1–42 b -Amyloid peptide requires PDK1/nPKC/Rac 1 pathway to induce neuronal death

1–42 b -Amyloid peptide requires PDK1/nPKC/Rac 1 pathway to induce neuronal death L Manterola 1,12 , M Hernando-Rodr ı ́ guez 2,12 , A Ruiz 3,4 , A Apraiz 5 , O Arrizabalaga 5 , L Vello ́ n 6 , E Alberdi 3,4 , F Cavaliere 3,4 , HM Lacerda 7 , S Jimenez 8,9 , LA Parada 10 , C Matute 3,4 and JL Zugaza 4,5,11 1–42 b -Amyloid (A b 1–42 ) peptide is a key molecule involved in the development of Alzheimer’s disease. Some of its effects are manifested at the neuronal morphological level. These morphological changes involve loss of neurites due to cytoskeleton alterations. However, the mechanism of A b 1–42 peptide activation of the neurodegenerative program is still poorly understood. Here, A b 1–42 peptide-induced transduction of cellular death signals through the phosphatidylinositol 3-kinase (PI3K)/ phosphoinositol-dependent kinase (PDK)/novel protein kinase C (nPKC)/Rac 1 axis is described. Furthermore, pharmacological inhibition of PDK1 and nPKC activities blocks Rac 1 activation and neuronal cell death. Our results provide insights into an unsuspected connection between PDK1, nPKCs and Rac 1 in the same signal-transduction pathway and points out nPKCs and Rac 1 as potential therapeutic targets to block the toxic effects of A b 1–42 peptide in neurons

Capital, credit and the business cycle in Marx

The purpose of this paper is to identify two inconsistencies that are found in the third chapter of Marx’s Das Kapital, dedicated to the study of credit. In the first one Marx states that the distinction between commercial and bank credit is only nominal, but he resorts to it in order to provide an explanation for the nineteenth century crisis in England, thus implying that the distinction was not only nominal, but real. The second inconsistency is noticed between Marx’s statement that real and money capital move in opposite directions during the trade cycle (without an explanation of how it is possible), and the second book of The Capital where Marx states that capital in the form of money and real capital must move in the same directions during the business cycle

Progress in Development of the Axel Rovers

Progress has been made in the development of a family of robotic land vehicles having modular and minimalist design features chosen to impart a combination of robustness, reliability, and versatility. These vehicles at earlier stages of development were described in two previous NASA Tech Briefs articles: "Reconfigurable Exploratory Robotic Vehicles" (NPO-20944), Vol. 25, No. 7 (July 2001), page 56; and "More About Reconfigurable Exploratory Robotic Vehicles" (NPO-30890), Vol. 33, No. 8 (August 2009), page 40. Conceived for use in exploration of the surfaces of Mars and other remote planets, these vehicles could also be adapted to terrestrial applications, including exploration of volcanic craters or other hostile terrain, military reconnaissance, inspection of hazardous sites, and searching for victims of earthquakes, landslides, avalanches, or mining accidents. In addition, simplified versions of these vehicles might be marketable as toys. The most basic module in this family of reconfigurable robots is the Axel rover, which has a cylindrical body with two main wheels and a trailing link. Inside its body are three motors and associated mechanisms for driving the two wheels and for rotating the link 360 around its symmetrical body. The actuated link serves several purposes: It is used as a lever arm to react to the wheels thrust to move Axel in multiple directions. It is used to rotate the Axel housing in order to tilt, to the desired angle, any sensors and instruments mounted on or in the Axel housing. It provides an alternative mobility mode, which is primarily used in its tethered configuration. Turn ing the link into the ground in lieu of driving the wheels causes the Axel housing and wheels to roll as a unit and thereby leads to a tumbling motion along the ground. With a tether mounted around Axel s cylindrical body, the link serves as a winch mechanism to reel and unreel the tether raising and lowering Axel over steep and vertical surfaces (Figure 1). Sensors, computation, and communication modules are also housed inside Axel s body. A pair of stereo vision cameras provides three-dimensional view for autonomous navigation and avoiding obstacles. Inertial sensors determine the tilt of the robot and are used for estimating its motion. In a fully developed version, power would be supplied by rechargeable batteries aboard Axel; at the time of reporting the information for this article, power was supplied from an external source via a cable. In and of itself, the Axel rover is fully capable of traversing and sampling terrains on planetary surfaces. By use of only the two main wheel actuators and the caster link actuator, Axel can be made to follow an arbitrary path, turn in place, and operate upside- down or right-side-up. If operated in a tethered configuration, as shown in Figure 1, it can be made to move down and up a steep crater wall, descend from an overhang to a cave, and ascend from the cave back to the overhang, all by use of the same three actuators. Such tethered operation could be useful in searching for accident victims or missing persons in mines, caves, and rubble piles. Running the tether through the caster link enhances the stability of Axel and provides a restoring force that keeps the link off the ground for the most part during operation on a steep slope. In its extended configuration, two Axel modules can dock to either side of a payload module to form the four wheeled Axel2 rover (Figure 2). Additional payload and Axel modules can dock to either side of the Axel2 to form the Axel3 rover, extending its payload capacity and its mobility capabilities

Molecular analysis of isoniazid and rifampin resistance in Mycobacterium tuberculosis isolates recovered from Barcelona.

