V(D)J

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Evidence for failure of V(D)J recombination in bone marrow pre B cells from X linked agammaglobulinemia

Evidence for failure of V(D)J recombination in bone marrow pre B cells from X linked agammaglobulinemia

representative of XLA pre-B cells. I report that LS-C mu is the predominant Ig molecule produced by XLA pre-B cells, with limited production of the D mu product of DJH intermediate stage of V(D)J recombination. Mature VHDJH recombinations were not detected with a variety of primers that amplify VH sequences. I conclude that XLA is associated with a limitation in V(D)J recombination […]

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The E<lambda>3-1 Enhancer is Essential for V(D)J Recombination of the Murine Immunoglobulin Lambda Light Chain Locus

The E<lambda>3-1 Enhancer is Essential for V(D)J Recombination of the Murine Immunoglobulin Lambda Light Chain Locus

Enhancers are essential for long range chromatin opening and the activation of V(D)J recombination at the antigen receptor loci. The murine immunoglobulin lambda light chain locus is a duplicated locus and, using a bacterial artificial chromosome spanning the 3’ half of the locus to generate transgenic mice, we have identified a critical enhancer element for lambda locus recombination. Four hypersensitive sites had been previously mapped downstream of the JC 1

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Off-Target V(D)J Recombination Drives Lymphomagenesis and Is Escalated by Loss of the Rag2 C Terminus

Off-Target V(D)J Recombination Drives Lymphomagenesis and Is Escalated by Loss of the Rag2 C Terminus

Tp53 / and Rag2 352/352 , Tp53 / mice revealed that, although off-target V(D)J recombination events are found in both geno- types, they are much more prevalent when Rag2 is C-terminally truncated. cRSSs identified in Rag2 352/352 ,Tp53 / tumors occur significantly more frequently outside H3K4me3-modified regions of the genome (as measured in normal pre-T cells) (Ji et al., 2010; Vigano et al., 2014) than those in Tp53 / mice. The significance of this bias is underscored by the fact that comparisons of a less specific ‘‘accessibility’’ (DNase I sensitivity and Rag2 binding) show inconsistent trends between genotypes and fail to reach statistical significance. These data establish a mechanistic link between the PHD domain located in RAG2’s C terminus, H3K4me3-modified chromatin, and suppression of off-target V(D)J recombination. The possibility of such a link has been suggested most recently in a biochemical study showing that RAG autoinhibition was relieved when the PHD finger of the Rag2 C terminus was allowed to interact with H3K4me3 peptides (Lu et al., 2015). The observations reported here support a role for H3K4me3-mediated reversal of autoinhibition in minimizing the oncogenic impact of faulty RSS recognition.

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Acetylation increases access of remodelling complexes to their nucleosome targets to enhance initiation of V(D)J recombination.

Acetylation increases access of remodelling complexes to their nucleosome targets to enhance initiation of V(D)J recombination.

We reported previously that histone acetylation stimulates V(D)J recombination in vivo but has no effect on RAG cutting on isolated mono-nucleosomes in vitro (18). Therefore, we firstly asked if acetylation enhances RAG cutting in vitro when arrays of nucleosomes are used as the chromatin template. We assembled plasmid DNA (pMAB2) carrying 12- and 23-spacer RSSs into highly acetylated or non-acetylated chromatin using Drosophila chromatin assembly extracts. These extracts were depleted of endogenous histones and subsequently ‘reprogrammed’ with non-acetylated or highly acetylated histones prepared from CV1 cells that had been either untreated or treated with the histone deacetylase inhibitor, trichostatin A (Figure 1A). Assembly results in highly chromatinized templates that contain physiologically spaced nucleosomes and a full complement of chromatin-associated proteins (27). Accurate comparison of RAG cutting on the acetylated and non-acetylated chromatin templates requires that both types of chromatin template have equivalent nucleosome density and spacing: Micrococcal nuclease assays confirmed that the nucleosome spacing was equivalent (average of 180 bp; Figure 1B). Further- more, our previous studies using psoralen-crosslinking and electron microscopy found that plasmids assembled with acetylated and non-acetylated histones that have the same superhelical density also contain the same absolute number of nucleosomes (27). Supercoiling analysis demonstrated that the plasmids used here were equiva- lently chromatinized with an average of 17 nucleosomes

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Transcription-coupled eviction of histones H2A/H2B governs V(D)J recombination.

