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The lamin protein family
- Travis Dittmer1Email author and
Affiliated with
- Tom Misteli1
Affiliated with
DOI: 10.1186/gb-2011-12-5-222
© BioMed Central Ltd 2011
Published: 31 May 2011
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DOI: 10.1186/gb-2011-12-5-222
© BioMed Central Ltd 2011
Published: 31 May 2011
The lamins are the major architectural proteins of the animal cell nucleus. Lamins line the inside of the nuclear membrane, where they provide a platform for the binding of proteins and chromatin and confer mechanical stability. They have been implicated in a wide range of nuclear functions, including higher-order genome organization, chromatin regulation, transcription, DNA replication and DNA repair. The lamins are members of the intermediate filament (IF) family of proteins, which constitute a major component of the cytoskeleton. Lamins are the only nuclear IFs and are the ancestral founders of the IF protein superfamily. Lamins polymerize into fibers forming a complex protein meshwork in vivo and, like all IF proteins, have a tripartite structure with two globular head and tail domains flanking a central α-helical rod domain, which supports the formation of higher-order polymers. Mutations in lamins cause a large number of diverse human diseases, collectively known as the laminopathies, underscoring their functional importance.
The lamins were first characterized biochemically as prominent 60 to 80 kDa proteins of the nuclear lamina and eventually identified as intermediate filament (IF) proteins by sequence homology [1–6]. The name intermediate filament refers to the average diameter of assembled intermediate fibers (10 to 12 nm), which is between that of actin microfilaments (7 to 10 nm) and that of microtubules (25 nm) [7]. The nuclear lamins represent one (type V) of six subtypes of the IF superfamily, defined on the basis of genomic structure and nucleotide sequence. Lamins are present only in metazoans and seem to be restricted to the animal kingdom as no obvious homologs have been identified in the fully sequenced genomes of several lower eukaryotes, including Arabidopsis thaliana, Saccharomyces cerevisiae and Schizosaccharomyces pombe.
Relative to the well-conserved cytoskeletal proteins tubulin and actin, IF proteins and lamins appeared more recently in evolutionary time and have undergone large divergence in sequence. Current evidence supports the hypothesis that all IF proteins arose from a common lamin-like progenitor, because all organisms known to have IF proteins also have lamins, but not all also have cytoplasmic IF proteins (the latter would be expected if lamins had evolved from a cytoplasmic IF). For example, the Drosophila genome encodes only two IF proteins, both of which are nuclear lamins [8], and the cnidarian Hydra vulgaris genome encodes a single IF protein, which is also a nuclear lamin [9]. In addition, the expression patterns of IF proteins indicate that lamins are the ancestral founder of the family. Expression of at least one lamin in all cell types is essential for viability, in contrast to cytoplasmic IFs, which are expressed in a cell-type- and tissue-specific pattern [10]. Sequence comparison further supports the notion of lamins as ancestral IFs. A lamin-specific 42 amino acid segment is present in primitive cytoplasmic IF proteins from some invertebrates but is absent from cytoplasmic IF proteins from all vertebrates and most invertebrates [11]. Given that the 42 amino acid segment is present in all lamins and some primitive cytoskeletal IF proteins, it seems that an ancestral lamin gave rise to the primordial cytoplasmic IF proteins, which later lost the 42 amino acid signature, probably through an exon deletion event. Furthermore, vertebrate nuclear lamins are more similar to invertebrate cytoplasmic IF proteins than they are to vertebrate cytoplasmic IF proteins, suggesting evolutionary proximity [12].
Several lines of evidence support the view that a B-type lamin appeared before A-type lamins. Almost all invertebrate lamins are B-type lamins, which are more similar to vertebrate B-type lamins than A-type lamins. Also, some invertebrates contain a single lamin, which is always a B-type lamin [9]. The intron-exon structure of the lamins supports a model in which a B-type lamin was the progenitor [13]. For example, intron positions of the human lamin B1 gene (LMNB1) are conserved in the lamin A/C (LMNA) and lamin B2 (LMNB2) genes; however, LMNB2 contains an intron between the regions encoding coil 1A and coil 1B that is not present in other IF proteins (including LMNA), indicating that LMNB2 and LMNA evolved from an LMNB1-like ancestor [13]. Moreover, in organisms with both A- and B-type lamins, such as mammals, B-type lamins are constitutively expressed in all somatic cells, whereas A-type lamins are developmentally regulated and expressed primarily in differentiated tissues.
Lamins are alternatively spliced to create multiple isoforms. The genomes of mammals encode three lamin genes, LMNA, LMNB1 and LMNB2, which collectively express at least seven protein isoforms. LMNA is alternatively spliced producing at least four isoforms: the two major isoforms lamin A and C, and the two minor isoforms C2 and AΔ10. Lamin A and C are identical for the first 566 amino acids, but lamin C lacks 98 amino acids at the carboxyl terminus that are present in pre-lamin A (before post translational processing) and contains a unique six amino acid carboxyl terminus (Figure 1). One major difference between lamins A and C is the absence in lamin C of the CAAX box, which is modified by farnesylation and has a role in targeting the lamins to the inner nuclear membrane. Some lamin isoforms are highly tissue-specific, such as human lamin B3, an alternatively spliced isoform of LMNB2, which is restricted to the male germ line [18]. Other lamin isoforms, such as lamins A and C, are ubiquitously expressed in virtually all differentiated cells. The functional significance of individual lamin isoforms is largely unknown. Overall, vertebrates encode more lamin genes and produce isoforms to a greater extent than invertebrates. Differential expression of different lamin isoforms creates functionally and structurally unique nuclear laminas. Whatever the roles of each lamin isoform, it is generally thought that increases in the numbers of lamin isoforms, either by gene duplications and/or alternative splicing, may have helped to meet the functional demands of increasing cellular variety and complexity.
Like all IF proteins, nuclear lamins have a tripartite structure consisting of a long α-helical domain flanked by globular amino-terminal (head) and carboxy-terminal (tail) domains (Figure 1). The central α-helical or rod domain spans approximately half of the lamin molecule (about 350 residues) and comprises four α-helical segments termed 1A, 1B, 2A and 2B. Each α-helical segment has heptad-repeat periodicity, characteristic of coiled-coil proteins, and is connected by short intervening sub-domains denoted L1, L12 and L2. The 2.2 Å structure of part of the carboxy-terminal coiled-coil segment 2B from human lamin A has been solved (Figure 1b), opening the way for more detailed studies on lamin assembly [19]. The amino-terminal head domain of the lamins is variable in size but is generally shorter than the same domain found in cytoplasmic IF proteins (which are about 40 to 100 residues long). The carboxy-terminal tail domain contains a nuclear localization signal, an Ig domain and a CAAX box (Figure 1). The structure of the human lamin A/C Ig domain contains a characteristic Ig fold and forms a compact β sandwich comprising two β sheets formed from nine β strands connected by short loops [20, 21]. The Ig domain is common to many proteins and mediates diverse protein-protein and protein-ligand interactions, which involve virtually every surface of the Ig domain. The Ig domains in lamins are suggested to represent a new class on the basis of the connectivity of strands and the presence of ancillary β strands, which may confer unique protein interaction properties [20].
Lamins dimerize using their α-helical rod domain, which contains the characteristic coiled-coil heptad repeat pattern. Coiled-coiled heptad repeats a and d preferentially contain hydrophobic residues and repeats e and g charged residues. Along the axis of the α helix is a hydrophobic seam, which acts as a dimerization interface between two lamin proteins, oriented in a parallel, unstaggered manner. Each α helix coils around the other, resulting in the lamin dimer, the basic building block of higher-order lamin assemblies (Figure 3). Electron microscopy studies show that the lamin dimer forms a rod about 50 nm long flanked at one end by two tightly packed globules, which correspond to two globular carboxy-terminal tail domains [26]. Interactions between A- and B-type lamins are possible. Pre-lamin A, lamin A, lamin B1 and lamin C can form homo- and hetero-dimers when ectopically expressed in yeast and in in vitro binding assays [27, 28]. The precise abundance of each species in vivo is not known, but the cellular ratio of the lamins is non-stoichiometric [29].
Higher-order polymerization of lamins involves head-to-tail parallel association between two or more lamin dimers, resulting in a lamin polymer (Figure 3). Head-to-tail association of lamin dimers involves an overlap of the highly conserved amino-terminal part of coil 1A and a carboxy-terminal part of coil 2B [19]. This head-to-tail association is unique to lamins, contrasting with the overlapping, half-staggered, anti-parallel side-by-side association of dimers observed for cytoplasmic IF proteins. The relatively short amino-terminal head domain is important for the formation of head-to-tail polymers in vitro and for IF formation in vivo [30]. The head domain requirement can be traced to 20 highly conserved residues, which include phosphorylation sites for cell-cycle dependent kinase 2 (CDC2), which is known to have a role in lamin disassembly in mitosis [31].
The study of higher-order lamin structures has been hampered by the difficulty of producing 10-nm filaments in vitro. So far, the Caenorhabditis elegans lamin is the only lamin that has been successfully assembled into 10 nm IF-like filaments in vitro [26, 32]. This B-type lamin has a truncated carboxy-terminal tail domain, possibly explaining the different assembly properties. It is also possible that formation of 10 nm filaments depends on the presence of membranes that are absent from the in vitro systems. Instead, most lamins form paracrystalline arrays in vitro, which display a unique axial repeat pattern [33].
Heterotypic lamin dimers can interact to form mixed isoform polymers in vitro [34]. However, it is unclear whether in vivo individual filaments contain both types of lamins within the same filament or whether lamins segregate into distinct filaments. Following mitosis, lamin A incorporates into the membrane after lamin B, suggesting that nuclear IFs are homotypic [35]. Nevertheless, this does not exclude the possibility of eventual reorganization of the nascent lamina or integration of heterotypic interactions, as suggested by high-resolution images of a mammalian somatic lamina that demonstrate domains of segregation and domains of overlap juxtaposed within the same nucleus [24].
