Frequency of consanguineous marriages among parents and grandparents of Down patients

Summary The existence of a rare autosomal gene which in the homozygous state would cause mitotic nondisjunction in the Down zygote has been hypothesized in the past by Alfi et al. (1980). This hypothesis can be supported or contradicted by the study of the frequency of consanguineous marriages among parents of affected children. Our study on 242 children affected with Down syndrome does not show any increase in the frequency of consanguineous marriages among their parents with respect to the general population, and therefore does not support the hypothesis of an autosomal gene controlling mitotic nondisjunction. Our data do not show any increase in the frequency of consanguineaous marriages even among paternal and maternal grandparents of the affected children, thus not supporting the other possible explanation of an autosomal recessive condition in one of the patient's parents which would cause meiotic nondisjunction.     

BH3‐in‐groove dimerization initiates and helix 9 dimerization expands Bax pore assembly in membranes

Pro‐apoptotic Bax induces mitochondrial outer membrane permeabilization (MOMP) by forming oligomers through a largely undefined process. Using site‐specific disulfide crosslinking, compartment‐specific chemical labeling, and mutational analysis, we found that activated integral membrane Bax proteins form a BH3‐in‐groove dimer interface on the MOM surface similar to that observed in crystals. However, after the α5 helix was released into the MOM, the remaining interface with α2, α3, and α4 helices was rearranged. Another dimer interface was formed inside the MOM by two intersected or parallel α9 helices. Combinations of these interfaces generated oligomers in the MOM. Oligomerization was initiated by BH3‐in‐groove dimerization, without which neither the other dimerizations nor MOMP occurred. In contrast, α9 dimerization occurred downstream and was required for release of large but not small proteins from mitochondria. Moreover, the release of large proteins was facilitated by α9 insertion into the MOM and localization to the pore rim. Therefore, the BH3‐in‐groove dimerization on the MOM nucleates the assembly of an oligomeric Bax pore that is enlarged by α9 dimerization at the rim.     

The same molecular mechanism at the maternal meiosis I produces mono- and dicentric 8p duplications.

We studied 16 cases of 8p duplications, with a karyotype 46,XX or XY,dup(8p), associated with mental retardation, facial dysmorphisms, and brain defects. We demonstrate that these 8p rearrangements can be either dicentric (6 cases) with the second centromere at the tip of the short arm or monocentric (10 cases). The distal 8p23 region, from D8S349 to the telomere, including the defensin 1 locus, is deleted in all the cases. The region spanning from D8S252 to D8S265, at the proximal 8p23 region, is present in single copy, and the remaining part of the abnormal 8 short arm is duplicated in the dicentric cases and partially duplicated in the monocentric ones. The distal edge of the duplication always spans up to D8S552 (8p23.1), while its proximal edge includes the centromere in the dicentric cases and varies from case to case in the monocentric ones. The analysis of DNA polymorphisms indicates that the rearrangement is consistently of maternal origin. In the deleted region, only paternal alleles were present in the patient. In the duplicated region, besides one paternal allele, some loci showed two different maternal alleles, while others, which were duplicated by FISH analysis, showed only one maternal allele. We hypothesize that, at maternal meiosis I, there was abnormal pairing of chromosomes 8 followed by anomalous crossover at the regions delimited by D8S552 and D8S35 and by D8S252 and D8S349, which presumably contain inverted repeated sequences. The resulting dicentric chromosome, 8qter-8p23.1(D8S552)::8p23.1-(D8S35)-8q ter, due to the presence of two centromeres, breaks at anaphase I, generating an inverted duplicated 8p, dicentric if the breakage occurs at the centromere or monocentric if it occurs between centromeres.     

Characterization and mapping of the 5′ portion of von Willebrand factor pseudogene

A genomic fragment containing the 5 boundary of the von Willebrand factor pseudogene was cloned, partially sequenced and used for in situ hybridization experiments on metaphase spreads from a Philadelphia chromosome (Ph¹)-positive chronic myelogenous leukemia patient. Data obtained indicate that the von Willebrand factor pseudogenic region is centromeric to the breakpoint cluster region on 22q11.2. This probe could be used for the study of deletions in the DiGeorge syndrome.     

