Inter-segmental coordination: motor pattern in humans stepping over an obstacle with mechanical ankle joint friction

This study examined the influence of a mechanical perturbation of the ankle joint on obstacle avoidance pattern. A decoupled control between the distal joint and the combined (hip-knee) proximal joints was observed according to the task requirement. In this context, a greater mechanical friction at the ankle should be compensated at this joint (local compensation) or alternatively, by regulating more combined proximal joints (knee and/or hip). The leading limb inter-segmental coordination was evaluated in both no constraint and constraint conditions in calculating ranges of motion (ROM), moments of force and powers (from heel-off to obstacle) at the ankle, knee and hip joints. Electromyographic activities were also analyzed. With the constraint, the dorsiflexor moment and the tibialis anterior activity remained unchanged while both ROM and power bursts (absorbed and generated) decreased. The hip and knee ROM remain invariant. At heel-off the absorption by hip extensors decreased and the forthcoming generation by knee flexors increased in the constraint condition. To quantify the inter-joint coordination, principal component analysis was used and indicated a high level of inter-joint coupling (synergy) that decreased with the constraint (i.e. less inter-joint coupling). At the ankle joint, the results suggest that the central command was the same in both conditions thus, not be adapted. At both the hip and knee joints, a combined joints modulation occurred to overcome additional friction.     

The transpososome: control of transposition at the level of catalysis

Studies of several transposable genetic elements have pinpointed the importance of the transpososome, a nucleoprotein complex involving the transposon ends and a transposon-encoded enzyme--the transposase--as a key in regulating transposition. Transpososomes provide a precise architecture within which the chemical reactions involved in transposon displacement occur. Data are accumulating that suggest they are dynamic and undergo staged conformational changes to accommodate different steps in the transposition pathway. This has been underpinned by recent results obtained particularly with Tn5, Tn10 and bacteriophage Mu.     

Quantification of the magnification and distortion effects of a pediatric flexible video-bronchoscope

Background

Flexible video bronchoscopes, in particular the Olympus BF Type 3C160, are commonly used in pediatric respiratory medicine. There is no data on the magnification and distortion effects of these bronchoscopes yet important clinical decisions are made from the images. The aim of this study was to systematically describe the magnification and distortion of flexible bronchoscope images taken at various distances from the object.

Methods

Using images of known objects and processing these by digital video and computer programs both magnification and distortion scales were derived.

Results

Magnification changes as a linear function between 100 mm (×1) and 10 mm (×9.55) and then as an exponential function between 10 mm and 3 mm (×40) from the object. Magnification depends on the axis of orientation of the object to the optic axis or geometrical axis of the bronchoscope. Magnification also varies across the field of view with the central magnification being 39% greater than at the periphery of the field of view at 15 mm from the object. However, in the paediatric situation the diameter of the orifices is usually less than 10 mm and thus this limits the exposure to these peripheral limits of magnification reduction. Intraclass correlations for measurements and repeatability studies between instruments are very high, r = 0.96. Distortion occurs as both barrel and geometric types but both types are heterogeneous across the field of view. Distortion of geometric type ranges up to 30% at 3 mm from the object but may be as low as 5% depending on the position of the object in relation to the optic axis.

Conclusion

We conclude that the optimal working distance range is between 40 and 10 mm from the object. However the clinician should be cognisant of both variations in magnification and distortion in clinical judgements.     

AK2 deficiency compromises the mitochondrial energy metabolism required for differentiation of human neutrophil and lymphoid lineages

