Postcranial remains of Baphetes and their bearing on the relationships of the Baphetidae (= Loxommatidae)

The first unequivocal postcranial remains of baphetids (= loxommatids) associated with skull roof and lower jaw material are reported from a specimen of Baphetes from the English Upper Carboniferous, Duckmantian. Characters of the mandible, including the incorporation in the symphysis of paired parasymphysial plates, permit the identification of a previously indeterminate jaw from the Langsettian (Westphalian A) of Nova Scotia, as baphetid. The postcranial remains include vertebrae, pectoral and pelvic limb and limb girdle elements that present a combination of unique characters extending the diagnosis of the family Baphetidae, together with plesiomophic and derived characters which suggest that baphetids are primitive stem group tetrapods.     

A new rheophilic South American darter (Crenuchidae: Characidium) from the rio Juruena basin,Brazil, with comments on morphological adaptations to life in fast-flowing waters

Characidium iaquira, a new species from the upper rio Juruena, rio Tapajós basin, Brazil, is described. The new species can be promptly distinguished from all congeners by having a unique v-shaped dark mark lying along the caudal-fin extension, in medium- and large-sized specimens, and a remarkable iridescent green colouration in life. Characidium iaquira is closely related to Characidium crandellii and Characidium declivirostre by sharing unambiguous synapomorphies such as branchiostegal membranes united to each other across the isthmus, a scaleless area extending from the isthmus to the pectoral girdle, and dermal flaps surrounding anterior and posterior naris independent, but touching each other distally. Morphological specializations of the paired fins in the three riffle-dwellers species are discussed, including the wing-like shape, robustness, and inclination of the pectoral fin.     

Effects of l-carnitine supplementation to suckling piglets on carcass and meat quality at market age

In a previous study, carnitine supplementation to piglets during the suckling period resulted in an increased total muscle fibre number at weaning in piglets of low birth weight. The objective of the present study was to investigate whether this effect is maintained until market age and whether this would attenuate the negative consequences of low birth weight on carcass and meat quality. Using a split-plot design with litter as block, sex as whole plot and treatment as subplot, the effects of early-postnatal l-carnitine supplementation on female and castrated male piglets of low birth weight were investigated on a total of 56 German Landrace piglets from 14 litters. From days 7 to 27 of age piglets were orally supplemented once daily with 400 mg of l-carnitine dissolved in 1 ml of water or received an equal volume of water without carnitine. From weaning (day 28) until slaughter (day 166 of age) all pigs were fed standard diets. At weaning, carnitine-supplemented piglets had a twofold increased concentration of free carnitine (P < 0.001) and a lower concentration of non-esterified fatty acids (P < 0.05) in blood plasma indicating that carnitine became bioavailable and increased fatty acid utilization during the period of supplementation. Growth performance was not influenced by treatment in any growth period. Dual-energy X-ray absorptiometry revealed no differences in body composition between groups in weeks 12, 16 and 20 of age. LW at slaughter, carcass weight, measures of meat yield and fat accretion, as well as body composition by chemical analyses and dissection of primal cuts did not differ between treatments. No differences between control and carnitine-treated pigs in total fibre number (P = 0.85) and fibre cross-sectional area (P = 0.68) in m. semitendinosus (ST) measured at slaughter could be observed. The carnitine group tended to exhibit a smaller proportion of slow-twitch oxidative fibres (P = 0.08), a greater proportion of fast-twitch glycolytic fibres (P = 0.11), and increased specific lactate dehydrogenase activity (P = 0.09) in ST indicating a more glycolytic muscle metabolism. Compared with the controls, a lower pH₂₄ value was observed (P = 0.05) in ST muscle of carnitine-supplemented pigs, which – in castrates only – was associated with an increased drip loss (P < 0.01). Meat quality traits in m. longissimus were not influenced by treatment. In conclusion, our hypothesis that early-postnatal carnitine supplementation to piglets of low birth weight permanently increases myofibre number and improves later carcass and meat quality could not be confirmed by this experiment.     

Magnolol inhibits colonic motility through down-regulation of voltage-sensitive L-type Ca2+ channels of colonic smooth muscle cells in rats

This study aimed to investigate the effect of magnolol (5,5′-diallyl-2,2′-biphenyldiol) on contraction in distal colonic segments of rats and the underlying mechanisms. Colonic segments were mounted in organ baths for isometric force measurement. Whole-cell voltage-sensitive L-type Ca²⁺ currents were recorded on isolated single colonic smooth muscle cells using patch-clamp technique. The spontaneous contractions and acetylcholine (ACh)- and Bay K 8644-induced contractions were inhibited by magnolol (3–100 μM). In the presence of Bay K8644 (100 nM), magnolol (10–100 μM) inhibited the contraction induced by 10 μM ACh. By contrast, tetrodotoxin (100 nM) and N_ώ-nitro-l-arginine methyl ester (l-NAME 100 μM) did not change the inhibitory effect of magnolol (10 μM). In addition, magnolol (3–100 μM) inhibited the L-type Ca²⁺ currents. The present results suggest that magnolol inhibits colonic smooth muscle contraction through downregulating L-type Ca²⁺ channel activity.     