Lamins are post-translationally modified in several ways. Almost all lamins contain a CAAX box at the carboxyl terminus, which serves as a substrate for post-translational farnesylation. This is achieved in three successive steps starting with the isoprenylation of the cysteine, followed by the proteolytic cleavage of the AAX motif and finally the carboxy-methylation of the farnesylated cysteine. The hydrophobic farnesyl moiety is thought to facilitate localization to and retention at the nuclear envelope. Nevertheless, carboxy-terminal farnesylation is not absolutely required for lamina localization because lamin C does not contain a CAAX box but does localize to the nuclear envelope. Once localized to the nuclear envelope, lamin A is processed further by the proteolytic removal of the carboxy-terminal 18 amino acids, including the farnesyl group, whereas B-type lamins retain the farnesyl moiety in their mature form [33].
Lamins are phosphorylated by multiple kinases and contain many conserved phosphorylation sites, with more than 30 known sites in human A-type lamins alone [36]. Three kinases known to modify and modulate lamins' activities are CDC2, protein kinase C (PKC) and protein kinase A (PKA). The mitotic kinase CDC2 induces lamin disassembly by phosphorylating conserved residues within the head and coiled-coil 2B domains [31]. Phosphorylation of Thr19, Ser22 and Ser392 causes depolymerization of lamin filaments in mitosis and meiosis. PKA phosphorylation sites are highly conserved and when phosphorylated inhibit lamin polymerization [37]. In addition, phosphorylation by PKC is known to regulate lamin uptake into the nucleus [38].
Lamin A also has two sumoylation consensus sites, one within the rod domain and another within the tail domain. Substitutions (E203G and E203K) within the rod domain disrupt the canonical SUMO E2 site, resulting in lower levels of sumoylated lamin in vivo and altered subnuclear localization [39].
B-type lamins are constitutively expressed in most cell types, whereas A-type lamins are developmentally regulated, being predominantly expressed in most differentiated cell types [40]. However, certain cells of the hematopoietic system do not express A-type lamins even when fully differentiated [41]. In mammalian germ cells and pronuclei, expression is limited to the two atypical lamin isoforms lamin B3 and C2, respectively, which are detected only in germ cells but are otherwise not expressed [18, 42]. In fish, amphibians and birds the species-specific lamin B3 (LIII) is expressed in oocytes. A- and B-type lamins are also found in fertilized mammalian eggs until 2 to 4 cleavage divisions, when A-type lamins are no longer detected. As embryogenesis proceeds, A-type lamins are again detected on day 8 to 9 in extra-embryonic tissues and on day 12 in the embryo itself [41, 43]. Mouse and human embryonic stem cells express lamins B1 and B2 but not lamins A or C. When embryonic stem cells move towards differentiation, lamin A/C is detected immediately before the pluripotent Oct-3/4 gene is downregulated, and immediately after stage-specific embryonic antigen-4 (SSEA-4) is activated. Interspecies differences in lamin expression have also been noted: lamin A is highly expressed in circulating erythrocytes in Gallus gallus (chicken) but is absent from the same cell type in amphibians [44, 45]. Because A-type lamins usually appear after cellular differentiation initiates, it is thought that A-type lamins facilitate 'locking-in' of the differentiated state [41].
Lamins have pivotal roles in nuclear reassembly after cell division. During mitosis, when the nuclear envelope breaks down and the lamina disassembles, A-type lamins are solubilized and distributed throughout the cytoplasm, whereas B-type lamins maintain close associations with the nuclear membrane. The differences in membrane attachment during mitosis are attributed to whether the lamin protein is farnesylated. Mature lamin B retains its farnesylation moiety, which anchors B-type lamins to the membrane during mitosis, whereas the farnesylation moiety is removed from lamin A, rendering it more soluble [52]. To facilitate disassembly of the lamina, lamins are phosphorylated by PKC and are dephosphorylated by type 1 protein phosphatase during reassembly [53]. When a nascent nuclear envelope forms around condensed chromosomes, A-type lamins are imported into the nucleus along with additional B-type lamins [35, 54].
Lamins are early targets for caspase degradation in cells undergoing apoptosis [55, 56]. Caspase-6 and caspase-3 are the major proteases responsible for A- and B-type lamin degradation [57]. At the onset of apoptosis, before detectable DNA cleavage or chromatin condensation occurs, lamins are cleaved at caspase recognition sites located within the L12 linker region and expression of uncleavable mutant lamin protein delays the onset of apoptosis [58]. Time-lapse experiments of green-fluorescent-protein-tagged lamins suggest that A- and B-type lamins have different dynamics following their initial cleavage [59]. A-type lamins are thought to rapidly translocate to the nucleoplasm and cytoplasm, whereas B-type lamins remain at the nuclear periphery.
From their primary sequence and their grouping within the IF superfamily, the lamins were originally hypothesized to provide mechanical support for the nucleus, conceivably as tensegrity elements that specify nuclear morphology and resistance to deformation [22]. In support of this, studies using Xenopus nuclear assembly systems show that cell-free extracts depleted of lamins assemble small and fragile nuclei [60]. Conversely, ectopic expression of the germ-cell-specific lamin B3 isoform, which lacks the amino terminus and part of the α-helical domain, in somatic cells induces a hook-shaped nuclear morphology reminiscent of spermatocytes [61]. Additional studies have demonstrated that human cells expressing a variety of lamin mutations often show a range of nuclear morphological phenotypes [62]. Fibroblast nuclei from Lmna -/- mice are deformed more easily and to a greater extent than those from Lmna +/+ littermates [63]. These nuclei are also more fragile, less resistant to physical compression, and deform in an isotropic manner, in contrast to the anisotropic deformation observed in Lmna +/+ nuclei [64]. Furthermore, the absence of lamin A/C from embryonic stem cells has been suggested as an explanation for the more malleable and deformable nuclei of this cell type [65]. The extent of B-type lamin involvement in nuclear mechanics is not as well understood because loss of lamin B1 from murine embryonic fibroblasts (MEFs) causes nuclear blebbing, but does not seem to affect mechanical properties [66].
Nuclei are mechanically linked to the cytoskeleton through lamin-interacting proteins that span the nuclear envelope (Figure 5). This linker of nucleoskeleton and cytoskeleton (LINC) complex consists of lamin-interacting proteins SUN1 or SUN2, which span the inner nuclear membrane where they, in turn, interact with a member of the nesprin family of proteins in the luminal space [70]. Nesprins span the outer nuclear membrane, where they associate in the cytoplasm with various cytoskeletal elements. The LINC complex has been implicated in serving functions important for nuclear migration, positioning, morphology and mechanics [71, 72].
Lamins are global regulators of chromatin (Figure 5). Transcriptionally silent regions of the genome, such as centromeres, telomeres and the inactive X chromosome, are preferentially positioned at the nuclear lamina [73, 74]. A direct role for lamins in the regulation of chromatin was demonstrated in studies of cardiomyocytes and MEFs derived from Lmna -/- mice, which show a partial loss of peripheral heterochromatin, ectopic chromosome condensation and mis-positioning of centromeric heterochromatin [75–77]. Disengagement and/or loss of heterochromatin are also observed in cells expressing a variety of mutant lamin A proteins [78–80]. Global heterochromatic changes induced by lamin perturbation are often mirrored by altered levels of chromatin-associated epigenetic histone marks; for example, decreased levels of the heterochromatin markers histone H3 lysine 9 trimethylation (H3K9me3) and H3K27me3 and increased levels of H4K20me3. Ectopic lamin expression also influences chromatin organization and associated histone marks; for example, hypermethylated H3K4, a mark of active genes, decreases following overexpression of wild-type lamin A in C2C12 myoblasts [81].
Lamins have at least two chromatin-binding regions. One chromatin interaction domain is located in the tail region between the end of the rod domain and the Ig domain, and the other is within the rod domain [82, 83]. Chromatin interactions are probably mediated through histones and/or chromatin-associated proteins, but lamins bind nonspecifically to DNA in vitro through contacts in the minor groove of the double helix [82, 84]; however, lamins associate with sequences known as scaffold/matrix attachment regions, which are involved in transcriptional regulation, DNA replication, chromosome condensation and chromatin organization [85]. Genome-wide mapping techniques have identified genome regions that preferentially associate with lamins, known as lamin-A-associated domains (LADs) [86]. These domains are generally gene-poor and are proposed to represent a repressive chromatin environment.
Recent studies have hinted at a role for lamins in DNA repair. Most of these studies have focused on the effects of expressing an unprocessed lamin A protein, which causes the premature aging disorder Hutchinson Gilford Progeria Syndrome (HGPS). The mutant lamin A protein, named progerin, expressed in HGPS patients has a deletion in the tail domain and consequently remains permanently farnesylated. Cells expressing progerin have a delayed recruitment of the repair factor p53-binding protein (53BP1) to sites of DNA damage, show increased levels of the double-stranded break marker γ-H2AX, and are more sensitive to DNA damaging agents [87]. Progerin expression also affects the localization and expression of the key DNA damage regulators ATR and ATM and the double-stranded break repair factors Rad50 and Rad51 [88]. Taken together, these studies suggest the necessity of normal lamin A function in repair of DNA damage. However, the mechanistic details linking lamins and DNA damage have yet to be fully elucidated.
