Data_Sheet_1_The impact of grandchild care on depressive symptoms of grandparents in China: The mediating effects of generational support from children.docx

ObjectivesDespite extensive studies about the direct effect of grandchild care on caregiver depression in China, understanding of its internal influencing mechanism has been limited. After controlling for socioeconomic factors, this study investigated whether the experience of caring for grandchildren had a long-term impact on the depression levels of grandparents, either directly or indirectly through generational support from adult children.MethodsThe subjects of this study were a total of 9,219 adults over 45 who participated in the China Health and Retirement Longitudinal Surveys in 2015 and 2018. We adopted a lag-behind variable to examine the impact of grandchild care on depressive symptoms of grandparents. The proposed mediation model was analyzed using bootstrap modeling, and the KHB method was conducted further to examine differences in the effects of generational support.ResultsThe experience of caring for grandchildren had a significant negative correlation with the depression level of Chinese grandparents. Moreover, children's support significantly mediated the impact of parenting experience on grandparents' depression. Significantly, instrumental support mediated the effect to the greatest extent, while emotional support from children contributed the least. The intermediary effect has urban–rural heterogeneity.ConclusionThese findings indicated that grandchild care significantly inhibited the depression level of Chinese grandparents through increased intergenerational support from adult children. The implications of the study's findings were discussed.</p

Metal-Organic Gels of Catechol-Based Ligands with Ni(II) Acetate for Dye Adsorption

Metal organic gels (MOGs) are a class of supramolecular complexes, which have attracted widespread interest because of the coupled advantages of inorganic and organic building blocks. A new compound terminated with catechol was synthesized. This new compound can be used to coordinate with Ni²⁺ to form MOGs. These MOGs show favorable viscoelasticity and wormhole-shaped porous structures, which were confirmed by transmission electron microscope and scanning electronic microscope images. Taking the benefits of porosity into account, the xerogel could serve as an adsorbent to adsorb dye molecules from the aqueous media. The experimental results indicate that xerogels possess good adsorption effect both on anionic and cationic dyes. Exhaustive research has been performed on the adsorption kinetics and isotherms, revealing that the adsorption process accords with the pseudo-second-order model and the Langmuir model

Table1_Clinical manifestations of 17 Chinese children with hereditary spherocytosis caused by novel mutations of the ANK1 gene and phenotypic analysis.DOCX

Background: Hereditary spherocytosis (HS) is an autosomal dominant (AD) and autosomal recessive (AR) disorder that is mostly caused by mutations of the erythrocyte membrane-related gene ANK1.Methods: Clinical and genetic testing data of 17 HS children with ANK1 gene mutations were retrospectively collected. Clinical manifestations and phenotypic analysis of HS were summarized based on our experience and literature review.Results: A total of 17 mutations of the ANK1 gene were identified from 17 probands (12 sporadic cases and five familial cases), including 15 novel mutations and two previously reported ones. Among the 15 novel variants of ANK1, there were four non-sense mutations, four frameshift mutations, three splicing mutations, three missense mutations and one in-frame deletion of three amino acids. In the present study, HS patients with mutations in membrane binding domains had significantly lower hemoglobin (Hb) levels and higher total bilirubin (T-Bil) levels than those with mutations in regulatory domains. After reviewing and analyzing all available published reports of Chinese HS patients carrying ANK1 mutations in PubMed and Chinese journals, there were no significant differences in Hb, Ret and T-Bil between different mutation types or mutation regions.Conclusion: Mutations of the ANK1 can be inherited or de novo. Clinical manifestations of HS in children caused by ANK1 mutations are similar to those of other types of hemolytic anemia. Our report expands the mutation spectrum of HS, thus providing references for clinical management and genetic counseling of HS.</p

The DNA Replication Factor <em>RFC1</em> Is Required for Interference-Sensitive Meiotic Crossovers in <em>Arabidopsis thaliana</em>

