Protocol for a seamless phase 2A-phase 2B randomized double-blind placebo-controlled trial to evaluate the safety and efficacy of benfotiamine in patients with early Alzheimer's disease (BenfoTeam).

BACKGROUND: Benfotiamine provides an important novel therapeutic direction in Alzheimer's disease (AD) with possible additive or synergistic effects to amyloid targeting therapeutic approaches. OBJECTIVE: To conduct a seamless phase 2A-2B proof of concept trial investigating tolerability, safety, and efficacy of benfotiamine, a prodrug of thiamine, as a first-in-class small molecule oral treatment for early AD. METHODS: This is the protocol for a randomized, double-blind, placebo-controlled 72-week clinical trial of benfotiamine in 406 participants with early AD. Phase 2A determines the highest safe and well-tolerated dose of benfotiamine to be carried forward to phase 2B. During phase 2A, real-time monitoring of pre-defined safety stopping criteria in the first approximately 150 enrollees will help determine which dose (600 mg or 1200 mg) will be carried forward into phase 2B. The phase 2A primary analysis will test whether the rate of tolerability events (TEs) is unacceptably high in the high-dose arm compared to placebo. The primary safety endpoint in phase 2A is the rate of TEs compared between active and placebo arms, at each dose. The completion of phase 2A will seamlessly transition to phase 2B without pausing or stopping the trial. Phase 2B will assess efficacy and longer-term safety of benfotiamine in a larger group of participants through 72 weeks of treatment, at the selected dose. The co-primary efficacy endpoints in phase 2B are CDR-Sum of Boxes and ADAS-Cog13. Secondary endpoints include safety and tolerability measures; pharmacokinetic measures of thiamine and its esters, erythrocyte transketolase activity as blood markers of efficacy of drug delivery; ADCS-ADL-MCI; and MoCA. CONCLUSION: The BenfoTeam trial utilizes an innovative seamless phase 2A-2B design to achieve proof of concept. It includes an adaptive dose decision rule, thus optimizing exposure to the highest and best-tolerated dose. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06223360, registered on January 25, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT06223360.

Hemolytic Anemia in the Setting of Atypical Pneumonia: A Case of Cold Agglutinin Disease.

Cold agglutinin hemolytic anemia (cAHA) is a rare autoimmune disorder characterized by the production of cold agglutinins. We present a case of secondary cAHA in a 23-year-old female with severe anemia and unexplained hemolysis. The patient exhibited findings indicative of hemolysis and a positive direct antiglobulin test (DAT) with complement alone. Additional investigations revealed incidental lung infiltrates, negative serology for infections and autoimmune diseases, and a low cold agglutinin titer. The patient showed a favorable response to doxycycline and supportive therapy, including multiple packed red blood cell transfusions. At the two-week follow-up, the patient had a stable hemoglobin level with no evidence of ongoing hemolysis. This case highlights the importance of considering secondary cAHA in patients with cold symptoms or unexplained hemolysis. Primary cAHA patients may require more aggressive treatment, including rituximab and sutilumab.

Leptoomidae, a new family of Eocene fossil Chalcidoidea (Hymenoptera), and family classification of Eocene fossil genera originally described in Neanastatinae (Eupelmidae).

