patients.

Materials And Methods: Between 2005 and 2007, adult patients with a hospital length of stay >24 h were prospectively recruited for the study.

Cdc14 targets the Holliday junction resolvase Yen1 to the nucleus in early anaphase.

The only canonical Holliday junction (HJ) resolvase identified in eukaryotes thus far is Yen1/GEN1. Nevertheless, Yen1/GEN1 appears to have a minor role in HJ resolution, and, instead, other structure-specific endonucleases (SSE) that recognize branched DNA play the leading roles, Mus81-Mms4/EME1 being the most important in budding yeast. Interestingly, cells tightly regulate the activity of each HJ resolvase during the yeast cell cycle.

The effectiveness of prophylactic inferior vena cava filters in trauma patients: a systematic review and meta-analysis.

Importance: Trauma is known to be one of the strongest risk factors for pulmonary embolism (PE). Current guidelines recommend low-molecular-weight heparin therapy for prevention of PE, but trauma places some patients at risk of excess bleeding. Experts are divided on the role of prophylactic inferior vena cava (IVC) filters to prevent PE.

Synthesis and study of antiproliferative, antitopoisomerase II, DNA-intercalating and DNA-damaging activities of arylnaphthalimides.

A series of arylnaphthalimides were designed and synthesized to overcome the dose-limiting cytotoxicity of N-acetylated metabolites arising from amonafide, the prototypical antitumour naphthalimide whose biomedical properties have been related to its ability to intercalate the DNA and poison the enzyme Topoisomerase II. Thus, these arylnaphthalimides were first evaluated for their antiproliferative activity against two tumour cell lines and for their antitopoisomerase II in vitro activities, together with their ability to intercalate the DNA in vitro and also through docking modelization. Then, the well-known DNA damage response in Saccharomyces cerevisiae was employed to critically evaluate whether these novel compounds can damage the DNA in vivo.

Nondisjunction of a single chromosome leads to breakage and activation of DNA damage checkpoint in G2.

The resolution of chromosomes during anaphase is a key step in mitosis. Failure to disjoin chromatids compromises the fidelity of chromosome inheritance and generates aneuploidy and chromosome rearrangements, conditions linked to cancer development. Inactivation of topoisomerase II, condensin, or separase leads to gross chromosome nondisjunction.