The CSF-1 receptor ligands IL-34 and CSF-1 exhibit distinct developmental brain expression patterns and regulate neural progenitor cell maintenance and maturation

The CSF-1 receptor (CSF-1R) regulates CNS microglial development. However, the localization and developmental roles of this receptor and its ligands, IL-34 and CSF-1, in the brain are poorly understood. Here we show that compared to wild type mice, CSF-1R-deficient (Csf1r-/-) mice have smaller brains of greater mass. They further exhibit an expansion of lateral ventricle size, an atrophy of the olfactory bulb and a failure of midline crossing of callosal axons. In brain, IL-34 exhibited a broader regional expression than CSF-1, mostly without overlap. Expression of IL-34, CSF-1 and the CSF-1R were maximal during early postnatal development. However, in contrast to the expression of its ligands, CSF-1R expression was very low in adult brain. Postnatal neocortical expression showed that CSF-1 was expressed in layer VI, whereas IL-34 was expressed in the meninges and layers II-V. The broader expression of IL-34 is consistent with its previously implicated role in microglial development. The differential expression of CSF-1R ligands, with respect to CSF-1R expression, could reflect their CSF-1R-independent signaling. Csf1r-/- mice displayed increased proliferation and apoptosis of neocortical progenitors and reduced differentiation of specific excitatory neuronal subtypes. Indeed, addition of CSF-1 or IL-34 to microglia-free, CSF-1R-expressing dorsal forebrain clonal cultures, suppressed progenitor self-renewal and enhanced neuronal differentiation. Consistent with a neural developmental role for the CSF-1R, ablation of the Csf1r gene in Nestin-positive neural progenitors led to a smaller brain size, an expanded neural progenitor pool and elevated cellular apoptosis in cortical forebrain. Thus our results also indicate novel roles for the CSF-1R in the regulation of corticogenesis.     

Gamma secretase-mediated Notch signaling worsens brain damage and functional outcome in ischemic stroke

Mice transgenic for antisense Notch and normal mice treated with inhibitors of the Notch-activating enzyme gamma-secretase showed reduced damage to brain cells and improved functional outcome in a model of focal ischemic stroke. Notch endangers neurons by modulating pathways that increase their vulnerability to apoptosis, and by activating microglial cells and stimulating the infiltration of proinflammatory leukocytes. These findings suggest that Notch signaling may be a therapeutic target for treatment of stroke and related neurodegenerative conditions.     

Quantitative trait loci associated with soybean seed weight and composition under different phosphorus levels

Seed size and composition are important traits in food crops and can be affected by nutrient availability in the soil. Phosphorus (P) is a non‐renewable, essential macronutrient, and P deficiency limits soybean (Glycine max) yield and quality. To investigate the associations of seed traits in low‐ and high‐P environments, soybean recombinant inbred lines (RILs) from a cross of cultivars Fiskeby III and Mandarin (Ottawa) were grown under contrasting P availability environments. Traits including individual seed weight, seed number, and intact mature pod weight were significantly affected by soil P levels and showed transgressive segregation among the RILs. Surprisingly, P treatments did not affect seed composition or weight, suggesting that soybean maintains sufficient P in seeds even in low‐P soil. Quantitative trait loci (QTLs) were detected for seed weight, intact pods, seed volume, and seed protein, with five significant QTLs identified in low‐P environments and one significant QTL found in the optimal‐P environment. Broad‐sense heritability estimates were 0.78 (individual seed weight), 0.90 (seed protein), 0.34 (seed oil), and 0.98 (seed number). The QTLs identified under low P point to genetic regions that may be useful to improve soybean performance under limiting P conditions.     

Multicomponent pattern and biological activities of seven Asphodeline taxa: potential sources of natural-functional ingredients for bioactive formulations

The current study was carried out to evaluate multicomponent pattern, biological and enzymatic activities of seven Asphodeline taxa root extracts as useful ingredients, due to the fact that these plants are commonly used as traditional food supplements in Turkish regions. The extracts were characterized for free anthraquinones and phenolics to obtain a specific chemical fingerprint useful for quality control. These analyzes were coupled to biological and enzymatic activities in order to obtain comprehensive information of the natural product. Free anthraquinones and phenolics were determined using validated HPLC-PDA methods. Antioxidant properties were determined by different procedures including free radical scavenging, reducing power, phosphomolybdenum and metal chelating assays. Ames assay was performed to evaluate mutagenic/antimutagenic properties. Enzyme inhibitory activities were tested against cholinesterase, tyrosinase, α-amylase and α-glucosidase. From the herein reported results, Asphodeline could be valuable for the production of bioactive products or food supplements for cosmetic and pharmaceutical industries.     