Many studies have documented a link between lamins and signal transduction pathways important for cellular differentiation and homeostasis (Figure 5) [89]. Through protein-protein interactions, lamins are thought to regulate the activity and availability of proteins within signaling cascades, including the retinoblastoma (Rb)/E2F, Wnt/β-catenin, transforming growth factor (TGF)β/Mothers against Decapentaplegic (SMAD) and mitogen activating protein (MAP) kinase pathways. A well characterized example is AP1 (Jun/Fos) regulation through extracellular signal-regulated kinase (ERK)/MAP kinase signaling. In this case, mitogen stimulation leads to the phosphorylation of ERK1/2, causing it to translocate into the nucleus. Once there, phosphorylated ERK1/2 binds to lamin A and phosphorylates c-Fos, which is normally sequestered at the nuclear envelope through interaction with lamin A. The phosphorylation of c-Fos causes its release from the nuclear envelope, allowing dimerization with c-Jun and activation of AP1 immediate-early genes [90]. Another example is the regulation of SMAD proteins, which mediate signaling downstream of TGFβ [91]. Following induction, SMADs are phosphorylated by TGFβ-receptor kinases, which stimulate their binding with co-SMADs, accumulation in the nucleus, and assembly with gene-specific transcription factors. A-type lamins modulate SMAD activity by binding to SMADs and promoting inactivation through their sequestration at the nuclear envelope. A-type lamins can also bind the SMAD antagonists MAN1 and PP2A, which dampen SMAD activity through sequestration and dephosphorylation [92].
Several lines of evidence support the view that lamins mediate transcriptional regulation. Developmentally associated changes in lamin expression often coincide with increased RNA polymerase II activity and accumulation of cell-type-specific transcripts [93]. Disruption of lamin organization, by expressing dominant-negative A-type lamins, inhibits RNA polymerase II transcription and perturbs the localization of the initiation factor TATA-binding protein [94, 95]. Lamin A/C associates with numerous transcriptional regulators, either directly or indirectly, including Rb, Gcl, Mok2, cFos and Srebp1 [96]. The transcription factor Oct-1 is sequestered at the nuclear envelope through associations with lamin B1, which is important for its regulation of oxidative stress gene expression [97]. Thus, lamins bind many transcriptional regulators and can affect gene expression by sequestration of these factors or by influencing the assembly of core transcriptional complexes [90, 97].
Lamins have also been implicated in replication. In assembly systems, lamin-depleted Xenopus nuclear extracts produce nuclei that are no longer competent to replicate their DNA [60, 98]. Additional support comes from an observed colocalization of lamins with sites of bromodeoxyuridine incorporation and at replication foci with proliferating cell nuclear antigen (PCNA) [99–101]. Expression of dominant-negative lamin B mutants, lacking the central rod domain, has been reported to inhibit DNA replication [102–104].
About 90% of known disease-associated polymorphisms are missense mutations, which are distributed throughout the lamin A/C protein [110]. A clear genotype-phenotype relationship has not emerged despite the description of over 1,000 sequence polymorphisms and about 350 disease-associated mutations (Figure 6). The creation of mouse models based on laminopathy mutations has provided some clues [111]. Efforts to unravel and explain the pathophysiological mechanisms are possibly confounded by largely unexplored genetic modifiers [112–114].
In contrast to numerous LMNA-related diseases, only two diseases are reported to be associated with mutations in the LMNB1 and LMNB2 genes. A duplication of LMNB1 resulting in higher LMNB1 dosage/expression in brain tissues is associated with the neurological condition autosomal-dominant leukodystrophy [107]. Several rare LMNB2 missense mutations are purportedly associated with acquired partial lipodystrophy [106]. The finding that expression of at least one B-type lamin in mammalian cells is essential for viability, and their ubiquitous expression, might explain the relative paucity of LMNB-associated diseases [10]. This seems to be the case because homozygous mice carrying insertional mutations in LMNB1 die at birth with lung and bone defects. Mice deficient for lamin B2 also die postnatally and display a lissencephaly phenotype, due in part to disrupted nuclear movement that is linked to defective neuronal migration [115].
The pathological mechanisms of these diseases remain obscure, although several models have been proposed. In a structural model, expression of lamin A/C variants causes nuclear fragility and increased sensitivity to physical stressors [116]. Other models have focused on the cellular roles of lamins, suggesting that LMNA mutations alter normal gene expression profiles, either directly through chromatin interactions or indirectly by disrupting protein-protein interactions [116]. One challenge has been to adequately explain how ubiquitously expressed proteins give rise to tissue-restricted diseases. The tissue-specific lamin A/C model predicts the existence of tissue-specific lamin A/C partners whose interaction is disrupted by particular lamin A protein variants.
Lamins are misregulated in some cancers, possibly making them useful as biomarkers. A-type lamin expression is decreased by about 80% in small-cell lung cancer lines but is high and unchanged in non-small-cell lung cancer lines [117]. Similarly, in primary lung carcinomas, primarily A-type but also to some extent B-type lamins show reduced expression [118], and both A- and B-type lamins are undetectable or reduced in most primary colon carcinomas, adenomas and primary gastric cancers [119]. However, reduced lamin expression does not always correlate with cancer tissues. Lamin A/C showed higher expression in cutaneous squamous cell carcinomas than in normal skin [120, 121]. Paradoxically, the absence of lamin A in basal cell carcinomas is correlated with rapid tumor proliferation rates, whereas the absence of lamin C is correlated with a slower proliferation rate. Lamin A is reported to be a promising biomarker for grading prostate cancers and may aid in prognosis [122]. In addition, increased levels of A-type lamins in colorectal cancer tissues correlates with a twofold increase in cancer-related mortality [123]. Lamin B1 is upregulated in hepatocellular carcinoma tumors and correlates with tumor size, stage and nodule number [124]. Furthermore, elevated levels of plasma lamin B1 can predict early stage hepatocellular carcinoma and might also prove to be a useful clinical biomarker for colorectal cancers [124, 125].
As architectural proteins of the nucleus, the lamins are positioned at the intersection of numerous diverse nuclear processes. Lamins are among the most prominent and best studied proteins in animals, yet many of their properties remain unknown. The lamin protein family is especially intriguing in light of its association with a large number of human diseases. Unraveling the basic functions of lamins will be essential to shed light on the molecular mechanisms of these diseases.
The meshwork of 10 nm filaments is the functional entity of lamins that must be understood if we are to understand different lamin properties and the consequences of lamin mutations. Already, some disease-associated lamin mutations are known to affect lamina formation [126]. Defective lamin assemblies may ultimately have an impact on the mechanical properties of the nucleus and/or interfere with nuclear processes, including signaling, nuclear import, transcription, DNA replication and DNA repair. A better understanding of the composition of the lamina and the influence of different lamin isoforms on its formation and function will provide additional important clues. Perhaps the most important goal will be to understand the tissue-specificity of lamins. Why do some LMNA mutations affect a particular tissue or subset of tissues despite near-ubiquitous expression of lamin A in all tissues? And why do different LMNA mutations manifest as dramatically different diseases?


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Publications (12)22.94 Total impact
Article: ChemInform Abstract: Characteristics of the High-Tc Superconducting Bi-Pb-Sr-Ca-Cu Oxides Derived from an Ethylenediaminetetraacetic Acid (EDTA) Precursor.[Show abstract] [Hide abstract]
ABSTRACT: In this paper the modified sol-gel method using ethylenediaminetetraacetic acid as a chelating agent to prepare high-T{sub c} superconducting Bi-Pb-Sr-Ca-Cu oxides is reported. Results revealed that the desirable Bi-based compounds can be acquired by such a process with a high percentage of the 110 K phase and a T{sub c} (zero) of 108 K. On the other hand, a new method is proposed to quantitatively evaluate the volume fraction of the 110 K phase in Bi-based superconducting materials, mainly composed of 85 and 110 K phases. That is a lever-rule type of relation, V = (Y {minus} 29.07{degrees})/ (28.81{degrees} {minus} 29.07{degrees}), where V is the volume fraction of the 110 K phase and Y = 20 for the X-ray diffraction peak emerging at about 29{degrees} with a CuK {alpha} radiation source and 28.81{degrees} {le} Y {le} 29.07{degrees}. The volume fraction of the 2223 phase estimated in this way is more reliable than that estimated by measuring the area ratios of XRD peaks and it is expected to be even more reliable than those derived from conventional methods based on perfect diamagnetism.
Article: Paramagnetic Meissner effect of high-temperature granular superconductors: Interpretation by anisotropic and isotropic models[Show abstract] [Hide abstract]
ABSTRACT: The field-cooled magnetization of high-T c superconducting ceramics measured in low magnetic fields exhibits the paramagnetic Meissner effect (PME), i.e., the diamagnetic signal initially increases with decrease in temperature but reaches a maximum at temperatureT d and later decreases with decrease in temperature. Even in some samples the signal is ultimately able to transform inversely into a paramagnetic regime once the sample is cooled below a temperatureT p as long as the applied field is sufficiently small. This PME has been observed in various high-Tc cuprates and is explained by disparate aspects. An anisotropic model, in which the granular superconductors are assumed to be ideally anisotropic, was first alternatively proposed in the present work so as to theoretically account for this effect. On the other hand, an isotropic model, suitable for granular superconductors with randomly oriented grains, was proposed to deal with the samples prepared by a conventional solid-state reaction method. The anomalous magnetization behavior in the present model was demonstrated to be the superposition of the diamagnetic signal, which occurs as a result of the intragranular shielding currents, over the paramagnetic one due to the induction of the intergranular component induced by these currents where the intergranular one behaved as the efective pinning centers. The PME was demonstrated by this model to exist parasitically in granular superconductors. This intergranular effect is therefore worthy of remark when evaluating the volume fraction of superconductivity for the samples from the Meissner signal, in particular, at a low magnetic field.
