Smc5/6 coordinates formation and resolution of joint molecules with chromosome morphology to ensure meiotic divisions

During meiosis, Structural Maintenance of Chromosome (SMC) complexes underpin two fundamental features of meiosis: homologous recombination and chromosome segregation. While meiotic functions of the cohesin and condensin complexes have been delineated, the role of the third SMC complex, Smc5/6, remains enigmatic. Here we identify specific, essential meiotic functions for the Smc5/6 complex in homologous recombination and the regulation of cohesin. We show that Smc5/6 is enriched at centromeres and cohesin-association sites where it regulates sister-chromatid cohesion and the timely removal of cohesin from chromosomal arms, respectively. Smc5/6 also localizes to recombination hotspots, where it promotes normal formation and resolution of a subset of joint-molecule intermediates. In this regard, Smc5/6 functions independently of the major crossover pathway defined by the MutLγ complex. Furthermore, we show that Smc5/6 is required for stable chromosomal localization of the XPF-family endonuclease, Mus81-Mms4Eme1. Our data suggest that the Smc5/6 complex is required for specific recombination and chromosomal processes throughout meiosis and that in its absence, attempts at cell division with unresolved joint molecules and residual cohesin lead to severe recombination-induced meiotic catastroph

The SMC-5/6 Complex and the HIM-6 (BLM) Helicase Synergistically Promote Meiotic Recombination Intermediate Processing and Chromosome Maturation during<i> Caenorhabditis elegans</i> Meiosis

Meiotic recombination is essential for the repair of programmed double strand breaks (DSBs) to generate crossovers (COs) during meiosis. The efficient processing of meiotic recombination intermediates not only needs various resolvases but also requires proper meiotic chromosome structure. The Smc5/6 complex belongs to the structural maintenance of chromosome (SMC) family and is closely related to cohesin and condensin. Although the Smc5/6 complex has been implicated in the processing of recombination intermediates during meiosis, it is not known how Smc5/6 controls meiotic DSB repair. Here, using Caenorhabditis elegans we show that the SMC-5/6 complex acts synergistically with HIM-6, an ortholog of the human Bloom syndrome helicase (BLM) during meiotic recombination. The concerted action of the SMC-5/6 complex and HIM-6 is important for processing recombination intermediates, CO regulation and bivalent maturation. Careful examination of meiotic chromosomal morphology reveals an accumulation of inter-chromosomal bridges in smc-5; him-6 double mutants, leading to compromised chromosome segregation during meiotic cell divisions. Interestingly, we found that the lethality of smc-5; him-6 can be rescued by loss of the conserved BRCA1 ortholog BRC-1. Furthermore, the combined deletion of smc-5 and him-6 leads to an irregular distribution of condensin and to chromosome decondensation defects reminiscent of condensin depletion. Lethality conferred by condensin depletion can also be rescued by BRC-1 depletion. Our results suggest that SMC-5/6 and HIM-6 can synergistically regulate recombination intermediate metabolism and suppress ectopic recombination by controlling chromosome architecture during meiosis

A válvula de Heimlich no tratamento do pneumotórax Heimlich valve in the treatment of pneumothorax

