Microbial nitrogen and phosphorus co-limitation across permafrost region

The status of plant and microbial nutrient limitation have profound impacts on ecosystem carbon cycle in permafrost areas, which store large amounts of carbon and experience pronounced climatic warming. Despite the long-term standing paradigm assumes that cold ecosystems primarily have nitrogen deficiency, large-scale empirical tests of microbial nutrient limitation are lacking. Here we assessed the potential microbial nutrient limitation across the Tibetan alpine permafrost region, using the combination of enzymatic and elemental stoichiometry, genes abundance and fertilization method. In contrast with the traditional view, the four independent approaches congruently detected widespread microbial nitrogen and phosphorus co-limitation in both the surface soil and deep permafrost deposits, with stronger limitation in the topsoil. Further analysis revealed that soil resources stoichiometry and microbial community composition were the two best predictors of the magnitude of microbial nutrient limitation. High ratio of available soil carbon to nutrient and low fungal/bacterial ratio corresponded to strong microbial nutrient limitation. These findings suggest that warming-induced enhancement in soil nutrient availability could stimulate microbial activity, and probably amplify soil carbon losses from permafrost areas.     

化学修饰提高胰岛素口服降血糖作用的研究

本文探索了用小分子化合物对胰岛素进行化学修饰,以增加口服降血糖的可能性.制备了乙酰胰岛素、琥珀酰胰岛素和半乳糖酰胰岛素.这些胰岛素不仅较好地保持了天然胰岛素的活性,而且其口服降血糖作用也较天然胰岛素明显增加,其中琥珀酰胰岛素是天然胰岛素的口服降血糖作用的二倍以上.这为口服或肛门给药的胰岛素新剂型的研制提供了科学依据.     

Rapid, transient induction of ER stress in the liver and kidney after acute exposure to heavy metal: evidence from transgenic sensor mice

Endoplasmic reticulum (ER) stress-responsive alkaline phosphatase (ES-TRAP) serves as a sensitive indicator for ER stress. In response to heavy metals including cadmium, nickel and cobalt, hepatocytes and renal tubular cells expressing ES-TRAP exhibited ER stress and decreased ES-TRAP activity. In ES-TRAP transgenic mice, acute exposure to cadmium showed rapid, transient decreases in the activity of serum ES-TRAP. It was inversely correlated with the induction of endogenous ER stress markers in the liver and kidney. Our result provides first evidence for the acute, reversible induction of ER stress in vivo after exposure to heavy metal.     

Transition from rolling to firm adhesion is regulated by the conformation of the I domain of the integrin lymphocyte function-associated antigen-1

The integrin lymphocyte function-associated antigen-1 (alpha(L)beta(2)), which is known for its ability to mediate firm adhesion and migration, can also contribute to tethering and rolling in shear flow. The alpha(L) I domain can be mutationally locked with disulfide bonds into two distinct conformations, open and closed, which have high and low affinity for the ligand intercellular adhesion molecule 1 (ICAM-1), respectively. The wild type I domain exists primarily in the lower energy closed conformation. We have measured for the first time the effect of conformational change on adhesive behavior in shear flow. We show that wild type and locked open I domains, expressed in alpha(L)beta(2) heterodimers or as isolated domains on the cell surface, mediate rolling adhesion and firm adhesion, respectively. alpha(L)beta(2) is thus poised for the conversion of rolling to firm adhesion upon integrin activation in vivo. Isolated I domains are surprisingly more effective than alpha(L)beta(2) in interactions in shear flow, which may in part be a consequence of the presence of alpha(L)beta(2) in a bent conformation. Furthermore, the force exerted on the C-terminal alpha-helix appears to stabilize the open conformation of the wild type isolated I domain and contribute to its robustness in supporting rolling. An allosteric small molecule antagonist of alpha(L)beta(2) inhibits both rolling adhesion and firm adhesion, which has important implications for its mode of action in vivo.     

双CSTR耦合系统中乙醇发酵过程中的分岔研究

本文首次运用现代分岔理论方法,研究了双CSTR耦合系统中乙醇发酵过程中的多定态和振荡现象．计算结果表明,当入口糖浓度大于某值时,多定态普遍存在．同时振荡受到底物浓度S_0、两耦合反应器的体积比V_(12)及稀释率D的影响.同单CSTR相比,双CSTR加强了反应深度,并通过适当改变V_(12),产率可大大提高.     

