During male pronuclei formation chromatin remodeling is uncoupled from nucleus decondensation

Male pronucleus formation involves sperm nucleus decondensation and sperm chromatin remodeling. In sea urchins, male pronucleus decondensation was shown to be modulated by protein kinase C and a cdc2-like kinase sensitive to olomoucine in vitro assays. It was further demonstrated that olomoucine blocks SpH2B and SpH1 phosphorylation. These phosphorylations were postulated to participate in the initial steps of male chromatin remodeling during male pronucleus formation. At final steps of male chromatin remodeling, all sperm histones (SpH) disappear from male chromatin and are subsequently degraded by a cysteine protease. As a result of this remodeling, the SpH are replaced by maternal histone variants (CS). To define if sperm nucleus decondensation is coupled with sperm chromatin remodeling, we have followed the loss of SpH in zygotes treated with olomoucine. SpH degradation was followed with anti-SpH antibodies that had no cross-reactivity with CS histone variants. We found that olomoucine blocks SpH1 and SpH2B phosphorylation and inhibits male pronucleus decondensation in vivo. Interestingly, the normal schedule of SpH degradation remains unaltered in the presence of olomoucine. Taken together these results, it was concluded that male nucleus decondensation is uncoupled from the degradation of SpH associated to male chromatin remodeling. From these results, it also emerges that the phosphorylation of SpH2B and SpH1 is not required for the degradation of the SpH that is concurrent to male chromatin remodeling.     

Caveolae and caveolae-like membrane domains in cellular signaling and disease: identification of downstream targets for the tumor suppressor protein caveolin-1

Caveolae are small, flask-shaped invaginations of the plasma membrane present on a large number of mammalian cells. Recent results obtained with knock-out mice for the gene caveolin-1 demonstrate that expression of caveolin-1 protein is essential for caveolae formation in vivo. Caveolae are implicated in a wide variety of cellular events including transcytosis, cholesterol trafficking and as cellular centers important in coordinating signalling events. Caveolae share this role and the property of detergent insolubility with plasma membrane assemblies rich in glycosphingolipids and cholesterol, often called lipid rafts, but preferably referred to here as caveolae-like membrane domains. Due to such widespread presence and usage in cellular function, caveolae and related domains are implicated in human diseases, including cancer. In particular, the protein caveolin-1 is suggested to function as a tumor suppressor protein. Evidence demonstrating such a role for caveolin-1 in human colon carcinoma cells will be discussed together with data from microarray experiments seeking to identify caveolin-1 target genes responsible for such behavior.     

MicroRNAs in cancer drug resistance: Basic evidence and clinical applications

Development of drug resistance has considerably limited the efficacy of cancer treatments, including chemotherapy and targeted therapies. Hence, understanding the molecular mechanisms underpinning the innate or the acquired resistance to these therapies is critical to improve drug efficiency and clinical outcomes. Several studies have implicated microRNAs (miRNA) in this process. MiRNAs repress gene expression by specific binding to complementary sequences in the 3' region of target messenger RNAs (mRNAs), followed by target mRNA degradation or blocked translation. By targeting molecules specific to a particular pathway within tumor cells, the new generation of cancer treatment strategies has shown significant advantages over conventional chemotherapy. However, the long-term efficacy of targeted therapies often remains poor, because tumor cells develop resistance to such therapeutics. Targeted therapies often involve monoclonal antibodies (mAbs), such as those blocking the ErB/HER tyrosine kinases, epidermal growth factor receptor (cetuximab) and HER2 (trastuzumab), and those inhibiting vascular endothelial growth factor receptor signaling (e.g., bevacizumab). Even though these are among the most used agents in tumor medicine, clinical response to these drugs is reduced due to the emergence of drug resistance as a result of toxic effects in the tumor microenvironment. Research on different types of human cancers has revealed that aberrant expression of miRNAs promotes resistance to the aforementioned drugs. In this study, we review the mechanisms of tumor cell resistance to mAb therapies and the role of miRNAs therein. Emerging treatment strategies combine therapies using innovative miRNA mimics or antagonizers with conventional approaches to maximize outcomes of patients with cancer.     

