CCN3 (NOV) is a novel angiogenic regulator of the CCN protein family

CCN3 (NOV) is a matricellular protein of the CCN family, which also includes CCN1 (CYR61), CCN2 (CTGF), CCN4 (WISP-1), CCN5 (WISP-2), and CCN6 (WISP-3). During development, CCN3 is expressed widely in derivatives of all three germ layers, and high levels of expression are observed in smooth muscle cells of the arterial vessel wall. Altered expression of CCN3 has been observed in a variety of tumors, including hepatocellular carcinomas, Wilm's tumors, Ewing's sarcomas, gliomas, rhabdomyosarcomas, and adrenocortical carcinomas. To understand its biological functions, we have investigated the activities of purified recombinant CCN3. We show that in endothelial cells, CCN3 supports cell adhesion, induces directed cell migration (chemotaxis), and promotes cell survival. Mechanistically, CCN3 supports human umbilical vein endothelial cell adhesion through multiple cell surface receptors, including integrins alphavbeta3, alpha5beta1, alpha6beta1, and heparan sulfate proteoglycans. In contrast, CCN3-induced cell migration is dependent on integrins alphavbeta3 and alpha5beta1, whereas alpha6beta1 does not play a role in this process. Although CCN3 does not contain a RGD sequence, it binds directly to immobilized integrins alphavbeta3 and alpha5beta1, with half-maximal binding occurring at 10 nm and 50 nm CCN3, respectively. Furthermore, CCN3 induces neovascularization when implanted in rat cornea, demonstrating that it is a novel angiogenic inducer. Together, these findings show that CCN3 is a ligand of integrins alphavbeta3 and alpha5beta1, acts directly upon endothelial cells to stimulate pro-angiogenic activities, and induces angiogenesis in vivo.     

Fused‐Ring Electron Acceptor ITIC‐Th: A Novel Stabilizer for Halide Perovskite Precursor Solution

Solution‐processed perovskite solar cells have great potential for low‐cost roll‐to‐roll fabrication. However, the degradation of aged precursor solutions will become a critical obstacle to mass production. In this report, a small molecule (ITIC‐Th) is employed to stabilize the perovskite precursor solution containing mixed cations and halides. It is found that ITIC‐Th can effectively suppress the formation of yellow δ‐phase in the films made from aged precursor solutions. Consequently, the devices fabricated from the aged precursor solution with ITIC‐Th experience much less efficiency drop with the increase of the precursor aging time—from 19.20% (fresh) to 16.55% (39 d), compared with the devices made from conventional precursor solutions dropping from 18.07% (fresh) to 1.76% (39 d). The characterizations suggest that ITIC‐Th is beneficial for CH₃NH₃⁺ cations to be incorporated into the crystal structure, facilitating the formation of perovskite phase. Furthermore, the presence of ITIC‐Th in the perovskite thin film gives rise to additional photocurrent as well as improved fill factor due to the well‐matched energy levels, the passivation of defects, and the complementary absorption spectra, suggesting a new route toward future high‐efficiency solar cells—incorporating organic non‐fullerene acceptors and halide perovskite materials into the same active layer.     

Maintaining connexin43 gap junctional communication in v-Src cells does not alter growth properties associated with the transformed phenotype

Loss of connexin expression and/or gap junctional communication (GJC) has been correlated with increased rates of cell growth in tumor cells compared to their normal communication-competent counterparts. Conversely, reduced rates of cell growth have been observed in tumor cells that are induced to express exogenous connexins and re-establish GJC. It is not clear how this putative growth-suppressive effect of the connexin proteins is mediated and some data has suggested that this function may be independent of GJC. In mammalian cells that express v-Src, connexin43 (Cx43) is phosphorylated on Tyr247 and Tyr265 and this results in a dramatic disruption of GJC. Cells that express a Cx43 mutant with phenylalanine mutations at these tyrosine sites form functional gap junctions that, unlike junctions formed by wild type Cx43, remain functional in cells that co-express v-Src. These cells still appear transformed; however, it is not known whether their ability to maintain GJC prevents the loss of growth restraints that confine "normal" cells, such as the inability to grow in an anchorage-independent manner or to form foci. In these studies, we have examined some of the growth properties of cells with Cx43 gap junctions that remain communication-competent in the presence of the co-expressed v-Src oncoprotein.     