Reticular dysgenesis is a human severe combined immunodeficiency that is primarily characterized by profound neutropenia and lymphopenia. The condition is caused by mutations in the adenylate kinase 2 (AK2) gene, resulting in the loss of mitochondrial AK2 protein expression. AK2 regulates the homeostasis of mitochondrial adenine nucleotides (ADP, ATP and AMP) by catalyzing the transfer of high-energy phosphate. Our present results demonstrate that AK2-knocked-down progenitor cells have poor proliferative and survival capacities and are blocked in their differentiation toward lymphoid and granulocyte lineages. We also observed that AK2 deficiency impaired mitochondrial function in general and oxidative phosphorylation in particular – showing that AK2 is critical in the control of energy metabolism. Loss of AK2 disrupts this regulation and leads to a profound block in lymphoid and myeloid cell differentiation.Severe combined immunodeficiencies are inherited disorders characterized by a block in the differentiation of the T lymphoid lineage and defects in other hematopoietic lineages.^{1, 2} The autosomal recessive severe combined immunodeficiency known as reticular dysgenesis (RD) is characterized by the absence of neutrophils, T and natural killer (NK) lymphocytes and by bilateral sensorineural deafness. Red blood cells, platelets and/or B cells are affected in some cases. Clinical manifestations appear in the first few weeks after birth, owing to profound neutropenia that cannot be corrected by administration of granulocyte colony-stimulating factor (G-CSF). At present, the only available treatment for RD is hematopoietic stem cell transplantation.³RD is known to be caused by mutations in the AK2 gene, leading to an absence of AK2 protein expression.^{4, 5} AK2 belongs to the adenylate kinase family and is widely expressed in many tissues and in all hematopoietic cells. The AK2 protein is located in the intermembrane space of mitochondria, whereas other members of the AK family are cytoplasmic (AK1, 5, 7 and 8), nuclear (AK6) or located in the mitochondrial matrix (AK3 and AK4).^{6, 7} The AK2 protein regulates intracellular ATP levels by catalyzing the reversible transfer of a phosphate group in the reaction ATP+AMP ↔ 2 ADP.⁶ It is known that AK2 senses AMP, modulates metabolic signaling processes and maintains energy homeostasis in the cell. Recent studies have shown that the differentiation of hematopoietic stem cells (HSCs) requires high energy levels, which are provided by the activation of oxidative phosphorylation (OXPHOS) in the mitochondria.⁸ It has also been suggested that deregulation of AK2 function could be involved in the alteration of mitochondrial metabolism and, consequently, in the development of human disease.⁹With a view to understand AK2''s involvement in hematopoiesis, we developed an in vitro RNA interference strategy via lentiviral-mediated gene transfer of AK2 short hairpin RNAs into human hematopoietic progenitors or cell lines. Our present results demonstrate that in the absence of AK2 protein expression, progenitor cells could neither proliferate nor differentiate into lymphoid and granulocyte lineages. We also identified AK2 as a major regulator of energy metabolism – suggesting a direct link between the differentiation block observed in RD patients and the regulation of mitochondrial function.     

Fetal microchimerism in kidney biopsies of lupus nephritis patients may be associated with a beneficial effect

IntroductionMicrochimeric male fetal cells (MFCs) have been associated with systemic lupus erythematosus, and published studies have further correlated MFC with lupus nephritis (LN). In the present study, we evaluated the frequency of MFC in the renal tissue of patients with LN.MethodsTwenty-seven renal biopsies were evaluated: Fourteen were from women with clinical and laboratory findings of LN, and thirteen were from controls. Genomic DNA was extracted from kidney biopsies, and the male fetal DNA was quantified using real-time quantitative polymerase chain reactions for the detection of specific Y chromosome sequences.ResultsMFCs were detected in 9 (64%) of 14 of patients with LN, whereas no MFCs were found in the control group (P = 0.0006). No differences in pregnancy history were found between patients with LN and the control group. Significantly higher amounts of MFCs were found in patients with LN with serum creatinine ≤1.5 mg/dl. Furthermore, women with MFCs had significantly better renal function at the time of biopsy (P = 0.03). In contrast, patients with LN without MFCs presented with more severe forms of glomerulonephritis (World Health Organization class IV = 60% and class V = 40%).ConclusionsOur data indicate a high prevalence of MFCs in renal biopsy specimens from women with LN, suggesting a role for MFCs in the etiology of LN. The present report also provides some evidence that MFCs could have a beneficial effect in this disease.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0615-4) contains supplementary material, which is available to authorized users.     

Chitotriosidase - a putative biomarker for sporadic amyotrophic lateral sclerosis

Background

Potential biomarkers to aid diagnosis and therapy need to be identified for Amyotrophic Lateral Sclerosis, a progressive motor neuronal degenerative disorder. The present study was designed to identify the factor(s) which are differentially expressed in the cerebrospinal fluid (CSF) of patients with sporadic amyotrophic lateral sclerosis (SALS; ALS-CSF), and could be associated with the pathogenesis of this disease.

Results

Quantitative mass spectrometry of ALS-CSF and control-CSF (from orthopaedic surgical patients undergoing spinal anaesthesia) samples showed upregulation of 31 proteins in the ALS-CSF, amongst which a ten-fold increase in the levels of chitotriosidase-1 (CHIT-1) was seen compared to the controls. A seventeen-fold increase in the CHIT-1 levels was detected by ELISA, while a ten-fold elevated enzyme activity was also observed. Both these results confirmed the finding of LC-MS/MS. CHIT-1 was found to be expressed by the Iba-1 immunopositive microglia.

Conclusion

Elevated CHIT-1 levels in the ALS-CSF suggest a definitive role for the enzyme in the disease pathogenesis. Its synthesis and release from microglia into the CSF may be an aligned event of neurodegeneration. Thus, high levels of CHIT-1 signify enhanced microglial activity which may exacerbate the process of neurodegeneration. In view of the multifold increase observed in ALS-CSF, it can serve as a potential CSF biomarker for the diagnosis of SALS.