Carolyn Rogers

Dinoflagellate Expressed Sequence Tag Data Indicate Massive Transfer of Chloroplast Genes to the Nuclear Genome

The peridinin-pigmented plastids of dinoflagellates are very poorly understood, in part because of the paucity of molecular data available from these endosymbiotic organelles. To identify additional gene sequences that would carry information about the biology of the peridinin-type dinoflagellate plastid and its evolutionary history, an analysis was undertaken of arbitrarily selected sequences from cDNA libraries constructed from Lingulodinium polyedrum (1012 non-redundant sequences) and Amphidinium carterae (2143). Among the two libraries 118 unique plastid-associated sequences were identified, including 30 (most from A. carterae) that are encoded in the plastid genome of the red alga Porphyra. These sequences probably represent bona fide nuclear genes, and suggest that there has been massive transfer of genes from the plastid to the nuclear genome in dinoflagellates. These data support the hypothesis that the peridinin-type plastid has a minimal genome, and provide data that contradict the hypothesis that there is an unidentified canonical genome in the peridinin-type plastid. Sequences were also identified that were probably transferred directly from the nuclear genome of the red algal endosymbiont, as well as others that are distinctive to the Alveolata. A preliminary report of these data was presented at the Botany 2002 meeting in Madison, WI.

Orbicularis oris muscle defects as an expanded phenotypic feature in nonsyndromic cleft lip with or without cleft palate

Nonsyndromic cleft lip ± cleft palate is a complex disease with a wide phenotypic spectrum; occult defects of the superior orbicularis oris muscle may represent the mildest subclinical form of the lip portion of the phenotype. This study used high‐resolution ultrasonography to compare the frequency of discontinuities in the OO muscle in 525 unaffected relatives of individuals with nonsyndromic cleft lip  ±  cleft palate versus 257 unaffected controls. OO muscle discontinuities were observed in 54 (10.3%) of the non‐cleft relatives, compared to 15 (5.8%) of the controls—a statistically significant increase (P = 0.04). Male relatives had a significantly higher rate of discontinuities than male controls (12.0% vs. 3.2%; P = 0.01); female relatives also had a higher rate of discontinuities than female controls, but the increase was not statistically significant (8.9% vs. 7.4%; P = 0.56). These data confirm the hypothesis that subepithelial OO muscle defects are a mild manifestation of the cleft lip phenotype. Identification of subepithelial OO muscle defects may be important in a clinical setting, as a means of providing more accurate recurrence risk estimates to relatives in cleft families. Furthermore, the expansion of the cleft lip  ±  cleft palate phenotypic spectrum should improve the power of genetic studies.

Integrated Plastic Surgery Residency Applicant Survey: Characteristics of Successful Applicants and Feedback about the Interview Process

Background: Integrated plastic surgery residency training is growing in popularity, bringing new challenges to program directors and applicants. The purpose of this study was to identify characteristics of successful applicants and to obtain feedback from applicants to improve the integrated plastic surgery residency training application and interview process. Methods: An anonymous survey assessing applicant academic qualifications, number of interviews offered and attended, and opinions about the application and interview process was distributed electronically to the 2006 integrated plastic surgery residency training applicant class. The number of interviews offered was used as an indicator of potential applicant success. Results: A 38 percent survey participation rate (139 of 367) was achieved. United States Medical Licensing Examination Step 1 score correlated with number of interview invitations (p ≤ 0.001). Successful Alpha Omega Alpha designation (p ≤ 0.001), high class rank (p = 0.034), presence of a plastic surgery residency program at the participant’s school (p = 0.026), and authorship of one or more publications (p ≤ 0.001) were associated with receiving greater number of interview invitations. Geographic location was an important consideration for applicants when applying to and ranking programs. Applicants desired interviews on weekdays and geographic coordination of interviews. Conclusions: Integrated plastic surgery residency training is highly competitive, with the number of interview invitations correlating with academic performance and, to a lesser extent, research. Applicant feedback from this survey can be used to improve the application and interview process.