Leptoomidae Gibson fam. nov. (Chalcidoidea) is described for the Eocene Baltic amber fossil genera Leptoomus Gibson, type genus, reassigned from Tanaostigmatidae, and Neanaperiallus Gibson, reassigned from Neanastatinae (Chalcidoidea: Eupelmidae) sensu Gibson (2009). One new species of Neanaperiallus, N. defunctus Fusu sp. nov., is described. The new family is differentiated from other families of Chalcidoidea that are partly characterized by a greatly enlarged acropleuron. In species of Leptoomidae the prepectus is anteriorly rounded to angulate and extends to or slightly over the posterolateral margin of the pronotum, with the dorsal prepectal margin intersecting the base of the tegula distinctly anterior to and forming an almost right-angle with the posterior margin of prepectus, and the posterior margin truncate along the anterior margin of the acropleuron. This prepectal structure is similar to that in Tanaostigmatidae and Cynipencyrtidae, except the prepectus is elongated anteriorly exterior to the pronotum in Tanaostigmatidae and interior to the lateral surface of the pronotum in Cynipencyrtidae. A difference in prepectal structure also indicates that an anteriorly elongated mesoscutal process internal to the pronotum in Encyrtidae is convergent to that of Cynipencyrtidae, and similarity in shape of the prepectus among Encyrtidae, Eopelma Gibson and Neanastatus Girault might be functionally correlated with an anterior elongation of the mesoscutal process. New or corrected morphological data are provided for the two included genera. Of other Eocene fossil genera originally classified in Neanastatinae, Brevivulva Gibson and Propelma Trjapitzin, are assigned to Neanastatidae sensu Burks et al. (2022) based on similar mesoscutellar structures. Possible relationships of Aspidopleura Gibson, a taxon with a puzzling combination of features, are discussed. Because Aspidopleura cannot be placed with confidence in any extinct or extant higher taxon it is treated as incertae sedis at family level within Chalcidoidea.

Nutritional metabolism and cerebral bioenergetics in Alzheimer's disease and related dementias.

Disturbances in the brain's capacity to meet its energy demand increase the risk of synaptic loss, neurodegeneration, and cognitive decline. Nutritional and metabolic interventions that target metabolic pathways combined with diagnostics to identify deficits in cerebral bioenergetics may therefore offer novel therapeutic potential for Alzheimer's disease (AD) prevention and management. Many diet-derived natural bioactive components can govern cellular energy metabolism but their effects on brain aging are not clear. This review examines how nutritional metabolism can regulate brain bioenergetics and mitigate AD risk. We focus on leading mechanisms of cerebral bioenergetic breakdown in the aging brain at the cellular level, as well as the putative causes and consequences of disturbed bioenergetics, particularly at the blood-brain barrier with implications for nutrient brain delivery and nutritional interventions. Novel therapeutic nutrition approaches including diet patterns are provided, integrating studies of the gut microbiome, neuroimaging, and other biomarkers to guide future personalized nutritional interventions.

Pharmacological thiamine levels as a therapeutic approach in Alzheimer's disease.

of the study.

The α-Ketoglutarate Dehydrogenase Complex as a Hub of Plasticity in Neurodegeneration and Regeneration.

Abnormal glucose metabolism is central to neurodegeneration, and considerable evidence suggests that abnormalities in key enzymes of the tricarboxylic acid (TCA) cycle underlie the metabolic deficits. Significant recent advances in the role of metabolism in cancer provide new insight that facilitates our understanding of the role of metabolism in neurodegeneration. Research indicates that the rate-limiting step of the TCA cycle, the α-ketoglutarate dehydrogenase complex (KGDHC) and its substrate alpha ketoglutarate (KG), serve as a signaling hub that regulates multiple cellular processes: (1) is the rate-limiting step of the TCA cycle, (2) is sensitive to reactive oxygen species (ROS) and produces ROS, (3) determines whether KG is used for energy or synthesis of compounds to support growth, (4) regulates the cellular responses to hypoxia, (5) controls the post-translational modification of hundreds of cell proteins in the mitochondria, cytosol, and nucleus through succinylation, (6) controls critical aspects of transcription, (7) modulates protein signaling within cells, and (8) modulates cellular calcium. The primary focus of this review is to understand how reductions in KGDHC are translated to pathologically important changes that underlie both neurodegeneration and cancer. An understanding of each role is necessary to develop new therapeutic strategies to treat neurodegenerative disease.

Altered succinylation of mitochondrial proteins, APP and tau in Alzheimer's disease.