Unilateral hysterectomy (cornuectomy) in the bitch and its effect on subsequent fertility

During caesarean section of bitches a beginning tissue necrosis of the uterus is often encountered. These alterations mostly require ovariohysterectomy that means the end of breeding life. The aim of this study was to create a model for unilateral hysterectomy during dystocia and to evaluate subsequent fertility. Unilateral cornuectomy was performed in 18 clinically healthy bitches of different ages, breeds, and at different stages of the sexual cyclus. Four bitches were not available for follow-up examinations. Twelve bitches were mated at the first obvious estrus period postoperatively and 10 pregnancies were diagnosed. Nine bitches delivered one to five puppies (mean 3.8) after a gestation period of 63-67 days. The puppies (n=38) were in a very good condition and showed high vitality. Unilateral cornuectomy of the uterus had no adverse effects and postoperative mating revealed pregnancy without complications and normal parturition. In the case of pathological changes in one uterine horn during a caesarean section unilateral hysterectomy seems to be an alternative to ovariohysterectomy.     

A life-threatening multilocalized hidradenitis suppurativa case

The patient was a 38-year-old man. He had been suffering from hidradenitis suppurativa (HS) for approximately 20 years. He had active lesions at both axillas, hip, scrotum, and perineum, and inactive lesions located behind the ears, lower abdomen, and posterior neck. He was monitored and treated at different branches; he continuously used antibiotics and was given steroids at times. Antibiotic resistance developed subsequently. His general situation was bad; vital signs were poor; and he was in a state of sepsis and preshock, so this case was regarded as life-threatening. Total excision was performed first on the lesion at the right axilla, then on the lesion at the left axilla, and the parascapular fasciocutaneous flap was reversed. A skin graft was applied to the triangular defect on the scapula. No relapse occurred. Then the lesions at the hip were managed. Broad excision was used twice with the patient under general anesthesia; because the lesions spread to the retrococcygeal and gluteal muscles, coccyx resection and partial gluteal muscle resection were implemented. The defect was eliminated with a progressive flap. At the intergluteal sulcus, small lesions emerging at the median line were debrided with the patient under local anesthesia, and together with secondary recovery, the disease was completely managed. Lesions at the perineum and scrotum and at both inguinal areas were broadly excised and grafted. No lesion has relapsed so far. One year later, Hodgkin's lymphoma was diagnosed, and the patient was treated with chemoradiotherapy easily, because there was no infective focus. The disease is in remission now. The patient weighs 110 kg, is healthy, and is working again.     

Chemical Characterization and Multidirectional Biological Effects of Different Solvent Extracts of Arum elongatum: in Vitro and in Silico Approaches

Arum elongatum (Araceae) is widely used traditionally for the treatment of abdominal pain, arterial hypertension, diabetes mellitus, rheumatism and hemorrhoids. This study investigated the antioxidant properties, individual phenolic compounds, total phenolic and total flavonoid contents (HPLC/MS analysis), reducing power and metal chelating effects of four extracts obtained from A. elongatum (ethyl acetate (EA), methanol (MeOH), methanol/water (MeOH/water) and infusion). The inhibitory activity of the extracts were also determined against acetylcholinesterase, butyrylcholinesterase, tyrosinase, amylase and glucosidase enzymes. The MeOH/water extracts contained the highest amount of phenolic contents (28.85 mg GAE/g) while the highest total flavonoid content was obtained with MeOH extract (36.77 mg RE/g). MeOH/water demonstrated highest antioxidant activity against DPPH⋅ radical at 38.90 mg Trolox equivalent per gram. The infusion extract was the most active against ABTS⁺⋅ (133.08 mg TE/g). MeOH/water extract showed the highest reducing abilities with the CUPRAC value of 102.22 mg TE/g and the FRAP value of 68.50 mg TE/g. A strong metal chelating effect was observed with MeOH/water extract (35.72 mg EDTAE/g). The PBD values of the extracts ranged from 1.01 to 2.17 mmol TE/g. EA extract displayed the highest inhibitory activity against AChE (2.32 mg GALAE/g), BChE (3.80 mg GALAE/g), α-amylase (0.56 mmol ACAE/g) and α-glucosidase (9.16 mmol ACAE/g) enzymes. Infusion extract was the most active against tyrosinase enzyme with a value of 83.33 mg KAE/g. A total of 28 compounds were identified from the different extracts. The compounds present in the highest concentration were chlorogenic acids, 4-hydroxybenzoic acid, caffeic acid, p-coumaric acid, ferulic acid, isoquercitrin, delphindin 3,5-diglucoside, kaempferol-3-glucoside and hyperoside. The biological activities of A. elongatum extracts could be due to the presence of compounds such as gallic acid, chlorogenic acids, ellagic acid, epicatechin, catechin, kaempferol, 4-hydroxybenzoic acid, caffeic acid, p-coumaric acid, ferulic acid, quercetin, isoquercitrin, and hyperoside. Extracts of A. elongatum showed promising biological activities which warrants further investigations in an endeavor to develop biopharmaceuticals.     

The Anticonvulsant Effects of Alpha-2 Adrenoceptor Agonist Dexmedetomidine on Pentylenetetrazole-Induced Seizures in Rats

Neurochemical Research - Alpha2-adrenoreceptor (α2-AR) is a noradrenergic receptor that is frequently studied for modulation of seizure activity. However, the precise role of this receptor...