Functional Diversity of Robo Receptor Immunoglobulin Domains Promotes Distinct Axon Guidance Decisions

SummaryRecognition molecules of the immunoglobulin (Ig) superfamily control axon guidance in the developing nervous system. Ig-like domains are among the most widely represented protein domains in the human genome, and the number of Ig superfamily proteins is strongly correlated with cellular complexity [1]. In Drosophila, three Roundabout (Robo) Ig superfamily receptors respond to their common Slit ligand to regulate axon guidance at the midline: Robo and Robo2 mediate midline repulsion, Robo2 and Robo3 control longitudinal pathway selection, and Robo2 can promote midline crossing [2–5]. How these closely related receptors mediate distinct guidance functions is not understood. We report that the differential functions of Robo2 and Robo3 are specified by their ectodomains and do not reflect differences in cytoplasmic signaling. Functional modularity of Robo2's ectodomain facilitates multiple guidance decisions: Ig1 and Ig3 of Robo2 confer lateral positioning activity, whereas Ig2 confers promidline crossing activity. Robo2's distinct functions are not dependent on greater Slit affinity but are instead due in part to differences in multimerization and receptor-ligand stoichiometry conferred by Robo2's Ig domains. Together, our findings suggest that diverse responses to the Slit guidance cue are imparted by intrinsic structural differences encoded in the extracellular Ig domains of the Robo receptors

Kekkon5 is an extracellular regulator of BMP signaling

AbstractPrecise spatial and temporal control of Drosophila Bone Morphogenetic Protein (BMP) signaling is achieved by a host of extracellular factors that modulate ligand distribution and activity. Here we describe Kekkon5 (Kek5), a transmembrane protein containing leucine-rich repeats (LRRs), as a novel regulator of BMP signaling in Drosophila. We find that loss or gain of kek5 disrupts crossvein development and alters the early profile of phosphorylated Mad and dSRF in presumptive crossvein cells. kek5 phenotypic effects closely mimic those observed with Short gastrulation (Sog), but do not completely recapitulate the effects of dominant negative BMP receptors. We further demonstrate that Kek5 is able to antagonize the BMP ligand Glass bottom boat (Gbb) and that the Kek5 LRRs are required for BMP inhibitory activity, while the Ig domain is dispensable in this context. Our identification of Kek5 as a modulator of BMP signaling supports the emerging notion that LIG proteins function as diverse regulators of cellular communication

An Electromyography Study of Muscular Endurance during the Posterior Shoulder Endurance Test

The primary purpose was to determine if there is a difference between the median frequency slopes of 5 posterior shoulder muscles during the initial portion of the Posterior Shoulder Endurance Test (PSET) at the 90° and 135° shoulder abduction positions. Fifty-five healthy volunteers (31 females) participated. The median frequency of the posterior deltoid (PD), upper trapezius (UT), middle trapezius (MT), lower trapezius (LT), and infraspinatus (INF) was measured during the PSET at 90° and 135° of shoulder abduction. External torque of 13 ± 1 Nm was used for females and 21 ± 1 Nm for males. A fixed effect multi-variable regression model was used to investigate the median frequency slopes. Males and females were analyzed separately. Median frequency slopes demonstrated fatigue in all 5 of the muscles. The PD fatigued greater than the UT in males (p = 0.0215) and greater than the LT in females (p = 0.008). The time to task failure (TTF) was greater at 90° than 135° for females and males (p = 0.016; p = 0.0193) respectively. The PSET causes fatigue in all of the muscles that were tested, with the PD fatiguing at a greater rate compared to one muscle for each sex. This investigation supports using TTF as a clinical measure of shoulder girdle endurance at 90° shoulder abduction

The alpha-effect in cyclic secondary amines: new scaffolds for iminium ion accelerated transformations

Five-membered secondary amine heterocycles containing an α-heteroatom were prepared and shown to be ineffective as catalysts for the iminium ion catalysed Diels–Alder reaction between cinnamaldehyde and cyclopentadiene. Their six-membered counterparts proved to be highly active catalysts. In stark contrast, the catalytic activity observed when comparing the non α-heteroatom cyclic amines proline methyl ester and methyl pipecolinate showed the five-membered ring amine was significantly more active. Concurrent density functional theoretical calculations suggest a rationale for the observed trends in reactivity, highlighting that LUMO activation through an iminium ion intermediate plays a key role in catalytic activity

