Physiological Features of the S- and M-cone Photoreceptors of Wild-type Mice from Single-cell Recordings

Cone cells constitute only 3% of the photoreceptors of the wild-type (WT) mouse. While mouse rods have been thoroughly investigated with suction pipette recordings of their outer segment membrane currents, to date no recordings from WT cones have been published, likely because of the rarity of cones and the fragility of their outer segments. Recently, we characterized the photoreceptors of Nrl−/− mice, using suction pipette recordings from their “inner segments” (perinuclear region), and found them to be cones. Here we report the use of this same method to record for the first time the responses of single cones of WT mice, and of mice lacking the α-subunit of the G-protein transducin (Gtα−/−), a loss that renders them functionally rodless. Most cones were found to functionally co-express both S- (λmax = 360 nm) and M- (λmax = 508 nm) cone opsins and to be maximally sensitive at 360 nm (“S-cones”); nonetheless, all cones from the dorsal retina were found to be maximally sensitive at 508 nm (“M-cones”). The dim-flash response kinetics and absolute sensitivity of S- and M-cones were very similar and not dependent on which of the coexpressed cone opsins drove transduction; the time to peak of the dim-flash response was ∼70 ms, and ∼0.2% of the circulating current was suppressed per photoisomerization. Amplification in WT cones (A ∼4 s−2) was found to be about twofold lower than in rods (A ∼8 s−2). Mouse M-cones maintained their circulating current at very nearly the dark adapted level even when >90% of their M-opsin was bleached. S-cones were less tolerant to bleached S-opsin than M-cones to bleached M-opsin, but still far more tolerant than mouse rods to bleached rhodopsin, which exhibit persistent suppression of nearly 50% of their circulating current following a 20% bleach. Thus, the three types of mouse opsin appear distinctive in the degree to which their bleached, unregenerated opsins generate “dark light.

The Multiple Process Model of Goal-Directed Reaching Revisited

Recently our group forwarded a model of speed-accuracy relations in goal-directed reaching. A fundamental feature of our multiple process model was the distinction between two types of online regulation: impulse control and limb-target control. Impulse control begins during the initial stages of the movement trajectory and involves a comparison of actual limb velocity and direction to an internal representation of expectations about the limb trajectory. Limb-target control involves discrete error-reduction based on the relative positions of the limb and the target late in the movement. Our model also considers the role of eye movements, practice, energy optimization and strategic behavior in limb control. Here, we review recent work conducted to test specific aspects of our model. As well, we consider research not fully incorporated into our earlier contribution. We conclude that a slightly modified and expanded version of our model, that includes crosstalk between the two forms of online regulation, does an excellent job of explaining speed, accuracy, and energy optimization in goal-directed reaching

Assignment of the Human and Mouse Prion Protein Genes to Homologous Chromosomes

Purified preparations of scrapie prions contain one major macromolecule, designated prion protein (PrP). Genes encoding PrP are found in normal animals and humans but not within the infectious particles. The PrP gene was assigned to human chromosome 20 and the corresponding mouse chromosome 2 using somatic cell hybrids. In situ hybridization studies mapped the human PrP gene to band 20p12→pter. Our results should lead to studies of genetic loci syntenic with the PrP gene, which may play a role in the pathogenesis of prion diseases or other degenerative neurologic disorders

Effects of a single dose of N-Acetyl-5-methoxytryptamine (Melatonin) and resistance exercise on the growth hormone/IGF-1 axis in young males and females

Melatonin and resistance exercise alone have been shown to increase the levels of growth hormone (GH). The purpose of this study was to determine the effects of ingestion of a single dose of melatonin and heavy resistance exercise on serum GH, somatostatin (SST), and other hormones of the GH/insulin-like growth factor 1 (IGF-1) axis. Physically active males (n = 30) and females (n = 30) were randomly assigned to ingest either a melatonin supplement at 0.5 mg or 5.0 mg, or 1.0 mg of dextrose placebo. After a baseline blood sample, participants ingested the supplement and underwent blood sampling every 15 min for 60 min, at which point they underwent a single bout of resistance exercise with the leg press for 7 sets of 7 reps at 85% 1-RM. After exercise, participants provided additional blood samples every 15 min for a total of 120 min. Serum free GH, SST, IGF-1, IGFBP-1, and IGFBP-3 were determined with ELISA. Data were evaluated as the peak pre- and post-exercise values subtracted from baseline and the delta values analyzed with separate three-way ANOVA (p < 0.05). In males, when compared to placebo, 5.0 mg melatonin caused GH to increase (p = 0.017) and SST to decrease prior to exercise (p = 0.031), whereas both 0.5 and 5.0 mg melatonin were greater than placebo after exercise (p = 0.045) and less than placebo for SST. No significant differences occurred for IGF-1; however, males were shown to have higher levels of IGFBP-1 independent of supplementation (p = 0.004). The 5.0 mg melatonin dose resulted in higher IGFBP-3 in males (p = 0.017). In conclusion, for males 5.0 mg melatonin appears to increase serum GH while concomitantly lowering SST levels; however, when combined with resistance exercise both melatonin doses positively impacts GH levels in a manner not entirely dependent on SST

