BCL-2 protein family: attractive targets for cancer therapy.
Acquired resistance to cell death is a hallmark of cancer. The BCL-2 protein family members play important roles in controlling apoptotic cell death. Abnormal over-expression of pro-survival BCL-2 family members or abnormal reduction of pro-apoptotic BCL-2 family proteins, both resulting in the inhibition of apoptosis, are frequently detected in diverse malignancies. The critical role of the pro-survival and pro-apoptotic BCL-2 family proteins in the regulation of apoptosis makes them attractive targets for the development of agents for the treatment of cancer. This review describes the roles of the various pro-survival and pro-apoptotic members of the BCL-2 protein family in normal development and organismal function and how defects in the control of apoptosis promote the development and therapy resistance of cancer. Finally, we discuss the development of inhibitors of pro-survival BCL-2 proteins, termed BH3-mimetic drugs, as novel agents for cancer therapy.


[Impact of cancer treatments on cognitive functions: the patients' view, their expectation and their interest in participating to cognitive rehabilitation workshops].
Cancer and chemotherapy can have adverse effects on cognitive functions and quality of life of patients. We wanted to know the patients' view on these disorders, but also their expectations in terms of assessment and support. A survey was conducted in day care hospital among 551 patients from three cancer centers. Most of the patients were between 40 and 74 years and suffered from breast cancer. Eighty-four percent were treated with chemotherapy. Forty-one percent of patients report memory problems, 26% were affected by specific concentration disorders, and 19% of the attention. On the whole, 52% of patients report at least one of the previous cognitive impairment. Among these patients, 80% evoked that the support of these problems was essential and 70% were willing to participate in "workshops" to deal with these disorders. The cognitive impairment occurrence is a real problem for patients receiving chemotherapy and becomes a priority in the global management of their disease. Studies assessing a specific support of theses symptoms should be encouraged to help patients.


Altered large-scale organization of shape processing in visual agnosia.
Recent findings suggest that both dorsal and ventral visual pathways process shape information. Nevertheless, a lesion to the ventral pathway alone can result in visual agnosia, an impairment in shape perception. Here, we explored the neural basis of shape processing in a patient with visual agnosia following a circumscribed right hemisphere ventral lesion and evaluated longitudinal changes in the neural profile of shape representations. The results revealed a reduction of shape sensitivity slopes along the patient's right ventral pathway and a similar reduction in the contralesional left ventral pathway. Remarkably, posterior parts of the dorsal pathway bilaterally also evinced a reduction in shape sensitivity. These findings were similar over a two-year interval, revealing that a focal cortical lesion can lead to persistent large-scale alterations of the two visual pathways. These alterations are consistent with the view that a distributed network of regions contributes to shape perception.


Influence of SiC and TiC nanoparticles reinforcement on the microstructure, tribological, and scratch resistance behavior of electroless Ni-P coatings.
Two different ceramic carbide nanoparticles (SiC, and TiC) were separately incorporated into the Ni-P matrix via the electroless deposition method. As prepared Ni-P, Ni-P-SiC, and Ni-P-TiC coatings were subjected to heat treatment at 400 °C for 1 h. The surface morphology, microstructural transformation, Vicker's microhardness, tribological and scratch resistance properties were studied with reference to the different carbide reinforcements as well as heat treatment. Inter-nodular space, craters and kinks are created due to the branching effect of nodules in the surface of the Ni-P-SiC (TiC) composite coatings. After the heat treatment, the matrix phase transformation was not altered due to the incorporation of SiC or TiC into the Ni-P coating; however, a slight increase in residual stress was identified from the XRD analysis. In addition, the content of carbon deposition was found to be higher in the matrix of Ni-P-SiC composite coating than that in the Ni-P-TiC coating. The agglomeration of SiC particles was higher than TiC particles in the coating matrix, which was also supported by the result of Zeta potential measurement. Heat treatment improved wear and coefficient of friction in the Ni-P-SiC and Ni-P-TiC composite coatings. Compared to Ni-P-SiC coating, Ni-P-TiC coating revealed the enhanced tribological and scratch resistance performance after the heat treatment.


