Spatial Chemoproteomics for Mapping the Active Proteome.

Functional regulation of cell signaling through dynamic changes in protein activity state as well as spatial organization represent two dynamic, complex, and conserved phenomena in biology. Seemingly separate areas of -omics method development have focused on building tools that can detect and quantify protein activity states, as well as map sub-cellular and intercellular protein organization. Integration of these efforts, through the development of chemical tools and platforms that enable detection and quantification of protein functional states with spatial resolution provide opportunities to better understand heterogeneity in the proteome within cell organelles, multi-cellular tissues, and whole organisms.

PARK7 Catalyzes Stereospecific Detoxification of Methylglyoxal Consistent with Glyoxalase and Not Deglycase Function.

The protein PARK7 (also known as DJ-1) has been implicated in several diseases, with the most notable being Parkinson's disease. While several molecular and cellular roles have been ascribed to DJ-1, there is no real consensus on what its true cellular functions are and how the loss of DJ-1 function may contribute to the pathogenesis of Parkinson's disease. Recent reports have implicated DJ-1 in the detoxification of several reactive metabolites that are produced during glycolytic metabolism, with the most notable being the α-oxoaldehyde species methylglyoxal.

Experience of a District General Hospital With a Diverse Community in Operated Colorectal Cancers According to Ethnic Background.

Background This study aimed to investigate disparities in colorectal cancer (CRC) patients' demographics according to the five major ethnicities of patients living in the catchment area of North Middlesex Hospital. Methodology This retrospective study included CRC patients operated on between January 1, 2010, and December 31, 2014. Records dating to the end of the five-year follow-up were extracted anonymously from a database of CRC outcomes at the North Middlesex University Hospital NHS Trust.

Outcome of Operated Colorectal Cancers in Relation to the Type of Initial Referral.

Aim Since the introduction of the target referral system, there has been controversy about its value and whether it affected the short- and long-term outcomes of colorectal cancer surgeries. With contradicting results, this study highlights differences in personal and tumour characteristics, management differences, and outcomes in each referral pathway, including target pathway referrals for suspected cancers, emergency presentations, routine referrals, and incidentally discovered cancers during screening. Methods A retrospective study of colorectal cancer (CRC) patients operated on between January 1, 2010, and December 31, 2014, with records dating to the end of the five-year follow-up, was extracted anonymously from the database of CRC outcomes at the North Middlesex University Hospital NHS Trust, London.

Widespread, Reversible Cysteine Modification by Methylglyoxal Regulates Metabolic Enzyme Function.

Methylglyoxal (MGO), a reactive metabolite byproduct of glucose metabolism, is known to form a variety of posttranslational modifications (PTMs) on nucleophilic amino acids. For example, cysteine, the most nucleophilic proteinogenic amino acid, forms reversible hemithioacetal and stable mercaptomethylimidazole adducts with MGO. The high reactivity of cysteine toward MGO and the rate of formation of such modifications provide the opportunity for mechanisms by which proteins and pathways might rapidly sense and respond to alterations in levels of MGO.

Biotin-decorated NIR-absorbing nanosheets for targeted photodynamic cancer therapy.

Targeted photodynamic therapy (PDT) is one of the promising approaches for the selective killing of cancerous cells without affecting the normal cells, and hence designing new strategies for targeted PDT is extremely important. Herein we report the design and synthesis of a new class of nanosheets derived from the self-assembly of the iodo-BODIPY-biotin conjugate as a photosensitizer for targeted PDT applications. The nanosheet exhibits a high extinction coefficient in the NIR region, high singlet oxygen efficiency, no toxicity in the dark and cell targeting ligands (biotin) on the surface, which are necessary features required for an ideal photosensitizer.

A DNA-based voltmeter for organelles.

The role of membrane potential in most intracellular organelles remains unexplored because of the lack of suitable tools. Here, we describe Voltair, a fluorescent DNA nanodevice that reports the absolute membrane potential and can be targeted to organelles in live cells. Voltair consists of a voltage-sensitive fluorophore and a reference fluorophore for ratiometry, and acts as an endocytic tracer.

Post-operative outcomes of open reduction and internal fixation versus circular external fixation in treatment of tibial plafond fractures: A systematic review and meta-analysis.

Introduction: Tibial plafond fractures (TPF) are complex injuries often resulting in poor outcomes. Combination of articular impaction, metaphysealcomminution and soft-tissue injury results in a significant treatment challenge. The aim of this study was to conduct a systematic review and meta-analysis to compare post-operative complications and functional outcomes of open reduction and internal fixation (ORIF) versus circular external fixation (CEF) for treatment of TPF.

Heteronemin, a marine natural product, sensitizes acute myeloid leukemia cells towards cytarabine chemotherapy by regulating farnesylation of Ras.

Cytarabine is a conventionally used chemotherapeutic agent for treating acute myeloid leukemia (AML). However, chemoresistance, toxic side-effects and poor patient survival rates retard the efficacy of its performance. The current study deals with the chemosensitization of AML cells using heteronemin, a marine natural product towards cytarabine chemotherapy.

Folic acid conjugation improves the bioavailability and chemosensitizing efficacy of curcumin-encapsulated PLGA-PEG nanoparticles towards paclitaxel chemotherapy.

Nanoencapsulation has emerged as a novel strategy to enhance the pharmacokinetic and therapeutic potential of conventional drugs. Recent studies from our lab have established the efficacy of curcumin in sensitizing cervical cancer cells and breast cancer cells towards paclitaxel and 5-FU chemotherapy respectively. Factors that hinder the clinical use of curcumin as a sensitizer or therapeutic agent include its poor bioavailability and retention time.

Effects of sleep deprivation on cognitive and physical performance in university students.

Sleep deprivation is common among university students, and has been associated with poor academic performance and physical dysfunction. However, current literature has a narrow focus in regard to domains tested, this study aimed to investigate the effects of a night of sleep deprivation on cognitive and physical performance in students. A randomized controlled crossover study was carried out with 64 participants [58% male ( = 37); 22 ± 4 years old (mean ± SD)].