Effects of Oenothera biennis L. and Hypericum perforatum L. extracts on some central nervous system myelin proteins,brain histopathology and oxidative stress in mice with experimental autoimmune encephalomyelitis

We investigated the effects of Oenothera biennis L. and Hypericum perforatum L. extracts on brain tissue histopathology, myelin oligodendrocyte glycoprotein (MOG), myelin basic protein (MBP), total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI) in mice with experimental autoimmune encephalomyelitis (EAE). Forty-seven C57BL/6J mice were divided into the following groups: multiple sclerosis (MS), control (healthy mice), MS + H. perforatum treated (MS + HP), MS + O. biennis treated (MS + OB). All groups except the control group were immunized by EAE methods. Two weeks after the immunization, the mice in the MS + HP group were fed normal food containing 18 ? 21 g/kg H. perforatum extract, the mice in MS + OB group were fed normal food containing 18 ? 21 g/kg O. biennis extract, and the mice in control and MS groups were fed normal food for six weeks. Brain tissue samples were collected from all mice for histopathological and biochemical analysis. Clinical signs of the disease were scored using functional systems scores (FSS) daily. The H. perforatum and O. biennis extracts ameliorated the increased brain tissue MOG and MBP values for animals with MS. H. perforatum and O. biennis extract decreased the TOS and OSI values for brain tissue and increased TAS levels in brain tissue of animals with MS. In addition, H. perforatum and O. biennis extracts decreased the clinical signs at the end of the experiment compared to the beginning of extract administration. We found that myelin was lost in MS group vs. control group. H. perforatum and O. biennis extract treatments decreased the amount of myelin loss in the MS + HP and MS + OB groups. We also observed amyloid deposition on vascular walls, in the cytoplasm of the neurons and in the intercellular space in the MS group. O. biennis and H. perforatum treated groups exhibited neither abnormal amyloid deposition nor obvious cell infiltration. The beneficial effects of O. biennis and H. perforatum for attenuating myelin loss and amyloid deposition suggest their therapeutic utility for treatment of MS.     

粘虫(Pseudaletia separata(Walker))生殖系统的解剖

本文内容是研究粘虫(Pseudaletia separata(Walker)生殖系统的形态构造。全文分为雄性内部生殖器、雄性外部生殖器、雌性内部生殖器及雌性外部生殖器四部分。 粘虫的雄性内生殖器中, 有睾丸一对, 左右并列, 呈扁椭圆形, 外被紫红色睾丸膜; 输精管一对, 基部膨大成二对贮精囊; 射精管分成复射精管及单射精管两部分。雄性外生殖器的构造极为复杂, 第9腹节的背、腹板分别形成马鞍状的背兜及基腹弧; 第10腹节仅有其附肢特化成钩形突、颚形突和背兜侧突等; 抱握器占雄性外生殖器中的大部分, 其顶上角具长约1毫米的端刺一枚, 此为本种特征之一, 可以此与近似种区别; 阳茎由基部球状的阳茎囊和端部柄状的阳茎端组成, 内具内阳茎及角状器:雄性外生殖器中有关器官的肌肉来源亦作了叙述。 精液是以贮存于精球的方式授入雌体, 精球分为精球体、精球柄及系带三部分。 雌性内生殖器中, 卵巢为多滋式, 一对, 各由四个卵巢管组成, 两组卵巢管再与一对侧输卵管相连, 后者通入中输卵管中, 中输卵管后端连有外生殖腔, 其外方的开口是为产卵孔; 受精囊为长形梨状物, 分成主囊及副囊两部分, 两者在顶部愈合, 并由此发出受精管与外生殖腔相通, 在主囊顶端有受精囊腺; 附腺一对, 与附腺囊相连, 后者通入附腺主囊, 并由此开口入外生殖腔。雌性外生殖器是由交配囊和产卵器组成, 前者复可分成囊导管、囊体及囊颈三部分, 其外方的开口为交配囊孔, 有导精管从囊颈连于外生殖腔; 产卵器由第8、9腹节组成, 非呈特殊构造。     

Ginger and alpha lipoic acid ameliorate age-related ultrastructural changes in rat liver

Because of the important role that oxidative stress is thought to play in the aging process, antioxidants could be candidates for preventing its related pathologies. We investigated the ameliorative effects of two antioxidant supplements, ginger and alpha lipoic acid (ALA), on hepatic ultrastructural alterations in old rats. Livers of young (4 months) and old (24 months) Wistar rats were studied using transmission electron microscopy. Livers of old rats showed sinusoidal collapse and congestion, endothelial thickening and defenestration, and inconsistent perisinusoidal extracellular matrix deposition. Aged hepatocytes were characterized by hypertrophy, cytoplasmic vacuolization and a significant increase in the volume densities of the nuclei, mitochondria and dense bodies. Lipofuscin accumulation and decreased microvilli in bile canaliculi and space of Disse also were observed. The adverse alterations were ameliorated significantly by both ginger and ALA supplementation; ALA was more effective than ginger. Ginger and ALA appear to be promising anti-aging agents based on their amelioration of ultrastructural alterations in livers of old rats.     