Article: Double resonant behavior of microstrip ring resonator in Tl‐based high Tc superconducting films[Show abstract] [Hide abstract]
ABSTRACT: High T c Tl–Ba–Ca–Cu–O superconducting thin films have been made by the dc magnetron sputtering followed by postannealing. In this study, a Tl‐based microstrip ring resonator was fabricated by using standard microelectronic photolithographic patterning and wet chemical etching. Experimental results indicated that these ring resonators exhibit the best unloaded Q of 3269 at its resonant frequency of 3.35 GHz and some other samples display the double resonant behavior at 77 K. The frequency difference of the double resonant peaks depends on the input microwave power, and the splitting is ascribed to spatial variations in the film microstructure. The physical properties of the films are about 1 μm thick, as high as 105 K transition temperature, and greater than 105 A/cm2 current density at zero magnetic field and 77 K. © 1994 American Institute of Physics.
Article: Growth parameter effect in superconducting YBa2Cu4O8 thin films by d.c. magnetron sputtering[Show abstract] [Hide abstract]
ABSTRACT: High- T c YBa2Cu4O8 (124) thin films have been made by d.c. magnetron sputtering deposition on (100) MgO substrates. The effect of several processing variables, including the ratio of oxygen to argon, total pressure, and substrate temperature, on the superconducting properties of the thin films, were systematically investigated. The as-prepared films annealed in flowing oxygen at 800C for 4 h under ambient pressure obtained nearly phase-pure 124 and exhibited superconducting onset transition at 75 K.
Article: Interpretation of the anomalous field-cooled-magnetization behavior of high-temperature granular superconductors at low magnetic field[Show abstract] [Hide abstract]
ABSTRACT: The field-cooled magnetization of high-[ital T][sub [ital c]] superconducting ceramics measured in low magnetic fields has exhibited an unusual phenomenon, i.e., the diamagnetic signal initially increases with a decrease in temperature but reaches a maximum at temperature [ital T][sub [ital d]] and subsequently decreases with a decrease in temperature. In some samples the signal could even transform inversely into a paramagnetic regime once the sample was cooled below a temperature [ital T][sub [ital p]], provided the applied field was sufficiently small. This phenomenon has been observed in various high-[ital T][sub [ital c]] cuprates and been explained with different viewpoints. An alternative theoretical model was proposed in this work to account for these phenomena. The anomalous magnetization behavior in the present model was demonstrated to be a superposition of the diamagnetic signal, which occurs as a result of the intragranular shielding currents, and the paramagnetic signal, due to the induction of the intergranular component induced by these currents. The intergranular effect was demonstrated by this model to exist in granular superconductors. This intergranular effect would therefore be considered in evaluating the volume fraction of superconductivity for the samples from the Meissner signal, in particular, at a low magnetic field.
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ABSTRACT: Pb-doped Bi-Sr-Ca-Cu high-Tc superconducting oxides have been prepared by a modified sol-gel process via the EDTA route. Upon decomposing the X-ray photoemission spectrum of the Cu 2p3/2 core level of the superconducting oxide into three components Cu1+, Cu2+ and Cu3+, we have found an obvious trend: the corresponding [Cu1+]/[Cu2+] ratio increased as more 110 K phase was formed in the sample. According to this trend, a defect model was proposed; it can reasonably explain some previous experimental results, such as a reduced oxygen atmosphere sintering, which effectively facilitates the formation of the 110 K phase, and the coexistence of copper and oxygen vacancies in Bi-system superconductors, observed by high-resolution transmission electron microscopy. On the other hand, the dimerization of holes in oxygen sites was also suggested to be a possible mechanism responsible for the increase in the ratio of [Cu1+]/[Cu2+].
Article: Effect of Ca2PbO4 Additions on the Formation of the 110 K Phase in Bi-Pb-Sr-Ca-Cu-O Superconducting Ceramics[Show abstract] [Hide abstract]
ABSTRACT: The growth of the Bi 2 Sr 2 Ca 2 Cu 3 O x phase in the high T c superconducting Bi‐Pb‐Sr‐Ca‐Cu‐O system through reacting Bi 2 Sr 2 CaCu 2 O x with Ca‐ or Cu‐rich intermediate phases, Ca 2 CuO 3 , CuO, and Ca 2 PbO 4 , has been studied. X‐ray diffraction and electrical and diamagnetic analyses revealed that the interaction and interdiffusion of these intermediate phase led to the formation of a high percentage of the 2223 phase and a sharp single‐step superconducting transition at T c (R = 0) = 108 K. Also, Ca 2 PbO 4 proved essential for accelerating the growth rate of the 110 K phase from the 85 K phase.
Article: Synthesis and characterization of Bi-Pb-Sr-Ca-Cu-O superconductor via ethylenediamine chelating
Article: Synthesis of High-Tc Superconducting Bi-Pb-Sr-Ca-Cu-O Ceramics Prepared by an Ultrastructure Processing via the Oxalate Route[Show abstract] [Hide abstract]
ABSTRACT: The oxalate precursor yielded by a sol-gel processing can be pyrolysed and oxidized at 840 C for 40h into the desired high-T c superconductor in the lead-doped Bi-Sr-Ca-Cu-O system withT c(onset) = 140 K andT c(zero) = 104K. The mechanisms of the sol-gel reaction were monitored by analysis of Fourier transformation infrared (FTIR) spectroscopy. Moreover, identification of the various phases existing on the specimens after firing at selected temperatures, was made by analysis by FTIR spectroscopy and X-ray diffractometry. Based on the experiment results, the mechanisms of forming Bi2Sr2CaCu2O8+ (phase 2212) might be identified as the reaction of Bi2Sr2CuO6+, Ca2CuO3 and CuO at 800 C. Furthermore, Bi2Sr2Ca2Cu3O10+ (phase 2223) might be synthesized by the reaction of phase 2212, Ca2CuO3 and CuO at 840 C. Ca2PbO4 found in lead-doped materials may catalyse the formation reaction of Ca2CuO3 at 650 C and play a role of a flux to fuse Bi2Sr2CaCu2O8+, CuO and residual Ca2CuO3 and then improve the further synthesis of Bi2Sr2Ca2Cu3O10+ at 840 C.
- [Show abstract] [Hide abstract]
ABSTRACT: Samples of Bi(Pb)-Sr-Ca-Cu-O oxide were synthesized by means of a pyrolyzed technique using nitrate solution. The zero resistance at 125 K has been observed, but it could not stable in cooling-heating temperature circles. Finally, the zero resistance (Tc) was down to 102 K and the susceptibility measurement revealed a sharp transition at 110 K.
Article: Preparation of High-Tc Duperconducting Oxide in the Bi-Sr-Ca-Cu-O System by Oxalate Gel Processing[Show abstract] [Hide abstract]
ABSTRACT: The high-Tc superconducting oxide in the Bi-Sr-Ca-Cu-O system, with superconducting transition temperature at about 80 K, has been fabricated by the sol-gel method using oxalic acid and nitrates as starting materials. Compared to the conventional solid-state reaction method, this chemical technique offers less fabricating time and lower sintering temperature to get a homogeneous superconductor. Thermal analysis, infrared spectra and X-ray diffraction data indicate that the mechanisms of decomposition and phase transformation of specimens prepared at various temperatures are greatly different.
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National Chiao Tung University
Hsin-chu-hsien, Taiwan, Taiwan
- Department of Electronics Engineering

subset: commoncrawl


text:
Lessons on The Loss of a Son
This time last year I received that phone call that every parent dreads and while other parents were preparing for graduation, proms, weddings and family reunions, I was preparing for a funeral. My 27-year-old son, Kyol had died in a car accident along with two other promising young men. Since that day, I have talked very little about it. I have talked very little about it because what do you say anyway, because it won't change anything, because you don't want to be made to feel like a victim and my personal favorite, because there's something deep inside that isn't quite ready to give up on the thought that this is all just a sick joke and any moment your child will come walking through the door. Well, of course I know Kyol isn't coming back but I am learning a lot about life and about myself. I thought sharing some of what I am learning would help someone else as they go through the difficulties and even tragedies of their life. There are many lessons, but here are five.
It's a short life
The first and obvious lesson is that life is shorter than we realize. Who doesn't know this, right? But in actuality few of us live like this is indeed the case. Take it from a dad who has preached his son's funeral, committed his body to the ground, pronounced the benediction and helped cover the grave with dirt – You don't have time for some of what you are doing. You don't have time to argue. You don't have time to be bitter. You don't have time to be jealous. You don't have time to be petty. You don't have time to work all the time. You don't have time to not say, "I love you." You don't have time to live someone else's life. You don't have time to act like you don't love when you really do. You don't have time to be unforgiving. Be more selective with how you spend everyday and with whom you spend it because you don't have time to waste.
Sorrow keeps showing up
Sorrow has a lot of faces (guilt, anger, confusion, regret, loneliness) and for all those people that tell you, "It's going to get better", well – THEY LIED. It doesn't get better. It doesn't go away. What will happen is that God will show you over and over again the separate miracles that are a result of your sorrow. These miracles won't ever replace the sorrow but they will give you something more life giving to focus on and you should do exactly that – focus on those separate miracles and stop waiting for the sorrow to check out.
Strength is available
The truth is sometimes a contradiction. Here is the truth. "We are always and at the same time stronger than we realize and not as strong as we thought yet always as strong as we need to be." – G. Allow me to give you permission to just be you. Forget trying to be strong. Just be you. The notion of, "when I am stronger then I will…." is a myth. Strength is added as we go. As you go back to your life, your job, your children, your dreams, God will provide you the strength you need.
Sight can't be selective
The first time I saw my son was moments from his birth. Ten fingers, ten toes, healthy and quite perfect. The last time I saw my son was in a body bag with a charred body, only recognizable by his dad. I have no regrets in unzipping that body bag, after having been warned that I would never forget what I was about to look at. Rather what I would never forget is what I said to my brother who stood there with me. Three words – "That's my son!" These glimpses or views of my son reminded me of life and how we should NOT see people. Too often we see people in terms of events and not in terms of humanity and relationship. We see the greatest successes or greatest failures in a person's life and then use those events to define them. Remember King David in the Bible? We define him in terms of Goliath (success) or Bathsheba (failure). But in between those events was the real man – "a man after God's own heart." It is the memory of the "in-betweens" that we find life and joy. Stop viewing people from the lens of birth and death because God always sees us as his child.