Corneal antifibrotic switch identified in genetic and pharmacological deficiency of vimentin

The type III intermediate filaments (IFs) are essential cytoskeletal elements of mechanosignal transduction and serve critical roles in tissue repair. Mice genetically deficient for the IF protein vimentin (Vim(-/-)) have impaired wound healing from deficits in myofibroblast development. We report a surprising finding made in Vim(-/-) mice that corneas are protected from fibrosis and instead promote regenerative healing after traumatic alkali injury. This reparative phenotype in Vim(-/-) corneas is strikingly recapitulated by the pharmacological agent withaferin A (WFA), a small molecule that binds to vimentin and down-regulates its injury-induced expression. Attenuation of corneal fibrosis by WFA is mediated by down-regulation of ubiquitin-conjugating E3 ligase Skp2 and up-regulation of cyclin-dependent kinase inhibitors p27(Kip1) and p21(Cip1). In cell culture models, WFA exerts G(2)/M cell cycle arrest in a p27(Kip1)- and Skp2-dependent manner. Finally, by developing a highly sensitive imaging method to measure corneal opacity, we identify a novel role for desmin overexpression in corneal haze. We demonstrate that desmin down-regulation by WFA via targeting the conserved WFA-ligand binding site shared among type III IFs promotes further improvement of corneal transparency without affecting cyclin-dependent kinase inhibitor levels in Vim(-/-) mice. This dissociates a direct role for desmin in corneal cell proliferation. Taken together, our findings illuminate a previously unappreciated pathogenic role for type III IF overexpression in corneal fibrotic conditions and also validate WFA as a powerful drug lead toward anti-fibrosis therapeutic development.     

香港的生物多样性及其保育工作

香港位于热带,属海洋性气候。地势崎岖多山,山地约占全港总面积的3/4。城市发展多集中在沿海平坦地带。目前香港的城市和乡镇面积约占总面积的20%,农地约占5%(当中大部份已遭荒废),余下的均为郊野地区,这包括天然林和人工林(约占14%)、灌丛(约占36%)及草地(约占17%)。由于良好的气候和地理条件,形成了众多不同的生态环境,使总面积仅1090 km²的弹丸之地孕育出种类多样的动植物,生物多样性十分丰富。香港约有2500种原生植物,包括被子植物约1900种,裸子植物7种,蕨类植物220多种及苔藓植物300多种。动物方面,已记录的野生哺乳类动物有40多种,鸟类超过459种,两栖类23种,爬行类70多种。昆虫种类繁多,其中蜻蜓目100多种,鳞翅目2200多种(蝴蝶200多种,蛾类2000多种)。有很多是国家保护物种和特有种。植物方面属国家一级保护的有1种——刺桫椤(Alsophila spinulosa);国家二级保护的有6种,如四药门花(Tetrathryrium subcordatum);国家三级保护的有8种,如穗花杉(Amentotaxus argotaenia)。此外,香港特有种有16种,例如紫萁科(Osmundaceae)的粤紫萁(Osmunda mildei)、马兜铃科(Aristolochiaceae)的香港细辛(Asarum hongkongense)和兰科(Orchidaceae)的谢氏卷瓣兰(Bulbophyllum tseanum)。动物方面有9种属国家一级保护,例如中华白海豚(Sousa chinensis);79种属国家二级保护。特有种则有卢氏小树蛙(Philautus romeri)、包氏双足蜥(Dibamus bogadeki)及多种昆虫。为了保护丰富的野生动植物及其栖息的环境,香港特别行政区政府制定了一些法例并推行了不少保护措施,例如设立了21个郊野公园和14个特别地区,占全港陆地总面积约38%。此外,还成立了2个禁区、3个海岸公园和1个海洋保护区。另一方面,政府还设立了59个“具特殊科学价值地点”,以保护及研究各种动植物、生态系统和特殊的地质地貌。香港地少人多,总人口超过600万,是世界上人口最稠密的地区之一。多年来香港这个生物宝库不断地遭受人类活动的威胁,近年来由于人口急剧上升,对土地需求迫切,不少郊野地区被开发利用,环境污染亦日益严重。此外,一些野生植物因具有药用价值、观赏价值或其他用途而遭盗伐或采集。上述种种因素已使香港野生动植物及其生境受到严重损害,一些物种更濒于灭绝,进行生物多样性的保育工作刻不容缓。因此,香港确实需要制定整体的生物多样性保护策略。有鉴于此,香港大学生态及分类学系于1996年展开了一项为期3年的香港生物多样性调查,以增加对动植物资源现况的了解,为保护香港的珍稀濒危物种和日益恶化的自然环境提出补救方案,并为制订长远的保育策略奠定基础。     