Abnormalities in brain glucose metabolism and accumulation of abnormal protein deposits called plaques and tangles are neuropathological hallmarks of Alzheimer's disease (AD), but their relationship to disease pathogenesis and to each other remains unclear. Here we show that succinylation, a metabolism-associated post-translational protein modification (PTM), provides a potential link between abnormal metabolism and AD pathology. We quantified the lysine succinylomes and proteomes from brains of individuals with AD, and healthy controls. In AD, succinylation of multiple mitochondrial proteins declined, and succinylation of small number of cytosolic proteins increased. The largest increases occurred at critical sites of amyloid precursor protein (APP) and microtubule-associated tau. We show that in vitro, succinylation of APP disrupted its normal proteolytic processing thereby promoting Aß accumulation and plaque formation and that succinylation of tau promoted its aggregation to tangles and impaired microtubule assembly. In transgenic mouse models of AD, elevated succinylation associated with soluble and insoluble APP derivatives and tau. These findings indicate that a metabolism-linked PTM may be associated with AD.

Ring the Bell for Sickle Cell: Encouraging Advocacy in an Underserved Community.

Sickle cell disease (SCD) was once a disease of childhood because of a limited life expectancy. Due to medical advances, it is now common for people with SCD to live into adulthood. Funding and resources for adults with SCD, however, remain limited. Adult patients would benefit from increased access to medical care, mental health care services, and workforce development. The Indiana Sickle Cell Consortium, a group of medical providers and community-based organizations, worked closely with people living with SCD and their family members to create a campaign advocating for state funding for programs for adults with SCD. This campaign culminated with the passage of a bill that provides $250,000 in funding for program development for adults with SCD. The bill also directs the Indiana Department of Health to carry out a needs assessment for people with SCD in Indiana. However, continued efforts are needed to reduce health disparities for people with SCD. The Indiana Sickle Cell Consortium will continue advocacy efforts in future legislative cycles and bring attention to the health inequities that affect people with SCD.

Serum Metabolomic and Lipidomic Profiling Reveals Novel Biomarkers of Efficacy for Benfotiamine in Alzheimer's Disease.

Serum metabolomics and lipidomics are powerful approaches for discovering unique biomarkers in various diseases and associated therapeutics and for revealing metabolic mechanisms of both. Treatment with Benfotiamine (BFT), a thiamine prodrug, for one year produced encouraging results for patients with mild cognitive impairment and mild Alzheimer's disease (AD). In this study, a parallel metabolomics and lipidomics approach was applied for the first exploratory investigation on the serum metabolome and lipidome of patients treated with BFT. A total of 315 unique metabolites and 417 lipids species were confidently identified and relatively quantified. Rigorous statistical analyses revealed significant differences between the placebo and BFT treatment groups in 25 metabolites, including thiamine, tyrosine, tryptophan, lysine, and 22 lipid species, mostly belonging to phosphatidylcholines. Additionally, 10 of 11 metabolites and 14 of 15 lipid species reported in previous literature to follow AD progression changed in the opposite direction to those reported to reflect AD progression. Enrichment and pathway analyses show that significantly altered metabolites by BFT are involved in glucose metabolism and biosynthesis of aromatic amino acids. Our study discovered that multiple novel biomarkers and multiple mechanisms that may underlie the benefit of BFT are potential therapeutic targets in AD and should be validated in studies with larger sample sizes.

A Rare Case of Primary Adenocarcinoma of the Eyelid: Case Presentation and Review of Literature.

