A new brain endocast of Homo erectus from Hulu Cave, Nanjing, China

A new brain endocast of Homo erectus from Hulu Cave, Tangshan, Nanjing is described and compared with a broad sample of endocasts of H. erectus, Neanderthals, and recent modern humans. The Nanjing 1 endocast is reconstructed based on two portions of endocranial casts taken from the original fossil fragments. The fossil was discovered in 1993, near Nanjing, South China and is dated to ～ 0.58-0.62 Ma. The cranial capacity is ～ 876 cc, as determined by endocast water displacement. There are some common features of Nanjing 1 and other H. erectus endocasts that differentiate them from the Neanderthals and modern humans in our sample. These include small cranial capacity, low height dimensions, simple middle meningeal vessel patterns, a high degree of cerebral-over-cerebellar lobe overhang, elongated and quite separated cerebellar lobes, and a narrow, low, short and flat frontal region. Some features are found to vary among H. erectus, Neanderthals and modern humans, such as the lateral Sylvian fissure position and the venous sinus and petalial patterns. The Nanjing 1 endocast has unique, large, superior frontal convolutions, and strongly protruding Broca's caps. In contrast to other Chinese H. erectus from Hexian and Zhoukoudian, Nanjing 1 lacks strong posterior projection of the occipital lobes. Bivariate and principal component analyses indicate that the small volume and shape of Nanjing 1 is most similar to KNM-WT 15000, KNM-ER 3883, Sangiran 2 and Hexian, illustrating the combination of narrow, low, and short frontal lobes with wide posterior lobes.     

Adipose tissue-deprived stem cells acquire cementoblast features treated with dental follicle cell conditioned medium containing dentin non-collagenous proteins in vitro

Adipose tissue-derived stem cells (ADSCs), which are easily harvested and show excellent pluripotency potential, have generated considerable interest in regenerative medicine. In this study, the differentiation of ADSCs was assessed after treatment with dental follicle cell conditioned medium (DFCCM) containing dentin non-collagenous proteins (dNCPs). ADSCs exhibited a fibroblast-like morphology and high proliferative capacity. However, after treatment with dNCPs/DFCCM, ADSCs changed from a fibroblast-like to cementoblast-like morphology and significantly lost their proliferative capacity. Alkaline phosphatase activity and in vitro mineralization behaviour of ADSCs were significantly enhanced. Mineralization-related markers including cementum attachment protein, bone sialoprotein, osteocalcin, osteopontin and osteonectin were detected at mRNA or protein levels, whereas dentin sialophosphoprotein and dentin sialoprotein were not detected, implying a cementoblast-like phenotype. These results demonstrate that ADSCs acquired cementoblast features in vitro with dNCPs/DFCCM treatment and could be a potential source of cementogenic cells for periodontal regeneration.     

Traumatic Brain Injury Induces an Up-Regulation of Hs1-Associated Protein X-1 (Hax-1) in Rat Brain Cortex

HS1-associated protein X-1 (Hax-1) is an intracellular protein with anti-apoptotic properties that, in addition to suppressing cell death by inhibiting the activation of initiator caspase-9 and death caspase-3, is involved in an increasing number of signaling cascades. However, its expression and function in the central nervous system lesion are still unclear. In this study, we performed a traumatic brain injury (TBI) model in adult rats and investigated the dynamic changes of Hax-1 expression in the brain cortex. Western blot and immunohistochemistry analysis revealed that Hax-1 was present in normal brain. It gradually increased, reached a peak at day 3 after TBI, and then declined during the following days. Double immunofluorescence staining showed that Hax-1 immunoreactivity (IR) was found in neurons, but not astrocytes and microglia. Moreover, the 3rd day post injury was the apoptotic peak implied by the alteration of caspase-3, Bcl-2 and TUNEL. All these results suggested that Hax-1 may be involved in the pathophysiology of TBI and further research is needed to have a good understanding of its function and mechanism.     

New aromatic substituted pyrazoles as selective inhibitors of human adipocyte fatty acid-binding protein

a-FABP is indespensible in inflammation and may serve as a new potential drug target for inflammation related diseases. We have successfully designed and synthesized a series of aromatic substituted pyrazoles as new human a-FABP inhibitors. The compounds strongly bound to the hydrophobic binding pocket of a-FABP, while showed significantly lower binding affinities to the closely related homologue protein h-FABP. The most potent and selective compound 5g bound to a-FABP with an apparent K_i value below 1.0 nM, while did not inhibit h-FABP at 50 μM and thus represents one of the most potent and selective a-FABP inhibitors to date. The strong binding capacity of these inhibitors was further validated by their effective blockade of inflammatory responses as determined by the production of pro-inflammatory cytokines upon LPS stimulation. Compound 5g may serve as a lead compound for developing new effective therapeutic agent for prevention and treatment of atherosclerosis, type 2 diabetes and other inflammatory and metabolic related diseases.     

