CXCL12 is a costimulator for CD4+ T cell activation and proliferation in chronic lymphocytic leukemia patients

Activated T cells from patients with chronic lymphocytic leukemia (CLL) provide survival and proliferative signals to the leukemic clone within lymphoid tissues. Recruitment of both, CLL cells and T lymphocytes, to this supportive microenvironment greatly depends on CXCL12 production by stromal and myeloid cells. CXCL12 also supplies survival stimuli to leukemic B cells, but whether it exerts stimulatory effects on T lymphocytes from CLL patients is unknown. In order to evaluate the capacity of CXCL12 to increase CD4⁺ T cell activation and proliferation in CLL patients, peripheral blood mononuclear cells were cultured with or without recombinant human CXCL12 or autologous nurse-like cells, and then T cell activation was induced by anti-CD3 mAb. CXCL12 increases the proliferation and the expression of CD25, CD69, CD154, and IFNγ on CD3-stimulated CD4⁺ T cells from CLL patients, similarly in T cells from ZAP-70⁺ to ZAP-70^? patients. Autologous nurse-like cells establish a close contact with CD4⁺ T cells and increase their activation and proliferation partially through a CXCR4-dependent mechanism. In addition, we found that activated T cells in the presence of CXCL12 enhance the activation and proliferation of the leukemic clone. In conclusion, CXCL12 production by lymphoid tissue microenvironment in CLL patients might play a key dual role on T cell physiology, functioning not only as a chemoattractant but also as a costimulatory factor for activated T cells.     

Side distinct sciatic nerve recovery differences between rats and mice

The Sciatic Functional Index (SFI) is widely used to evaluate functional recovery after sciatic nerve injury, primarily in the rat, and more recently shown useful in the mouse. This quantitative, non-invasive method allows tracking of regeneration capability, visible in the gait of the animal. Using a Martin micro needle holder, carrying a force measured to be 49.2 N, the left sciatic nerve was crushed for 60 s. We accumulated data from walking tracks collected preoperatively and 1, 7, 14, 21, and 28 days after injury. SFI values were first calculated in the traditional manner. Then using the preoperative values as the normal value in the postoperative calculations, SFI was again calculated; this isolated the calculations to either injured or contra lateral leg giving a “split” plot. The traditional SFI calculations resulted in typical shaped graphs for both rats and mice. However, the “split” SFI calculations showed how rats and mice differ in their recovery from sciatic nerve injury. The mouse graph shows the intact leg remaining stable and the injured leg having functional impairment, which then recovers. The rat graph showed functional impairment of the injured leg, however, the intact leg had an increase in SFI values as if to compensate until the injured leg showed recovery.     

The influence of the different morphological changes on gastric mucosa on somatostatin cell number in antrum mucosa and serum somatostatin

The aim of our paper was to investigate the influence of the different morphological changes on gastric mucosa on somatostatin D-cell number in antral mucosa and serum Somatostatin. We analyzed according to Sydney classification to what extent the severity of gastritis affect the observed hormonal values. somatostatin D-cell number in antral mucosa and serum Somatostatin values were compared between three groups of patients; mild, moderate and severe chronic gastritis. The average number of somatostatin cell in biopsy sample of antrum mucosa was 30.41 +/- 35.38 (N = 17) in the case of middle form, 18.69 +/- 26.65 (N = 56) in moderate and in severe case of chronic gastritis 5.23 +/- 5.93 (N = 7) cells in mm2 of mucosa. The level of somatostatin in the serum of middle form gastritis were 26.43 +/- 28.76, moderate 19.95 +/- 35.93 and severe 17.88 +/- 17.66 pg/mL. In order to determine the number of somatostatin cells in antrum mucosa and serum somatostatin with present morphological changes of mucosa, it might helpful to exclude the patients with non-ulcer dyspepsia, but with the higher risk of premalignant and malignant changes.     