Primary mucinous adenocarcinoma (PMA) of the eyelid is a very rare malignancy with an incidence of 0.07 per million. Most cases are elderly males with an indolent course of local growth over months. We report a rare case of a 61-year-old gentleman with an aggressive course of PMA. The patient presented with a painless lower right eyelid swelling that developed over a four-month period. Incisional biopsy of the mass disclosed mucinous adenocarcinoma, positive for cytokeratin (CK)7 but negative for thyroid transcription factor 1, S100, and CK20 expression. Magnetic resonance imaging of the orbits revealed an enhancing infiltrative mass extending from the right lower eyelid to the medial canthus and posteriorly into the orbit, the right ethmoid sinuses, and extraconal fat within the orbit. Workup for metastatic disease including scans of chest, abdomen, and pelvis as well as positron emission tomography/computed tomography were negative for other masses. The patient underwent extensive surgery that included exenteration of the right orbit and cervical lymph node dissection followed by adjuvant radiation therapy and chemotherapy due to the extent of periorbital tumor invasion of contiguous tissues. Diagnosis of PMA is a clinical challenge, and immunohistochemistry is essential for diagnosis. To confirm it as a primary tumor, exclusion of metastasis from elsewhere is appropriate. Reported treatment modalities include Mohs micrographic surgery or excision with frozen section and safety margin. Exenteration of the orbit may be indicated depending on the extent of orbital invasion by the tumor. There is limited evidence to guide treatment and follow-up, with information consisting mostly of published case reports and case series.

The human brain acetylome reveals that decreased acetylation of mitochondrial proteins associates with Alzheimer's disease.

Metabolic changes that correlate to cognitive changes are well-known in Alzheimer's disease (AD). Metabolism is often linked to functional changes in proteins by post-translational modifications. The importance of the regulation of transcription by acetylation is well documented. Advanced mass spectrometry reveals hundreds of acetylated proteins in multiple tissues, but the acetylome of human brain, its functional significance, and the changes with disease are unknown. Filling this gap is critical for understanding the pathophysiology and development of therapies. To fill this gap, we assessed the human brain acetylome in human brain and its changes with AD. More than 5% of the 4,442 proteins from the human brain global proteome were acetylated. Acetylated proteins were primarily found in the cytosol (148), mitochondria (100), nucleus (91), and plasma membrane (58). The comparison of the brain acetylome in controls to that of patients with AD revealed striking and selective differences in terms of its abundances of acetylated peptides/sites. Acetylation of 18 mitochondrial proteins decreased, while acetylation of two cytosolic proteins, tau and GFAP, increased. Our experiments demonstrate that acetylation at some specific lysine sites alters enzyme function. The results indicate that general activation of de-acetylases (i.e., sirtuins) is not an appropriate therapeutic approach for AD.

Revision of the Old World genus Mesocomys Cameron (Hymenoptera: Eupelmidae).

The Old World genus Mesocomys Cameron (1905) (Hymenoptera: Eupelmidae: Eupelminae) is revised. Eleven species, including two newly described species, are recognized and keyed in two previously established species groups, the albitarsis and the pulchriceps species groups sensu Gibson (1995), but with additional features provided to distinguish members of the two groups. Five species are recognized in the pulchriceps group-Mesocomys anelliformis n. sp., M. longiscapus n. sp., M. orientalis Ferrière, 1935, M. pauliani Ferrière, 1951, and M. pulchriceps Cameron, 1905. Seven species are assigned to the albitarsis group, but one, M. aegeriae Sheng, 1996 is treated as a nomen dubium; the six recognized and keyed species in the albitarsis group are M. albitarsis (Ashmead, 1904), M. breviscapis Yao, Yang Zhao, 2009, M. menzeli (Ferrière, 1930b), M. obscurus (Ferrière, 1930b) revised stat., M. superansi Yao, Yang Zhao, 2009, and M. trabalae Yao, Yang Zhao, 2009. Within the albitarsis group, the species are further discussed relative to two newly established species subgroups, the albitarsis subgroup for M. albitarsis, M. menzeli and M. obscurus, and the aegeriae subgroup for M. aegeriae, M. breviscapis, M. superansi and M. trabalae. Females of the albitarsis subgroup possess a finely sculptured mesoscutal medial lobe in combination with partly infuscate fore wings and/or at least partly pale flagellum, whereas females of the aegeriae subgroup possess a much more coarsely sculptured mesoscutal medial lobe and hyaline fore wings in combination with a dark flagellum. Members of the albitarsis species group are restricted to the Oriental and eastern Palaearctic regions except for a single female of the aegeriae subgroup seen from Algeria that is provisionally identified as M. breviscapis; members of the pulchriceps group are restricted to the Afrotropical region except for M. orientalis from the Oriental region. Newly placed in synonymy are M. aegeriae Sheng, 1998 under M. aegeriae Sheng, 1996 n. syn., M. sinensis Yao, Yang Zhao, 2009 under M. breviscapis Yao, Yang Zhao, 2009 n. syn., M. atulyus Narendran, 1995 under M. orientalis Ferrière, 1935 n. syn., M. vuilleti (Crawford, 1912) under M. pulchriceps Cameron, 1905 n. syn., and Semianastatus orientalis Kalina, 1984 and Mesocomys kalinai Özdikmen, 2011 under M. albitarsis (Ashmead, 1904) n. syns. Lectotypes are newly designated for M. menzeli, M. obscurus, M. orientalis, M. pauliani, M. pulchriceps and M. vuilleti. Morphological features characteristic of the genus and of the highly dimorphic sexes are described and illustrated, and the species are keyed, described, and illustrated through macrophotography. Phylogenetics are discussed for the genus, the two species groups, and species within the pulchriceps group. Distribution and host records are also summarized for each species.