Transcription-coupled eviction of histones H2A/H2B governs V(D)J recombination.

This process transiently exposes 35-40 bp of DNA, thus increasing the probability of the RSS being available for RAG cutting. H2A/H2B eviction occurs with a displacement time of approximately six minutes in vivo (Kimura and Cook, 2001); this fits well with our observed transient accessibility of the RSSs. We also suggest that the transient nature of this eviction is well suited to the regulation of V(D)J recombination: Accessibility of the RSSs for a protracted period risks too much RAG cutting and genome instability whereas too little accessibility would impinge on the efficiency of the recombination reaction. It also implies that only a limited number of RSSs will become available for recombination at any one time, thus reducing the risk of RAG cutting at multiple sites. The transient eviction also fits well with the requirement for the stochastic use of different RSSs: Each RSS has a chance of being accessible and bound by RAGs but this opportunity is short-lived. Also consistent with the stochastic nature of recombination, nucleosome mapping studies showed that RSSs do not occupy the same translational position on the nucleosome at either the J κ or J λ 1 regions, implying

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Nucleotide pool imbalance and adenosine deaminase deficiency induce alterations of N region insertions during V(D)J recombination

Nucleotide pool imbalance and adenosine deaminase deficiency induce alterations of N region insertions during V(D)J recombination

Plasmid constructs. The human TdT expression vector was con- structed by inserting a 1944-bp blunt-ended cDNA into the EcoRV site of the pCDNA3 vector. The Rag-1 and Rag-2 expression vectors have been described previously (22) and were obtained from M. Oettinger (Harvard University, Cam- bridge, Massachusetts, USA). The human pCJ and pSJ V(D)J recombination substrates have also been described previous- ly (23) and were obtained from M. Lieber (Washington Uni- versity, St. Louis, Missouri, USA). An F1 origin of replication was cloned in front of the pTrp promoter of both pCJ and pSJ to facilitate single-strand template isolation for sequenc- ing. pSJ undergoes deletion to retain a signal joint on the plasmid, and pCJ undergoes deletion to retain a coding joint. Cell culture and transfections. Jurkat (mature T), Nalm-6 (pre B), Molt-4 (immature T), Raji (mature B), KT-1 (pre T), and KE-37 (mature T) cell lines were maintained in RPMI medi- um supplemented with 10% FBS. For DNA transfections, cells in exponential growth at a density of 1 × 10 6 /ml were

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Genetic pathway to recurrent chromosome translocations in murine lymphoma involves V(D)J recombinase

Genetic pathway to recurrent chromosome translocations in murine lymphoma involves V(D)J recombinase

Following cleavage of antigen receptor DNA in SCID mice, the inability to efficiently rejoin DNA ends could potentially lead to illegitimate recombination. In SCID thymocytes, p53 is activated by DNA breaks, leading to early apoptosis (33, 43). In the absence of p53 function, SCID pro-B cells may survive longer, permitting Rag- mediated DNA breaks at the IgH locus to be rejoined by activities other than the DNA-PK complex. Such alterna- tive DNA repair pathways may be less stringent in prefer- entially rejoining antigen receptor DNA ends to each other than in involving another locus, leading to a higher frequency of chromosome translocations. In p53-deficient mice, which have normal lymphoid development, pres- ence of the DNA-PK complex may ensure efficient rejoin- ing of DNA breaks during V(D)J recombination so that unresolved DNA breaks are relatively rare. Our data con- firm previous observations that thymic lymphomas com- monly occurring in p53 –/– mice are not associated with

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Biophysics of V(D)J Recombination and Genome Packaging: In Singulo Studies on RAG, HMGB1, and TFAM

Biophysics of V(D)J Recombination and Genome Packaging: In Singulo Studies on RAG, HMGB1, and TFAM