Photonic crystals of coated metallic spheres

It is shown that simple face-centered-cubic (fcc) structures of both metallic and coated metallic spheres are ideal candidates to achieve a tunable complete photonic bandgap (CPBG) for optical wavelengths using currently available experimental techniques. For coated microspheres with the coating width to plasma wavelength ratio $l_c/\lambda_p \leq 10$ and the coating and host refractive indices $n_c$ and $n_h$, respectively, between 1 and 1.47, one can always find a sphere radius $r_s$ such that the relative gap width $g_w$ (gap width to the midgap frequency ratio) is larger than 5% and, in some cases, $g_w$ can exceed 9%. Using different coatings and supporting liquids, the width and midgap frequency of a CPBG can be tuned considerably.Comment: 14 pages, plain latex, 3 ps figures, to appear in Europhys. Lett. For more info on this subject see http://www.amolf.nl/research/photonic_materials_theory/moroz/moroz.htm

Reconstructing palaeoclimate and hydrological fluctuations in the Fezzan Basin (southern Libya) since 130 ka: a catchment-based approach

We propose a novel method to evaluate regional palaeoclimate that can be used to alleviate the problems caused by the discontinuous nature of palaeoenvironmental data found in deserts. The technique involves processing satellite imagery and DEM’s to map past rivers, catchments and evaluate the areas and volumes of palaeolakes. This information is used to determine the new Lake Evaluation Index (LEI) that allows a qualitative estimate of the amount of sediment received by lakes and how long-lived those lakes are. Lakes with considerable longevity and large sediment stores are selected for study. Validation is performed using image interpretation of remote sensing data, UltraGPR surveys and fieldwork. These techniques are also used to identify and study spring deposits and fluvial landforms that provide valuable palaeoclimate information. The method is applied to the Fezzan Basin in southern Libya focusing on the Wadi ash Shati and Wadi el-Agial catchments. Results indicate that the palaeohydrology is accurately mapped except within dune fields. We analysed the sedimentology of the key deposits identified by this methodology, developing a chronology using optically stimulated luminescence (OSL) and radiocarbon dating. We find evidence for relatively humid conditions during MIS 5c/d and e, as well as during the early to middle Holocene. Larger lakes and more extensive river systems were present during MIS 5 than are found during the Holocene, suggestive of greater humidity. The Holocene humid period started at ~11 ka and continued until ~5 ka being interrupted by abrupt periods of aridity at ~8.2 ka and ~6 ka that coincide with North Atlantic cooling. After each of these arid events the climate was less humid than previously, suggesting that they were superimposed upon an overall drying trend. The termination of the Holocene humid period in the Sahara has received much scrutiny in recent years, and sediments of Palaeolake Shati provide a continuous record of this. We do not find evidence to support the hypothesis of either sudden or gradual aridification of the Sahara at ~5 ka, instead we find that that aridity started to develop at ~6.5 ka, whereupon the lake levels oscillated until finally drying-up by 5.3 ka. Most of the other lakes in the Fezzan also dried up at ~ 5ka. We suggest that thousands of years of aridification prior to 5 ka shrunk these lakes so that additional aridity at this time led to their final desiccation. Because lakes are prodigious dust sources this mechanism potentially explains the rapid rise in dust flux to the Atlantic at 5 ka, with this final drying being the culmination of longer term aridity, albeit overprinted with considerable climate variability

Relationship Between Changes in Upper Body Fat-Free Mass and Bench Press Performance in American Football Players