Store-operated Ca entry and depolarization explain the anomalous behaviour of myometrial SR: Effects of SERCA inhibition on electrical activity,Ca and force

In the myometrium SR Ca²⁺ depletion promotes an increase in force but unlike several other smooth muscles, there is no Ca²⁺ sparks-STOCs coupling mechanism to explain this. Given the importance of the control of contractility for successful parturition, we have examined, in pregnant rat myometrium, the effects of SR Ca²⁺-ATPase (SERCA) inhibition on the temporal relationship between action potentials, Ca²⁺ transients and force. Simultaneous recording of electrical activity, calcium and force showed that SERCA inhibition, by cyclopiazonic acid (CPA 20 μM), caused time-dependent changes in excitability, most noticeably depolarization and elevations of baseline [Ca²⁺]_i and force. At the onset of these changes there was a prolongation of the bursts of action potentials and a corresponding series of Ca²⁺ spikes, which increased the amplitude and duration of contractions. As the rise of baseline Ca²⁺ and depolarization continued a point was reached when electrical and Ca²⁺ spikes and phasic contractions ceased, and a maintained, tonic force and Ca²⁺ was produced. Lanthanum, a non-selective blocker of store-operated Ca²⁺ entry, but not the L-type Ca²⁺ channel blocker nifedipine (1–10 μM), could abolish the maintained force and calcium. Application of the agonist, carbachol, produced similar effects to CPA, i.e. depolarization, elevation of force and calcium. A brief, high concentration of carbachol, to cause SR Ca²⁺ depletion without eliciting receptor-operated channel opening, also produced these results. The data obtained suggest that in pregnant rats SR Ca²⁺ release is coupled to marked Ca²⁺ entry, via store operated Ca²⁺ channels, leading to depolarization and enhanced electrical and mechanical activity.     

Ca handling alterations and vascular dysfunction in diabetes

More than 65% of patients with diabetes mellitus die from cardiovascular disease or stroke. Hyperglycemia, due to either reduced insulin secretion or reduced insulin sensitivity, is the hallmark feature of diabetes mellitus. Vascular dysfunction is a distinctive phenotype found in both types of diabetes and could be responsible for the high incidence of stroke, heart attack, and organ damage in diabetic patients. In addition to well-documented endothelial dysfunction, Ca²⁺ handling alterations in vascular smooth muscle cells (VSMCs) play a key role in the development and progression of vascular complications in diabetes. VSMCs provide not only structural integrity to the vessels but also control myogenic arterial tone and systemic blood pressure through global and local Ca²⁺ signaling. The Ca²⁺ signalosome of VSMCs is integrated by an extensive number of Ca²⁺ handling proteins (i.e. channels, pumps, exchangers) and related signal transduction components, whose function is modulated by endothelial effectors. This review summarizes recent findings concerning alterations in endothelium and VSMC Ca²⁺ signaling proteins that may contribute to the vascular dysfunction found in the diabetic condition.     

Wolframin deficiency is accompanied with metabolic inflexibility in rat striated muscles

The protein wolframin is localized in the membrane of the endoplasmic reticulum (ER), influencing Ca2+ metabolism and ER interaction with mitochondria, but the exact role of the protein remains unclear. Mutations in Wfs1 gene cause autosomal recessive disorder Wolfram syndrome (WS). The first symptom of the WS is diabetes mellitus, so accurate diagnosis of the disease as WS is often delayed. In this study we aimed to characterize the role of the Wfs1 deficiency on bioenergetics of muscles. Alterations in the bioenergetic profiles of Wfs1-exon-5-knock-out (Wfs1KO) male rats in comparison with their wild-type male littermates were investigated using high-resolution respirometry, and enzyme activity measurements. The changes were followed in oxidative (cardiac and soleus) and glycolytic (rectus femoris and gastrocnemius) muscles. There were substrate-dependent alterations in the oxygen consumption rate in Wfs1KO rat muscles. In soleus muscle, decrease in respiration rate was significant in all the followed pathways. The relatively small alterations in muscle during development of WS, such as increased mitochondrial content and/or increase in the OxPhos-related enzymatic activity could be an adaptive response to changes in the metabolic environment. The significant decrease in the OxPhos capacity is substrate dependent indicating metabolic inflexibility when multiple substrates are available.     