Manipulation of Cell:Cell Contacts and Mesoderm Suppressing Activity Direct Lineage Choice from Pluripotent Primitive Ectoderm-Like Cells in Culture

In the mammal, the pluripotent cells of embryo differentiate and commit to either the mesoderm/endoderm lineages or the ectoderm lineage during gastrulation. In culture, the ability to direct lineage choice from pluripotent cells into the mesoderm/endoderm or ectoderm lineages will enable the development of technologies for the formation of highly enriched or homogenous populations of cells. Here we show that manipulation of cell:cell contact and a mesoderm suppressing activity in culture affects the outcome of pluripotent cell differentiation and when both variables are manipulated appropriately they can direct differentiation to either the mesoderm or ectoderm lineage. The disruption of cell:cell contacts and removal of a mesoderm suppressor activity results in the differentiation of pluripotent, primitive ectoderm-like cells to the mesoderm lineage, while maintenance of cell:cell contacts and inclusion, within the culture medium, of a mesoderm suppressing activity results in the formation of near homogenous populations of ectoderm. Understanding the contribution of these variables in lineage choice provides a framework for the development of directed differentiation protocols that result in the formation of specific cell populations from pluripotent cells in culture.     

The effect of age at introduction and number of milk-portions on the behaviour of group housed dairy calves fed by a computer controlled milk feeder

This study is an investigation of the effect of age at introduction (6 days versus 14 days) and number of milk-portions (four milk-portions a day versus eight milk-portions a day) on integration into a large dynamic group of calves, fed by a computer controlled milk feeder. Forty calves (Jerseys, Danish Reds and Holstein-Friesians) were allocated equally to the two age conditions (A6 and A14) and the two milk-portion conditions (M4 and M8) in a 2 × 2 factorial design, according to sex and breed, and introduced into the group in pairs (one A6 and one A14). The behaviour of each pair was video-recorded for 8 h from 8 a.m. to 4 p.m. and 1 h from 1 to 2 a.m. on days 1, 8 and 15 after introduction.

The A6 calves performed less licking and sniffing, changed posture more often and tended to spend less time standing than the A14 calves. In the course of time A14 calves lay closer to other calves than the A6 calves.

The M8 calves, which were offered the same daily milk allowance as the M4 calves stood for a longer time in the milk feeding station and the M8 calves also sucked the empty teat more frequently than the M4 calves. Finally, the M8 calves initiated more social play behaviour than the M4 calves. On the first day after introduction the M8 calves lay closer to other calves than the M4 calves.

The results suggest that calves integrate better into a group when introduced at the age of 14 days than at the age of 6 days. Distributing the milk into eight daily milk-portions, rather than four milk-portions in the first period after introduction, increased milk feeder occupancy, which may facilitate learning to use the milk feeder. Surprisingly, more milk-portions also stimulated play behaviour, which is suggested to be due to M8 calves encountering more calves in the milk feeder area.