At our concentrations of RAG1/2c and HMGB1, the binding events associated with RAG1/2c in the presence (or absence) of HMGB1 were relatively frequent however the downstream product of this binding, paired complex formation, was comparatively rare; in our experiment the bead spends just 4% of the total experiment time in the paired com- plex state. We directly observed paired complex formation on DNA substrates with both a 12RSS and 23RSS. We do not see evidence of this complex when only a 12RSS (or no RSS) is present and we confirm that the apparent length of the paired complex state is consistent with a tether that has been shortened by the 12/23 intersignal spacing of the substrate when using both a 1200bp and an 1800bp spacing. The paired complex was relatively short lived, which is at odds with kinetic models derived from cleavage experiments with oligonucleotide RSS substrates that predict slow hairpin formation with a long lived paired complex [26]. Furthermore, the paired complex did not always result in a cleaved DNA product; 72%of paired complexes do not lead to DNA cleavage. Our preliminary conclusion from this reversibility is that, in vivo, the RAG recombinase could sample multiple RSSs adjacent to particular V or D gene segments after establishing the recombination center at the J gene segments of immunoglobulin and T-cell receptor loci, which could impact the relative abundance of a particular VDJ or VJ alleles [30]. Our assay positions us to measure the mean dwell time of every 12/23 rule-regulated V, D and J assembly reaction carried out to generate all immunoglobulins and T-cell receptors during lymphoid development.

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Cut-and-Run: A Distinct Mechanism by which V(D)J Recombination Causes Genome Instability

Cut-and-Run: A Distinct Mechanism by which V(D)J Recombination Causes Genome Instability

V(D)J recombination is essential to generate antigen receptor diversity but is also a potent cause of genome instability. Many chromosome alterations that result from aberrant V(D)J recombination involve breaks at single recombination signal sequences (RSSs). A long-standing question, however, is how such breaks occur. Here, we show that the genomic DNA that is excised during recombination, the excised signal circle (ESC), forms a complex with the recombinase proteins to efficiently catalyze breaks at single RSSs both in vitro and in vivo . Following cutting, the RSS is released while the ESC-recombinase complex remains intact to poten- tially trigger breaks at further RSSs. Consistent with this, chromosome breaks at RSSs increase markedly in the presence of the ESC. Notably, these breaks co- localize with those found in acute lymphoblastic leu- kemia patients and occur at key cancer driver genes. We have named this reaction ‘‘cut-and-run’’ and sug- gest that it could be a significant cause of lympho- cyte genome instability.

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Discussion on  A new method of measuring plastic limit of fine materials  by Sivakumar V , Glynn D , Cairns P , and Black J A

Discussion on A new method of measuring plastic limit of fine materials by Sivakumar V , Glynn D , Cairns P , and Black J A

where w is the water content, c is water content at d ¼ 1 mm and m is the slope of the (linear) log-log relationship. The water content at the plastic limit is determined by regression and extrapolation of corresponding curves to a penetration depth of 2 mm. It is evident that predicted and measured plastic limits are in reasonable agreement; however, it must be noted that there is inconsistency in some soils, where the predicted plastic limit using the Feng (2000) approach was significantly less well correlated. In response to this graph, the authors conducted an additional independent investiga- tion of two soils used as part of the original study in order to evaluate both approaches. Index properties of Ampthill and kaolin clay were assessed at four leading geotechnical testing laboratories in Northern Ireland and the plastic limits measured using the rolling thread method are reported in Table 5. As per the Feng (2000) approach, cone penetration tests were carried out to obtain multiple cone penetrations in the range 8–23 mm at various water contents. On the assumption that the average plastic limit measured using the rolling thread technique reported by the laboratories is a benchmark for the actual plastic limit, it appears that the Feng (2000) approach overestimates plastic limit in the case of Ampthill clay and underestimates the plastic limit in the case of kaolin. As per the Sivakumar et al. (2009) method, the plastic limit of Ampthill clay is overestimated by 3% whereas kaolin is in good agreement, although one should note the fact that the variation in the plastic limit of kaolin reported by the four laboratories is relatively high.

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J P Oberholzer: ’n Waardering

