With the goal of improving previously reported Mn bipyridine electrocatalysts in terms of increased activity and reduced overpotential, a bulky bipyridine ligand, 6,6'-dimesityl-2,2'-bipyridine (mesbpy), was utilized to eliminate dimerization in the catalytic cycle. Synthesis, electrocatalytic properties, X-ray diffraction (XRD) studies, and infrared spectroelectrochemistry (IR-SEC) of Mn(mesbpy)(CO)3Br and [Mn(mesbpy)(CO)3(MeCN)](OTf) are reported. Unlike previously reported Mn bipyridine catalysts, these Mn complexes exhibit a single, two-electron reduction wave under nitrogen, with no evidence of dimerization. The anionic complex, [Mn(mesbpy)(CO)3](-), is formed at 300 mV more positive potential than the corresponding state is formed in typical Mn bipyridine catalysts. IR-SEC experiments and chemical reductions with KC8 provide insights into the species leading up to the anionic state, specifically that both the singly reduced and doubly reduced Mn complexes form at the same potential. When formed, the anionic complex binds CO2 with H(+), but catalytic activity does not occur until a ~400 mV more negative potential is present. The Mn complexes show high activity and Faradaic efficiency for CO2 reduction to CO with the addition of weak Brønsted acids. IR-SEC experiments under CO2/H(+) indicate that reduction of a Mn(I)-CO2H catalytic intermediate may be the cause of this unusual "over-reduction" required to initiate catalysis.

Meiosis is a cellular program that generates haploid gametes for sexual reproduction. While chromosome events that contribute to reducing ploidy (homologous chromosome pairing, synapsis, and recombination) are well conserved, their execution varies across species and even between sexes of the same species. The telomere bouquet is a conserved feature of meiosis that was first described nearly a century ago, yet its role is still debated. Here we took advantage of the prominent telomere bouquet in zebrafish, Danio rerio, and super-resolution microscopy to show that axis morphogenesis, synapsis, and the formation of double-strand breaks (DSBs) all take place within the immediate vicinity of telomeres. We established a coherent timeline of events and tested the dependence of each event on the formation of Spo11-induced DSBs. First, we found that the axis protein Sycp3 loads adjacent to telomeres and extends inward, suggesting a specific feature common to all telomeres seeds the development of the axis. Second, we found that newly formed axes near telomeres engage in presynaptic co-alignment by a mechanism that depends on DSBs, even when stable juxtaposition of homologous chromosomes at interstitial regions is not yet evident. Third, we were surprised to discover that ~30% of telomeres in early prophase I engage in associations between two or more chromosome ends and these interactions decrease in later stages. Finally, while pairing and synapsis were disrupted in both spo11 males and females, their reproductive phenotypes were starkly different; spo11 mutant males failed to produce sperm while females produced offspring with severe developmental defects. Our results support zebrafish as an important vertebrate model for meiosis with implications for differences in fertility and genetically derived birth defects in males and females.

The development of efficient hydrogen evolving electrocatalysts that operate near neutral pH in aqueous solution remains of significant interest. A series of low-valent iron clusters have been investigated to provide insight into the structure-function relationships affecting their ability to promote formation of cluster-hydride intermediates and to promote electrocatalytic hydrogen evolution from water. Each of the metal carbonyl anions, [Fe4N(CO)12](-) (1(-)), [Fe4C(CO)12](2-) (2(2-)), [Fe5C(CO)15](2-) (3(2-)), and [Fe6C(CO)18](2-) (4(2-)) were isolated as their sodium salt to provide the necessary solubility in water. At pH 5 and -1.25 V vs SCE the clusters afford hydrogen with Faradaic efficiencies ranging from 53-98%. pH dependent cyclic voltammetry measurements provide insight into catalytic intermediates. Both of the butterfly shaped clusters, 1(-) and 2(2-), stabilize protonated adducts and are effective catalysts. Initial reduction of butterfly shaped 1(-) is pH-independent and subsequently, successive protonation events afford H1(-), and then hydrogen. In contrast, butterfly shaped 2(2-) undergoes two successive proton coupled electron transfer events to form H22(2-) which then liberates hydrogen. The higher nuclearity clusters, 3(2-) and 4(2-), do not display the same ability to associate with protons, and accordingly, they produce hydrogen less efficiently.

During meiosis I, ring-shaped cohesin complexes play important roles in aiding the proper segregation of homologous chromosomes. RAD21L is a meiosis-specific vertebrate cohesin that is required for spermatogenesis in mice but is dispensable for oogenesis in young animals. The role of this cohesin in other vertebrate models has not been explored. Here, we tested if the zebrafish homolog Rad21l1 is required for meiotic chromosome dynamics during spermatogenesis and oogenesis. We found that Rad21l1 localizes to unsynapsed chromosome axes. It is also found between the axes of the mature tripartite synaptonemal complex (SC) in both sexes. We knocked out rad21l1 and found that nearly all rad21l1-/- mutants develop as fertile males, suggesting that the mutation causes a defect in juvenile oogenesis, since insufficient oocyte production triggers female to male sex reversal in zebrafish. Sex reversal was partially suppressed by mutation of the checkpoint gene tp53, suggesting that the rad21l1 mutation activates Tp53-mediated apoptosis or arrest in females. This response, however, is not linked to a defect in repairing Spo11-induced double-strand breaks since deletion of spo11 does not suppress the sex reversal phenotype. Compared to tp53 single mutant controls, rad21l1-/- tp53-/- double mutant females produce poor quality eggs that often die or develop into malformed embryos. Overall, these results indicate that the absence of rad21l1-/- females is due to a checkpoint-mediated response and highlight a role for a meiotic-specific cohesin subunit in oogenesis but not spermatogenesis.