Genetic and genomic evidence that sucrose is a global regulator of plant responses to phosphate starvation in Arabidopsis

Plants respond to phosphate (Pi) starvation by exhibiting a suite of developmental, biochemical, and physiological changes to cope with this nutritional stress. To understand the molecular mechanism underlying these responses, we isolated an Arabidopsis (Arabidopsis thaliana) mutant, hypersensitive to phosphate starvation1 (hps1), which has enhanced sensitivity in almost all aspects of plant responses to Pi starvation. Molecular and genetic analyses indicated that the mutant phenotype is caused by overexpression of the SUCROSE TRANSPORTER2 (SUC2) gene. As a consequence, hps1 has a high level of sucrose (Suc) in both its shoot and root tissues. Overexpression of SUC2 or its closely related family members SUC1 and SUC5 in wild-type plants recapitulates the phenotype of hps1. In contrast, the disruption of SUC2 functions greatly inhibits plant responses to Pi starvation. Microarray analysis further indicated that 73% of the genes that are induced by Pi starvation in wild-type plants can be induced by elevated levels of Suc in hps1 mutants, even when they are grown under Pi-sufficient conditions. These genes include several important Pi signaling components and those that are directly involved in Pi transport, mobilization, and distribution between shoot and root. Interestingly, Suc and low-Pi signals appear to interact with each other both synergistically and antagonistically in regulating gene expression. Our genetic and genomic studies provide compelling evidence that Suc is a global regulator of plant responses to Pi starvation. This finding will help to further elucidate the signaling mechanism that controls plant responses to this particular nutritional stress.     

门齿孔位置在中国古人类化石与现代人群的表现及其演化意义

魏敦瑞在研究周口店北京直立人化石时发现,位于上颌骨硬腭表面的门齿孔位置在周口店标本靠后,而在现代人靠近齿槽。此后,门齿孔位置作为具有演化意义的形态特征被用于古人类学研究。迄今,对门齿孔位置在中国古人类化石表现的专门研究仅有周口店一件标本,而在现代中国人的数据尚属空白。鉴于此,本文对门齿孔位置在中国古人类化石以及现代中国人标本进行了观察、测量和数据统计。在此基础上,结合世界其他地区古人类数据资料,本文对门齿孔位置在中国古人类化石的表现特点及其演化意义进行了探讨。本研究发现,从更新世早期到更新世晚期,门齿孔位置在中国古人类呈现由后向前的总体变化趋势。更新世早期和中期直立人(郧县曲远河口、周口店)的门齿孔位置都比较靠后;中更新世晚期的部分中国古人类(大荔、长阳、华龙洞)的门齿孔位置前移,并与现代人接近,而金牛山和巢县门齿孔位置比较靠后,位于直立人范围;在更新世晚期,所有中国古人类都比较靠前,位于现代人变异范围。本文对现代人标本的观测显示,门齿孔位置在现代中国人比较靠前。现代人门齿孔大小及形态存在较大变异,这种表现特点在一定程度上影响对门齿孔位置及演化意义的判定。几乎全部现代人标本门齿孔前缘呈...     

Oryza sativa dicer-like4 reveals a key role for small interfering RNA silencing in plant development

MicroRNAs and small interfering RNAs (siRNAs) are two classes of small regulatory RNAs derived from different types of precursors and processed by distinct Dicer or Dicer-like (DCL) proteins. During evolution, four Arabidopsis thaliana DCLs and six rice (Oryza sativa) DCLs (Os DCLs) appear to have acquired specialized functions. The Arabidopsis DCLs are well characterized, but those in rice remain largely unstudied. Here, we show that both knockdown and loss of function of rice DCL4, the homolog of Arabidopsis DCL4, lead to vegetative growth abnormalities and severe developmental defects in spikelet identity. These phenotypic alterations appear to be distinct from those observed in Arabidopsis dcl4 mutants, which exhibit accelerated vegetative phase change. The difference in phenotype between rice and Arabidopsis dcl4 mutants suggests that siRNA processing by DCL4 has a broader role in rice development than in Arabidopsis. Biochemical and genetic analyses indicate that Os DCL4 is the major Dicer responsible for the 21-nucleotide siRNAs associated with inverted repeat transgenes and for trans-acting siRNA (ta-siRNA) from the endogenous TRANS-ACTING siRNA3 (TAS3) gene. We show that the biogenesis mechanism of TAS3 ta-siRNA is conserved but that putative direct targets of Os DCL4 appear to be differentially regulated between monocots and dicots. Our results reveal a critical role of Os DCL4-mediated ta-siRNA biogenesis in rice development.     

