Influence of Ca2+ and pH on the folding of the prourotensin II precursor

Proper folding is a crucial step for the trafficking of proteins through the secretory pathway. We hypothesized that the secretory granules of endocrine cells provide optimal folding conditions of prohormone precursors for cleavage. Here, using circular dichroism and in vitro processing on purified prourotensin II (ProUII), we show that the precursor undergoes pH- and Ca(2+)-dependent conformational and stability changes. ProUII has a stable tertiary structure at pH 5.5 in presence of Ca(2+) and is correctly cleaved in these conditions by prohormone convertases. Taken together, our results support the notion that precursors may need to be optimally folded in the lumen of secretory granules for their processing.     

How do trees respond to species mixing in experimental compared to observational studies?

For decades, ecologists have investigated the effects of tree species diversity on tree productivity at different scales and with different approaches ranging from observational to experimental study designs. Using data from five European national forest inventories (16,773 plots), six tree species diversity experiments (584 plots), and six networks of comparative plots (169 plots), we tested whether tree species growth responses to species mixing are consistent and therefore transferrable between those different research approaches. Our results confirm the general positive effect of tree species mixing on species growth (16% on average) but we found no consistency in species‐specific responses to mixing between any of the three approaches, even after restricting comparisons to only those plots that shared similar mixtures compositions and forest types. These findings highlight the necessity to consider results from different research approaches when selecting species mixtures that should maximize positive forest biodiversity and functioning relationships.     

Development of pyridopyrimidines as potent Akt1/2 inhibitors

This communication reports a new synthetic route of pyridopyrimidines to facilitate their structural optimization in a library fashion and describes the development of pyridopyrimidines that have excellent enzymatic and cell potency against Akt1 and Akt2. This series also shows a high level of selectivity over other closely related kinases and significantly improved caspase-3 activity with the more optimized compounds.     

Effect of aging on fatigue characteristics of elbow flexor muscles during sustained submaximal contraction.

The purpose of this study was to compare fatigue-related measures of central and peripheral mechanisms between young and elderly subjects for a task performed with elbow flexor muscles. Ten young and nine elderly subjects performed a sustained submaximal fatigue task at 35% of their maximum voluntary contraction torque. Measures of neuromuscular function, reflecting changes in neuromuscular propagation, voluntary activation, excitation-contraction-relaxation processes, and metabolite buildup, were taken before, during, and after the fatigue task. The main results were the absence of neuromuscular propagation failure in either young or elderly subjects, the presence of central fatigue at the end of the fatigue task in 7 of 9 elderly but only 3 of 10 young subjects, and lesser changes in twitch torque contraction-relaxation variables and electromyographic median frequency in elderly compared with young subjects. The lesser fatigue-related changes in twitch contraction speed and median frequency in elderly compared with young subjects could reflect the increase in type I-to-type II fiber area reported with old age. The presence of significant central fatigue can apparently minimize some of the potential differences present in peripheral fatigue sites.     

The propeptide Asn1-Tyr126 is the storage form of rat atrial natriuretic factor.

Granules from rat atria were isolated by differential centrifugation and by a 53% (v/v) Percoll gradient after tissue homogenization in 0.25 M-sucrose/50 mM-Na2EDTA. About 40% of the immunoreactive ANF (atrial natriuretic factor) sedimented with the atrial granules during differential centrifugations. On the Percoll gradient, two distinct bands were observed. Cell debris, mitochondria, lysosomes, myofilaments and microsomes were mostly contained in the lightest-density (rho) (1.03-1.07 g/ml) fraction, as demonstrated by electron microscopy and by enzymic markers such as lactate dehydrogenase, monoamine oxidase, cytochrome c reductase, beta-glucuronidase and acid phosphatase. Atrial granules were mostly contained in the denser (rho 1.11-1.15 g/ml) band and were only slightly contaminated by lysosomes, as shown by beta-glucuronidase activity. Analysis of the ANF content in these isolated granules by h.p.l.c., amino acid composition and sequencing demonstrated that it was only the pro-ANF [ANF-(Asn1-Tyr126)-peptide]. The precursor was present in all granules, as demonstrated by immunocytochemistry. Since hormonal propeptides usually undergo intracellular processing, and the matured peptides are subsequently stored in the secretory granules, these results indicate that the processing pathway of ANF may be different from that of other hormonal peptides.     