<div><p>During meiotic recombination, induced double-strand breaks (DSBs) are processed into crossovers (COs) and non-COs (NCO); the former are required for proper chromosome segregation and fertility. DNA synthesis is essential in current models of meiotic recombination pathways and includes only leading strand DNA synthesis, but few genes crucial for DNA synthesis have been tested genetically for their functions in meiosis. Furthermore, lagging strand synthesis has been assumed to be unnecessary. Here we show that the <em>Arabidopsis thaliana</em> DNA <em>REPLICATION FACTOR C1</em> (<em>RFC1</em>) important for lagging strand synthesis is necessary for fertility, meiotic bivalent formation, and homolog segregation. Loss of meiotic <em>RFC1</em> function caused abnormal meiotic chromosome association and other cytological defects; genetic analyses with other meiotic mutations indicate that <em>RFC1</em> acts in the <em>MSH4</em>-dependent interference-sensitive pathway for CO formation. In a <em>rfc1</em> mutant, residual pollen viability is MUS81-dependent and COs exhibit essentially no interference, indicating that these COs form via the MUS81-dependent interference-insensitive pathway. We hypothesize that lagging strand DNA synthesis is important for the formation of double Holliday junctions, but not alternative recombination intermediates. That <em>RFC1</em> is found in divergent eukaryotes suggests a previously unrecognized and highly conserved role for DNA synthesis in discriminating between recombination pathways.</p> </div

Meiotic recombination rate in <i>rfc1-2</i> and a revised model for RFC1 in meiotic recombination.

<p>A. Estimation of the recombination rate in wild type and <i>rfc1-2</i>. Curves in graphs indicate the distribution of meiotic recombination frequency on <i>Arabidopsis</i> chromosome 2 and 3 <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003039#pgen.1003039-Giraut1" target="_blank">[38]</a>. Markers with red (R), cyan (C) and yellow (Y) fluorescence are located on the corresponding chromosome positions. The recombination rates in wild type and mutant are shown in the table below. The same trend was obtained from two independent biological replicates. NOR, Nucleolar organizer region; Chr, chromosome. Block box represents the centromere. B. A revised model for RFC1 function in type I CO formation during meiotic recombination. As shown in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003039#pgen-1003039-g001" target="_blank">Figure 1A</a> or original DSBR model <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003039#pgen.1003039-Szostak1" target="_blank">[3]</a>, NCOs and COs are proposed to require leading strand DNA synthesis. However, formation of dHJ requires the capture of the second ssDNA end and the stabilization and extension, respectively, of the DNA heteroduplex with the help of the MSH4/5 complex and MER3. In the revised model, we hypothesize that the Type I pathway needs the RFC1-dependent lagging strand DNA synthesis (green dotted arrow) during D-loop extension, which occurs simultaneously with leading strand synthesis (red dotted arrows) that uses the 3′ invading end as the primer, consistent with a DNA replication mechanism in eukaryotes and supported by this study. C. A possible mechanism for the formation of multivalents in <i>rfc1-2</i>. RFC1 is required for dHJ formation between homologs. In the absence of RFC1, MUS81-dependent Type II COs are formed between homolog and non-homologs, resulting in the formation of multivalents.</p

A model for meiotic recombination and phenotypes of wild type and the <i>rfc1-2</i> mutant.

<p>(A) DNA double-strand breaks are resected to yield 3′ ssDNA overhangs. One of the single strands invades a homologous duplex to form a SEI intermediate. NCOs by the SDSA pathway accounts the majority of DSBs. The ZMM-dependent pathway requires the formation of dHJ and results in ∼80% of COs (Type I), whereas the MUS81-Mms4 dependent pathway produces ∼20% COs (Type II). The formation of both COs and NCOs requires DNA synthesis, but with distinct amounts. (B–N) Phenotypes of wild type and <i>rfc1-2.</i> Wild type (B) and <i>rfc1-2</i> (C) plants showed similar vegetative growth, but the mutant had shorter seedpods (arrow). A mutant flower (E) had normal organs similar to those in wild type (D). Wild type seedpods (F) and shorter <i>rfc1-2</i> mutant seedpods (G). Dissected young wild type (H) and mutant seedpods (I), with very few seeds. The boxed regions were enlarged from H and I. A wild type anther with viable pollen grains stained in red (J); a mutant anther (K) with few viable pollen grains (arrow) and a larger number of nonviable pollen grains stained in dark green. A wild type tetrad with four microspores (L). <i>rfc1-2</i> mutant polyads with additional small microspores (arrow) (M and N). Bar = 20 mm (B and C), 500 µm (D and E), 1 mm (F–I), 50 µm (J and K), and 10 µm (L–N).</p

Genetic analysis of <i>RFC1</i> with other meiotic recombination genes.