Algorithmic approaches to aid species' delimitation in multidimensional morphospace

Background  

The species is a fundamental unit of biological pattern and process, but its delimitation has proven a ready source of argument and disagreement. Here, we discuss four key steps that utilize statistical thresholds to describe the morphological variability within a sample and hence assess whether there is evidence for one or multiple species. Once the initial set of biologically relevant traits on comparable individuals has been identified, there is no need for the investigator to hypothesise how specimens might be divided among groups, nor the traits on which groups might be separated.     

Changes in the endurance shuttle walk test in COPD patients with chronic respiratory failure after pulmonary rehabilitation: the minimal important difference obtained with anchor- and distribution-based method

Background

Although the endurance shuttle walk test (ESWT) has proven to be responsive to change in exercise capacity after pulmonary rehabilitation (PR) for COPD, the minimally important difference (MID) has not yet been established. We aimed to establish the MID of the ESWT in patients with severe COPD and chronic hypercapnic respiratory failure following PR.

Methods

Data were derived from a randomized controlled trial, investigating the value of noninvasive positive pressure ventilation added to PR. Fifty-five patients with stable COPD, GOLD stage IV, with chronic respiratory failure were included (mean (SD) FEV₁ 31.1 (12.0) % pred, age 62 (9) y). MID estimates of the ESWT in seconds, percentage and meters change were calculated with anchor based and distribution based methods. Six minute walking distance (6MWD), peak work rate on bicycle ergometry (Wpeak) and Chronic Respiratory Questionnaire (CRQ) were used as anchors and Cohen’s effect size was used as distribution based method.

Results

The estimated MID of the ESWT with the different anchors ranged from 186–199 s, 76–82% and 154–164 m. Using the distribution based method the MID was 144 s, 61% and 137 m.

Conclusions

Estimates of the MID for the ESWT after PR showed only small differences using different anchors in patients with COPD and chronic respiratory failure. Therefore we recommend using a range of 186–199 s, 76–82% or 154–164 m as MID of the ESWT in COPD patients with chronic respiratory failure. Further research in larger populations should elucidate whether this cut-off value is also valid in other COPD populations and with other interventions.

Trial registration

ClinicalTrials.Gov (ID {"type":"clinical-trial","attrs":{"text":"NCT00135538","term_id":"NCT00135538"}}NCT00135538).

Electronic supplementary material

The online version of this article (doi:10.1186/s12931-015-0182-x) contains supplementary material, which is available to authorized users.     

Effect of 10 kV, 30 microT, 60 Hz electric and magnetic fields on milk production and feed intake in nonpregnant dairy cattle

Milk production is the main agricultural income in the province of Québec, and the electrical distribution network traverses the rural dairy production region. This study evaluates the hypothesis that electric and magnetic fields may affect dairy production. Sixteen multiparous nonpregnant lactating Holstein cows (weighing 662 +/- 65 kg and with 150.4 +/- 40 days of lactation) were confined to wooden metabolic crates during the experiment with a 12:12 h light:dark cycle. The cows were divided into two replicates of eight cows each and exposed to a vertical EF of 10 kV/m and an uniform horizontal MF of 30 microT at 60 Hz. Replicate one was exposed for three periods. Each period was represented by an estrous cycle ranging from 24 to 27 days. During the first period, the electric and magnetic fields (E&MF) were off; during the second period they were on; and during the final period, they were off. The second replicate was exposed for three periods also, but the exposure protocol was reversed (first period, on; second period, off; last period, on). Exposure to E&MF (on) resulted in an average decrease of 4.97, 13.78, and 16.39% in milk yield, fat corrected milk yield, and milk fat, respectively; and an increase of 4.75% in dry matter intake.     

Compliance of a cobalt chromium coronary stent alloy – the COVIS trial

Aim

Female cardiac transplant recipients' aerobic capacity is 60% lower than sex and age-predicted values. The effect of exercise training on restoring the impaired aerobic endurance and muscle strength in female cardiac transplant recipients is not known. This study examined the effect that aerobic and strength training have on improving aerobic endurance and muscle strength in female cardiac transplant recipients.

Methods

20 female cardiac transplant recipients (51 ± 11 years) participated in this investigation. The subjects performed a baseline six-minute walk test and a leg-press strength test when they were discharged following cardiac transplantation. The subjects then participated in a 12-week exercise program consisting of aerobic and lower extremity strength training. Baseline assessments were repeated following completion of the exercise intervention.

Results

At baseline, the cardiac transplant recipients' aerobic endurance was 50% lower than age-matched predicted values. The training program resulted in a significant increase in aerobic endurance (pre-training: 322 ± 104 m vs. post-training: 501 ± 99 m, p < 0.05) and leg-press strength (pre-training: 48 ± 16 kg. vs. post-training: 78 ± 27 kg, p < 0.05).

Conclusion

Aerobic and strength training are effective interventions that can partially restore the impaired aerobic endurance and strength found in female cardiac transplant recipients.