Does lemming winter grazing impact vegetation in the Canadian Arctic?

In low-productivity environments such as the tundra, it has been proposed that regular, multi-annual population cycles of lemmings could be driven by winter food depletion in years of peak abundance. If lemming population dynamics is controlled by food resources, we predict that (1) winter grazing should negatively impact the abundance of food plants, (2) this impact should be proportional to lemming density and (3) high lemming winter grazing pressure should result in reduced plant growth during the following summer. We tested these predictions on Bylot Island, Nunavut, Canada, where two species of lemmings are present: the brown (Lemmus trimucronatus) and collared lemming (Dicrostonyx groenlandicus). We installed 16 exclosures in their preferred wintering habitat (snowbeds) and annually sampled plant biomass inside and outside exclosures at snow melt and at peak growth during the summers of 2009–2012, covering a full population cycle. Winter grazing had no impact on total vascular plant or moss biomass at snow melt in all years. Among plant families, only Caryophyllaceae, which was uncommon, showed a decline. In moss taxa, a negative effect was found on Polytrichum in only 1 year out of three. Overall, plant regrowth during the subsequent summer showed annual variation and tended to be reduced in the 2 years of high lemming abundance. However, this could be a consequence of summer grazing. Overall, the impact of lemming winter grazing on plants was weak and short-lived, even in years of high lemming abundance. Therefore, our results are not consistent with the hypothesis that food depletion during winter was the cause of the lemming decline following peak abundance at our study site. Other factors may limit lemming populations and prevent them from reaching densities high enough to exhaust their food resources.     

Muscle activation characteristics associated with differences in physiological tremor amplitude between the dominant and non-dominant hand

The aim of this study was to assess differences in physiological tremor amplitude of the hand between the dominant and non-dominant side of right-handed individuals. Mechanical loading of the hand and frequency analysis were used in an attempt to identify the physiological mechanisms involved in observed differences. Seventeen healthy right-handed adults participated in a single session where physiological tremor of the outstretched left and right hands was recorded under different loading conditions (0 g up to 5614 g). Physiological tremor amplitude was quantified through accelerometry and electromyographic (EMG) signals of wrist extensor and flexor muscles were also recorded. The main findings were: ～30% greater amplitude of fluctuations in acceleration for the non-dominant compared with the dominant hand, no difference in the frequency content of acceleration or demodulated EMG signals between dominant and non-dominant sides across all loads, and condition-dependent associations between the amplitude of fluctuations in acceleration and EMG amplitude and frequency content. These associations suggest a potential role of central modulation of neural activity to explain dominance-related differences in physiological tremor amplitude of the hand.     

Influence of test position on neck muscle fatigue in healthy controls

BackgroundIt has been suggested that increased fatigue of neck muscles could be related to neck pain. However, studies on the matter present contradicting results which could be explained by the different test positions used.PurposeThe purpose of this study was to investigate the influence of test position on muscle fatigue of neck flexor and extensor muscles in healthy controls.MethodsTwenty-five women without neck pain sustained neck flexion and neck extension isometric contractions at 25% and 75% of their maximal voluntary contraction (MVC) in two test positions: sitting and supine lying. Using surface electromyography, the change over time of the median frequency of the power spectrum (MDF slope) of the myoelectric signal of the sternocleidomastoid and splenius capitis muscles was measured and compared between both positions.ResultsAt 75% MVC, splenius capitis muscles presented higher fatigue in lying compared to sitting, while sternocleidomastoid demonstrated no difference between positions. No statistically significant effect of test position was found at 25% MVC for both sternocleidomastoid and splenius capitis muscles as they generally did not present myoelectric manifestations of fatigue.ConclusionThese results underline the need to standardise the test position when investigating neck muscle fatigue, especially for neck extensors at high loads.