We studied the presence of mutations in the whole katG gene and specific regions of the oxyR-ahpC and mabA-inhA regulatory region in 61 Mycobacterium tuberculosis isoniazid-resistant isolates. An 81-bp region of the rpoB gene was also sequenced in 17 rifampin-resistant strains. Alterations in the katG gene were detected in 55% of the isolates. Mutation in codon 315 was the most prevalent (32%). Strains showed a high level of resistance, and most maintained a substantial catalase-peroxidase activity. Three strains with an isoniazid MIC of ≥32 µg/ml lacked catalase-peroxidase activity. Two of them had deletions in the catalytic domain of the KatG protein. One strain with deletion and three strains with mutations in the C-terminal domain showed low-level resistance and conserved the catalase-peroxidase activity. Mutations in the mabA-inhA regulatory region were identified in 32% of the isolates. All had low-level resistance, and the vast majority conserved catalase-peroxidase activity. Seventeen percent of the isoniazid-resistant isolates had no detectable alterations at the studied loci. Resistance to rifampin was associated with mutations in the 81-bp of the rpoB gene in all cases. IS6110 analysis indicated that recent transmission contributed substantially to the emergence of isoniazid- resistant tuberculosis in Barcelona through short transmission chains. A rapid genotypic assay, including the 315-katG codon and the -15 nucleotide of the mabA-inhA regulatory region, may cover 62% of isoniazid- resistant strains in Barcelona. In contrast, the targeting of the 81-bp region of rpoB would detect all our rifampin-resistant isolates

State-of-the-art of spatial arch bridges

The paper describes a new form of bridge called a spatial arch bridge. This bridge type was developed in response to the demand for landmark structures, which have started to appear in the modern urban landscape to provide a symbol of originality, innovation and progress. Spatial arch bridges are defined as bridges in which the vertical deck loads produce bending moments and shear forces not contained in the arch plane, owing to their geometrical and structural configuration. Moreover, the arch itself may not be contained in a plane. The different variables and geometries that create such a structural configuration have been studied and classified. A wide compilation of examples of this bridge type has been made in chronological order, according to their construction date, from Maillarts first concrete spatial arch bridges to the latest designs and materials

Efficacy of short-course colchicine treatment in hospitalized patients with moderate to severe COVID-19 pneumonia and hyperinflammation: a randomized clinical trial

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si lo hubiere, y los autores pertenecientes a la UAMSome patients with COVID-19 pneumonia develop an associated cytokine storm syndrome that aggravates the pulmonary disease. These patients may benefit of anti-inflammatory treatment. The role of colchicine in hospitalized patients with COVID-19 pneumonia and established hyperinflammation remains unexplored. In a prospective, randomized controlled, observer-blinded endpoint, investigator-initiated trial, 240 hospitalized patients with COVID-19 pneumonia and established hyperinflammation were randomly allocated to receive oral colchicine or not. The primary efficacy outcome measure was a composite of non-invasive mechanical ventilation (CPAP or BiPAP), admission to the intensive care unit, invasive mechanical ventilation requirement or death. The composite primary outcome occurred in 19.3% of the total study population. The composite primary outcome was similar in the two arms (17% in colchicine group vs. 20.8% in the control group; p = 0.533) and the same applied to each of its individual components. Most patients received steroids (98%) and heparin (99%), with similar doses in both groups. In this trial, including adult patients with COVID-19 pneumonia and associated hyperinflammation, no clinical benefit was observed with short-course colchicine treatment beyond standard care regarding the combined outcome measurement of CPAP/BiPAP use, ICU admission, invasive mechanical ventilation or deat

Clinical validation of a novel postural support device for hospitalized sub-acute post stroke wheelchair users

Purpose: We present a novel wheelchair posture support device (WPSD) and its clinical validation. The device was developed in order to assure correct sitting posture and to reduce the time spent by caregivers for re-positioning of hospitalized, wheelchair-bound, post-acute stroke patients. Method: The device was validated with 16 subjects during a period of 5 days in which use of the device was compared with regular care practice. Results: The device was used for the five consecutive days in 69% of patients, while for 6% it was not suitable; 25% did not complete the 5 days for reasons unrelated to the device. Caregivers needed to re-position the patients that used the device for the full 5 days (n=11) on an average 52% less often when using the device, as compared to regular practice. Furthermore, the device was rated as usable and functional by the caregivers while significantly reducing perception of trunk and shoulder pain in patients during its use. Conclusions: The newly designed WPSD is a valuable system for the improvement of medical assistance to wheelchair-bound post-stroke patients by reducing pain and number of re-positioning manoeuvres. The WPSD might be applicable to any group of patients who need posture control in either wheelchair or common chair with arms support.The FIK initiative; funding the development of the Varstiff material technology. Fundaci on Bot ın’s ‘‘Mind the Gap’’ program co-funding the design process of the WPSD. Spherium Biomed co-funding the study with the WPSD