<p>Chromosome behavior of male meiocytes at pachytene and metaphase I. (A–B) <i>spo11-1-1^−/−</i>. (C–D) The <i>spo11-1-1^−/− rfc1-2^−/−</i> double mutant showing similar chromosome behaviors to those of the <i>spo11-1-1^−/−</i> single mutant. (E–F) <i>rad51-3^−/−</i>. (G–H) The <i>rad51-3^−/− rfc1-2^−/−</i> double mutant showing similar phenotypes to those of the <i>rad51-3^−/−</i> single mutant. (I–J) <i>msh4-1^−/−</i>. (K–L) The <i>msh4-1^−/− rfc1-2^−/−</i> double mutant showing similar phenotypes to those of the <i>rfc1-2^−/−</i> single mutant. (M–N) <i>ptd.</i> (O–P) The <i>ptd-1^−/− rfc1-2^−/−</i> double mutant showing similar to the <i>rfc1-2^−/−</i> single mutant. (Q and R) <i>mus81.</i> (S–T) The <i>mus81-1^−/− rfc1-2^−/−</i> double mutant lacking multivalent, unlike the <i>rfc1-2^−/−</i> single mutant. (U–X) Viability of pollen grains in wild type (U), <i>mus81-1^−/−</i> (V), <i>rfc1-2^−/−</i> (W) and <i>mus81-1^−/− rfc1-2^−/−</i> (X), the <i>mus81-1^−/− rfc1-2^−/−</i> double mutants showing almost no viable pollen grains. Bar, (A–T) 10 µm, (U–X) 500 µm.</p

RAD51 localization in wild type and <i>rfc1-2.</i>

<p>(A–H) Localization of RAD51. (A and E) leptotene, (B and F) zygotene, (C, D and G) pachytene, (H) An enlarged image from (G), (D) the <i>rad51</i> mutant. The <i>rfc1-2</i> mutant showed RAD51 foci highly similar to the wild type ones before pachytene, but with persisted signals at pachytene (G). In each row of three panels, the left panel shows blue colored chromosomes strained with DAPI; the middle panel shows red colored signals for proteins as indicated above the panel; and the right panel shows the merged image of DAPI and protein signals. Bar, 10 µm.</p

FISH analysis of the chromosome interaction in wild type and <i>rfc1-2.</i>

<p>(A) Wild type and (B) <i>rfc1-2</i> interphase nuclei with telomere clusters (circled). (C) Wild type and (D) <i>rfc1-2</i> pachytene cells with telomere signals. (E) Wild type and (F) <i>rfc1-2</i> leptotene cells with two chromosome 1 BAC F19K16 signals (arrow). (G) A wild type pachytene cell with one signal, and a mutant pachytene cell (H) with two separated signals (arrow). (I, K, M, O, Q) Wild type and (J, L, N, P, R) <i>rfc1-2</i> meiocytes with a centromere probe. Leptotene with 10 signals (I1 and J1) and pachytene with five signals (K1 and L1). At Metaphase I, wild type had 10 signals on five bivalents (M1), but <i>rfc1-2</i> showed non-homolog association (N1, arrow), At anaphase I and telophase II, wild type had 5 signals in each group (O1 and Q1), but <i>rfc1-2</i> showed chromosome missegregation with 4 or 6 signals in each group (P1 and R1). Wild type (S) had one BAC F19K16 signal at metaphase I, but <i>rfc1-2</i> (T) had two signals (arrow). At anaphase I and II, wild type (U and W) had two signals on each side, but <i>rfc1-2</i> (V and X) showed chromosomes missegregation with unequal signals (arrow). Red dots represent the signals of different probes. The superimposed images were produced by merging FISH signals with DAPI-stained chromosomes. Bar, 10 µm.</p