God's sovereignty is a guarantee
God is still God and He is still a good God. I wouldn't want his job. I can barely hold my little world together so it hardly seems feasible to question He who has the whole world in His hands. When I consider the totality of life, I must confess, "God is still totally awesome."
Perhaps, you can add to my experience and even help me or others. What lessons have you learned during your greatest loss?
I welcome your feedback.
The Round Table Interview with Dr. Robert Smith
Welcome to The Round Table. At the Round Table I share interviews with prominent personalities in various industries and disciplines to provide an "electronic convocation" where information and inspiration is imparted. At the Round Table in this episode is Dr. Robert Smith, Jr., Beeson Divinity School, Samford University, Birmingham, Al. Enjoy the interview. i welcome your feedback.
Why Time Matters
I have noticed with increasing regularity our innate disregard for time. It is evidenced by medical practitioners who make us wait way beyond an appointment time, people that show up late for appointments, children with consistent lateness to school, leaders who begin meetings late, churches who start programs beyond the time advertised, church goers showing up late for church or those who are always "running late."
More than 300 years ago, François Fénelon, a 17th century cleric, understood the value of time. He wrote, "Time is precious, but we do not know yet how precious it really is. We will only know when we are no longer able to take advantage of it…. Liberal and generous in every way, God in the wise economy of his providence teaches us how we should be prudent about the proper use of time. He never gives us two moments at the same time. He never gives us a second moment without taking away the first. And he never grants us that second moment without holding the third one in his hand, leaving us completely uncertain as to whether we will have it." A.W. Tozer wrote, "Time is a resource that is nonrenewable and nontransferable. You cannot store it, slow it up, hold it up, divide it up or give it up. You can't hoard it up or save it for a rainy day–when it's lost it's unrecoverable. When you kill time, remember that it has no resurrection."
Time is precious and our most valuable commodity. Yet, as important as it is we seem to have a consistent disrespect for it. We use expressions like, "I'm just killing time" or "I'm just wasting time." It is not until we are talking about time ending that we begin to quantify it, which is when we begin to say things like, "His days are numbered." In all actuality our days have always been numbered. Literally every day, hour and minute of our lives should be numbered.
Ask a student who has failed a grade how important a year is; a mother giving birth to a premature baby how important a month is; a businessman whose flight was delayed how important an hour is; a man who had a heart attack requiring CPR how important a minute is; a person barely missing a head-on collision how important a second is or an Olympic athlete missing a gold medal how important a millisecond is.
Time matters because:
- It is a proof I live with principles. Time comes from God. It is a gift. It is so much of a gift that we call the very moment we are living in a "present." A person who wastes time is wasting or not caring for a gift. If we can't be trusted with time it can be easily argued that we can't be trusted with money, gifts or opportunities. Being chronically late may be saying, "I can't be trusted." When we schedule an appointment we are establishing an opportunity to show that we are capable of doing what we say we will do. When I say, "I will meet you at 3:00 pm" and we show up at 3:15 pm it may be saying, "Don't believe what I say."
- It is proof I want to see progress. There can be no progress as long as we procrastinate. As we learn to live in the moment it becomes a catalyst to propel us into greater things in the future. The best predictor about tomorrow is my management, stewardship and decisions today.
- It is proof of how I see people. People are the prize and they should matter to us enough to give them our time, be on time and give us undivided time. When we give someone our time we are saying, "You matter to me because I am giving you what I can never be given back." There will always be something else to do, somewhere else to be, an email or text message to check or a Facebook status to "like."
- It is proof I have priorities. Saying, "Yes" to an activity, meeting or commitment is also saying "No" to another. Our calendar is a statement that we will not allow the moment to crowd out the important and that we are not victimized by the "tyranny of the urgent." Priorities will always be scheduled and when they are we don't miss those appointments because we have already determined it to be important to us. We don't just miss dinner with the family, miss church, miss a meeting or miss a rehearsal but rather have chosen to not see it as a priority.
- It is proof I am clear on my purpose. When we are certain of what our God given assignment is we are less likely to accept meaningless and unproductive invitations. Our activities and commitments should strengthen and support our ultimate goals.
- It is proof that I am planning. Technically we don't manage time we only manage ourselves. Stop saying, "I don't have enough time" because we have as much as everyone else. Instead of starting with tasks, start with time allotments and plan what is needful and impactful for your life. Plan to be with God. Plan to be with family. Plan to be happy. Plan to finish school. Plan to retire. Plan to go to the doctor. Plan to take a vacation. Plan to sleep in. When we don't plan for ourselves others are happy to do it for us and that can lead to a rather unfulfilling life.
God the provider of our time best communicates the urgency and importance of our time. Psalm 90:4 tells us, "For a thousand years in your sight are like a day that has just gone by, or like a watch in the night." A "watch" was equivalent to three hours. If normal life expectancy is 70 years (Psalm 90:10) and a thousand years equals three hours, we find the following:
70 yrs. x 3 hrs. /1000 yrs. x 60 min/hr. = 12.6 min = 12 min 36 sec. So the next time you are late remember we only have 12 minutes and 36 seconds anyway.
Don't let a life end waiting on you.
Why do you think time matters? I welcome your feedback
The "WELLS" we drink from
Wells are not something we think about because we have ample clean water in this modern day culture of ours.
A well is basically a hole that has been drilled, bored or dug into the ground to access water. One of the first steps in establishing a healthy community is to ensure access to clean water. This clean water is necessary for drinking, sanitation and for irrigation. This requires someone dig a well, the people use the well and the well be protected from contamination and blockage. But my real interest in wells is not so much scientific or geological as it is metaphorical. I would have to credit former Morehouse College President Dr. Robert Franklin as the one who first got me thinking about wells when he established the expectations that all Morehouse Men must meet. Even in our daily conversations we subconsciously place a lot of emphasis on wells.
"All's WELL that ends WELL"
"He's alive and WELL"
"Leave WELL enough alone"
If we are going to do WELL, be WELL, represent WELL and finish WELL then someone is going to need to dig some WELLS, drink from those WELLS and maintain those WELLS. The Dominican priest and theologian Gustavo Gutierrez was correct when he said, "We Drink From Our Own Wells." Could it be that our society is not healthy because one of the first steps to being healthy is clean water and in this modern culture of digital media, entertainment and influence we have begun ignoring our wells? I guess it is indeed true that "you never miss your water until your WELL runs dry." What wells am I referring to?
Well ENGAGED – We must become more active and involved in our community and in the lives of our families. A lack of parenting coupled with complacency must be two of the more pressing issues of our day. When parents allow television programming to engage their child more than they do, there is a problem with the well. Television actually changes the way the brain develops, shortens attention span and even changes brain chemistry. Despite the digital craze around learning there is still no substitute for a caring adult in the life of a child.
Well EDUCATED – It is a "type of salvation." No, education can't get me to heaven but is sure makes the trip around earth a lot easier. The world is changing and we must keep pace. Education is vital to advance contributions to civic, political and community life. Education is necessary for its role in advancing social justice and to open the worlds of cultural and artistic excellence. Being well educated means being well read. It is too much we need to learn to ever have gaps of idle time. We should always have a book with us. Until we, as a society, value conjugating the verb " to be" as valuable as running a touch down, dunking a basketball or gyrating on stage then the water of a respectful, balanced society will not flow.
Well EMPLOYED – Work will always be a tool for life fulfillment. I am grateful for the work ethic instilled in me by my parents. It is this work ethic that breaks the spirit of entitlement and ensures that we contribute to our surroundings. Everyone should be required to do something in the place they dwell in. If everyone in the home benefits from the environment then each person should have a definite, measurable and active role to play while there. It is dangerous to raise children who will become adults with an unrealistic, unmerited expectation of a favorable outcome at the hands of someone else. Watch how easy it is for a person to eat your food and leave the plate on the table or to walk past something on the floor or to leave a bed unmade.
Well ENTRUSTED – Integrity is always going to be en vogue. Whatever we do we should do it well and to the best of our ability. We should finish what we start; return things where we got them; pay back the money we borrow; keep our promises; be punctual; not allow circumstance to dictate our behavior; and just learn to show up.
Well EXPOSED – There is more to life than the family, county, city or school I grew up a part of. Until we learn to value experiences more than things we will forever be stuck in a shallow world that only the least desirable fish swim in. Exposure, especially through travel is a means of personal development and aids us in both appreciating where we come from while simultaneously creating in us a desire for better.
Well EXPRESSED – Before people really know us all they can do is see us and hear us, so self-expression through our wardrobe and our words become paramount. We have always worn clothes so I guess this well has just become contaminated and is evidenced when pajamas are worn in public; underclothes are readily displayed; sunglasses are worn inside; women abandon dresses and men disdain a blazer and tie. Compare the attire and apparel of the college students sitting at the Woolworth counter in 1960 to protest segregation and the college student of today or the clothing worn while crossing the Edmund Pettus Bridge compared to clothing today while just crossing the street
Our words are representing us no better. We must be well spoken and strive for meaningful and valuable conversation learning how to effectively communicate our complex emotions and ideas.
Well ESTABLISHED – This means we must become grounded enough and stable enough to be able to give back to our society. Whether we are a Jew embracing the Tikkun olam (Hebrew: תיקון עולם) meaning "repairing the world" or "perfecting the world; " A Muslim paying Zakat (a proportion of surplus wealth which must be given on a yearly basis to poor and the needy) and voluntary charity; or A Christian loving our neighbor as ourselves and being our brothers keeper we all have a personal responsibility to be keepers of the wells that other people will drink from. When we are mindful of the wells we are digging and the wells we are drinking from I would imagine we could all say, "It is WELL with my soul."