The telomere bouquet is a hub where meiotic double-strand breaks, synapsis, and stable 1 homolog juxtaposition are coordinated in the zebrafish, Danio rerio Abstract 7Meiosis is a cellular program that generates haploid gametes for sexual reproduction. While 8 chromosome events that contribute to reducing ploidy (homologous chromosome pairing, 9 synapsis, and recombination) are well conserved, their execution varies across species and even 10 between sexes of the same species. The telomere bouquet is a conserved feature of meiosis that 11 was first described nearly a century ago, yet its role is still debated. Here we took advantage of the 12 prominent telomere bouquet in zebrafish, Danio rerio, and super-resolution microscopy to show 13 that axis morphogenesis, synapsis, and the formation of double-strand breaks (DSBs) all take place 14 within the immediate vicinity of telomeres. We established a coherent timeline of events and tested 15 the dependence of each event on the formation of Spo11-induced DSBs. First, we found that the 16 axis protein Sycp3 loads adjacent to telomeres and extends inward, suggesting a specific feature 17 common to all telomeres seeds the development of the axis. Second, we found that newly formed 18 axes near telomeres engage in presynaptic co-alignment by a mechanism that depends on DSBs, 19 even when stable juxtaposition of homologous chromosomes at interstitial regions is not yet 20 evident. Third, we were surprised to discover that ~30% of telomeres in early prophase I engage 21 in associations between two or more chromosome ends and these interactions decrease in later 22 stages. Finally, while pairing and synapsis were disrupted in both spo11 males and females, their 23 reproductive phenotypes were starkly different; spo11 mutant males failed to produce sperm while 24 females produced offspring with severe developmental defects. Our results support zebrafish as an 25 important vertebrate model for meiosis with implications for differences in fertility and genetically 26 derived birth defects in males and females. 28Author Summary 29Inherent to reproduction is the transmission of genetic information from one generation to the next. 30In sexually reproducing organisms, each parent contributes an equal amount of genetic 31 information, packaged in chromosomes, to the offspring. Diploid organisms, like humans, have 32 two copies of every chromosome, while their haploid gametes (e.g. eggs and sperm) have only 33 one. This reduction in ploidy depends on the segregation of chromosomes during meiosis, 34 resulting in gametes with one copy of each chromosome. Missegregation of the chromosomes in 35 the parents leads to abnormal chromosome numbers in the offspring, which is usually lethal or has 36 detrimental developmental effects. While it has been known for over a century that homologous 37 chromosomes pair and recombine to facilitate proper segregation, how homologs find their 38 partners has remained elusive. A structure that has been central to the discussion of homolog 39 pairing is...

Meiosis produces haploid gametes that will give rise to the next diploid generation. Chromosome segregation errors occurring at one or both meiotic divisions result in aneuploidy, which can lead to miscarriages or birth defects in humans. During meiosis I, ring-shaped cohesin complexes play important roles to aid in the proper segregation of homologous chromosomes. While REC8 is a specialized meiosis-specific cohesin that functions to hold sister chromatids together, the role of its vertebrate-specific paralog, RAD21L, is poorly understood. Here we tested if Rad21l1, the zebrafish homolog of human and mouse RAD21L, is required for meiotic chromosome dynamics during oogenesis and spermatogenesis. We found that Rad21l1 is an abundant component of meiotic chromosomes where it localizes to both the chromosome axes and the transverse filament of the synaptonemal complex (SC). Knocking out rad21l1 causes nearly the entire mutant population to develop as fertile males, suggesting the mutation triggers a sex reversal from female to male due to a failure in oocyte production. The rad21l1−/− mutant males display normal fertility at sexual maturity. Sex reversal was partially suppressed in the absence of tp53, suggesting that the rad21l1−/− mutation causes defects leading to a Tp53 dependent response, specifically in females. The rad21l1−/−;tp53−/− double mutant females produced elevated rates of decomposing eggs and deformed offspring compared to tp53−/− controls. This response, however, is not linked to a defect in repairing Spo11-induced double-strand breaks since deletion of Spo11 does not suppress the sex reversal phenotype. Overall, our data highlight an exceptional sexually dimorphic phenotype caused by knocking out a meiotic-specific cohesin subunit. We propose that Rad21l1 is required for maintaining the integrity of meiotic chromatin architecture during oogenesis.Author SummaryA prominent symptom of age-linked reproductive decline in women is the increased rate of miscarriage and birth defects due to aneuploidy. Aneuploidy can arise when chromosomes fail to segregate properly during meiosis, the process of creating haploid gametes from a diploid germ cell. Oocyte progression normally arrests prior to anaphase I, after homologous chromosomes have formed crossovers, but before ovulation, which triggers the first round of segregation. This prolonged arrest makes oocytes especially vulnerable to degradation of meiotic chromosome structure and homolog connections over time. Cohesin complexes play a major role in maintaining the meiotic chromosome architecture. Here we assess the role of the vertebrate-specific Rad21l1 cohesin subunit in zebrafish. We find that while males appear mostly unaffected by loss of Rad21l1, oocyte production is massively compromised, leading to sex reversion to males. Sex reversion can be partially prevented in the absence of Tp53, demonstrating that loss or Rad21l1 leads to a Tp53-dependent response in oocytes. Strikingly, double mutant rad21l1 tp53 females produce large numbers of poor quality eggs and malformed offspring. This demonstrates a cohesin-linked vulnerability in female meiosis not present in males and sheds light on a potential mechanism associated with the decline in female reproductive health.