B cell receptor-mediated antigen gathering requires ubiquitin ligase Cbl and adaptors Grb2 and Dok-3 to recruit dynein to the signaling microcluster

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Highlights? Grb2, Dok-3 and Cbl recruit dynein to BCR microclusters for antigen gathering ? BCR microclusters localize to and move on the microtubule network ? Disruption of microtubule network or dynein recruitment abrogates antigen gathering     

Unbalanced translocation 9;16 in two children with dysmorphic features, and severe developmental delay: Evidence of cross-over within derivative chromosome 9 in patient #1

We describe 2 children with dysmorphic features, and severe developmental delay presenting with overlapping unbalanced translocations of 9q34.3 and 16p13. Patient #1: A 4 year old African-American female with normal karyotype with a pericentric inversion on one chromosome 9 known to be a benign variant. Low resolution array CGH revealed a single BAC clone loss at 9q34.3 and a single BAC clone gain at 16p13.3, confirmed by FISH. Whole genome SNP array analysis refined these findings, identifying a terminal 1.28 Mb deletion (138,879,862-140,164,310) of 9q34.3 and a terminal 1.62 Mb duplication (45,320-1,621,753) of 16p13.3. Sub-telomeric FISH showed an unbalanced cryptic translocation involving the inverted chromosome 9 and chromosome 16. FISH of the father showed a balanced t(9;16)(q34.3;p13.3) involving the non-inverted chromosome 9, and a pericentric inversion on the normal 9 homologous chromosome. The presence of two rearrangements on chromosome 9, both an unbalanced translocation and a pericentric inversion, indicates recombination between the inverted and derivative 9 homologues from her father. Patient #2: A 1 year old Iraqi-Moroccan female with normal karyotype. Array-CGH identified a 0.56 Mb deletion of 9q34.3 (139,586,637-140,147,760) and an 11.31 Mb duplication of 16p13.3p13.13 (31,010-11,313,519). Maternal FISH showed a balanced t(9;16)(q34.3;p13.13). Both patients present with similar clinical phenotype.     

Commonly used tropical medicinal plants exhibt distinct in vitro antioxidant activities against hepatotoxins in rat liver

Lipid peroxidation in biological systems has been considered as one of the major mechanisms of cell injury in aerobic organisms subjected to oxidation stress. Plants, among other functions, are considered to act as free radical scavengers and as antioxidants. Iron II (Fe²⁺), sodium nitroprusside (SNP) and nitropropionic acid stimulate the production of free radicals and lipid peroxidation. In this study, four commonly used tropical medicinal plants (Kigelia africana, Calotropis procera, Hibiscus sabdariffa and Alchornea cordifolia) were studied (in vitro) for their effects on the formation of thiobarbituric acid reactive substances (TBARS) induced by different pro-oxidants (10 μM FeSO₄, 5 μM -sodium SNP and 2 mM 3-nitropropionic acid) in rat liver homogenate. All the pro-oxidants significantly increased (P<0.05) the formation of TBARS, which indicates increased lipid peroxidation in the rat liver (in vitro). However, all the plant extracts statistically (P<0.05) reduced the production of TBARS in a concentration-dependent manner in all the tested pro-oxidant-induced oxidative stresses. Alchornea cordifolia appeared to offer the highest protection. The results of the present study suggest that the use of these plants in the treatment of various diseases, especially liver disease, is probably due to their ability to act as antioxidants.     