What WELLS would you add to my list to ensure our society remain healthy? I welcome your feedback.
The Economic Impact of The Church
I have often said, "everyone in the community will not belong to our church but our church does belong to everyone in our community." I believe many churches feel this same way. This "giving back to our community" philosophy gives us our meaning for existence and forges a wonderful collaboration with the Faith community, families, Firms and Foundations. This collaboration or intersection between church and city, the sacred and secular results in a real economic value that has been empirically measured for the past 25 years and was the impetus behind the creation of the White House Office of Faith-based and Community Initiatives. For example, large churches increase property values –According to a large study (tracking over 5000 houses), houses within a half-mile of a large church generally experience a 6.27% increase in property value. A church with over 1500 attendees could easily draw 40 new families to relocate – especially so when a demographically young church moves into a city with below average home costs. (Carroll, Clauretie & Jensen), Journal of Real Estate Finance and Economics – University of Nevada in Las Vegas. Churches are statistically proven to decrease crime rates – particularly decreasing levels of assault, burglary, larceny (Bainbridge 1989), as well as drug use (Fagan 2006).
How is this tangible economic value realized? Well, cities are filled with people. These people must navigate their way through a web of careers, relationships and life experiences. It is much easier to navigate when support services are available. As people navigate through life the needs will be vast and varied – marriages will need saving, children will need teaching, teenagers will need tutoring, suicides will need averting and fathers will need mentoring. When these needs are met an "economic halo effect" is the result. What's it worth to keep a father active in a child's life anyway? The economic thinking is rather quite linear. If a man stops supporting his children, the mother becomes the primary provider for the family. Statistically, the need to use subsidies or government services is greatly increased. Services like before school programs, day care and after school programs become more essential. Depending on the nature of the father's absence (i.e. divorce, imprisonment, death), his children, particularly boys, will need counseling or the aid of government services to become productive and contributing members of society. Without these support services, the children may likely fall into a criminal lifestyle which produces an economic strain on the community. Additionally, the diminished income resulting from the father's absence could mean that as the children graduate high school and pursue college or trade schools, they must incur greater debt to finance their education. This increased debt will result in less local purchasing power which add up to real tangible dollars taken away from the community. Of course, there is an option. The church could intervene by offering programs and services to avert that father's absence. Dr. Ram Cnaan, Professor and Director of the Program for Religion and Social Policy Research of The University of Pennsylvania has done extensive research on this topic and his research has concluded a rather startling outcome – "When measured in terms of dollars and cents, churches provide greater economic benefit and health to the community per capita than any other business or industry."
Examples of how this economic benefit is generated:
- Weddings
- Funerals
- Baptisms
- Artistic performances
- Charter Schools
- Counseling programs
- Operating budgets
- Salaries of staff and wages for building repairs (roofers, plumbers, electricians, etc.)
- The monetary value of goods that the market does not price
- Rehabilitation
- Responsible parenting
- Neighborhood pride
- Social service delivery
- Playgrounds
- Recreation space
- Volunteer hours
- Preventing suicide
- Helping people gain employment
- Crime prevention and re-entry
- Ending drug and alcohol dependence
- Enhancing health
- Preventive health
- Teaching pro-social values to children
- Teaching youth civic behavior
- Naturalization assistance
- Caring for the elderly
- Preventing divorce
- Ending abusive relationships
- Job training programs
- Community development corporations
- Businesses incubation
As local churches work more in tandem with the community around it, it becomes clear that congregations are not insular clubs that are unconcerned about the rest of a community but rather assets that benefit the community significantly and are therefore worthy of support.
The contributions of local congregations benefit individuals, local business; the community at large and local governments and by taking a quantitative approach the economic impact of the local church is clearly seen. So, for every dollar given, donation received, offering provided, rezoning application approved, variance on a building permit granted, and foundation grant given thank you for helping us fund the needed programs and services that create a quality of life for all our residents.
What economic impact do you see local churches providing? I welcome your feedback.
Biblical Money Management
Word Tabernacle 10th Anniversary Video
Christmas and Racial Reconciliation
Race has always been a part of all our lives. For that reason if no other it will remain both highly debated and widely misunderstood. It will always be an emotional issue. It's near impossible to celebrate Christmas and not consider race. The Christmas saga is widely racial as it is the story of the birth of the mixed racial Savior of the world. A read through the genealogy of Jesus would reveal within his bloodline are Canaanites, Sodomites, Hittites and Jews. No wonder Paul writes to the church in Galatia that in Christ there is no distinction between race, class or sex. Yet, our nation and our communities are re-segregating around issues of race, class and sex… while the evangelical faith community is largely silent.
Silence is dangerous because it opens a window of opportunity for those with an agenda and in need of a platform to facilitate the conversation and further widen the distance between us. The church cannot be silent during this hour.
Recent stories spanning, Missouri, New York City and Cleveland have sparked a national conversation. What is alarming is these stories have proven we do not live in a post racist America. Most whites view the problem as circumstance while blacks view it as systemic. The difference in our views is simply a matter of experience. Whites and blacks have different experiences with law enforcement. Pragmatically speaking both whites and blacks must share in a healthy exchange of listening to one another. White people must stop defending the systems that protect and serve them while ignoring that many of those systems have a racial bias. To say, "I am not a racist" while ignoring systemic racial bias is a contradiction. Much of this bias comes from our white pulpits and community leaders that seem incapable of admitting selling unlicensed cigarettes while posing no threat hardly qualifies for the death sentence. Likewise, Black people have a role to play. Blacks must stop "cherry-picking" crimes against the black community. To boycott whites for KKK behavior and ignore blacks who shoot up their own communities, call each other "nigga" and perpetuate stereotypes hardly creates public trust and credibility. In similar fashion to white America, much of this perspective is facilitated amongst community and faith leaders. To show no interest in a city or a community until it creates a big enough platform to warrant involvement does not exude effective leadership.
- To celebrate the birth of Jesus who dies that the demands of justice might be met (for the wages of sin is death) yet ignore the scales of injustice is not Christmas.
- To celebrate the birth of Jesus who would live to shed his blood that we might be reconciled to a Holy and loving God as the ultimate act of grace and we not exhibit grace is not Christmas.
- To celebrate the birth of Jesus who survived a government policy of male genocide while ignoring the fact that black males are far more likely to be sentenced, convicted, executed and murdered than white males is not Christmas.
- To celebrate the birth of Jesus who would later proclaim, "I have come that you might have life" and we not desire all people of every background have a chance at life is not Christmas.
- To celebrate the birth of Jesus who we are to be crucified with so that we no longer live but Christ in us and still allow the labels of Black, White, Democrat, Republican, Conservative or Liberal to be our primary identity is not Christmas.
America once again is reminded that at the heart of our skin problem is a sin problem. This is good news during this holiday season because we know the answer to the sin problem is Jesus Christ. As we celebrate the birth of Jesus may we not misrepresent His birth in the eyes of a world that desperately need him.
Only under the Lordship of Jesus Christ can the cultural and contextual cloudy lenses of class, sex and race by which the tragedies of Ferguson and Long Island are viewed can be brought into its clearest focus.
What are your thoughts on the issue of racial reconciliation during this Christmas season and beyond?
Determined To Thrive
For a season of my life I worked as a Pharmacy Technician in a local hospital while paying my way through college. My job was to fill prescription drug orders for inpatients. One of my assigned areas was the Neonatal Intensive Care Unit. It was not uncommon to read on the patient record the diagnosis, FTT. FTT was short for Failure To Thrive. When a child is below a healthy weight and shows evidence of being underdeveloped he/she is given this diagnosis. Typically FTT is discovered during infancy and can be a result of any number of causes. What is interesting is that even if you have many healthy organs and normal operating systems, the entire person is still considered FTT.
Such is the case with many of us. We have areas in our lives where things are in order and operating in a healthy manner yet there is still that underlying issue that has consistently gone unaddressed and as a result we fail to thrive. Consider the potential impact of a toothache. Your heart, lungs and every major organ in your body could be operating perfectly. But an aching tooth could easily render you ineffective, distracted and uncomfortable. In the same way we must address as a lifestyle our wholistic health. What does it mean to thrive? To thrive is "to increase in stature; grow vigorously; to prosper in any undertaking."
We are all familiar with the expression, "taking two steps forward and one back." Thriving is about addressing the entire person. Thriving is about ensuring we continue taking steps forward and when we must take a step back it is part of an intentional strategy to exponentially and synergistically improve our lives. Thriving is about cultivating the entire person, specifically:
- Spiritually because only a Biblically based value system and personal relationship with God is able to empower us in a way that stands the test of both time and eternity. Our value system cannot be built on the shaky foundation of culture, politics, race or socioeconomics. Only a foundation of truth is solid enough to not collapse under the weight of personal agenda, bigotry and injustice.
- Physically because God still places his Spirit inside of a body. When we are sick, tired or out of shape it has an adverse effect on how we perform tasks and responsibilities. What I put in my body; where I take my body; Who I let touch my body and what I do with my body all impact to what extent I thrive.
- Emotionally because it is unhealthy to ignore our emotions and they're ability to be used by God to assist us in decision making. Although we should not make emotional decision we should also not make decisions before we have taken the time to inventory, assess and address our feelings. Grief, anger, fear, joy, trust are all God given. Learning to process our emotions is a necessary practice.
- Socially because relationships matter. The state of our family matters, as do our friendships and casual fellowships. Those we spend time with have a powerful and valuable "banking property." We give them "card access" to our time, feelings, dreams, resources, ideas, experiences and mind and on a regular basis and in many instances a daily basis, transactions are being made. If we wouldn't trust a person to our ATM card with the pin we should question why we give them access to our personal resources that are much more valuable than money. Our time should be spent with those who already value themselves, are willing to make an investment in others and are willing to participate in a mutually beneficial relationship.