Reconstruction of the lateral mandibulectomy defect: Management based on prognosis and location and volume of soft tissue resection

Objective: To examine how the accompanying soft tissue resection of the oral cavity, oropharynx, neck, or face affects the reconstructive management of the lateral mandibulectomy defect.

Automated facial image analysis: detecting improvement in abnormal facial movement after treatment with botulinum toxin A.

The purpose of this study was to evaluate the ability of Automated Facial Image Analysis (AFA) to detect changes in facial motion after Botox injections in patients with facial nerve disorders accompanied by abnormal muscle activity. Eight subjects received Botox for oral to ocular synkinesis (n = 6), ocular to oral synkinesis (n = 1), and/or depressor anguli oris overactivity (n = 3). Subjects were video-recorded during 2 directed facial action tasks before and after Botox treatment. AFA measurement and Facial Grading System (FGS) scores were used to evaluate the effects of Botox. After Botox, AFA detected a decrease in abnormal movements of the eyelids in all patients with oral to ocular synkinesis, a decrease in oral commissure movement for the patients with ocular to oral synkinesis, and an increase in oral commissure movement in all patients with depressor overactivity. The FGS scores failed to demonstrate any change in facial movement for the case of ocular to oral synkinesis and for 2 cases of depressor overactivity. AFA enables recognition of subtle changes in facial movement that may not be adequately measured by observer based ratings of facial function.

Comparative microanatomy of the orbicularis oris muscle between chimpanzees and humans: evolutionary divergence of lip function

The orbicularis oris muscle plays a role in the production of primate facial expressions and vocalizations, nutrient intake, and in some non‐human primates it is used as a prehensile, manipulative tool. As the chimpanzee (Pan troglodytes) is the closest living relative of humans, a comparison of the orbicularis oris muscle between these species may increase our understanding of the morphological specializations related to the differing functional demands of their lips and the factors responsible for their divergent evolution. To this end, this study compares the microanatomy of the mid‐line upper fibers of the orbicularis oris muscle between chimpanzees and humans. A mid‐line portion of the orbicularis oris muscle was harvested from the upper lips of three chimpanzee and five human cadavers. The sampled blocks included the area between the lateral borders of the nasal alar cartilages in both species. Each sample was processed for paraffin histology, sectioned and stained with a variety of protocols. Sections were examined for fiber direction and relative thickness of muscle layers. Ratios of cross‐sectional connective tissue area vs. cross‐sectional muscle tissue area, muscle fiber diameter and relative dermal thickness were calculated for each species. In both species, a clear pars marginalis layer was recognized, contrary to previous reports that only humans possess this layer. In chimpanzees, the relative fiber diameter and relative amount of muscle tissue (i.e. based on ratio of connective tissue area : muscle tissue area) were significantly (P < 0.05) greater than in humans. In contrast, measurements of relative dermal thickness showed that humans have a greater average dermal thickness of the upper lip than chimpanzees. Taken together, these results suggest that both human and chimpanzee orbicularis oris muscle upper fibers meet the specific functional demands associated with their divergent vocal and facial display repertoires, the development of human speech, and the use of the upper lip as a prehensile tool in chimpanzees.

Maternal attitudes to newborn screening for fragile X syndrome.

Although fragile X syndrome (FXS) is the commonest cause of inherited intellectual disability the mean age of diagnosis in Australia is 5.5 years. Newborn screening for FXS can provide an early diagnosis, preventing the “diagnostic odyssey”, allowing access to early interventions, and providing reproductive information for parents. Parents of affected children support newborn screening, but few clinical studies have evaluated community attitudes. A pilot study in 2009–2010 was performed in a tertiary hospital to explore feasibility and maternal attitudes. FXS testing of male and female newborns was offered to mothers in addition to routine newborn screening. Mothers were provided with information about FXS, inheritance pattern, carrier status, and associated adult‐onset disorders. One thousand nine hundred seventy‐one of 2,094 mothers (94%) consented to testing of 2,000 newborns. 86% completed the attitudinal survey and 10% provided written comments. Almost all parents (99%) elected to be informed of both premutation and full mutation status and there was little concern about identification of carrier status or associated adult‐onset disorders. Most mothers (96%) were comfortable being approached in the postnatal period and supported testing because no extra blood test was required. Mothers considered an early diagnosis beneficial to help prepare for a child with additional needs (93%) and for reproductive planning (64%). Some were anxious about the potential test results (10%) and others felt their feelings towards their newborn may change if diagnosed with FXS (16%). High participation rates and maternal attitudes indicate a high level of maternal acceptance and voluntary support for newborn screening for FXS.

