Idiopathic Radiation Recall Dermatitis Developing Nine Months after Cessation of Cisplatin Therapy in Treatment of Squamous Cell Carcinoma of the Tonsil

To report on a suspected case of idiopathic radiation recall dermatitis in an individual nine months after radiation and chemotherapy treatment of squamous cell carcinoma of the right tonsil. Radiation recall dermatitis is the development of a reaction in a previously irradiated area of skin after the administration of an aggravating medication. A review of the literature revealed several cases of radiation recall dermatitis that occur following radiation therapy and the institution of chemotherapy. Other medications have also been implicated in radiation recall dermatitis; however, this patient has not started any new medications since completion of his combined therapy. The patient developed this skin reaction in a distribution pattern identical to the area that received the highest radiation dose suggesting a possible link between radiation recall dermatitis and radiation dose. Radiation recall dermatitis is a reaction that is typically seen shortly after the reinstitution of chemotherapy during radiation therapy. This case illustrates that other medical etiologies are possible and suggests a relationship between radiation recall dermatitis and the total radiation dose an area receives

Calorie Restriction Enhances Longevity Without Reducing Lifetime Fecundity or Glucose Titers in Female Lubber Grasshoppers

Calorie restriction, under eating while avoiding malnutrition, enhances longevity in many organisms, in part by delaying fecundity or lowering blood glucose. Calorie restriction begun at middle-age can also enhance longevity. We tested four diets on longevity of female lubber grasshoppers: ad libitum (free access to food), calorie restriction (60% or 71% of ad libitum), and delayed calorie restriction (60% after day 50). Constant calorie restriction increased longevity in grasshoppers by at least 66%. These diets lowered body mass, but it did not reduce lifetime fecundity or chronically lower blood glucose levels. Calorie restriction reduced the levels of stored protein after egg laying. Delayed calorie restriction also increased longevity (also by 66%), but because the body mass gain of this group did keep pace with ad libitum grasshoppers when they were fed identically, this result needs retesting. These extensions of lifespan likely are due to slowed aging

Role of N-Terminal Amino Acids in the Potency of Anthrax Lethal Factor

Anthrax lethal factor (LF) is a Zn+2-dependent metalloprotease that cleaves several MAPK kinases and is responsible for the lethality of anthrax lethal toxin (LT). We observed that a recombinant LF (LF-HMA) which differs from wild type LF (LF-A) by the addition of two residues (His-Met) to the native Ala (A) terminus as a result of cloning manipulations has 3-fold lower potency toward cultured cells and experimental animals. We hypothesized that the “N-end rule”, which relates the half-life of proteins in cells to the identity of their N-terminal residue, might be operative in the case of LF, so that the N-terminal residue of LF would determine the cytosolic stability and thereby the potency of LF. Mutational studies that replaced the native N-terminal residue of LF with known N-end rule stabilizing or destabilizing residues confirmed that the N-terminal residue plays a significant role in determining the potency of LT for cultured cells and experimental animals. The fact that a commercially-available LF preparation (LF-HMA) that is widely used in basic research studies and for evaluation of vaccines and therapeutics is 3-fold less potent than native LF (LF-A) should be considered when comparing published studies and in the design of future experiments

A SARS-CoV-2 protein interaction map reveals targets for drug repurposing

The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 2.3 million people, killed over 160,000, and caused worldwide social and economic disruption1,2. There are currently no antiviral drugs with proven clinical efficacy, nor are there vaccines for its prevention, and these efforts are hampered by limited knowledge of the molecular details of SARS-CoV-2 infection. To address this, we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins physically associated with each using affinity-purification mass spectrometry (AP-MS), identifying 332 high-confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (29 FDA-approved drugs, 12 drugs in clinical trials, and 28 preclinical compounds). Screening a subset of these in multiple viral assays identified two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the Sigma1 and Sigma2 receptors. Further studies of these host factor targeting agents, including their combination with drugs that directly target viral enzymes, could lead to a therapeutic regimen to treat COVID-19

Astronomical calibration of the Jurassic time scale from cyclostratigraphy in British mudrock formations

Three British Jurassic mudrock formations have been investigated, via time–series analysis, for evidence of sedimentary cyclicity related to orbital–climatic (Milankovitch) cyclicity: the Blue Lias, the Belemnite Marls and the Kimmeridge Clay Formation. Magnetic–susceptibility measurements through the Blue Lias (uppermost Triassic to Sinemurian) were used to generate high–resolution time–series. The data indicate the presence of a regular sedimentary cycle that gradually varies in wavelength according to sedimentation rate. Tuning of this cycle to the 38ka Jurassic obliquity cycle produces spectral evidence for two additional regular cycles of small amplitude. These correspond to the 95 ka component of orbital eccentricity and the 20 ka orbital–precession cycles. Cycle counting allowed the minimum duration of four ammonite zones to be estimated and the duration of the Hettangian stage is estimated to be at least 1.29 Ma. Calcium carbonate measurements through the Belemnite Marls (lower Pliensbachian) are characterized by two scales of cyclicity that can be firmly linked to orbital–precession (20 ka) and the 123 ka component of eccentricity. A time–scale has been developed from the precession–related sedimentary cycles, with cycle counts used to constrain the duration of two ammonite zones. In the Kimmeridge Clay Formation (Kimmeridgian–Tithonian), magnetic–susceptibility measurements made on exposures, core material and down boreholes can be correlated at the decimetre scale. Only measurements of magnetic susceptibility made below the Yellow Ledge Stone Band (midway through the formation) are suitable for analysis of the bedding–scale cyclicity. A large–amplitude sedimentary cycle detected in the lower part of the formation is probably related to the orbital–obliquity cycle (38 ka). In certain stratigraphic intervals, there is evidence for small–amplitude cycles related to orbital precession (20 ka). This study of the British Jurassic shows that, in the Rhaetian–Sinemurian, the dominant cyclicity was related to obliquity. In the Pliensbachian this had shifted to dominantly precession, and in the Kimmeridgian obliquity again dominated. These shifts in cycle dominance presumably reflect changing local or global palaeoclimatic and/or palaeoceanographic conditions

Acute whole-body vibration elicits post-activation potentiation

Whole-body vibration (WBV) leads to a rapid increase in intra-muscular temperature and enhances muscle power. The power-enhancing effects by WBV can, at least in part, be explained by intra-muscular temperature. However, this does not exclude possible neural effects of WBV occurring at the spinal level. The aim of this study was to examine if muscle twitch and patellar reflex properties were simultaneously potentiated from an acute bout of WBV in a static squat position. Six male and six female athletes performed three interventions for 5 min, static squat with WBV (WBV+, 26 Hz), static squat without WBV (WBV−) and stationary cycling (CYCL, 70 W). Transcutaneous muscle stimulation consisting of a single 200 μs pulse and three patellar tendon taps were administered prior to and then 90 s, 5, 10 min post-intervention. Ninety-seconds after WBV+ muscle twitch peak force (PF) and rate of force development (RFD) were significantly higher (P < 0.01) compared to WBV− and CYCL. However the patellar tendon reflex was not potentiated. An acute continuous bout of WBV caused a post-activation potentiation (PAP) of muscle twitch potentiation (TP) compared to WBV− and CYCL indicating that a greater myogenic response was evident compared to a neural-mediated effect of a reflex potentiation (RP)