An Anticarsia gemmatalis multiple nucleopolyhedrovirus mutant, vApAg, induces hemocytes apoptosis in vivo and displays reduced infectivity in larvae of Anticarsia gemmatalis (Hübner) (Lepidoptera: Noctuidae)

An Anticarsia gemmatalis multiple nucleopolyhedrovirus (AgMNPV) mutant, vApAg, induces apoptosis in a cell culture derived from Anticarsia gemmatalis (UFL-AG-286), reducing viral progeny. We have investigated apoptosis induction in vivo by vApAg in A. gemmatalis larvae and its correlation to infectivity reduction. LC₅₀, LD₅₀, LT₅₀ and the mean time to death of larvae were determined for vApAg and AgMNPV. Apoptosis was accessed for hemocytes of infected larvae using light and transmission electron microscopy. All types of hemocytes can be infected by vApAg. After 12 h post-infection (h p.i.), typical cellular modifications associated to nucleopolyhedrovirus infection were observed. Apoptosis becomes evident after 24 h p.i., and massive after 72 h p.i. Necrosis of infected cells was also observed. Despite cell death, hemocytes produced budded viruses and polyhedra. Pl and gh1-type hemocytes presented phagocytic activity. Agarose gel electrophoresis revealed fragmentation of hemocytes DNA at late times post-infection. The LC₅₀ and LD₅₀ were between five- and six-fold higher for vApAg. The LT₅₀ and the mean time to death were higher for vApAg in a same treatment or for a similar mortality induced by AgMNPV. These results show correlation of apoptosis and the reduced infectivity of vApAg in A. gemmatalis larvae.     

Comparing genetic counseling with non-genetic health care interactions: Two of a kind?

OBJECTIVE: Increasingly clinicians other than genetic counselors will advise people with genetic risks. Although some express concerns about this development because of the need for non-genetic clinicians to have additional training, we argue that genetic counseling has more in common with other health care interactions than is generally assumed. METHODS: In this narrative review we investigate the health communication literature taking the perspective that all provider-patient/client interactions share the following goals: forming a relationship, the exchange of information, decision making, promoting health-related behavior and providing support. RESULTS: We found that both non-genetic and genetic 'disciplines' endorse an egalitarian relationship, based on a patient-centered approach and both have difficulties with attuning to the patients' agendas and enhancing patient understanding. Shared decision making is increasingly the preferred model for geneticists and non-geneticists alike, and both need skills to constructively discuss patients' risk-reducing behavior and provide emotional support. CONCLUSION: Rather than developing separate vocabularies and research traditions, the discipline of genetic counseling may benefit by drawing on non-genetic patient-provider interaction research. PRACTICE IMPLICATIONS: Since geneticists face the same challenges as non-geneticists, medical training should continue to improve basic consultation skills, regardless of whether the consultation involves genetic information.     

Detection of cytokeratins in ghost cells of calcifying cystic odontogenic tumor indicates an altered keratinization and hair follicle differentiation for their development

Calcifying cystic odontogenic tumors (CCOTs) are benign cystic lesions of odontogenic origin characterized by an ameloblastoma-like epithelium and the presence of a group of cells named ghost cells. The pattern of cytokeratin (Ck) expression on these lesions remains unclear and needs to be clarified. To this end, the expression of Ck6, Ck13, Ck14, Ck18, and Ck19 in the epithelium lining of 7 cases of CCOTs was evaluated by immunohistochemistry. For this, the epithelium lining was divided into 3 distinct regions: basal layer, suprabasal layer, and the compartment composed of ghost cells. In this study, 6 cases (85.7%) were classified as type 1 and 1 (14.3%) as type 4. All cases were negative for Ck13 and Ck18, despite the epithelial layer, as well as in the ghost cells. Ck6 was only positive in the ghost cells. Positivity for Ck14 and Ck19 was found in the basal and suprabasal layers, including the ghost cells. The results showing positivity for Ck14 and Ck19 in all of the analyzed cases reinforce CCOT as being of odontogenic origin, and the restricted expression of Ck6 in the ghost cells may be indicative that these cells suffer an altered differentiation into hair follicles in CCOTs.     