Sporopollenin based materials as a versatile choice for the detoxification of environmental pollutants - A review.
Before making the transfer to land, plants survive in water for millions of years to avoid the severe circumstances that prevail on lands, such as drought and UV radiation. All land plant spores are coated in sporopollenin, a substance that has developed to endow pollen and spore shells with exceptional, one-of-a-kind qualities. In a nutshell, sporopollenin-coated spores are a unique invention only seen in land plants. Sporopollenin, discovered in the outer exine layer of pollen walls, is a lipid and phenolic-based polymer with high carbon, hydrogen, and oxygen cross-linking. Products based on sporopollenin can remediate toxic pollutant contamination in the aquatic environment. This research and development are now underway. In this review, we show how sporopollenin-based adsorbents act in environmental challenges and their immense promise for this application via remarkable physical and chemical characteristics. A comparison is made of the benefits of various sporopollenin-modified structures. This strategy will further our understanding of how a biopolymer's structure can be accommodated to address emerging environmental challenges, revealing more about sporopollenin's dynamical nature.


Bombesin and its analogues inhibit interleukin-2-induced proliferation of CTLL-2 cells.
Specifically interleukin-2 (IL-2)-dependent CTLL-2 cells were incubated in short term culture in the presence of IL-2 together with bombesin and two analogues, [Lys3]bombesin and [Tyr4]bombesin in different concentrations. Cell proliferation, determined by [3H]thymidine incorporation was significantly inhibited by 35.6 +/- 5%, 39.0 +/- 5.6% and 57.0 +/- 11% (mean +/- S.E.M. of 3 independent experiments). A typically U-shaped dose-response relationship was observed, showing a maximum effect between 10(-12) and 10(-10) M. Our data support the hypothesis that this effect is mediated by a specific receptor for bombesin and closely related peptides on CTLL-2 cells. As IL-2 plays a critical role in the clonal expansion of activated lymphocytes, antagonism of the effect of IL-2 is of high biological significance.


Overweight, Obesity, and Lung Function in Children and Adults-A Meta-analysis.
There is conflicting evidence on the effect of obesity on lung function in adults and children with and without asthma. We aimed to evaluate the relation between overweight or obesity and lung function, and whether such relationship varies by age, sex, or asthma status. We searched PubMed, Scopus, CINAHL, Cochrane, and EMBASE for all studies (in English) reporting on obesity status (by body mass index) and lung function, from 2005 to 2017. Main outcomes were forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC, forced expiratory flow between 25th and 75th percentile of the forced vital capacity (FEF25-75), total lung capacity (TLC), residual volume (RV), and functional residual capacity (FRC). Random-effects models were used to calculate the pooled risk estimates; each study was weighed by the inverse effect size variance. For each outcome, we compared overweight or obese ("obese") subjects with those of normal weight. All measures of lung function were decreased among obese subjects. Obese adults showed a pattern (lower FEV1, FVC, TLC, and RV) different from obese children (more pronounced FEV1/FVC deficit with unchanged FEV1 or FVC). There were also seemingly different patterns by asthma status, in that subjects without asthma had more marked decreases in FEV1, TLC, RV, and FRC than subjects with asthma. Subjects who were obese (as compared with overweight) had even further decreased FEV1, FVC, TLC, RV, and FRC. Obesity is detrimental to lung function, but specific patterns differ between children and adults. Physicians should be aware of adverse effects of obesity on lung function, and weight control should be considered in the management of airway disease among the obese.


Activation of blood coagulation, fibrinolytic and kallikrein systems during storage of plasma.
This study deals with the question of how blood coagulation, kallikrein and fibrinolytic systems are affected by storage of plasma at +6 degrees C. Blood was collected into citrate phosphate dextrose adenine (CPD) or acid citrate dextrose (ACD) and the plasma samples were stored at +6 degrees C for 35 days. Samples were taken at weekly intervals for assays of various parameters of the different systems. No significant changes were observed in the levels of the main thrombin inhibitor, antithrombin III. At the end of the storage period, however, fibrinopeptide A levels increased markedly, particularly in the ACD plasma, indicating thrombin activation. There was no change in the plasminogen level, but a decrease in the levels of antiplasmin and urokinase inhibitors and an increase in the level of the fibrinogen degradation fragment B beta 15-42 were observed, indicating activation of the fibrinolytic system. The level of antikallikrein activity decreased sharply in ACD plasma; CPD plasma was less affected. This decrease was parallel to the increase in spontaneous proteolytic activity and correlated with the increase in fibrinopeptide A. Prolonged storage of plasma of +6 degrees C thus resulted in the activation of coagulation, fibrinolytic and kallikrein systems and decrease in inhibitors. The activation was much more pronounced in ACD than in CPD plasma.