J P Oberholzer: ’n Waardering

bepaalde beskouing bevestig. Albei het die intense annoede van die Transvaalse Afrikaners wat tot die einde toe geveg of tot die einde toe in krygsgevangekampe deurgebring het, aan eie iyf gevoel. G root- oupa O berholzer was volgens alle getuienis ’n ryk man met ’n groot hoëveldplaas en etlike plase in wat hulle genoem het die Bosveld, m aar wat eintlik die middelveld was in die omgewing van die huidige V erena. G rootoum a is tydens die oorlog dood en is begrawe in die Standertonse konsentrasiekamp. D irek na die oorlog het vererwing plaasgevind en ek het self die boedeldokum ente gesien by die Mees- te r van die Hooggeregshof. D it was net die grond sonder ’n bees, skaap of implement. In ’n verklaring van een van die skoonseuns is bevestig dat al die lewende hawe en losgoed tydens die oorlog verlore gegaan het. M et oupa Nel-hulle het dit nie anders gegaan nie. My ouers het dus albei in hul klein kinderjare iets belewe van die voor- spoed van die vooroorlogse Transvaalse boere en baie van die na-oor- logse arm oede. Ook dit het hulle houding ten opsigte van politieke sake beinvloed. O upa Nel sowel as oupa O berholzer was tradisioneel Sappe, Botha- en Smutsmense, m aar pa het al vroeg skeie gebreek sodat ek van huis meer tuis was by die opkomende nasionalisme soos dit verwoord is deur generaal Hertzog. Vir dr Malan was daar in my wêreld min ooghare. Die Ossewa-Brandwag wat in die vroee veer- tigerjare goed op dreef gekom het, het my al op hoërskool aangetrek en alhoewel ek nooit werklik aktief betrokke was nie, het ek in hierdie tyd reeds as ’n soort juniorlid van die beweging gegeld. D it was ’n rare tyd, ’n tyd van onderlinge spanning birme families en tussen fami­ lies en noudat ek terugkyk, ’n tyd waarin waarskynlik baie mense nie presies geweet het wat die voile implikasies was van die standpunte wat hulle gehuldig het nie. Jy was vir of teen ’n leier, hoew el die besonderhede van die beleid waarvoor of waarteen jy was, nie altyd so duidelik was nie.

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Proefskrif  en boekbesprekings

Proefskrif en boekbesprekings

v e rb o n d e is a a n die Calvin College, G ra n d Rapids, Michigan. D r J N Or- kar het gepraat o or ‘Agricultural D e ­ velo pm ent in Nigeria’. Hy is verb on­ de aan die Christian Refo rm ed World R e li e f Commission. Die derde refe- r a a t is gelew er d e u r E B ruw er & E M unane oor ‘The community and our e l e p h a n t ’. A lb e i is v e r b o n d e a a n C h u r c h A id a n d N e e d , g e s e t e l in Suid-Afrika. P ro f M o n s m a m a a k in sy refera at gebruik van die G E R stu- diestuk oor ‘T h e church an d its social c a l l i n g ’. Hy b e r e d e n e e r a r m o e d e vanuit die p e rs p e k tie f van die skep- ping, die rol wat die so n d e sp eel en die b e te k e n is wat die verlossing het te n o p s i g te v an d ie k o n in k r y k van G od. Die resultaat van hierdie p e rs ­ pektief as vertrekpunt is dat die mens as skepping van G od omskryf word as r e n tm e e s te rs van die skepping. Die sonde word verstaan as selfsug wat in die w êre ld gekom het e n r e n t m e e f - te r s k a p n e g a ti e f a a n g e t a s het. Die Mosaiese w et het die funksie om die invloed hiervan te rem deur aan fami­ lies te gee wat nodig is om van te leef. Verlossing word om skry f as die her- stel van G o d se koninkryk op aarde wat meebrin g dat die C hris te n hom- self in diens van die a rm e m o e t gee. Verlossing be te k e n dus dat ’n Chris­ ten a r m o e d e en lyding m o e t elimi- neer. Dit moet gedoen word op drie vlakke, naamlik die vo ors ie nin g van kos en klere, ontwikkeling van ’n self- h e l p s k e m a e n die v e rw y d e rin g van

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Abstract V������ J., C���� P., C���� C., H����� S., D������ M. (2003):

Abstract V������ J., C���� P., C���� C., H����� S., D������ M. (2003):

The reaction of 3-MCPD with cysteine in neu- tral media leads predominantly to the formation of S-(2,3-dihydroxypropyl)cysteine (Figure 1). N-(2,3-dihydroxypropyl)amino acids are the ma- jor products in alkaline media (V������ et al. 1991). Analogous reactions can be expected with reduced glutathione. The thiol group of either cysteine or glutathione can open the ring of epoxides. For in- stance, 3-chloro-2-hydroxypropylmercapturic acid (Figure 2) has been identified (together with free 3-MCPD) in urine of rats dosed intraperitoneally with epichlorohydrin (D� R���� et al. 1996). This acid arose as a detoxification product by the reac- tion of epichlorohydrin with glutathione and by hydrolysis of the adduct. Reactions of 3-MCPD with cysteine and other thiols may, at least partly, explain the absence of 3-MCPD in, e.g., roasted coffee. It is well known that green coffee beans contain higher levels of cysteine than, e.g., barley during roasting of which 3-MCPD forms. During roasting of coffee, several volatile thiols are formed such as 2-furfurylthiol, 3-methylbut-2-enthiol and other compounds (B����� & G����� 1999).

