The effect of chronic deafferentation on mental imagery: a case study

Visual- and motor imagery rely primarily on perceptual and motor processes, respectively. In healthy controls, the type of imagery used to solve a task depends on personal preference, task instruction, and task properties. But how does the chronic loss of proprioceptive and tactile sensory inputs from the body periphery influence mental imagery? In a unique case study, we investigated the imagery capabilities of the chronically deafferented patient IW when he was performing a mental rotation task. We found that IW''s motor imagery processes were impaired and that visual imagery processes were enhanced compared to controls. These results suggest that kinaesthetic afferent signals from the body periphery play a crucial role in enabling and maintaining central sensorimotor representations and hence the ability to incorporate kinaesthetic information into the imagery processes.     

Antigen-specificity of oligoclonal abnormal protein bands in multiple myeloma after allogeneic stem cell transplantation

Myeloma patients may develop oligoclonal immunoglobulins, so-called abnormal protein bands (APB), after stem cell transplantation. APB do not correspond to the patient's paraprotein and confer a good prognosis. We set out to investigate whether such APB represent a humoral anti-myeloma immune response by screening immunoglobulins of 15 myeloma patients after allogeneic stem cell transplantation and a control group of healthy donors for reactivity with myeloma protein extracts. While the immunoglobulins of healthy donors did not react with myeloma protein extracts, patient-derived immunoglobulins showed variable levels of interaction, depending on the presence of APB on immunofixation. Most commonly, we detected interactions with heat-shock proteins, followed by neutral alpha-glucosidase, alpha-enolase and vimentin, as well as proliferating cell nuclear antigen and MAGEA4. More than 80% of targets were upregulated in myeloma. Heat-shock protein 60 (HSP60) was subsequently evaluated as an exemplary antigen. We found that HSP60 was aberrantly displayed on the surface of primary myeloma cells. Indeed, patient-derived APB-containing immunoglobulins recognized surface HSP60 suggesting that this antigen becomes accessible to the immune system after aberrant membrane exposition. We conclude that immunoglobulin fractions with APB recognize recurrent myeloma antigens and that this humoral response may contribute to the more favorable prognosis in patients with APB.     

Transgenic over-expression of interleukin-33 in osteoblasts results in decreased osteoclastogenesis

Interleukin-33 (IL-33) is the most recently identified member of the IL-1 family of cytokines, which is primarily known for its proinflammatory functions. We have previously reported that IL-33 is expressed by bone-forming osteoblasts, and that administration of recombinant IL-33 to bone marrow cultures inhibits their differentiation into bone-resorbing osteoclasts. Likewise, while the inhibitory effect of IL-33 on osteoclast differentiation was fully abolished in cultures lacking the IL-33 receptor ST2, mice lacking ST2 displayed low bone mass caused by increased osteoclastogenesis. Although these data suggested a physiological role of IL-33 as an inhibitor of bone resorption, direct in vivo evidence supporting such a function was still missing. Here we describe the generation and bone histomorphometric analysis of a transgenic mouse model (Col1a1-Il33) over-expressing IL-33 specifically in osteoblasts. While we did not observe differences in osteoblast number and bone formation between wildtype and Col1a1-Il33 mice, the number of osteoclasts was significantly reduced compared to wildtype littermates in two independent transgenic lines. Since we did not observe quantitative differences in the populations of eosinophils, neutrophils, basophils or M2-macrophages from the bone marrow of wildtype and Col1a1-Il33 mice, our data demonstrate that an inhibition of osteoclastogenesis is one of the major physiological functions of IL-33, at least in mice.     