A qualitative participatory study to identify experiences of coronary heart disease patients to support the development of online self-management services

ObjectiveWeb-based self-management services remain underutilized in current practice. Our aim was to gain insight into disease and self-management experiences of patients in early and progressive stages of coronary heart disease (CHD), to understand moderating effects of daily life experiences on the utilization of web-based self-management services and preconditions for use.MethodsWe applied generative research techniques, which stem from the field of product design and are characterized by the use of creative processes. Three groups of patients with CHD received a sensitizing package to document and reflect on their health, and were subsequently either interviewed or participated in a focus group session.ResultsIn total, 23 patients participated in this study. Emerging themes were (1) fear for recurrent events, (2) experiences with professional care, (3) the perceived inability to prevent disease progression, (4) the desire to go on living without thinking about the disease every day, (5) the social environment as a barrier to or facilitator for self-management, and (6) the need for information tailored to personal preferences.ConclusionHow patients experience their disease varies between stable and post-acute stages, as well as between early and progressive stages of CHD. Patients in post-acute stages of the disease seem to be most amenable to support, while patients in stable stages want to live their life without being reminded of their disease. In the context of self-management, web-based services should be adapted to the variation in needs that occur in the different stages of CHD and new strategies to fit such services to these needs should be developed. Furthermore, they should be tailored to patients’ individual health situation and preferences, support patient empowerment, and manage expectations regarding the progression of their disease.     

Hepatoprotective effects of pecan nut shells on ethanol-induced liver damage

The hepatoprotective activity of the aqueous extract of the shells of pecan nut was investigated against ethanol-induced liver damage. This by-product of the food industry is popularly used to treat toxicological diseases. We evaluated the phytochemical properties of pecan shell aqueous extract (AE) and its in vitro and ex vivo antioxidant activity. The AE was found to have a high content of total polyphenols (192.4 ± 1.9 mg GAE/g), condensed tannins (58.4 ± 2.2 mg CE/g), and antioxidant capacity, and it inhibited Fe²⁺-induced lipid peroxidation (LP) in vitro. Rats chronically treated with ethanol (Et) had increased plasmatic transaminases (ALT, AST) and gamma glutamyl transpeptidase (GGT) levels (96%, 59.13% and 465.9%, respectively), which were effectively prevented (87; 41 and 383%) by the extract (1:40, w/v). In liver, ethanol consumption increased the LP (121%) and decreased such antioxidant defenses as glutathione (GSH) (33%) and superoxide dismutase (SOD) (47%) levels, causing genotoxicity in erythrocytes. Treatment with pecan shell AE prevented the development of LP (43%), GSH and SOD depletion (33% and 109%, respectively) and ethanol-induced erythrocyte genotoxicity. Catalase activity in the liver was unchanged by ethanol but was increased by the extract (47% and 73% in AE and AE + Et, respectively). Therefore, pecan shells may be an economic agent to treat liver diseases related to ethanol consumption.     

Electromyogram changes during sustained contraction after resistance training in women in their 3rd and 8th decades

The present study aimed at investigating the neuromuscular adaptations to 6 weeks of resistance training in women in their third (6 experimental, 8 controls) and eighth decades (8 experimental, 8 controls). The surface electromyogram (sEMG) was measured from the biceps brachii muscle during constant-force isometric contractions lasting 12 s at 80% of maximal voluntary contraction (MVC). All the signals were analysed adopting in the time domain the root mean square (RMS) as a measure of amplitude and in the frequency domain the median frequency (MDF) of the power spectrum. Quantitative analysis was performed from the 3rd to the 6th second, to describe the early phase of the contraction (“Early”), starting from point at which 80% of the MVC was reached, and from the 9th to the 12th second, to describe the last part of the constant-force sustained contraction (“Late”). After training, the MVC increased by 22.4% in the young (P < 0.0001) and by 13.4% in the older (P < 0.05) women. The “Early” RMS increased by 60.4% with respect to the pre-training condition in the young (P < 0.01) but not in the older women. In contrast, the “Late” RMS increased by 46.7% in the older (P < 0.05) but not in the young women. The MDF remained unchanged in both groups. These results indicate that young and older women showed different training-induced adaptation of the motor unit (MU) activation pattern, in order to keep a constant level of force during a sustained isometric contraction at 80% of MVC. Accepted: 11 March 2000