龙虎交战针法联合悬吊训练对腰椎间盘突出症患者腰背伸肌群功能、神经传导速度和血清炎症因子的影响

摘要 目的：观察龙虎交战针法联合悬吊训练对腰椎间盘突出症（LDH）患者腰背伸肌群功能、神经传导速度和血清炎症因子的影响。方法：纳入我院2018年4月-2021年8月期间接收的LDH患者82例。按照随机数字表法将患者分为对照组（悬吊训练,n=41）和实验组（龙虎交战针法联合悬吊训练,n=41）。观察两组患者腰椎功能恢复情况、疼痛症状改善情况以及腰背伸肌群功能、神经传导速度和血清炎症因子的变化情况。结果：实验组的临床总有效率高于对照组（P<0.05）。治疗后,两组日本骨科协会下腰痛评价表（JOA）评分升高,且实验组高于对照组（P<0.05）。治疗后,两组Oswestry功能障碍指数（ODI）、视觉疼痛模拟评分法（VAS）评分下降,且实验组低于对照组（P<0.05）。治疗后,两组平均功率、腰背伸状态下峰力矩升高,且实验组高于对照组（P<0.05）。治疗后,两组腰背屈伸比下降,且实验组较对照组低（P<0.05）。治疗后,两组腓总神经和胫神经的传导速度均升高,且实验组较对照组高（P<0.05）。治疗后,两组血清白细胞介素-1β（IL-1β）、白介素-1（IL-1）、基质金属蛋白酶 3（MMP-3）、肿瘤坏死因子-α（TNF-α）水平均下降,且实验组低于对照组（P<0.05）。结论：龙虎交战针法联合悬吊训练可促进LDH患者腰椎功能改善,减轻疼痛症状,改善腰背伸肌群功能和腓总神经、胫神经的神经传导速度,降低机体血清炎症因子水平,具有较好的临床应用价值。     

Binding and Functional Folding (BFF): A Physiological Framework for Studying Biomolecular Interactions and Allostery

EF-hand Ca²⁺-binding proteins (CBPs), such as S100 proteins (S100s) and calmodulin (CaM), are signaling proteins that undergo conformational changes upon increasing intracellular Ca²⁺. Upon binding Ca²⁺, S100 proteins and CaM interact with protein targets and induce important biological responses. The Ca²⁺-binding affinity of CaM and most S100s in the absence of target is weak (^CaK_D > 1 μM). However, upon effector protein binding, the Ca²⁺ affinity of these proteins increases via heterotropic allostery (^CaK_D < 1 μM). Because of the high number and micromolar concentrations of EF-hand CBPs in a cell, at any given time, allostery is required physiologically, allowing for (i) proper Ca²⁺ homeostasis and (ii) strict maintenance of Ca²⁺-signaling within a narrow dynamic range of free Ca²⁺ ion concentrations, [Ca²⁺]^free. In this review, mechanisms of allostery are coalesced into an empirical “binding and functional folding (BFF)” physiological framework. At the molecular level, folding (F), binding and folding (BF), and BFF events include all atoms in the biomolecular complex under study. The BFF framework is introduced with two straightforward BFF types for proteins (type 1, concerted; type 2, stepwise) and considers how homologous and nonhomologous amino acid residues of CBPs and their effector protein(s) evolved to provide allosteric tightening of Ca²⁺ and simultaneously determine how specific and relatively promiscuous CBP-target complexes form as both are needed for proper cellular function.     

Expression of connexin43 gap functions between cultured vascular smooth muscle cells is dependent upon phenotype

The smooth muscle cell is the predominant cell type of the arterial media. In the adult vascular system, smooth muscle cells are found primarily in the contractile phenotype, but following injury or during atherosclerotic plaque formation the secretory synthetic phenotype is expressed. Recently it has been shown that gap junction connexin43 messenger RNA levels are six times higher in cultured smooth muscle cells in the synthetic phenotype than in intact aorta. We have modulated rabbit aortic smooth muscle cells in culture between the synthetic phenotype and one resembling the contractile phenotype, and correlated gap junction expression with phenotype. A dual labelling technique with antibodies against smooth muscle myosin and a synthetic peptide constructed to match a portion of the connexin43 gap junction protein was used for these experiments. Gap junctions are numerous between synthetic phenotype cells but few are observed between contractile cells. Rat aortic smooth muscle cells were also cultured and the growth and structure of gap junctions followed in the synthetic phenotype by use of freeze-fracture electron microscopy and immunohistochemical techniques. Junctional plaques are similar in structure to those observed in cardiac muscle, their size and number increasing with time in culture. The increased numbers of gap junctions between synthetic phenotype smooth muscle cells may be important during vessel development, following injury, or in atherosclerotic plaque formation.