PRDM12 Is Required for Initiation of the Nociceptive Neuron Lineage during Neurogenesis

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Effects of climate on pine processionary moth fecundity and on its egg parasitoids

Climate change may be affecting the fecundity of phytophagous insects as well as impacting their natural enemies. However, temperature impacts these two insect groups differently, disrupting population regulation mechanisms, and ultimately, possibly culminating in an outbreak of the host. The pine processionary moth (PPM) is one of the most harmful insects of the Mediterranean basin. Not only are PPM larvae harmful to plants, but they are also dangerous to humans because of their urticating hairs. Although some information is available on climate change effects on the PPM, little is known about its potential effects on PPM egg parasitoids, especially on their distribution range or on their role in controlling PPM populations. The aim of this article was to verify the effects of climate on PPM fecundity and on its egg parasitoids. Our results show that climate warming may affect the PPM positively, but not its egg parasitoids. Specifically, during our study mild winters directly favored the PPM, while increasing summer temperatures (over 30°C) also favored the PPM indirectly, by decreasing parasitism rates. We predict that ever‐milder winters will not only favor PPM development, but also encourage it to spread in otherwise previously inhospitable environments.     

Perinatal stem cells: A promising cell resource for tissue engineering of craniofacial bone

In facing the mounting clinical challenge and suboptimal techniques of craniofacial bone defects resulting from various conditions, such as congenital malformations, osteomyelitis, trauma and tumor resection, the ongoing research of regenerative medicine using stem cells and concurrent advancement in biotechnology have shifted the focus from surgical reconstruction to a novel stem cell-based tissue engineering strategy for customized and functional craniofacial bone regeneration. Given the unique ontogenetical and cell biological properties of perinatal stem cells, emerging evidence has suggested these extraembryonic tissue-derived stem cells to be a promising cell source for extensive use in regenerative medicine and tissue engineering. In this review, we summarize the current achievements and obstacles in stem cell-based craniofacial bone regeneration and subsequently we address the characteristics of various types of perinatal stem cells and their novel application in tissue engineering of craniofacial bone. We propose the promising feasibility and scope of perinatal stem cell-based craniofacial bone tissue engineering for future clinical application.     

Respiratory gas monitoring in patients with chronic respiratory failure during intensive positive pressure ventilation vs aerosol therapy

Summary The aim of this study is to evaluate the variations of respiratory gas concentration with transcutaneous blood gas measurements (tcm PO₂; tcm PCO₂) during intermittent positive pressure ventilation (I.P.P.V.) and aerosol therapy in patients (5 female, 5 male; 43–75 years) with chronic obstructive pulmonary diseases (COPD) with haemo gas analysis values PO₂<76 mmHg. The subjects underwent transcutaneous blood gas monitoring, 16 minutes during therapy (I.P.P.V. or aerosol) and 14 minutes of recovery. ANOVA analysis of variance was used for statistical analysis. During I.P.P.V. tcm PO₂ increase from the base value (60.6±9 mmHg) already after 2 minutes until the 16th minute (69.7±9); 2 minutes after the end of I.P.P.V. tcm PO₂ falls below the basic one (57.6±7) and then exceeds the basic value until the 14th minute (63.5±10) (p=ns). The base tcm PCO₂ (41.2±7) decreases reaching the maximum decrement at the 16th minute of therapy (32±6.6); at the end of I.P.P.V. it increases without exceeding the base value (39.5±7) (p<0.01). During aerosol therapy, tcm PO₂ increases from the basic one (62.4±10) (maximum after 16 minutes 70±9.5), then it decreases (64±11) and increases againg reaching the maximum growth after 14 minutes of recovery (65.7±11) (p=ns). The tcm PCO₂ values show a decrement below the base value (42.7±4.5) reaching its maximum at the 16th minute of therapy (38.8±7); at the end of aerosol the tem PCO₂ increases (42.5±4.6) (p=ns). The tcm PO₂ variations (I.P.P.V. vs aerosol) did not show any significant statistical difference. At the end of the therapies the tcm PO₂ falls a little more after I.P.P.V. than after aerosol (57.6±7.3 vs 64±11, p=ns); the tcm PCO₂ base values are similar during the two therapies (41.2±7 vs 42.7±4.5, p=ns), but the tcm PCO₂ decrements reach a significant statistical difference after 8–10–12–16 minutes (p<0.05); during the recovery time after 2 minutes (34±6.5 vs 40±6.3, p<0.05) and this difference disappeared at the last recording. We calculate the tcm PO₂ increment and the tcm PCO₂ decrement from the base value. The tcm PO₂ increment is higher during I.P.P.V. than during aerosol therapy. The tcm PCO₂ decrement shows how the tcm PCO₂ falls during I.P.P.V. and how these values remain below the base one until the end of the rest time. Data reported here demonstrate that mechanical physiokinesi therapy improves COPD ventilation so that the respiratory pattern could be ameliorated and preserved.