Writing and drawing with both hands as indicators of hemispheric dominance

Brain lateralization is a common term used to describe dominance of one brain hemisphere over another for a specific function. The right hand dominance in writing, controlled by the left hemisphere, is preceded by development of communicative gesticulation and followed by development of speech in the same hemisphere. We assumed that some people are not aware of their own capability of using the other hand for tasks involving fine motor sequential movements. To prove this hypothesis, the participants were asked to perform one trained task (writing) and one less-trained task (drawing) with a dominant and a non-dominant hand. The final sample was comprised of 1189 children from 14 elementary schools and 8 high schools in the Osijek area, of which 685 elementary school children were attending 1st to 4th grade and 504 high school children were attending 3rd and 4th grade. The participants were asked to write two words, draw a specific object (a vase with flowers) and fill out a questionnaire with 10 questions concerning the classification of handedness and cerebral hemisphere dominance. The self-reported cerebral lateralization assessed in the questionnaire was compared with the drawing and the writing performance. The self-reported and objectively measured hand dominance deviated in the cases of the ambidextrous who consider themselves right-handers. Given the fact that the number of ambidextrous persons was greater in elementary schools than in high schools, we concluded how training of the right hand decreases the ability of using both hands equally for either of the tested functions - writing and drawing.     

Tactile and Proprioceptive Temporal Discrimination Are Impaired in Functional Tremor

Background and Methods

In order to obtain further information on the pathophysiology of functional tremor, we assessed tactile discrimination threshold and proprioceptive temporal discrimination motor threshold values in 11 patients with functional tremor, 11 age- and sex-matched patients with essential tremor and 13 healthy controls.

Results

Tactile discrimination threshold in both the right and left side was significantly higher in patients with functional tremor than in the other groups. Proprioceptive temporal discrimination threshold for both right and left side was significantly higher in patients with functional and essential tremor than in healthy controls. No significant correlation between discrimination thresholds and duration or severity of tremor was found.

Conclusions

Temporal processing of tactile and proprioceptive stimuli is impaired in patients with functional tremor. The mechanisms underlying this impaired somatosensory processing and possible ways to apply these findings clinically merit further research.     

When Dread Risks Are More Dreadful than Continuous Risks: Comparing Cumulative Population Losses over Time

People show higher sensitivity to dread risks, rare events that kill many people at once, compared with continuous risks, relatively frequent events that kill many people over a longer period of time. The different reaction to dread risks is often considered a bias: If the continuous risk causes the same number of fatalities, it should not be perceived as less dreadful. We test the hypothesis that a dread risk may have a stronger negative impact on the cumulative population size over time in comparison with a continuous risk causing the same number of fatalities. This difference should be particularly strong when the risky event affects children and young adults who would have produced future offspring if they had survived longer. We conducted a series of simulations, with varying assumptions about population size, population growth, age group affected by risky event, and the underlying demographic model. Results show that dread risks affect the population more severely over time than continuous risks that cause the same number of fatalities, suggesting that fearing a dread risk more than a continuous risk is an ecologically rational strategy.     

In vivo 5-flourouracil-induced apoptosis on murine thymocytes: involvement of FAS,Bax and Caspase3

Apoptosis is a highly regulated and programmed cell breakdown process characterized by numerous changes. It was reported as the major mechanism of anticancer drug-induced cells death. Unfortunately, many of these drugs are non-specific and cause severe side effects. The effects of 5-fluorouracil (5-FU) on the apoptotic events in normal murine thymus were evaluated using an in vivo model. A single dose of 5-FU (150 mg/kg ip) was injected to CF-1 mice. A multiparametric analysis of thymic weight, cellularity, viability, architectural organization, apoptosis, DNA fragmentation, and the expression of several apoptotic proteins was evaluated in 10 days time-course study post-5-FU dosing. Total organ weights, thymocyte counts, and cell viabilities diminished drastically from the second day. The thymus architecture assessed through electron scanning microscopy revealed deep alterations and the lost of cell-cell contact between the first and the third days. DNA fragmentation and apoptotic indexes (May Grünwald Giemsa staining, double fluorescent dyes, and TdT-mediated dUTP nick-end labeling assay) revealed that cell death was maximal on the second day (three times over control). Furthermore, the pro-apoptotic proteins FAS and Bax were strongly up-regulated during the first 2 days. The aforementioned morphological and biochemical changes were also accompanied within the same period by caspase 3 activation. This study revealed that in vivo apoptosis in normal thymus after 5-FU administration is related to FAS, Bax, and Caspase 3 co-expressions under the current experimental conditions, these findings, therefore, contribute to a new insight into the molecular mechanisms involved during 5-FU administration upon the thymus and the possible events committed in the lymphophenia associated with chemotherapy.     

Cadmium-induced responses in duckweed <Emphasis Type="Italic">Lemna minor</Emphasis> L.