Thermodynamics makes Progress.
On April 1-4 the Institute of Physics and the Physical Society is to hold an international conference on thermodynamics at Cardiff. This article, by one of the organizers, highlights some of the topics which are likely to provide particular interest for the participants.


A complex signaling cascade links the serotonin2A receptor to phospholipase A2 activation: the involvement of MAP kinases.
Previous studies in our laboratory have shown that in NIH3T3-5HT2A cells, 5-HT-induced AA release is PLA2-coupled and independent of 5-HT2A receptor-mediated PLC activation. Although 5-HT2A receptor-mediated PLC activation is known to be Galphaq-coupled, much less is understood about 5-HT2A receptor-mediated PLA2 activation. Therefore, the studies presented here were aimed at elucidating the signal transduction pathway linking stimulation of the 5-HT2A receptor to PLA2 activation. By employing various selective inhibitors, toxins, and antagonistic peptide constructs, we propose that the 5-HT2A receptor can couple to PLA2 activation through two parallel signaling cascades. Initial experiments were designed to examine the role of pertussis toxin-sensitive G proteins, namely Galphai/o, as well as pertussis toxin-insensitive G proteins, namely Galpha12/13, in 5-HT-induced AA release. Furthermore, inactivation of both Gbetagamma heterodimers and Rho proteins resulted in decreased agonist-induced AA release, without having any effect on PLC-IP accumulation. We also demonstrated 5-HT2A receptor-mediated phosphorylation of ERK1,2 and p38. Moreover, pretreatment with selective ERK1,2 and p38 inhibitors resulted in decreased 5-HT-induced AA release. Taken together, these results suggest that the 5-HT2A receptor expressed in NIH3T3 cells can couple to PLA2 activation though a complex signaling mechanism involving both Galphai/o-associated Gbetagamma-mediated ERK1,2 activation and Galpha12/13-coupled, Rho-mediated p38 activation.


Density of Aedes aegypti (Diptera: Culicidae) in a low-income Brazilian urban community where dengue, Zika, and chikungunya viruses co-circulate.
Low-income urban communities in the tropics often lack sanitary infrastructure and are overcrowded, favoring Aedes aegypti proliferation and arboviral transmission. However, as Ae. aegypti density is not spatially homogeneous, understanding the role of specific environmental characteristics in determining vector distribution is critical for planning control interventions. The objectives of this study were to identify the main habitat types for Ae. Aegypti, assess their spatial densities to identify major hotspots of arbovirus transmission over time and investigate underlying factors in a low-income urban community in Salvador, Brazil. We also tested the field-collected mosquitoes for arboviruses. A series of four entomological and socio-environmental surveys was conducted in a random sample of 149 households and their surroundings between September 2019 and April 2021. The surveys included searching for potential breeding sites (water-containing habitats) and for Ae. aegypti immatures in them, capturing adult mosquitoes and installing ovitraps. The spatial distribution of Ae. aegypti density indices were plotted using kernel density-ratio maps, and the spatial autocorrelation was assessed for each index. Visual differences on the spatial distribution of the Ae. aegypti hotspots were compared over time. The association of entomological findings with socio-ecological characteristics was examined. Pools of female Ae. aegypti were tested for dengue, Zika and chikungunya virus infection. Overall, 316 potential breeding sites were found within the study households and 186 in the surrounding public spaces. Of these, 18 (5.7%) and 7 (3.7%) harbored a total of 595 and 283 Ae. aegypti immatures, respectively. The most productive breeding sites were water storage containers within the households and puddles and waste materials in public areas. Potential breeding sites without cover, surrounded by vegetation and containing organic matter were significantly associated with the presence of immatures, as were households that had water storage containers. None of the entomological indices, whether based on immatures, eggs or adults, detected a consistent pattern of vector clustering in the same areas over time. All the mosquito pools were negative for the tested arboviruses. This low-income community displayed high diversity of Ae. aegypti habitats and a high degree of heterogeneity of vector abundance in both space and time, a scenario that likely reflects other low-income communities. Improving basic sanitation in low-income urban communities through the regular water supply, proper management of solid wastes and drainage may reduce water storage and the formation of puddles, minimizing opportunities for Ae. aegypti proliferation in such settings.