Uterine Carcinosarcoma in a Young Female: Case Report and Literature Review.

Uterine carcinosarcoma (USC) is a rare, aggressive primary neoplasm of the Uterus that represents less than 5% of all uterine malignancies. It usually affects older females in their seventh decade. USC disproportionally affects black women more and it has a worse prognosis than other endometrial carcinomas. We present a case of uterine carcinosarcoma in a young Caucasian female who presented with vague symptoms of nausea, vomiting, and severe iron deficiency anemia.

Selective linkage of mitochondrial enzymes to intracellular calcium stores differs between human-induced pluripotent stem cells, neural stem cells, and neurons.

Mitochondria and releasable endoplasmic reticulum (ER) calcium modulate neuronal calcium signaling, and both change in Alzheimer's disease (AD). The releasable calcium stores in the ER are exaggerated in fibroblasts from AD patients and in multiple models of AD. The activity of the alpha-ketoglutarate dehydrogenase complex (KGDHC), a key mitochondrial enzyme complex, is diminished in brains from AD patients, and can be plausibly linked to plaques and tangles. Our previous studies in cell lines and mouse neurons demonstrate that reductions in KGDHC increase the ER releasable calcium stores. The goal of these studies was to test whether the relationship was true in human iPSC-derived neurons. Inhibition of KGDHC for one or 24 hr increased the ER releasable calcium store in human neurons by 69% and 144%, respectively. The effect was mitochondrial enzyme specific because inhibiting the pyruvate dehydrogenase complex, another key mitochondrial enzyme complex, diminished the ER releasable calcium stores. The link of KGDHC to ER releasable calcium stores was cell type specific as the interaction was not present in iPSC or neural stem cells. Thus, these studies in human neurons verify a link between KGDHC and releasable ER calcium stores, and support the use of human neurons to examine mechanisms and potential therapies for AD.

Benfotiamine and Cognitive Decline in Alzheimer's Disease: Results of a Randomized Placebo-Controlled Phase IIa Clinical Trial.

BACKGROUND: In preclinical models, benfotiamine efficiently ameliorates the clinical and biological pathologies that define Alzheimer's disease (AD) including impaired cognition, amyloid-ß plaques, neurofibrillary tangles, diminished glucose metabolism, oxidative stress, increased advanced glycation end products (AGE), and inflammation. OBJECTIVE: To collect preliminary data on feasibility, safety, and efficacy in individuals with amnestic mild cognitive impairment (aMCI) or mild dementia due to AD in a placebo-controlled trial of benfotiamine. METHODS: A twelve-month treatment with benfotiamine tested whether clinical decline would be delayed in the benfotiamine group compared to the placebo group. The primary clinical outcome was the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog). Secondary outcomes were the clinical dementia rating (CDR) score and fluorodeoxyglucose (FDG) uptake, measured with brain positron emission tomography (PET). Blood AGE were examined as an exploratory outcome. RESULTS: Participants were treated with benfotiamine (34) or placebo (36). Benfotiamine treatment was safe. The increase in ADAS-Cog was 43% lower in the benfotiamine group than in the placebo group, indicating less cognitive decline, and this effect was nearly statistically significant (p = 0.125). Worsening in CDR was 77% lower (p = 0.034) in the benfotiamine group compared to the placebo group, and this effect was stronger in the APOEɛ4 non-carriers. Benfotiamine significantly reduced increases in AGE (p = 0.044), and this effect was stronger in the APOEɛ4 non-carriers. Exploratory analysis derivation of an FDG PET pattern score showed a treatment effect at one year (p = 0.002). CONCLUSION: Oral benfotiamine is safe and potentially efficacious in improving cognitive outcomes among persons with MCI and mild AD.