Although duckweed Lemna minor L. is a known accumulator of cadmium, detailed studies on its physiological and/or defense responses to this metal are still lacking. In this study, the effects of 10 μM CdCl₂ on Lemna minor were monitored after 6 and 12 days of treatment, while growth was estimated every 2 days. Cadmium treatment resulted in progressive accumulation of the metal in the plants and led to a decrease in the growth rate to 54% of the control value. The metal also considerably impaired chloroplast ultrastructure and caused a significant reduction in pigment content, i.e., at day 12, by 30 and 34% for chlorophylls a and b, and by 25% for carotenoids. During cadmium treatment, the contents of malondialdehyde and endogenous H₂O₂ progressively increased (rising 77 and 46% above the controls by day 12), indicating that cadmium induced considerable oxidative stress. On the other hand, higher activities of pyrogallol peroxidase (PPX), ascorbate peroxidase (APX) and catalase (CAT), as well as the induction of a new APX isoform, in cadmium-treated plants, clearly showed activation of an antioxidative response. At day 6, only PPX activity was significantly above the controls (15%), while, at day 12, PPX, APX and CAT activities were increased (74, 78 and 63%). Cadmium also led to accumulation of the heat shock protein 70 (HSP70) and induced an additional isoform of this protein. The obtained results suggest that cadmium (10 μM) is phytotoxic to Lemna minor, inducing oxidative stress, and that antioxidative enzymes and HSP70 play important roles in the defense against cadmium toxicity. M. Tkalec and T. Prebeg contributed equally to this work     

Characterization of intermediate phenotypes induced by chemically undefined laboratory media in virulent Bordetella bronchiseptica strains

The expression of many virulence factors of Bordetella bronchiseptica is regulated by the bvgAS locus and reduced in response to environmental signals called modulators. Virulent strains can alternate between virulent (Bvg(+)), intermediate (Bvg(i)), and modulated (Bvg(+)mod) phenotypes. Potential vaccine antigens can be expressed by Bvg1 strains grown only in the absence of modulators. In the present study we evaluated filamentous hemagglutinin (FHA) and outer membrane protein (OMP) expression in Bvg(+) B. bronchiseptica strains grown in chemically undefined media: nutrient agar (NA), tryptic soy agar (TSA), tryptose phosphate broth (TPB), and brain-heart infusion (BHI). Our results suggest that TSA and TPB usually induce semimodulation, since Bvg(+) strains cultured in these media retained the expression of FHA and virulence-associated OMPs in the 30 kDa region, but failed to express other virulence markers such as OMPs in the regions of 90 and 200 kDa, though they expressed flagellin (avirulence marker). On the other hand, NA and BHI usually induce modulation. Thus the assayed chemically undefined media should not be used in vaccine production. Semimodulation induced by TSA and TPB can be accurately detected by SDS-PAGE Sarkosyl-insoluble OMP-enriched profiles. The reduction or absence of OMPs in the regions of 90 and 200 kDa is the most sensitive marker, and in some cases the presence of flagellin in intermediate profiles is another trait of the Bvg(i) phenotypes. Therefore these markers could be useful for selecting media for vaccine production. We also characterized the phenotype of Bvg(+) strains grown in Stainer-Scholte broth, an expensive medium, with and without glutathione, and we have detected no differences; this is the first attempt to reduce the cost of a Bordetella growth medium for veterinary vaccine production.     

Arbuscular mycorrhizal fungi in a mountain grassland II: Seasonal variation of colonization studied, along with its relation to grazing and metabolic host type

The relationships among seasons, host metabolic type, grazing and arbuscular mycorrhizal colonization were analyzed in a high South American native grassland. This study investigated seasonal changes and grazing effects on the symbiotic endomycorrhizal interaction in 5 Poaceae [C(3) metabolic pathway: Briza subaristata Lam., Deyeuxia hieronymi (Hack.) Türpe and Poa stuckertii (Hack.) Parodi; with C(4) metabolic pathway: Eragrostis lugens Nees and Sorghastrum pellitum (Hack.) Parodi; and a Rosaceae (Alchemilla pinnata Ruíz & Pav.)]. All hosts were dominant species in the mountain grassland in central Argentina. It was found that the seasons markedly influenced endomycorrhizal colonization, whereas grazing did not affect this interaction. C(4) grasses presented the highest root colonization. Hosts Briza subaristata (C(3) metabolic pathway) and Sorghastrum pellitum (C(4) metabolic pathway) showed Arum- and Paris-type colonization and intermediate forms.