Objetivos: A válvula de Heimlich foi descrita para substituir os sistemas de drenagem sob selo d'água. O Serviço de Cirurgia Torácica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo realizou este estudo com o objetivo de avaliar sua eficiência no tratamento do pneumotórax, bem como a facilidade de manipulação, segurança e tolerância pelo paciente. Métodos: Foram analisados 108 pacientes com pneumotórax de diferentes etiologias, de junho/97 a agosto/2000. A maioria (76%) apresentava pneumotórax classificado radiologicamente como médio ou grande, sendo três deles hipertensivos, dos quais um bilateral. Utilizaram-se para a drenagem da cavidade pleural cateteres plásticos de teflon ou poliuretano tipo pig-tail 10,2F, 14F ou retos 11F conectados à válvula de Heimlich. Nos pacientes pós-toracotomias, a válvula foi conectada diretamente ao dreno torácico. Resultados: O período de permanência da válvula variou de um a 120 dias (mediana de quatro dias). A tolerância ao sistema foi considerada boa por 89% dos pacientes. Não ocorreram complicações atribuíveis ao sistema. A presença de derrame associado em 20 pacientes (18,5%) não impediu o bom funcionamento do sistema. Apenas dois (1,8%) pacientes evoluíram com enfisema subcutâneo progressivo, optando-se então por dreno tubular 36F sob selo d'água. Em um paciente (0,9%) indicou-se toracotomia para descorticação pulmonar. Vinte pacientes (18,5%) foram tratados no ambulatório. Conclusões: A válvula de Heimlich mostrou-se eficiente na resolução do pneumotórax de diferentes etiologias e nas fístulas aéreas pós-operatórias. A manipulação foi mais simples do que as historicamente observadas nos sistemas convencionais. A boa tolerância e segurança referidas pelos pacientes foram fator determinante na precocidade da alta hospitalar e incentivo ao tratamento ambulatorial.<br>Objective: Heimlich valve has been described as a substitute for water-sealed drainage systems. The objective of this study by the Thoracic Surgery Service of the "Hospital das Clínicas", University of São Paulo Medical Center, is to assess its effectiveness in the treatment of pneumothorax and its ease of operation, safety, and patient toleration. Methods: From June/97 to August/00, 107 patients with pneumotoraxes of different etiologies were analyzed. The majority (76%) were classified radiologically as suffering from moderate or large pneumothorax, three hypertensive pneumothorax, and one was bilateral. The pleural cavity was drained with teflon or polyurethane plastic pig-tail catheters (10.2F, 14F, straight 11F connected to the Heimlich valve or the valve was connected directly to the thoracic drain in post-thoracotomy patients). Results: The valve remained in place for one to 120 days (mean 4 days). Tolerance to the system was good in 89% of cases. There were no serious complication linked to the system. Associated pleural effusion in 20 patients (18.5%) did not prevent the system from functioning well. Only two patients (1.8%) developed subcutaneous emphysema, and therefore, a 36F Tubular drain under water seal was chosen. Thoracotomy for decortication was indicated in one patient (0.9%). Twenty patients (18.5%) were treated on an outpatient basis. Conclusions: The Heimlich valve confirmed its effectiveness in resolving pneumothorax of different etiologies and in postoperative air leaks. Its operation was simpler than that of conventional systems. The good toleration and safety mentioned by the patients was a determining factor in early hospital discharge and a motive for outpatient treatment

Environmental exposure to organochlorine pesticides and deficits in cochlear status in children

The aim of this study was to examine the hypothesis that organochlorine pesticides (OCPs), hexachlorobenzene (HCB), β-hexachlorocyclohexane (β-HCH), and 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (p,p'-DDT) and its metabolite 1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene (p,p'- DDE) are ototoxic to humans. A multivariate general linear model was designed, in which the statistical relation between blood serum concentrations of HCB, β-HCH, p,p'-DDT, or p,p'-DDE at different ages (at birth, 6, 16, and 45 months) and the distortion product otoacoustic emissions (DPOAEs) was treated as multivariate outcome variables. Polychlorinated biphenyl (PCB) congeners and OCPs were strongly correlated in serum of children from our cohort. To ascertain that the association between DPOAEs at a given frequency and concentration of a pesticide is not influenced by PCBs or other OCP also present in serum, we calculated benchmark concentrations (BMCs) relating DPOAEs to a serum pesticide alone and in presence of confounding PCB-153 or other OCPs. We found that BMCs relating DPOAEs to serum pesticides are not affected by confounders. DPOAE amplitudes were associated with serum OCPs at all investigated time intervals, however, in a positive way with prenatal exposure and in a negative way with all postnatal exposures. We observed tonotopicity in the association of pesticides with amplitude of DPOAEs as its strength was frequency dependent. We conclude that exposure to OCPs in infancy at environmental concentrations may be associated with hearing deficits

The role of attention in remembering important item-location associations

When encountering an excess of information, people are able to selectively remember high-value information by strategically allocating attention during the encoding period, termed value-directed remembering. This has been demonstrated in both the episodic verbal and visuospatial memory domains. Importantly, the allocation of attention also plays a crucial role in the binding of identity and location information in visuospatial memory. We examined how taxing attentional resources to various degrees during encoding might affect visuospatial memory and selectivity. Participants studied items paired with point values indicating their value in a grid display and were asked to maximize their point score (a summation of the points associated with correctly remembered information). Participants viewed items under either a sequential or simultaneous presentation format and in either the presence or absence of a secondary tone discrimination task. While participants in the divided attention conditions recalled fewer item-location associations overall, participants in all encoding conditions prioritized high-value information in memory, providing further evidence that selectivity can be maintained even when attentional resources are taxed. However, differences between presentation formats emerged when conducting spatial resolution analyses examining errors. Errors in the simultaneous conditions were only influenced by item value when attention was full during encoding, while errors in the sequential conditions were not influenced by item value, regardless of available attentional resources. The results suggest participants can strategically allocate attention during encoding even under cognitively-demanding conditions and that gist-based visuospatial memory may only be influenced by information importance when adequate attentional resources are available