Review of the species of Anastatus (Hymenoptera: Eupelmidae) known from China, with description of two new species with brachypterous females.

Fourteen species of Anastatus (Anastatus) Motschulsky, 1859 (Hymenoptera: Eupelmidae) are treated from China, of which A. (Anastatus) flavaeratus Peng and Tang n. sp. and A. (Anastatus) pariliquadrus Peng and Tang n. sp. are described based on brachypterous females. Two new synonyms are proposed, A. flavipes Sheng and Wang, 1997 under A. japonicus Ashmead, 1904 n. syn., and A. huangi Sheng and Yu, 1998 under A. gastropachae Ashmead, 1904 n. syn. The species previously reported from China under the name A. acherontiae Narayanan, Subba Rao and Ramachandra, 1960 is newly identified as Anastatus echidna (Motschulsky, 1863). Anastatus colemani Crawford, 1912, is excluded from the Chinese mainland fauna, and A. dendrolimus Kim and Pak, 1965, A. kashmirensis Mathur, 1956, and A. tenuipes Bolívar y Pieltain, 1925 are excluded from the Chinese fauna. Two previously recorded extralimital species, A. bifasciatus (Geoffroy, 1785) and A. colemani are treated as possibly present in China even though their presence was not confirmed and the records likely are based on misidentifications. Anastatus ramakrishnai (Mani, 1935), originally described from India, is compared with A. dexingensis Sheng and Wang, 1997 and A. formosanus Crawford, 1913, with the suggestion that the name could be synonymous with one of the latter two names. The males of nine species and females of all Anastatus species recognised from China are keyed, diagnosed, and illustrated. Information on recorded hosts and distribution is summarised for all the species.

Selective NADH communication from α-ketoglutarate dehydrogenase to mitochondrial transhydrogenase prevents reactive oxygen species formation under reducing conditions in the heart.

In heart failure, a functional block of complex I of the respiratory chain provokes superoxide generation, which is transformed to H2O2 by dismutation. The Krebs cycle produces NADH, which delivers electrons to complex I, and NADPH for H2O2 elimination via isocitrate dehydrogenase and nicotinamide nucleotide transhydrogenase (NNT). At high NADH levels, α-ketoglutarate dehydrogenase (α-KGDH) is a major source of superoxide in skeletal muscle mitochondria with low NNT activity. Here, we analyzed how α-KGDH and NNT control H2O2 emission in cardiac mitochondria. In cardiac mitochondria from NNT-competent BL/6N mice, H2O2 emission is equally low with pyruvate/malate (P/M) or α-ketoglutarate (α-KG) as substrates. Complex I inhibition with rotenone increases H2O2 emission from P/M, but not α-KG respiring mitochondria, which is potentiated by depleting H2O2-eliminating capacity. Conversely, in NNT-deficient BL/6J mitochondria, H2O2 emission is higher with α-KG than with P/M as substrate, and further potentiated by complex I blockade. Prior depletion of H2O2-eliminating capacity increases H2O2 emission from P/M, but not α-KG respiring mitochondria. In cardiac myocytes, downregulation of α-KGDH activity impaired dynamic mitochondrial redox adaptation during workload transitions, without increasing H2O2 emission. In conclusion, NADH from α-KGDH selectively shuttles to NNT for NADPH formation rather than to complex I of the respiratory chain for ATP production. Therefore, α-KGDH plays a key role for H2O2 elimination, but is not a relevant source of superoxide in heart. In heart failure, α-KGDH/NNT-dependent NADPH formation ameliorates oxidative stress imposed by complex I blockade. Downregulation of α-KGDH may, therefore, predispose to oxidative stress in heart failure.