H-Index Is Important for Postural Control for People with Impaired Foot Sole Sensation

Introduction

People with Peripheral Neuropathy (PN), especially those with impaired sensory inputs through the small-afferent fiber (type II afferent fibers) reflex loop (SAF), might depend more on the large-afferent fiber (type I afferent fibers) reflex loop (LAF) for postural control.

Purpose

To examine whether the function of the LAF reflex loop, reflected by the H-reflex and ankle joint proprioception, influences postural control when the SAF reflex loop is impaired, as indicated by reduced foot sole cutaneous sensation.

Methods

Thirteen participants (8 women, 5 men) diagnosed with PN and 12 age-matched controls (7 women, 5 men) completed the testing protocol. Measures of interest included the H-index, active (AAP) and passive (PAP) ankle proprioception, plantar pressure sensitivity (PPS), average sway velocity (V_AVG) and area (A₉₅) during 30 seconds eyes-closed standing, 6-minute walk distance (6MWD) and timed up-and-go duration (TUG).

Results

Statistically significant group-dependent regression was observed between V_AVG and H-index. Compared to the control group, the PN group demonstrated reduced PPS (2.0 ± 1.9 vs. 4.2 ± 1.2, P < .05) and H-index (63.6 ± 10.9 vs. 76.4 ± 16.0, P < .05), greater V_AVG (3.5 ± 2.1 vs. 1.6 ± 0.6cm/s, P < .05) and A₉₅ (10.0 ± 10.1 vs. 2.5 ± 1.5cm², P < .05), shorter 6MWD (442.2 ± 93.0 vs. 525.3 ± 68.2m, P < .05), and longer TUG (9.4 ± 1.6 vs. 6.5 ± 1.3s, P < .05). Within the PN group, but not the control group, the H-index was correlated with V_AVG (r = -.56, P < .05). Moreover, within the PN group only, PAP scores were correlated with 6MWD (r = -.68, P < .05) and TUG (r = -.59, P < .05) performance. No other statistically significant group difference, correlation or group-dependent regression was observed.

Conclusion

V_AVG, 6MWD, and TUG correlated with LAF reflex loop function observed among those with impaired functioning of the SAF reflex loop. This observation suggests that the LAF reflex loop may be critical to the control of balance in those individuals suffering from small-fiber PN.     

Asymmetric amyloid fibril elongation: a new perspective on a symmetric world

Amyloids are insoluble, fibrous proteins formed through the aggregation of misfolded proteins. They accumulate in the tissue of individuals with degenerative diseases, such as Parkinson's and Alzheimer's. The purpose of this study was to determine whether fibril growth from an initial model fibril seed is unidirectional or bidirectional. The prevailing theory on amyloid formation is that a symmetric fibril elongates equally from both ends. This study provides evidence to the contrary; the process occurs predominately unidirectionally, demonstrating that amyloid fibrils may be asymmetric and propagate mostly in one direction. Alexa Fluor 568 labeled insulin fibrils were seeded into a native insulin solution and allowed to elongate at 65°C while the kinetics of fibril growth was monitored. The resulting elongated fibrils were labeled with thioflavin-T, and the fluorescent images of the fibrils show that a majority of the elongated fibrils propagated along only one end of the seed, with the remaining labeled fibrils having bidirectional elongation or no elongation. Using a crystallographic model, we offer a structural explanation for asymmetric growth of the insulin fibrils. Thus, instead of the current view that fibrils grow symmetrically from both ends of the fibril, this is the first evidence that insulin amyloid fibrils formed in solution are asymmetric and appear to grow from only one end.     

Miniaturized lensless imaging systems for cell and microorganism visualization in point-of-care testing

Low-cost, robust, and user-friendly diagnostic capabilities at the point-of-care (POC) are critical for treating infectious diseases and preventing their spread in developing countries. Recent advances in micro- and nanoscale technologies have enabled the merger of optical and fluidic technologies (optofluidics) paving the way for cost-effective lensless imaging and diagnosis for POC testing in resource-limited settings. Applications of the emerging lensless imaging technologies include detecting and counting cells of interest, which allows rapid and affordable diagnostic decisions. This review presents the advances in lensless imaging and diagnostic systems, and their potential clinical applications in developing countries. The emerging technologies are reviewed from a POC perspective considering cost effectiveness, portability, sensitivity, throughput and ease of use for resource-limited settings.