Anatomical Basis for Apparent Subepithelial Cleft Lip: A Histological and Ultrasonographic Survey of the Orbicularis Oris Muscle

Objective: To determine if there is an anatomic basis for subepithelial orbicularis oris muscle defects by directly comparing ultrasonographic images of the upper lip with corresponding histological sections obtained from cadavers. Methods: Ultrasound was performed on the upper lips of previously frozen, unpreserved cadaver heads (n  =  32), followed by dissection and sectioning of the upper lips. The ultrasound sequences were scored by a panel of raters, classifying the orbicularis oris muscle as negative, positive, or unknown for the presence of an orbicularis oris discontinuity (subepithelial defect). Based on ultrasound, six lip specimens were chosen for histological sectioning, were stained with hematoxylin-eosin and Gomori trichrome stain, and were evaluated with light microscopy at low (8×) and intermediate (100×) magnification. Results: One cadaver was scored positive for an orbicularis oris muscle discontinuity based on ultrasound; whereas, the remaining cadavers were scored negative. Of the cadavers with negative ultrasound scores, two were noted to have orbicularis oris muscles with “irregular” features (e.g., excessive localized thinning or asymmetry). From histology, the area of discontinuity as visualized on the positively scored ultrasound was characterized by both disorganized orbicularis oris muscle fibers and excess connective tissue within the muscle belly. In contrast, the localized thinning observed on some of the negatively scored ultrasounds was not confirmed by histology. Conclusions: Abnormalities of the orbicularis oris muscle visualized by ultrasound have an anatomic basis as revealed through histology. Ultrasound is a useful tool for noninvasively identifying discontinuities of the orbicularis oris muscle.

THOC2 Mutations Implicate mRNA-Export Pathway in X-Linked Intellectual Disability

Export of mRNA from the cell nucleus to the cytoplasm is essential for protein synthesis, a process vital to all living eukaryotic cells. mRNA export is highly conserved and ubiquitous. Mutations affecting mRNA and mRNA processing or export factors, which cause aberrant retention of mRNAs in the nucleus, are thus emerging as contributors to an important class of human genetic disorders. Here, we report that variants in THOC2, which encodes a subunit of the highly conserved TREX mRNA-export complex, cause syndromic intellectual disability (ID). Affected individuals presented with variable degrees of ID and commonly observed features included speech delay, elevated BMI, short stature, seizure disorders, gait disturbance, and tremors. X chromosome exome sequencing revealed four missense variants in THOC2 in four families, including family MRX12, first ascertained in 1971. We show that two variants lead to decreased stability of THOC2 and its TREX-complex partners in cells derived from the affected individuals. Protein structural modeling showed that the altered amino acids are located in the RNA-binding domains of two complex THOC2 structures, potentially representing two different intermediate RNA-binding states of THOC2 during RNA transport. Our results show that disturbance of the canonical molecular pathway of mRNA export is compatible with life but results in altered neuronal development with other comorbidities.

Reconstruction of the through-and-through anterior mandibulectomy defect: indications and limitations of the double-skin paddle fibular free flap.

Objectives/Hypothesis: The purpose of this report is to describe our recent experience using a double‐skin paddle fibular free flap (DSPFFF) for reconstruction of the through‐and‐through anterior mandibulectomy defect and to present a reconstructive algorithm based on the extent of lip and mental skin resection.