- Intellectually because good decision-making requires critical thinking and the ability to synthesize a variety of data. Reading and exposure to multiple facets of life and the world around us ensures we understand our options and the consequences to our choices.
- Financially because it costs money to live in this society. Without the ability to knowledgeably earn, invest, spend and give we place ourselves in a perpetual cycle of "time for money." Eventually we run out of money before we run out of time. The objective is for our money to outlast our time.
You might be now wondering, "How in the world do I balance all of this?" This is perhaps one of the most practical aspects of Christianity. Our Christian beliefs are holistic. We believe that everything is within the purposes of God and the care and growth of the total person is in perfect harmony with God's redemptive purposes. More and more I am convinced that we dishonor the name of Christ when we "cherry pick" the aspect of life we are most proficient at and ignore the others in some ritual of self-glorification. The man who manages his money wisely but ignores his obesity is no more justified than the man who is in great physical health but refuses to pay his debts. The church protesting abortion but ignoring racism and injustice is no more validated than the church protesting racism and injustice but ignoring abortion. The Deacon who teaches Sunday school but pays his employees poorly is no more justified than the member who misses Sunday school so they can work overtime. It is this lack of balance that is causing our failure to thrive.
Will you join me with a lifestyle change that will result in our determination to thrive?
What will you do to thrive? What area of your life is lacking and has the greatest potential to cause you to FTT?
I welcome your feedback.
God's Not Dead
Tonight our church featured for family night, the movie, God's Not Dead. I was grateful for those that attended. I highly recommend it to everyone whether you are a believer or not. I also think this is an excellent movie for middle and high school students but the entire family will benefit from the themes that are woven throughout. I'd like to share a few of those that were most evident to me.
God can fix anything. Everyone in the movie had some issue or challenge and the one deal changer in all of them was a legitimate, abiding relationship with God. The moment we allow God in He begins the process of setting in order anything that is out of order. It's almost as if He is waiting to be let in. We wrongly assume the relationship is wrong or the situation is wrong when in actuality it is simply devoid of God's presence and power. Doing things God's way results in great joy, peace and blessings.
God must be first. Several characters in the movie had to choose between family or friends and God. Admittedly, it is painful when those we care most for have differing opinions than we do regarding faith. What is evident is when we aim to please God he will ensure that the voids that are created are filled with something or someone far healthier for us. He also uses our faith as a tool to attract those we care so deeply for. We must worship with those closest to us but we must not worship those closest to us.
Don't make decisions out of fear. Fear is paralyzing. When the motivation of our decision-making is fear of being alone, fear of people not being pleased, fear of failure or fear of being ashamed then we have already greatly hindered God's work in us. God's love for us provides us with a faith not a fear in that love. We then have faith that we will not be alone, faith we will not be ashamed and faith we will not fail.
Forgiveness is powerful. It releases both the offended and the offender. Often we are unaware of the deep-seated oppression and bondage the offender is sitting with. In other words everyone is hurting. We cannot heal a negative action with another negative action nor can we deny the depth of hurt attached to what others do to us. The very act of forgiveness attaches a sense of worth which alone can motivate us to change in ways punishing people will never accomplish.
We must share our faith more. There are so many individuals and people groups that do not have a relationship with Jesus Christ. We must be willing to witness regarding Jesus not in a condemning or judgmental way but out of our own biblically based experience. There is power in personal experience and conviction, when we recognize our faith is more than feelings.
God's favor is real. What we often see as messy and hurtful are really disguises for the blessings of God. If we believe in God's goodness (God is good all the time and all the time God is good) then we know he will never give us less than what is good. There are moments when our prayer for healing is answered in sickness or even death. Moments when prayers of comfort result in moments of heartache only for us to discover that was actually the place of his favor and blessings.
Have you seen the movie? What did you learn? I welcome your feedback.


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Bold Monogram Personalized Wine Bottle Label
Personalized Wine Bottle Label
Transform any wine bottle!
Our exclusive Bold Monogram Personalized Wine Bottle Labels will transform an ordinary wine bottle into a one matching your party theme. Best of all, you can personalize the wine bottle labels with your own custom text and colors. The Bold Monogram Personalized Wine Bottle Labels are perfect for your wedding.
Labels are water resistant and are recommended for refrigerated use.
Wine Bottle Label features:
- Free personalization!
- Measures 3 1/4 inches wide x 5 1/4 inches high.
- Printed on white vinyl sticker material.
- Labels are water resistant.
- Recommended for refrigerator use.
Please allow ample time for delivery. Our ship date for this product is noted in your shopping cart. Many items are shipped separately, so please allow extra time for these items to arrive. Shipping charges are based on the value of the merchandise and not the number of shipments. For additional shipping information, please contact our Customer Service Department at (firstname.lastname@example.com or 1-800-314-8794).
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We stayed here as a result of reviews that we saw on Trip Advisor. A great advantage of this little cabin is that it is close to Door County Bakery. This cabin was as clean as any motel that we have stayed at and brings you back to travel in the 50's. They do have a TV which many motels... More
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Fragrance Fit for a Princess
Inspired by a night time stroll under a starry Mediterranean sky, Les Nuits d'Hadrien is a citrusy, spicy and warm. Wonderful in a sunny and warm summer evening: elegant and classic.
Weight: 3.4 oz
Special Shipping Information: This product may not be available for 1 or 2 day shipping due to federal regulations that require it to ship via ground ship methods only. This product can only be shipped within the 48 contiguous states.
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|Les Nuits d'Hadrien Eau de Toilette-3.4 ounces
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Philippines Drinking in Riches of Coconut Water
As the state legislature continues its current session, it's considering a number of topics raised in Governor Abercrombie's state of the state address. Next week, President Obama gives his state of the union speech. In a similar event in the Philippines, an unusual topic gained much attention: coconut water. HPR's Bill Dorman explains in today's Asia Minute.
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This week's performances are: THE UNFORTUNATES – A masterful musical by 3 Blind Mice, with a vibrant variety of American music styles in a world premiere production. KING LEAR – A riveting tragedy that is considered by many to be Shakespeare's greatest play. THIRD PERFORMANCE TBAAfternoon: Check-in at the historic Ashland Springs Hotel between 3:00-5:00 PM.Dinner: Enjoy a delightful dinner at the elegant Ashland Springs Hotel. The Hotel has a variety of deliciously unique salads, hearty soups, pasta dishes, and grilled options. Using fresh and local ingredients you'll find this to be a remarkable feast with a special Northwest flair.Evening: Get to know what this exciting week has in store! Meet your fellow Road Scholars and program staff during an informative overview of the program. Learn about the in-depth classes and fascinating field trips you'll be experiencing this week and prepare for Monday morning's first glimpse of the Oregon Shakespeare Festival campus. Come prepared with your questions about any of the fun events this week.
INTRODUCTION TO THE OREGON SHAKESPEARE FESTIVAL: Immerse yourself in theatre life with a viewing of an intriguing set change captured on film, followed by an inspirational presentation highlighting the spirit of the Oregon Shakespeare Festival. Learn about an infamous mishap and how the Ashland community came together to ensure that the show went on.Lodging: Ashland Springs HotelMeals Included: Dinner
PREVIEWS, REVIEWS, & STARS: These core classes of the program will be taught daily by an Oregon Shakespeare Festival actor who will be your guide for the week's performances, lead review discussions, and introduce you to several actors straight off the OSF stages.Lunch: Today lunch will be on your own to take advantage of more than 80 restaurants in Ashland. You'll find everything from sushi or traditional pub fare to fine dining in downtown Ashland.Afternoon: Explore the wonders of Southern Oregon or take in another show on your own at the Oregon Shakespeare Festival. Stroll through the beautiful parks of Ashland, visit the many galleries and shops downtown, sample your way through a handful of the 88 wineries in this up-and-coming wine region, or indulge in the sweets offered at Dagoba Chocolate in Ashland and Harry & David in Medford. Spend an afternoon in neighboring Jacksonville to enjoy the charming character of this old gold-rush mining town registered as a National Historic Landmark.Dinner: Meet back with the group after your afternoon's adventures and enjoy one of the many restaurants that Ashland has to offer. You might eat a stand-out meal at Standing Stone, which takes pride in sustainability and their use of local ingredients. All of their beef, chicken, and eggs are sourced from their own organic, free-range farm one mile from the restaurant. Relax in the fun atmosphere of a working brewery.Evening: PERFORMANCE: Formerly the New Theatre, renamed this year after the late OSF Development Director Peter D. Thomas, this theatre offers an intimacy and versatility in seating arrangements unique to each show. Tonight you will be seeing The Unfortunates. This masterful musical by 3 Blind Mice takes us through a vibrant variety of American music styles while telling a compelling story of humanity and compassion in this world premiere production.Lodging: Ashland Springs HotelMeals Included: Breakfast, Dinner
PREVIEWS, REVIEWS, & STARS: After a coffee break, explore more of the week's performance themes as you meet again with your OSF actor instructor. Relive the highlights from the play you watched yesterday, learn about the themes and setting of the play you will see today, and meet one of the many talented OSF actors.Lunch: Experience Oregon's oldest grape-growing wine region first hand with a fabulous tasting at a local winery. Learn about how the unique terroir of the Rogue Valley produces the conditions for a wide range of popular grape varietals. Linger awhile longer for a delightful lunch with your fellow participants.Dinner: Tonight dinner will be on your own to take advantage of more than 80 restaurants in Ashland. You'll find everything from sushi or traditional pub fare to fine dining in downtown Ashland.Evening: PERFORMANCE: TBALodging: Ashland Springs HotelMeals Included: Breakfast, Lunch
PREVIEWS, REVIEWS, & STARS: After a coffee break, return to the classroom for today's discussion of the Oregon Shakespeare Festival plays. Each year, almost 400,000 theatre patrons travel to Ashland to watch these award-winning shows. In this intimate class setting, review yesterday's performance, meet yet another special guest, and get ready for today's production with your OSF guide.Lunch: Enjoy a delicious meal at the historic Ashland Springs Hotel.Afternoon: PERFORMANCE: Formerly the New Theatre, renamed this year after the late OSF Development Director Peter D. Thomas, this theatre offers an intimacy and versatility in seating arrangements unique to each show. Today you will be seeing King Lear, a contemporary staging of this riveting tragedy that is considered by many to be Shakespeare's greatest play. NOTE: Contains some violence and sexuality.Dinner: Enjoy one of the many restaurants that Ashland has to offer. You might eat at Pasta Piatti, a local favorite in downtown Ashland where you'll find traditional and specialty Italian dishes. Enjoy your hearty meal in this cozy and welcoming setting.