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Dissecting the Epigenetic Regulation of V-beta Recombination

Dissecting the Epigenetic Regulation of V-beta Recombination

generation of a diverse and dynamic repertoire of antigen receptor molecules. The genes for receptors are generated de novo during lymphocyte development by the somatic DNA rearrangement process, V(D)J recombination (89). How V(D)J recombination is differentially used to assemble the various Ig and TCR genes during B and T cell development appears rooted in the sequence and conformation of the antigen receptor genes themselves, and not imposed at the level of the recombinase enzymes. To date, limited insight has been gained regarding the cis elements that control V(D)J recombinational accessibility. Clearly, enhancers positioned within each locus are critical for rearrangement of their associated gene segments, playing dual roles to both target histone acetylation events that relax heterochromatin condensation, and separately driving activation of promoters that flank individual gene segments (83). A growing body of evidence also suggests that these germline promoters contribute to recombinational accessibility (83); though their mechanism of action remains unclear.

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P J Hoedemaker, teoloog en kerkman

P J Hoedemaker, teoloog en kerkman

Vele liberalen gruwden bovendien van Kuypers antitheseieer en -poli­ tick die naar iiun gevoelen N ederland volgens de scheidslijn van v66r of tegen de confessionele partij, vooral vóór of tegen die van Kuyper, verdeelde in christen en niet-christen. Kuyper trok alles naar zijn, on- m iskenbaar, form idabele persoonlijkheid toe en toonde geen oog te hebben voor de eenheid van de natie en het nationale belang dat elk kabinet, dus, ook het zijne, diende te behartigen. Te denken valt hier- bij aan de jrolarisatie-strategie van de Partij van de A rbeid in de jaren ’70 van deze eeuw . H oe zeer tegengesteld v erd er ook, liberaal en socialist w aren het nu eens: tegen Kuyper en zijn kabinet. M aar ook voelden christenen van andere confessionele partijen ernstige bezwa- ren tegen Kuypers autoritaire optreden, zijn antitheseieer en weinig openstaan voor denkbeelden van anderen die m inder dan zijn volge- lingen overtuigd w aren van het succes van het kabinet-K uyper. Ook en vooral als m en de daden toetste aan de beginselen w aarvan het pretendeerde uit te gaan.

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P J Hoedemaker: ‘Wat ék bedoel, is die behoud van die kerk’

P J Hoedemaker: ‘Wat ék bedoel, is die behoud van die kerk’

Dat H oedem aker inderdaad anders was en teenoor die formidabeie figuur van Kuyper ’n eie selfstandigheid geopenbaar het, biyk uit meer as net hulle verskil oor die wese van die kerk en die Vrije Universiteit. Kuyper was ’n man van sisteem. Hy kon sy saak logies en sistematies uiteensit sodat dit oorsigtelik geken kon word. H oedem aker was anders, want as man van die praktyk, was ook sy akademiese en studeerkam erw erk altyd op die praktyk gerig; vir hom die werk in die kerk, die gem eente. D aarop was sy gesprek en diskussie gerig, of dit met Kuyper of die owerheid was, of met Luther of met Rome. Die werklikheid, in sy geval die kerk, is vir hom baie ryker en groter as sy gedagtes daaroor. Daarom sien hy nie kans om sy denke tot ’n eenvoudige sisteem terug te dwing nie. Hoedem aker is ’n boeiende figuur, sonder cliche’s en afgeronde sisteme. Maar dit het ook veroorsaak dat hy vir baie ander moeilik was om te verstaan. Dit was in die diskussie en polemiek met soveel om hom dat hy sy gedagtes ontwikkel het (Abma 1989:34).

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North south asymmetry of the substorm intensity depending on the IMF BY
               component

North south asymmetry of the substorm intensity depending on the IMF BY component

ionospheric dynamo effects and seasonal differences in con- ductivity of the polar ionosphere in the northern and south- ern hemispheres (Forbes and Harel, 1989; Zakharov and Pudovkin, 1996). The influence of seasonal ionospheric con- ductivity variations on the field-aligned currents is also ob- served for non-stationary processes. Osaki et al. (1996) es- tablished that geomagnetic pulsation amplitudes in H- and D-components in the summer hemisphere were larger than in the winter one.