Solution phase, solid state, and theoretical investigations on the MacMillan imidazolidinone

A combination of soln. phase NMR, X-ray crystallog. studies, and DFT calcns. provide a consistent structural conformation for iminium ions derived from the MacMillan imidazolidinone

Reproducibility and Discriminant Validity of the Posterior Shoulder Endurance Test in Healthy and Painful Populations

OBJECTIVE: This investigation measured the reproducibility and discriminant validity of the Posterior Shoulder Endurance Test (PSET) on painful and non-painful populations. DESIGN: Reliability and validity study. SETTING: Laboratory setting. PARTICIPANTS: Thirty subjects (male = 11; female = 19). MAIN OUTCOME MEASURES: Time to failure (TTF) was the primary outcome measure to determine reliability of the PSET. Discriminant validity identified with receiver operator characteristic (ROC) curves utilized TTF separately in men and women since they used different loads. RESULTS: There were 25/30 subjects (painful = 12; non-painful = 13) tested a second time. ICC, SEM, and MDC90 ranged respectively from 0.77, 13.1 s, 30.6 s in the painful group to 0.85, 7.3 s, 17 s in the non-painful group. The male ROC curve AUC was 0.833 with 47 s resulting in the best combination of sensitivity = 0.833, and specificity = 0.80. The female ROC curve AUC was 0.633 with 46 s resulting in the best combination of sensitivity = 0.600 and specificity = 0.889 at 46 s. CONCLUSION: The PSET is a reliable way to measure shoulder girdle muscular endurance. These data suggest that the PSET discriminates painful and non-painful individuals better in men compared to women

Semi-Permanent Vacuum Closure with Multiple Retubulation Capability

A vacuum system (20) includes an enclosure (22) having a vacuum-tight wall (26) and an internally threaded aperture (66) through the wall (26). A tip-off fitting (24) has a base (50) with a bore (52) therethrough, a hollow tube (62) fixed to the base (50) with a vacuum-tight seal, such that an interior (64) of the tube (62) is in communication with the bore (52) in the base (50), and an external thread (58) on the exterior of the base (50). The external thread (58) on the exterior of the base (50) is dimensioned to threadably engage the internal thread (68) on the aperture (66). There is a disengageable vacuum sealant (70) such as a layer of indium metal between the external thread (58) of the base (50) and the internal thread (68) of the aperture (66). The vacuum system (20) is evacuated through the tip-off fitting (24) and sealed by closing off the hollow tube (62). At a later time, the vacuum system can be brought to atmospheric pressure and then reseated by replacing the tip-off fitting with another tip-off fitting and repeating the evacuation and sealing

Bioenergy production using high rate, low F:M anaerobic digestion

Any scheme to create renewable energy from waste streams will undoubtedly utilize some degree of anaerobic conversion of organics to biogas (a mixture of methane and carbon dioxide). Traditionally, anaerobic treatment has been utilized as a pretreatment step (e.g., anaerobic lagoon) or as a sludge stabilization step at the tail end of a treatment scheme. The difficulty in using anaerobic digestion as the main treatment step is threefold: anaerobic bacteria are slow growers, anaerobic bacteria are difficult to separate from the non-productive solids, and toxic and/or inhibitory conditions can cause the digestion process to deteriorate to the point of process failure. The research presented here takes a fresh look at anaerobic digestion and provides an alternate strategy that reduces the required detention time and eliminates the necessity of operating at mesophilic or thermophilic temperatures. The anaerobic treatment of municipal wastewater was successfully performed with the Static Granular Bed Reactor (SGBR). Five-day, carbonaceous biochemical oxygen demand (CBOD5) and total suspended solids were reduced to less than 30 mg/L in the effluent at HRTs of 24 hours and above and at an HRT of eight hours. Suspended solids accumulated within the reactor on top of the granule bed, and were easily wasted from a valved port. Due to the limiting rate of hydrolysis, biodegradable suspended solids were not fully metabolized, and methane recovery of chemical oxygen demand (COD) removed by the reactor was incomplete.Bajada New Energy, General Membrane, EcoGroup, Econetique, Energy Investment, JMV Vibro Blocks, Solar Engineering, Solar Solutionspeer-reviewe