Microparticle delivery of Interleukin-7 to boost T-cell proliferation and survival

In HIV infections, homoeostasis of T cells is dysregulated such that there is a depletion of CD4⁺ T cells and a progressive loss of naïve CD4⁺ and CD8⁺ T cells. Methodologies that can improve the function of some or all of these cells will likely enhance immune responsiveness in HIV infection. Interleukin‐7 (IL‐7) is a cytokine that has been shown to be critical in homeostatic expansion of naïve CD8⁺ and CD4⁺ cells in lymphopenic hosts, as well as regulating effector T cell to memory T‐cell transition and memory T‐cell homeostasis. In animal studies and clinical trials, repeated injections of IL‐7 are used to boost both CD4⁺ and CD8⁺ cell counts. Daily injections, however, are painful, inconvenient, and provide a frequent route for pathogen entry. We developed a poly (D ,L ‐lactide‐co‐glycolide; PLGA) microparticle controlled release system to administer IL‐7 in which a single injection of microparticles can provide therapeutic delivery of IL‐7. IL‐7 encapsulated PLGA microparticles were first synthesized using a water/organic/water double emulsion method, release from the particles was then optimized using in vitro release studies and therapeutic effectiveness was finally studied in animal studies. These PLGA microparticles showed effective delivery of IL‐7 for 1 week in vitro. These results were translated to in vivo delivery as well, which was followed for 9 days. Controlled release of IL‐7 in mice demonstrated biological activity in both CD4⁺ and CD8⁺ T cells in mice, which was consistent with previously reported results using daily injections. Biotechnol. Bioeng. 2012; 109:1835–1843. © 2012 Wiley Periodicals, Inc.     

Hybrid breeding in autogamous cereals

Hybrid breeding in autogamous cereals has a long history of attempts with moderate success. There is a vast amount of literature investigating the potential problems and solutions, but until now, market share of hybrids is still a niche compared to line varieties. Our aim was to summarize the status quo of hybrid breeding efforts for the autogamous cereals wheat, rice, barley, and triticale. Furthermore, the research needs for a successful hybrid breeding in autogamous cereals are intensively discussed. To our opinion, the basic requirements for a successful hybrid breeding in autogamous cereals are fulfilled. Nevertheless, optimization of the existing hybridization systems is urgently required and should be coupled with the development of clear male and female pool concepts. We present a quantitative genetic framework as a first step to compare selection gain of hybrid versus line breeding. The lack of precise empirical estimates of relevant quantitative genetic parameters, however, is currently the major bottleneck for a robust evaluation of the potential of hybrid breeding in autogamous cereals.     

Modeling Non-inherited Antibiotic Resistance

A mathematical model is presented for the increase and decrease of non-inherited antibiotic resistance levels in bacteria. The model is applied to experimental data on E. coli exposed to amoxicillin or tetracyclin in different concentrations. The parameters of the model are estimated using a Monte Carlo Markov Chain method. The model accurately describes build-up and decline of antibiotic resistance caused by physiological adaptations as long as no genetic changes have occurred. The main conclusion of the analysis is that short time periods are sufficient to re-obtain low MIC-values after long-lasting exposure to these antibiotics.     

Form,function and evolution of the mouthparts of blood-feeding Arthropoda

This review compares the mouthparts and their modes of operation in blood-feeding Arthropoda which have medical relevance to humans. All possess piercing blood-sucking proboscides which exhibit thin stylet-shaped structures to puncture the host's skin. The tips of the piercing structures are serrated to provide anchorage. Usually, the piercing organs are enveloped by a soft sheath-like part which is not inserted. The piercing process includes either back and forth movements of the piercing structures, or sideways cutting motions, or the apex of the proboscis bears teeth-like structures which execute drilling movements. Most piercing-proboscides have a food-canal which is separate from a salivary canal. The food-canal is functionally connected to a suction pump in the head that transports blood into the alimentary tract. The salivary canal conducts saliva to the tip of the proboscis, from where it is discharged into the host. Piercing blood-sucking proboscides evolved either from (1) generalized biting-chewing mouthparts, (2) from piercing mouthparts of predators, or plant sap or seed feeders, (3) from lapping or sponging mouthparts. Representatives of one taxon of Acari liquefy skin tissue by enzymatic action. During feeding, many blood-feeding arthropods inadvertently transmit pathogens, which mostly are transported through the discharged saliva into the host.