Comprehensive analysis of spectral distribution of a large cohort of Chinese patients with non‐syndromic oculocutaneous albinism facilitates genetic diagnosis

Non‐syndromic oculocutaneous albinism (nsOCA) is a group of genetically heterogeneous autosomal recessive disorders with complete lack or decrease pigmentation in skin, hair, and eyes. TYR, OCA2, TYRP1, SLC45A2, SLC24A5, and LRMDA were reported to cause OCA1‐4 and OCA6‐7, respectively. By sequencing all the known nsOCA genes in 114 unrelated Chinese nsOCA patients combined with In silico analyses, splicing assay, and classification of variants according to the standards and guidelines of American College of Medical Genetics and Genomics, we detected seventy‐one different OCA‐causing variants separately in TYR, OCA2, SLC45A2, and SLC24A5, including thirty‐one novel variants (13 in TYR, 11 in OCA2, and 7 in SLC45A2). This study shows that OCA1 is the most common (75/114) and OCA2 ranks the second most common (16/114) in Chinese. 99 patients of our cohort were caused by variants of all the known nsOCA genes. Cutaneous phenotypes of OCA1, OCA2, and OCA4 patients were shown in this study. The second OCA6 case in China was identified here. These data expand the spectrum of OCA variants as well phenotype and facilitate clinical implement of Chinese OCA patients.     

Partial Biological Characterization of Cancer Stem-like Cell Line (WJ<Subscript>2</Subscript>) of Human Glioblastoma Multiforme

To provide suitable models for human GBM cancer stem cells in vitro and in vivo, and investigate their biological characteristics, a new human GBM cancer stem-like cell line, WJ2, was established in this experiment through serial passages from adherent monolayer culture to nonadherent tumor sphere culture in turns; Its partial biological characteristics were studied through cell proliferation and tumor sphere assay; cell cycle distribution, side population, and CD133 phenotype were analyzed with FCM. The expressions of CD133, Nestin, and GFAP of cancer stem-like cells and xenograft tumor cells were detected with RT-PCR and immunohistochemistry. Biological characterization, side population, CD133 phenotype and CD133 Nestin, BCRP-1, Wnt-1 gene expression revealed the stemness of this cancer stem-like cell line. Tumorigenicity heterotransplanted in nude mice; histopathological characteristics of xenograft tumor, and expressions of CD133, Nestin, and GFAP of xenograft tumor cells indicated that xenograft tumors recapitulated the phenotype and biological characterization of human primary GBM. All findings of this experimental study suggested that WJ₂ cancer stem-like cell line could accurately mimic human GBM cancer stem cell in vitro and in vivo; it would be useful in the cellular and molecular studies as well as in testing novel therapies of CSC-based anti-cancer therapies for human GBM.     

Expression of G-protein-coupled receptor kinase 6 (GRK6) after acute spinal cord injury in adult rat

Spinal cord injury frequently results in permanent loss of neurological function. It includes many complex molecular and biochemical mechanisms. G-protein-coupled receptor kinase 6 (GRK6) is an intracellular kinase that regulates the sensitivity of certain G-protein-coupled receptors. Some studies reported GRK2 and GRK5 modulate the NFκB pathway in macrophages. Additionally, GRK2 is referred to as regulating activation of spinal cord microglia and GRK6 expression is significantly elevated in most brain regions in the MPTP-lesioned parkinsonian monkeys. However, the expression and function of GRK6 in nervous system lesion and repair are not well understood. In this study, we performed an acute spinal cord injury (SCI) model in adult rats. Western blot analysis showed the expression of GRK6 was upregulated significantly at protein level in spinal cord after SCI. Immunohistochemistry and immunofluorescence revealed wide expression of GRK6 in the normal spinal cord. After injury, GRK6 expression was increased predominantly in microglia, which expressed F4/80 (marker of macrophages and activated microglia) strongly. To understand whether GRK6 played a role in microglia activation, we applied lipopolysaccharide (LPS) to induce microglia activation in vitro. Western blot analysis demonstrated up-regulation in GRK6 protein expression after LPS stimulation was time- and dose-dependent and that up-regulation in F4/80 expression was concomitant with GRK6. These data suggested that GRK6 might be involved in the pathophysiology of SCI.