African histoplasmosis: report of four cases from north-eastern Nigeria.
Four cases of African histoplasmosis with lesions of the skin, subcutaneous tissues and lymph nodes diagnosed histologically are described from the Borno State of Nigeria. Three of the cases were autochthonous to this State, whereas the fourth one originated from the Anambra State of Nigeria. These cases constitute the first record of African histoplasmosis from the arid zone of the north-eastern part of Nigeria.


Recovery-oriented social work practice in mental health and addictions: a scoping review protocol.
Social work is a key profession in the field of mental health worldwide and the profession has values that are aligned with a recovery paradigm. However, there are gaps in understanding how social workers are applying the recovery paradigm in practice. This study will scope and synthesise the literature related to recovery and social work practice in mental health and addictions. There will also be an exploration of best practices and gaps in recovery-oriented social work practice. Using a scoping review framework developed by Arksey and O'Malley, we will conduct our search in five academic databases: PsycINFO, Medline, CINAHL Plus, Sociological Abstracts and Social Services Abstracts. Articles meeting inclusion criteria will be charted to extract relevant themes and analysed using a qualitative thematic analysis approach. This review will provide relevant information about best practices and gaps in recovery-oriented social work practice in mental health and addictions. The study will inform the development of mental health curricula in social work programmes and clinical settings. Results will be disseminated through a peer-reviewed journal and at conferences focusing on mental health, addictions, and social work education. Ethics approval is not required for this scoping review.


Ketogenic diet ameliorates autism spectrum disorders-like behaviors via reduced inflammatory factors and microbiota remodeling in BTBR T+ Itpr3tf/J mice.
Autism Spectrum Disorder (ASD) is increasing, but its complete etiology is still lacking. Recently, application of ketogenic diet (KD) has shown to reduce abnormal behaviors while improving psychological/sociological status in neurodegenerative diseases. However, KD role on ASD and underlying mechanism remains unknown. In this work, KD administered to BTBR T+ Itpr3tf/J (BTBR) and C57BL/6J (C57) mice reduced social deficits (p = 0.002), repetitive behaviors (p < 0.001) and memory impairments (p = 0.001) in BTBR. Behavioral effects were related to reduced expression levels of tumor necrosis factor alpha, interleukin-1β, and interleukin-6 in the plasma (p = 0.007; p < 0.001 and p = 0.023, respectively), prefrontal cortex (p = 0.006; p = 0.04 and p = 0.03) and hippocampus (p = 0.02; p = 0.09 and p = 0.03). Moreover, KD accounted for reduced oxidative stress by changing lipid peroxidation levels and superoxide dismutase activity in BTBR brain areas. Interestingly, KD increased relative abundances of putatively beneficial microbiota (Akkermansia and Blautia) in BTBR and C57 mice while reversing the increase of Lactobacillus in BTBR feces. Overall, our findings suggest that KD has a multifunctional role since it improved inflammatory plus oxidative stress levels together with remodeling gut-brain axis. Hence, KD may turn out be a valuable therapeutic approach for ameliorating ASD-like conditions even though more evidence is required to evaluate its effectiveness especially on a long term.


Effects of ascorbic acid on α-l-arabinofuranosidase and α-l-arabinopyranosidase activities from Bifidobacterium longum RD47 and its application to whole cell bioconversion of ginsenoside.
Bifidobacterium longum RD47 was cultured in 24 kinds of modified MRS broths containing various ingredients to select the most promising source that induces microbial enzymes. Among the various ingredients, ascorbic acid significantly enhanced α-l-arabinofuranosidase and α-l-arabinopyranosidase activities in Bifidobacterium longum RD47. Addition of 2 % ascorbic acid (w/v) to MRS showed the maximum enzyme activities. Both whole cell and disrupted cell homogenates showed efficient ρ-nitrophenyl-β-d-glucopyranoside and ρ-nitrophenyl-β-d-glucofuranoside hydrolysis activities. The initially enhanced α-l-arabinopyranosidase and α-l-arabinofuranosidase activities by ascorbic acid were maintained over the cell disruption process. The optimal pH of α-l-arabinofuranosidase and α-l-arabinopyranosidase was 5.0 and 7.0, respectively. Both enzymes showed the maximum activities at 40.0 °C. Under the controlled condition using Bifidobacterium longum RD47, ginsenoside Rb2, and Rc were converted to ginsenoside Rd.