Horizontal pushing strength and strength endurance are relevant attributes for blocking and block shedding in American football. Since most positions in American football require the ability to either block or shed a block, and since bench press repetitions to failure (RTF) with 225 pounds is a component of the NFL draft combine, improving horizontal pushing strength and strength endurance have been key areas of emphasis for strength and conditioning coaches working with these athletes. PURPOSE: The purpose of this analysis was to quantify the relationship between changes in upper body fat-free mass (FFM) and metrics of bench press performance in American football players. METHODS: Body composition and muscular performance were assessed in NCAA Division III American football players. Upper body FFM was obtained from dual-energy X-ray absorptiometry (DXA; Hologic Horizon) before and after a seven-week offseason training period. Barbell bench press one-repetition maximum (1RM), incline barbell bench press 1RM, and RTF with 225 pounds on the barbell bench press were also determined before and after the training period. Using Spearman’s rank correlations, the relationships between percent changes in upper body FFM and bench press 1RM (n=19), bench press RTF with 225 pounds (n=15), and incline bench press 1RM (n=18) were evaluated. RESULTS: Relative changes in bench press 1RM and DXA upper body FFM exhibited a weak, non-significant correlation (ρ: 0.38, p: 0.11). However, there was a moderate strength, significant correlation between relative changes in bench press RTF with 225 pounds and DXA upper body FFM (ρ: 0.53, p: 0.04). For relative changes in incline bench press 1RM, there was a weak, non-significant correlation with DXA upper body FFM (ρ: 0.24, p: 0.36). CONCLUSION: Of the performance tests assessed, only changes in bench press RTF with 225 pounds and changes in DXA upper body FFM were positively correlated. Therefore, strength and conditioning coaches working with athletes who plan on entering the NFL draft may want to consider dedicating time to increasing upper body FFM gains prior to the draft as it appears to be positively correlated with performance on this NFL combine test

Efficacy and tolerability of an endogenous metabolic modulator (AXA1125) in fatigue-predominant long COVID: a single-centre, double-blind, randomised controlled phase 2a pilot study

Background: ‘Long COVID’ describes persistent symptoms, commonly fatigue, lasting beyond 12 weeks following SARS-CoV-2 infection. Potential causes include reduced mitochondrial function and cellular bioenergetics. AXA1125 has previously increased β-oxidation and improved bioenergetics in preclinical models along with certain clinical conditions, and therefore may reduce fatigue associated with Long COVID. We aimed to assess the efficacy, safety and tolerability of AXA1125 in Long COVID. / Methods: Patients with fatigue dominant Long COVID were recruited in this single-centre, double-blind, randomised controlled phase 2a pilot study completed in the UK. Patients were randomly assigned (1:1) using an Interactive Response Technology to receive either AXA1125 or matching placebo in a clinical based setting. Each dose (33.9 g) of AXA1125 or placebo was administered orally in a liquid suspension twice daily for four weeks with a two week follow-up period. The primary endpoint was the mean change from baseline to day 28 in the phosphocreatine (PCr) recovery rate following moderate exercise, assessed by 31P-magnetic resonance spectroscopy (MRS). All patients were included in the intention to treat analysis. This trial was registered at ClinicalTrials.gov, NCT05152849. / Findings: Between December 15th 2021, and May 23th 2022, 60 participants were screened and 41 participants were randomised and included in the final analysis. Changes in skeletal muscle phosphocreatine recovery time constant (τPCr) and 6-min walk test (6MWT) did not significantly differ between treatment (n = 21) and placebo group (n = 20). However, treatment with AXA1125 was associated with significantly reduced day 28 Chalder Fatigue Questionnaire [CFQ-11] fatigue score when compared with placebo (least squares mean difference [LSMD] −4.30, 95% confidence interval (95% CI) −7.14, −1.47; P = 0.0039). Eleven (52.4%, AXA1125) and four (20.0%, placebo) patients reported treatment-emergent adverse events; none were serious, or led to treatment discontinuation. / Interpretation: Although treatment with AXA1125 did not improve the primary endpoint (τPCr-measure of mitochondrial respiration), when compared to placebo, there was a significant improvement in fatigue-based symptoms among patients living with Long COVID following a four week treatment period. Further multicentre studies are needed to validate our findings in a larger cohort of patients with fatigue-dominant Long COVID. / Funding: Axcella Therapeutics