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Enkele Aantekeninge by die debat oor die uitleg van die Dordtse Leerreëls wat in 1871 deur Ds  J J  Kotze van Darling en Ds  Andrew Murray Jnr gevoer is

Enkele Aantekeninge by die debat oor die uitleg van die Dordtse Leerreëls wat in 1871 deur Ds J J Kotze van Darling en Ds Andrew Murray Jnr gevoer is

22Die Dordtse Leerreëls, Hoofstuk 1:1: Aangesien alle mense in Adam gesondig en aan die vloek en die ewige dood skuldig geword het . . . Hoofstuk 1:7: . . . die hele menslike geslag wat deur hulle eie skuld van die eerste regtheid in die sonde en verderf verval het. Nederlandse Qeloofsbelydenis, art. xvi: O ns glo dat nadat die ganse geslag van Adam deur die sonde van die eerste mens in verderf en ondergang gestort is G od Hom self sodanig betoon het as wat Hy is naamlik barmhartig en regverdig. Barmhartig: deurdat Hy uit hierdie verderf trek en verlos diegene wat Hy in sy ewige en onveranderlike raad uit louter goedertierenheid uitverkies het in Jesus Christus onse Heer sonder om enigsinds hulle werke in aanmerking te neem. Hier word die afrikaanse vertaling, gemakshalwe, gesiteer soos dit verskyn in die Kerkboek van die Nederduitsch Hervormde Kerk van Afrika, Kaapstad 1955. 2SVgl. Dordtse Leerreëls, Hoofstuk 1:5. D s. Kotzé lê dit as volg uit: G od roept maar

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Die Mistiek  'n beskouing volgens die standpunt van N A  Berdyaev (Berdjajew)

Die Mistiek 'n beskouing volgens die standpunt van N A Berdyaev (Berdjajew)

B y die beoefening van die mistiek word, soos by baie ander dinge, middele die doeleindes op sigseiwe. A sk ese met sy vyandigheid teen- oor die mens en die wéreld mag verw arring bring t.o.v. die werklike doeleindes van die mistiek nl. die transfigurasie in G od. Dit mag laste op die mens lê wat te moeilik is om te dra en terselfdertyd groot spanning in die siel veroorsaak. D ie moeilikheid van die geestelike iewe lê reeds opgesluit in die streng vereiste om versoening teweeg te bring tussen afskeiding van die vele en konsentrasie op die Eenheid met die bevryding en die transfigurasie in die G ees van a! die diwerse elemente in die wereld en by die mens. D aar My twee weë moontlik en dis moontlik om die twee weë te laat saam sm e!t. D ie een weg beteken afskeiding van die mens en die wéreld en konsentrasie op G od. die versaking van die vele vir die Een, Ew ige, Onveranderlike. D ie ander weg is die van orientasie tot die mens en die wereld, tot die vele en tot die wat onderhewig is aan verandering. Die Griekse filo­ sofie kon hierdie probleem nie oplos nie en dit het gelei tot die dualisme. S elfs Plato kon die oplossing nie vind nie, hoewel sy stelling van Eros 'n poging daartoe w as. Die Christelikheid erken in beginsel 'n oplos­ sing van hierdie moeilike probleem en poog om die dualisme te bowe te kom. D ie volheid van die Christelike w aarheid styg bo die menslike begrip uit, en selfs die mistiek het tekort geskiet in hierdie opsig. W eereen s bevind ons onsself voor die probleem waarmee die Griekse filosowe, en veral Plato en Plotinus gew orstel het. Sleg s in die liefde vir Christus en die volheid daarvan is hier 'n oplossing te vinde. Die skeppende vermoë van die mens is 'n verwesenliking van liefde, van Eros. wat illuminasie en eenheid teweeg bring. Die taak van die geestelike lewe is 'n moeilike taak en blyk onmoontlik te wees vir die natuurlike mens, want dit kan slegs geskied deur vereniging van die vrye geestelike afsondering en konsentrasie op die Ew ige met die liefde vir die mensdom en die wéreld wat alles transfigureer en om- skep. D ie opperste doel van die mistiek is nie eenwording met God nie, m aar 'n uitkeer uit die self tot elke skepsel. Dit is die verwesen­ liking van liefde en skeppende krag, w ant liefde is skeppend. Op hierdie w yse word die gebod van Christus om G od bo alles lief te hé en jou n aaste soos jouself, vervul.

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