Nerve Transfers to Recover External Rotation of the Shoulder after Brachial Plexus Injuries in Adults

Restoration of external rotation of the shoulder in adults with partial brachial plexus palsies is challenging. While nerve grafts are possible, nerve transfers are currently the most use method for satisfactory restoration of function. Numerous nerve transfers have been described, although the transfer of the spinal accessory nerve to the suprascapular nerve remains the gold standard. The suprascapular nerve and the nerve to the teres minor muscle are the two preferred targets to restore external rotation of the shoulder. There are numerous nerve donors, but their use obviously depends on the initial injury. The most common donors are the spinal accessory nerve, the rhomboid nerve, branches of the radial nerve, the C7 root fascicle or the ulnar nerve. The choice for the transfer depends on the available nerves and first of all on chosen approach, whether it be cervical or scapular. It also depends on the other associated reconstruction procedures, grafts, or nerve transfers for the recovery of other functions, specifically, elevation of the shoulder and flexion of the elbow. The objective of this chapter is to present the main nerve transfers and to propose a therapeutic strategy

The Transcription Factor E4F1 Coordinates CHK1-Dependent Checkpoint and Mitochondrial Functions

Recent data support the notion that a group of key transcriptional regulators involved in tumorigenesis, including MYC, p53, E2F1, and BMI1, share an intriguing capacity to simultaneously regulate metabolism and cell cycle. Here, we show that another factor, the multifunctional protein E4F1, directly controls genes involved in mitochondria functions and cell-cycle checkpoints, including Chek1, a major component of the DNA damage response. Coordination of these cellular functions by E4F1 appears essential for the survival of p53-deficient transformed cells. Acute inactivation of E4F1 in these cells results in CHK1-dependent checkpoint deficiency and multiple mitochondrial dysfunctions that lead to increased ROS production, energy stress, and inhibition of de novo pyrimidine synthesis. This deadly cocktail leads to the accumulation of uncompensated oxidative damage to proteins and extensive DNA damage, ending in cell death. This supports the rationale of therapeutic strategies simultaneously targeting mitochondria and CHK1 for selective killing of p53-deficient cancer cells

PEGylated and functionalized aliphatic polycarbonate polyplex nanoparticles for intravenous administration of HDACS siRNA in cancer therapy

peer reviewe

Viral to metazoan marine plankton nucleotide sequences from the Tara Oceans expedition

A unique collection of oceanic samples was gathered by the Tara Oceans expeditions (2009-2013), targeting plankton organisms ranging from viruses to metazoans, and providing rich environmental context measurements. Thanks to recent advances in the field of genomics, extensive sequencing has been performed for a deep genomic analysis of this huge collection of samples. A strategy based on different approaches, such as metabarcoding, metagenomics, single-cell genomics and metatranscriptomics, has been chosen for analysis of size-fractionated plankton communities. Here, we provide detailed procedures applied for genomic data generation, from nucleic acids extraction to sequence production, and we describe registries of genomics datasets available at the European Nucleotide Archive (ENA, www.ebi.ac.uk/ena). The association of these metadata to the experimental procedures applied for their generation will help the scientific community to access these data and facilitate their analysis. This paper complements other efforts to provide a full description of experiments and open science resources generated from the Tara Oceans project, further extending their value for the study of the world's planktonic ecosystems

The Copernicus Marine Environment Monitoring Service Ocean State Report

The Copernicus Marine Environment Monitoring Service (CMEMS) Ocean State Report (OSR) provides an annual report of the state of the global ocean and European regional seas for policy and decision-makers with the additional aim of increasing general public awareness about the status of, and changes in, the marine environment. The CMEMS OSR draws on expert analysis and provides a 3-D view (through reanalysis systems), a view from above (through remote-sensing data) and a direct view of the interior (through in situ measurements) of the global ocean and the European regional seas. The report is based on the unique CMEMS monitoring capabilities of the blue (hydrography, currents), white (sea ice) and green (e.g. Chlorophyll) marine environment. This first issue of the CMEMS OSR provides guidance on Essential Variables, large-scale changes and specific events related to the physical ocean state over the period 1993–2015. Principal findings of this first CMEMS OSR show a significant increase in global and regional sea levels, thermosteric expansion, ocean heat content, sea surface temperature and Antarctic sea ice extent and conversely a decrease in Arctic sea ice extent during the 1993–2015 period. During the year 2015 exceptionally strong large-scale changes were monitored such as, for example, a strong El Niño Southern Oscillation, a high frequency of extreme storms and sea level events in specific regions in addition to areas of high sea level and harmful algae blooms. At the same time, some areas in the Arctic Ocean experienced exceptionally low sea ice extent and temperatures below average were observed in the North Atlantic Ocean

Plos Med

Background The ε4 allele of apolipoprotein E (APOE) gene and increasing age are two of the most important known risk factors for developing Alzheimer disease (AD). The diagnosis of AD based on clinical symptoms alone is known to have poor specificity; recently developed diagnostic criteria based on biomarkers that reflect underlying AD neuropathology allow better assessment of the strength of the associations of risk factors with AD. Accordingly, we examined the global and age-specific association between APOE genotype and AD by using the A/T/N classification, relying on the cerebrospinal fluid (CSF) levels of β-amyloid peptide (A, β-amyloid deposition), phosphorylated tau (T, pathologic tau), and total tau (N, neurodegeneration) to identify patients with AD. Methods and findings This case–control study included 1,593 white AD cases (55.4% women; mean age 72.8 [range = 44–96] years) with abnormal values of CSF biomarkers from nine European memory clinics and the American Alzheimer’s Disease Neuroimaging Initiative (ADNI) study. A total of 11,723 dementia-free controls (47.1% women; mean age 65.6 [range = 44–94] years) were drawn from two longitudinal cohort studies (Whitehall II and Three-City), in which incident cases of dementia over the follow-up were excluded from the control population. Odds ratio (OR) and population attributable fraction (PAF) for AD associated with APOE genotypes were determined, overall and by 5-year age categories. In total, 63.4% of patients with AD and 22.6% of population controls carried at least one APOE ε4 allele. Compared with non-ε4 carriers, heterozygous ε4 carriers had a 4.6 (95% confidence interval 4.1–5.2; p < 0.001) and ε4/ε4 homozygotes a 25.4 (20.4–31.2; p < 0.001) higher OR of AD in unadjusted analysis. This association was modified by age (p for interaction < 0.001). The PAF associated with carrying at least one ε4 allele was greatest in the 65–70 age group (69.7%) and weaker before 55 years (14.2%) and after 85 years (22.6%). The protective effect of APOE ε2 allele for AD was unaffected by age. Main study limitations are that analyses were based on white individuals and AD cases were drawn from memory centers, which may not be representative of the general population of patients with AD. Conclusions In this study, we found that AD diagnosis based on biomarkers was associated with APOE ε4 carrier status, with a higher OR than previously reported from studies based on only clinical AD criteria. This association differs according to age, with the strongest effect at 65–70 years. These findings highlight the need for early interventions for dementia prevention to mitigate the effect of APOE ε4 at the population level