Share your thoughts about this week's program with your new Road Scholar friends and highlight your favorite experiences.Evening: Return to the classroom to learn more about the OSF productions.
Class topics vary each week. Among others, subjects may include the costume design process, the life of an actor, how the stage manager runs the show, Shakespearean language and literary history, or how an actor researches a role.
Lodging: Ashland Springs HotelMeals Included: Breakfast, Lunch, Dinner
With an average snowfall of 44 feet, not all entrances are open year round. Roads can close from October to July. Rim Drive is typically open by the beginning of July. This 33 mile drive has spectacular viewpoints.
For the latest road, weather, and trail information please call (541)594-3000. Current conditions at the park, including web cams, road and facility status can be found on the "Current Conditions" page of their website.For additional information, visit: www.nps.gov/crla
For decades Jacksonville, which had become the county seat, flourished as the commercial and cultural center of Southern Oregon. It wasn't until 1884, when the railroad was routed through the neighboring town of Medford, did the prestige of Jacksonville begin to wane. As residents and businesses moved away to those communities along the rail lines, Jacksonville settled into a new role-that of an agricultural center.
The combination of the County Seat being moved to Medford in 1927, the Great Depression and World War II had serious economic impact on Jacksonville. But never a community to give in, residents and business leaders sought to preserve the heritage of Southern Oregon's first town. Although no longer a boom town, Jacksonville discovered a new way to lure those with the pioneer spirit, capturing it's colorful past and inviting a new generation of explorers to experience it.
The Britt Festival in Jacksonville is a must see when visiting this unique town. The festival began in 1963 with its first summer outdoor concert. Britt exclusively offered classical music until 1978 when they started to incorporate other world-class artists. With an array of performances, including the Classical Festival in the beginning of August, you won't want to miss these wonderful outdoor concerts.
In 1966, Jacksonville was designated a National Historic Landmark. Over 100 buildings in Jacksonville are on the National Register of Historic Places.
The information provided above is from www.jacksonvilleor.us. Call 541-899-1231 or visit the website for additional information.For additional information, visit: www.jacksonvilleor.us
The development of today's park began in 1914 with the hiring of John McLaren (also designer of San Francisco's Golden Gate Park) as landscape architect. Lithia Park embodies the distinctive characteristics of park design in the tradition of Frederick Law Olmsted. McLaren's landscape plan for Lithia Park was organic in layout, following the natural canyon of the water course. The plantings were naturalistic to the extent that native alders, oaks, conifers and madrones were incorporated, but other plants, such as willows, maples, sycamores, and numerous ornamental varieties were introduced and selected for hardiness, form and color. Once within the Park, the visitor can walk along the trail on the east side of Ashland Creek to the Park headquarters and obtain a map showing the location of both historic and more modern park features including a trail guide to the most significant trees throughout the Park.
Lithia Park is located at 59 Winburn Way in downtown Ashland and is open to the public. Trail guides and other booklets about the park can be obtained from the park office of Ashland Parks and Rec. Dept., open Monday-Friday 8:00 AM to 5:00 PM.For additional information, visit: www.nps.gov/nr/travel/ashland/lit.htm
The Rogue Valley Region of Southern Oregon has three distinct subregions for grapes: the Rogue River subregion along Interstate 5 from Ashland to Grants Pass, the growing area of the state with the steepest elevation; the westernmost Illinois Valley, at a high elevation and more heavily influenced by the marine climate of the Pacific Ocean; the smaller Applegate Valley, locus for part of the Southern route of the Oregon Trail, further inland and sheltered from Pacific marine air.
The Rogue Valley is the most elevated, warm and dry wine growing region in Oregon. Chardonnay, Riesling, Gewürztraminer, and Pinot Gris are grown in all parts of the Rogue. The inland subregions of the Rogue, including the Applegate Valley, have a dry and warm climate suitable for production of the best Bordelaise varieties such as Cabernet Sauvignon, Merlot, Semillon and Cabernet franc. The Illinois subregion is noted for its high quality Burgundian varieties Pinot Noir, Pinot Gris, Merlot and Chardonnay.For additional information, visit: www.winesoforegon.com/rogue-valley-wineries-vineyards.htm
This museum is a quick five-minute walk from Cox Hall.For additional information, visit: www.sou.edu/sma/


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ArcSoft ShowBiz
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ShowBiz 5 is perfect video editor and movie making software
Articles ArcSoft ShowBiz
ShowBiz 5 is a superb movie making application that lets you quickly and easily create movies, edit videos, and liven up your movie with tons of cool effects, and share via popular Social Media, mobile devices, and DVD/Blu-ray Disc™.
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Use Rotate & Flip to correct position and Crop & Trim to get rid of unwanted parts.
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ShowBiz 5 includes both a Storyboard and Timeline mode.
Arrange the clips and photos, add a transition, drop in cool effects and music in Storyboard mode.
Stretch the Timeline to add effects and audio at a precise point.
Hide a track to focus on a specific layer and mute the audio in Timeline mode.
Adjustable screen and thumbnails allows for easy viewing of multiple tracks and your source files.
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Supports left-right, top-bottom, and red-cyan formats.
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Export as a 3D file, or write to a DVD/AVCHD/Blu-ray disc.
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Gives you the tools to perfect your movie by adding a superb soundtrack.
Compose your ideal soundtrack using multiple audio tracks.
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1. Instant Share directly from cameras
2. Compose with Picture-in-Picture
3. Create 3D movies
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Review last updated: 23/10/13
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Garage Door Opening Sound Effect - Free Download
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Electric Garage door opening. You can clearly hear the electric lift motor running ad the screeching metal sounds as the door is moving and opening.
Garage Door Opening, 4.8 out of 5 based on 18 ratings
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Low-Quality mono .MP3 FileDownload Garage Door Opening Sound Effect- To Download: (Right Click > Save link as)
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What does TCGST stand for?
What does TCGST mean? This page is about the various possible meanings of the acronym, abbreviation, shorthand or slang term: TCGST.
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Tank Crew Gunnery Skills Test
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"TCGST." Abbreviations.com. STANDS4 LLC, 2016. Web. 11 Feb. 2016. <http://www.abbreviations.com/TCGST>.


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Nutritional Information
1. In a large bowl, with a mixer, beat 6 tablespoons butter and the granulated sugar until well blended. Add ricotta, egg, and 1/2 teaspoon lemon extract; beat until well mixed.
2. In a medium bowl, mix flour, baking powder, baking soda, and salt. Add to butter mixture, stir to mix, then beat until well blended.
3. Butter 14- by 17-inch baking sheets. Drop batter in 1-tablespoon portions about 1 1/2 inches apart on sheets.
4. Bake cookies in a 325° oven until golden brown, 20 to 25 minutes. If baking more than 1 pan at once, switch pan positions every 10 minutes. With a wide spatula, transfer cookies to racks.
5. Melt 2 tablespoons butter. In a deep bowl, mix butter, powdered sugar, 1/4 teaspoon lemon extract, and milk until smooth. One at a time, hold cookies by the edges and dip rounded tops into icing; set in a single layer, icing up, on racks and let stand until icing is firm, about 10 minutes. Serve, or store airtight up to 1 day; freeze to store longer.
Nutritional analysis per cookie.


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burn the witch ! by suikuzuWatch
©2014-2016 suikuzu
said the delphox
Because Greninja can suck it.
More like burning witch, which Delphox can be interpreted as.
asdgfasdgfasdgfasdgf So cute!!!
What does the fox say?
Actually the fox says: "Shut up! That song is annoying and it sucks and it's very offensive to foxes!"
So that means she weighs the same as a duck... she's a WITCH!
So fluffy-desu.
Love your take on her fur!
wow, really gorgeous !
Lovely one ^^
I love this pic. Delphox looks so cute!
Ah, I love this! The pose and expression are just great ♥
I miss your pokemans ; v ;
The title reminds me of the song Burn The Witch by Queens Of The Stone Age.
"We found the witch... may we burn her" quote comes to mind
In Soviet Kalos, witch burns you.
Ironic much! just made up my morning! and very cool artistry indead!
Burn them! Burrrn themmm! I am in love with how you made this, the color style and overall look of this is stellar!
I absolutely ADORE the pose, facial expression, and colors!
How ironic.
I like the fluffyness of the fur.
I like the fluffyness of the fur.
Aww! Silly Delphox. Love the coloring.
maaaan, thats some amazing colouring.
I love how you drew the fur!
Love the paws and the shading!
hypocracy huehuehuehuheuhue
Loving that pose! Good job!
wow its amazing!
Amazing work!
How adorable! Now if only they were this cute in game... (Still loves my Delphox dangit!)
Everything about this picture I love: the title, the description, the facial expression, the feet...everything!
Einfach nur geil
Delphox likes to see stuff burn ^^
no sui stop :c i will eat my screen if you post such well coloured art all the time ;_;
LOL But Delphox, you are based on a witch! XD But you're still cute.
rar rar raga rarrr cuteeee
Looks great with a pose like that.
Super cute!! I really love her pose
Delphox is a witch.
But she's our witch.