Redescription of Anastatus mantoidae Motschulsky, the type species of Anastatus Motschulsky 1859, and Anastatus echidna (Motschulsky), the type species of Cacotropia Motschulsky 1863, with respect to taxonomy of Anastatus (Hymenoptera: Eupelmidae: Eupelminae).

Both sexes of Anastatus mantoidae Motschulsky, the type species of Anastatus Motschulsky, 1859, and females of Anastatus echidna (Motschulsky), the type species of Cacotropia Motschulsky, 1863, the oldest junior synonym of Anastatus (Hymenoptera: Eupelmidae: Eupelminae), are redescribed and illustrated based on original type material and compared to more recently collected material. Anastatus mantoidae, previously known only from Sri Lanka, is newly reported from Indonesia (Java and Sumatra) and Thailand, and a very similar species, A. motschulskyi n. sp., is newly described based on both sexes from Malaysia (Sabah) and Thailand and compared to A. mantoidae. Anastatus echidna, also originally known only from Sri Lanka, is newly reported from India, Pakistan and Thailand, and potential synonymy of one or both of Anastatus amarus (Subba Rao, 1957) and Anastatus acherontiae Narayanan, Subba Rao Ramachandra Rao, 1960, under A. echidna is discussed.

Anastatus Motschulsky (Hymenoptera, Eupelmidae): egg parasitoids of Caligula japonica Moore (Lepidoptera, Saturniidae) in China.

Four species of Anastatus Motschulsky (Hymenoptera, Eupelmidae, Eupelminae) are newly reported as egg parasitoids of the Japanese giant silkworm, Caligula japonica Moore and, as an alternate laboratory host, the Chinese oak silk moth, Antheraea pernyi (Guérin-Méneville) (Lepidoptera, Saturniidae) in China. The four species, A. fulloi Sheng & Wang, 1997, A. gansuensis Chen & Zang, sp. nov., A. japonicus Ashmead, 1904, and A. meilingensis Sheng, 1998, were reared initially from eggs of C. japonica collected in Gansu, Jilin and Liaoning provinces and subsequently cultured in the laboratory on eggs of A. pernyi. An illustrated key to differentiate females of the four species, and males of some of the species is provided. Key features are illustrated, both sexes of the new species are described, and diagnoses of females of the other species are given.

Succinylation Links Metabolism to Protein Functions.

Post-translational modifications (PTMs) are important regulators of protein function, and integrate metabolism with physiological and pathological processes. Phosphorylation and acetylation are particularly well studied PTMs. A relatively recently discovered novel PTM is succinylation in which metabolically derived succinyl CoA modifies protein lysine groups. Succinylation causes a protein charge flip from positive to negative and a relatively large increase in mass compared to other PTMs. Hundreds of protein succinylation sites are present in proteins of multiple tissues and species, and the significance is being actively investigated. The few completed studies demonstrate that succinylation alters rates of enzymes and pathways, especially mitochondrial metabolic pathways. Thus, succinylation provides an elegant and efficient mechanism to coordinate metabolism and signaling by utilizing metabolic intermediates as sensors to regulate metabolism. Even though the brain is one of the most metabolically active organs, an understanding of the role succinylation in the nervous system is largely unknown. Data from other tissues and other PTMs suggest that succinylation provides a coupling between metabolism and protein function in the nervous system and in neurological diseases. This review provides a new insight into metabolism in neurological diseases and suggests that the drug development for these diseases requires a better understanding of succinylation and de-succinylation in the brain and other tissues.